w 


TEXT-BOOK  OF 


EMBRYOLOGY 


BY 


FREDERICK  RANDOLPH  BAILEY,  A.  M.,  M.  D. 

FORMERLY  ADJUNCT  PROFESSOR  OF  HISTOI^OGY  AND  EMBRYOLOGY,  COLLEGE  OF  PHYSICIANS  AND 
SURGEONS  (MEDICAL  DEPARTMENT  OF  COLUMBIA  UNIVERSITY) 


AND 

ADA:  r  MARION  MILLER,  A.  M. 

PROFESSOR    OF  ANATOMY,    THE   LONG    ISLAND   COLLEGE   HOSPITAL 


tfourtb  3EMtton 


WITH 
FIVE  HUNDRED  AND  THREE  ILLUSTRATIONS 


NEW  YORK 

WILLIAM  WOOD  AND  COMPANY 
MDCCCCXXI 


COPYRIGHT,  1921, 
BY  WILLIAM  WOOD  &  COMPANY. 


PREFACE  TO  THE  FOURTH  EDITION 


In  the  present  edition  the  plan  of  the  book  has  been  modified  in  certain  respects. 
The  chapter  on  the  cell  has  been  omitted  because  in  the  opinion  of  the  authors  the 
previous  training  of  the  student  who  commences  the  study,  of  the  embryology  of 
vertebrates  has  been  sufficient  to  bring  to  his  attention  the  salient  features  of  cell 
organization.  In  former  editions  the  early  processes  of  development,  viz:  cleav- 
age, gastrulation,  and  mesoderm  formation,  were  treated  as  topics  in  separate 
chapters.  The  present  plan  comprises  the  treatment  of  the  early  stages  in  succes- 
sion in  a  given  animal  form;  individual  chapters  are  devoted  to  Amphioxus,  the 
frog,  the  chick,  and  the  mammal.  This  change  has  been  made  because  it  is  our 
opinion  gained  from  experience  in  teaching  that  the  student  acquires  a  better 
understanding  of  the  development  of  the  germ  layers  by  following  the  processes  as 
a  continuous  series  in  a  given  animal.  A  number  of  old  illustrations  have  been 
replaced  by  new  figures  the  sources  of  which  have  been  duly  credited. 

Apart  from  the  insertion  of  the  chapter  on  fcetal  membranes  the  second  part 
of  the  book,  comprising  organogeny,  has  been  revised  only  in  so  far  as  the  results 
of  recent  investigation  have  modified  the  ideas  expressed  in  the  previous  edition. 

We  wish  to  express  our  appreciation  of  the  helpful  criticisms  of  our  colleagues 
and  other  friends. 

THE  AUTHORS. 
JULY,  1921. 


518843 


PREFACE  TO  THE  FIRST  EDITION 


The  Text-book,  as  originally  planned,  is  an  outgrowth  of  the  course  in 
Embryology  given  at  the  Medical  Department  of  Columbia  University.  It  was 
intended  primarily  to  present  to  the  student  of  medicine  the  most  important 
facts  of  development,  at  the  same  time  emphasizing  those  features  which 
bear  directly  upon  other  branches  of  medicine.  As  the  work  took  form,  it 
seemed  best  to  broaden  its  scope  and  make  it  of  greater  value  to  the  genera! 
student  of  embryology  and  allied  sciences.  With  the  opinion  that  illustrations 
convey  a  much  clearer  conception  of  structural  features  than  verbal  description 
alone,  the  writers  have  made  free  use  of  figures. 

The  plan  of  adding  brief  "Practical  Suggestions"  at  the  end  of  each  chapter 
has  been  so  thoroughly  satisfactory  in  the  Text-book  of  Histology,  especially 
in  connection  with  laboratory  work,  that  it  has  been  adopted  here.  These 
"suggestions"  are  not  intended  to  be  complete  descriptions  of  embryological 
technic,  but  are  for  the  purpose  of  furnishing  the  laboratory  worker  with  cer- 
tain of  the  more  essential  practical  hints  for  studying  the  structures  described 
in  the  chapter.  To  avoid  frequent  repetition,  some  of  the  best  methods  of 
procuring,  handling,  and  preparing  embryological  material,  and  some  of  the 
more  important  formulae  are  given  in  the  Appendix,  which  is  intended  to  be 
used  mainly  for  the  carrying  out  of  the  "Practical  Suggestions." 

The  development  of  the  Germ  Layers  has  been  treated  rather  elaborately 
from  a  comparative  standpoint,  because  this  has  been  found  the  most  satisfac- 
tory method  of  teaching  the  subject. 

In  the  chapter  on  the  Nervous  System  the  aim  has  been  to  give  a  general 
conception  of  the  subject,  which,  if  once  mastered  by  the  student,  will  give 
him  an  insight  into  the  structure  and  significance  of  the  nervous  system  that 
will  bring  this  difficult  subject  more  fully  within  his  grasp. 

In  Part  II  (Organogenesis),  at  the  end  of  each  chapter  there  is  given  a  brief 
description  of  certain  developmental  anomalies  which  may  occur  in  connection 


vi  PREFACE. 

with  the  organs  described  in  the  chapter.  In  Chapter  XIX  (Teratogenesis) 
the  nature  and  origin  of  the  more  complex  anomalies  and  monsters  are  dis- 
cussed, and  also  the  causes  underlying  the  origin  of  malformations. 

The  writers  wish  to  thank  Dr.  Oliver  S.  Strong  for  his  painstaking  work  on 
the  chapter  on  the  Nervous  System.  Dr.  Strong  in  turn  wishes  to  acknowledge 
his  indebtedness  to  Dr.  Adolf  Meyer  for  important  ideas  underlying  the  treat- 
ment of  his  subject,  and  also  for  many  valuable  details.  He  expresses  his 
thanks  also  to  Professors  C.  J.  Herrick,  H.  von  W.  Schulte  and  G.  L.  Streeter 
for  helpful  criticisms  and  suggestions.  The  writers  would  also  express  their 
thanks  to  Dr.  H.  McE.  Knower  for  helpful  criticisms  on  Part  I  and  the 
chapter  on  Teratogenesis;  to  Dr.  Edward  Learning  for  making  the  photo- 
graphs reproduced  in  the  text;  to  the  American  Journal  of  Anatomy  for  the 
loan  of  plates;  and  to  Messrs.  William  Wood  &  Company  for  their  uniform 
courtesy  and  kindness. 

FREDERICK  RANDOLPH  BAILEY. 
APRIL  i,  1909.  ADAM  MARION  MILLER. 


CONTENTS 


PART  I.— GENERAL  DEVELOPMENT 

CHAPTER  I 

THE  GERM  CELLS i 

The  Ovum i 

The  Spermatozoon 6 

References  for  Further  Study 10 

CHAPTER  II 

MATURATION n 

Spermatogenesis — Maturation  of  the  Sperm 1 1 

Maturation  of  the  Ovum 16 

Significance  of  Mitosis  and  Maturation 20 

Sex  Determination 21 

Ovulation. 23 

References  for  Further  Study 26 

CHAPTER  III 

FERTILIZATION 27 

Significance  of  Fertilization 33 

References  for  Further  Study 34 


//EAR 


CHAPTER  IV 


ARLY  DEVELOPMENT  OF  AMPHIOXUS 35 

Cleavage 35 

Gastrulation 38 

Mesoderm    Formation 42 

References  for  Further  Study 47 

CHAPTER  V 

EARLY  DEVELOPMENT  OF  THE  FROG 49 

Cleavage 51 

Gastrulation 55 

Mesoderm  Formation    .....* 59 

References  for  Further  Study 65 

vii 


viii  CONTENTS 

CHAPTER  VI 

EARLY  DEVELOPMENT  OF  THE  CHICK 66 

Cleavage  .    ...    ....    .    .    .    .    .    . 67 

Gastrulation    .    .    .    .    .    .    .    .    .    ,   -.  .    . 70 

Origin  of  the  Mesoderm    .    .    .    .....    ."•'• 77 

Body  Form.    .    .    .    .    .    .    .    .    :,  .    .    . 81 

References  for  Further  Study  . 82 

CHAPTER  VII 

EARLY  MAMMALIAN  DEVELOPMENT 84 

Cleavage 85 

Ectoderm  and  entoderm 88 

Mesoderm 93 

The  Germ  Layers  in  Man 99 

References  for  Further  Study 106 

CHAPTER  VIII 

DEVELOPMENT  OF  THE  EXTERNAL  FORM  OF  THE  BODY 107 

General  Form 107 

The  Face 118 

The  Extremities 121 

Age,  Length  and  Weight  of  the  Body 122 

References  for  Further  Study 125 

CHAPTER  IX 

THE  DEVELOPMENT  OF  CONNECTIVE  TISSUES  AND  THE  SKELETAL  SYSTEM.   129 

Histogenesis 131 

Fibers  and  Fibrils .    ...''. 134 

Adipose  Tissue.  .    .    .    .  -.    ;.-;>..- ,•••'•• 135 

Cartilage -. 136 

Osseous  Tissue    .    .    .    .    /'.-,.;,    : .-".,. .''•„• . '.    ,    , 137 

Intramembranous  Ossification .    .    .    . 137 

Intracartilaginous  Ossification . 140 

The  Development  of  the  Skeletal  System  .    ....  '. 146 

The  Axial  Skeleton.   .    .    .    .    .    .    .    .    .    .   ; 146 

The  No  tochord   .    .,...-.    ....   .    .    .    .   , I46 

The  Vertebrae  .    .    .    .    .    .    1',".    .    . I47 

The  Ribs. .'  i  v    ...    .  ;. 152 

The  Sternum '  .        ^ 

The  Head  Skeleton 154 

Ossification  of  the  Chondrocranium    .    


CONTENTS  ix 

Membrane  Bones  of  the  Skull !6o 

Bones  Derived  from  the  Branchial  Arches 162 

The  Appendicular  Skeleton T66 

Development  of  Joints 173 

Anomalies 177 

References  for  Further  Study -.  181 

CHAPTER  X 

THE  DEVELOPMENT  OF  THE  VASCULAR  SYSTEM 185 

The  Blood  Vascular  System ^5 

Principles  of  Vasculogenesis ..193 

The  Heart !    .  196 

The  Septa. 202 

The  Valves 205 

Changes  after  Birth 206 

The  Arteries 209 

The  Veins 219 

Histogenesis  of  the  Blood  Cells 236 

The  Lymph  Vascular  System 242 

The  Lymph  Glands 249 

The  Spleen 252 

Glomus  Coccygeum 254 

Anomalies 254 

References  for  Further  Study 259 

CHAPTER  XI 

THE  DEVELOPMENT  OF  THE  MUSCULAR  SYSTEM 262 

The  Skeletal  Musculature 262 

Muscles  of  the  Trunk 264 

Muscles  of  the  Head 269 

Muscles  of  the  Extremities 272 

Histogenesis  of  Striated  Voluntary  Muscle  Tissue   .    .    .    .    .    .    .    .276 

The  Visceral  Musculature 280 

Histogenesis  of  Heart  Muscle '280 

Histogenesis  of  Smooth  Muscle 281 

Anomalies 282 

References  for  Further  Study 283 

CHAPTER  XII 

THE  DEVELOPMENT  OF  THE  ALIMENTARY  TUBE  AND  APPENDED  ORGANS    .  285 

The  Mouth  .   .    ,   . .286 

The  Tongue.    .    .-   ..-..;. v^   •    ....  289 


x  CONTENTS 

The  Teeth    .......    .    .  -.    , .    .  291 

The  Salivary  Glands  .  .  ,  ; 296 

The  Pharynx  .  .  .  .  .  .  .  .  .  .  .  . 298 

The  Branchial  Epithelial  Bodies  .  ....  . 300 

The  (Esophagus  and  Stomach  ...:.. .  304 

The  Intestine  .........  v 3°6 

Histogenesis  of  the  Gastrointestinal  Tract 311 

The  Development  of  the  Liver. 314 

Histogenesis  of  the  Liver .  318 

The  Development  of  the  Pancreas 319 

Histogenesis  of  the  Pancreas . 322 

Anomalies '. 323 

References  for  Further  Study  .  . 327 

CHAPTER  XIII 

THE  DEVELOPMENT  OF  THE  RESPIRATORY  SYSTEM 330 

The  Larynx 331 

The  Trachea 333 

The  Lungs .  334 

Changes  in  the  Lungs  at  Birth 337 

Anomalies; 338 

References  for  Further  Study 338 

CHAPTER  XIV 

THE  DEVELOPMENT  OF  THE  COELOM,  THE  PERICARDIUM,  PLEUROPERITONEUM, 

DIAPHRAGM  AND  MESENTERIES 340 

The  Pericardia!  Cavity,  Pleural  Cavities  and  Diaphragm  ...'....  341 

The  Pericardium  and  Pleura 347 

The  Omentum  and  Mesentery 347 

The  Greater  Omentum  and  Omental  Bursa 348 

The  Lesser  Omentum 349 

The  Mesenteries      .    .    .    .    .    ...    .    .    . 350 

The  Peritoneum 352 

Anomalies -••."• 352 

References  for  Further  Study  .    .    .    . 353 

CHAPTER  XV 

THE  DEVELOPMENT  OF  THE  UROGENITAL  SYSTEM. 354 

The  Pronephros  ......    .^^.  ......... 354 

The  Mesonephros  .    .    ...    ....    ...    . 356 

The  Kidney  (Metanephros) .     ....;;;;..:.;. 361 

The  Ureter,  Renal  Pelvis,  and  Straight  Renal  Tubules 361 


CONTENTS  xi 

The  Convoluted  Renal  Tubules  and  Glomeruli 363 

The  Renal  Pyramids  and  Renal  Columns 367 

Changes  in  the  Position  of  the  Kidneys 369 

The  Urinary  Bladder,  Urethra,  and  Urogenital  Sinus 370 

The  Genital  Glands 373 

The  Germinal  Epithelium  and  Genital  Ridge 3*73 

Differentiation  of  the  Genital  Glands 375 

The  Ovary 376 

The  Testicle     .    .    . 381 

Determination  of  Sex 382 

The  Ducts  of  the  Genital  Glands  and  the  Atrophy  of  the  Meso- 

nephroi 383 

In  the  Female 383 

Oviduct.   . 384 

Uterus  and  Vagina 385 

In  the  Male 386 

Changes  in  the  Positions  of  the  Genital  Glands  and  the  Development 

of  their  Ligaments 387 

Descent  of  the  Testicles 389 

Descent  of  the  Ovaries 392 

The  External  Genital  Organs 393 

The  Development  of  the  Suprarenal  Glands 396 

The  Cortical  Substance 397 

The  Medullary  Substance 397 

Anomalies • 399 

References  for  Further  Study 405 

CHAPTER  XVI 

THE  DEVELOPMENT  OF  THE  INTEGUMENTARY  SYSTEM 407 

The  Skin 407 

The  Nails -   409 

The  Hair 410 

The  Glands  of  the  Skin 412 

The  Mammary  Glands 412 

Anomalies 4J4 

References  for  Further  Study  .    .    .    .  '*\  < 416 

CHAPTER  XVII 

THE  NERVOUS  SYSTEM 417 

General  Considerations • 4X7 

General  Plan  of  the  Vertebrate  Nervous  System .     ..........   420 

Spinal  Cord  and  Nerves 427 

The  Epichordal  Segmental  Brain  and  Nerves 429 


xii  CONTENTS 

The  Cerebellum .....    .  436 

The  Mid-Brain  Roof 437 

The  Prosencephalon •    •  437 

General  Development  of  the  Human  Nervous  System  During  the  First 

Month 442 

His  togenesis  of  the  Nervous  System •••    •    •  " 448 

Epithelial  Stage — Cell  Proliferation 449 

Early  Differentiation  of  the  Nerve  Elements 453 

Differentiation  of  the  Peripheral  Neurones  of  the  Cord  and  Epi- 

chordal  Segmental  Brain  ......   :.    .    .  '. 456 

Efferent  Peripheral  Neurones 45^ 

Afferent  Peripheral  and  Sympathetic  Neurones 459 

Development  of  the  Lower  (Intersegmental)  Intermediate  Neurones  472 

Further  Differentiation  of  the  Neural  Tube •'.-." 476 

The  Spinal  Cord. -47^ 

The  Epichordal  Segmental  Brain ...".. 482 

The  Cerebellum v  .    .  - 495 

Corpora  Quadrigemina .    .  •_  -I  ;. ', '  <  • 500 

The  Diencephalon 501 

The  Telencephalon  (Rhinencephalon,  Corpora  Striata  and  Pallium)  508 

Rhinencephalon  ..*... 510 

Corpora  Striata  and  Pallium .    ...    .    .    .    .  511 

The  Archipallium 516 

The  Neopallium \. 522 

Anomalies 530 

References  for  Further  Study  .....    .  - .    .    .  \    ".    ....  531 

CHAPTER  XVIII 

THE  ORGANS  OF  SPECIAL  SENSE ........ 533 

The  Eye ..'.....  533 

The  Lens »    .    .    .  535 

The  Optic  Cup 539 

The  Retina .    .  '!   ,    .    r    .    .540 

The  Chorioid  and  Sclera ....'.    4  .......  545 

The  Vitreous .    .    . 545 

The  Optic  Nerve .    .    .    .546 

The  Ciliary  Body,  Iris,  Cornea,  Anterior  Chamber 547 

The  Eyelids 548 

The  Nose 549 

The  Ear 552 

The  Inner  Ear •;  ....    .    .    .  ^^2 

The  Acoustic  Nerve -.'.  .  ; .  ..  558 

The  Middle  Ear •        •    •    •  559 


CONTENTS  xiii 

The  Outer  Ear 560 

Anomalies 561 

References  for  Further  Study 562 

CHAPTER  XIX 

FOETAL  MEMBRANES 563 

Foetal  Membranes  in  Birds  and  Reptiles 563 

The  Amnion 563 

The  Yolk  Sac 567 

The  Allantois 570 

The  Chorion  or  Serosa 571 

Fcetal  Membranes  in  Mammals 571 

Amnion,  Chorion,  Yolk  Sac,  Allantois,  Umbilical  Cord 572 

Further  Development  of  the  Chorion 575 

The  Fcetal  Membranes  in  Man    .    . 579 

The  Amnion 579 

The  Yolk  Sac 581 

The  Allantois 582 

The  Chorion  and  Decidua 583 

The  Decidua  Parietalis 587 

The  Decidua  Capsularis    . 587 

The  Decidua  Basalis 588 

The  Umbilical  Cord 596 

The  Expulsion  of  the  Placenta  and  Membranes 598 

Anomalies 598 

References  for  Further  Study 599 

CHAPTER  XX 

TERATOGENESIS 601 

Malformations  Involving  More  Than  One  Individual 601 

Classification,  Description,  Origin 601 

Symmetrical  Duplicity 602 

Origin  of  Symmetrical  Duplicity 607 

Asymmetrical  Duplicity .  •    •    •  608 

Origin  of  Asymmetrical  (Parasitic)  Duplicity 610 

Malformations  Involving  One  Individual 612 

Description,  Origin 612 

Defects  in  the  Region  of  Neural  tube 612 

Origin  of  Malformations  in  the  Region  of  Neural  Tube.     .    .    .615 
Defects  in  Regions  of  the  Face  and  Neck,  and  their  Origin   .    .616 

Defects  in  the  Thoracic  and  Abdominal  Regions,  and  their  Origin  618 

Causes  Underlying  the  Origin  of  Monsters 620 

The  Production  of  Duplicate  (Polysomatous)  Monsters  .    .    ...    .  621 


CONTENTS 


The  Production  of  Monsters  in  Single  Embryos 622 

The  Significance  of  the  Foregoing  in  Explaining  the  Production  of 

Human  Monsters 623 

References  for  Further  Study 624 


INTRODUCTION 


While  Embryology  as  a  science  is  of  comparatively  recent  date,  recorded 
observations  upon  the  development  of  the  foetus  date  back  as  far  as  1600  when 
Fabricius  ab  Aquapendente  published  an  article  entitled  "De  Formato  Fcetu.'; 
Four  years  later  the  same  author  added  some  further  observations  under  the 
title,  "  De  Formatione  Foetus."  Harvey  (1651),  using  a  simple  lens,  studied  and 
described  the  chick  embryo  of  two  days'  incubation.  Harvey's  idea  was  that 
the  ovum  consisted  of  fluid  in  which  the  embryo  appeared  by  spontaneous 
generation.  Regnier  de  Graaf  (1677)  described  the  ovarian  follicle  (Graafian 
follicle),  and  in  the  same  year  was  announced  the  discovery  by  Von  Loewenhoek 
of  the  spermatozoon.  These  and  other  embryologists  of  this  period  held  what 
is  now  known  as  the  prejormation  theory.  According  to  this  theory,  the  adult 
form  exists  in  miniature  in  the  egg  or  germ,  development  being  merely  an 
enlarging  and  unfolding  of  preformed  parts.  With  the  discovery  of  the 
spermatozoon  the  "  pref ormationists  "  were  divided  into  two  schools,  one  hold- 
ing that  the  ovum  was  the  container  of  the  miniature  individual  (ovists),  the 
other  according  this  function  to  the  spermatozoon  (animalculists).  According 
to  the  ovists,  the  ovum  needed  merely  the  stimulation  of  the  spermatozoon  to 
cause  its  contained  individual  to  undergo  development,  whereas  the  animalcu- 
lists looked  upon  the  spermatozoon  as  the  essential  embryo-container,  the  ovum 
serving  merely  as  a  suitable  food-supply  or  growing-place. 

Nearly  a  hundred  years  of  almost  no  further  progress  in  embryological 
knowledge  came  to  a  close  with  the  publication  of  Wolff's  important  article, 
"Theoria  Generationis,"  in  1759.  Wolff's  theory  was  theory  pure  and  simple, 
with  very  little  basis  on  then  known  facts,  but  it  was  significant  as  being  ap- 
parently the  first  clear  statement  of  the  doctrine  of  epigenesis.  The  two  es- 
sential points  in  Wolff's  theory  were:  (i)  that  the  embryo  was  not  preformed; 
that  is,  did  not  exist  in  miniature  in  the  germ,  but  developed  from  a  more  or  less 
unformed  germ  substance;  (2)  that  union  of  male  and  female  substances  was 
necessary  to  initiate  development.  The  details  of  Wolff's  theory  were  wrong 
in  that  he  looked  upon  the  ovum  as  a  structureless  substance  and  upon  the 
seminal  fluid  and  not  upon  the  spermatozoon  as  the  male  fecundative  agent. 
Dollinger  and  his  two  pupils,  von  Baer  and  Pander,  were  the  next  to  make 
important  contributions  to  Embryology.  Von  Baer's  publication  in  1829  was 
of  extreme  significance  in  the  development  of  embryological  knowledge,  for 

XV 


xvi  INTRODUCTION. 

in  it  we  have  the  first  definite  description  of  the  primary  germ  layers  as  well  as 
the  first  accurate  differentiation  between  the  Graafian  follicle  and  the  ovum. 
It  will  be  remembered  that  the  cell  was  not  as  yet  recognized  as  the  unit  of 
organic  structure.  Only  comparatively  gross  Embryology  was  thus  possible. 
With  the  recognition  of  the  cell  as  the  basis  of  animal  structure  (Schleiden  and 
Schwann,  1839)  the  entire  field  of  histogenesis  was  opened  to  the  embryologist; 
the  ovum  became  known  as  a  typical  cell,  while  a  little  later  (Kolliker,  Reichert 
and  others,  about  1840)  was  established  the  function  of  the  spermatozoon 
and  the  fact  that  it  also  was  a  modified  cell  structure.  From  this  time  we 
may  consider  the  two  fundamental  facts  of  Histology  and  of  Embryology, 
respectively,  as  firmly  fixed  beyond  controversy;  for  Histology,  the  fact  that 
the  body  consists  wholly  of  cells  and  cell  derivatives;  for  Embryology,  the 
fact  that  all  of  these  cells  and  cell  derivatives  develop  from  a  single  original 
cell — the  fertilized  ovum. 

The  adult  body  being  thus  composed  of  an  enormous  number  of  cells,  vary- 
ing in  structure  and  in  function,  forming  the  different  tissues  and  organs,  and 
these  cells  having  all  developed  from  the  single  fertilized  germ  cell,  it  is  the 
province  of  Embryology  to  trace  this  development  from  the  union  of  male 
and  female  germ  cells  to  the  cessation  of  developmental  life. 

While  Embryology  thus  properly  begins  with  the  fertilized  ovum,  that  is, 
with  the  first  cell  of  the  new  individual,  certain  preliminary  considerations  are 
essential  to  the  proper  understanding  of  this  cell  and  its  future  development. 
These  are  the  structure  of  the  ovum  and  of  the  spermatozoon  and  their  de- 
velopment preparatory  to  union.  Also,  as  it  is  with  cells  and  cell  activities 
that  Embryology  has  largely  to  deal,  it  is  necessary  to  consider  the  structure 
of  the  typical  animal  cell  and  the  processes  by  which  cells  undergo  division  or 
proliferation. 

While  the  subject  of  this  work  is  distinctly  human  Embryology,  it  is  neither 
possible  nor  advisable  to  confine  our  study  wholly  to  human  material.  It  is  not 
possible,  for  the  reason  that  material  for  the  study  of  the  earliest  stages  in  the 
human  embryo  (first  12  days)  is  entirely  wanting,  while  human  embryos  of 
under  20  days  are  extremely  rare.  Again,  even  later  stages  in  human  develop- 
ment are  often  best  understood  by  comparison  writh  similar  stages  in  lower 
forms.  For  practical  study  by  the  student,  human  material  for  all  even  of 
the  later  stages  is  rarely  available,  so  that  recourse  must  frequently  be  had  to 
material  from  lower  animals.  Such  study  is,  however,  usually  thoroughly 
satisfactory  if  the  student  has  sufficient  knowledge  of  comparative  anatomy,  and 
the  deductions  regarding  human  development,  from  the  study  of  development 
in  lower  forms,  are  rarely  in  error,  ' 


PART  I. 


GENERAL  DEVELOPMENT. 


CHAPTER  I. 
THE  GERM  CELLS. 

The  vertebrate  animal  body  is  a  complex  of  numerous  types  of  cells. 
The  great  majority  of  the  cells  are  engaged  in  carrying  on  the  various  activi- 
ties of  daily  life.  Muscle  cells  contract  and  produce  motion  and  locomotion; 
red  blood  corpuscles  carry  oxygen  from  the  lungs  to  all  parts  of  the  body; 
epithelial  cells  synthesize  and  secrete  substances  which  are  used  in  some  man- 
ner or  excrete  waste  products;  nerve  cells  convey  impulses  from  one  region  to 
another  and  thus  bring  distant  parts  into  communication.  All  these  are 
integral  parts  of  the  body,  working  in  harmony  in  response  to  the  demands 
put  upon  them.  They  are  usually  spoken  of  as  somatic  cells  (soma-body) 
because  they  compose  the  bulk  of  the  body  and  are  concerned  in  its  specific 
activities  which  collectively  constitute  the  general  body  economy.  When 
death  occurs  all  these  cells  die  and  disintegrate  without  leaving  any 
descendants. 

Within  the  body  is  another  group  of  cells  which  differ  in  certain  respects 
from  the  somatic  cells.  They  are  confined  to  the  genital  or  sex  glands,  to  the 
testis  in  the  male  and  the  ovary  in  the  female.  They  probably  play  no  part 
in  the  general  body  economy;  they  are  concerned  in  perpetuating  the  race. 
During  the  life  of  an  individual  of  a  given  generation  they  are  discharged  at 
certain  times  from  the  glands  that  contain  them,  and  under  proper  conditions 
then  develop  into  a  new  individual  of  the  succeeding  generation.  For  this 
reason  they  are  known  as  germ  cells.  While  these  cells  contain  the  same 
visible  elements  as  the  somatic  cells,  that  is,  nuclear  and  cytoplasmic  com- 
ponents, there  are  differences  in  internal  organization  which  make  these  cells 
alone  capable  of  producing  a  new  member  of  the  species.  Under  ideal  con- 
ditions of  reproduction,  therefore,  they  do  not  die  and  disintegrate,  as  do  the 
somatic  cells,  but  are  carried  along  into  and  with  successive  generations, 
always  constituting  the  plasm  from  which  new  individuals  arise.  Each 
sex  has  its  own  peculiar  type  of  cell;  the  female  carries  the  ovum  (ovium, 
female  sex  cell  or  germ  cell),  the  male  carries  the  spermatozoon  (spermium, 
sperm,  male  sex  cell  or  germ  cell). 

THE  OVUM. 

The  ovum  is  among  the  largest  cells  in  the  animal  body,  but  varies  in  size 
from  a  fraction  of  a  millimeter  in  some  of  the  invertebrates  and  in  mammals 
to  several  inches  in  the  largest  birds.  The  differences  in  size  are  due  in  large 

1 


^,NTE;XT-BOOK  OF  EMBRYOLOGY. 


measure  to  differences  in  the  amounts  of  food  or  yolk  stored  within  the  egg. 
Taking  the  human  ovum  as  an  example  of  ova  containing  a  small  amount  of 
yolk  (deutoplasm) ,  it  is  not  truly  spherical  in  shape  but  ovoid,  with  an  aver- 
age diameter  of  slightly  less  than  0.2  mm.  As  seen  in  section  in  the  ovary 
it  presents  the  appearance  of  the  traditional  typical  cell  (Fig.  i).  Surround- 
ing the  ovum  is  the  zona  pellucida,  a  thick,  highly  refractive  membrane 
which  sometimes  shows  a  faint  radial  striation.  Immediately  outside  of  this 


Zona 
pellucida 


FIG. 


. — From  a  section  of  the  ovary  of  a  1 2-year  old  girl.  The  primary  oocyte  lies  in  a  large 
mature  Graafian  follicle  and  is  surrounded  by  the  cells  of  the  "  germ  hill "  (the  inner  edge  of 
which  is  shown  in  the  upper  left-hand  corner  of  the  figure).  Photograph. 


membrane  one  or  two  layers  of  the  epithelial  cells  of  the  Graafian  follicle 
are  arranged  radially  as  the  corona  radiata.  The  zona  pellucida  is  probably 
composed  of  differentiated  cytoplasm  of  the  inner  ends  of  these  cells.  Some 
investigators  have  described  a  delicate  mtelline  membrane  between  the  zona 
pellucida  and  the  ovum ;  others  have  not  observed  it.  If  this  is  present  it  is 
probably  a  true  cell  membrane,  a  product  of  the  egg  cytoplasm. 

The  egg  cytoplasm  (historically  called  the  vitellus,  whence  the    term 
vitelline  that  is  so  frequently  used  in  embryology)  is  more  opaque  and  more 


THE  GERM  CELLS.  3 

coarsely  granular  than  the  cytoplasm  of  most  cells,  due  to  the  presence  of 
granules  or  globules  of  yolk.  These  globules  are  suspended  in  the  cytoplasm 
and  composed  of  fatty  and  albuminous  substances  that  are  later  utilized  in  the 
growth  of  the  embryonic  cells.  It  should  be  added  that  the  composition  of 
the  yolk  in  the  human  ovum  is  assumed,  but  analysis  of  the  yolk  of  the  hen's 
egg  has  shown  a  large  percentage  of  lipins  including  lecithin,  with  some  pro- 
teins also,  and  a  similar  composition  of  the  yolk  granules  in  other  ova  is  a 
reasonable  assumption.  Lecithin  (lekythos),  is  a  term  that  was  used  by  the 
ancients  to  designate  the  yolk  of  an  egg.  The  yolk  globules  are  congregated 
near  the  center  of  the  cell,  surrounding  the  nucleus,  while  a  zone  of  cytoplasm 
nearly  destitute  of  yolk  forms  the  peripheral  portion  of  the  ovum.  In  his 
recent  study  of  the  maturation  of  the  human  ovum  Thomson  describes  and 
illustrates  a  centrosphere  which  then  disappears  after  the  formation  of  the 
second  polar  body. 

The  nucleus  is  situated  near  but  not 
quite  in  the  center  of  the  ovum  amidst 
the  yolk  granules.  Its  volume  bears  about 
the  same  ratio  -  to  the  volume  of  the  egg 
cytoplasm  as  the  nuclear  volume  of  the 
average  somatic  cell  bears  to  its  cyto- 
plasmic  mass.  A  distinct  nuclear  mem- 
brane encompasses  the  usual  nuclear 
structures.  The  chromatin  seems  rather 
scanty,  the  nucleus  thus  being  conspic- 
uously vesicular.  The  single  nudeolus 

(plasmosome)  is  intensely  stainable,  and  FIG.  2.— Ovumof  frog(Ranasylvatica). 
in  a  fresh  human  ovum  has  been  observed  T1f  <*ark  shading  represents  the 

cytoplasmic  pole,  the  light  shad- 
to  perform  amoeboid  movement.  ing  immediately  below  represents 

The  frog's  egg  will  serve  as  an  example  sl^S^SS^^mm^e^ 

of  an  ovum  with  a  moderate  amount  of  f  nts  the  gelatinous  substance 

11-  (secondary  egg  membrane). 

yolk    suspended    in    the    Cytoplasm,    yet 

enough  yolk  to  produce  a  definite  and  visible  effect  upon  the  organization 
of  the  cell  and  to  influence  strongly  the  future  processes  of  development. 
The  female  frog  deposits  the  eggs  in  clusters  in  quiet  water  where  they  may 
be  observed  resting  on  the  bottom  or  sticking  to  leaves  and  twigs.  The 
eggs  are  enclosed  in  a  jelly-like  substance,  each  cell  with  its  own  gelatinous 
capsule  or  membrane  (Fig.  2).  Each  egg  is  spherical  and  measures  from  ij^ 
to  3  mm.  in  diameter,  depending  upon  the  species  of  frog.  Externally  some- 
thing more  than  one-half  of  the  cell  is  black  owing  to  the  presence  of  pig- 
ment granules,  and  the  remainder  is  nearly  white.  If  the  eggs  have  been 
free  in  the  water  for  a  few  minutes  the  dark  sides  are  turned  upward.  A 


4  TEXT-BOOK  OF  EMBRYOLOGY. 

delicate  vitelline  membrane,  not  easily  seen,  surrounds  each  ovum.  This 
is  a  true  cell  membrane,  a  product  of  the  egg  cytoplasm.  Outside  of  this  is  a 
tough  membrane  called  the  chorion  and  then  the  gelatinous  capsule,  both 
being  secondary  egg  membranes  produced  by  the  cells  of  the  oviduct  and 
not  by  the  cytoplasm  of  the  ovum. 

If  the  egg  is  bisected  through  the  centers  of  the  dark  and  light  areas  the 
two  halves  are  exactly  alike.  The  cut  surface  of  either  half  shows  three 
substances:  pigment,  cytoplasm  and  yolk.  The  pigment  forms  a  superficial 
layer  which  coincides  with  the  dark  superficial  area.  It  is  a  product  of 
cytoplasmic  activity  without  any  known  importance  in  future  development. 
The  portion  of  the  egg  not  covered  by  pigment  contains  a  large  amount  of 
yolk,  in  fact  more  yolk  than  cytoplasm,  in  the  form  of  globules  of  different 
sizes.  The  remainder  of  the  egg  contains  some  yolk  but  the  cytoplasm  is 
excessive.  Therefore  we  may  speak  of  the  cytoplasmic  or  animal  pole  and 
the  yolk  or  vegetal  pole  of  the  egg,  the  former  approximately  indicated  on 
the  surface  by  the  dark  area  and  the  latter  by  the  light  area.  The  yolk  has 
a  slightly  higher  specific  gravity  than  the  cytoplasm,  which  accounts  for  the 
fact  that  if  the  egg  is  left  free  in  its  natural  medium  the  dark  pole  turns  up- 
ward. An  egg  like  this  in  which  more  yolk  is  accumulated  at  one  side  than 
at  the  other  is  known  as  a  telolecithal  ovum  as  distinguished  from  one  of  the 
homolecithal  type  in  which  the  yolk  granules  are  distributed  uniformly  or 
nearly  so,  as  in  the  mammalian  ovum. 

The  nucleus  of  the  frog's  ovum  is  proportionately  smaller  than  in  the 
case  of  an  egg  with  a  small  quantity  of  yolk.  It  is  conspicuously  eccentric, 
situated  nearer  the  animal  than  the  vegetal  pole.  Being  thus  situated  it 
obviously  tends  to  occupy  the  center  of  the  cytoplasmic  mass.  The  nuclear 
membrane  encloses  the  usual  nuclear  components;  the  chromatin  is  rather 
scanty  and  numerous  small  nucleoli  (plasmosomes)  are  present. 

The  freshly  laid  hen's  egg  may  be  chosen  as  an  example  of  a  large  ovum 
with  a  relatively  great  quantity  of  yolk  (Fig.  3) .  The  shape  is  characteristic. 
The  outer  covering  is  the  shell,  a  calcareous  substance.  If  the  shell  is  broken 
the  tough  shell-membrane  appears;  this  is  a  double  layer  with  a  considerable 
air  space  between  the  layers  at  the  larger  end  of  the  egg.  Enclosed  by  this 
membrane  is  the  thick  layer  of  albuminous  substance  with  a  denser  twisted 
portion,  the  chalaza,  at  each  end  of  the  egg.  All  these  structures  are  second- 
ary egg  membranes  secreted  around  the  ovum  proper  by  the  epithelium  of 
the  oviduct  during  its  passage  through  that  organ. 

The  ovum  proper  consists  of  the  large  spherical  mass  of  yolk,  25  mm. 
or  more  in  diameter,  and  a  small  disk  of  cytoplasm,  3  or  4  mm.  in  diameter, 
which  rests  upon  the  yolk.  If  the  unbroken  egg  is  allowed  to  lie  in  one 
position  for  a  minute  or  two  the  disk  will  be  found  uppermost  when  the  shell 


THE  GERM  CELLS. 


is  opened  owing  to  the  slightly  higher  specific  gravity  of  the  yolk.  At  the 
time  of  laying,  however,  development  has  proceeded  for  several  hours,  for 
fertilization  normally  occurs  in  the  oviduct  before  the  secondary  egg-mem- 
branes are  deposited.  The  ovum  proper  must  be  examined  in  the  ovary  or 
immediately  after  its  escape  therefrom  in  order  to  see  it  before  development 
begins.  At  this  time  the  yolk  mass  is  quite  similar  to  that  of  the  egg  after 
laying,  and  the  small  disk  of  cytoplasm  containing  a  single  flat  nucleus  is 
attached  to  one  side  of  the  yolk.  While  a  few  small  yolk  granules  are  sus- 
pended in  the  cytoplasm,  there  is  an  abrupt  transition  from  the  cytoplasmic 
disk  to  pure  yolk.  By  far  the  greater  part  of  the  yolk  contains  no  cytoplasm 
but  consists  solely  of  nutritive  substances  which  are  later  carried  to  and 
assimilated  by  the  growing  embryo. 


Germinal  disk  (cytoplasm) 


White  yolk 


Albumen  ("  white 


Vitelline  membrane 


White  yolk 


Shell 


Shell  membrane 
(outer  layer) 


Chalaza 

Shell  membrane 
(inner  layer) 


Yellow  yolk  (deutoplasm) 
FIG.  3. — Diagram  of  a  vertical  section  through  an  unfertilized  hen's  egg.     Bonnet. 


The  presence  of  the  large  quantity  of  yolk  in  the  ova  of  birds  and  reptiles 
is  correlated  with  the  long  period  during  which  embryos  of  these  animals 
undergo  development  within  their  shells  before  hatching  and  attaining 
ability  to  get  their  own  food.  In  the  case  of  the  frog  the  moderate  amount 
of  yolk  in  the  egg  serves  as  food  for  the  growing  embryo  until  it  becomes  a 
free-swimming  larva  or  tadpole.  An  embryo  of  a  mammal  develops  for  a 
long  period  in  the  uterus  of  its  mother  from  an  ovum  with  scanty  yolk,  but 
provision  is  made  for  drawing  nourishment  directly  from  the  maternal  blood 
during  this  time. 

A  simple  classification  of  ova  is  made  on  the  basis  of  the  amount  and 
distribution  of  the  yolk  content.  The  term  meiolecithal  is  used,  to  designate 
ova  in  which  the  yolk  granules  are  few  (many  invertebrates,  Amphioxus, 
mammals).  Mesolecithal  ova  are  those  which  contain  moderate  quantities 
of  yolk  (amphibians).  Ova  that  possess  large  yolk  content  are  classed  as 


6  TEXT-BOOK  OF  EMBRYOLOGY. 

polylecithal  (certain  fishes,  reptiles,  birds) .  It  has  been  stated  earlier  in  the 
chapter  that  in  case  the  yolk  is  accumulated  in  greater  quantity  toward  one 
pole  the  ovum  is  telolecithal,  while  in  case  of  nearly  uniform  distribution  it  is 
homolecithal.  The  yolk  has  a  slightly  higher  specific  gravity  than  the 
cytoplasm,  in  consequence  of  which  the  animal  pole  of  the  egg  turns. upward, 
except  in  most  of  the  teleost  ova  where  the  yolk  is  composed  of  oil  droplets 
that  are  lighter  than  the  cytoplasm.  In  many  insect  eggs  the  yolk  is  cen- 
trally placed  and  the  cytoplasm  forms  an  outer  layer;  these  are  known  as 
centrolecithal  ova. 

THE  SPERMATOZOON. 

Compared  with  the  ovum  the  spermatozoon  is  an  exceedingly  small  cell 
bearing  little  resemblance  to  the  ordinary  or  typical  cell.  It  is  so  small 
in  most  animals  that  the  ovum  of  the  same  species  exceeds  it  in  bulk  several 
hundred  thousand  times.  Its  peculiar  shape  and  structure  are  correlated 
with  its  high  degree  of  motility,  the  cytoplasm  being  drawn  out  into  a  long 
slender  tail  or  flagellum  which  in  the  living  cell  is  lashed  about  and  thus 
drives  the  whole  cell  along.  All  spermatozoa  of  vertebrates  are  of  the 
flagellate  type,  the  human  spermatozoon  serving  as  an  example. 

With  the  usual  preparation  the  human  spermatozoon  shows  a  head,  a 
middlepiece  or  body,  and  a  tail,  measuring  in  total  length  from  50  to  60  micra. 
On  side  view  the  head  is  nearly  oval,  usually  a  little  narrower  at  the  front 
end;  on  edge  it  appears  pear-shaped.  The  nucleus  is  situated  in  the  head, 
nearer  the  attachment  of  the  body,  and  a  thin  layer  of  cytoplasm,  the  galea 
capitis,  surrounds  the  nucleus  and  is  continued  forward  as  the  acrosome.  The 
head  is  about  4.5  micra  in  length,  2  to  3  in  width  and  i  to  2  in  thickness,  being 
much  smaller  than  a  red  blood  corpuscle.  The  body  is  attached  to  the 
broader  end  of  the  head  and  is  cylindrical,  measuring  about  6  micra  in  length. 
Sometimes  a  narrower  portion,  the  neck,  is  visible  at  the  point  of  attachment. 
Without  sharp  demarkation  the  body  continues  into  the  slender  tail  which 
runs  to  a  point  and  measures  from  40  to  50  micra  in  length. 

Special  preparations  of  spermatozoa  reveal  other  details  of  structure 
(Fig.  4).  The  body  contains  a  delicately  fibrillated  cord,  the  axial  thread, 
which  is  continued  throughout  the  tail,  narrowing  to  a  point  at  its  terminus. 
Surrounding  the  axial  thread  is  a  capsule  of  cytoplasm  which,  however,  does 
not  extend  to  the  tip  of  the  tail,  thus  leaving  the  axial  thread  naked  for  a 
short  distance.  In  the  body  the  cytoplasm  contains  a  spiral  fiber,  perhaps 
of  a  mitochondrial  nature,  winding  round  the  axial  filament;  other  mitochon- 
dria also  are  present.  The  body  contains  the  centrosome  which  takes  the 
form  of  a  double  structure;  one  part,  the  anterior  end  knob,  is  attached  to 
the  posterior  surface  of  the  head  close  to  the  nucleus,  the  other  part,  the 


THE  GERM  CELLS. 


Acrosome 

X~\ 


Galea 
capitis 


Neck         HHC     Anterior  end  knob 
Posterior  end  knob 


Body 


End  ring 


Spiral  fibers 

„  Sheath  of 
axial  thread 


posterior  end  knob,  is  situated  a  little  farther  back.  A  derivative  of  the  centro- 
some,  as  shown  during  development  of  the  spermatozoon,  is  the  end  ring 
which  marks  the  boundary  between  body  and  tail. 

Spermatozoa  of  other  animals,  both  vertebrates  and  invertebrates,  show  a 
great  variety  of  forms.     A  few  of  these  are 
illustrated  in  Fig.  5.     Some  are  simple  in 
form  and  structure,  others  are  complex  and 
even     bizarre.     Almost     throughout     the 
series,   however,    there   is   some   structure        Head* 
that  lends  itself  to  the  function  of  motility. 

In  the  tubules  of  the  mammalian  testis, 
where  the  spermatogenic  cells  develop  into 
the  mature  spermatozoa,  the  sperms  are 
not  motile.  They  acquire  some  degree  of 
motility  in  the  tubules  of  the  epididymis 
and  the  highest  degree  only  after  they  are 
mixed  with  the  secretions  of  the  prostate 
gland  and  other  accessory  sex  glands. 
They  are  active  in  the  fluid  of  the  female 
genital  tract  where  they  swim  against  the 
current  produced  by  the  cilia  of  the  epithe- 
lium -lining  the  tract.  Their  rate  of 
progress  has  been  variously  estimated  from 
1.5  to  3.5  mm.  per  minute.  It  is  not 
known  how  long  spermatozoa  remain  alive 
in  the  female  genital  tract.  They  have 
been  found  in  the  vagina  seventeen  days 
and  in  the  cervix  of  the  uterus  eight  days 
after  cohabitation,  and  in  one  case  where 
the  oviducts  were  removed  more  than 
three  weeks  after  cohabitation  active 
sperm  cells  were  found  but  whether  they 
were  capable  of  fertilizing  an  ovum  could 
not  be  determined.  Spermatozoa  can  en- 
dure considerable  variation  in  tempera- 
ture; they  are  most  active  in  a  slightly 
alkaline  medium  but  die  quickly  in  an  acid 
medium.  The  number  of  spermatozoa 
produced  by  an  individual  is  almost  incomparably  greater  than  the  num- 
ber of  ova.  It  has  been  estimated  that  only  about  400  ova  reach  maturity 
during  the  reproductive  period  of  a  little  more  than  30  years  in  a 


Main  segment 
of  tail 


Axial  thread 
-Capsule 


Terminal 
filament 


FIG.  4. — Diagram  of  a  human 
tozob'n.     Meves,  Bonnet. 


^ 


TEXT-BOOK  OF  EMBRYOLOGY. 


N 


FIG.  5. — Various  types  of  spermatozoa.  A,  B,  A  teleost;  C,  D,  bird;  E,  F,  snail;  G,  Ascaris;  H, 
an  annulate;  /,  bat;  /,  opossum;  K,  rat;  L,  salamander;  M,  N,  O,  P,  crustaceans,  k, 
End  knob;  w,  middle  piece;  u,  undulatory  membrane.  From  Kellicott,  General  Embry- 
ology. 


THE  GERM  CELLS.  9 

woman,  while  a  single  ejaculation  of  semen  may  contain  two  hundred 
million  spermatozoa. 

Significance  of  Germ  Cell  Organization.— One  feature  of  this  has  already 
been  mentioned  in  connection  with  the  morphological  differences  between  the 
male  and  female  germ  cells:  The  spermatozoon  is  adapted  for  locomotion 
while  the  ovum  is  passive  and  frequently  laden  with  yolk.  This  diversity  in 
structure  is  truly  correlated  with  a  physiological  division  of  labor.  The  two 
cells  must  unite  before  development  of  a  new  organism  can  proceed;  the  egg 
is  non-motile  and  contains  nutriment  for  the  future  embryo,  the  sperm  by 
virtue  of  its  motility  approaches  the  egg  and  finally  enters  it. 

Another  feature  of  organization  is  embodied  in  the  chromatin.  The 
chromatin  is  a  visible  substance  and  is  regarded  as  the  inheritance  material. 
Its  constitution  is  such  that  it  determines  in  large  measure  the  course  of 
development  of  the  embryo  arising  from  the  united  germ  cells  and  the  quali- 
ties or  characters  of  the  adult.  Parts  of  the  chromatin  contain  or  comprise 
factors  which  give  rise  to  certain  characters  in  the  developed  organism. 
These  factors,  or  genes  as 'they  are  frequently  called  by  students  of  heredity, 
are  not  visible  things  but  are  probably  expressed  in  the  physico-chemical 
nature  of  the  chromatin.  There  is  ample  evidence  for  their  presence,  upon 
which  is  based  the  modern  theory  of  heredity  or  Mendelian  inheritance.  One 
set  of  factors  is  present  in  the  ovum  and  another  in  the  sperm.  Their  rela- 
tion to  the  chromosomes  and  their  behavior  will  be  considered  in  the  two 
succeeding  chapters. 

There  are  certain  characters  of  the  embryo  that  are  derived  directly  from 
the  cytoplasm  of  the  ovum ;  so  chromatin  is  not  the  only  germ  cell  substance 
that  influences  development.  Since  these  characters  come  from  the  female 
parent  and  not  from  the  male,  this  is  sometimes  called  maternal  inheritance 
as  distinguished  from  Mendelian  inheritance.  The  cytoplasm  of  the  sperm 
seems  to  be  useful  only  as  a  temporary  locomotor  apparatus.  The  egg  cyto- 
plasm is  so  organized  that  it  becomes  potent  in  determining  the  course  of 
development.  In  the  case  of  an  ovum  that  contains  a  moderate  amount  of 
yolk,  as  in  the  frog,  or  a  large  quantity,  as  in  the  bird,  there  is  an  obvious 
polar  differentiation  or  polarity  which  is  visibly  expressed  in  the  distribution 
of  the  cytoplasm  and  yolk.  This  polarity  of  the  egg  determines  the  polarity 
of  the  future  adult  animal.  It  will  be  seen  in  a  later  chapter  that  the  egg  of 
Amphioxus  is  bilaterally  symmetrical,  and  that  the  bilateral  character  of 
the  developing  animal  follows  upon  that  of  the  egg.  This  is  true  also  of 
the  frogs  and  fishes.  Other  evidence  of  the  internal  organization  of  the 
egg  cytoplasm  in  certain  invertebrates  is  seen  in  collections  of  various  pig- 
ments in  the  ova;  and  it  is  possible  to  predict  accurately  the  part  of  the  em- 
bryo that  will  be  derived  from  the  portion  of  the  cytoplasm  containing  a  given 


10  TEXT-BOOK  OF  EMBRYOLOGY. 

pigment.  These  few  examples  are  sufficient  to  indicate  that  cytoplasmic 
organization  of  the  ovum  determines  in  a  measure  the  course  of  development 
of  the  future  embryo. 

References  for  Further  Study. 

CONKLIN,  E.  G.:  Heredity  and  Environment  in  the  Development  of  Men.      1920. 

KEIBEL,  F.  and  MALL,  F.  P.:  Manual  of  Human  Embryology.     Vol.  I,  Chap.  I,  1910. 

KELLICOTT,  W.  E.:  Text-book  of  General  Embryology.     Chap.  Ill,  1913. 

WALDEYER,  W.:  In  Hertwig's  Handbuch  der  vergleichenden  und  experimentellen 
Entwickelungslehre  der  Wirbeltiere.  Bd.  I,  Teil  I,  Kap.  I,  1906.  Contains  extensive 
bibliography. 

WILSON,  E.  B.:  The  Cell  in  Development  and  Inheritance.     2d  Ed.,  1900. 


CHAPTER  II. 
MATURATION. 

It  was  stated  in  the  preceding  chapter  that  among  the  vertebrates  the 
essential  condition  for  the  production  of  a  new  individual  was  the  union  of 
two  sexually  different  cells.  Since  the  number  of  chromosomes  is  constant 
for  all  the  cells  of  a  species,  such  a  union  would  cause  a  doubling  of  chromo- 
somes unless  the  latter  were  reduced  to  one-half  of  their  normal  number. 
Such  a  reduction  actually  takes  place,  .and  forms  the  essential  part  of  the 
maturation  processes  of  the  germ  cells. 

SPERMATOGENESIS— MATURATION  OF  THE  SPERM. 

The  spermatozoa  arise  from  the  germinal  epithelium  of  the  testis.  In 
the  mammal  this  epithelium  consists  of  two  kinds  of  cells:  (i)  the  supporting 
cells  (of  Sertoli)  and  (2)  the  spermatogenic  cells  in  various  stages  of  develop- 
ment (Fig.  6).  Of  the  latter  the  basal  layer  consists  of  small  round  or  oval 
cells  which  are  known  as  spermatogonia.  Internal  to  these  are  the  larger 
spermatocytes  having  large  vesicular  nuclei  with  densely  staining  chromatin. 
Between  these  and  the  lumen  of  the  seminiferous  tubule  are  several  layers  of 
small  round  or  oval  cells,  the  spermatids.  The  spermatids  have  the  reduced 
number  of  chromosomes,  and  by  direct  transformation  give  rise  to  the  mature 
spermatozoa  which  may  either  lie  free  in  the  lumen  of  the  tubule  or  have  their 
heads  embedded  in  the  supporting  cells. 

The  way  in  which  the  maturation  or  reduction  divisions  take  place  in  the 
higher  animals,  such  as  mammals,  is  difficult  to  demonstrate  on  account  of 
the  small  size  of  the  cells.  The  following  account  is  based  on  data  obtained 
from  the  study  of  lower  forms  (amphibia,  fishes,  insects,  Ascaris)  whose 
maturation  processes  have  been  demonstrated  with  great  accuracy.  Ascaris 
and  some  of  the  insects  show  the  later  stages  with  remarkable  clearness. 
It  is  reasonable  to  suppose  that  the  maturation  processes  of  the  mamma- 
lian germ  cells  agree  essentially  with  those  of  lower  forms. 

The  spermatogonia  divide  by  ordinary  mitosis,  each  daughter  cell  receiv- 
ing the  full  or  diploid  number  of  chromosomes.     After  several  generations  ^ 
some  of  the  spermatogonia  pass  through  a  period  of  growth  and  are  then 
known  as  primary  spermatocytes.     During  this  period  important  changes 
take  place  in  the  nucleus.     The  chromatin  granules  become  concentrated 

11 


12 


TEXT-BOOK  OF  EMBRYOLOGY. 


6.—  Schematic  outline  of  sper- 


into  a  dense  mass  in  which  very  little  struc- 
ture is  made  out.  After  the  period  of 
growth  the  nucleus  assumes  again  the  reticu- 
lar  appearance.  Then  when  the  spireme  is 
formed  and  segmentation  occurs,  previous 
to  division,  only  the  haploid  or  one-half  the 
normal  number  of  chromosomes  appears.  This 
seems  to  be  due  to  an  actual  fusion  of 
chromosomes  by  pairs,  such  fusion  occurring 
during  the  period  of  growth  and  being  known 
as  synapsis  of  chromosomes.  In  some  cases 
the  double  nature  of  the  chromosomes  is  still 
visible  while  in  other  cases  the  fusion  is 
complete. 

The  fused  chromosomes  now  prepare  for 
division.  However,  instead  of  dividing 
longitudinally  into  two  parts,  a  double  split- 
ting occurs  and  each  chromosome  is  divided 
into  four  elements.  Such  a  quadruple  chro- 
mosome is  termed  a  tetrad.  Since  each  tetrad 
represents  a  double  chromosome,  the  number 
of  tetrads  in  any  species  will  be  equal  to  one- 
half  its  normal  number  of  chromosomes  (Fig. 
7,  D).  The  tetrads  arrange  themselves  in  the 
equatorial  plane  of  the  spindle  and  cell  division 
begins  (Fig.  7,  E,  F,  G)  .  Each  tetrad  is  sepa- 
rated into  two  dyads,  and  then  one  dyad 
from  each  tetrad  goes  to  each  of  the  two 
resulting  daughter  cells  or  secondary  sperma- 
tocytes  (Fig.  7,  H)'.  A  new  spindle  is  formed 
in  each  of  the  secondary  spermatocytes  and 
the  cells  divide  again,  without  the  return  of 
the  nucleus  to  the  resting  stage.  The  dyads 
go  to  the  equatorial  plane  (Fig.  7,  7,  /,  K). 
Each  dyad  is  separated  into  two  monads, 
each  daughter  cell  or  spermatid  receiving  one 
monad  from  each  dyad  (Fig.  7,L).  Aprimary 


lying  close  to  the  basement 


membrane  and  multiplying  by  ordinary  mitosis.  9-16,  Spermatogonia  during  period 
of  growth,  resulting  in  primary  spermatocytes.  17,  18,  19,  Primary  spermatocytes  divid- 
ing. 20,  Secondary  spermatocytes.  21,  Secondary  spermatocytes  dividing,  resulting  in 
spermatids  (22-25).  26-31,  Transformation  of  spermatids  into  spermatozoa,  a  few  of 
which  are  seen  fully  formed  (32). 


MATURATION. 


13 


spermatocyte  gives  rise  therefore  to  four  spermatids  in  which  the  number  of 
chromosomes  is  reduced  to  one-half  the  normal. 

After  the  last  spermatocyte  division  and  the  resulting  formation  of  the 
spermatid,  the  nucleus  of  the  latter  acquires  a  membrane  and  intranuclear 
network,  thus  passing  into  the  resting  condition.  Without  further  division 


FIG.  7. — Reduction  of  chromosomes  in  spermatogenesis  in  Ascaris  megalocephala  (bivalens). 
Brauer,  Wilson. — A — G,  Successive  stages  in  the  division  of  the  primary  spermatocyte. 
The  original  reticulum  undergoes  a  very  early  division  of  the  chromatin  granules  which 
then  form  a  doubly  split  spireme  (B).  This  becomes  shorter  (C),  and  then  breaks  in  two 
to  form  the  2  tetrads  (D,  in  profile,  E,  on  end).  F,  G,  H,  First  division  to  form  2  secondary 
spermatocytes,  each  receiving  2  dyads.  /,  Secondary  spermatocyte.  /,  K,  The  same 
dividing.  L,  Two  resulting  spermatids,  each  containing  2  single  chromosomes. 

the  spermatid  now  becomes  transformed  into  a  spermatozoon  (Fig.  8).  This 
is  accomplished  by  rearrangement  and  modification  of  its  component  struc- 
tures. The  centrosome  either  divides  completely,  forming  two  centrosomes,  or 
partially,  forming  a  dumbbell-shaped  body  between  the  nucleus  and  the  sur- 
face of  the  cell.  The  nucleus  passes  to  one  end  of  the  cell  and  becomes  oval 


14 


TEXT-BOOK  OF  EMBRYOLOGY. 


in  shape.  Its  chromatin  becomes  very  compact  and  finally  condensed  in  the 
homogeneous  chromatin  mass  which  forms  the  greater  part  of  the  head  of  the 
spermatozoon.  Both  centrosomes  apparently  take  part  in  the  formation  of 
the  middle  piece.  The  one  lying  nearer  the  center  becomes  disk-shaped  and 
attaches  itself  to  the  posterior  surface  of  the  bead.  The  more  peripheral 
centrosome  also  becomes  disk-shaped  and  from  the  side  directed  away  from 
the  head  a  long  delicate  thread  grows  out — the  axial  filament.  The  central 


Head 

Anterior  end  knob 
Posterior  end  knob 


Head 

.  Anterior  end  knob 
Posterior  end  knob 
"•  End  ring 


Tail 


Nucleus 

Cytoplasm 
Proximal  centrosome 


Distal  centrosome 


FIG.  8. — Transformation  of  a  spermatid  into  a  spermatozoon  (human). 

Meves,  Bonnet. 


Schematic. 


portion  of  the  outer  centrosome  next  becomes  detached  and  in  mammals 
forms  a  knob-like  thickening — end  knob — at  the  central  end  of  the  axial 
filament.  In  amphibians  this  part  of  the  outer  centrosome  appears  tq  pass 
forward  and  to  attach  itself  to  the  inner  centrosome.  In  both  cases  the  rest 
of  the  outer  centrosome  in  the  shape  of  a  ring  passes  to  the  posterior  limit  of 
the  cytoplasm.  As  the  two  parts  of  the  posterior  centrosome  separate,  the 
cytoplasm  between  them  becomes  reduced  in  amount,  at  the  same  time  giv- 
ing rise  to  a  delicate  spiral  thread — the  spiral  filament — which  winds  around 


MATURATION. 


15 


the  axial  filament  of  the  middle  piece.  Meanwhile  the  axial  filament  has 
been  growing  in  length  and  part  of  it  projects  beyond  the  limit  of  the  cell. 
The  cytoplasm  remaining  attached  to  the  anterior  part  of  the  filament  sur- 
rounds it  as  the  sheath  of  the  middle  piece.  In  mammals  there  appears  to  be 
more  cytoplasm  than  is  needed  for  the  formation  of  the  sheath  of  the  middle 
piece,  and  a  large  part  of  it  degenerates  and  is  cast  aside.  The  sheath  which 
surrounds  the  main  part  of  the  axial  filament  appears  in  some  cases  at  any 
rate  to  develop  from  the  filament  itself.  The  galea  capitis  or  delicate  film 


XY 


.XY2 


B  C 

FIG.  9. — Three  stages  in  spermatogenesis  in  man  (negro).     Wieman. 

In  a  is  shown  a  nucleus  of  a  primary  spermatocyte  during  the  growth  period;  p,  plasmosome;  x 
and  y,  accessory  chromosomes.  In  b  is  shown  the  metaphase  in  a  primary  spermatocyte 
in  which  there  are  1 2  bivalent  chromosomes  that  have  resulted  from  synapsis  of  the  24  in 
the  spermatogonium,  the  x  and  y  uniting  with  each  other.  In  c  is  shown  a  later  stage  of 
spermatocyte  division  in  which  the  xy  pair  has  divided  longitudinally,  the  daughter  chro- 
mosomes passing  toward  the  poles  of  the  spindle  ahead  of  the  main  group. 

of   cytoplasm   which   covers   the   head  is  also  a  derivative  of  the  cyto- 
plasm of  the  spermatid. 

The  developing  spermatozoa  lie  with  their  heads  directed  toward  the 
basement  membrane,  and  attached,  probably  for  purposes  of  nutrition,  to 
the  free  ends  of  the  Sertoli  cells  (Fig.  6) .  Their  tails  often  extend  out  into 


16  TEXT-BOOK  OF  EMBRYOLOGY. 

the  lumen  of  the   tubule.     When   fully  developed  they  become  detached 
from  the  Sertoli  cells  and  lie  free  in  the  lumen  of  the  tubule. 

The  work  done  within  the  past  decade  on  spermatogenesis  in  the  human 
has  established  the  relation  of  chromosome  behavior  here  to  that  in  the 
lower  animals,  showing  some  interesting  coincidences.  In  the  last  of  several 
studies  by  different  investigators,  Wieman  has  critically  observed  conditions 
in  both  the  white  and  the  negro.  In  division  of  the  spermatogonium  24 
chromosomes  appear,  two  of  which  are  designated  idiochromosomes  (XY 
pair).  During  the  period  of  growth  to  a  primary  spermatocyte  the  XY  pair 
persists  as  a  deeply  staining  bipartite  body  (Fig.  9,  a).  In  the  prophase  of 
primary  spermatocyte  division  pairing  or  synapsis  results  in  12  bivalent 
chromosomes,  the  XY  pair  retaining  its  identity  (Fig.  9,  V).  When  meta- 
kinesis  occurs  the  XY  element  divides  lengthwise,  but  whether  the  other  1 1 
divide  lengthwise  or  transversely  has  not  been  determined  (Fig.  9,  c).  In 
division  of  the  secondary  spermatocyte  the  n  chromosomes  divide,  each 
giving  one-half  of  itself  to  a  spermatid;  but  the  XY  element  gives  X  to  one 
spermatid  and  Y  to  the  other.  The  result  of  this  chromosomal  behavior  is, 
therefore,  that  the  usual  reduction  in  number  is  accomplished  but  that  the 
spermatids,  and  hence  the  spermatozoa,  are  of  two  classes  differing  as  to  the 
X  and  Y  chromatin  content. 

MATURATION  OF  THE  OVUM. 

The  female  germ  cell,  before  it  is  fertilized,  goes  through  a  process  of 
maturation  similar  to  that  of  the  male  germ  cell.  The  result  is  essentially 
the  same:  the  mature  ovum  contains  a  reduced  number  of  chromosomes. 
There  is  this  difference,  however,  that  while  the  chromatin  elements  are 
distributed  equally  during  the  reduction  divisions,  one  cell  alone  retains 
practically  all  the  cytoplasm  and  deutoplasm  present  in  the  primary  oocyte. 
This  cell  becomes  the  functional  ovum  while  the  other  cells  are  pinched  off  as 
minute  bodies,  containing  but  little  of  the  cytoplasm,  which  are  known  as 
polar  bodies  and  eventually  degenerate  and  disappear. 

The  early  maturation  stages  of  the  female  sex  cell  are  very  similar  to 
those  of  the  male.  The  oogonia  contain  the  diploid  number  of  chromosomes 
and  divide  by  ordinary  mitosis.  After  several  generations  they  pass  through 
a  period  of  growth  and  are  then  known  as  primary  oocytes.  During  the 
growth  period  there  occurs  a  condensation  of  the  chromatin,  and  synapsis 
of  the  chromosomes  probably  takes  place  at  this  time.  The  nucleus  then 
resumes  its  reticular  structure.  Following  this  the  spireme  is  formed, 
preparatory  to  division,  and  segments  into  the  haploid  number  of  chromo- 
somes. From  this  stage  the  process  varies  somewhat  in  different  animals. 


MATURATION, 


17 


In  Ascaris,  whose  diploid  number  of  chromosomes  is  four,  both  maturation 
divisions  occur  after  the  sperm  has  entered  the  egg  and  lies  embedded  there 


FIG.  10. — Maturation  of  the  ovum  of  Ascaris  megalocephala  (bivalens).  Boveri,  Wilson.  A, 
The  ovum  with  the  spermatozoon  just  entering  at  x"  ',  the  egg  nucleus  contains  2  tetrads 
(one  not  clearly  shown),  the  somatic  number  of  chromosomes  being  4.  B,  Tetrads  in  pro- 
file. C,  Tetrads  on  end.  D,  E,  first  spindle  forming.  F,  Tetrads  dividing.  G,  First  polar 
body  formed,  containing  2  dyads;  2  dyads  left  in  the  ovum.  H,  /,  Dyads  rotating  in  pre- 
paration for  next  division.  /,  Dyads  dividing.  K,  Each  dyad  divided  into  2  single  chro- 
mosomes, thus  completing  the  reduction. 


as  the  male  pronucleus.     An  achromatic  spindle  forms  near  the  surface  of 
the  ovum  and  the  two  tetrads  go  to  the  equatorial  plane  (Fig.  10,  E).     Each 


18 


TEXT-BOOK  OF  EMBRYOLOGY. 


tetrad  separates  into  two  dyads,  and  one  dyad  from  each  tetrad  passes 
into  a  small  mass  of  cytoplasm  which  becomes  detached  from  the  egg  cell  as 
the  first  polar  body  (Fig.  10,  F,  G).  A  new  spindle  forms  without  the  return 
of  the  nucleus  to  the  resting  stage,  and  each  dyad  divides  into  two  monads. 
The  second  polar  body  is  now  given  off  in  the  same  manner  as  the  first 
(Fig.  10,  H,  7,  /,  K).  One  monad  from  each  dyad  passes  into  a  small  mass 
of  cytoplasm  and  is  separated  from  the  egg  cell.  The  maturation  is  now 
complete.  The  nucleus  of  the  mature  ovum  contains  the  haploid  number 
of  chromosomes  and  is  ready  for  union  with  the  male  pronucleus. 


D  10  F 

FIG.  n. — From  sections  of  ova  of  the  mouse,  showing  stages  in  the  maturation  process.     Sobotta. 

A,  Ovum  showing  prophase  of  maturation  division.    /,  fat;  z.p.,  zona  pellucida. 

B,  Ovum  showing  maturation  spindle  with  chromatin  segments  undivided. 

C,  Ovum  showing  diaster  stage  of  maturation  division,  formation  of  ist  polar  body  (p.b.), 

and  sperm  nucleus  (male  pronucleus,  m.pn.)  just  after  its  entrance. 

D,  Ovum  showing  polar  body  (p.b.)  and  male  (m.pn.)  and  female  (f.pn.)  pronuclei. 

E,  Ovum  showing  both  polar  bodies  (p.b.}  and  pronuclei. 

F,  Ovum  showing  pronuclei  preparing  to  unite. 

The  maturation  of  the  mouse  ovum,  described  by  Mark  and  Long,  may 
be  taken  as  an  example  of  mammalian  maturation.  The  diploid  number  of 
chromosomes  is  twenty,  but  when  the  growth  of  the  primary  oocyte  is 
completed  and  the  cell  prepares  for  division  only  ten  chromosomes  are 
present.  Each  chromosome  is  V-shaped  and  shows  the  structure  of  a  tetrad. 
While  still  in  the  Graafian  follicle  the  first  polar  body  is  given  off  and  lies 
as  a  small  globule  beneath  the  zona  pellucida.  The  egg  cell  and  the  first 


MATURATION.  19 

polar  body  constitute  secondary  oocytes,  comparable  with  the  secondary 
spermatocytes  of  the  male.  The  egg  now  leaves  the  ovary  and  reaches  the 
oviduct.  If  a  sperm  enters  the  ovum,  another  spindle  forms  and  a  second 
polar  body  is  given  off.  The  nucleus  of  the  mature  ovum  or  female  pronu- 
cleus,  with  the  haploid  number  of  chromosomes,  is  now  ready  for  union 
with  the  male  pronucleus.  (See  Fig.  1 1 .) 

Comparing  maturation  in  the  male  and  female  sex  cells,  it  is  to  be  noted 
that  the  spermatogonia  and  oogonia  proliferate  by  ordinary  mitosis,  main- 
taining the  somatic  or  diploid  number  of  chromosomes  up  to  a  certain  period 
in  their  life  history.  They  then  enter  upon  a  period  of  growth  in  size,  result- 
ing in  primary  spermatocytes  and  primary  oocytes.  When  these  prepare 
for  division  the  nuclear  reticulum  in  each  case  resolves  itself  into  the  haploid 
number  of  chromosomes.  During  division  this  reduced  number  is  given 
to  each  resulting  secondary  spermatocyte  or  oocyte. 

There  is,  however,  this  marked  peculiarity  about  the  division  of  the 
primary  oocyte,  that  while  the  division  of  the  nuclear  material  is  equal  the 
division  of  the  cytoplasm  is  very  unequal,  most  of  the  latter  remaining  in  one 
cell,  the  secondary  oocyte  proper.  The  other  cell,  very  small  owing  to  its 
lack  of  cytoplasm,  is  extruded  from  the  oocyte  proper  as  the  first  polar  body. 
The  same  condition  obtains  in  the  next  division.  One  cell,  the  mature  ovum, 
retains  most  of  the  cytoplasm,  the  other  being  detached  as  the  second  polar 
body.  In  some  cases  the  first  polar  body  also  divides.  Thus  the  primary 
oocyte  gives  rise  to  three  or  four  cells,  each  of  which  has  the  reduced  number 
of  chromosomes.  One  of  them  becomes  the  mature  ovum,  the  others  are 
cast  off  as  apparently  useless  cells  and  eventually  disappear.  The  primary 
spermatocyte,  on  the  other  hand,  gives  rise  to  four  functioning  cells  which 
are  equal  in  cytoplasmic  content.  (See  Fig.  12.) 

The  apparent  difference  between  maturation  of  the  male  and  female  sex 
cells — the  single  functional  cell  in  the  female  as  contrasted  with  four  in  the 
male — loses  some  of  its  character  when  one  notes  that  in  some  forms  the 
polar  bodies  are  not  so  rudimentary  as  is  generally  the  case.  Thus  in  certain 
forms  one  or  more  of  the  polar  bodies  may  develop  into  cells  very  similar  to 
the  mature  egg  cell,  may  be  penetrated  by  spermatozoa,  and  may  even  be 
fertilized  and  proceed  a  short  distance  in  segmentation.  There  is  perhaps 
warrant  for  considering  the  polar  bodies  as  rudimentary  or  abortive  ova. 

The  time  of  formation  of  the  polar  bodies  varies  in  different  animals. 
In  a  few  (echinoderms)  they  are  formed  before  the  sperm  enters  the  egg. 
In  Ascaris  they  are  both  formed  after  the  entrance  of  the  sperm.  In  other 
forms,  like  the  mouse,  the  first  polar  body  is  formed  while  the  egg  is  still  in 
the  Graafian  follicle,  the  second  one  after  the  entrance  of  the  sperm.  The 
only  recorded  observations  on  maturation  of  the  human  ovum  are  those  of 


20 


TEXT-BOOK  OF  EMBRYOLOGY. 


Thomson's.  In  an  extensive  series  of  ovaries  he  has  observed  both  polar 
bodies  and  the  spindles  preceding  extrusion.  Both  maturation  divisions 
occur  before  the  Graafian  follicle  ruptures  and  discharges  the  ovum,  the 
time  of  formation  of  the  second  polar  body  therefore  differing  from  that  in 
other  mammals. 

From  the  data  in  the  above  description  it  is  evident  that  the  phenomena 
of  maturation  are  essentially  similar  in  the  male  and  female  sex  cells.  In 
the  female  two  or  three  of  the  cells  are  indeed  abortive,  probably  in  order  to 
insure  a  large  amount  of  food  material  to  the  functioning  ovum;  but  the 
result,  the  reduction  of  the  number  of  chromosomes  in  the  mature  sex  cell 


Oogonia 


Primary 
oocyte 


Secondary 
oocyte 


Spermatogonia 


Proliferation 


Primary 
spermatocyte 


Growth 

Secondary 
spermatoeyte 

Spermatid 
Maturation 
Spermatozoon 


j 


[if! 


Prolifera- 
tion 


Growth 


Maturation 


Trans- 
formation 


FIG.  12. — Diagram  representing  the  histogenesis  of  (a)  the  female  sex  cells  and  (6)  the  male  sex 

cells.     Modified  from  Boveri. 

to  one-half  the  number  characteristic  of  other  cells  of  the  species,  is  always 
the  same. 

Significance  of  Mitosis  and  Maturation. 

The  earlier  investigators  regarded  maturation  merely  as  a  means  of  re- 
ducing the  number  of  chromosomes  in  the  mature  germ  cells,  so  as  to  prevent 
a  doubling  of  chromatin  material  at  the  subsequent  fertilization.  This, 
however,  seems  to  be  but  a  minor  object  of  maturation.  As  a  matter  of 
fact,  the  reduction  of  the  chromatin  mass  is  not  one-half  but  three-quarters 
and  even  more.  It  is  also  well  known  that  the  chromatin  mass  increases  or 
diminishes  under  certain  conditions  during  the  life  history  of  a  cell. 

The  chief  significance  of  maturation  is  to  be  considered  rather  from  the 
standpoint  of  heredity.  Modern  biologists  are  convinced  that  the  chromatin 
particles  constitute  the  inheritance  substance  of  the  cell.  During  mitosis 


MATURATION.  21 

the  chromatin  granules  arrange  themselves  in  a  continuous  thread,  the 
spireme,  which  differs  qualitatively  in  different  regions.  The  chromosomes, 
which  are  only  segments  of  the  spireme,  likewise  differ  from  end  to  end.  In 
ordinary  mitosis  these  chromosomes  split  longitudinally,  half  of  each  chromo- 
some going  to  each  of  the  resulting  daughter  cells.  This  is  an  equational 
division  in  which  the  chromatin  material  is  exactly  halved. 

In  maturation,  however,  a  synapsis  of  the  chromosomes  takes  place,  the 
latter  fusing  in  pairs.  The  chromosomes  of  each  pair  are  probably  separated 
again  in  one  of  the  subsequent  maturation  divisions,  the  reduction  division. 
If  the  chromosomes  are  qualitatively  different,  then  the  mature  germ  cells 
resulting  from  this  division  will  be  of  two  different  kinds,  varying  more  or 
less  in  their  content  of  hereditary  factors.  Experimental  evidence  confirms 
this  interpretation  of  maturation. 

There  is  another  interesting  point  to  be  considered.  The  recent  work  of 
cytologists  leads  to  the  assumption  that  the  fusion  of  chromosomes  during 
synapsis  is  not  a  matter  of  chance,  but  takes  place  in  a  definite  manner. 
The  chromosomes  in  the  primordial  germ  cells  seem  to  form  a  series  of  homol- 
ogous pairs  the  members  of  which  fuse  during  synapsis.  The  individual 
pairs  can  often  be  distinguished  from  other  pairs  by  differences  in  shape  01 
size.  There  is  much  evidence  to  support  the  belief  that  each  pair  consists  oi 
one  paternal  and  one  maternal  chromosome,  which  had  been  brought  to- 
gether at  the  antecedent  fertilization.  This  seems  to  indicate  also  that  the 
chromosomes  retain  their  identity  even  when  resolved  into  the  chromatic 
reticulum  of  the  resting  nucleus.  The  reduction  division  will  separate  the 
fused  chromosomes,  and  the  resulting  mature  germ  cells  will  be  either  paternal 
or  maternal  in  their  chromatic  constitution.  The  maturation  processes  there- 
fore produce  a  segregation  of  the  paternal  and  maternal  chromosomes. 

The  cytological  data  described  above,  which  support  and  in  turn  are 
supported  by  a  great  mass  of  experimental  evidence,  illustrate  Mendel's  law 
of  segregation.  This  law  is  that  the  units  contributed  by  two  parents  sepa- 
rate in  the  germ  cells  without  having  had  any  influence  upon  each  other. 
For  instance,  when  a  mouse  with  gray  coat  color  is  mated  with  a  mouse  with 
black  coat  color,  one  parent  contributes  a  unit  for  gray  and  the  other  a  unit 
for  black.  These  units  will  separate  during  the  maturation  of  the  germ 
cells,  and  the  resulting  spermatozoa  and  ova  will  again  recover  the  pure 
paternal  or  maternal  units. 

Sex  Determination. 

In  the  great  bulk  of  cytological  and  experimental  studies  of  recent  years 
there  is  abundant  evidence  for  the  belief  that  certain  chromosomes  play  an 
important  part  in  the  determination  of  sex.  In  the  grasshopper  (Steno- 


22 


TEXT-BOOK  OF  EMBRYOLOGY. 


bothrus  viridulus)  the  somatic  number  of  chromosomes  in  the  male  is  seven- 
teen and  in  the  female  eighteen.  Owing  to  the  odd  number  there  is  an 
unusual  complication  in  the  maturation  of  the  male  germ  cell.  When 
synapsis  occurs  eight  pairs  of  chromosomes  are  formed  but  the  odd  chromo- 
some, which  can  usually  be  distinguished  by  its  appearance,  is  left  without  a 
mate  (Fig.  13,  4).  At  the  first  maturation  division  this  univalent  chromo- 


FIG.  13. — Stages  in  the  spermatogenesis  of  a  grasshopper  (Stenobothrus  viridulus).  Meek,  i, 
Spermatogonium  in  process  of  division,  having  17  chromosomes  (8  pairs  and  one  odd). 
2,  Representing  growth  period  of  spermatogonium.  3-6,  Division  of  the  primary  sperma- 
tocytes — sixteen  of  the  chromosomes  are  paired  while  the  "accessory"  has  no  mate  and 
passes  as  a  whole  to  one  of  the  two  secondary  spermatocytes.  7-8,  Division  of  the  second- 
ary spermatocyte  with  the  odd  chromosome,  the  latter  splitting  and  giving  one-half  to 
each  resulting  spermatid.  x,  "Accessory"  chromosome. 

some  does  not  divide  but  passes  as  a  whole  to  one  of  the  resulting  cells,  thus 
giving  two  kinds  of  secondary  spermatocytes  (Fig.  13,  5).  When  the 
secondary  spermatocytes  divide,  however,  the  odd  chromosome  in  one  of 


MATURATION.  23 

them  also  divides  like  the  other  chromosomes,  each  of  the  resulting  sperma- 
tids  receiving  one-half  (Fig.  13,  #).  Thus  two  kinds  of  sperms  are  formed 
in  equal  numbers,  containing  respectively  eight  and  nine  chromosomes.  The 
odd  chromosome  is  also  known  as  the  accessory  or  X-chromosome. 

In  the  ovum  no  such  complication  arises,  there  being  two  accessory 
chromosomes  which  unite  in  synapsis.  All  the  mature  ova  will  therefore 
contain  nine  chromosomes.  As  a  result,  there  are  two  combinations  possible 
when  the  male  and  female  sex  cells  unite:  an  ovum  may  be  fertilized  by  a 
sperm  containing  either  eight  or  nine  chromosomes.  In  the  first  case  the 
somatic  number  in  the  fertilized  egg  will  be  seventeen  and,  the  egg  will  develop 
into  a  male.  In  the  second  case  the  somatic  number  will  be  eighteen  and  the 
resulting  individual  will  be  a  female.  In  the  example  given,  therefore,  the 
presence  or  absence  of  the  accessory  or  odd  chromosome  will  determine 
the  sex. 

The  presence  of  accessory  chromosomes  has  been  demonstrated  in  many 
invertebrates,  especially  insects.  They  have  also  been  described  in  several 
vertebrates  such  as  the  rat,  fowl,  guinea-pig,  and  even  man.  In  many  cases 
the  accessory  chromosome  of  the  male  germ  cell  has  a  mate  which  differs, 
however,  in  some  way  (size,  appearance,  etc.)  and  is  designated  the  Y- 
chromosome.  An  ovum  fertilized  by  a  spermatozoon  containing  the  Y- 
chromosome  will  give  rise  to  a  male;  if  fertilized  by  one  containing  the 
X-chromosome  the  egg  will  develop  into  a  female. 

There  are  many  cases,  particularly  among  parthenogenetic  forms,  where 
sex  cycles  arise,  which  cannot  be  explained  by  chromosomal  behavior.  In 
these  cases  nutrition  seems  to  play  an  important  part  in  determining  the 
:  sex  of  the  individual.  But  as  to  the  great  majority  of  forms  investigated,  the 
weight  of  evidence  supports  the  view  that  the  chromosomes  are  the  chief 
agents  in  sex  determination. 

Ovulation. 

Ovulation  is  the  discharge  of  the  ovum  from  the  ovary,  whether  in  the 
human  female  or  any  of  the  lower  animals.  Our  attention  will  here  be  con- 
fined to  the  phenomenon  as  it  occurs  in  mammals. 

Before  the  ovum  escapes  from  the  ovary  it  is  contained  in  a  structure 
known  as  the  Graafian  follicle,  which  consists  of  a  wall  of  epithelium,  the 
granular  layer,  enclosing  a  space  filled  with  a  viscid  fluid,  the  follicular  fluid. 
Surrounding  the  follicle  is  a  special  layer  of  connective  tissue,  the  theca  fol- 
liculi,  which  is  a  part  of  the  ovarian  stroma  and  contains  many  small  blood 
vessels.  The  egg  cell  is  situated  within  a  thickened  portion  of  the  epithelial 
wall,  the  germ  hill.  The  growth  of  the  follicle  itself  will  be  described  in  the 
chapter  on  the  geni to-urinary  system. 


24  TEXT-BOOK  OF  EMBRYOLOGY. 

When  the  Graafian  follicle  is  mature,  having  reached  its  maximum  size, 
it  produces  a  bulge  on  the  ovary;  and  there  is  only  a  thin  membrane,  com- 
posed of  the  granular  layer,  the  theca  and  the  germinal  epithelium  of  the 
ovary,  between  the  follicular  cavity  and  the  exterior  of  the  ovary  (Fig.  14). 
At  a  certain  time  this  membrane  breaks  and  the  follicular  fluid  gushes  out, 
carrying  with  it  the  ovum  and  some  of  the  cells  of  the  germ  hill.  The  ovum 
is  then  free  in  the  abdominal  cavity  whence  normally  it  passes  into  the 
open  end  of  the  oviduct,  or  Fallopian  tube.  The  cause  of  the  rupture  of  the 
follicle  has  not  been  ascertained;  but  there  are  certain  facts  which  throw  light 
upon  it.  In  the  dog  ovulation  occurs  during  oestrus,  or  the  period  of  "heat," 
independently  of  approach  of  the  male.  In  the  mouse,  the  rat  and  the 


Germinal 

epithelium 


Germ  hill  Theca  foUicui£ 

with  ovum        (vascular  layer) 


Theca  folliculi  (fibrous  layer) 
Stratum  granulosum 


FIG.  14. — From  section  of  human  ovary,  showing  mature  Graafian  follicle  ready  to  rupture. 

Kollmann's  Atlas. 

guinea-pig  ovulation  also  occurs  spontaneously  during  oestrus.  In  the 
rabbit  ovulation  occurs  about  ten  hours  after  coitus,  and  it  has  been  shown 
experimentally  that  the  follicle  does  not  rupture  after  any  stimulus  except 
coitus.  The  sheep  ovulates  spontaneously  during  the  earlier  "heat "periods 
of  the  breeding  season,  but  in  the  later  periods  coitus  seems  necessary  to 
bring  about  the  rupture  of  the  follicle.  In  the  bat,  however,  there  are  pecu- 
liar circumstances:  Copulation  takes  place  in  the  autumn,  the  spermatozoa 
remaining  alive  in  the  uterus  until  the  following  spring,  and  then  ovulation 
occurs  apparently  in  response  to  seasonal  temperature  changes  without  even 
a  "heat"  period.  These  are  only  a  few  instances  out  of  a  great  number  of 


MATURATION.  25 

observations,  but  they  show  that  in  general  ovulation  occurs  during  the 
oestrus  or  period  of  "heat"  in  the  female,  sometimes  coincident  with  copu- 
lation. Just  prior  to  the  oestrus  period  there  is  a  marked  increase  of  blood 
flow  to  the  generative  organs,  during  a  pro-cestrual  period  or  pro-cestrus. 
During  oestrus  the  increased  blood  flow  is  maintained  and  may  be  accen- 
tuated at  the  approach  of  the  male,  and  it  has  been  suggested  that  an  in- 
crease in  blood  pressure  in  the  ovary  is  at  least  one  of  the  factors  in  causing 
the  rupture  of  the  Graafian  follicle.  Another  contributing  factor  may  be 
an  increase  in  the  quantity  of  fluid  within  the  follicle  thereby  increasing 
the  intrafollicular  pressure. 

In  monkeys  there  is  a  slight  menstrual  flow  which  may  occur  periodically 
the  year  round,  but  there  seems  to  be  a  limited  season  for  ovulation  and  con- 
ception. Menstruation  and  ovulation  therefore  do  not  necessarily  coincide. 
In  the  human  the  menstrual  flow  is  a  pronounced  feature  during  the  years  of 
reproductive  activity  of  the  female,  recurring  at  average  intervals  of  28  days 
except  during  pregnancy  and  usually  during  lactation.  It  is  generally  ad- 
mitted that  the  time  of  menstrual  flow  corresponds  to  the  pro-cestrual  period 
of  the  lower  mammals,  that  is,  the  period  immediately  preceding  the  oestrus 
or  rutting  time.  It  would  be  expected  that  in  the  human  female  the  period 
of  sexual  desire  would  follow  menstruation.  It  seems,  however,  that  condi- 
tions of  modern  society  have  disturbed  the  natural  cycle  of  physiological 
activities,  although  there  is  reason  to  believe  that  in  primitive  man  there  was 
at  least  an  approximation  to  conditions  in  the  lower  mammals.  In  highly 
civilized  man  there  appears  to  be  no  particular  period  of  sexual  desire,  and 
there  is  considerable  evidence  that  ovulatiqn  is  not  always  associated  with 
menstruation  but  may  occur  at  any  time  during  the  intermenstrual  period. 
With  the  disappearance  of  a  fixed  oestrus  in  the  human  female  the  definite 
relation  between  ovulation  and  the  oestrus  has  broken  down,  although  bio- 
logically the  most  favorable  condition  for  conception  is  ensemination  just 
after  the  menstrual  flow. 

Earlier  in  this  chapter  it  was  stated  that  the  number  of  ova  in  the  two 
ovaries  approximated  70,000.  Allowing  one  ovum  to  each  ovulation,  not 
more  than  about  400  of  these  attain  maturity  during  the  years  of  a  woman's 
reproductive  activity,  the  others  along  with  their  follicles  probably  degener- 
ating within  the  ovaries.  The  general  concensus  of  opinion  is  that  in  the  great 
majority  of  cases  only  one  ovum  escapes  at  ovulation  either  from  one  ovary 
or  the  other.  One  possible  exception  to  this  occurs  in  the  case  of  twin  off- 
spring where  the  twins  are  not  identical.  There  is  good  evidence  that  iden- 
tical twins  arise  from  a  single  ovum,  and  it  is  not  impossible  even  that  ordinary 
twins  develop  from  the  same  ovum. 


26  TEXT-BOOK  OF  EMBRYOLOGY. 

References  for  Further  Study. 

BUCHNER,  P.:  Praktikum  der  Zellenlehre.    Teil  I.     1915. 

CONKLIN,  E.  G.:  Heredity  and  Environment  in  the  Development  of  Men.  3d  Ed., 
1920. 

CRAGIN,  E.  B.:  Text-book  of  Obstetrics.     1915. 

HERTWIG,  R.:  Eireife  und  Befruchtung.  In  Hertwig's  Handbuch  der  vergleichenden 
und  experimentellen  Entwickelungslehre  der  Wirbeltiere.  Bd.  I,  Teil  I,  Kap.  II,  1903. 
Contains  extensive  bibliography. 

KELLICOTT,  W.  E.:  Text-book  of  General  Embryology.     Chap.  IV,  1913. 

MARSHALL,  F.  H.  A.:  The  Physiology  of  Reproduction.     1910. 

MORGAN,  T.  H.:  Heredity  and  Sex.     1913. 

MORGAN,  T.  H.:  The  Physical  Basis  of  Heredity.     1919. 

THOMSON,  A.:  The  Maturation  of  the  Human  Ovum.  Journal  of  Anatomy,  Vol.  53, 
1919. 

WIEMAN,  H.  L.:  The  Chromosomes  of  Human  Spermatocytes.  American  Journal 
of  Anatomy,  Vol.  21,  1917. 

WILSON,  E.  B.:  The  Cell  in  Development  and  Inheritance.     1900. 


CHAPTER  III. 
FERTILIZATION. 

When  the  complex  maturation  processes  described  in  the  preceding 
chapter  are  completed,  the  spermatozoon  is  ready  for  union  with  the  mature 
ovum.  This  union,  which  forms  the  starting  point  of  a  new  individual  in  all 
sexual  reproduction,  is  known  as  fertilization,  and  the  resulting  cell  is  the 
fertilized  ovum,  or  zygote. 

The  details  of  the  process  vary  in  different  animals.  Its  essence  is  the 
entrance  of  the  spermatozoon  into  the  ovum  and  the  union  of  the  nucleus  of 
the  spermatozoon  with  the  nucleus  of  the  ovum.  At  the  time  of  its  entrance 
into  the  egg,  the  sperm  head  is  small  and  its  chromatin  extremely  condensed. 
Soon  after  entering  the  ovum,  however,  the  sperm  head  undergoes  develop- 
ment into  a  typical  nucleus,  the  male  pronucleus.  This  male  pronucleus  is 
to  all  appearances  exactly  similar  in  structure  to  the  nucleus  of  the  egg  which 
latter  is  now  known  as  the  female  pronucleus.  The  chromatin  networks  in 
both  pronuclei  next  pass  into  the  spireme  stage,  the  spiremes  segmenting 
into  chromosomes  of  which  each  pronucleus  contains  one-half  the  somatic 
number.  The  nuclear  membranes  meanwhile  disappear  and  the  chromo- 
somes lie  free  in  the  cytoplasm.  During  these  changes  in  the  pronuclei,  the 
amphiaster  has  formed  and  the  male  and  the  female  chromosomes  mingle  in 
its  equatorial  plane.  At  this  stage  no  actual  differentiation  can  be  made 
between  male  chromosomes  and  female  chromosomes,  the  differentiation 
shown  in  Fig.  15  being  schematic.  The  picture  is  now  that  of  the  end  of  the 
prophase  of  ordinary  mitosis,  the  somatic  number  of  chromsomes  being 
arranged  in  a  plane  midway  between  the  two  centrosomes.  With  the  ming- 
ling of  male  and  female  chromosomes  fertilization  proper  comes  to  an  end. 
The  further  steps  are  also  identical  with  those  of  ordinary  mitosis.  Each 
chromosome  splits  longitudinally  into  two  exactly  similar  parts,  one  of  which 
is  contributed  to  each  daughter  nucleus,  and  the  cell  body  divides  into  two 
equal  parts.  There  thus  result  from  the  first  division  of  the  fertilized  ovum, 
two  cells  which  are  apparently  exactly  alike  and  each  of  which  contains 
exactly  the  same  amount  of  male  and  of  female  chromosome  elements. 

The  amphiaster  of  the  fertilized  ovum  appears  to  develop  as  in  ordinary 
mitosis.  As  to  the  origin  of  the  centrosomes,  however,  much  uncertainty 
still  exists.  The  middle  piece  of  the  spermatozoon  always  enters  the  ovum 
with  the  head.  It  has  already  been  shown  that  one  or  two  spermatid  centro- 

27 


28 


TEXT-BOOK  OF  EMBRYOLOGY. 


somes  take  part  in  the  formation  of  the  middle  piece.  Male  centrosome 
elements  are  therefore  undoubtedly  carried  into  the  ovum  in  the  middle 
piece.  It  is  equally  well  known,  for  some  forms  at  least,  that  the  centrosome 
of  the  ovum  disappears  just  after  the  extrusion  of  the  second  polar  body.  In 
a  considerable  number  of  forms  the  development  of  the  egg  centrosome  from, 


Female 
x^  pronucleus 


Head  of 
—spermatozoon 
with  centrosome 


Female  pronucleus 


Male  pronucleus 


•gsr Centrosome 


Male  pronucleus 
Female  pronucleus 


Chromosomes  of 
female  pronucleus 


Chromosomes  of 
male  pronucleus 


Centrosome 


Chromosome  from 
female  pronucleus 


„  Chromosome  from 
male  pronucleus 


— -  Centrosome 


FIG.  15. — Diagram  of  fertilization  of  the  ovum.     (The  somatic  number  of  chromosomes  is  4.) 

Boveri,  Bohm  and  von  Damdoff. 

or  in  close  relation  to  the  middle  piece  of  the  spermatozoon  has  been  observed. 
The  details  of  fertilization  as  it  occurs  in  the  sea-urchin  have  been  carefully 
described  by  Wilson.  In  cases  of  this  type  (Fig.  16)  the  tail  of  the  spermato- 
zoon remains  outside  the  egg  while  the  head  and  middle  piece,  almost  imme- 


FERTILIZATION. 


29 


diately  after  entering,  turn  completely  around  so  that  the  head  points  away 
from  the  female  pronucleus.  An  aster  with  its  centrosomes  next  appears, 
developing  from,  or  in  very  close  relation  to  the  middle  piece.  The  aster  and 
sperm  nucleus  now  approach  the  female  pronucleus,  the  aster  leading  and  its 
rays  rapidly  extending.  On  or  before  reaching  the  female  pronucleus  the 


a 


K 


•^mm+-^: 

FIG.  1 6. — Fertilization  of  the  eggs  of  the  star-fish  and  sea-urchin. 

A,  B,  C,  entrance  of  the  sperm  into  the  cytoplasm  (star-fish).  D,  mature  spermatozoon  of  the 
sea-urchin;  E-H,  successive  stages  in  the  penetration  of  the  sperm  nucleus  (c?AO  and  cen- 
trosome  (cf"C)  into  the  cytoplasm;  I-L,  stages  ;n  the  approach  of  the  sperm  nucleus  (c?N) 
to  the  egg  nucleus  (9./V),  the  division  of  the  sperm  centrosome  (cfO)  and  the  first 
cleavage  spindle.  Fol,  Wilson,  from  Conklin  Heredity  and  Environment. 

aster  divides  into  two  daughter  asters  which  separate  with  the  formation  of 
the  usual  central  spindle,  while  the  two  pronuclei  unite  in  the  equatorial 


30  TEXT-BOOK  OF  EMBRYOLOGY. 

plane  and  give  rise  to  the  chromosomes  of  the  cleavage  nucleus.  In  the  sea- 
urchin  the  polar  bodies  are  extruded  before  the  entrance  of  the  spermato- 
zoon. In  cases  where  the  polar  bodies  are  not  extruded  until  after  the 
entrance  of  the  spermatozoon  the  amphiaster  forms  while  waiting  for  their 
extrusion,  the  nuclei  joining  subsequently.  When  the  sperm  head  finds  the 
polar  bodies  already  extruded,  union  of  the  two  pronuclei  may  take  place  first, 
followed  by  division  of  the  centrosomes  and  the  formation  of  the  amphiaster. 

The  coming  together  of  ovum  and  spermatozoon  is  apparently  determined 
in  some  cases  by  a  definite  attraction  on  the  part  of  the  ovum  toward  the 
spermatozoon.  This  attraction  seems  to  be  of  a  chemical  nature,  but  is 
often  not  limited  to  the  attraction  of  spermatozoa  of  the  same  species. 
Foreign  spermatozoa  will  be  attracted  and  will  enter  the  ovum  if  they  are 
physically  able  to  do  so.  The  entrance  of  these  spermatozoa  may  even 
start  the  process  of  cleavage,  though  such  cleavage  is  usually  abnormal  and 
does  not  progress  very  far.  That  this  attraction  is  not  dependent  upon 
the  integrity  of  the  ovum  as  an  organism  is  shown  by  the  fact  that  small 
pieces  of  egg  cytoplasm  free  from  nuclear  elements  exert  the  same  attractive 
force,  so  that  spermatozoa  are  not  only  attracted  to  them,  but  will  actually 
enter  them.  In  other  cases  the  stimulus  for  fertilization  is  obviously  one  of 
contact.  The  spermatozoa  of  some  fishes  will  swim  around  at  random  until 
they  touch  any  object  when  they  become  attached  and  are  unable  to  escape. 
Fertilization  in  these  cases  is  therefore  a  matter  of  chance  favored  by  the 
enormous  number  of  sperms  produced,  and  by  the  special  breeding  habits 
which  insure  a  close  proximity  of  sperms  and  eggs. 

Of  eggs  which  are  enclosed  by  a  distinct  membrane,  the  vitelline  mem- 
brane, some  (e.g.,  those  of  amphibians  and  of  mammals)  are  permeable  to 
the  spermatozoon  at  all  points;  others  have  a  definite  point  at  which  the 
spermatozoon  must  enter,  this  being  of  the  nature  of  a  channel  through  the 
membrane — the  micropyle.  In  some  instances  a  little  cone-shaped  pro- 
jection from  the  surface  of  the  egg,  the  attraction  cone,  either  precedes  or 
immediately  follows  the  attachment  of  the  spermatozoon  to  the  egg  (Fig. 
15).  Instead  of  a  projection  there  may  be  a  depression  at  the  point  of 
entrance. 

There  seems  to  be  no  question  that  but  one  spermatozoon  has  to  do  with 
the  fertilization  of  a  particular  ovum.  In  mammals  only  one  spermatozoon 
normally  pierces  the  vitelline  membrane  although  several  may  penetrate 
the  zona  pellucida  to  the  perivitelline  space.  Should  more  than  one  sper- 
matozoon enter  such  an  egg — as,  for  example,  in  pathological  polyspermy — 
the  result  is  an  irregular  formation  of  asters  and  polyasters  (Fig.  17),  and 
the  early  death  of  the  egg  either  before  or  soon  after  a  few  attempts  at 
cleavage.  In  some  insects,  and  in  selachians,  reptiles  and  birds,  a  number  of 


FERTILIZATION. 


31 


spermatozoa  normally  enter  an  ovum,  but  only  one  goes  on  to  form  a  male 
pronucleus. 

The  ovum  thus  not  only  exerts  an  attractive  influence  toward  spermato- 
zoa, but  it  apparently  exerts  this  influence  only  until  the  one  requisite  to  its 
fertilization  has  entered,  after  which  it  appears  able  to  protect  itself  against 
the  further  entrance  of  male  elements.  As  to  the  means  by  which  this  is 
accomplished  little  is  known,  although  several  theories  have  been  advanced. 
It  may  be  that  when  the  single  spermatozoon  necessary  to  accomplish 
fertilization  has  entered  the  ovum,  it  sets  up  within  the  ovum  such  changes 
as  to  destroy  the  attractive  powers  of  the  ovum  toward  other  spermatozoa,  or 
as  even  to  prevent  their  entrance.  In  the  case  of  eggs  where  the  spermato- 
zoon enters  through  a  micropyle,  it  has  been  suggested  that  the  tail  of  the 


FIG.  17. — Polyspermy  in  sea-urchin  eggs  treated  with  0.005  per  cent,  nicotine  solution.     O.  and  R. 

Hertwig,  Wilson. 

B,  Showing  ten  sperm  nuclei,  three  of  which  have  conjugated  with  female  pronucleus.    C,  Later 
stage  showing  polyasters  formed  by  union  of  sperm  amphiasters. 

first  spermatozoon  remaining  in  the  opening  might  effectually  block  the 
entrance  to  other  spermatozoa;  or  the  passage  of  the  first  spermatozoon 
might  set  up  such  mechanical  or  chemical  changes  in  the  canal  as  would 
prevent  further  access.  In  most  cases  of  eggs  which  have  no  vitelline  mem- 
brane previous  to  fertilization,  such  a  membrane  is  formed  immediately  after 
the  entrance  of  the  first  spermatozoon,  a  natural  inference  being  that  this 
membrane  may  prevent  the  entrance  of  any  more  spermatozoa.  Biologists, 
however,  are  inclined  to  discredit  the  view  that  the  fertilization  membrane  is 
a  protection  against  polyspermy. 

The  time  and  place  of  fertilization  are  matters  of  scientific  interest  and 
practical  importance.  In  the  lower  vertebrates,  fishes  and  amphibians,  the 
female  discharges  the  ova  into  the  water  at  the  breeding  season  and  the  male 
likewise  discharges  the  spermatozoa.  The  sperms  swim  about  and  come  in 
contact  with  and  penetrate  the  ova  shortly  after  they  are  discharged.  If 
fertilization  does  not  occur  both  kinds  of  germ  cells  soon  begin  to  disinte- 


32  TEXT-BOOK  OF  EMBRYOLOGY. 

grate,  neither  kind  remaining  alive  as  a  rule  for  more  than  a  few  hours. 
Among  these  animals  the  medium  in  which  fertilization  occurs  is  necessarily 
water,  and  since  it  takes  place  outside  of  the  animal  body  it  is  called  external 
fertilization. 

In  reptiles,  birds  and  mammals  the  spermatozoa  enter  the  genital  tract 
of  the  female  and  there  come  in  contact  with  and  enter  the  ova.  This  is 
internal  fertilization,  but  the  medium  in  which  it  occurs  is  fluid — the  secre- 
tions of  the  female  genital  tract.  A  fluid  medium  is  essential  because  the 
progress  of  the  sperm  depends  upon  its  flagellate  activity.  In  reptiles  and 
birds  the  spermatozoa  move  through  the  genital  passages  to  the  ovarian 
portion  of  the  oviduct  where  they  enter  the  ova  before  the  secondary  egg- 
membranes,  the  albumen  and  the  shell,  are  deposited.  After  fertilization 
development  begins  at  once  and,  in  birds  at  least,  continues  until  the  egg  is 
laid  and  exposed  to  the  lower  external  temperature.  If  it  has  been  fertil- 
ized, the  egg  at  the  breakfast  table  has  undergone  a  considerabled  degree  of 
development,  the  small  white  disk  on  the  surface  of  the  yolk  attesting  this 
phenomenon. 

In  mammals  the  bulk  of  evidence  shows  that  fertilization  occurs  as  a  rule 
in  the  upper  third  of  the  oviduct,  that  is,  the  third  nearest  the  ovary,  the 
spermatozoa  having  advanced  from  the  vagina  through  the  uterus  and  lower 
portion  of  the  oviduct  against  the  current  created  by  the  action  of  the  cilia 
on  the  epithelial  lining  of  these  structures.  Development  begins  at  once 
and  while  it  is  in  progress  the  ovum  (as  it  is  still  named  even  after  develop- 
ment has  set  in)  is  carried  down  the  oviduct  and  into  the  uterus  where  it 
becomes  attached  to  or  embedded  in  the  mucous  membrane  and  continues 
its  transformation  into  an  embryo.  In  the  human  also  fertilization  probably 
takes  place  in  the  great  majority  of  cases  in  the  upper  (outer)  third  of  the 
oviduct  (Fallopian  tube) .  The  time  required  by  the  spermatozoa  to  reach 
this  region  after  insemination  has  not  been  determined  with  accuracy.  It  is 
supposed  that  they  advance  into  the  oviducts  within  a  few  hours  after 
insemination.  If  ovulation  has  occurred  prior  to  this  and  a  mature  ovum  is 
moving  through  either  oviduct,  fertilization  may  take  place  soon  after 
cohabitation. 

That  fertilization  in  the  human  may  and  sometimes  does  occur  elsewhere 
than  in  the  upper  third  of  the  oviduct  is  attested  by  the  position  of  the  grow- 
ing embryo.  Occasionally  an  embryo  develops  in  the  abdominal  cavity, 
which  probably  shows  that  spermatozoa  have  passed  all  the  way  through 
either  oviduct.  In  rarer  instances  development  of  the  ovum  sets  in  on  the 
surface  of  the  ovary  or  even  within  a  Graafian  follicle.  It  has  been  stated 
that  fertilization  may  occur  in  the  uterus,  but  there  is  little  evidence  to 
support  this  conclusion. 


FERTILIZATION.  33 

Significance  of  Fertilization. 

The  meaning  of  such  a  widely  occurring  phenomenon  as  fertilization  has 
been  interpreted  differently  by  different  scientists,  and  the  question  is  still 
far  from  definite  solution.  There  are  several  views  which  may  be  briefly 
mentioned. 

The  earlier  belief  that  fertilization  was  a  necessary  antecedent  to  cleavage 
of  the  ovum  has  been  destroyed  by  the  evidence  of  recent  years.  Loeb  and 
others  have  been  able  to  induce  artificial  parthenogenesis  in  forms  reproduc- 
ing normally  by  sexual  reproduction.  Thus  cleavage  has  been  started  by 
chemical  stimulation  in  the  eggs  of  many  molluscs,  echinoderms,  ccelenter- 
ates,  and  even  in  some  of  the  chordates  (teleosts  and  amphibians).  By 
fertilizing  pieces  of  egg  cytoplasm  containing  no  nuclear  material,  partheno- 
genesis of  the  sperm  has  likewise  been  induced.  While  cleavage  induced  in 
this  manner  progresses  only  a  short  way,  the  evidence  points  to  the  con- 
clusion that  fertilization  is  not  an  absolutely  necessary  factor  in  reproduction 
although  it  normally  occurs  in  the  great  majority  of  cases. 

Another  view  is  that  fertilization  rejuvenates  protoplasm.  According  to 
this  view  protoplasm  tends  gradually  to  pass  into  a  state  of  senility  in  which 
its  activity  is  diminished.  With  the  admixture  of  new  protoplasm  when 
fertilization  occurs  a  new  period  of  vigor  is  initiated.  The  life  cycles  of 
certain  Protozoa  are  brought  to  the  support  of  this  hypothesis.  In  these 
Protozoa  a  long  period  of  reproduction  by  a  series  of  cell  divisions  is  followed 
by  some  form  of  conjugation  in  which  two  individuals  come  together  and 
exchange  a  part  of  their  nuclear  material.  After  conjugation  protoplasmic 
activity  is  renewed  and  each  of  the  conjugants  starts  again  on  a  long  period 
of  reproduction.  It  is  probable  that  the  admixture  of  new  protoplasm  in 
fertilization  among  Metazoa  produces  a  similar  invigorating  effect. 

Another  interpretation  of  fertilization  is  that  this  process,  called  amphi- 
mixis in  this  connection,  is  important  as  a  source  of  variation.  Since  the 
chromatin  of  different  individuals  varies  more  or  less,  fertilization  will  pro- 
duce new  combinations  and  therefore  tend  to  the  production  of  new  forms. 
However,  there  is  very  little  evidence  that  forms  which  reproduce  sexually 
show  more  variations  than  those  reproducing  by  parthenogenesis. 

In  the  opinion  of  most  modern  investigators  the  union  of  the  two  germ 
cells,  one  from  each  parent,  may  result  in  rejuvenation  of  the  protoplasm,  it 
may  be  a  stimulus  to  reproduction,  a  controlling  factor  in  variation;  but 
probably  no  one  of  these  things  expresses  the  whole  significance  of  fertiliza- 
tion, nor  can  any  one  of  them  necessarily  be  ruled  out.  The  chief  interest 
of  the  process  at  the  present  time  is  centered  around  its  relation  to  the  phe- 
nomena of  heredity  and  is  intimately  associated  with  the  interpretation  of  the 


34  TEXT-BOOK  OF  EMBRYOLOGY. 

maturation  processes  of  the  germ  cells.  The  fact  of  heredity  is  the  resem- 
blance between  offspring  and  parents.  From  the  standpoint  of  fertilization 
in  its  relation  to  heredity  the  significant  point  is  that  the  offspring  may 
develop  qualities  that  were  the  individual  possessions  of  either  one  parent  or 
the  other.  The  chromatin,  regarded  as  the  heredity  material,  is  the  only 
substance  which  is  contributed  in  equal  or  approximately  equal  parts  by  the 
two  parents.  The  union  of  the  germ  cells  brings  the  chromatin  of  the  parents 
together  in  the  fertilized  ovum  or  zygote  which  develops  into  a  new  individual. 
Upon  these  facts  rests  the  possibility  that  the  offspring  may  inherit  equally 
from  both  parents. 

References  for  Further  Study. 

BUCHNER,  P.:  Praktikum  der  Zellenlehre.     Teil  I,  1915. 

CONKLIN,  E.  G.:  Heredity  and  Environment  in  the  Development  of  Men.  3d  Ed., 
1920. 

HERTWIG,  R.:  Befruchtung.  In  Hertwig's  Handbuch  der  vergleichenden  und  experi- 
mentellen  Entwickelungslehre  der  Wirbeltiere.  Bd.  I,  Teil  I,  Kap.  II,  1903.  Contains 
extensive  bibliography. 

KELLICOTT,  W.  E.:  Text-book  of  General  Embryology.     Chap.  V,  1913. 

LOEB,  J.:  Die  chemische  Entwickelungserregung  des  thierischen  Eies.     1909. 

MARSHALL,  F.  H.  A.:  The  Physiology  of  Reproduction.     1910. 

MINOT,  C.  S.:  The  Problem  of  Age,  Growth,  Death.     1907. 

MORGAN,  T.  H.:  Heredity  and  Sex.     1913. 

MORGAN,  T.  H.:  The  Physical  Basis  of  Heredity.     1919. 

WILSON,  E.  B.:  The  Cell  in  Development  and  Inheritance.     1900. 


CHAPTER  IV. 
EARLY  DEVELOPMENT  OF  AMPfflOXUS. 

Although  the  ova  of  Amphioxus  are  not  used  extensively  for  teaching 
purposes  in  the  laboratory,  a  study  of  the  early  developmental  stages  is  a 
valuable  aid  to  the  reasonable  comprehension  of  certain  embryological  facts. 
The  simplicity  of  these  first  steps,  whether  it  points  to  primitiveness  or  not, 
affords  a  view  of  certain  fundamental  principles  of  development  which  makes 
the  study  of  higher  vertebrate  forms  much  easier  and  renders  their  formative 
processes  much  more  intelligible.  This  simplicity  is  probably  correlated  with 
the  freedom  of  the  egg  from  a  large  amount  of  yolk;  and  it  will  be  seen  that 
many  of  the  modifications  of  the  processes  of  development  in  the  vertebrates 
seem  to  be  produced  by  the  greater  amount  of  yolk  in  their  ova. 

Cleavage. — The  ovum  of  Amphioxus  has  certain  peculiarities  which  are 
important  in  their  effect  upon  cleavage.  While  it  contains  only  a  small 


PV 


FIG.  1 8. — Diagram  of  a  median  sagittal  section  through  an  Amphioxus  ovum.       Cerfontaine, 

from  Kellicott. 
The  arrow  indicates  the  direction  of  the  polar  axis.     AD,  antero-dorsal  region;  PV,  postero- 

ventral  region;  N,  male  and  female  pronuclei;  p,  yolk-free  area;  S,  tail  of  sperm;  y,  yolk 

area;  II,  second  polar  body. 

quantity  of  yolk,  being  regarded  as  a  meiolecithal  ovum,  this  material  is 
situated  slightly  off  center  and  the  nucleus  lies  outside  of  the  yolk  (Fig.  18). 
This  condition  really  effects  a  polarity  of  the  cell.  The  first  polar  body  is 
given  off  from  the  yolk-free  portion  of  the  egg.  This  marks  the  animal  pole 
and  also  the  side  which  will  be  the  anterior  part  of  the  embryo.  The  sperm 
enters  the  egg  at  the  vegetative  pole  and  seems  to  stimulate  the  formation  of 

35 


36 


TEXT-BOOK  OF  EMBRYOLOGY. 


the  second  polar  body.  The  sperm  nucleus  and  centrosome  then  traverse 
the  yolk  area  to  meet  the  mature  egg  nucleus  which  in  the  meantime  has 
migrated  toward,  but  not  quite  to,  the  center  of  the  egg.  The  division  of  the 
^perrn  centrosome  to  form  a  disaster  and  the  arrangement  of  the  chromosomes 
of  the  two  pronuclei  in  the  equatorial  plane  comprise  the  preparatory  step 
for  the  first  cleavage.  These  phenomena  are  identical  with  the  prophase  of 
mitosis  (Fig.  19). 

The  position  that  the  spindle  assumes  is  determined  by  three  factors: 
the  point  where  the  first  polar  body  is  extruded,  the  point  where  the  sperm 

enters,  and  the  location  of  the  yolk-free 
area.  A  plane  bisecting  this  area  and  pass- 
ing through  the  other  two  points  will  divide 
the  egg  into  symmetrical  halves.  The  spindle 
takes  its  position  at  right  angles  to  this 
plane.  The  first  cleavage  therefore  will  pro- 
duce two  equal  and  symmetrical  daughter 
cells,  or  blastomeres,  the  first  cleavage  plane 
coinciding  with  the  plane  of  symmetry  of  the 
ovum.  These  two  blastomeres  will  become 
the  right  and  left  halves  of  the  embryo,  the 
plane  of  symmetry  of  the  ovum  representing 

FIG.  19.— Prophase  of  first  cleavage    the  sagittal  plane  of  the  embryo.     With  the 

anterior  portion  already  indicated  by  the 
point  of  extrusion  of  the  first  polar  body,  the 
orientation  of  the  first  two  blastomeres  rela- 
tive to  the  future  embryo  is  now  complete. 

The  second  cleavage  plane  falls  at  a  right  angle  to  the  first,  cutting  both 
the  animal  and  the  vegetative  pole.  The  division  is  slightly  unequal,  how- 
ever, the  result  being  two  slightly  smaller  blastomeres  and  two  slightly 
larger  blastomeres  (Fig.  20,  A ) .  These  are  arranged  symmetrically  on  the  two 
sides  of  the  median  plane.  The  third  cleavage  plane  lies  at  right  angles  to 
the  other  two,  and  division  of  the  cells  is  again  slightly  unequal  (a  condition 
often  called  subequal),  the  result  being  four  pairs  of  cells  of  four  different 
sizes  (Fig.  20,  B) .  The  smallest  cells  are  those  derived  from  the  portion  of  the 
ovum  which  contained  less  yolk,  the  largest  are  those  derived  from  the  por- 
tion which  contained  more  yolk.  All  the  cells  have  divided  completely,  a 
circumstance  which  gives  rise  to  the  term  total  cleavage;  and  this  condition 
obtains  throughout  the  later  stages.  All  the  cells  at  a  given  cleavage  thus  far 
have  divided  at  the  same  time,  a  fact  which  is  expressed  in  the  term  regular 
cleavage.  If  cleavage  were  to  continue  regularly  the  result  at  succeeding 
divisions  would  be  16,  32,  64,  128  cells,  and  so  on.  Regularity  is  lost,  how- 


figure  in  ovum  of  Amphioxus. 
The  chromosomes  of  the  male 
and  female  pronuclei  are  ming- 
led in  the  equatorial  plane. 
Sobotta,  from  Kellicott. 


EARLY  DEVELOPMENT  OF  AMPHIOXUS. 


37 


ever,  during  the  fourth  cleavage,  some  of  the  cells  dividing  before  others,  with 
the  result  that  numbers  other  than  those  just  given  will  be  found.  The 
smallest  cells,  with  the  least  amount  of  yolk  are  the  first  to  divide  and  they 
divide  more  rapidly  than  the  large  cells  with  a  greater  yolk  content;  the  inert 
non-protoplasmic  substance  retards  the  progress  of  division. 


FIG.  20. — Cleavage  in  Amphioxus.     Cerfontaine,  from  Kellicott. 

A,  four-cell  stage  seen  from  animal  pole;  B,  eight-cell  stage  seen  from  animal  pole,  showing  four 
sizes  of  blastomeres;  C,  sixteen-cell  stage  seen  from  left  side;  A,  thirty-two-cell  stage  seen 
from  vegetal  pole;  E,  32-64  cells  seen  from  antero-dorsal  region;  F,  half  of  early  blastula 
containing  about  128  cells,  a,  Animal  pole;  ad,  antero-dorsal;  I,  left;  pv,  postero-ventral; 
r,  right;  v,  vegetal  pole. 

Division  succeeds  division  in  the  blastomeres,  with  the  irregularity 
noted  in  the  preceding  paragraph.  The  cleavage  planes  vary  considerably  in 
direction  in  different  individuals.  At  the  i6-cell  stage  the  micromere  group 
assumes  a  sort  of  dome  form  and  the  macromere  group  in  similar  form  fits 
into  the  hollow  of  the  dome  (Fig.  20,  C) .  The  early  blastomeres  remain  well 


38  TEXT-BOOK  OF  EMBRYOLOGY. 

rounded  so  that  even  at  the  four-cell  stage  there  is  a  small  central  cavity  (Fig. 
20,  A).  As  cleavage  progresses  the  cells  become  more  closely  arranged  and 
pushed  away  from  the  central  cavity  (Fig.  20,  D,  E,  F).  At  the  i28-cell 
stage  all  the  cells  are  arranged  in  a  simple  epithelial  layer  around  a  rela- 
tively large  central  cavity,  the  segmentation  cavity  or  Uastoccel.  The  entire 
structure  is  now  the  bias  tula.  Other  divisions  occur  until  the  blastula  con- 
tains about  256  cells.  There  is  a  gradual  transition  from  the  micromeres  at 
one  pole  of  the  hollow  sphere  to  the  macromeres  at  the  opposite  pole.  It 
should  be  recalled  here  that,  on  account  of  the  position  of  the  yolk-free  por- 
tion of  the  ovum,  the  micromeres  lie  where  the  anterior  region  of  the  embry- 
onic body  will  arise  and  the  macromeres  where  the  posterior  region  will 
develop.  About  four  hours  elapse  between  the  time  the  first  cleavage  occurs 
and  the  time  the  256-cell  blastula  is  formed. 

Gastrulation. — This  process  comprises  the  conversion  of  the  single 
walled  blastula  into  the  double  walled  gastrula.  The  vegetative  pole 
becomes  flattened,  the  macromeres  assuming  columnar  form.  The  cells  at 
the  dorsal  margin  of  the  flattened  pole  begin  to  proliferate  more  rapidly 
than  elsewhere,  as  shown  by  the  increased  number  of  mi  to  tic  figures  (Fig.  21, 
A,  B).  This  area  of  accelerated  division  then  extends  in  both  directions 
around  the  margin  of  the  flat  pole,  forming  the  germ  ring.  Beginning  at  the 
dorsal  margin  the  macromeres  are  folded,  or  invaginated,  into  the  blastocoel 
until  the  blastoccel  is  obliterated  (Fig.  21,  C,  D,  E,  F,  G).  A  rough  analogy 
is  the  pushing  in  of  one  side  of  a  hollow  rubber  ball.  The  invagination,  how- 
ever, is  more  rapid  along  the  dorsal  margin  of  the  plate  of  macromeres,  and 
as  the  infolding  progresses  there  is  formed  a  plate  of  small  cells  which  arise 
through  the  more  rapid  proliferation  in  the  germ  ring  (Fig.  21,  D,  E).  On 
the  ventral  side  the  ingrowth  is  but  slight,  the  whole  plate  of  macromeres 
behaving  as  if  hinged  at  this  point.  By  these  processes  the  blastula,  with  a 
single  layer  of  cells,  has  been  converted  into  the  gastrula,  with  a  double 
layer  of  cells  and  a  new  cavity  which  opens  to  the  exterior. 

The  outer  layer  of  cells  is  the  ectoderm  which  is  in  direct  contact  with 
the  environment  of  the  developing  organism.  The  inner  layer  is  the  ento- 
derm  which  forms  the  lining  of  the  new  cavity,  or  archenteron,  in  the  interior 
of  the  organism.  The  entoderm  consists  of  two  types  of  cells,  the  larger 
cells  with  considerable  yolk  content  which  lie  on  the  ventral  side  or  in  the 
floor  of  the  archenteron  and  the  smaller  cells  forming  the  dorsal  lining  of  the 
archenteron  which  were  produced  by  the  rapid  divisions  in  the  germ  ring. 
This  latter  group  in  part  really  had  a  brief  existence  as  ectodermal  cells  and 
then  contributed  to  entoderm  by  being  inflected  round  the  rim  of  the  opening 
between  the  archenteron  and  the  exterior.  The  inflection  of  the  cells  in 
question,  often  called  involution  is  therefore  one  of  the  factors  in  gastrula- 


EARLY  DEVELOPMENT  OF  AMPHIOXUS. 


39 


tion.  The  circular  opening  between  the  archenteron  and  the  exterior  is  the 
blastopore.  Its  margins  are  its  lips  which  can  be  differentiated  into  dorsal, 
ventral  and  lateral  lips.  At  these  lips  the  entoderm  and  ectoderm  are 
continuous. 

Another  factor  in  gastrulation  is  a  process  known  as  epiboly.  When 
invagination  is  complete,  that  is,  when  the  macromere  pole  of  the  blastula 
has  infolded  until  the  blastoccel  is  obliterated,  the  gastrula  approximates  a 


FIG.  21. — Gastrulation  in  Amphioxus.     Cerfontaine,  from  Kellicott. 

A,  blastula  with  slightly  flattened  vegetal  pole,  showing  rapid  cell  division  in  postero-dorsal 
region  (germ  ring);  5,  more  pronounced  flattening  of  the  vegetal  pole;  C,  beginning  of 
invagination  in  postero-dorsal  region;  D,  further  invagination,  showing  obliteration  of  the 
blastocoel  and  formation  of  the  archenteron  as  the  result  of  invagination;  E,  invagination 
almost  complete;  F,  beginning  elongation  of  gastrula  and  narrowing  of  blastopore;  G, 
continued  elongation  of  gastrula  and  narrowing  of  blastopore.  Observe  the  mitotic  figures 
in  the  germ  ring  in  all  stages.  In  D  and  E  the  inflection  of  cells  (involution)  around  the 
dorsal  lip  of  the  blastopore  can  be  appreciated.  In  F  and  G  the  process  of  epiboly  is 
represented  in  the  backward  growth  of  the  lip  of  the  blastopore.  a,  Animal  pole;  ar, 
archenteron;  b,  blastopore;  dl,  dorsal  lip  of  blastopore;  ec,  ectoderm;  en,  entoderm;  gr, 
germ  ring;  s,  blastocoel;  v,  vegetal  pole;  vl,  ventral  lip  of  blastopore;  //,  second  polar  body. 

hemisphere  and  the  form  of  the  archenteron  coincides.  Then,  along  with 
the  rapid  cell  proliferation  in  the  dorsal  part  or  the  germ  ring  and  the  forma- 
tion of  the  plate  of  entodermal  cells  mentioned  in  the  preceding  paragraph, 


40  TEXT-BOOK  OF  EMBRYOLOGY. 

the  dorsal  lip  of  the  blastopore  extends  backward.  The  lip  protrudes,  one 
might  say.  The  extension  gradually  affects  also  the  lateral  lips  and  finally 
to  a  slight  degree  the  ventral  lip.  This  whole  process  of  growth  backward, 
which  is  due  to  the  rapid  cell  division  in  the  germ  ring — most  rapid  dorsally, 
less  rapid  laterally,  least  rapid  ventrally,  effects  a  posterior  elongation  of 
the  gastrula  and  a  diminution  in  the  size  of  the  blastopore  (Fig.  21,  E,  F,  G). 
This  is  the  first  step  in  the  lengthwise  growth  of  the  animal  as  a  whole. 
The  whole  process  of  gastrulation  has  occupied  about  three  hours. 

The  account  here  given  differs  in  one  respect  from  that  of  the  British 
investigator,  MacBride.  It  has  been  stated  that  inflection,  or  involution,  is 
one  of  the  factors  in  gastrulation.  MacBride  maintains  that  involution 
does  not  occur,  but  that  the  rapid  cell  division  occurring  in  the  lips  of  the 
blastopore  produces  both  ectoderm  and  entoderm  in  equal  amounts.  Cell 
proliferation  is  the  only  process  which  adds  to  the  number  of  entodermal  as 
well  as  of  ectodermal  components,  and  this  at  the  same  time  produces  the 
backward  extension  of  the  lips  of  the  blastopore  which  is  recognized  as  epi- 
boly.  He  bases  his  conclusion  on  nuclear  characters.  In  the  bias  tula  all 
the  nuclei  are  vesicular.  Soon  after  gastrulation  begins  the  nuclei  of  the 
ectodermal  cells  become  more  intensely  stainable  while  those  of  the 
entodermal  cells  retain  their  vesicular  nature,  all  the  invaginated  cells  pos- 
sessing the  vesicular  nuclei.  This  probably  indicates  a  physiological  dif- 
ferentiation. In  the  germ  ring  two  types  of  the  rapidly  dividing  cells  can  be 
distinguished,  one  with  vesicular  nuclei  and  the  other  with  deeply  staining 
nuclei.  The  former  are  added  to  the  entoderm,  the  latter  to  the  ectoderm. 
There  is  therefore  a  zone  of  growth  in  which  cells  are  produced  and  added 
directly  to  the  two  layers  without  inflection  round  the  lip  of  the  blastopore. 

The  gastrula  is  now  somewhat  elongated  antero-posteriorly,  somewhat 
flattened  on  the  dorsal  side  and  is  bilaterally  symmetrical,  with  the  archen- 
teron  opening  to  the  exterior  at  the  caudal  end  through  the  small  blastopore 
(Fig.  2 1 ,  G) .  Even  at  this  time  it  is  not  amiss  to  note  a  certain  fundamental 
arrangement  of  structure  and  anticipate  in  a  measure  its  biological  signifi- 
cance when  carried  over  into  later  stages.  The  ectoderm,  the  outer  layer 
of  the  gastrula,  is  in  immediate  contact  with  the  environment,  which  fact 
implies  that  response  to  external  stimuli  and  protection  are  effected  through 
this  layer.  In  Amphioxus,  as  well  as  in  certain  other  lower  forms,  strong 
cilia  develop  on  the  ectodermal  cells  by  the  motion  of  which  the  gastrula 
changes  its  position.  In  later  stages  it  will  be  seen  that  the  nervous  sytem, 
that  complex  mechanism  for  transmitting  stimuli  from  one  part  of  the  body 
to  another,  is  developed  from  ectoderm.  The  outer  layer  of  the  integu- 
mentary system  with  certain  of  its  derivatives,  primarily  protective  in 
nature,  is  also  a  product  of  ectoderm.  The  archenteron  with  its  lining  of 


EARLY  DEVELOPMENT  OF  AMPHIOXUS. 


entoderm  constitutes  the  primitive  gut,  the  only  opening  of  which  is  the 
blastopore,  serving  as  both  mouth  and  anus.  Already  the  simple  alimentary 
system  is  confined  to  the  interior  of  the  organism,  shut  off  from  the  outside 
except  through  an  opening  for  the  intake  of  food  and  output  of  waste. 
Among  the  invertebrates  the  sponges  and  corals  never  develop  beyond  the 
two  layered,  or  didermic,  gastrula  stage  such  as  we  here  see  in  Amphioxus. 
It  is  worth  noting  also  that  in  Amphioxus  the  cells  with  yolk  content  are 
members  of  the  entoderm  group;  in  other  words,  a  temporary  food  supply, 


Notochord 


Neural 
plate 


—  Ectoderm — 
Neural  plate 

Ccelom  — 


Intestine 


Entoderm. 


Parietal 
mesoderm 
Visceral 
mesoderm 

Intestine 
Entoderm 


FIG.  22. — From  transverse  sections  through  Amphioxus  embryos,  showing  successive  stages  in 
formation  of  mesoderm,  neural  tube  and  notochord.     Bonnet. 

scanty  as  it  is  here,  is  stored  in  the  lining  of  the  gut.  From  this  simple  primi- 
tive gut  the  whole  alimentary  system  is  elaborated,  complex  as  it  may 
become.  The  mouth,  however,  is  not  a  derivative  of  the  blastopore,  but 
develops  as  a  new  opening  into  the  cephalic  end  of  the  gut  cavity.  The 
anal  opening  too  in  most  vertebrates  arises  independently. 

Before  considering  the  formation  of  the  middle  germ  layer,  or  mesoderm, 
it  is  desirable  to  observe  certain  changes  affecting  the  exterior  of  the  gastrula 
which  are  correlated  with  the  development  of  the  nervous  system,  because 
they  occur  prior  to  the  appearance  of  the  mesoderm  and  produce  a  setting 
for  part  of  this  layer.  Along  the  flattened  dorsal  surface  of  the  gastrula  a 


42 


TEXT-BOOK  OF  EMBRYOLOGY. 


piate  of  ectodermal  cells  sinks  slightly  below  the  general  surface  level  and 
becomes  demarkated  from  the  surrounding  ectoderm.  The  plate  extends 
from  almost  the  cephalic  (anterior)  extremity  of  the  gastrula  to  the  dorsal 
lip  of  the  blastopore  and  even  slightly  affects  the  lateral  lips.  These  cells 
thus  circumscribed  constitute  the  neural  plate;  in  this  manner  the  rudiment 
of  the  nervous  system  appears  (Fig.  22,  a).  The  ectoderm  bordering  the 
margins  of  the  neural  plate  becomes  elevated  above  the  general  surface 
level  to  form  the  neural  ridges*  These  also  form  a  rim  around  the  blastopore. 
The  neural  plate  then  sinks  farther  below  the  surface  level  and  at  the  same 
time  the  ridges  slide  across  it  toward  the  mid-dorsal  line  until  they  meet 
and  fuse  with  each  other.  Thus  a  roof  is  made  over  the  neural  plate,  with  a 
small  space  between  the  two  structures  (Fig.  22,  b,  c).  The  median  fusion 
begins  some  distance  in  front  of  the  blastopore  and  from  there  progresses 
both  forward  and  backward.  The  closure  is  not  complete  in  front  for  some 


Neuropore 

Primitive  segment  — 
Coelom  (myocoel) 
Intestine 


Epidermis  (ectoderm) 
Neural  tube 


Anterior  \  lip  cf 
Posterior  /  blastopore 


Unsegmented 
mesoderm 


FIG.  23. — From  vertical  section  through  Amphioxus  embryo  with  5  primitive  segments.   Hatschek. 

time,  and  the  opening  thus  left  is  called  the  neuropore  (Fig.  23).  The  neural 
ridges  close  in  over  the  blastopore  as  they  do  over  the  neural  plate,  so  that  the 
blastopore  no  longer  opens  to  the  exterior  but  into  the  space  between  the 
neural  plate  and  its  ectodermal  roof  (Fig.  23). 

\J  Mesoderm  Formation. — Closely  following  the  appearance  of  the  neural 
plate  in  the  elongated  gastrula,  one  may  observe  the  rudiment  of  the  middle 
germ  layer  and  the  first  indication  of  the  axial  structure,  the  notocord,  that 
gives  the  name  Chordata  to  the  great  division  of  the  animal  kingdom  which 
includes  not  only  the  true  vertebrates  but  also  such  forms  as  Amphioxus, 
Balanoglossus  and  the  Tunicata.  In  a  transverse  section  of  the  gastrula, 
in  the  roof  of  the  archenteron  the  entoderm  exhibits  a  change  which  produces 
three  distinguishable  parts.  An  axial  part,  lying  beneath  the  center  of  the 
neural  plate,  is  the  rudiment  of  the  notocord.  Two  dorso-lateral  parts,  bi- 
laterally  symmetrical,  are  the  rudiments  of  the  mesoderm  (Fig.  22).  The 
notocord  rudiment  advances  to  the  cephalic  extremity  of  the  gastrula,  and 
extends  caudally  to  the  blastopore.  The  mesoderm  rudiment  reaches  from 
the  forward  end  of  the  archenteron  to  the  blastoporal  region  where  the  two 


EARLY  DEVELOPMENT  OF  AMPHIOXUS.  43 

parts  diverge  in  the  lateral  lips  of  theaperture\  The  portion  along  the  archen- 
teron  is  the  gastral  mesoderm,  that  around  me"  blastopore  the  peristomaLj 

The  neural  plate  becomes  depressed  along  its  center  and  the  edges  turned^ 
upward,  forming  the  neural  groove.  Depression  and  elevation  continue 
until  the  two  edges  meet  dorsally  in  the  median  plane.  Fusion  of  the 
edges  begins  not  far  from  the  anterior  end  and  progresses  both  forward  and 
backward  until  the  entire  structure  becomes  tubular.  Thus  the  neural 
tube  with  its  central  canal  is  formed  (Fig.  22,  d}.  At  the  caudal  end  the  cen- 
tral canal  remains  in  open  communication  with  the  archenteron  owing  to 
the  fact  that  when  the  ectoderm  grew  over  the  neural  plate  it  also  grew  over 
the  blastopore.  The  opening  thus  left  is  the  neurenteric  canal  (Fig.  23). 
So  long  as  the  neuropore  also  persists  at  the  cephalic  end  of  the  neural  tube 
there  is  direct  communication  between  the  exterior  and  the  archenteron  via 
the  central  canal  and  the  neurenteric  canal.  In  Amphioxus  the  neuropore  - 
persists  until  the  mouth  is  formed. 

//The  depression  of  the  center  of  the  neural  pjate  produces  a  depression 
*also  of  the  notocord  rudiment  and  the  mesial  edges  of  the  mesoderm  bands. 
One  effect  of  this  is  an  inverted  groove,  the  enteroccel,  along  each  side  of  the 
notocord,  so  that  the  mesoderm  appears  to  bulge  outward  (Fig.  22,  a,  b). 
The  grooves  extend  almost  the  entire  length  of  the  embryo  and  speedily 
grow  deeper,  the  mesoderm  intruding  between  entoderm  and  ectoderm 
and  becoming  clearly  differentiated  from  the  notocord  and  the  remainder  of 
the  entoderm  (Fig.  22,  c).  Near  the  cephalic  end  of  the  embryo  a  trans- 
verse fold  drops  from  the  dorsal  part  of  the  mesoderm  on  each  side,  which 
closes  the  groove  and  delimits  the  most  anterior  portion  from  that  imme- 
diately behind  it.  The  portion  thus  delimited,  with  its  fellow  of  the  opposite 
side,  constitutes  the  first  pair  of  mesodermal  somites.  Another  portion  is 
delimited  in  the  same  manner  to  form  the  second  pair  of  somites.  Then 
the  third  pair  is  formed;  and  so  on  toward  the  caudal  end  of  the  embryo 
(Figs.  23  and  24).  The  development  of  mesodermal  somites  therefore  takes 
place  from  before  backward. 

Each  somite  assumes  a  cuboidal  form  and  is  hollow,  the  cavity  being  a 
portion  of  the  original  groove-like  enteroccel,  and  the  cells  surrounding  the 
cavity  comprise  a  simple  cuboidal  epithelium.  For  a  short  time  an  opening 
between  the  enteroccel  and  gut  cavity  remains,  but  later  this  is  closed  as  the 
mesoderm  becomes  entirely  cut  off  from  the  entoderm  and  the  latter  again 
forms  a  continuous  lining  of  the  gut.  These  processes  too  occur  from  before 
backward. 

The  fact  that  the  formation  of  mesodermal  somites  progresses  from  before 
backward,  that  is,  from  the  cephalic  end  of  the  body  toward  the  caudal  end, 
illustrates  a  fundamental  principle  of  growth.  The  distinction  between  gas- 


44 


TEXT-BOOK  OF  EMBRYOLOGY. 


tral  and  peristomal  mesoderm  has  already  been  stated,  and  since  mesoderm 
development  is  initiated  shortly  after  the  gastrula  begins  to  elongate  the 
true  gastral  portion  is  relatively  short.  Whatever  is  added  to  this  comes 
from  the  region  of  the  blastopore.  In  the  germ  ring  cell  proliferation  con- 
tinues rapidly  and  from  the  cells  thus  produced  components  of  all  three  germ 
layers  are  differentiated.  In  other  words,  the  elongation  of  the  embryo  as  a 
whole,  with  its  three  germ  layers,  is  due  chiefly  to  this  cell  proliferation  and 
differentiation  at  its  caudal  end.  Not  only  the  mesoderm  but  also  the  gut, 
the  neural  tube  and  other  structures  which  will  subsequently  appear,  in- 
crease and  develop  from  before  backward. 


Anterior  (cephalic)  end 


Epidermis 
(ectoderm) 


Entoderm 


—  Mesoderm 


Unsegmented 
mesoderm 


Archenteron 


Posterior  (caudal)  end 
FIG.  24. — From  horizontal  section  through  Amphioxus  embryo  with  5  primitive  segments;  seen 

from  dorsal  side.     Hatschek. 

The  communication  between  the  cavities  of  the  primitive  segments  (ccelom)  and  the  archenteron 

can  be  seen  in  the  last  4  segments. 

The  original  gastral  mesoderm  gives  rise  to  perhaps  not  more  than  the 
first  two  pairs  of  somites.  The  succeeding  somites  arise  from  mesoderm 
that  originates  in  the  region  around  the  blastopore.  By  the  time  about 
fourteen  pairs  of  somites  have  developed  the  mesoderm  no  longer  arises  as 
outgrowths  from  the  entoderm  of  the  gut  wall  but  directly  from  the  proliferat- 
ing cells  in  the  region  around  the  neurenteric  canal.  As  a  matter  of  fact 
the  formation  of  somites  now  does  not  quite  keep  pace  with  the  differentia- 
tion of  the  middle  layer  and  just  in  front  of  the  blastoporal  region  there  is  a 
short  band  of  undivided  mesoderm  (Figs.  23  and  24).  As  this  band  grows 
at  its  caudal  end  it  is  gradually  being  cut  up  into  somites  from  its  anterior 


EARLY  DEVELOPMENT  OF  AMPHIOXUS.  45 

end.  The  somites  appear  as  bilaterally  symmetrical  structures,  but  when 
five  or  six  pairs  have  arisen  the  symmetry  is  disturbed  since  each  somite 
on  the  right  comes  to  lie  a  little  behind  its  fellow  on  the  left  thus  giving 
an  alternation  which  is  carried  on  into  the  adult. 

Only  the  first  few  somites  develop  with  enteroccelic  cavities,  the  remainder 
originating  as  solid  structures  although  the  cells  are  arranged  radially  around 
a  central  point.  However,  the  solid  ones  subsequently  acquire  cavities. 
The  enteroccel  has  been  regarded  as  an  indication  of  a  primitive  character, 
since  in  the  higher  animals  the  somites  do  not  contain  any  cavities  derived 
from  the  gut  cavity  but  arise  as  solid  structures.  On  the  other  hand  the 
solid  somites  may  indicate  the  primitive  condition  and  the  appearance  of 
enteroccelic  cavities  may  be  a  secondary  character  in  Amphioxus. 

The  rudiment  of  the  notocord,  mentioned  previously,  which  is  composed 
of  the  entodermal  cells  immediately  ventral  to  the  neural  tube  and  between 
the  two  mesodermal  outgrowths,  extending  from  the  cephalic  extremity  of 
the  embryo  to  the  blastoporal  region,  requires  brief  attention.  While  the 
mesodermal  rudiments  are  being  cut  off  from  the  parent  entoderm  the 
notocordal  cells  become  rearranged  into  a  compact  rod-like  structure  lying 
between  the  somites  of  the  two  sides  (Fig.  22,  d).  As  the  somites  enlarge 
this  rod  is  constricted  from  the  adjacent  entoderm,  which  then  closes  across 
the  top  of  the  gut  cavity,  and  occupies  its  definitive  position  ventral  to  the 
neural  tube.  Clearly  the  notocord  in  Amphioxusj)riginates  from  entoderm. 
As  the  embryo  continues  to  grow  in  length  the  notocord  too  is  lengthened  by 
the  addition  of  cells  to  its  caudal  end  in  the  region  of  the  neurenteric  canal. 

Continued  development  of  the  mesodermal  somites  comprises  their 
farther  intrusion  between  ectoderm  and  entoderm  and  changes  in  their 
component  cells.  When  first  formed,  the  somites  are  composed  of  columnar 
or  cuboidal  epithelial  cells  in  a  single  layer  surrounding  the  central  cavity  if 
present,  or,  if  the  enteroccel  is  absent,  radiating  from  a  common  center  (Figs. 
23  and  24).  The  somites  are  block-like  in  shape  and  located  lateral  to  the 
developing  notocord  and  neural  tube.  The  changes  to  be  described  begin 
in  the  anterior  somites  and,  in  accordance  with  the  principle  of  growth 
already  mentioned,  progress  from  there  backward.  The  cavity  in  the 
somite  becomes  larger  and  the  surrounding  cells  become  flatter.  With  the  en- 
largement of  the  cavity  the  ventral  portion  of  the  somite  extends  ventrally 
between  ectoderm  and  entoderm  (Fig.  22,  d).  It  seems  that  the  whole 
structure  becomes  dilated  in  the  direction  of  least  resistance.  The  outer  por- 
tion of  the  wall  is  apposed  to  ectoderm  and  is  called  the  somatic  or  parietal 
mesoderm;  the  inner  layer  is  in  contact  with  entoderm  and  is  spoken  of  as 
splanchnic  or  visceral  mesoderm.  The  dilated  cavity  is  the  codomic  space 
^(Figs.  22  and  25).  Continued  ventral  extension  brings  the  dilating  struc- 


46 


TEXT-BOOK  OF  EMBRYOLOGY. 


ture  around  the  ventral  aspect  of  the  gut  until  it  meets  its  fellow  of  the  oppo- 
site side  in  the  sagittal  plane,  thus  separating  ectoderm  from  entoderm.  The 
sagittal  partition  between  the  ccelomic  spaces  of  the  two  sides  then  breaks 
down  and  each  side  is  in  free  communication  with  the  other  ventral  to  the 
gut.  The  cells  of  the  entire  dilated  structure  have  become  decidedly  flat- 
tened except  those  in  contact  with  the  notocord  and  neural  tube  which 
become  more  elongated  columns  and  comprise  the  muscle  plate  or  myotome 
(Fig.  25).  The  portion  of  the  cavity  contiguous  to  the  myotome  is  now 
known  as  the  myocoel  while  the  remainder  of  the  coelomic  space  is  the  splanch- 
nocoel. Subsequently  a  partition  appearing  between  the  myoccel  and 
splanchnocoel  completely  separates  the  two  cavities.  The  myotomes,  in  the 
sites  of  the  original  somites,  retain  their  segmental  character.  The  parti- 

Neural  tube 


Epidermis  (ectoderm) 


Coelom 

Primitive  segment 
Intestine 

Entoderm 


Notochord 

Primitive  segment 
Muscle  plate 
Cutis  plate 
Myocoel 


Coelom 


Splanchnocc 
Parietal  mesoderm 
Visceral  mesoderm 


\  lat.  plate 


Ventral        Subintestinal 
mesentery  vein 


FIG.  25. — Diagram  to  show  differentiation  of  primitive  segment  into  muscle  plate  (myotome)  and 
cutis  plate  and  relation  of  myocoel  and  splanchnocoel.     Bonnet,     Compare  with  Fig.  22,  d. 

tions  between  adjacent  splanchnoccelic  cavities,  on  the  other  hand,  break 
down  and  the  common  cavity  thus  produced,  which  is  now  known  as  the 
coelom,  no  longer  bears  the  segmental  character  but  is  continuous  on  both 
sides  of  and  below  the  gut. 

The  biological  significance  of  ectoderm  and  entoderm  has  been  briefly 
noted.  Between  these  two  layers  the  mesoderm  appears  and  presently 
begins  to  elaborate  and  to  contribute  to  their  support ;  support  in  the  broadest 
sense  of  the  term.  As  the  organism  continues  to  develop,  the  middle  germ 
layer  becomes  a  framework  within  and  around  which  the  refinements  of  the 
two  primary  layers  are  suspended.  The  whole  series  of  connective  tissues 
is  of  mesodermal  origin,  and  this  applies  even  to  the  cartilaginous  and  bony 
skeleton.  The  muscles,  all  three  varieties,  whose  activities  are  associated 
with  motion  and  locomotion  are  derivatives  of  the  mesoderm.  The  blood 


EARLY  DEVELOPMENT  OF  AMPHIOXUS.  47 

vessels  and  lymphatics,  the  tubes  through  which  substances  are  carried 
from  one  part  of  the  body  to  another,  the  blood  and  lymph  also  which  are 
the  vehicles  for  these  substances,  all  are  mesodermal  in  origin.  The  organs 
of  excretion  too  arise  from  this  intermediate  layer.  The  reproductive 
organs,  growth  centers  of  the  germ  cells.,  originate  here.  It  is  not  difficult 
to  see,  therefore,  that  in  the  higher  and  more  complex  animal  forms  many  of 
the  activities  of  the  ectodermal  and  entodermal  derivatives  which  are  cor- 
related with  response  to  external  stimuli  and  with  alimentation  are  made 
possible  by  structures  elaborated  from  the  mesoderm. 

While  Amphioxus  is  not  a  true  vertebrate  because  it  never  acquires  a 
vertebral  column,  yet  we  may  observe  in  it  a  relatively  simple  arrangement 
of  structure  which  foreshadows  the  fundamental  vertebrate  organization. 
After  the  development  of  the  mesoderm  and  ccelom  the  embryo  as  a  whole 
obviously  comprises  a  tube  within  a  tube;  the  gut,  extending  from  mouth 
to  anus,  is  the  inner  tube,  the  body  wall  is  the  outer  tube,  and  the  two  are 
separated  by  the  ccelom  or  body  cavity.  This  is  a  typical  vertebrate  char- 
acteristic. The  neural  tube  or  central  nervous  system,  situated  in  the  dorsal 
body  wall,  is  another  feature  which  links  Amphioxus  with  the  vertebrates. 
The  notocord  which  is  regarded  as  the  axial  supporting  structure  in  Am- 
phioxus appears  also  in  higher  animal  forms.  In  the  true  vertebrates  the 
notocord  is  not  transformed  into  the  axial  skeleton  which  is  the  chief  longi- 
tudinal supporting  skeleton,  but  the  axial  mechanism  is  built  around  the 
notocord.  Another  impressive  attribute  of  the  vertebrates  is  the  series 
of  mesodermal  somites,  although  it  must  be  remembered  that  this  is  not 
exclusively  chordate  property,  for  some  of  the  invertebrates,  for  instance  the 
worms,  possess  it.  This  transverse  segmentation,  or  metamerism,  affects 
not  only  the  mesoderm  and  certain  of  its  derivatives  but  involves  also  struc- 
tures that  arise  from  ectoderm.  In  the  vertebrates  the  units  of  the  spinal 
column,  arising  from  the  somites,  maintain  their  integrity  throughout  the  life 
of  the  animal.  The  ribs  and  intercostal  muscles  are  expressions  of  metamer- 
ism. Many  of  the  blood  vessels  are  arranged  segmentally.  Even  the 
primitive  kidney  arises  as  a  segmental  organ.  Among  the  ectodermal 
derivatives,  the  nervous  system  reflects  the  metameric  quality  in  the  develop- 
ment of  the  spinal  nerves.  Obviously  many  features  of  vertebrate  organiza- 
tion depend  upon  the  principle  of  metamerism. 

References  for  Further  Study. 

CERFONTAINE,  P.:  Recherches  sur  le  development  de  1' Amphioxus.  Archives  de 
Biologie,  tome  22,  1907. 

HATSCHEK,  B.:  Studien  uber  die  Entwickelung  des  Amphioxus.  Arbeiten  aus  dem 
2007.  Institut  zu  Wien,  Bd.  4,  1881. 


48  TEXT-BOOK  OF  EMBRYOLOGY. 

HERTWIG,  R.:  Furchungsprozess.  In  Hertwig's  Handbuch  der  vergleichenden  und 
experimentellen  Entwickelungslehre  der  Wirbeltiere,  Bd.  I,  Teil  I,  Kap.  Ill,  1903.  Contains 
extensive  bibliography. 

KELLICOTT,  W.  E.:  Chordate  Development.     Chap.  I,  1913. 

MACBRIDE,  E.  W.:  Text-book  of  Embryology.     Vol.  I,  1914. 

MORGAN,  T.  H.  and  HAZEN,  A.  P.:  The  Gastrulation  of  Amphioxus.  Journal  of 
Morphology,  Vol.  16,  1900. 

WILLEY,  A.:  Amphioxus  and  the  Ancestry  of  the  Vertebrates.     1894. 

WILSON,  E.  B.:  Amphioxus  and  the  Mosaic  Theory  of  Development.  Journal  oj 
Morphology,  Vol.  8,  1893. 


CHAPTER  V. 


EARLY  DEVELOPMENT  OF  THE  FROG. 

Most  students  have  seen  the  eggs  of  the  frog  either  in  the  laboratory 
or  in  a  pond  during  the  springtime.  They  probably  have  observed  the  little 
objects  embedded  in  the  jelly-like  mass,  scores  of  them  in  a  cluster,  each 
egg  in  its  own  gelatinous  capsule,  and  all  the  capsules  clinging  to  one  another. 
Each  ovum  is  a  sphere,  a  little  more  than  a  millimeter  in  diameter  in  the 
common  wood  frog  and  as  much  as  3  mm.  in  some  other  species,  with  a 
dark  side  and  a  light  side;  and  if  the  ovum  has  been  at  rest  in  its  natural 
environment  for  a  few  minutes  the  dark  side  is  uppermost  (Fig.  2). 

The  dark  color  is  due  to  the  presence  of  brown  pigment  granules.  The 
portion  of  the  egg  where  there  is  less  pigment  contains  an  abundance  of  yolk 
globules  suspended  in  the  cytoplasm,  while  the  darker  part  consists  of 
cytoplasm  with  fewer  yolk  globules.  The  nucleus  of  the  cell  is  located  in 
the  part  containing  the  more  cytoplasm 
and  is  therefore  eccentric.  The  distribu- 
tion of  cytoplasm,  yolk  and  pigment  is 
apparently  an  expression  of  the  internal 
organization  of  the  egg,  yielding  here  a 
visible  polarity.  The  cytoplasmic  or 
,aiiimal  pole  contains  the  nucleus  and 
abundant  pigment,  the  latter  mostly  near 
the  surface;  the  yolk  or  vegetal  pole  con- 
tains less  cytoplasm  and  pigment  but 
abundant  deutoplasm  (Fig.  26).  As  far 
as  determined,  the  egg  is  radially  sym- 
metrical around  the  axis  extending  from 
the  center  of  the  animal  pole  to  the  center 
of  the  vegetal  pole;  that  is,  assuming  this 
axis  to  be  vertical,  the  egg  possesses  the 
same  organization  in  all  radii  drawn  from 
the  axis  in  any  given  horizontal  plane. 
The  polarity  and  symmetry _of  the  egg  are 
important  factors  in  development. 

The  eggs  are  expelled  by  the  female  frog  into  the  water  and  the  sper- 
matozoa discharged  by  the  male  mingle  with  the  egg  clusters.     A  sperm 
4  49 


FIG. 


26.  —  Section  through  the  fully 
formed  ovarian  egg  of  a  frog. 
Morgan.  The  protoplasmic  or 
animal  pole  is  toward  the  top  of 
the  page.  Note  that  the  nucleus 
is  situated  nearer  the  animal  pole, 
that  is,  in  the  center  of  the  cyto- 
plasmic mass.  The  yolk  globules 
can  be  seen  in  the  lower  part  of 
the  figure. 


50 


TEXT-BOOK  OF  EMBRYOLOGY. 


burrows  through  the  gelatinous  capsule  and  thin  vitelline  membrane  of  an 
egg  and  enters  the  cytoplasm  usually  about  40  degrees  from  the  center  of 
the  animal  pole.  There  seems  to  be  some  determining  factor  in  the  entrance 
of  the  sperm  at  or  near  that  particular  parallel,  but  the  point  of  entrance  may 
lie  in  any  meridian  of  the  egg.  The  first  sperm  that  enters  the  cytoplasm 
seems  to  set  up  changes,  probably  of  a  physico-chemical  nature,  which  bar 
admittance  to  other  sperms.  The  sperm  head  and  the  body  containing  the 
centrosome  move  through  the  cytoplasm  for  some  distance  toward  the 
center  of  the  egg,  then  rotate  so  that  the  body  is  in  advance  of  the  head  and 
change  their  course  in  the  direction  of  the  egg  nucleus.  The  trail  of  the 
sperm  is  marked  by  an  extra  amount  of  pigment,  indicating  probably  some 


B 


FIG.  27. — A  frog's  egg  before  and  after  fertilization,  showing  the  formation  of  the  gray  crescent. 
A,  Unfertilized  egg  seen  from  the  side;  B,  unfertilized  egg  seen  from  the  vegetal  pole.  C, 
fertilized  egg  seen  from  the  side;  D,  from  the  vegetal  pole,  c,  Gray  crescent;  w,  non- 
pigmented  vegetal  pole.  Kellicott. 

increase  in  cytoplasmic  activity.  The  course  of  the  sperm  toward  the 
center  of  the  egg  is  the  penetration  path,  the  course  toward  the  egg  nucleus, 
the  copulation  path. 

The  sperm  nucleus,  as  soon  as  it  enters  the  egg,  appears  to  stimulate 
the  cytoplasm  to  activities  leading  to  a  rearrangement  of  the  egg  substances 
and  thus  to  a  reorganization.  Beginning  at  the  point  where  the  sperm 
enters,  the  cytoplasm  streams  toward  the  animal  pole  and  the  yolk  toward 
the  vegetal  pole,  a  sharper  polar  differentiation  thus  resulting.  On  the 
supposition  that  this  influence  of  the  sperm  spreads  like  a  wave  from  the 
point  of  entrance,  it  follows  that  the  original  rotatory  symmetry  of  the  egg  is 
disturbed  and  a  new  symmetry  established  which  is  a  bilateral  one,  with  the 
plane  containing  the  penetration  path  as  the  median  plane.  In  other  words 


EARLY  DEVELOPMENT  OF  THE  FROG.  51 

the  egg  has  become  bilaterally  symmetrical,  with  the  plane  of  symmetry 
cutting  the  center  of  the  animal  pole,  the  center  of  the  vegetal  pole  and  the 
point  of  entrance  of  the  sperm.  There  is  also  a  visible  external  change  in 
the  distribution  of  pigment.  On  the  side  of  the  egg  opposite  the  point  where 
the  sperm  entered,  some  of  the  pigment  granules  over  a  crescent-shaped  area 
at  the  lower  border  of  the  pigmented  surface  are  carried  from  their  original 
position,  leaving  this  area  lighter  in  color.  The  name,  gray  crescent,  is 
given  to  the  lighter  area  which  extends  more  than  half  way  round  the  egg 
(Fig.  27). 

The  rearrangement  of  the  egg  substances  disturbs  the  center  of  gravity  of 
the  egg.  The  original  axis,  extending  from  the  center  of  the  animal  pole  to 
the  center  of  the  vegetal  pole,  is  inclined  at  an  angle  of  about  30  degrees  to 
the  vertical,  the  margin  of  the  highly  pigmented  pole  being  tilted  accordingly 
out  of  the  horizontal.  The  gray  crescent  lies  on  the  higher  side.  The  verti- 
cal axis  of  the  egg  is  now  the  gravitational  axis,  and,  from  the  manner  in 
which  the  internal  rearrangement  of  egg  substances  has  presumably  occurred, 
a  gravitational  plane  will  bisect  the  egg  into  symmetrical  halves,  bisecting  the 
gray  crescent  and  containing  both  the  gravitational  axis  and  the  original 
polar  axis.  All  these  changes  have  been  caused  or  at  least  initiated  by  the 
sperm. 

Cleavage. — When  the  sperm  nucleus  reaches  the  egg  nucleus  via  the  copu- 
lation path  the  two  nuclei  join  to  form  the  single  nucleus  of  the  fertilized 
ovum.  The  sperm  centrosome  divides  into  two  which  take  positions  at 
opposite  poles  of  the  single  nucleus.  A  spindle  develops  between  the  cen- 
trosomes,  and  the  chromosomes  assemble  in  the  equatorial  plane  of  the 
spindle.  The  direction  that  the  spindle  assumes  does  not  appear  to  be  wholly 
a  matter  of  chance.  In  the  first  place  it  forms  at  right  angles  to  the  egg  axis; 
for  it  is  generally  true  that  the  spindle  of  a  cell  in  division  lies  in  the  direc- 
tion of  the  greatest  cytoplasmic  mass.  If  the  egg  is  not  subjected  to  pres- 
sure, the  spindle  tends  to  lie  in  the  plane  of  egg  symmetry  or  at  right  angles 
to  it,  although  there  may  be  many  variations.  If  there  is  pressure  from 
without,  the  spindle  tends  to  lie  at  right  angles  to  the  direction  of  pressure. 
The  factors  other  than  pressure  which  influence  the  direction  of  the  spindle 
have  not  been  determined;  but  it  appears  that  the  spindle  has  a  tendency  at 
least,  to  assume  a  position  of  symmetry  relative  to  the  structure  or  internal 
organization  of  the  egg.  This  means  therefore  that  the  first  cleavage  plane, 
which  of  course  cuts  the  spindle  at  right  angles,  tends  to  divide  the  egg  in  or 
near  the  plane  of  symmetry  or  at  right  angles  to  it.  In  about  25  per  cent, 
of  instances  the  first  cleavage  plane  deviates  but  little  from  the  plane  of  egg 
symmetry;  in  about  10  per  cent,  it  lies  transversely  to  the  plane  of  symme- 
try. It  is  also  true  that  the  first  cleavage  plane  tends  to  coincide  with  the 


52  TEXT-BOOK  OF  EMBRYOLOGY. 

median  plane  of  the  future  embryo.  Summing  up,  it  may  be  stated  that 
there  is  a  tendency  in  the  frog  for  the  median  plane  of  the  egg,  the  first 
cleavage  plane  and  the  median  plane  of  the  embryo  to  coincide;  but,  remem- 
bering that  all  these  planes  contain  the  egg  axis,  any  other  relation  may  be 
encountered. 

On  the  surface  the  first  cleavage  furrow  appears  as  a  shallow  groove  on 
the  pigmented  side  of  the  egg  and  then  gradually  extends  around  to  the  yolk 
pole.  This  is  the  surface  indication  of  the  division  which  separates  the  egg 
into  halves  or  blastomeres.  If  the  cleavage  plane  coincides  with  the  plane  of 
symmetry,  the  two  blastomeres  are  symmetrical  and  the  gray  crescent  is 
divided  symmetrically;  otherwise  the  two  blastomeres  are  asymmetrical  in 
internal  structure.  The  division  is  total,  but  the  two  cells  remain  flattened 
against  each  other  in  close  contact.  It  should  be  noted  also  that  the  division 
is  retarded  in  the  vegetal  portion  of  the  egg  by  the  yolk  globules  in  the  cyto- 
plasm. The  retardation  is  so  marked  that  the  cleavage  furrow  of  the  second 
division  appears  at  the  animal  pole  before  the  first  furrow  has  reached  the 
vegetal  pole.  The  second  furrow  crosses  the  first  at  right  angles  at  the  pig- 
mented pole  and  extends  around  to  the  yolk  pole  in  the  same  manner  as  the 
first.  The  second  cleavage  plane,  of  which  this  second  furrow  is  the  surface 
marking,  intersects  the  first  at  right  angles  and  thus  divides  each  of  the  first 
two  blastomeres  into  equal  parts.  The  direction  of  the  plane  is  determined 
by  the  position  of  the  spindle  in  each  primary  blastomere,  this  lying  in  the 
direction  of  the  greatest  cytoplasmic  mass.  The  first  four  blastomeres  are 
approximately  equal  in  size  and  contain  equal  amounts  of  cytoplasm  and  yolk. 
They  remain  in  close  contact  so  that  collectively  they  still  form  a  sphere 
which  is  marked  on  the  surface  by  shallow  grooves. 

The  third  cleavage  planes  intersect  the  first  two  at  right  angles  but  lie 
nearer  the  animal  pole  than  the  vegetal  pole,  the  furrow  on  the  surface 
appearing  about  60  degrees  from  the  animal  pole.  In  this  manner  the  four 
blastomeres  are  divided  into  eight  (Fig.  28,  A).  The  upper  four  members 
are  smaller  and  contain  an  excess  of  cytoplasm  while  the  lower  four  are 
larger  and  contain  an  excess  of  yolk.  This  condition  gives  rise  to  the  terms 
micromeres  and  macromeres.  In  some  instances  the  third  cleavage  plane 
deviates  from  the  latitudinal,  even  to  being  meridional,  in  one  or  more  blasto- 
meres. Typically  the  fourth  cleavages  are  meridional,  producing  eight 
micromeres  and  the  same  number  of  macromeres.  Here  again  the  planes  may 
deviate  from  the  meridional  position  and  disturb  the  typical  pattern.  Not 
all  the  blastomeres  necessarily  divide  at  the  same  time,  as  might  be  implied 
from  the  description.  The  lack  of  synchronism  is  especially  true  between 
micromeres  and  macromeres  because  in  the  latter  the  process  of  division  is 
retarded  to  a  marked  degree  by  the  inert  yolk.  From  the  fifth  cleavage  on, 


EARLY  DEVELOPMENT  OF  THE  FROG. 


53 


the  micromeres  very  noticeably  divide  more  rapidly  than  the  macromeres 
with  the  result  that  the  former  become  more  numerous  than  the  latter 
(Fig.  28,  B,  C,  D,  E,  F,  G).  It  is  often  stated  that  the  rate  of  cleavage  is 
directly  proportional  to  the  amount  of  cytoplasm  and  inversely  proportional 
to  the  amount  of  yolk. 


B 


H 


FIG.  28.—  Cleavage  of  the  frog's  egg.     Morgan. 

A,  Eight-cell  stage;  B,  beginning  of  sixteen-cell  stage;  C,  thirty-two-cell  stage;  Z>,  forty-eight- 
cell  stage  (more  regular  than  usual);  E,  F,  G,  later  stages;  H,  I,  formation  of  blastopore. 

Returning  for  a  moment  to  the  first  four  blastomeres,  the  inner  edge  of 
each  does  not  quite  make  contact  with  its  neighbor,  and  so  a  minute  space 
is  left  where  the  first  two  cleavage  planes  intersect.  This  rounding  of  the 
corners  is  probably  due  to  the  tendency  for  each  cell  to  assume  spherical 
form,  which  is  the  natural  consequence  of  its  semifluid  nature  and  surface 
tension.  When  the  third  cleavage  planes  cut  the  first  two  at  right  angles 
somewhat  above  the  equator,  producing  eight  cells,  the  inner  corners  of 


54  TEXT-BOOK  OF  EMBRYOLOGY. 

these  are  rounded  off  and  the  space  here  is  somewhat  augmented.  In  the 
interior  of  the  mass  there  is  therefore  a  small  cavity  which,  since  the  upper 
four  cells  are  smaller  than  the  lower,  is  eccentric.  As  the  blastomeres  con- 
tinue to  divide  around  it,  the  cavity  increases  in  size  but  remains  eccentric. 
During  the  first  few  divisions  there  is  only  a  single  layer  of  cells  around  the 
cavity;  then  some  of  the  cells  divide  parallel  to  the  surface  and  a  double 
layer  appears  and  then  several  layers.  The  multiplicity  of  layers  is  espe- 
cially characteristic  of  the  yolk  cells.  The  entire  structure  is  a  hollow  sphere 
called  the  blastula  and  the  eccentric  cavity  within,  known  as  the  blasto- 
ccel  or  segmentation  cavity,  has  a  dome-shaped  roof  of  micromeres  and  a 
floor  of  macromeres  (Fig.  29).  The  peripheral  stratum  of  closely  compacted 

Micromeres 


Macromeres 
FIG.  29.— From  a  sagittal   section   through   blastula  of  frog.     Bonnet,     mz.,   Marginal  zone. 

cells  is  the  most  highly  pigmented  while  the  cells  beneath  are  less  pig- 
mented  and  somewhat  more  loosely  arranged.  The  blastula  is  about  the 
same  size  as  the  egg  before  it  began  to  divide.  It  is  similar  to  Amphioxus 
in  that  it  is  a  hollow  sphere,  but  is  different  in  that  the  blastoccel  is  eccen- 
tric and  the  cells  form  several  layers  instead  of  one.  (Compare  Figs.  20 
and  29.)  As  the  cells  multiply,  those  in  the  highest  part  of  the  dome-like 
roof  of  the  blastoccel  migrate  toward  the  equator  so  that  the  roof  becomes 
thinner  and  the  lateral  wall  becomes  thicker.  The  thicker  lateral  wall, 
which  also  exhibits  rapid  cell  proliferation,  is  called  the  germ  ring  and  prob- 
ably corresponds  to  a  similar  zone  of  rapidly  dividing  cells  in  Amphioxus  at 
the  beginning  of  gastrulation.  On  the  side  of  the  blastula  where  the  gray 
crescent  is  situated  the  germ  ring  migrates  across  the  equator  and  down  about 


EARLY  DEVELOPMENT  OF  THE  FROG.  55 

halfway  to  the  yolk  pole.  This  downward  migration  displaces  the  yolk  cells 
in  the  interior  upward,  producing  an  elevation  in  the  floor  of  the  blastoccel. 
As  subsequent  development  proves,  the  side  where  the  germ  ring  reaches  the 
lowest  point  marks  the  caudal  end  of  the  embryo.  During  the  formation 
and  early  migration  of  the  germ  ring  the  blastula  increases  about  one-fifth 
in  size  but  remains  spherical.  Some  water  perhaps  filters  into  the  blastoccel, 
although  part  of  its  contents  is  probably  products  of  cell  activities. 

Gastrulation. — In  the  frog  as  in  Amphioxus  gastrulation  comprises  the 
change  of  a  single-layered  structure,  the  blastula,  into  a  double-layered 
structure,  the  gastrula.  The  processes  by  which  this  change  is  effected  are 
more  complex  in  the  frog,  the  visible  factor  in  the  complexity  being  the 
greater  quantity  of  yolk.  The  inert  yolk  stored  within  an  egg  is  always  an 
influence  in  development. 

Viewing  first  the  exterior  of  the  blastula,  a  slight  groove  appears  on  the 
posterior  side  across  the  median  sagittal  plane  at  the  lowest  part  of  the  germ 
ring,  that  is,  about  midway  between  the  equator  and  the  center  of  the  yolk 
pole.  The  small  pigmented  cells  bound  the  groove  above,  the  larger 
yolk  cells  below  (Fig.  28,  H).  As  development  proceeds  the  groove 
becomes  longer,  following  the  boundary  between  the  two  types  of  cells, 
which  is  of  course  the  lower  margin  of  the  germ  ring.  It  thus  takes  on 
the  from  of  a  crescent.  Continuing  to  elongate  in  the  same  directon,  the 
two  horns  of  the  crescent  would  eventually  meet  and  the  groove  would  thus 
become  a  ring  encircling  the  blastula  at  the  boundary  between  the  pigmented 
and  yolk  areas.  This  actually  occurs,  but  in  the  meantime  the  pigmented 
area  extends  farther  down  owing  to  the  descent  of  the  germ  ring  and  the  down- 
ward progress  is  more  rapid  on  the  posterior  side  where  the  groove  first 
appeared.  The  result  of  this  is  that  by  the  time  the  horns  of  the  crescent 
meet  to  form  a  ring,  the  ring  is  much  smaller  than  if  there  had  been  no  down- 
ward movement;  and  since  the  original  groove  was  bounded  above  by  pig- 
mented cells  it  now  follows  that  the  ring  is  bounded  all  round  on  the  outside 
by  pigmented  cells.  For  the  same  reason  the  ring  is  bounded  on  the  inside 
by  yolk  cells.  These  are  the  only  yolk  cells  now  visible  on  the  surface. 
Subsequently  the  ring  becomes  still  smaller  and  then  flattened  from  side  to 
side  and  finally  reduced  to  a  small  slit.  (See  Fig.  30.) 

The  changes  on  the  surface  are  merely  partial  expressions  of  the  com- 
plicated processes  in  the  interior.  In  a  sagittal  section  of  the  blastula 
at  the  time  the  superficial  groove  appears,  the  initial  step  in  these 
processes  can  be  observed.  The  groove  appears  as  a  slight  indentation  above 
which  are  the  smaller  cells  of  the  germ  ring  and  below,  the  larger  yolk  cells. 
At  this  side  is  seen  also  the  elevation  of  the  floor  of  the  blastoccel  caused  by 
the  rising  of  the  yolk  cells;  and  there  is  a  slight  separation  of  this  elevation 


56  TEXT-BOOK  OF  EMBRYOLOGY. 

from  the  smaller  cells.  The  groove  represents  the  beginning  of  a  process  of 
invagination  which,  however,  is  much  less  conspicuous  than  that  in  Amphi- 
oxus  where  the  whole  side  of  the  blastula  is  invaginated.  In  the  frog  the 
yolk  cells,  laden  with  inert  substance,  are  much  less  yielding  to  such  factors 
as  would  produce  invagination. 

The  successive  stages  of  gastrulation  as  seen  in  sagittal  section  can  be 
followed  clearly  in  Fig.  31.  The  pictures  are  more  vivid  than  verbal  des- 
cription. The  groove  can  be  seen  to  grow  deeper  in  successive  stages,  turn- 
ing upward  into  the  elevation  of  yolk  cells,  seeming  to  push  that  elevation 
before  it,  and  following  the  roof  of  the  blastoccel  across  to  the  opposite  side. 
When  well  on  its  way,  the  groove  expands  into  a  broad  space  which  finally 
occupies  the  interior  of  the  structure  in  much  the  same  way  as  did  the  blasto- 


FIG.  30. — Diagrams  showing  the  position  of  the  blastopore  at  successive  stages  of  gastrulation 
in  the  frog's  egg.  A,  posterior  view;  B,  lateral  view.  Figures  1-5  indicate  the  shape  and 
position  of  the  blastopore  during  the  internal  changes;  figure  5  indicates  its  position  after 
the  rotation  of  the  gastrula.  Compare  Figs.  31  and  35.  Kellicott. 

ccel.  This  broad  space  is  the  archenteron  which  opens  to  the  exterior  through 
the  annular  groove  which  was  described  on  surface  view,  the  opening  being 
the  blastopore.  The  yolk  cells  which  are  inside  the  ring  can  here  be  seen  to 
fill  the  blastopore  like  a  plug;  collectively  they  are  called  the  yolk  plug.  It 
should  also  be  noted  that  the  yolk  cells  form  an  elevation  in  the  floor  of  the 
blastoccel  on  the  side  opposite  the  invagination.  As  a  matter  of  fact  the 
elevation  occurs  all  the  way  round  the  blastoccel  as  does  also  the  cleft  between 
the  elevation  and  the  smaller  cells. 

Invagination  is  probably  not  as  important  a  factor  here  as  it  seems  to  be 
although  it  plays  a  part;  it  certainly  is  not  as  important  as  in  Amphioxus. 
It  must  be  remembered  that  the  cells  of  the  germ  ring  are  multiplying  rapidly 
when  the  invagination  groove  appears.  The  rapid  proliferation  continues 
during  the  processes  thus  far  observed  and  many  cells  migrate  inward  around 
the  lip  of  the  blastopore.  This  perhaps  is  comparable  with  a  similar  series 
of  rapid  divisions  and  migration  in  the  germ  ring  in  Amphioxus.  Conse- 


EARLY  DEVELOPMENT  OF  THE  FROG. 


57 


FIG.  31. — Median  sagittal  sections  showing  successive  stages  of  gastrulation  in  the  frog's  egg. 

Bracket,  from  Kellicott. 

A,  beginning  of  gastrulation;  B,  slight  advance  in  invagination  and  beginning  of  epiboly;  C, 
invagination  and  epiboly  progressing,  inflection  of  cells  (involution)  occurring  around  dorsal 
lip  of  blastopore  which  is  now  an  obvious  structure;  D,  epiboly  has  resulted  in  covering  of  a 
large  part  of  yolk  by  lip  of  blastopore;  E,  blastopore  is  now  circular  and  filled  with  the  yolk 
plug  (cf.  Fig.  30,  A,  4)  and  the  archenteron  appears  as  a  small  space;  F,  the  blastoccel  is 
nearly  obliterated;  G,  gastrulation  completed. 

a,  Archenteron;  b,  blastopore;  c,  rudiment  of  notocord;  ec,  ectoderm;  en,  entoderm;  gc,  gastrular 
cleavage,  ge,  entoderm  (protentoderm) ;  m,  peristomal  mesoderm;  np,  neural  plate;  w/, 
transverse  neural  ridge;  s,  blastocoel. 


58  TEXT-BOOK  OF  EMBRYOLOGY. 

quently  many  of  the  cells  that  form  the  roof  of  the  archenteron  are  not 
brought  in  by  the  invagination  but  by  involution. 

There  is  still  another  factor  in  gastrulation.  It  has  already  been 
noted  that  on  surface  view  the  groove  moves  downward  as  the  highly  pig- 
men  ted  cells  along  its  upper  or  dorsal  lip  encroach  upon  the  non-pigmented 
area,  so  that  when  the  groove  becomes  ring-shaped  only  a  small  yolk  area  is 
visible.  This  downward  growth  over  the  yolk  area,  or  epiboly,  which  is 
more  rapid  on  the  side  where  the  groove  began,  results  in  the  enclosure  of 
more  and  more  yolk  cells  so  that  only  those  comprising  the  yolk  plug  are 
left  exposed.  It  is  this  process  (epiboly)  therefore  which  causes  the 
lessening  of  the  crescent  and  ring  as  seen  on  surface  view.  (Compare  Fig. 

30.) 

These  processes  which  are  grouped  under  the  term  gastrulation  have 
converted  the  single-layered  blastula  into  the  double-layered  gastrula.  The 
outer  layer  composed  of  several  strata  of  pigmented  cells  is  the  ectoderm  which 
is  in  contact  with  the  environment.  The  inner  is  the  entoderm  which  lines 
the  archenteric  cavity.  Two  types  of  entodermal  cells  are  distinguishable: 
those  forming  the  roof  and  sides  of  the  archenteron  which  contain  a  moderate 
amount  of  pigment  and  those  forming  the  floor  which  hold  little  pigment  but 
an  abundance  of  yolk.  The  two  primary  germ  layers  are  continuous  at  the 
rim  of  the  blastopore. 

Two  other  features  which  are  incidental  to  the  processes  of  gastrulation 
must  be  noted  because  of  their  bearing  upon  future  development.  Recalling 
the  migration  of  the  crescentic  groove,  which  eventually  becomes  the  ring 
around  the  yolk  plug,  it  is  obvious  from  the  manner  in  which  the  migration 
occurs  that  the  cells  along  the  horns  of  the  crescent  are  drawn  toward  the 
median  region.  The  name  given  to  this  phenomenon  is  concrescence.  The 
result  of  it  is  that  the  cells  are  piled  up  in  a  median  linear  strand,  from  which 
the  rudiments  of  certain  organs  emerge.  The  outer  feature  is  the 
flattening  of  the  ring  from  side  to  side,  concomitant  with  the  withdrawal 
/inward  and  disappearance  of  the  yolk  plug,  so  that  the  two  lateral  margins 
approximate,  leaving  only  a  narrow  slit  leading  from  the  exterior  into  the 
archenteric  cavity.  Subsequently  the  slit  is  closed  by  fusion  of  its  walls, 
but  part  of  the  depression  in  its  site  becomes  the  anal  pit  or  proctodaeum. 

At  this  stage  the  gastrula  is  still  spherical  and  only  slightly  larger  than 
the  blastula.  It  possesses  the  same  fundamental  arrangement  of  structure 
as  the  gastrula  of  Amphioxus.  The  ectoderm  forms  contact  with  the  envir- 
onment, implying  response  to  stimuli  and  protection;  and  the  organs  corre- 
lated with  these  functions  are  derived  from  this  layer.  The  archenteric 
cavity  with  its  lining  of  endoderm  is  confined  to  the  interior  of  the  developing 
organism  and  comprises  the  primitive  alimentary  system.  Within  the 


EARLY  DEVELOPMENT  OF  THE  FROG.  59 

cells  of  the  entoderm  is  the  food  that  must  suffice  until  the  animal  reaches  a 
stage  when  it  is  able  to  obtain  a  supply  from  the  outside;  but  the  rudiment 
of  the  future  complex  alimentary  mechanism  is  already  formed.  The 
blastopore  is  not  a  free  opening,  as  in  Amphioxus,  but  is  obstructed  by  the 
yolk  plug.  The  latter  is  eventually  withdrawn  and  the  anus  develops  in 
the  site  of  a  part  of  the  blastopore.  The  mouth  is  a  new  opening  which 
develops  at  the  forward  end  of  the  gut.  A  somewhat  more  detailed  discus- 
sion of  the  biological  significance  of  the  blastula  is  given  on  page  40,  in  the 
chapter  on  Amphioxus. 

Mesoderm  Formation. — In  order  to  detect  the  beginning  of  the  middle 
germ  layer  it  is  necessary  to  look  back  into  the  period  of  gastrulation.  Gas- 
trulation  and  mesoderm  formation  overlap  each  other.  In  a  sagittal  section 
of  the  blastula  just  as  gastrulation  commences,  the  cells  of  the  germ  ring 
are  continuous  with  the  yolk  cells  above  the  groove  that  indicates  the  begin- 
ning of  in  vagina  tion  (Fig.  31,  A).  This  transition  zone,  traced  through  the 
subsequent  stages  of  development,  is  composed  of  cells  which  occupy  a  posi- 
tion always  in  the  angle  between  ectoderm  and  entoderm  and  merge  with 
these  layers  (Fig.  31,  B,  C,  D,  E,  F).  The  cells  in  question  comprise  the 
early  mesoderm.  Appearing  as  it  does  in  the  angle  between  the  other  layers 
in  the  lip  of  the  blastopore,  it  is  obvious  that  when  the  blastopore  becomes 
circular  the  mesoderm  takes  the  form  of  a  circular  band.  In  Amphioxus  it 
was  clear  that  the  mesoderm  originated  from  entoderm  (see  p.  42),  but  in 
the  frog  the  first  mesodermal  cells  bear  such  relation  to  the  other  layers  that 
their  origin  is  not  so  readily  determined.  In  later  stages,  however,  it  will 
be  apparent  that  mesoderm  arises  from  yolk  entoderm. 

In  the  description  of  gastrulation  it  was  pointed  out  (p.  58)  that  during 
the  migration  of  the  crescentic  groove  and  its  transformation  into  a  ring 
the  cells  along  the  horns  of  the  crescent  were  drawn  medially  and  piled  up  in 
an  axial  strand  which  then  extended  upward  and  forward  from  the  dorsal  lip 
of  the  blastopore.  The  mesodermal  cells  appear  in  the  dorsal  lip  of  the 
crescentic  groove  and,  as  the  migration  of  the  groove  goes  on,  they  are 
affected  in  the  same  way  as  the  other  cells  in  this  region.  Therefore  the 
band  of  mesodermal  cells  around  the  blastopore  is  broader  at  the  dorsal  side. 
In  other  words,  a  band  of  mesodermal  cells  extends  upward  and  forward 
from  the  dorsal  lip  of  the  blastopore,  forming  a  part  of  the  axial  strand. 
And  since  the  proliferation  and  involution  of  cells,  which  occur  during  gas- 
trulation, tend  to  carry  the  mesodermal  cells  upward  and  forward  and  since 
the  mesodermal  cells  themselves  are  proliferating,  the  mesoderm  soon 
becomes  almost  as  extensive  dorsally  as  the  entoderm. 

In  the  dorsal  axial  strand  of  cells,  which  later  will  be  considered  more  in 
detail,  the  three  layers  are  at  first  merged.  Lateral  to  this  the  mesoderm 


60 


TEXT-BOOK  OF  EMBRYOLOGY. 


becomes  clearly  delimited  from  ectoderm,  at  least  a  potential  cleft  separating 
the  two  layers.     For  a  short  distance  laterally  the  mesoderm  also  becomes 


Notocord 


Mesoderm 
Protentoderm 


Ectoderm 


Yolk  entoderm 


Remnant  of 
segmentation  cavity 


FIG.  32. — Transverse  section  of  embryo  of  frog  (Rana  fusca).     Bonnet.     The  section  is  taken  in 
front  of  (anterior  to)  the  blastopore. 

delimited  from  entoderm,  but  farther  laterally  it  is  fused  with  entoderm 
(Fig.  32).     Then  as  development  proceeds  the  superficial  cells  of  the  yolk 


Neural  crest 

Neural  canal 

Mesodermal  somite  = 

Notocord 


Ccelom  _ 


Ventral  mesoderm  < 


Yolk  cells 


Ectoderm 

Parietal  mesoderm 
Visceral  mesoderm 


Entoderm 


FIG.  33. — Transverse  section  through  embryo  of  frog  (Rana  fusca).     Bonnet. 

entoderm,  with  which  the  mesoderm  is  merged,  become  differentiated  and 
split  off  or  delaminated  and  added  to  the  mesoderm.  In  this  manner  the 
mesoderm  becomes  more  extensive  until  finally  it  reaches  all  the  way  round 

r  *-v 


EARLY  DEVELOPMENT  OF  THE  FROG.  61 

ventrally  between  the  other  layers,  although  it  is  not  complete  for  some 
time  (Fig.  33).  There  is  ample  evidence  here  that  this  portion  of  the  meso- 
derm  is  a  derivative  of  entoderm  (yolk  entoderm).  The  mesoderm  that 
develops  along  the  crescentic  groove  and  around  the  blastopore  is  often 
called  peristomal;  that  which  arises  elsewhere  is  known  as  gastral  mesoderm. 
v/^  The  behavior  of  the  mesoderm  that  is  involved  in  the  dorsal  axial  strand 
above  or  anterior  to  the  blastopore  is  rather  complex  because  out  of  that 
strand  arises  one  of  the  early  axial  structures  of  the  embryo,  the  notocord. 
First  a  slight  cleft  between  ectoderm  and  mesoderm  gradually  extends  from 
each  side  toward  the  mid-dorsal  line,  but 
just  before  reaching  the  line  abruptly 

turns  ventrally.  This  cleft  as  it  bends  :^^^5^^S^^^-  ec 
ventrally  leaves  a  group  of  cells  in  the 
axial  line  which  is  still  continuous  with 
ectoderm  above  and  entoderm  below. 
The  axial  group  of  cells  is  the  rudiment 
of  the  notocord.  (Fig.  34.)  Just  above 
or  anterior  to  the  blastopore,  in  the  re- 
gion where  entoderm  and  mesoderm  are  ,  . 

FIG.  34. — Portion  of  a  transverse  section 

still  continuous  at  the  lower  lateral  angles  Of   the  larva  of   a  frog  (Rana 

c,i  IT  •      £  fusca).    Hertwie.    a,  Archenteron; 

of  the  notocord  rudiment,  a  pair  of  grooves  c  ind<cates  enterocoel  formation^ 

appear   which    are    not   particularly    con-  ec,   ectoderm;    en,   entoderm;   m, 

.  ...  .  .  mesoderm;  «,  notocord;  p,  neural 

SplCUOUS   but  which   seem    to   be  evagma-  plate;  y,  yolk  entoderm. 

tions    from    the    archenteron    (Fig.    34). 

Farther  forward  the  grooves  are  slightly  more  conspicuous,  but  still 
farther  forward  disappear.  It  has  been  argued  that  these  grooves  are 
homologous  with  the  enteroccelic  evaginations  in  Amphioxus  where  the 
mesoderm  arises  by  outgrowth  from  the  entoderm.  On  the  other  hand  it  has 
also  been  argued  that  the  more  primitive  mode  of  mesodermal  development 
is  represented  in  the  frog  and  that  the  simplicity  of  origin  is  secondarily 
acquired  in  Amphioxus.  Whether  pr  not  these  grooves  are  enteroccelic 
evaginations  in  the  frog,  soon  after  their  appearance  the  notocord  rudi- 
ment becomes  separated  from  entoderm  below,  from  ectoderm  above,  and 
lies  in  the  axial  line  between  what  are  now  the  paraxial  masses  of  meso- 
derm on  the  two  sides  (Fig.  33  )  The  notocord  therefore  becomes  an  inde- 
pendent structure  except  at  its  caudal  end  where  it  merges  with  all  the 
layers  which  in  turn  are  merged  with  one  another  at  the  blastopore.  A 
similar  fusion  is  present  in  Amphioxus  (p.  45) ;  and  out  of  this  mass  of  cells, 
as  development  proceeds  from  before  backward,  the  three  germ  layers  and 
the  notocord  are  differentiated. 

During  gastrulation  a  certain  shift  in  position  of  the  structure  as  a  whole 


62 


TEXT-BOOK  OF  EMBRYOLOGY. 


is  observed.  In  the  completed  blastula  it  was  noted  that  the  yolk  pole 
was  directed  downward  owing  to  the  slightly  higher  specific  gravity  of  the 
yolk.  During  gastrulation  it  is  obvious  that  the  center  of  gravity  of  the 
whole  mass  is  shifted.  This  can  readily  be  seen  if  one  follows  the  changes  in 
sagittal  sections  (Fig.  31).  As  a  result  the  whole  structure  rotates  through 
an  angle  of  about  90  degrees  (Fig.  35).  The  blastopore  therefore  assumes 
a  position  which  is  nearly  on  a  level  with  the  center  of  the  gastrula.  After 


FIG.  35. — Diagrams  of  median  sagittal  sections  through  an  eight-cell  stage  and  four  stages  during 
gastrulation  of  the  frog's  egg.  Kopsch,  from  Kellicott.  The  arrow  marks  the  vertical. 
If  one  compares  the  shaded  parts  of  the  figure  with  the  fixed  vertical  line  it  is  seen  that  the 
gastrula  rotates  through  an  angle  of  about  90  degrees  in  the  counter-clockwise  direction. 

the  rotation  the  dorsal  and  ventral  sides  and  the  cephalic  and  caudal  sides 
(ends)  of  the  gastrula  and  of  the  future  embryo  are  fixed. 

The  completed  gastrula  is  still  spherical,  but  then  at  once  it  begins  to 
elongate  in  the  direction  of  the  axis  drawn  from  the  blastopore  to  the  opposite 
pole.  The  dorso-caudal  region  is  drawn  out  into  a  bud-like  structure;  the 
dorsal  side  becomes  flat  or  slightly  concave  in  the  cephalo-caudal  direction; 
the  ventral  side  remains  broadly  convex  owing  to  the  presence  of  the  yolk  in 


EARLY  DEVELOPMENT  OF  THE  FROG. 


63 


the  ventral  wall  of  the  archenteron  (gut)  (Fig.  36) .  This  growth  in  length  is  the 
beginning  of  the  characteristic  cephalo-caudal  elongation  of  the  larva  and 
adult.  It  is  due  in  part  to  proliferation  of  cells  generally  but  chiefly  due  to 
proliferation  at  the  caudal  end  in  the  region  dorsal  to  the  blastopore.  .  Here 
as  in  Amphioxus  growth  takes  place  largely  from  before  backward;  and  the 
bud-like  process  in  the  dorso-caudal  region  is  one  of  the  outward  expressions 
of  the  growth. 

nf  nf 

9 


FIG.  36. — Postero-lateral  views  of  successive  stages  following  gastrulation  in  the  frog.  Ziegler, 
from  Kellicott.  A,  blastopore  in  process  of  closing,  neural  folds  slightly  indicated;  B, 
gastrula  slightly  elongated,  blastopore  closed,  neural  groove  and  folds  obvious;  C,  anal 
portion  of  blastopore  still  visible  at  bottom  of  proctodaeum,  neural  folds  closing  dorsally; 
D,  neural  folds  nearly  closed,  branchial  arches  appearing,  tail  bud  forming;  E,  neural  folds 
fused,  tail  bud  more  conspicuous. 

b,  Blastopore  containing  yolk  plug;  bi,  dorsal  part  of  blastopore  (rudiment  of  neurenteric  canal) ; 
fe,  ventral  part  of 'blastopore  (rudiment  of  anus);  ba,  branchial  arches;  g,  neural  gro  ve ;  nf, 
neural  folds;  np,  neural  plate;  p,  proctodaeum,  with  anal  portion  of  the  blastopore  at  the 
bottom;  s,  oral  sucker;  t,  tail  bud;  x,  neural  folds  covering  the  blastopore  thus  establishing 
the  neurenteric  canal. 

In  order  to  bring  the  development  of  the  frog  up  to  a  point  corresponding 
to  the  stage  of  Amphioxus  reached  at  the  end  of  the  previous  chapter,  it  is 


64 


TEXT-BOOK  OF  EMBRYOLOGY. 


en 


nc 


b  — 


necessary  still  to  consider  briefly  the  appearance  of  the  neural  tube  and  some 
further  changes  in  the  mesoderm.  During  the  latter  part  of  the  gastrula- 
tion  period  a  band  of  ectoderm  extending  forward  from  the  dorsal  lip  of  the 
blastopore  over  the  dorsum  of  the  gastrula  becomes  slightly  thicker.  This 
band  of  cells,  the  neural  plate,  is  narrow  near  the  blastopore  and  becomes 

broader  farther  forward  (Fig. 
36,5).  During  the  withdrawal 
of  the  yolk  plug  and  the  closure 
of  the  blastopore  the  margin  of 
the  plate  becomes  thicker  and 
elevated  above  the  surface  level 
to  form  the  neural  ridges.  The 
depression  between  the  ridges 
is  the  neural  groove  (Fig.  33). 
At  the  cephalic  end  of  the  plate 
the  ridges  curve  medially  and 
meet  each  other,  forming  the 
transverse  neural  fold.  The 
ridges  grow  higher,  the  groove 
becoming  correspondingly 
deeper,  and  finally  lean  far 
enough  toward  the  median 
sagittal  plane  to  meet  and  fuse 
in  the  mid-dorsal  line,  so  that  a 
tube  is  formed  with  the  lumen 
as  the  central  canal.  The  fusion 
of  the  ridges  usually  begins 


ms 


ht 


FIG. 


37. — Median  sagittal  sections  of  frog  larvae. 
Marshall.  A ,  just  prior  to  closure  of  blastopore ; 
B,  just  after  closure  of  blastopore.  a,  anal 


aperture;   &,  blastopore;   e,  epiphysis;  ec,  ecto-  aum]t    mirlwav    between     their 

derm;  en,  entoderm;  /,  fore-brain;  g,  mid-gut;  h,  ' 

hind-brain;  ht,  rudiment  of  heart;  hy,  hypophy-  cephalic   and    caudal   ends,  and 

sis;  I,  rudiment  of  liver;  m,  mid-brain;  ms,  meso-  -                      . 

derm;  n,  no tocord;  nc,  neurenteric  canal ;  o,  oral  then     continues     torward      and 

evagination;   p    proctodaeum;  ph i,  pharynx;  r,  backward.      The  Caudal  portion 

rectum;  s,  spinal  cord;  y,  yolk  entoderm. 

of  the  neural  tube  encloses  the 

dorsal  part  of  the  blastopore  which  thus,  as  in  Amphioxus,  becomes  the 
neurenteric  canal,  the  communicating  aperture  between  the  central  canal  and 
the  archenteron  (Fig.  3  7) .  After  the  dorsal  closure  of  the  tube  the  non-neural 
ectoderm  forms  a  continuous  layer  so  that  the  tube  is  completely  covered 
(Fig.  33).  The  broader  cephalic  portion  of  the  neural  tube  is  the  rudiment 
of  the  brain,  the  narrower  remaining  part  is  the  beginning  of  the  spinal  cord. 
In  the  mesoderm  lateral  to  the  neural  plate  and  notocord  the  cells  for 
a  time  proliferate  more  rapidly  than  elsewhere  and  produce  a  rather  stout 
mass  (Fig.  33)  extending  from  the  head  to  the  blastopore.  From  this  mass 


EARLY  DEVELOPMENT  OF  THE  FROG.  65 

laterally  the  mesoderm  extends  between  ectoderm  and  entoderm  as  pre- 
viously described.  Just  behind  the  head  region  the  paraxial  mass  suffers  a 
rearrangement  of  its  cells  so  that  a  block  is  delimited  transversely.  Just 
behind  this  another  block  is  formed  in  the  same  manner;  a  similar  process 
produces  a  third,  and  so  on  toward  the  caudal  region.  The  blocks  themselves 
consist  of  closely  compacted  cells  while  in  the  intervals  between  them  the 
cells  are  loosely  arranged.  These  blocks  are  the  mesodermal  somites  which 
in  their  arrangement  express  the  fundamental  metameric  or  segmental  prin- 
ciple of  all  vertebrates  and  many  invertebrates.  Lateral  to  the  somites  a 
cleft  appears  in  the  originally  single  layer  of  mesoderm  thus  dividing  it  into 
two  layers  (Fig.  33).  The  cleft  commences  near  the  somites  and  gradually 
extends  all  the  way  round  ventrally;  it  also  extends  into  some  of  the  somites. 
This  cleft  is  the  rudiment  of  the  ccelom  or  body  cavity,  and  its  extension 
into  the  somites  probably  corresponds  to  the  myoccel  in  Amphioxus  The 
layer  of  mesoderm  ectal  to  the  ccelom  and  apposed  to  the  ectoderm  is  called 
the  somatic  or  parietal  layer;  the  layer  ental  to  the  ccelom  and  apposed  to 
entoderm  is  the  visceral  or  splanchnic  mesoderm. 

At  this  stage  of  development  in  the  frog  the  fundamental  vertebrate 
organization  is  expressed  in  the  general  arrangement  of  structure  (Fig.  37). 
The  body  as  a  whole  consists  of  a  tube  within  a  tube;  the  rudimentary  diges- 
tive system,  extending  lengthwise  in  the  growing  animal,  is  the  inner  tube, 
the  outer  tube  is  the  body  wall,  and  the  body  cavity  or  ccelom  separates  the 
two  tubes.  The  dorsally  located  neural  canal,  the  notocord  around  which 
the  vertebral  column  develops  in  the  true  vertebrate,  and  the  series  of  meso- 
dermal somites  are  at  this  time  simple  structural  patterns  from  which  the 
complex  vertebrate  organization  is  evolved. 

References  for  Further  Study. 

BRACKET,  A.:  Recherches  sur  Fontogenese  des  Amphibiens  urodeles  et  anoures. 
Archives  de  Biologie,  tome  19,  1902. 

EYCLESHYMER,  A.  C.:  The  early  Development  of  Amblystoma,  with  Observations  on 
some  other  Vertebrates.  Journal  of  Morphology,  Vol.  10,  1895. 

HERTWIG,  R.:  Furchungsprozess.  In  Hertwig's  Handbuch  der  vergleichenden  und 
experimentellen  Entwickelungslehre  der  Wirbeltiere.  Bd.  I,  Teil  I,  Kap.  Ill,  1903.  Contains 
extensive  bibliography. 

JENKINSON,  J.  W.:  On  the  Relation  between  the  Symmetry  of  the  Egg  and  the  Sym- 
metry of  Segmentation  and  the  Symmetry  of  the  Embryo  in  the  Frog.  Biometrika, 
Vol.  7,  1909. 

KELLICOTT,  W.  E.:  Chordate  Development.     Chap.  II,  1913. 

MORGAN,  T.  H.:  The  Development  of  the  Frog's  Egg.     1897. 


v 


CHAPTER  VI. 
EARLY  DEVELOPMENT  OF  THE  CHICK. 


Probably  every  student  has  seen  a  hen's  egg,  or  the  egg  of  some  other 
bird,  and  knows  its  size,  shape  and  appearance.  If  the  calcareous  shell  is 
broken,  the  whitish  shell-membrane  is  found  closely  applied  to  the  inner 
surface.  Enclosed  by  the  membrane  is  the  glairy,  transparent  '" white" 
or  albumen.  Through  this  can  be  seen  the  yellow  spherical  yolk  mass.  It 
requires  close  observation  to  discern  the  delicate  transparent  vitelline  mem- 
brane around  the  yolk.  If  the  egg  has  been  in  one  position  for  a  few  minutes 
the  tiny  white  germ  disk,  less  than  a  quarter  of  an  inch  in  diameter,  will 
appear  on  the  upper  side  of  the  yolk.  The  yolk  mass  and  germ  disk  to- 
gether constitute  the  ovum  which  was  discharged  from  the  Graafian  follicle  of 
the  ovary.  The  vitelline  membrane  is  a  true  cell-membrane,  a  product  of  the 
egg  cytoplasm.  All  the  structures  on  the  outside  of  this  are  secondary  egg- 
membranes  deposited  by  the  epithelium  of  the  oviduct  as  the  ovum  passed 
along.  If  the  egg  has  been  fertilized  before  it  is  laid  the  germ  disk  represents 
a  considerably  advanced  stage  of  development,  for  fertilization  occurs  in 
the  extreme  upper  end  of  the  oviduct  and  during  the  time  the  egg  is  traver- 
sing the  tube,  a  period  of  about  24  hours,  the  early  formative  processes  have 
gone  on.  In  order  to  observe  the  earliest  stages  it  is  necessary  therefore  to 
obtain  and  study  the  egg  before  it  is  laid. 

In  the  chapter  on  the  germ  cells  it  was  pointed  out  that  the  bird's  egg 
represents  the  polylecithal  type  in  which  the  quantity  of  yolk  or  deutoplasm 
reaches  the  maximum  (p.  6) .  The  cytoplasm,  with  the  nucleus,  comprises 
a  small  disk,  about  3  mm.  in  diameter  and  0.5  mm.  thick,  which  rests  upon 
the  yolk.  The  bulk  of  the  yolk  contains  no  cytoplasm  at  all,  and  the  transi- 
tion from  pure  yolk  to  pure  cytoplasm  is  rather  abrupt.  The  vast  accumu- 
lation of  yolk  in  the  bird's  egg  is  correlated  with  the  long  period  that  the 
growing  embryo  remains  within  the  shell  when  it  must  depend  upon  an  in- 
ternal food  supply.  The  reptilian  egg  represents  the  same  type.  The 
course  of  development  is  greatly  modified  by  the  yolk  content,  and  since 
the  mammals  are  probably  descended  from  forms  (reptiles)  whose  eggs 
contained  much  yolk,  a  study  of  the  developmental  processes  of  a  polyleci- 
thal egg  throws  much  light  upon  the  development  of  mammals  whose  eggs 
contain  but  little  yolk  although  resembling  in  their  mode  of  development 
their  ancestral  type. 

66 


EARLY  DEVELOPMENT  OF  THE  CHICK. 


67 


When  the  ovum  escapes  from  the  ovary  it  immediately  enters  the  oviduct. 
The  spermatozoa  having  traversed  the  oviduct,  at  once  from  four  to  twenty- 
five  of  them  enter  the  cytoplasm.  Polyspermy  is  apparently  a  normal  inci- 
dent, although  only  one  sperm  nucleus  unites  with  the  egg  nucleus.  The 
entrance  of  the  sperms  seems  to  stimulate  the  formation  of  the  polar  bodies 
(maturation),  and  as  soon  as  this  is  accomplished  one  of  the  sperm  nuclei 
unites  with  the  mature  egg  nucleus  to  form  the  nucleus  of  the  fertilized  ovum. 


c  d 

FIG.  38. — Cleavage  in  hen's  egg.     Coste.     Germinal  disk  and  part  of  yolk,  seen  from  above. 

^  Cleavage. — As  soon  as  the  two  pronuclei  unite  in  the  cytoplasmic  disk 
a  spindle  appears  in  preparation  for  the  first  division.  The  spindle  is  parallel 
to  the  surface  and  the  first  cleavage  is  therefore  vertical.  The  cleavage 
plane  is  indicated  on  the  surface  by  a  slight  furrow  near  the  center  of  the  disk, 
the  margin  of  the  disk  being  undivided.  The  first  two  blastomeres  are  there- 
fore not  completely  separated  from  each  other.  The  new  spindle  in  each 
primary  blastomere  forms  parallel  to  the  long  axis  of  the  cell,  and  the  second 
division  occurs  at  right  angles  to  the  first  and  is  also  vertical.  The  plane  of 


68  TEXT-BOOK  OF  EMBRYOLOGY. 

the  second  cleavage  is  again  indicated  by  a  slight  furrow  near  the  center  of 
the  disk.  The  first  four  blastomeres  are  separated  only  near  their  apices, 
the  peripheral  region  remaining  unaffected  (Fig.  38,  a).  The  third  cleavage 
has  not  been  observed  in  the  hen's  egg.  As  a  rule  the  fourth  cleavage  tends 
to  cut  off  the  apices  of  the  preceding  blastomeres  so  that  a  central  group  of 
small  cells  is  surrounded  by  a  peripheral  group  of  large  cells  which  are  not 
completely  divided  (Fig.  38,  b  and  c).  About  this  time  some  of  central  cells 
also  divide  in  the  horizontal  plane.  In  subsequent  divisions  the  central 
continue  to  divide  more  rapidly  than  the  marginal  cells,  although  among 
the  latter  the  intercellar  boundaries  are  extending  still  farther  toward  the 
dge  of  the  disk  (Fig.  38,  d).  As  divisions  succeed  one  another  some  of  the 
nuclei  of  the  marginal  cells  migrate  out  into  the  yolk  surrounding  the  disk, 
the  cytoplasm  also  encroaching  upon  the  yolk  and  mingling  with  it.  In 
this  manner  the  disk  gradually  becomes  more  extensive  in  all  directions. 


FIG.  39.— From  a  vertical  section  through  the  germ  disk  of  a  fresh-laid  hen's  egg.     Duval,  Hertni'g. 
g.d.,  Upper  layer  of  germ  disk;  s.c.,  segmentation  cavity;  w.y.,  white  yolk  (see  Fig.  3). 

During  this  time  a  narrow  space  appears  between  the  center  of  the  disk  and 
the  underlying  yolk.  This  space  is  the  beginning  of  the  blastoccel  or  seg- 
mentation cavity.  Its  roof  is  composed  of  the  smaller  central  cells;  its  floor 
is  the  yolk,  and  around  its  margin  it  is  walled  in  by  the  larger  partially  seg- 
mented cells  and  yolk  (Fig.  39).  If  the  living  blastoderm  is  observed  from 
above  the  area  over  the  blastoccel  appears  clear  and  is  called  the  area  pellu- 
cida;  the  area  peripheral  to  the  blastoccel  appears  opaque  and  is  known  as 
the  area  opaca. 

^  /  It  is  not  difficult  at  this  time  to  make  a  comparison  between  the  develop- 
ing hen's  egg  and  the  eggs  of  the  frog  and  Amphioxus.  Obviously  the  stage 
described  above  corresponds  to  the  blastula.  The  small  cells  forming  the 
roof  of  the  blastoccel  are  homologous  with  the  micromeres  in  the  frog's 
blastula;  the  yolk  mass,  which  in  the  bird's  egg  remains  wholly  unsegmented 
except  around  the  margin  of  the  blastoderm,  is  comparable  with  the  macro- 
meres;  the  partially  segmented  cells  of  the  margin  of  the  disk  probably  corre- 
sponds to  the  transition  zone  which  was  designated  as  the  germ  ring.  In 


EARLY  DEVELOPMENT  OF  THE  CHICK. 


69 


the  Amphioxus'  ovum  there  is  only  a  small  quantity  of  yolk,  but  enough  to 
result  in  the  formation  of  a  few  larger  cells  in  the  blastula  which  are  homo- 
logous with  the  macromeres  in  the  frog  and  the  yolk  mass  in  the  bird.  The 
blastoccel  in  the  bird  is  reduced  to  a  minimum  owing  to  the  fact  that  the 
cytoplasm  comprises  only  a  small  disk  which  rests  upon  the  relatively  great 
mass  of  yolk.  (Compare  Figs.  20,  29  and  39.) 

Before  going  on  to  the  process  by  which  ectoderm  and  entoderm  arise, 
it  is  necessary  to  consider  briefly  the  transition  between  the  margin  of  the 
germ  disk  and  the  yolk.  The  incompletely  divided  marginal  cells,  which  are 
larger  than  the  central  cells,  border  upon  the  unsegmented  yolk  around  the 
disk.  This  yolk  at  first  contains  no  nuclei  and  is  called  the  periblast  ring. 
Then  as  the  marginal  cells  continue  to  divide,  the  peripheral  daughter  nuclei 
migrate  into  the  periblast  which  thus  becomes  a  nucleated  yolk  ring  but  is 
yet  wholly  unsegmented  and  merged  with  the  yolk.  This  nucleated  yolk 
ring  receives  the  name  germ  wall.  The  nuclei  here  continue  to  divide  and 


FIG.  40.  —  Cross  section  through  the  center  of  the  blastoderm  of  a  pigeon,  14^  hours  after  fer- 
tilization. Blount,  from  Lillie.  i,  Marginal  cells;  2,  periblast;  3,  nuclei  in  the  subgerminal 
region. 


then  cell  boundaries  appear.  Some  of  the  boundaries  become  complete, 
and  discrete  cells  are  thus  formed  which  apparently  join  the  group  already 
forming  the,  cellular  disk  or  blastoderm.  Other  daughter  nuclei  migrate 
farther  and  other  cells  are  formed  and  added  to  the  margin  of  the  blasto- 
derm (Fig.  40).  In  this  manner  the  blastoderm  increases  in  size,  extending 
in  all  directions  farther  over  the  yolk.  It  is  probable  that  the  cytoplasm 
of  these  cells  is  capable  of  using  the  yolk  to  build  up  into  more  cytoplasm, 
a  process  comparable  With  digestion  and  assimilation. 

It  is  possible  at  this  time,  or  even  before,  to  determine  the  position  of 
the  future  embryo  relative  to  the  disk.  If  the  disk  is  viewed  from  above  in 
its  natural  position  in  the  shell,  with  the  larger  end  of  the  egg  toward  the 
left,  the  edge  of  the  disk  toward  the  observer  will  indicate  the  caudal  end  of 
the  embryo,  and  the  long  axis  of  the  embryo  will  lie  at  right  angles  to  the  long 
axis  of  the  egg. 


70 


TEXT-BOOK  OF  EMBRYOLOGY. 


\  /  Gastrulation. — In  the  bird  as  in  the 
lower  forms  gastrulation  is  the  process 
by  which  the  single  layered  blastula  is 
converted  into  the  double  layered  gas- 
trula.  In  the  bird  the  blastula  consists  -, 
of  a  disk  of  cells,  the  blastoderm,  resting  - 
upon  the  yolk,  the  blastoccel  being  a 
shallow  cavity  beneath  the  center  of  the 
disk.  Between  the  twentieth  and  tenth 
hours  before  the  egg  is  laid  the  cells  of 
the  blastoderm  are  rearranged  so  that 
a  sector  of  the  posterior  or  caudal  third 
becomes  thinner  and  composed  ^)f  only 
a  single  layer  of  cells  (Fig.  41)^  In 
front  of  the  sector  there  is  a  graaual 
increase  in  thickness  and  at  the  anterior 
or  cephalic  border  the  blastoderm  may 
be  seven  cells  thick.  Around  the  caudal 
edge  of  the  sector  the  germ  wall  is  inter- 
rupted so  that  the  margin  of  the  disk 
rests  dir ec tly  upon  the  yolk .  The  bias to- 
coel  during  this  time  becomes  larger. 

^  Gastrulation  is  initiated  by  the  tuck- 
ing or  rolling  under  of  the  caudal  margin 
of  the  sector.  The  cells  thus  rolled  in 
or  involuted  continue  to  proliferate  and 
at  the  same  time  seem  to  migrate  for- 
ward toward  the  cephalic  border  and 
outward  toward  the  lateral  borders  of 
the  blastoderm  (Fig.  42).  They  do  not 
at  first  form  a  complete  layer  but  are 
more  or  less  scattered.  This  new  layer 
of  cells  is  the  entoderm  while  the  original 
layer  which  now  lies  over  it  comprises 
the  ectoderm.  The  two  layers  are  con- 
tinuous at  the  margin  of  the  sector 
where  involution  began.  This  margin 
is  the  anterior  lip  of  the  bias  to  pore,  a 
minute  cleft  between  the  margin  and 
the  yolk  behind  it,  which  leads  from  the 
exterior  into  the  space,  now  the  arch- 
enter  on,  beneath  the  double  layered 


EARLY  DEVELOPMENT  OF  THE  CHICK. 


71 


/>••>••%**•*•  I7*  Ills 

^/^A.V*.«  •*!••••  •*     l^'^l 

•v.   /  >-?v-:  ••-.•  •••*  -._•      5?  '*  o  -a 


72 


TEXT-BOOK  OF  EMBRYOLOGY. 


blastoderm.  Concomitant  with  involution  there  is  a  considerable  thick- 
ening of  the  lip  of  the  blastopore  where  the  ectoderm  and  entoderm  are 
continuous. 

•^  It  has  been  noted  that  the  germ  wall  is  interrupted  along  the  posterior 
margin  of  the  sector  after  the  disk  has  here  been  reduced  to  one  layer  of  cells. 
The  margin  of  the  sector  is  obviously  a  crescent,  so  that  the  blastopore  also 
is  originally  crescent-shaped  (Fig.  43,  A).  Then  as  gastrulation  proceeds 
the  horns  of  the  crescent  are  withdrawn  toward  the  median  line,  and  concomi- 


FIG.  43. — Diagrammatic  reconstructions  showing  surface  views  of  blastoderms  of  the  pigeon. 
Patterson,  from  Lillie.  A ,  from  same  blastoderm  as  shown  in  Fig.  41 ,  the  line  CD  indicating 
the  plane  of  section  of  Fig.  41;  the  numbers  1-7  indicate  the  thickness  of  the  blastoderm  in 
numbers  of  cells;  the  broken  line  around  i  includes  the  sector  which  is  one  cell  thick,  at  the 
posterior  margin  of  which  invagination  begins;  GW,  germ  wall.  B,  from  same  blastoderm 
as  shown  in  Fig.  42;  the  arrows  at  the  posterior  margin  indicate  the  advance  and  approach 
of  the  two  halves  of  the  margin;  E,  indicates  extent  of  entoderm;  O,  extension  of  disk  mar- 
gin beyond  germ  wall;  PA,  outer  margin  of  area  pellucida;  R,  margin  where  invagination  is 
progressing  (lip  of  blastopore) ;  Y  and  Z  together  indicate  region  of  germ  wall.  C,  from  a 
blastoderm  of  pigeon  38  hours  after  fertilization;  E  indicates  extent  of  entoderm;  R,  mass 
of  cells  where  blastopore  closed;  SG,  portion  of  blastoccel  not  yet  crossed  by  migrating 
entodermal  cells;  other  abbreviations  as  in  B. 


tantly  the  two  free  ends  of  the  germ  wall  approach  each  other  (Fig.  43,  B). 
Eventually  the  ends  of  the  germ  wall  meet  and  the  blastopore  is  closed ;  and 
since  the  germ  wall  lies  behind  the  closed  blastopore,  the  latter  is  no  longer 
situated  on  the  edge  of  the  disk  but  is  included  within  it  (Fig.  43,  C). 


EARLY  DEVELOPMENT  OF  THE  CHICK. 


73 


The  processes  of  development  thus  far  described  go  on  while  the  egg 
is  traversing  the  oviduct.  Development  ceases  when  the  egg  is  laid  and  cools; 
it  begins  again  only  if  the  temperature  is  raised.  If  the  temperature  remains 
below  about  25°  (Centigrade)  there  is  no  appreciable  development,  but  if 
brought  up  to  about  38°,  which  is  the  optimum,  development  progresses 
normally.  And  from  now  on,  the  ages  of  embryos  are  reckoned  from  the 


Area  opaca 
—  Area  pellucida 

—  Primitive  streak 


~  Area  pellucida 

f-    Area  opaca 

T~  Primitive  streak 

—  Blastopore 

(crescentic  groove) 


FIG.  44. — Surface  views  of  blastoderms  of  Haliplana,  showing  formation  of  primitive  streak. 

Schauinsland. 

beginning  of  incubation;  not  from  the  time  the  egg  is  laid  nor  from  the  time 
cleavage  begins. 

Gastrulation  in  the  bird  seems  to  be  a  simple  process  as  compared  with 
that  in  the  frog;  in  some  respects  it  is  even  simpler  than  in  Amphioxus. 
Rapid  cell  proliferation  is  of  course  a  common  incident  in  all  three  cases, 
particularly  along  the  lip  of  the  blastopore.  In  Amphioxus  invagination 
plays  the  important  part;  involution  and  epiboly  are  less  prominent.  In  the 


Area  opaca 
Area  pellucida 
Head  process 


Hensen's  node 


Primitive  streak 


Primitive  groove 


Post,  lip  of 
blastopore 


FIG.  45. — Surface  view  of  embryonic  disk  of  chick.     Bonnet. 

fro'g  invagination  is  greatly  reduced,  while  involution  and  epiboly  are  the 
most  conspicuous  features.  In  the  bird  invagination  and  epiboly  can  scarcely 
be  said  to  occur  at  all;  involution  appears  to  be  the  essential  process,  and 
with  it  a  specially  marked  migration  of  entodermal  cells  beneath 
the  ectoderm.  If  an  immediate  cause  for  the  differences  in  the  three  forms 
is  sought,  the  yolk  content  of  the  egg  offers  itself  as  a  mechanical  influence 
which  must  be  accepted  as  a  most  important  factor. 


74  TEXT-BOOK  OF  EMBRYOLOGY. 

A  When  incubation  commences  certain  changes  in  the  appearance  of  the 
Wastoderm  can  be  seen  on  the  surface.'»Lpurmg  the  first  day  a  narrow  band, 
which  is  slightly  more  opaque  than  the  Surrounding  area,  appears  in  front  of 
the  closed  blastopore  and  extends  forward  more  than  half  way  across  the 
area  pellucida.  It  seems  to  grow  from  the  blastopore;  as  a  matter  of  fact, 
however,  the  blastopore  recedes  and  leaves  the  band  in  its  trail.  This  is  the 
primitive  streak  (Figs.  44  and  45).  While  the  streak  grows  the  area  pellucida 
elongates  in  the  same  direction  and  becomes  oval,  the  broader  end  being 
anterior.  Then  a  transparent  line  appears  along  the  center  of  the  streak 
and  terminates  in  front  in  a  slight  enlargement.  In  front  of  this  enlargement 
the  streak  is  a  little  more  opaque  than  elsewhere.  The  transparent  line 
indicates  the  primitive  groove,  which  is  flanked  by  the  primitive  folds,  and  its 


•  Area  opaca 
Area  pellucida- 

M^^^Br 

•  Head  process 
•Medullary  folds 

Hensen's  node" 
Primitive  streak 


FIG.  46. — Surface  view  of  chick  blastoderm.     Bonnet. 

broadened  terminus  is  the  primitive  pit;  the  denser  portion  of  the  streak  in 
front  of  the  pit  is  the  primitive  knot  (Hensen's  knot).  Following  the 
development  of  the  primitive  streak  there  appears  in  front  of  it  a  narrow 
band,  less  conspicuous  than  the  streak  but  continuous  with  and  extending 
forward  from  the  primitive  knot.  This  is  known  as  the  primitive  axis  or 
head  process  (Fig.  46).  During  these  changes  in  appearance  the  blastoderm 
also  increases  in  total  area. 

The  primitive  streak  and  the  structures  associated  with  it  can  be  inter- 
preted properly  only  in  terms  of  sections.  A  transverse  section  through 
the  streak  near  its  center  shows  both  ectoderm  and  entoderm  merged  with  an 
intermediate  layer  which  is  obviously  mesoderm  (Fig.  47,  A ) .  It  is  the  thick- 
ness of  mass  resulting  from  the  fusion  of  the  three  layers  which  gives  the 
opaque  appearance  of  the  primitive  streak  when  seen  from  the  surface. 
The  primitive  groove  is  a  linear  depression  in  the  dorsal  side  of  the  streak,  and 


EARLY  DEVELOPMENT  OF  THE  CHICK. 


75 


the  primitive  folds  are  the  elevations  flanking  the  depression.  The  ectoderm 
is  thickened  perceptibly  for  some  distance  on  both  sides  of  the  groove,  thus 
forming  the  early  neural  plate.  Beyond  the  neural  plate  the  non-neural 
ectoderm  extends  laterally  to  the  edge  of  the  blastoderm,  in  fact  forming  its 
margin.  The  entoderm  is  a  thin  layer  which  extends  laterally  until  it  merges 
with  the  yolk  to  form  the  germ  wall.  The  cavity  beneath  is  the  archenteron, 
extending  from  the  germ  wall  on  one  side  to  that  on  the  opposite  side.  The 
mesoderm  at  this  time  is  not  an  extensive  layer,  for  it  constitutes  only  a  por- 
tion of  the  mass  of  the  primitive  streak  and  extends  laterally  only  a  short 
distance  between  the  other  two  layers  as  scattered  irregular  cells. 


Primitive  groove  and  folds 


Ectoderm 


—  Ectoderm 

Mesoderm 
— •  Entoderm 


FIG.  47. — Transverse  sections  of  blastoderm  of  chick  (21  hours'  incubation).     Hertwig. 

a,  Section  through  primitive  groove,  posterior  to  Hensen's  node. 

b,  Section  through  Hensen's  node. 

\/A  transverse  section  through  the  primitive  pit  shows  essentially  the  same 
structural  arrangement  as  in  the  streak  farther  caudally  (Fig.  47,  B).  In 
some  birds  the  pit  opens  into  the  archenteron,  but  not  in  the  chick.  The 
region  of  the  primitive  knot  also  shows  the  same  arrangement,  the  knot 
itself  being  an  elevation  just  in  front  of  the  pit.  Caudally  the  primitive 
groove  becomes  more  shallow  and  finally  disappears,  the  caudal  end  of  the 
streak  broadening  out  as  the  primitive  plate. 

The  morphological  significance  of  the  primitive  streak  is  a  question 
which  has  not  yet  been  unequivocally  answered.  It  is  generally  agreed,  but 
not  universally,  that  the  streak  is  the  homologue  of  the  blastopore  in  the 
lower  animals  on  the  ground  that  all  three  germ  layers  are  fused  as 
they  are  in  the  lip  of  the  blastopore,  that  it  marks  the  caudal  end  of  the 


76  TEXT-BOOK  OF  EMBRYOLOGY. 

embryo  as  does  the  blastopore,  and  that  in  some  birds  the  primitive  pit 
opens  into  the  archenteron  in  the  same  manner  as  the  blastopore.  It  has 
already  been  pointed  out  that  the  caudal  margin  of  the  sector  where  the  blas- 
toderm has  been  reduced  to  the  thickness  of  one  layer  of  cells  was  rolled  or 
tucked  under  when  gastrulation  began,  and  that  the  germ  wall  was  lacking 
along  this  margin.  It  was  also  stated  that  as  gastrulation  proceeded  the 
two  ends  of  the  germ  wall  approached  each  other  and  eventually  met  behind 
the  margin  of  the  sector,  and  that  the  two  horns  of  the  crescentic  groove 
were  withdrawn  toward  the  median  line  and  finally  closed  (Fig.  43).  Imme- 
diately after  these  phenomena  the  primitive  streak  appears,  extending  for- 
ward from  the  center  where  the  horns  of  the  crescent  were  drawn  in  and  closed. 
It  would  seem  therefore  that  the  formation  of  the  primitive  streak  is  a  con- 
tinuation of  the  gastrulation  process. 

Head  process        Neural  plate 

Ectoderm 
Mesoderm 
^l—  Entoderm 

Yolk  cell 


FIG.  48. — Transverse  section  of  blastoderm  of  chick  (21  hours'  incubation).     Hertwig.     Section 
through  head  process,  anterior  to  Hensen's  node. 

In  Fig.  46  there  can  be  seen  the  slightly  opaque  band  extending  for- 
ward from  the  primitive  streak  which  has  been  designated  the  primitive  axis 
or  head  process.  In  cross  section  (Fig.  48)  it  is  obvious  that  the  opacity  is 
due  to  the  fused  mass  of  entoderm  and  mesoderm,  while  the  ectoderm  here  is  a 
separate  layer.  In  a  longitudinal  section  which  includes  both  axis  and  streak 
(Fig.  49)  the  ectoderm  is  observed  to  fuse  with  the  other  two  layers  at  the 
anterior  end  of  the  streak.  It  is  probable  that  the  primitive  axis  is  not  the 
result  of  a  forward  growth  from  the  end  of  the  streak,  but  is  the  result  of 
the  separation  of  the  ectoderm  from  the  other  two  layers  from  before  back- 
ward. That  is,  if  one  imagines  the  primitive  streak  at  its  full  development 
before  the  axis  has  appeared,  and  then  imagines  a  wedge  started  just  beneath 
the  ectoderm  and  driven  backward,  one  can  readily  see  that  the  ectoderm 
will  be  separated  from  the  underlying  and  still  fused  mesoderm  and  entoderm. 
As  this  continues  the  axis  thus  becomes  longer.  The  streak  does  not  become 
correspondingly  shorter,  however,  because  it  increases  at  the  caudal  end; 
in  other  words,  as  the  primitive  axis  increases  in  length  the  primitive  streak 
recedes  or  is  carried  backward  by  additions  to  its  own  organization.  This 


EARLY  DEVELOPMENT  OF  THE  CHICK. 


77 


exemplifies  again  the  general  principle  that  growth  and  differentiation  in  the 
early  stages  proceed  from  before  backward. 
x|  Origin  of  the  Mesoderm.— The 
presence  of  the  mesoderm  between 
the  other  two  layers  in  and  lateral 
to  the  primitive  streak  has  already 
been  noted  (Fig.  47).  The  cells 
composing  the  mesoderm  appear  to 
arise  in  the  streak  and  migrate  lat- 
erally as  irregular  elements  which  are 
so  scattered  that  they  do  not  at  first 
form  a  complete  layer.  Whether 
they  originate  from  ectoderm  or 
entoderm  is  difficult  to  determine. 
The  interpretation  by  those  who 
have  studied  the  problem  most  care- 
fully is  that  the  early  mesoderm  cells 
originate  and  differentiate  from  the 
thickened  ectoderm  along  the  prim- 
itive groove.  The  migrating  cells 
multiply  rapidly  and  soon  a  complete 
layer  is  formed  which  extends  across 
the  pellucid  area  until  its  margin 
overlaps  the  opaque  area.  The 
growth  of  the  mesoderm  is  at  first 
most  rapid  around  the  caudal  end  of 
the  primitive  streak,  then  it  extends 
across  the  clear  area  laterally,  and 
finally  reaches  forward  on  the  two 
sides  as  horns  which  meet  in  front  of 
the  developing  embryo  but  leave  an 
area  (the  proamnion)  in  the  head 
region  unoccupied  by  mesoderm  until 
much  later. 

When  the  mesoderm  overlaps  the 
opaque  area  this  area  thus  becomes 
three-layered,  comprising  ectoderm, 
mesoderm  and  germ  wall.  The  meso- 
derm, if  it  does  not  actually  merge 
with  the  germ  wall,  at  least  establishes  intimate  contact  with  it.  While  the 
mesodermal  cells  that  arose  in  the  primitive  streak  continue  to  proliferate, 


11  = 

IP 


.       . 
tl  °  SS 


<a    r-g 

I     *«*     «0     S 

I  § 


78  TEXT-BOOK  OF  EMBRYOLOGY. 

thus  augmenting  the  layer  generally,  there  is  also  evidence  that  new  meso- 
dermal  cells  are  added  by  differentiation  of  the  entodermal  elements  of  the 
germ  wall.  This  probable  origin  of  mesodermal  cells  from  the  yolk  cells  of 
the  germ  wall  is  comparable  with  the  formation  of  mesoderm  around  the  gut 
in  the  frog  (p.  60).  As  the  germ  wall  recedes  by  encroachment  of  the 
entoderm  upon  the  yolk,  and  the  pellucid  area  becomes  correspondingly  more 
extensive,  the  mesoderm  likewise  increases  in  extent. 

^j  Almost  as  soon  as  the  margin  of  the  mesoderm  overlaps  the  germ  wall 
and  begins  to  extend  over  the  area  opaca,  small  dense  clusters  of  cells  appear 
in  the  mesoderm  in  close  relation  to  the  yolk  cells.  These  are  the  blood  is- 
lands from  which  arise  the  early  blood  vessels  and  blood  cells,  and  the  area 
occupied  by  them  is  known  as  the  area  vasculosa  (Fig.  51).  They  appear, 
first  caudal  to  the  primitive  streak  and  then  farther  forward  on  both  sides, 
almost  keeping  pace  with  the  mesoderm'  itself.  The  islands  increase  in 
size  and  coalesce  irregularly  to  form  a  network  or  plexus  which  is  one  of  the 
conspicuous  features  of  the  blastoderm  (Fig.  156).  The  cells  at  the  pe- 

Neural  plate  Notochord 

I' —  Ectoderm 

—  Mesoderm 
. — .  Entoderm 
— •  Archenteron 


FIG.  50. — Transverse  section  of  blastoderm  of  chick  (40  hours'  incubation).     Hertwig.     Section 
taken  short  distance  anterior  to  Hensen'  node. 

riphery  become  flat  and  arranged  edge  to  edge  to  form  endothelial  tubes  or 
vessels  within  which  the  central  cells  are  contained  as  primitive  blood  cells 
(Fig.  158).  The  plexus  then  gradually  extends  across  the  pellucid  area 
toward  the  axis  of  the  blastoderm  where  the  embryonic  body  is  developing. 
It  is  obvious  that  blood  vessels  and  blood  cells  develop  relatively  earlier  in 
the  bird  than  in  either  Amphioxus  or  the  frog. 

The  notocord  develops  out  of  the  fused  mass  of  entoderm  and  meso- 
derm of  the  primitive  axis,  whether  from  the  one  layer  or  the  other  being  diffi- 
cult to  determine.  It  thus  becomes  a  rod  of  cells  extending  forward  from 
the  front  end  of  the  primitive  streak  and  separating  the  mesoderm  on  one 
side  from  that  on  the  other.  The  formation  of  the  notocord  as  the  axial 
structure  of  the  future  embryo  destroys  the  primitive  axis,  and  the  ento- 
derm now  becomes  a  distinct  and  separate  layer  (Fig.  50) . 

Summing  up,  it  may  be  said  that  about  the  beginning  of  the  second  day 
of  incubation  the  mesoderm  comprises  a  sheet  of  cells  between  ectoderm 
and  entoderm.  It  extends  caudally  and  laterally  from  the  primitive  streak 
where  it  i?  merged  with  the  other  two  layers.  In  front  of  the  streak  it  ex- 


EARLY  DEVELOPMENT  OF  THE  CHICK. 


79 


tends  laterally  from  the  notocord  (which  here  separates  the  sheet  into  the 
two  lateral  portions)  and  forward  like  a  horn  over  the  area  opaca  on  each 
side.  Over  a  portion  of  the  area  opaca  the  network  of  blood  islands  and 
vessels  forms  a  prominent  differentiated  part  of  the  mesoderm. 

\/  From  this  time  on,  the  changes  in  the  mesoderm  are  rapid  and  extensive. 
The  cells  multiply  rapidly,  resulting  in  a  thickening  of  the  layer  generally. 
Along  each  side  of  the  notocord  the  paraxial?  portion  becomes  distinctly 
thicker  and  then  shades  off  into  the  thinner  lateral  portion.  A  short  dis- 
tance ahead  of  the  primitive  streak  the  paraxial  band  becomes  marked  off 


Neuropore 


Fore-brain  vesicle 


Head  fold 


Area  pellucida 

Area  vasculosa 
Area  opaca 

Yolk 


Edge  of 
blastoderm 


~  Proamnion 


Mid-  and  hind- 
brain  vesicles 


Neural  fold 


PFic.  51. — Dorsal  view  of  chick  embryo  with  ten  pairs  of  mesodermal  somites.  Bonnet. 
:ransversely  into  blocks  by  a  loosening  of  the  cells  between  the  blocks. 
These  are  bilaterally  symmetrical  and  are  at  once  recognized  as  mesodermal 
somites  (Fig.  51).  The  pair  that  appears  first  is  the  second  pair  of  somites 
in  the  series,  the  first  pair  of  the  series  being  represented  by  a  close  aggre- 
gation of  cells  in  front  of  the  first  cleft.  This  has  been  shown  experimentally 
by  delicately  injuring  the  first  pair  with  an  electric  needle  and  then  allowing 
the  blastoderm  to  continue  to  develop  for  several  hours;  it  was  found  that 
the  other  somites  of  the  series  appeared  behind  the  injury.  A  third  pair 


80 


TEXT-BOOK  OF  EMBRYOLOGY. 


appears  behind   the  second,   then  a  fourth  pair,  and  so  on  through  the 


series. 


Developing  from  before  backward,  the  somites  here  as  in  Amphioxus  and 
the  frog  again  illustrate  the  general  principle  that  growth  progresses  from 
before  backward.  The  first  somites  appear  only  a  short  distance  in  front 
of  the  primitive  streak,  about  where  the  anterior  end  of  the  primitive  axis 
was  located,  and  the  paraxial  band  of  mesoderm  between  the  somites  and  the 
streak  is  wholly  unsegmented.  Then,  as  successive  somites  appear  and  the 
band  becomes  thus  far  segmented,  new  cells  are  constantly  added  at  the 
caudal  end  of  the  band  as  the  primitive  streak  recedes,  so  that  eventually 
the  whole  series  of  somites  (more  than  40  pairs  in  the  chick)  is  still  followed 
by  the  primitive  streak  which  now  lies  at'  the  caudal  end  of  the  embryo. 


Ectoderm 


Neural        Primitive 
tube  segment 


Entoderm 


Coelom 


FIG.  52. — Transverse  section  of  chick  embryo  (2  days  incubation).     Photograph. 
The  parietal  mesoderm  (lying  above  the  coelom)  is  not  labeled.     The  two  large  vessels  under 
the  primitive  segments  are  the  primitive  aortae.     Spaces  separating  germ  layers  are  due  to 
shrinkage. 

Each  somite  is  composed  of  massive  epithelium  whose  cells  converge 
toward  a  small  central  cavity  (myoccel).  The  latter  cavity,  however, 
contains,  a  few  loosely  arranged  cells  (Fig.  52).  Laterally  each  somite  is 
continuous  with  a  much  thinner  mass  or  plate  of  cells,  known  as  the  inter- 
mediate cell  mass  or  nephrotome,  which  in  turn  merges  with  the  lateral 
mesoderm  of  the  area  pellucida. 

The  sheet  of  lateral  mesoderm  becomes  separated  into  two  plates  or 
layers,  an  outer  which  is  apposed  to  ectoderm  and  an  inner  apposed  to  ento- 
derm.  In  many  places  small  clefts  appear  among  the  cells,  grow  larger  and 
finally  coalesce  to  form  a  continuous  cavity,  the  ccelom,  which  in  its  greatest 


EARLY  DEVELOPMENT  OF  THE  CHICK.  81 

extent  reaches  from  the  outer  edge  of  the  nephrotome  to  the  margin  of  the 
area  vasculosa.  The  cleft-like  ccelom  develops  on  the  ectodermal  side  of 
the  blood  islands  and  vessels,  so  that  these  structures  are  at  first  confined 
to  the  inner  layer  of  mesoderm  which  lies  close  to  the  entoderm.  The 
ccelom  is  the  rudiment  of  the  serous  cavities  of  the  adult — the  pleural,  peri- 
cardial  and  peritoneal  cavities.  The  layer  of  mesoderm  apposed  to  ectoderm 
is  known  as  the  parietal  or  somatic  layer,  while  that  apposed  to  entodeim 
is  called  the  visceral  or  splanchnic  layer  (Fig.  52).  By  comparison  with 
Amphioxus  and  the  frog  it  is  seen  that  ectoderm  and  somatic  mesoderm  con- 
stitute the  body  wall  and  that  entoderm  and  visceral  mesoderm  comprise 
the  wall  of  the  archenteron  or  gut  cavity,  although  in  the  chick  the  germ 
layers  at  this  stage  are  still  spread  out  on  the  surface  of  the  large  yolk 
mass. 

Another  structure  of  early  origin,  as  in  the  lower  forms  dealt  with  in  the 
preceding  chapters,  is  the  neural  plate.  When  the  primitive  axis  appears, 
the  ectoderm  is  moderately  thickened  into  a  broad  band  over  the  axis  itself 
and  extending  backward  over  the  primitive  streak.  This  thickened  ecto- 
derm represents  the  rudiment  of  the  nervous  system  and  is  known  as  the 
neural  or  medullary  plate  (Fig.  50).  Laterally  it  gradually  becomes  thinner 
and  shades  off  into  the  non-neural  ectoderm.  As  development  proceeds 
the  anterior  end  of  the  plate  becomes  broader,  indicating  already  the  heavier 
brain  region.  The  plate  is  composed  of  columnar  epithelium  possibly 
pseudo-stratified.  When  the  somites  begin  to  develop,  a  broad  groove — the 
neural  groove — appears  along  the  center  of  the  plate,  thus  producing  ridges 
—the  neural  ridges  or  folds — along  the  sides  of  the  groove.  The  ridges  be- 
come higher  and  bend  in  toward  the  median  line  until  they  meet  over  the 
groove.  The  meeting  occurs  first  in  the  region  of  the  brain;  then  fusion 
occurs  and  a  tube— the  neural  tube — is  thus  formed  (Fig.  52).  The  meeting 
and  fusion  gradually  progress  backward.  It  is  obvious  from  these  conditions 
that  the  neural  tube  in  the  main  is  formed  from  before  backward;  in  fact 
even  when  closure  has  occurred  in  the  brain  region,  the  caudal  region  ex- 
hibits still  the  flat  neural  plate  while  the  intermediate  portion  shows  all 
stages  between  the  two  extremes. 

Body  Form.— In  Amphioxus  and  the  frog  the  cylindrical  body  form  of 
the  embryo  results  from  simple  elongation  of  the  gastrula.  In  these  forms 
the  yolk  is  wholly  encompassed  by  the  egg  cytoplasm,  is  contained  in  the 
entodermal  cells  of  the  gastrula,  and  is  wholly  enclosed  within  the  embryonic 
body,  being  gradually  consumed  as  the  organism  develops.  In  the  bird 
only  a  small  portion  of  the  great  quantity  of  yolk  is  enclosed  within  the 
cytoplasm  of  the  mature  egg;  the  cytoplasm  is  really  only  a  small  disk  resting 
upon  the  yolk.  As  development  proceeds  the  cytoplasmic  disk  takes  the 


82  TEXT-BOOK  OF  EMBRYOLOGY. 


only  active  part;  in  the  gastrula  the  two  primary  germ  layers  are  simply 
spread  out  on  the  surface  of  the  yolk  mass;  the  appearance  of  the  mesoderm 
does  not  alter  the  general  conditions.  Finally,  however,  in  the  latter  part 
of  the  incubation  period,  the  germ  layers  grow  over  the  entire  surface  of 
the  yolk  like  membranes;  but  this  does  not  imply  that  the  yolk  is  enclosed 
within  the  embryonic  body. 

The  body  of  the  embryo  arises  from  a  relatively  small  portion  of  the 
blastoderm,  and  its  position  is  indicated  by  the  primitive  streak  and  head 
process  which  lie  in  its  long  axis.  As  they  develop,  the  neural  tube  and 
mesodermal  somites  produce  a  thickening  of  the  blastoderm  which  becomes 
slightly  elevated  like  a  rounded  ridge  above  the  general  level  of  the  surface 
(Fig.  52).  Just  in  front  of  the  cephalic  end  of  the  neural  tube  a  transverse 
crescentic  groove,  the  head  fold,  appears  and  sharply  delimits  the  cephalic 
end  of  the  body.  The  rapidly  growing  brain  then  projects  over  the  groove, 
giving  the  appearance  that  the  germ  layers  at  the  bottom  of  the  groove  are 
being  tucked  beneath  the  head-end  of  the  embryo.  The  horns  of  the  cres- 
centic head  fold  extend  caudally  along  the  sides  of  the  thickening  produced 
by  the  neural  tube  and  somites,  thus  delimiting  the  body  region  laterally. 
These  lateral  grooves  become  deeper  from  before  backward  and  eventually 
reach  the  level  of  the  primitive  streak.  Finally  a  transverse  fold,  the  tail 
fold,  appears  caudal  to  the  primitive  streak  and  becomes  continuous  on 
each  side  with  the  lateral  fold.  The  whole  embryonic  body  thus  becomes 
surrounded  and  delimited  by  a  gutter. 

The  gutter  or  groove  becomes  deeper  as  the  embryo  continues  to  grow; 
the  head-end  of  the  body  projects  farther  over  the  head  fold  and  the  tail- 
end  farther  over  the  tail  fold.  The  effect  is  much  as  if  the  body  was  being 
constricted  or  pinched  off  from  the  remainder  of  the  blastoderm.  The 
remainder  of  the  blastoderm,  composed  of  the  extraembryonic  portion  of 
the  germ  layers,  engages  in  the  development  of  the  yolk  sac  and  certain 
other  appendages  which  are  useful  during  the  period  of  incubation.  The 
yolk  sac  and  not  the  embryonic  body  contains  the  yolk  that  was  present  in 
the  ovum.  The  yolk  sac  is  an  appendage  of  the  gut,  it  is  true,  but  the  yolk 
substance  is  carried  to  the  embryo  by  the  blood  circulating  through  the 
vitelline  vessels. 

References  for  Further  Study. 

BLOUNT,  MARY:  The  early  Development  of  the  Pigeon's  Egg  with  especial  Reference 
to  the  Supernumerary  Sperm  Nuclei,  the  Periblast  and  the  Germ  Wall.  Biological 
Biilletin,  Vol.  13,  1917. 

DUVAL,  M.:  Atlas  d'Embryologie.     Paris,  1889. 

HARPER,  E.  H.:  The  Fertilization  and  early  Development  of  the  Pigeon's  Egg.  Am. 
Journal  of  Anat.,  Vol.  3, 1904. 


EARLY  DEVELOPMENT  OF  THE  CHICK.  83 

KELLICOTT,  W.  E.:  Chordate  Development.     Chap.  IV,  1913. 

LILLIE,  FRANK  R.:  The  Development  of  the  Chick.     2nd  Ed.,  1908. 

PATTERSON,  J.  T.:  Studies  on  the  Early  Development  of  the  Hen's  Egg.  I.  History 
of  the  Early  Cleavage  and  of  the  Accessory  Cleavage.  Journal  of  Morphology, Vol.  21, 1910. 

PATTERSON,  J.  T.:  Gastrulation  in  the  Pigeon's  Egg.  A  Morphological  and  Experi- 
mental Study.  Journal  of  Morphology,  Vol.  20,  1909. 

PEEBLES,  FLORENCE:  The  Location  of  the  Chick  Embryo  upon  the  Blastoderm. 
Journal  of  Experimental  Zoology,  Vol.  i,  1904. 


CHAPTER  VII. 
EARLY  MAMMALIAN  DEVELOPMENT. 

It  is  perhaps  unfortunate  for  the  student  beginning  the  study  of  embry- 
ology that  no  mammalian  form  can  be  taken  for  the  early  developmental 
stages  and  regarded  as  wholly  typical  of  the  subclass.  While  there  are 
certain  fundamental  principles  of  development  in  common  in  all  placental 
mammals,  there  are  also  features  which  vary  in  different  orders.  In  this 
chapter  no  attempt  will  be  made  to  set  forth  one  line  of  development  as 
typical,  nor  will  all  the  variations  in  the  different  orders  be  presented.  We 
shall  attempt  to  present  the  fundamental  principles  as  exemplified  in  certain 
of  the  mammalian  forms  and  to  sketch  briefly  the  early  stages  of  human 
ontogeny. 

The  mammalian  ovum  represents  the  meiolecithal  type  in  which  there  is 
only  a  small  quantity  of  yolk.  Taking  the  human  ovum  as  an  example, 
the  cell  is  approximately  two-tenths  of  a  millimeter  in  diameter  and  is  not 
truly  spherical  but  slightly  ovoid  in  shape  (Thomson).  In  section  it  presents 
the  appearance  of  the  traditional  typical  cell  (Fig.  i).  The  cytoplasm  is 
coarsely  granular  owing  to  the  presence  of  suspended  globules  of  deutoplasm 
or  yolk.  Most  of  the  yolk  globules  are  congregated  near  the  center  of  the 
cell,  around  the  nucleus,  while  the  peripheral  cytoplasm  is  nearly  destitute 
of  yolk.  The  nucleus  is  slightly  eccentric  and  exhibits  a  distinct  nuclear 
membrane,  a  single  plasmosome  and  rather  scanty  chromatin. 

In  most  mammals  on  which  observations  have  been  made  maturation 
or  reduction  of  chromosomes  begins  in  the  ovary,  the  first  polar  body  being 
formed  before  the  Graafian  follicle  ruptures.  The  second  polar  body  is 
formed  after  the  ovum  escapes  from  the  follicle;  in  the  mouse  for  example  it 
is  extruded  when  the  ovum  reaches  the  oviduct  and  after  the  sperm  has 
entered  the  cytoplasm.  According  to  recent  observations  made  by  Thomson 
on  an  extensive  series  of  human  ovaries,  both  polar  bodies  are  extruded  by 
the  ovum  prior  to  ovulation.  The  phenomena  of  ovulation  are  discussed 
in  the  chapter  on  "The  Germ  Cells,"  p.  23,  et  seq. 

It  is  generally  agreed  that  the  normal  site  of  fertilization  of  the  mammalian 
ovum  is  the  upper  (or  outer)  third  of  the  oviduct  or  Fallopian  tube.  The 
spermatozoa  pass  from  the  vagina  through  the  uterus  and  into  the  oviducts 
where  they  remain  viable  and  capable  of  fertilizing  for  a  considerable  period 
of  time,  perhaps  several  days  or  even  weeks.  In  the  oviduct  the  ovum  is  met 
by  numerous  spermatozoa  and  one  of  the  latter  penetrates  the  egg  cytoplasm. 

84 


EARLY  MAMMALIAN  DEVELOPMENT.  85 

In  the  white  rat,  as  an  example,  the  entire  sperm  enters  the  ovum.  After 
entrance  the  middle-piece  shows  increased  stainability  and  the  spiral  thread, 
which  is  probably  of  mitochondrial  origin,  becomes  evident.  The  sperm 
head  containing  the  nucleus  enlarges  and  becomes  vacuolated  and  the 
centrioles  and  polar  rays  appear.  As  the  sperm  nucleus  forms  the  male 
pronucleus,  the  chromosomes  remaining  after  the  second  maturation  division 
of  the  egg  are  resolved  into  the  female  pronucleus.  The  two  pronuclei  come 
in  contact  near  the  center  of  the  ovum. 

Observations  on  mammalian  ova  are  not  yet  sufficient  to  justify  any 
conclusions  regarding  the  effect  of  fertilization  on  the  polarity  or  internal 
organization  of  the  cells.  It  has  been  therefore  impossible  to  trace  in  sub- 
sequent stages  of  development  any  relation  between  egg  organization  and 
the  planes  and  constitution  of  the  body  in  the  mammal. 

Cleavage. — As  in  the  lower  forms,  cleavage  of  the  fertilized  mammalian 
ovum  is  primarily  a  series  of  mitotic  divisions  resulting  in  a  solid  cluster  of 


a  b  c  d 

FIG.  53. — Four  stages  in  the  cleavage  of  the  ovum  of  the  white  rat.  Huber.  A,  from  a  model 
of  an  ovum  in  the  pronuclear  stage,  24  hours  after  insemination;  B,  from  a  model  of  a 
2-cell  stage,  2  days  after  insemination;  C,  from  a  model  of  a  4-cell  stage,  3  days  and  i  hour 
after  insemination;  D,  from  a  model  of  an  8-cell  stage,  3  days  and  u  hours  after  insemina- 
tion. 

cells.  This  has  been  observed  in  detail  in  several  mammals:  the  opossum 
(Hartman),  the  white  rat  (Huber),  the  white  mouse  (Sobotta),  and  a  few 
others.  Cleavage  in  these  formsjsjrregulaPand  the  blastomeres  are  approxi- 
mately equal  in  size  (Figs.  53  and  54).  The  cluster  is  known  as  the  morula, 
which  corresponds  to  the  similar  stage  in  lower  animals. 

In  certain  mammals,  for  example  the  bat  (van  Beneden),  the  superficial 
cells  of  the  morula  become  differentiated  from  those  in  the  interior  and  form 
a  continuous  covering  layer  (Fig.  55,  a  and  b).  Following  this  differentiation, 
many  of  the  internal  cells  become  vacuolated,  the  vacuoles  coalesce  and  finally 
the  cells  disappear  thus  leaving  a  cavity.  At  one  side  of  this  cavity  some  of 
the  internal  cells  remain  intact  and  attached  in  a  cluster,  known  as  the 
inner  cell  mass,  to  the  covering  layer  (Fig.  55,  c  and  d).  In  other  mammals, 
for  instance  the  white  rat  (Huber),  a  cavity  is  formed  within  the  morula  by 
displacement  of  the  central  cells  toward  the  periphery,  most  of  the  cells 
moving  to  one  side  where  they  form  a  cluster  which  is  continuous  with  the 


86 


TEXT-BOOK  OF  EMBRYOLOGY. 


FIG.  54. — Four  stages  in  cleavage  of  the  ovum  of  the  mouse.     Sobotta.     Small  cell  marked  with 

x  is  the  polar  body. 


FIG.  55. — Four  stages  in  the  development  of  the  bat.     van  Beneden. 

a,  Section  of  morula;  b,  section  of  later  stage  of  morula,  showing  differentiation  of  outer  layer  of 
cells;  c,  section  of  still  later  stage,  showing  vacuolization  of  central  cells;  d,  section  showing 
outer  layer  (trop'hoderm)  and  inner  cell  mass. 


EARLY  MAMMALIAN  DEVELOPMENT. 


87 


thinner  portion  of  the  wall  (Fig.  56).  In  the  opossum  (Hartman)  no  true 
morula  is  formed,  since  during  even  the  earliest  cleavage  stages  the  cells  are 
arranged  in  a  layer  around  a  central  cavity  which  in  this  case  contains  some 


FIG.  56.  FIG.  57. 

FIG.  56. — Sections  of  blastocysts  of  the  white  rat,  5  days  after  insemination.  Huber.  Note  the 
cavity  within  the  structure  and  the  cluster  of  cells,  comparable  to  the  inner  cell  mass 
which  forms  part  of  the  vesicle. 

FIG.  57. — Section  of  a  1 6-cell  stage  of  an  ovum  of  the  opossum.     Hartman.     Blastocyst  formation 
is  anticipated  in  that  the  cells  are  arranged  around  the  cleavage  cavity,  and  will  be  com- 
pleted when  the  gaps  (i)  are  closed.     The  black  masses  represent  yolk  globules  in  the 
t.    cytoplasm  and  in  the  cleavage  cavity. 

yolk  material  (Fig.  57).     In  Fig.  58  there  is  shown  a  section  of  the  developing 
ovum  of  the  lemur,  Tarsius  spectrum,  in  which  the  covering  layer  and  inner 


FIG.  58. — Section  of  the  blastocyst  of  the  lemur,  Tarsius  spectrum.     Hubrecht,  from  Quain's 
Anatomy,     i,  Inner  cell  mass;  2,  trophoderm. 

cell  mass  are  very  evident  (Hubrecht).  The  hollow  structure  illustrated  in 
the  four  forms  above  is  called  the  blastocyst  (or  not  quite  so  correctly,  the 
blastodermic  vesicle).  It  is  not  regarded  as  homologous  to  the  blastula  of 


88  TEXT-BOOK  OF  EMBRYOLOGY. 

lower  forms.  The  inner  cell  mass  is  destined  to  form  the  embryo  proper 
while  the  covering  layer  gives  rise  to  certain  accessory  structures.  The 
covering  layer  receives  the  name  trophoderm  (trophoblast)  because  in  sub- 
sequent development  the  nutriment  for  and  waste  from  the  growing  embryo 
must  pass  through  it. 


FIG.  59. — Sections  of  blastodermic  vesicle  of  bat,  showing  (a)  formation  of  the  entoderm  and 
(b  and  c]  of  the  amniotic  cavity,     van  Beneden. 

v/  Ectoderm  and  Entoderm. — In  the  lower  forms  described  in  the  earlier 
chapters  the  two  primary  germ  layers  arose  through  the  process  of  gas- 
trulation.  In  mammals  generally  gastrulation  is  masked  under  highly 
modified  processes  which  are  probably  determined  by  the  peculiarities  of 
cleavage  and  blastocyst  formation  in  the  mammalian  ovum.  It  is  usually 
difficult  to  recognize  any  phenomenon  in  germ  layer  formation  in  mammals 


EARLY  MAMMALIAN  DEVELOPMENT. 


as  wholly  comparable  to  invagination  or  epiboly  or  involution  in  the  lower 
forms.  The  results  are  arrived  at  by  abbreviated  or  caenogenetic  steps  in 
which  the  characteristics  of  the  lower  forms  are  profoundly  modified. 

Taking  the  bat  again  as  an  example,  some  of  the  cells  of  the  inner  cell 
mass  bordering  the  cavity  of  the  blastocyst,  or  yolk  cavity,  become  differen- 
tiated, proliferate  and  migrate  around  on  the  inner  surface  of  the  trophoderm, 
forming  there  a  complete  layer  and  lining  for  the  cavity.  This  new  layer  is 
the  primary  entoderm  (Fig.  59,  a;  compare  with  Fig.  55,  d).  Immediately 
following  the  formation  of  the  entoderm  many  of  the  cells  of  the  inner  cell 
mass  become  vacuolated  and  disappear,  resulting  in  the  formation  of  a  cavity 
between  the  overlying  trophoderm  and  the  cells  contiguous  to  the  entoderm. 
This  new  cavity  is  the  amniotic  cavity  (Fig.  59,  b  and  c).  The  two  cavities  are 


fern. 


1fefe«S^ 


FIG.  60. — Three  stages  in  the  formation  of  the  germ  layers  in  the  lemur,  Tarsius  spectrum. 
Hubrecht,  from  Quain's  Anatomy,  fcm.,  Inner  cell  mass;  emb.  ect.,  embryonic  ectoderm; 
ent.,  entoderm. 

separated  therefore  by  a  double-layered  plate,  the  embryonic  disk,  the  layer 
bordering  the  amniotic  cavity  comprising  the  embryonic  ectoderm  (Fig.  59,  c). 
In  the  lemur,  Tarsius  spectrum,  the  differentiating  entodermal  cells,  instead 
of  spreading  over  the  inner  surface  of  the  trophoderm,  form  a  small  sac 
within  the  larger  cavity  (Fig.  60,  a,  b,  c).  In  Tarsius  the  inner  cell  mass 
seems  to  invaginate  from  its  outer  side  and  the  definite  layer  of  cells  thus 
resulting  becomes  the  embryonic  ectoderm  (Fig.  60,  c).  Subsequently  the 
inverted  ectoderm  becomes  straightened  out  so  that  the  embryonic  disk  is 
flat.  In  either  case  the  embryonic  disk  is  destined  to  give  rise  to  the' 
embryonic  body. 

In  the  white  rat  the  progress  of  development  following  the  formation  of 
the  blastocyst  is  marked  by  a  curious  inversion  of  the  inner  cell  mass,  giving 
rise  to  a  condition  known  as  inversion  or  entypy  of  the  germ  layers.  This 


90 


TEXT-BOOK  OF  EMBRYOLOGY. 


FIG.  61. — Sections  of  blastocysts  of  the  white  rat,  showing  inversion  (entypy)  of  the  germ  layers. 
Huber.  A,  blastocyst  6  days  and  14  hours  after  insemination.  B,  blastocyst  8  days  and 
1 8  hours  after  insemination,  with  egg-cylinder  cut  longitudinally.  C,  similar  section  of 
blastocyst  7  days  and  22  hours  after  insemination  (younger  than  B  but  further  advanced 
in  development),  showing  beginning  of  proamniotic  cavity.  D,  similar  section  of  blastocyst 
8  days  after  insemination  (younger  than  B  but  further  advanced  in  development),  showing 
more  advanced  proamniotic  cavity. 

i,  Ectoplacental  cone;  2,  ectodermal  node;  3,  primary  embryonic  ectoderm;  4,  extraembryonic 
ectoderm;  5,  transitory  ectoderm  (original  wall  of  blastocyst);  6,  proamniotic  cavity; 
7,  visceral  entoderm;  8,  cells  of  parietal  entoderm;  9,  primary  embryonic  entoderm. 


EARLY  MAMMALIAN  DEVELOPMENT.  91 

condition  is  characteristic  of  a  number  of  rodents,  including  the  rat,  guinea- 
pig  and  mouse.  The  cluster  of  cells  on  one  side  of  the  blastocyst  increases 
in  size  by  proliferation  of  the  cells  and  enlargement  of  individual  members  of 
the  group  so  that  it  projects  outward  somewhat  and  inward  into  the  cavity  of 
the  vesicle  (Fig.  61,  A).  Within  the  cluster  a  small  group  of  cells  becomes 
differentiated  (staining  more  deeply)  which  represents  the  rudiment  of  the 
ectodermal  node.  The  layer  of  cells  covering  this  node  on  the  side  toward 
the  cavity  is  the  entoderm.  The  group  of  cells  projecting  outward  is  known 
as  the  ectoplacental  cone.  Following  this,  the  vesicle  elongates  and  the 
ectodermal  node  appears  to  be  forced  farther  into  the  blastocyst  cavity  by  a 
group  of  cells  which  develops  between  the  node  and  the  ectoplacental  cone 
and  which  is  extraembryonic  ectoderm  (Fig.  61,  B).  The  entoderm  is  more 
extensive,  covering  the  ectodermal  node  and  much  of  the  extraembryonic 
ectoderm.  At  this  stage  it  is  evident  that  entoderm  is  outside  of  ectoderm, 
the  condition  which  has  given  rise  to  the  term  'inversion  of  the  germ  layers.' 
The  two  layers  together  constitute  the  egg-cylinder  (of  Sobotta). 

As  development  proceeds  there  is  still  further  elongation  of  the  vesicle, 
with  concomitant  lengthening  of  the  egg-cylinder.  Within  the  ectodermal 
node  a  cavity  appears,  and  around  this  the  cells  arrange  themselves  in  the 
form  of  a  simple  columnar  epithelium.  The  space  is  known  as  the  proamni- 
tic  cavity  (Fig.  61,  C).  The  original  wall  of  the  blastocyst,  except  at  the 
ectoplacental  cone,  is  drawn  out  into  a  thin  membrane-like  layer.  The 
cone  itself  is  longer.  Following  this  stage  a  number  of  discrete  spaces  appear" 
among  the  extraembryonic  ectodermal  cells  and  then  coalesce  to  form  one 
continuous  cavity  which  breaks  through  into  and  becomes  continuous  with 
the  proamniotic  cavity  of  the  original  node  (Fig.  61,  D).  The  cells  around 
this  new  cavity  are  also  arranged  as  a  simple  columnar  epithelium;  but  the 
boundary  line  between  embryonic  and  extraembryonic  ectoderm  is  still 
evident.  At  this  time,  when  the  ova  are  eight  days  old,  there  is  not  yet  any 
indication  of  bilaterality  in  the  egg-cylinder. 

In  slightly  later  stages,  shown  in  cross  section  in  Fig.  62,  A  and  B  the 
columnar  entoderm  surrounding  the  extraembryonic  ectoderm  exhibits  an 
outer  vacuolated  zone  and  an  inner  granular  zone,  while  the  entoderm  of  the 
embryonic  region  becomes  flat.  A  little  further  along  in  development  a  new 
group  of  cells  appears  between  embryonic  ectoderm  and  entoderm  on  one 
side  of  the  egg-cylinder  near  the  junction  between  embryonic  and  extra- 
embryonic  regions  (Fig.  63,  A).  This  group  of  cells  spreading  out  between 
the  other  two  layers  is  the  early  mesoderm,  which  here  is  evidently  a  deriva- 
tive of  embryonic  ectoderm  since  it  is  not  even  attached  to  the  entoderm. 
The  area  where  thg  mesoderm  appears  marks  the  site  of  the  primitive  streak 
and  therefore  the  caudal  end  of  the  future  embryo.  The  proamniotic 


TEXT-BOOK  OF  EMBRYOLOGY. 


cavity  becomes  triangular  in  cross  section  in  this  region,  the  change  in  shape 
being  regarded  as  due  to  the  formation  of  the  primitive  streak  (Fig.  63,  B). 
It  is  interesting  to  note  here  that  development  up  to  this  stage  has  re- 
quired nine  days  out  of  the  21-23  days  of  gestation  in  the  white  rat.     The 


exect. 


FIG.  62. — Cross  sections  of  an  egg-cylinder  of  the  white  rat,  8  days  and  17  hours  after  insemina- 
tion. Huber.  A,  section  which  corresponds  to  a  level  just  above  the  two  crosses  in  Fig. 
61,  D.  B,  section  which  corresponds  to  a  level  about  half  an  inch  below  the  two  crosses  in 
Fig.  61,  D.  ex.ect.,  extraembryonic  ectoderm;  p.ect.,  transitory  ectoderm  (original  wall 
of  blastocyst);  pr.c.,  proamniotic  cavity;  pr.emb.ect.,  primary  embryonic  ectoderm; 
Pr.emb.ent.,  primary  embryonic  entoderm;  v.ent.,  visceral  entoderm. 

slow  progress  of  the  early  cleavage  stages  is  regarded  as  due  to  the  lack 
of  nutriment  as  the  ova  pass  through  the  oviduct.  Even  when  the  ova 
reach  the  uterus  they  become  imbedded  very  slowly  in  the  uterine  mucosa, 


pr.emb.»ct 


FIG.  63  —  Cross  sections  of  egg-cylinders  of  the  white  rat.  A ,  8  days  and  1 7  hours  after  insemina- 
tion; B,  8  days  and  16  hours  after  insemination.  Huber.  These  sections  are  taken  through 
the  region  of  the  primary  embryonic  ectoderm  and  would  therefore  correspond  to  levels 
below  the  crosses  in  Fig.  61,  D.  mes.,  Mesoderm;  p.ect.,  transitory  ectoderm  (original 
wall  of  blastocyst);  pr.c.,  proamniotic  cavity;  pr.emb.ect.,  primary  embryonic  ectoderm; 
pr.emb.ent.,  primary  embryonic  entoderm;  pr.gr.,  primitive  groove;  pr.str.,  primitive 
streak;  v.ent.,  visceral  entoderm. 

probably  receiving  on  that  account  a  minimum  of  nourishment.  During 
development  the  original  wall  of  the  blastocyst  becomes  reduced  to  a  mem* 
brane  around  which  maternal  blood  circulates  as  the  vesicles  become  em- 


EARLY  MAMMALIAN  DEVELOPMENT. 


93 


bedded  in  the  uterine  mucosa.  As  soon  as  the  blood  is  present  the  entodermal 
cells,  and  also  the  cells  of  the  ectoplacental  cone,  take  on  the  vacuolated 
appearance  and  haemoglobin  can  be  demonstrated  in  the  cytoplasm.  On 
the  whole,  however,  the  mechanism  for  nourishing  the  developing  ovum 
appears  to  lack  the  efficiency  of  that  in  other  mammals.  On  this  account 
Sobotta  has  presented  the  conclusion  that  the  inversion  of  the  germ  layers 
is  an  attempt  on  the  part  of  the  developing  organism  to  increase  the  ento- 
dermal surface  and  to  put  the  layer  of  entoderm  in  closer  contact  with  the 
source  of  nutriment,  that  is,  the  maternal  blood. 

Mesoderm. — Returning  now  to  the  bat,  it  has  already  been  noted  (page 
89)   that  the  embryonic  disk  is  nearly  flat  and  composed  of  ectoderm  and 


Embryonic  disk 
Hensen's  node 


Peristomal 
mescderm 


FIG.  64. — Embryonic  disk  of  dog.     Bonnet.    The  letters  and  figures  on  the  right  (Si-S4)  indicate 

planes  of  sections  shown  in  Fig.  ;  5 

entoderm  (Fig.  59,  c).  In  the  dog  the  disk  is  of  similar  form  and  construc- 
tion, but  has  no  amniotic  cavity  over  it.  In  the  dog's  disk  then  a  linear 
opacity  appears  which  extends  about  two-thirds  of  the  way  across  the  disk 
(Fig.  64).  Obviously  this  band  represents  the  primitive  streak.  In  cross 
section  the  primitive  streak  is  seen  to  be  composed  of  ectoderm  and  ento- 
derm fused  with  an  intermediate  layer  of  mesoderm  (Fig.  65,  S$  and  S^). 
The  arrangement  of  the  layers  here  corresponds  exactly  with  that  in  the  bird. 
(Compare  Fig.  47.)  The  mesoderm  extends  laterally  between  ectoderm 
and  entoderm  as  a  number  of  more  or  less  scattered  cells.  Sections  taken 
in  front  of  the  primitive  streak  show  the  entoderm  and  mesoderm  fused  to- 


94 


TEXT-BOOK  OF  EMBRYOLOGY. 


gather  while  the  ectoderm  is  a  separate  layer  (Fig.  65,  Si  and  52).     This 
disposition  of  the  layers  is  characteristic  of  the  primitive  axis  in  the  bird. 


Ectoderm 


Si 


Mesoderm 


Yolk  entoderm 

Pr.int.co. 
P.gr.  Ectoderm 


Yolk  entoderm  Pr.st. 

FIG.  65. — Transverse  sections  of  embryonic  disk  of  dog.     Bonnet. 

Sections  of  disk  shown  in  Fig.  64.  Letters  and  numbers  at  right  (Si-S4)  indicate  plane  of  sections 
in  Fig.  64.  P.gr.,  Primitive  groove;  Pr.int.co.,  primitive  intestinal  cord;  Pr.st.,  all  three 
germ  layers  fused  in  primitive  streak. 


Primitive  streak    Entoderm     Mesoderm    Ectoderm 


FIG.  66. — Transverse  sections  of  embryonic  disks  of  rabbit,     (a)  Kolliker,  (b)  Rabl. 

a,  section  through  primitive  streak  of  embryo  of  6  days  and  18  hours;  b,  section  through  Hensen's 

node  of  embryo  of  7  days  and  3  hours. 

(Compare  Fig.  48.)     The  conditions  as  portrayed  in  the  rabbit  (Fig.  66, 


EARLY  MAMMALIAN  DEVELOPMENT. 


95 


a  and  b)  and  in  the  white  rat  (Fig.  63)  point  to  the  conclusion  that  the  meso- 
derm  originates  from  the  ectoderm. 

In  the  primates  thus  far  studied  the  mesoderm  develops  before  the 
primitive  streak  appears  in  the  embryonic  disk.  In  Tarsius  spectrum  the 
.middle  germ  layer  appears  between  trophoderm  and  entoderm  while  the  disk 
is  still  composed  only  of  the  two  primary  layers  (Fig.  67).  In  Semnopithecus 
nasicus  a  similar  condition  obtains  (Fig.  68).  In  the  human  ovum  de- 
scribed by  Bryce  and  Teacher  the  mesoderm  is  an  extensive  layer  when  the 


FIG.  67. — Median  longitudinal  section  through  the  embryonic  disk  and  yolk  sac  of  the  lemur, 
Tarsius  spectrum.  Hubrecht,  from  Quain's  Anatomy,  emb.ect.,  Embryonic  ectoderm; 
mes,  mesoderm;  pp,  entoderm;  y.s.,  yolk  sac. 

germ  disk  is  still  rudimentary  (Fig.  73).  The  origin  of  the  mesoderm  in 
these  cases  is  problematical.  In  the  lemur  Hubrecht  maintains  that  it  is 
derived  from  the  ectoderm.  In  Semnopithecus  Selenka  considers  it  to  be  of 
entodermal  origin.  The  mesoderm  of  the  embryonic  disk  itself  appears 
somewhat  later  in  the  same  manner  as  in  the  lower  mammals,  that  is,  from 
the  thickened  ectoderm  along  the  primitive  streak  (Fig.  69). 
J  Following  the  development  of  the  primitive  streak  in  the  dog's  disk  the 
disk  becomes  oval,  and  anterior  to  the  streak  an  opaque  band  appears  which 
is  comparable  to  the  primitive  axis  of  the  bird's  blastoderm  (Fig.  70,  a\ 


96 


TEXT-BOOK  OF  EMBRYOLOGY. 


compare  with  Fig.  46).  Transverse  sections  of  the  disk  are  shown  in  Fig. 
70,  b,  Si,  Sz,  SB,  Si,  £5).  The  mesoderm  has  increased  and  now  comprises 
an  extensive  layer  between  ectoderm  and  entoderm.  From  this  stage 


emly.  ea. 


FIG.  68. — Median  longitudinal  section  of  an  early  embryo  of  Semnopithecus  nasicus.  Selenka, 
from  Quain's  Anatomy,  am,  Amniotic  cavity;  con.stk.,  belly  stalk;  emby.ect.,  embryonic 
ectoderm;  ent,  entoderm;  mes,  mesoderm;  y.s.,  yolk  sac. 

forward  the  course  of  development  in  the  mammal  follows  the  general  line 
of  development  in  the  bird.     The  mesoderm  near  the  axial  line  becomes  more 


B 


FIG.  69. — Transverse  sections  through  the  embryonic  disk  of  the  lemur,  Tarsius  spectrum,  after 
the  appearance  of  the  primitive  streak.  Hubrecht,  from  Quain's  Anatomy.  A  is  a  section 
through  the  primitive  node;  B  is  a  section  through  the  primitive  streak  posterior  to  the  node. 

massive  and  segmented  transversely  to  form  the  mesodermal  somites  (Fig. 
71).  More  laterally  the  mesoderm  cleaves  into  two  layers,  the  parietal  and 
visceral,  the  cleft  itself  representing  the  rudiment  of  the  ccelom  (Fig.  72). 


EARLY  MAMMALIAN  DEVELOPMENT. 


97 


Embryonic  disk 
Hensen's  node 


Primitive  streak 

and  groove 

Embryonic  disk 


Head  process 

_. Prim.  int.  cord 
—  (protentoderm) 


Mesoderm 


Ectoderm 


Mesoderm 


Yolk  entod 


Ectoderm 


Chordal  plate  (prol 
Primitive  groo\ 


Mesoderm 


1      Mesoderm 


Mesoderm 


Mesoderm 


Yolk  entoderm 


FIG.  70.— Surface  view  of  embryonic  disk  of  dog  and  transverse  sections  of  same.     Bonnet. 
a,  Disk  somewhat  further  advanced  than  that  in  Fig.  64;  the  letters  and  figures  (Si-S6)  indicate 

planes  of  sections  in  b;  rn.gr.,  medullary  groove. 
7 


TEXT-BOOK  OF  EMBRYOLOGY, 


Prim,  pericard. 
cavity 
Anlage 
of  heart 


Telencephalcn 
Diencephalon 
Mesencephalon 
Metencephalon 

M  y  elencephalon 


Peripheral  limit 
of  coelom 


FIG.  71. — Dorsal  view  of  dog  embryo  with  ten  pairs  of  mesodermal  somites.     Bonnet. 


Neural         Mes.        Intermed. 
groove        somite      cell  mass 


Chordal      Prim, 
plate         aorta 


Coelom        Entoderm       Blood  vessels 
FIG.  72. — Transverse  section  of  dog  embryo  with  ten  pairs  of  mesodermal  somites.     Bonnet. 


EARLY  MAMMALIAN  DEVELOPMENT. 


99 


Between  the  mesodermal  somites  and  the  cleft  portion  of  the  mesoderm  a 
small  group  of  cells  represents  the  intermediate  cell  mass  or  nephrotome. 

The  formation  of  the  neural  plate  and  tube  from  the  axial  band  of  ecto- 
derm is  quite  similar  to  its  development  in  the  lower  forms.  Subsequently 
the  disk  is  bent  or  rolled  into  the  typical  cylindrical  vertebrate  body,  a  pro- 
cess described  in  the  chapter  on  "External  Form"  (p.  109  et  seq.). 

The  Germ  Layers  in  Man. 

There  are  no  observations  on  the  development  of  the  human  ovum  prior 
to  the  appearance  of  all  three  germ  layers.  Consequently  nothing  is  known 


tro. 


cyt.      P.e. 


tro.      n.z. 


tro.1  tro.1 

FIG.  73. — Section  of  a  human  ovum  of  about  14  days,  embedded  in  the  uterine  mucosa. 

Bryce  and  Teacher. 

Cap.,  Capillary;  cyt.,  cellular  layer  (cyto-trophoderm) ;  ep.,  uterine  epithelium;  gl.,  uterine 
gland;  n.z.,  necrotic  zone  of  decidua  (uterine  mucosa);  P.e.,  point  of  entrance  of  the 
ovum;  tro.,  syncytial  layer  (plasmodi-trophoderm) ;  tro.1,  masses  of  vacuolating  syncytium 
invading  capillaries.  The  cavity  of  the  vesicle  is  filled  with  mesoderm  in  which  are  em- 
bedded the  amniotic  cavity  (the  larger)  and  the  yolk  cavity. 

concerning  fertilization,  cleavage,  the  first  differentiation  of  cells,  the  forma- 
tion of  the  embryonic  disk,  or  the  mode  of  origin  of  the  germ  layers.  In  the 
youngest  human  embryo  that  has  been  recorded,  the  one  described  by  Bryce 
and  Teacher  in  1908,  all  three  germ  layers  are  already  present.  The  age  of 
this  embryo  was  reckoned  to  be  about  14  days. 

In  certain  respects  the  Bryce-Teacher  embryo  (Fig.  73)  bears  fundamental 
resemblances  to  corresponding  stages  of  lower  mammals,  especially  the  lower 
primates;  in  other  respects  there  are  differences  which  are  not  irreconcilable, 


100 


TEXT-BOOK  Of  EMBRYOLOGY. 


however,  with  the  general  principles  of  mammalian  ontogeny.  The  vesicle- 
like  structure  of  the  entire  developing  organism  is  a  fairly  close  approxima- 
tion to  the  trophodermal  sac  of  the  lower  forms.  In  both  cases  the  rudi- 
ment of  the  embryonic  body  is  contained  within  the  sac.  In  the  human 
embryo  in  question  there  are  two  cavities  within  the  vesicle;  the  larger  is 
regarded  as  the  amniotic  cavity  lined  with  ectoderm,  and  the  smaller  as  the 
cavity  of  the  yolk  sac  lined  with  entoderm.  The  double  wall  between  the 
two  would  be  the  embryonic  disk.  The  precocious  development  of  the  meso- 
derm,  which  as  a  loosely  arranged  tissue  fills  in  all  the  space  between  the 


Coagulurn 


Trophoderm 


Uterine  epithelium 


Gland 


Decidua  basalis 


FIG.  74. — Section  through  very  young  human  chorionic  vesicle  embedded  in  the 

uterine  mucosa.    Peters. 

The  vesicle  measured  2.4  x  1.8  mm.,  the  embryo  .19  mm.  Peters  reckoned  the  age  as  3  or  4  days, 
but  later  studies  of  other  embryos  go  to  show  that  the  age  is  much  greater;  Bryce  and 
Teacher  estimate  it  at  14  to  15  days. 

trophoderm  and  the  two  small  cavities,  is  one  of  the  remarkable  features  of 
this  embryo.  The  trophoderm  is  a  most  elaborate  layer  and  has  sent  out 
irregular  projections  into  the  uterine  mucosa  in  which  the  whole  structure 
is  already  embedded.  The  early  embedding  or  implantation  and  the  elabo- 
ration of  the  trophoderm  are  probably  closely  correlated. 

In  a  slightly  older  embryo  described  by  Peters  (Fig.  74)  a  space  has  ap- 


*     *  *a 

,  j  ••,  /     j*,  •* 

0  '     ' 

EARLY  MAMMALIAN  DEVELOPI&E^m  \ti 

i^  '.*•/''•-  Wl 

-*e&9 

^%       ^  fc^X? 
i    \ 

Strand  of  mesoderm 
in  exocoelom 

*            V              y 

Trophoderm 

t  «*^  V  %i; 

1^*-%       tL___ 

Entoderm 
Amniotic  cavity 

il^,*  ;   %V  ^'-    "V^^ 

t 

Entoderm 
of  yolk  sac 

—  :/        **•           ^^Sfe- 

^^o-         %j,  SB"  "'' 

Mesoderm 

"*'  s         fpi? 

of  yolk  sac 

?«  v                                 ^9HL 

*%    r  c  ^ 

I  *•»  ^-.-'  

>  75- — Section  through  human  chorion,   amnion,  embryonic  disk,   and  yolk  sac.    Peters. 

Compare  with  Fig.  74. 


Yolk  sac 


Amnion 


Neural  groove   — "^EE 


Chorion 


FIG.  76.— Dorsal  view  of  human  embryo,  two  millimeters  in  length,  with  yolk  sac. 

von  Spee,  Kollmann. 
The  amnion  is  opened  dorsally. 


\  -TEXT-BOOK  OF  EMBRYOLOGY. 

Chorionic  villi 


Chorion 

Mesoderm 
of  chorion 


Blood  vessel 


FIG.  77. — Medial  section  of  human  embryo  shown  in  Fig.  76.     von  Spee,  Kollmann. 

Ecto- 
Mesoderm    derm    Primitive  groove 


Ectoderm 

Parietal  mesoderm 
Visceral  mesoderm 
Entoderm 
FIG.  ?&. — Transverse  section  through  primitive  streak  of  embryo  shown  in  Fig.  76.     von  Spee. 

Parietal  mesoderm  Primitive  groove 

Visceral  mesoderm  Primitive  fold 


Entoderm 
FIG.  79. — Transverse  section  through  primitive  groove  of  rabbit  embryo,     van  Beneden. 


EARLY  MAMMALIAN  DEVELOPMENT. 


103 


peared  within  the  mesoderm,  so  that  one  portion  remains  as  a  lining  for  the 
trophodermal  wall  and  the  remainder  closely  invests  the  yolk  sac  and  amnion 
and  also  forms  a  layer  between  ectoderm  and  entoderm  in  the  embryonic 
disk  (Fig.  75).  The  disk  is  therefore  composed  of  all  three  germ  layers,  but 
there  is  still  no  indication  of  a  primitive  streak.  It  would  seem  that  in  the 
highest  primate  the  mesoderm  develops  independently  of  the  primitive 
streak;  but  whether  it  arises  from  ectoderm  or  entoderm  it  is  not  possible  in 
the  present  state  of  our  knowledge  to  determine. 


D 


FIG.  80. — Diagrams  representing  hypothetical  stages  in  the  development  of  the  human  embryo. 
A,  Morula;  compare  with  Fig.  55,  a.  B,  Morula  with  differentiated  superficial  cells;  compare  with 
Fig-  55)  b.  C,  Central  cells  have  become  vacuolized  to  form  the  yolk  cavity,  leaving  a  small 
group  (the  inner  cell  mass)  attached  to  the  enveloping  layer  (trophoderm) ;  compare  with 
Fig-  5  5 ,  d.  D,  Cells  of  the  inner  cell  mass  which  are  adjacent  to  the  yolk  cavity  have  become 
differentiated  and  have  begun  to  grow  around  the  cavity,  forming  the  entoderm;  compare 
with  Fig.  59,  a. 

In  a  somewhat  older  human  embryo  described  by  von  Spee  a  dorsal  view 
of  the  embryonic  disk  shows  close  resemblances  to  conditions  in  the  lower 
mammals  (Fig.  76).  The  position  of  the  primitive  streak  is  indicated  by  the 
conspicuous  primitive  groove.  Anterior  to  this  the  neural  groove  extends 
almost  the  full  length  of  the  disk  which  has  become  considerably  elongated. 
The  yolk  sac  is  now  suspended  from  the  ventral  side  of  the  disk. 


104 


TEXT-BOOK  OF  EMBRYOLOGY. 


A  longitudinal  section  in  the  medial  sagittal  plane  shows  the  embryonic 
disk  separating  the  yolk  cavity  from  the  amniotic  cavity  (Fig.  77).  The 
mesoderm  is  an  extensive  layer  investing  both  amnion  and  yolk  sac  and 
forming  a  strong  band  which  attaches  the  embryonic  body  to  the  outer  wall 
of  the  vesicle  (now  the  chorion).  A  cross  section  through  the  primitive 
streak  shows  a  striking  resemblance  to  a  corresponding  section  of  the  em- 
bryonic disk  of  a  rabbit.  (Compare  Figs.  78  and  79.)  The  three  germ  layers 
are  fused  in  the  streak,  and  the  mesoderm  extends  laterally  on  both  sides 
between  the  other  two  layers. 


Parietal_ 
Mesoder 


FIG.  81. — Diagrams  representing  hypothetical  stages  in  the  development  of  the 

human  embryo  (to  follow  Fig.  80). 

A,  Entoderm  surrounds  the  yolk  cavity;  part  of  the  cells  of  the  inner  cell  mass  have  become 
vacuolated,  thus  forming  the  amniotic  cavity,  while  the  remainder  constitute  the  embryonic 
ectoderm;  compare  with  Fig.  59.  B,  Mesoderm  (represented  by  dotted  portion)  has  ap- 
peared between  the  entoderm  and  trophoderm,  between  the  entoderm  and  ectoderm  of  the 
embryonic  disk,  and  in  the  roof  of  the  amnion.  C,  The  mesoderm  around  the  yolk  cavity 
has  split  into  a  parietal  and  a  visceral  layer,  the  cleft  between  being  the  rudiment  of  the  ex- 
traembryonic  body  cavity  (exoccelom). 

In  further  development  the  behavior  of  the  germ  layers  during  the  forma- 
tion of  the  neural  tube,  the  origin  of  the  mesodermal  somites,  the  appearance 
of  the  ccelom  in  the  lateral  portion  of  the  mesoderm,  and  the  formation  of 


EARLY  MAMMALIAN  DEVELOPMENT. 


105 


the.notocord  corresponds  in  main  outline  to  their  behavior  in  the  lower 
mammals  and  in  birds. 

The  series  of  diagrams  in  Figs.  80,  81  and  82  has  been  constructed  to  give 
the  student  a  general  idea  of  the  changes  that  occur  in  the  early  stages  of 
human  development.  It  must  be  recognized,  however,  that  the  diagrams 
represent  purely  hypothetical  stages  up  to  the  conditions  shown  in  diagram 
B  in  Fig.  81  which  corresponds  roughly  to  the  Bryce-Teacher  embryo  (Fig. 
73) ;  even  in  this  diagram  the  extent  of  the  mesoderm  is  much  less  than  in  the 


JeUfSbtt 


Belly  Stalk 
AlUjtois 


D 


FIG.  82. — Diagrams  representing  stages  of  development  of  the  human  embryo  (to  follow  Fig.  81). 

A,  A  stage  that  corresponds  approximately  to  those  of  Peters'  and  Bryce-Teacher's  embryos  (Figs. 
74  and  73).  Owing  to  the  rapid  enlargement  of  the  chorionic  vesicle,  the  extraembryonic 
body  cavity  has  become  much  larger  than  in  Fig.  81 ,  C.  B,A  stage  (in  longitudinal  section) 
corresponding  to  that  of  von  Spec's  embryo  (Fig.  77) .  Only  a  part  of  the  chorion  is  shown; 
the  embryonic  disk  is  slightly  constricted  from  the  yolk  sac;  note  the  belly  stalk,  comparing 
with  A .  C,  Transverse  section,  same  stage  as  B.  D,  Longitudinal  section,  stage  somewhat 
later  than  B.  Note  the  greater  degree  of  constriction  between  the  embryo  and  yolk  sac, 
and  the  larger  amnion. 

known  human  embryo.  In  Fig.  82  diagram  A  approximates  the  Peters 
embryo  (Fig.  74),  diagram  D  the  von  Spee  embryo  (Fig.  77).  The  history 
of  the  accessory  structures  which  are  shown  in  part  will  be  considered  in  the 
chapter  on  "Fcetal  Membranes." 


106  TEXT-BOOK  OF  EMBRYOLOGY. 

References  for  Further  Study. 

VAN  BENEDEN,  E.:  Recherches  sur  les  premiers  stades  du  developpement  du  Murin 
(Vespertiliomurinus).  Anat.  Anzeiger,  Bd.  16,  1899. 

BONNET,  R.:  Lehrbuch  der  Entwicklungsgechichte.     1907. 

BRYCE,  T.  H.:  Embryology.     Vol.  I  of  Quain's  Anatomy,  1908. 

BRYCE,  T.  H.  and  TEACHER,  J.  H.:  Early  Development  and  Imbedding  of  the  Human 
Ovum.  1908. 

\J         HARTMAN,   G.:  Studies  in   the   Development   of   the  Opossum.     Jour,  of  Morph., 
Vol.  27,  1916. 

HERTWIG,  O.:  Die  Lehre  von  den  Keimblattern.  In  Hertwig's  Handbuch  der  vergl. 
u.  experiment.  Entwickelungslehre  der  Wirbeltiere,  Bd.  I,  Teil  I,  1903. 

HERZOG,  M.:  A  Contribution  to  our  Knowledge  of  the  earliest  known  Stages  of  Pla- 
centation  and  Embryonic  Development  in  Man.     Am.  Jour,  of  Anat.,  Vol.  9,  1909. 
v       HUBER,   G.   C.:  The  Development  of  the   Albino  Rat,   Mus  norvegicus  albinus. 
Memoirs  of  the  Wistar  Institute,  No.  5,  1915. 

HUBRECHT,  A.  A.  W.:  Furchung  und  Keimblattbildung  bei  Tarsius  spectrum. 
V ' erhandelingen  der  Koninklijke  Akademie  van  Wetenschappente  Amsterdam,  Bd.  7,  1902. 

KEIBEL,  F.  and  MALL,  F.  P.:  Manual  of  Human  Embryology.     Chap.  IV,  1910. 

MELISSINOS,  K.:  Die  Entwicklung  des  Eies  der  Mause  von  der  ersten  Furchungs- 
phanomenen  bis  zur  Festsetzung  der  Allantois  an  der  Ectoplacentarplatte.  Arch.  f. 
mikr.  Anat.,  Bd.  70,  1907. 

PETERS,  H.:  Ueber  die  Embettung  des  menschlichen  Eies  und  das  bisher  bekannte 
menschliche  Placentationstadium.  Leipzig,  1899. 

SOBOTTA,  J.:  Die  Befruchtung  und  Furchung  des  Eies  der  Maus.  Arch.  /.  mikr. 
Anat.,  Bd.  45,  1895. 

SOBOTTA,  J.:  Die  Entwickelung  des  Eies  der  Maus  vom  Schlusse  der  Furchung- 
periode  bis  zum  Auftreten  der  Amnionfalte.  Arch.  f.  mikr.  Anat.,  Bd.  61,  1903. 

THOMSON,  A.:  The  Maturation  of  the  Human  Ovum.    Journal  of  Anatomy. .   Vol. 

53,  1919- 

VON  SPEE,  G. :  Beobachtungen  an  einer  menschlichen  Keimscheibe  mit  offener  Med- 
ullarrinne  und  Canalis  neurentericus.  Arch.f.  Anat.  u.  Physiol.,  Anat.  Abth.,  1889. 


CHAPTER  VIII. 
DEVELOPMENT  OF  THE  EXTERNAL  FORM  OF  THE  BODY. 

General  Form. 

The  vertebrate  body  is  fundamentally  cylindrical.  The  trunk  is  con- 
tinued forward  into  the  neck  which  in  turn  supports  the  head.  The  extremi- 
ties are  appendages  of  the  trunk.  This  form  arises  during  the  development  of 
the  organism  as  a  whole  from  the  spherical  egg  cell.  In  Amphioxus  the 
spherical  form  is  retained  until  the  gastrula  begins  to  elongate;  in  the  frog 
the  same  is  true.  In  both  these  animals  the  simple  elongation  of  the  gastrula 
is  the  first  step  in  the  change  to  the  cylindrical  shape.  In  the  bird  the  egg  is 
spherical,  but  the  cytoplasmic  portion  of  the  egg  is  a  disk  and  out  of  this 
disk  the  early  cylindrical  body  is  established  by  a  process  of  folding.  The 
mammalian  ovum  also  is  spherical,  but  the  part  of  the  structure  resulting 
from  the  early  processes  of  development  which  gives  rise  to  the  body  is  a  disk; 
and  out  of  this  disk  the  cylindrical  body  arises  by  folding  in  much  the  same 
manner  as  in  the  bird. 

Since  cleavage  and  the  formation  of  the  blastodermic  vesicle  in  man  has 
not  been  observed,  it  is  necessary  to  take  some  other  mammalian  form  for 
the  early  stages.  In  most  mammals  cleavage  results  in  a  solid  mass  of  cells 
called  the  morula  (Fig.  55,  a).  In  certain  forms,  like  the  bat,  the  superficial 
cells  of  the  mass  become  differentiated  from  those  in  the  interior,  the  result 
being  an  enveloping  layer  and  a  central  mass  (Fig.  55,  b).  In  the  opossum 
during  cleavage  the  blastomeres  arrange  themselves  around  a  central  cavity 
so  that  no  definite  morula  is  formed  (Fig.  57) .  In  the  case  of  the  solid  sphere, 
vacuoles  appear  within  the  central  cells  and  then  coalesce  to  establish  a  large 
cavity  which  occupies  the  greater  part  of  the  interior  of  the  sphere.  There 
remain  then  the  enveloping  layer  and  a  few  of  the  central  cells  which  are 
attached  to  the  enveloping  layer  over  a  small  area  and  which  comprise  the 
inner  cell  mass  (Fig.  55,  c,  d) .  The  cavity  of  the  sphere  in  the  mammal  is  prob- 
ably not  homologous  with  the  blastocoel  in  the  lower  forms.  The  vacuoliza- 
tion  of  the  central  cells  has  been  interpreted  as  an  attempt  at  yolk  formation. 
Whether  the  interpretation  is  correct  or  not,  the  cells  surrounding  the  cavity 
behave  in  many  respects  as  if  yolk  were  present;  and  the  cavity  subsequently 
becomes  the  cavity  of  the  yolk  sac  of  the  embryo. 

Following  the  formation  of  the  yolk  cavity,  the  contiguous  cells  of  the 
inner  cell  mass  proliferate  and  migrate  to  form  a  complete  lining  for  the 

107 


108  TEXT-BOOK  OP    EMBRYOLOGY. 

cavity.  These  cells  comprise  the  primitive  entoderm.  Meanwhile  the  cen- 
tral cells  of  the  inner  cell  mass  undergo  vacuolization,  leaving  now  only  the 
enveloping  layer  and  a  single  layer  of  cells  applied  to  the  entoderm.  This 
single  layer  is  the  embryonic  ectoderm  and  the  newly  formed  space  the  amniotic 
cavity  (Fig.  59,  c).  The  entire  structure  is  known  as  the  blastodermic  vesicle 
or  blastocyst;  the  interior  contains  two  cavities  separated  from  each  other  by 
a  plate  or  disk  composed  of  ectoderm  and  entoderm  and  called  the  embryonic 
disk.  At  this  point  it  must  suffice  to  say,  without  entering  into  details,  that 
the  mesoderm  appears  as  a  third  layer  between  ectoderm  and  entoderm  in 
the  embryonic  disk  and  between  entoderm  and  enveloping  layer.  The  meso- 
derm increases  rapidly  and  soon  forms  an  extensive  but  loosely  arranged  tissue 
between  the  entoderm  and  the  enveloping  layer  in  the  wall  of  the  vesicle. 
The  enveloping  layer  becomes  known  as  the  trophoderm  because  it  comes  in 
direct  contact  in  the  mammal  with  the  uterine  mucosa  and  through  it  must 
pass  all  the  nutritive  materials  from  the  uterus  to  the  interior  of  the  vesicle. 

Up  to  the  time  and  stage  when  the  mesoderm  becomes  a  loosely  arranged 
tissue  filling  much  of  the  interior  of  the  blastodermic  vesicle,  nothing  is 
known  of  the  development  of  the  human  ovum.  What  is  probably  the 
youngest  human  embryo,  described  by  Bryce  and  Teacher,  is  shown  in  sec- 
tion in  Fig.  73.  The  trophoderm  is.  the  outer  layer  of  the  vesicle  and  has 
sent  out  numerous  irregular  projections  into  the  uterine  mucosa  in  which  the 
vesicle  is  already  embedded.  The  interior  of  the  vesicle  is  occupied  for  the 
most  part  by  the  loose  mesoderm.  Embedded  in  the  mesoderm  are  two  cav- 
ities, the  smaller  being  the  yolk  cavity  lined  by  entoderm  and  the  larger  the 
amniotic  cavity  lined  by  ectoderm ;  the  cavities  are  separated  from  each  other 
by  the  embryonic  disk.  This  embryo  was  reckoned  to  be  13  or  14  days  old. 

A  slightly  older  human  embryo  has  been  described  by  Peters  (Fig.  74). 
It  is  now  reckoned  to  be  about  15  days  old,  although  Peters  regarded  it  at 
the  time  as  being  much  younger.  The  trophoderm  exhibits  about  the  same 
characters  as  in  the  Bryce-Teacher  embryo.  The  mesoderm  shows  a  great 
cleft  or  space  within  it;  a  rather  thin  layer  is  applied  to  the  trophoderm  and 
also  surrounds  the  yolk  and  amniotic  cavities  and  forms  the  middle  layer  of 
the  disk  between  the  two  cavities.  The  space  within  the  mesoderm  is  the 
exoccelom  or  extraembryonic  body  cavity.  The  layer  applied  to  the  tropho- 
derm is  the  somatic  or  parietal  mesoderm  which  with  the  trophoderm  itself 
comprises  the  chorion.  The  wall  of  the  yolk  sac  is  composed  of  entoderm 
and  visceral  or  splanchnic  mesoderm.  The  amniotic  cavity  is  surrounded 
by  ectoderm  and  parietal  mesoderm.  The  embryonic  disk  is  attached  to 
the  chorion  at  one  side  by  a  strand  of  mesoderm  known  as  the  belly  stalk. 
The  chief  difference  between  this  and  the  Bryce-Teacher  embryo  is  the  great 
cleft  in  the  mesoderm. 


DEVELOPMENT  OF  THE  EXTERNAL  FORM  OF  THE  BODY.      109 

Disregarding  now  the  chorion  and  exoccelom,  which  are  no  longer  in- 
volved in  the  form  of  the  embryonic  body,  certain  advances  in  development 
are  seen  in  an  embryo  described  by  von  Spee.  In  Fig.  77  a  sagittal  section 
shows  the  large  yolk  sac  separated  from  the  amniotic  cavity  by  the  embryonic 
disk.  The  anterior  margin  of  the  disk  is  bent  ventrally  by  a  fold  of  the  germ 
layers.  Figure  76  shows  a  dorsal  surface  view  of  the  embryo;  the  amnion 
has  been  cut  away.  The  embryonic  disk  is  considerably  elongated  cephalo- 
caudally.  A  gutter  or  groove  surrounds  the  disk,  and  if  compared  with  the 
sagittal  section  which  has  the  fold  at  the  cephalic  end  it  can  readily  be  seen 
that  this  groove  is  an  early  step  in  the  constriction  or  pinching  off  of  the 
disk  from  the  yolk  sac.  The  margins  of  the  disc  are  being  bent  ventrally 
and  tucked  beneath  the  central  portion;  and  since  the  disk  is  elongated 
the  folding  process  will  result  in  a  cylindrical  body  form.  Even  now  the 
impression  is  obtained  that  the  yolk  sac  is  suspended  from  the  ventral  side 
of  the  embryo  by  a  narrower  structure,  the  early  yolk  stalk.  The  dorsal 
surface  of  the  disk  is  indented  by  the  neural  groove  which  extends  nearly 
the  whole  length  of  the  developing  body. 

Somewhat  more  advanced  than  the  von  Spee  embryo  is  one  described  by 
Eternod  (Fig.  83).  Eternod's  embryo  is  2.11  mm.  in  length  and  possesess 
eight  primitive  segments.  The  figure  shows  the  amnion  cut  away  on  the 
dorsal  side  and  the  yolk  sac  on  the  ventral  side.  The  body  is  more  markedly 
cylindrical  than  the  preceding  stage,  and  more  elongated.  The  constriction 
between  the  embryo  and  the  yolk  sac  is  well  marked,  and  the  narrower  yolk 
stalk  can  be  better  appreciated.  At  the  caudal  end  the  belly  stalk  forms  the 
attachment  to  the  chorion.  The  neural  folds  are  partly  fused  to  form  the 
neural  tube.  The  cephalic  end  of  the  neural  plate  is  notably  larger,  a 
character  which  already  indicates  the  beginning  of  the  head.  One  might 
say  that  the  yolk  stalk  is  becoming  smaller;  but  as  a  matter  of  fact  the 
diminution  is  more  apparent  than  real.  The  apparent  diminution  is  caused 
by  the  relatively  more  rapid  increase  in  size  of  the  embryonic  body  and  yolk 
sac.  At  this  point  it  should  be  mentioned  that  the  bending  and  tucking 
under  the  body  of  the  lateral  body  walls  naturally  results  in  the  contact 
and  eventual  fusion  of  the  two  sides  in  the  mid- ventral  line.  In  this  manner 
the  ventral  body  wall  is  formed.  The  line  of  fusion  is  significant  in  its  rela- 
tion to  certain  malformation :  For  instance,  the  fusion  is  sometimes  defective 
or  incomplete,  allowing  some  of  the  viscera  to  protrude.  (See  Chap.  XX  on 
"Teratogenesis.")  If  the  fusion  is  normal  the  ventral  body  wall  is  complete 
and  closed  except  at  the  attachment  of  the  umbilical  cord  through  which 
pass  the  blood  vessels  that  carry  nutriment  to  the  embryo  and  waste  products 
away  from  it. 

The  changes  that  occur  in  the  simple  cylindrical  body  after  the  ventral 


110 


TEXT-BOOK  OP  EMBRYOLOGY. 


body  wall  is  closed  comprise  the  differentiation  of  the  head,  neck  and  trunk 
regions  and  the  development  of  the  extremities  as  appendages  of  the  trunk. 
Even  in  Eternod's  embryo  (Fig.  83)  the  region  where  the  brain  is  developing 
is  greater  in  diameter  than  the  other  part  of  the  embryo.  Thus  the  begin- 
ning of  the  head  is  indicated  by  an  increase  in  size  due  primarily  to  the  growth 
of  the  brain.  The  end  of  the  head  region  is  bent  ventrally  almost  at  a  right 
angle  to  the  long  axis  of  the  embryo,  the  bend  occurring  in  the  mid-brain 
and  being  known  as  the  cephalic  flexure.  This  is  the  first  of  the  flexures 


Heart 


Ant.  entrance  to 
prim,  gut  (Ant. 
intest.  portal) 


Post,  entrance  to 
prim,  gut  (Post, 
intest.  portal) 


Cerebral  plate 


Amnion 


Yolk  sac 
(cut  edgej 

Yolk  sac 


—  Neural  tube 


Primiti\  e 
segment 


Neural  fold 
Neural  groove 


Belly  stalk  - 


a  b 

FIG.  83. — (a)  Ventral  view;  (b)  dorsal  view  of  human  embryo  with  8  pairs  of  mesodermal  somites 

(2.11  mm.).     Eternod.     From  models  by  Ziegler. 

In  b  the  amnion  has  been  removed,  merely  the  cut  edge  showing;  in  a  the  yolk  sac  has 

been  removed. 

that  appear  as  development  proceeds.  On  the  cephalic  side  of  the  yolk  sac 
attachment  is  a  protrusion  which  indicates  the  position  of  the  heart  in  what 
now  may  be  called  the  cervical  region  or  neck.  Between  the  protrusion 
caused  by  the  heart  and  the  fore-brain  there  is~a  depression  which  fore- 
shadows the  oral  and  nasal  cavities  and  is  now  called  the  oral  fossa . 

In  Fig.  84,  showing  the  dorso-lateral  aspect  of  an  embryo  2.5  mm.  long 
and  possessing  14  primitive  segments,  the  beginning  of  the  head,  the  cephalic 


DEVELOPMENT  OF  THE  EXTERNAL  FORM  OF  THE  BODY. 


Ill 


flexure,  the  oral  fossa,  the  protrusion  in  the  cervical  region  caused  by  the 
heart,  the  belly  stalk,  and  the  constriction  between  body  and  yolk  sac  are  all 


Fore-brain  — 


Mid-brain 


Hind-brain 


Omphalornesenteric 


-  Yolk  sac 


**.  —  Amnion 


Belly  stalk 


FIG.  84. — Dorso-lateral  view  of  human  embryo  with  fourteen  pairs  of  mesodermal 
somites  (2.5  mm.).     Kollmann. 

clearly  indicated.     It  is  worthy  of  note  that  the  heart  appears  in  the  cervical 
region;  during  later  development  it  recedes  into  thorax. 


—  Second  branchial  arch 
Third  branchial  groove 
Heart 


FIG.  85. — Human  embryo  of  2.6  mm.     His,  from  Keibel  and  Mall. 

One  of  the  early  human  embryos  described  by  His  is  shown  in  Fig.  85. 
The  veil-like  structure  around  the  embryo  is  the  amnion.  This  embryo 
measures  2.6  mm.  and  was  estimated  to  be  18-21  days  old  (the  estimate  in 


112 


TEXT-BOOK  OF  EMBRYOLOGY. 


the  light  of  more  recent  studies  probably  being  too  low).  The  body  is  more 
robust  than  in  the  preceding  stage.  In  addition  to  the  cephalic  flexure  the 
dorsum  in  profile  is  a  curve,  with  three  rather  prominent  regions  of  curvature; 
a  cervical  flexure,  a  dorsal  flexure  and  a  sacral  flexure.  The  whole  embryo  is 
slightly  twisted  around  its  long  axis,  the  head  turned  toward  the  left  and  the 
caudal  end  toward  the  right.  In  the  cervical  region  are  three  vertical  de- 
pressions which  diminish  in  size  from  before  backward.  Alternating  with 
these  are  prominences  which  also  diminish  from  before  backward.  These 
alternating  depressions  and  prominences  are  the  branchial  grooves  and  arches 


Mid-brain  flexure 


Eye 


Maxillary  process 


Heart 


Hind  limb  bud 


Fore  limb  bud  Umbilical  cord 

FIG.  86. — Human  embryo  of  4  mm.     Rabl,  from  Kollfnan's  Atlas. 

which  are  homologues  of  the  gill  slits  and  gill  bars  in  fishes.  The  first  arch 
lies  in  front  of  the  first  groove  and  bounds  the  oral  fossa  laterally;  its  two 
subdivisions,  the  mandibular  process  and  maxillary  process,  with  the  notch 
between  representing  the  future  angle  of  the  mouth,  are  already  differentiated. 
Through  the  development  of  the  first  arch  the  depth  of  the  oral  fossa  is 
considerably  increased.  The  heart  causes  a  conspicuous  protrusion  on  the 
ventral  side  of  the  cervical  region.  The  constriction  between  the  body  of 
the  embryo  and  the  yolk  sac  is  marked,  and  this  attenuated  portion  of  the 
yolk  sac  is  from  now  on  spoken  of  as  the  yolk  stalk.  The  structure  attached 
caudal  the  yolk  stalk  and  turned  over  the  right  side  of  the  embryo  is  the  belly 
stalk  which  later  will  be  included  in  the  umbilical  cord. 


DEVELOPMENT  OF  THE  EXTERNAL  FORM  OF  THE  BODY. 


113 


An  embryo  of  4  mm.  is  shown  in  Fig.  86.  All  the  flexures  are  accen- 
tuated, so  that  the  head  and  tail  are  close  together.  The  fourth  branchial 
arch  has  appeared  behind  the  third  groove  and  a  fourth  groove  behind  the 
fourth  arch.  The  small  structure  behind  the  fourth  groove  may  be  the 
rudimentary  fifth  arch.  The  arches  diminish  rather  uniformly  from  the 
first  to  the  last.  The  rudiment  of  the  eye  is  visible  on  the  side  of  the  fore- 
brain  region  as  a  circular  eminence  surrounded  by  a  slight  groove.  The  heart 


Cervical  Cervical 

depression  flexure 


Dorsal  flexure 


Branchial  arch    IV 
Branchial  groove  III 
'Branchial  arch  III 
Branchial  groove  II 

Branchial  arch  II 
Branchial  groove  I 

Branchial  arch  I 
Mandibular  process 

•-  Maxillary  process 

•-Eye 

Nasal  pit 

Heart 
Yolk  stalk 


Lower  limb  bud 


Primitive  segments 


Upper  limb  bud  Liver         Sacral  flexure 

FIG.  87. — Human  embryo  with  twenty-seven  primitive  segments  (7  mm.,  26  days). 


Mall. 


protuberance  is  strikingly  prominent.  Certain  new  features  have  appeared 
at 'this  stage,  the  limb  buds.  The  fore-limb  bud  is  a  rounded  eminence 
opposite  the  anterior  part  of  the  dorsal  flexure;  the  hind-limb  a  similar 
structure  opposite  the  sacral  flexure.  The  limb  buds,  as  tar  as  surface 
appearance  goes,  are  Simply  outgrowths  from  the  body  wall  starting  as  small 
rounded  eminences  which,  as  development  proceeds,  become  larger  and  finally 
differentiated  into  the  various  parts  of  the  extremities. 

In  a  7-mm.  embryo  described  by  Mall  (Fig.  87),  the  flexures  are  slightly 
more  accentuated  than  in  the  4-mm.   stage.     The  branchial  arches  and 


114 


TEXT-BOOK  OF  EMBRYOLOGY. 


grooves  are  still  prominent.  The  first  groove,  of  which  the  dorsal  part 
marks  the  site  of  the  external  auditory  meatus,  is  at  this  time  particularly 
well  developed.  The  eye  is  a  stronger  feature  than  in  the  preceding  stage. 
The  distinct  depression  in  front  of  the  first  arch  is  the  nasal  fossa.  The 
limb  buds  are  larger  than  in  the  4-mm.  embryo.  The  general  curvature  of 
the  embryo  is  so  sharp  at  this  stage  that  the  rudimentary  tail  is  almost  in 
contact  with  the  head. 

In  Fig.  88,  showing  an  embryo  of  7.5  mm.  with  27  primitive  segments, 
the  head  is  somewhat  larger  in  proportion  to  the  body.     This  character 


Branchial  groove  III 


Branchial  arch  III; 

Branchial  groove  II 

Branchial  arch  II 

Branchial  groove  I 
Mandibular  process 

Maxillary  process 
Eye 

Naso-optic  furrow 
Nasal  pit 


Yolk  sac 


Heart 


Lower 
limb  bud 


Liver 


limb  bud 
FIG.  88. — Human  embryo  with  28  primitive  segments  (7.5  mm.).     Photograph. 


Umbilical 
cord 


Yolk  stalk 


becomes  accentuated  as  development  proceeds  and  is  especially  noticeable 
up  to  the  time  of  birth.  The  cervical  and  sacral  flexures  are  still  sharp,  but 
the  dorsal  flexure  is  not  quite  so  prominent.  From  now  on,  the  body  becomes 
more  nearly  straight.  The  rotundity  of  the  ventral  side  of  body  is  due  to 
the  heart  and  liver,  the  two  organs  now  lying  close  together.  The  branchial 
arches  are  not  actually  smaller  but  appear  less  prominent.  The  second 
arch  has  enlarged  and  grown  back  over  the  third  and  fourth,  partially  hiding 
them.  The  limb  buds' are  larger;  and  the  fore-limb  bud  now  shows  a  trans- 
verse constriction  dividing  it  into  a  proximal  and  a  distal  portion,  the  latter 
being  the  rudiment  of  the  hand. 


DEVELOPMENT  OF  THE  EXTERNAL  FORM  OF  THE  BODY.      115 

Figure  89  shows  an  embryo  of  n  mm.  All  the  flexures  are  slightly 
reduced  except  the  cephalic.  The  cephalic  flexure,  which  primarily  affects 
the  embryonic  brain,  persists  as  the  mid-brain  flexure  of  the  adult.  Two 
slight  concavities  have  appeared  in  the  dorsal  profile,  the  occipital  depres- 
sion and  the  cervical  depression.  The  latter  becomes  more  conspicuous 
as  development  proceeds  and  persists  as  the  depression  at  the  back  of  the 
neck  in  the  adult.  The  first  branchial  arch  is  a  strong  feature  of  the  head, 
the  maxillary  process  being  especially  prominent.  This  process  has  grown 
forward  to  form  intimate  contact  with  the  nasal  region.  The  second  arch 
now  hides  the  third  and  fourth  arches,  and  the  depression  behind  the  second 

Cervical  flexure 
Occipital  depression 


Cervical  depression 


Dorsal  flexure 


Umbilical  cord 

X/f 

Sacral  flexure 
FIG.  89. — Human  embryo  n  mm.  long  (31-34  days).     His. 

is  known  as  the  precermcal  sinus.  The  first  groove  can  be  more  readily 
appreciated  as  the  site  of  the  external  auditory  meatus,  as  can  also  the 
surrounding  parts  of  the  first  and  second  arches  be  better  appreciated  as 
rudiments  of  the  concha.  The  distal  part  of  the  fore-limb  bud  is  flattened 
like  a  paddle,  and  the  radial  depressions  in  it  mark  the  boundaries  between 
the  digits.  In  the  proximal  portion  the  fore-arm  and  arm  are  faintly  in- 
dicated. The  hind-limb  bud  is  divided  by  a  constriction  into  a  proximal  and 
distal  portion;  the  latter  is  the  beginning  of  the  foot.  During  development 
the  fore-limb  is  always  at  a  slightly  more  advanced  stage  than  the  hind-limb. 
The  ventral  rotundity  of  the  body  is  pronounced. 

In  an  embryo  measuring  15.5  mm.  (Fig.  90)  the  dorsal  flexure  is  much 
reduced  and  the  axis  of  the  body  is  approaching  the  definitive  line.     The 


116 


TEXT-BOOK  OF  EMBRYOLOGY. 


\ 


FIG.  90. — Human  embryo  of  15.5  mm.  (39-40  days).     His. 


FIG.  91.  FIG.  92.  FIG.  93. 

FIG.  91. — Human  embryo  of  17.5  mm.  (47-51  days).  His. 
FIG.  92. — Human  embryo  of  18.5  mm.  (52-54  days).  His. 
FIG.  93. — Human  embryo  of  23  mm.  (2  months).  His. 


DEVELOPMENT  OF  THE  EXTERNAL  FORM  OF  THE  BODY. 


117 


cervical  flexure  is  still  prominent,  as  is  also  the  ventral  rotundity  of  the 
body.  The  neck  is  now  clearly  differentiated.  The  external  auditory 
meatus  and  the  surrounding  rudiments  of  the  concha  are  plainly  indicated. 
The  limb  buds  are  turned  more  nearly  at  right  angles  to  the  long  axis  of  the 
body.  The  leg  and  thigh  show  early  differentiation;  the  fingers  are  beginning 
to  elongate  and  radial  grooves  on  the  foot  indicate  the  boundaries  between 
the  toes.  The  tail,  which  was  a  prominent  feature  in  the  earlier  stages,  is 
proportionately  small;  in  the  human  it  is  at  most  a  rudimentary  structure 
represented  by  the  coccyx,  and  while  in  the  early  embryo  it  is  fairly  large 
it  does  not  keep  pace  with  the  body  during  development. 


FIG.  94. — Human  embryo  of  78  mm. 
(3  months).     Minot. 


FIG.     95.  —  Human    embryo    of    4    months 
Natural  size.     Kollmann. 


After  the  stage  shown  in  Fig.  90  the  cervical  flexure  continues  to  dimin- 
ish and  the  head  comes  to  lie  more  nearly  in  line  with  the  long  axis  of  the 
body.  The  rotundity  of  the  abdomen  gradually  becomes  less  as  the  heart 
and  liver  approach  the  proportions  of  the  adult.  The  tail  as  an  external 
structure  disappears  altogether,  the  buttocks  increasing  markedly.  During 
the  second  month  the  external  genitalia  develop  and  the  sex  of  the  embryo 
can  be  distinguished.  The  general  changes  in  form  can  be  followed  by  com- 
paring Figs.  91,  92,  93,  94  and  95. 

In  the  early  stages  of  human  development,  say  during  the  first  month, 


118 


TEXT-BOOK  OF  EMBRYOLOGY. 


it  is  not  uncommon  to  speak  of  all  the  membranes  with  the  enclosed  embryo 
as  the  ovum.  During  the  first  two  months  the  developing  organism  itself 
is  usually  called  an  embryo.  By  the  end  of  the  second  month  when  the 
embryo  has  reached  the  length  of  about  an  inch  (25  mm.)  it  has  acquired  a 
form  (Fig.  93)  which  in  general  resembles  that  of  the  adult  and  is  henceforth 

referred  to  as  afcetus. 

The  Face 

When  the  fore-brain  bends  ventrally  and  the  heart  appears  on  the  ventral 
side  of  the  embryo  in  what  will  be  the  cervical  region,  there  is  thus  produced 
between  the  two  structures  a  depression  or  pit  called  the  oral  fossa  (Fig.  84). 
This  fossa  is  the  rudiment  of  the  oral  and  nasal  cavities  and  around  it  the 


Cerebral  hemisphere 


Lat.  nasal  process 

Nasal  pit 

Med.  nasal  process 

Angle  of  mouth 


Eye 

Naso-optic  furrow 
Maxillary  process 
Mandibular  process 


FIG.  96. — Ventral  view  of  head  of  8  mm.  human  embryo.     His. 

structures  develop  which-  give  rise  to  the  face.  Behind  the  fore-brain  and 
dorsal  to  the  heart,  as  the  embryo  develops,  a  series  of  slit-like  depressions 
appear  at  right  angles  to  the  long  axis  of  the  body.  Between  the  depressions 
are  elevations.  These  structures  are  in  the  lateral  wall  of  the  embryonic 
pharynx,  and  are  known  as  branchial  grooves  and  arches  (Figs.  85  and  86). 
It  has  been  previously  stated  that  they  are  homologous  with  the  gill  slits 
and  gill  bars  of  fishes.  The  first  two  arches  and  the  first  groove  are  involved 
in  the  formation  of  the  face. 

The  first  branchial  arch  becomes  the  largest  of  the  series  and,  on  ac- 
count of  its  position,  bounds  the  oral  fossa  laterally  (Fig,  85).  Its  presence 
serves  to  deepen  the  fossa.  Growing  from  the  cephalic  side  of  the  arch,  a 
strong  process  insinuates  itself  between  the  arch  and  the  fore-brain  region. 
This  is  called  the  maxillary  process,  while  the  original  part  of  the  arch  is  the 
mandibular  process.  The  latter  grows  rapidly,  extends  ventrally  and  finally 


DEVELOPMENT  OF  THE  EXTERNAL  FORM  OF  THE  BODY. 


119 


meets  and  fuses  with  its  fellow  of  the  opposite  side  in  the  midventral .  line 
caudal  to  the  oral  fossa  (Fig.  96).  The  maxillary  process  still  bounds  the 
oral  fossa  laterally.  Meanwhile  a  broad  downward  projection  from  the 
front  of  the  fore-brain  region — the  naso-frontal  process — comes  in  contact 
laterally  with  the  maxillary  process  (Fig.  96).  Along  the  line  of  contact  a 
furrow  is  left,  which  extends  obliquely  upward  to  the  eye  rudiment  and  is 
known  as  the  naso-optic  furrow. 

The  various  structures  that  have  been  mentioned  bound  the  oral  fossa 
which  has  now  become  a  deep  quadrilateral  pit.     Cranially  (above)  the  fossa 


Mid-brai 


Cerebral  hemisphere 


Lat.  nasal  process 
Nasal  pit 

Med.  nasal  process 
Angle  of  mouth 


Eye 

Naso-optic  furrow 

Maxillary  process 
Mandibular  process 
Branchial  grooves 

<jl| Branchial  arch  II 


FIG.  97. — Ventral  view  of  head  of  11.3  mm.  human  embryo.     Rabl. 

is  bounded  by  the  broad,  rounded,  unpaired  naso-frontal  process;  caudally 
(below)  it  is  bounded  by  the  paired  mandibular  processes;  laterally  by  the 
paired  maxillary  processes.  Between  the  maxillary  and  mandibular  pro- 
cesses on  each  side  a  notch  marks  the  future  angle  of  the  mouth.  In  general 
it  may  be  stated  that  the  naso-frontal  process  gives  rise  to  the  nose  and 
middle  of  the  upper  lip,  the  maxillary  processes  to  the  lateral  parts  of  the 
upper  lip  and  the  cheeks,  the  mandibular  processes  to  the  lower  jaws,  chin 
and  lower  lip. 

The  naso-frontal  process  extends  farther  downward  toward  the  mandi- 
bular processes,  so  that  the  oral  fossa  becomes  more  nearly  enclosed  and  the 
entrance  to  it  reduced  to  a  slit.  At  the  same  time  two  secondary  processes 


120 


TEXT-BOOK  OF  EMBRYOLOGY. 


develop  on  each  side  from  the  naso-frontal,  one,  the  medial  nasal  process, 
near  the  median  line  and  the  other,  the  lateral  nasal  process,  more  laterally. 
Between  the  two  processes  the  nasal  pit  marks  the  entrance  to  the  future 
nasal  cavity  (nostril).  The  maxillary  process  grows  farther  toward  the 


Nasal  fossa 

Naso-optic  furrow — 4- 
Mouth  slit~~| 

Branchial  groove  I 


Cerebral  hemisphere 

Naso-frontal  process 

'Lateral  nasal  process 
Medial  nasal  process 
Maxillary  process 

Mandibular  process 


FIG.  98. — Ventral  view  of  head  of  13.7  mm.  human  embryo.     His. 

medial  line  and  forms  contact  with  the  lateral  and  medial  nasal  processes 
(Figs.  96  and  97). 

Further  development  consists  essentially  of  fusions  between  the  various 
elements  already  present  and  of  changes  in  the  relative  proportions  of  these 


Branchial  groove  I 
(external  ear) 


Nose  ~ 

Lat.  nasal  process 
Maxillary  process 

Med.  nasal  process 


FIG.  99.— Ventral  view  of  head  of  human  embryo  of  8  weeks.     His. 

elements.  The  two  medial  nasal  processes  come  close  together  to  form  a 
single  medial  process  which  gives  rise  to  the  middle  portion  of  the  upper  lip 
and  the  adjacent  portion  of  the  nasal  septum  (Figs.  98  and  99).  The  maxil- 
lary process  expands  generally  to  form  the  cheek  and  lateral  portion  of  the 


DEVELOPMENT  OF  THE  EXTERNAL  FORM  OF  THE  BODY.      121 

upper  lip  and  at  the  same  time  fuses  with  the  nasal  processes.  This  fusion 
obliterates  the  naso-optic  furrow  and  shuts  off  the  connection  between  the 
nasal  pit  and  mouth  slit  (Figs.  98  and  99).  Internally  the  concomitant 
formation  of  the  palate  separates  the  oral  and  nasal  cavities.  The  lateral 
nasal  process  gives  rise  to  the  wing  of  the  nose.  The  nose  at  first  is  a  broad, 
flat  structure  but  later  becomes  elevated,  elongated  and  narrower.  The 
lower  jaw,  lower  lip  and  chin  are  formed  by  the  mandibular  processes.  At 
first  the  chin  is  short  vertically  but  broad  transversely.  Later  it  becomes 
longer  and  a  transverse  furrow  divides  the  middle  portion  into  the  lower  lip 
and  chin. 

The  Extremities. 

The  rudiments  of  the  extremities  or  limbs  appear  in  human  embryos 
about  the  end  of  the  third  week.  They  arise  as  small  rounded  protuberances 
on  the  lateral  body  wall,  the  upper  limb  buds  just  caudal  to  the  level  of  the 
cervical  flexure  and  the  lower  opposite  the  sacral  flexure  (Fig.  86) .  The  first 
to  appear  are  the  upper  buds,  the  lower  appearing  a  little  later.  The  differ- 
ence in  time  of  appearance  is  reflected  through  embryonic  and  fcetal  life  in 
the  slight  advance  in  the  degree  of  development  of  the  upper  over  the  lower. 

During  the  fourth  week  the  limb  buds  become  elongated,  and  a  transverse 
constriction  on  each  bud  marks  off  a  distal  from  a  proximal  portion.  The 
proximal  portion  remains  approximately  cylindrical  while  the  distal  portion 
becomes  flat  like  a  paddle  (Fig.  88) .  The  flattened  end-piece  is  the  beginning 
of  the  hand  (or  foot),  which  is  thus  the  first  part  of  the  extremity  to  be  differ- 
entiated. During  the  sixth  week  the  proximal  portion,  which  in  the  mean- 
time has  become  still  longer,  is  marked  off  by  a  bend  at  the  elbow  (or  knee) 
into  two  segments,  the  fore-arm  and  arm  (or  leg  and  thigh). 

During  the  fifth  week  the  rudimentary  digits  (fingers  and  toes)  appear 
on  the  flattened  distal  segments  of  the  developing  extremities.  They  are 
first  indicated  by  radial  depressions  on  the  flat  surface,  the  digits  being  the 
elevations  between  the  depressions  (Figs.  89  and  90).  The  digits  grow 
rapidly  in  thickness  and  length  thus  producing  an  apparent  deepening  of  the 
interdigital  grooves  and  also  forming  protrusions  around  the  distal  free 
borders  of  the  limb-buds  (Fig.  90).  The  depressed  areas  comprise  a  series 
of  membranes  resembling  the  web  in  the  feet  of  certain  aquatic  animals. 
The  digits  grow  more  rapidly  than  the  web,  the  latter  eventually  being  con- 
fined to  the  proximal  part  of  the  interdigital  spaces.  After  the  seventh  week 
the  angle  between  the  thumb  and  second  digit  approaches  a  right  angle;  a 
lesser  degree  of  approach  to  a  right  angle  holds  true  in  case  of  the  great  toe 
(Figs.  91,  92  and  93). 

As  the  limbs  first  elongate  their  long  axes  lie  nearly  parallel  with  the  long 


122  TEXT-BOOK  OF  EMBRYOLOGY. 

axis  of  the  body  (Fig.  89) .  Later  they  are  directed  ventrally  nearly  at  right 
angles  to  the  body  axis  (Fig.  92).  The  radial  margins  of  the  upper  extremi- 
ties are  turned  toward  the  head  (cephalad) ,  as  are  the  tibial  margins  of  the 
lower.  The  palmar  surfaces  of  the  hands  and  plantar  surfaces  of  the  feet 
are  turned  inward  or  toward  the  projected  sagittal  plane  of  the  body.  The 
elbow  is  turned  slightly  outward  and  toward  the  tail,  the  knee  slightly  out- 
ward and  toward  the  head.  From  these  conditions  it  is  inferred  that  the 
radial  side  of  the  upper  extremity  is  homologous  with  the  tibial  side  of  the 
lower  extremity,  and  the  palmar  surface  of  the  hand  with  the  plantar  surface 
of  the  foot. 

In  order  to  acquire  positions  relative  to  the  body  as  found  in  post-natal 
life,  the  extremities  must  undergo  further  changes.  These  consist  of  torsion 
around  their  long  axes  and  rotation  through  an  angle  of  90  degrees.  The 
right  upper  extremity  twists  to  the  right,  and  the  right  lower  to  the  left.  The 
left  upper  twists  to  the  left,  and  the  left  lower  to  the  right.  At  the  same 
time  they  swing  backward  through  an  angle  of  90  degrees  so  that  they  come 
to  lie  parallel  with  the  long  axis  of  the  body.  The  result  is  that  the  radial 
side  of  the  upper  extremity  is  turned  outward  or  away  from  the  sagittal  plane 
of  the  body  and  the  tibial  side  of  the  lower  inward  or  toward  the  sagittal  plane  of 
the  body.  In  the  upper  extremity  this  is,  of  course,  the  supine  position  of 
the  fore-arm  in  which  the  radius  and  ulna  are  parallel. 

Age,  Length  and  Weight  of  the  Body. 

The  age  of  human  embryos  is  a  matter  of  importance  to  the  embryologist 
who  desires  to  trace  development  in  general  or  that  of  any  organ,  and  to  the 
obstetrician  who  is  interested  in  the  scientific  phase  of  his  work.  Develop- 
ment commences  when  fertilization  occurs  and  the  age  of  the  embryo  should 
be  dated  from  that  time.  Unfortunately  it  is  not  possible  to  determine 
exactly  when  fertilization  takes  place.  This  is  impossible  for  several  reasons : 
first,  because  fertilization  cannot  be.  directly  observed;  second,  because  even 
if  the  time  of  cohabitation  is  known  the  period  required  by  the  sperm  to 
reach  the  ovum  cannot  be  exactly  determined;  and  third,  because  the  time 
that  the  ovum  escapes  from  the  ovary  and  passes  into  the  oviduct  is  not 
known. 

In  view  of  these  uncertain  factors  which  cannot  be  controlled,  the  age 
of  a  human  embryo  can  be  determined  only  within  certain  limits.  In  a  few 
cases  on  record  the  time  of  coitus  was  known,  and  assuming  that  an  ovum  was 
in  the  tube  ready  for  fertilization,  the  copulation  age  could  be  reckoned. 
This,  however,  does  not  give  the  exact  fertilization  age,  which  is  the  actual 
age,  because  it  requires  some  time  for  the  spermatozoa  to  pass  through  the 
uterus  and  oviducts.  In  the  Bryce-Teacher  embryo,  for  instance,  coitus 


DEVELOPMENT  OF  THE  EXTERNAL  FORM  OF  THE  BODY.      123 

occurred  16  days  prior  to  abortion.  The  fertilization  age  was  computed  to  be 
about  14  days.  An  embryo  described  by  Eternod  was  aborted  21  days  after 
coitus,  and  the  fertilization  age  was  reckoned  at  about  19  days.  Other  cases 
of  a  similar  nature  have  been  studied  and  the  actual  age  of  the  embryo  in 
each  case  was  regarded  as  two  days  less  than  the  copulation  age.  Such  reck- 
oning could  be  done  only  in  those  cases  where  the  time  of  coitus  and  of  abortion 
are  both  known. 

In  the  majority  of  cases  the  only  datum  available  is  the  time  that  the 
last  menstrual  flow  occurred.  In  these  cases  the  age  of  the  embryo  is  reck- 
oned from  the  beginning  of  the  last  menstrual  period,  and  is  known  as  the 
menstrual  age.  This  at  best  can  be  only  an  approximate  age  because  even  if 
the  date  of  coitus  is  known  the  date  of  ovulation  is  undetermined  and  there- 
fore the  time  that  the  sperm  and  ovum  meet  is  unknown.  It  has  been  shown 
that  in  perhaps  the  majority  of  cases  ovulation  occurs  in  the  intermenstrual 
period,  on  the  average  about  the  middle  of  its  duration,  and  therefore 
fertilization  would  not  bear  a  direct  time  relation  to  menstruation.  The 
condition  of  the  corpus  luteum,  if  it  could  be  determined,  would  be  of  great 
value  in  reckoning  the  age  of  the  embryo  resulting  from  the  development  of 
the  ovum  that  escaped  from  that  particular  follicle.  The  method  of  reck: 
oning  from  the  first  day  of  the  last  menstruation  i?  used  by  obstetricians  for 
determining  the  probable  time  of  birth. 

In  statistics  collected  by  Issmer  the  average  duration  of  pregnancy  in 
1220  cases  was  found  to  be  280  days,  when  estimated  from  the  first  day  of 
the  last  menstrual  period;  and  in  628  cases  it  was  found  to  be  269  days  from 
the  date  of  fruitful  cohabitation.  It  would  seem  therefore,  on  the  basis  of 
these  statistics,  that  deducting  about  10  days  from  the  menstrual  age  would 
give  the  approximate  copulation  age  which  is  not  far  removed  from  the  actual 
age. 

The  length  of  an  embryo  can  be  determined  by  direct  measurement. 
It  is  the  general  practice  to  take  the  greatest  length  of  the  embryo  in  a 
straight  line  in  its  natural  attitude,  not  including  the  extremities.  In  em- 
bryos between  4  and  14  mm.,  when  the  body  is  much  curved,  one  point  of 
measurement  lies  on  the  apex  of  the  cervical  flexure  and  the  other  on  the 
apex  of  the  sacral  flexure.  (See  Figs.  87  and  88.)  This  is  known  as  the  neck- 
rump  length.  In  later  stages  where  the  curvature  is  reduced  and  the  body 
is  more  nearly  straight,  the  measurement  falls  between  the  apex  of  the 
cephalic  flexure  and  the  apex  of  the  sacral  flexure.  (See  Figs.  90  and  91.) 
This  is  known  as  the  crown-rump  length.  The  relation  of  length  to  age  has 
been  the  subject  of  much  study,  but  no  formula  for  deducing  the  age  from 
the  length,  which  can  be  determined,  has  been  wholly  satisfactory.  The 
formula  given  by  Mall  some  years  ago  was  later  abandoned  by  him  as  un- 


124 


TEXT-BOOK  OF  EMBRYOLOGY. 


reliable.  This  formula  (for  embryos  from  i  to  100  mm.)  was  that  the  age 
can  be  expressed  by  the  square  root  of  the  length  in  millimeters  multiplied 
by  100  (Vlength  in  millimeters  X  100).  At  present  it  can  be  said  in  general 
that  embryos  of  2  to  3  mm.  will  fall  within  the  fourth  week  of  develop- 
ment, embryos  of  5  to  6  mm.  will  come  about  the  end  of  the  fifth  week,  those 
of  10  mm.  at  the  end  of  the  sixth  week,  and  those  of  about  25  mm.  at  the 
end  of  the  eighth  week.  The  following  table  gives  the  approximate  greatest 
length  at  the  ends  of  the  lunar  months  following  the  second  month: 


3d  lunar  month 70-  90  mm. 

4th  lunar  month 100-170  mm. 

5th  lunar  month 180-270  mm. 

6th  lunar  month 280-340  mm. 


7th  lunar  month.  .  . 
8th  lunar  month .  .  . 
9th  lunar  month.  .  . 
loth  lunar  month.  . 


350—380  mm. 

425  mm. 

467  mm. 
490—500  mm. 


Some  interesting  observations  have  been  made  on  the  increase  in  volume 
of  the  embryo  (and  foetus)  and  of  its  parts  during  development.  It  has 
been  estimated  that  the  human  ovum,  which  is  about  0.2  mm.  in  diameter 
weighs  about  four  millionths  of  a  gram  (0.000004  gm.)  and  that  at  the  end  of 
the  first  month  the  embryo  weighs  about  four  hundred ths  of  a  gram  (0.04 
gm.).  It  thus  appears  that  the  human  ovum  increases  approximately 
10,000  times  in  weight  during  the  first  month  of  development.  On  the  same 
basis  the  relative  growth  rate — which  is  the  ratio  of  the  gain  during  a  given 
period  to  the  weight  at  the  beginning  of  the  period — during  the  second 
calendar  month  is  74,  during  the  third  month  n,  during  the  fourth  month 
1.75,  during  the  fifth  month  0.82,  during  the  sixth  month  0.67,  during  the 
seventh  month  0.50,  during  the  eighth  month  0.47  and  during  the  ninth 
month  0.45  (Jackson).  The  accompanying  table  taken  from  Jackson's 
work  gives  the  relative  growth  rate  of  the  embryo  in  each  of  the  ten  lunar 
months  of  pregnancy. 


Lunar 
month 

Weight  at  first 
of  month,     (a) 

Weight  at  end 
of  month.     (6) 

Relative  monthly 
growth,      (b  —  a\ 

grams. 

grams. 

(     a     ) 

I  

o  .  000004 

o  04 

II  

o  04. 

yyyy  • 

III. 

3, 

*6 

/4- 

IV  

• 

36 

ou  • 
T  2O 

V  

ow  • 
1  20 

•y  -2Q 

2  -33 

VI  

-2-20 

OOU  • 
600 

•  75 
o  8? 

VII  

600 

IOOO 

VIII.... 

IOOO 

IX  

I  ^OO 

o.  50 

X  

2  2OO 

0.47 

°-45 

DEVELOPMENT  OF  THE  EXTERNAL  FORM  OF  THE  BODV.      125 

The  head  attains  its  maximum  relative  size  during  the  second  month  when 
its  weight  is  about  45  per  cent,  of  the  total  weight  of  the  embryo.  There- 
after it  gradually  diminishes  in  relative  size  until  birth  when  it  constitutes 
about  26  per  cent,  of  the  total  weight.  The  trunk  is  relatively  largest  during 
the  first  month  when  its  weight  is  about  65  per  cent,  of  the  total  and  then  de- 
creases to  between  40  and  45  per  cent,  in  the  later  fcetal  months.  The 
extremities  gradually  increase  in  relative  size  after  their  appearance;  the 
upper  extremities  forming  about  10  per  cent,  of  the  total  weight  at  birth  and 
the  lower  about  20  per  cent. 

Although  the  relative  growth  rates  of  the  various  organs  have  also  been 
estimated  it  does  not  seem  desirable  to  include  them  in  the  chapter  which 
treats  of  the  external  formc  Two  organs  might  be  mentioned,  however, 
which  have  a  marked  influence  on  the  contour  of  the  body ;  that  is,  the  heart 
and  liver.  In  embryos  about  10  mm.  long  the  heart  constitutes  nearly  4 
per  cent,  of  the  total  body  volume.  Thereafter  it  diminishes  in  relative  size 
to  less  than  i  per  cent,  at  birth.  Figures  8  5  and  86  show  the  marked  protrusion 
produced  by  this  organ  on  the  ventral  side  of  the  body.  In  embryos  of 
around  30  mm.  the  liver  forms  more  than  10  per  cent,  of  the  total  volume  of 
the  body;  in  fact  it  is  relatively  large  during  both  the  second  and  third 
months.  Figures  87  and  88  show  the  effect  of  the  organ  on  the  contour  of 
the  body,  in  conjunction  with  the  heart. 

References  for  Further  Study. 

BRYCE,  T.  H.  and  TEACHER,  J.  H.:  Early  Development  and  Imbedding  of  the  Human 
Ovum.  Glasgow,  1908. 

His,  W.:  Anatomic  menschlicher  Embryonen.     With  atlas,  1880-1885. 

JACKSON,  C.  M.:  On  the  Prenatal  Growth  of  the  Human  Body  and  the  Relative 
Growth  of  the  various  Organs  and  Parts.  Am.  Jour,  of  Anat.,  Vol.  9,  1909. 

KEIBEL.  F.:  Die  Entwickelung  der  ausseren  Korperform  der  Wirbeltierembryonen, 
inbesondere  der  menschlichen  Embryonen  aus  der  ersten  2  Monaten.  In  Band  I,  Teil 
II  of  Hertwig's  Handbuch  der  vergl.  und  experiment.  Entwickelungslehre  der  Wirbeltiere, 
1902. 

KEIBEL,  F.  and  ELZE,  C.:  Normentafel  der  Entwickelungsgeschichte  des  Menschen. 
Jena,  1908. 

KEIBEL,  F.  and  MALL,  F.  P.:  Manual  of  Human  Embryology.     Chap.  VIII,  1910. 

KOLLMAN,  J.:  Handatlas  der  Entwickelungsgeschichte  des  Menschen.    Jena,  1907. 

MALL,  F.  P.:  On  the  Age  of  Human  Embryos.    Am.  Jour,  of  Anat.,  Vol.  23, 1918. 

RABL,  C.:  Die  Entstehung  des  Gesichtes.    Leipzig,  1902. 

TRIEPEL,  H.:  Alter  menschlicher  Embryonen  und  Ovulationstermin.  Anat.  An- 
zeiger,  Bd.  48,  1915. 


PART  II. 
ORGANOGENESIS. 


CHAPTER  IX. 

THE  DEVELOPMENT  OF  THE  CONNECTIVE  TISSUES  AND  THE 

SKELETAL  SYSTEM. 

All  the  connective  or  supporting  tissues  of  the  body,  except  neuroglia, 
are  derived  from  the  mesoderm.  This  Goes  not  imply,  however,  that  all  the 
mesoderm  is  transformed  into  connective  tissues;  for  such  structures  as  the 
endothelium  of  the  blood  vessels  and  lymphatic  vessels,  probably  blood  itself, 
the  epithelium  lining  the  serous  cavities,  smooth  and  striated  muscle,  and  a  part 
of  the  epithelium  of  the  urogenital  system  are  derived  from  mesoderm. 

Primitive  groove 


FIG.  ioo. — Transverse  section  of  chick  embryo  of  27  hours'  incubation.     Photograph. 


The  origin  of  the  mesoderm  itself  has  been  discussed  elsewhere  (p.  93). 
In  this  connection  it  is  sufficient  to  recall  that  it  is  situated  between  the  ectoderm 
and  entoderm  and  consists  of  several  layers  of  closely  packed  cells  (Fig.  ioo). 
The  axial  portion  in  the  neck  and  body  regions  becomes  differentiated  into  the 
mesodermic  somites.  At  the  same  time  a  cleft  (the  coelom)  separates  the  more 
peripheral  portion  into  a  parietal  and  a  visceral  layer  (Figs.  101  and  103).  In 
the  head  region  where,  in  the  higher  animals,  there  is  little  or  no  indication  of 

129 


130 


TEXT-BOOK  OF  EMBRYOLOGY. 


Ectoderm 


Ectoderm 


Coelom 


FIG.  101. — Transverse  section  of  chick  embryo  (2  days'  incubation).     Photograph. 
The  parietal  mesoderm   (lying  above  the  ccelom)   is  not  labeled.     The  two  large  vessels  under 
the  primitive  segments  are  the  primitive  aortae.     Spaces  separating  germ  layers  are  clue  to 
shrinkage. 


Mesoderm 
(mesenchyme) 


Neural  tube 


Ectoderm  Pharynx  Entoderm 

FIG.  102.— Transverse  section  through  head  region  of  chick  embryo  of  42  hours' 
incubation.     Photograph. 


THE  CONNECTIVE  TISSUES  AND  THE  SKELETAL  SYSTEM. 


131 


somites  and  ccelom,  the  mesoderm  simply  fills  in  the  space  between  the  ecto- 
derm and  entoderm  (Fig.  102).     Portions  of  the  mesoderm  in  all  these  re- 
gions are  destined  to  give  rise  to  connective  tissues.     Each  mesodermic  somite! 
soon  becomes  differentiated  into  three  parts — the  sclerotome,  cutis  plate  and  ( 
myotome  (Fig.  104).     Of  these,  only  the  sclero tome  and  cutis  plate  are  directly 
concerned  in  the  formation  of  connective  tissues,  the  myotomes  giving  rise  to 
striated  voluntary  muscle.     The  sclerqtomes  are  destined  to  give  rise  to  the 


Neural  tube 


tf      \  Primitive  segment 


Intermediate 
cell  mass 


Visceral  mesoderm  —ft 


Mesothelium 


f'^Xx^® 


Lateral 
body  wall 


Umbilical  vein 


FIG.  103. — Transverse  section  of  human  embryo  with  13  primitive  segments;  section  taken 
through  the  6th  segment.     Kollmann. 

vertebrae  and  other  forms  of  connective  tissue  in  their  neighborhood,  the  cutis 
plates  to  a  part,  at  least,  of  the  corium  of  the  skin.  The  parietal  and  visceral 
layers  of  the  mesoderm  (excepFthe  mesothelium  lining  the  ccelom)  and  the 
mesoderm  of  the  head  region  are  destined  to  give  rise  to  the  various  types  of 
connective  tissue  forming  parts  of  the  other  organs  of  the  body. 

HISTOGENESIS. 

The  sclerotomes  and  cutis  plates  at  first  constitute  parts  of  the  mesoorermic 
somites,  and  are  composed  of  epithelial-like  cells  with  little  intercellular  sub- 
stance. The  intercellular  substance  gradually  increases  in  amount  so  that  the 


132 


TEXT-BOOK  OF  EMBRYOLOGY. 


Neural  crest    A 


( Cutis  plate 
Myotome  ] 

I  Muscle  plate 

Scl.1 


Pronephros  - 

\ 

Parietal  mesoderm— 

Intestine 


Upper 
limb  bud 


Visceral  mesoderm 


FIG.  104. — Transverse  section  of  human  embryo  of  the  3rd  week.     Scl.1,  Break  in  myotome  at 
point  where  sclerotome  is  closely  attached.     Kollmann. 


Neural  tube   — 


Intersegmental 
artery 


Intersegmental 

artery 


"^  Sclerotome 


Myocoel 


FIG.  105. — Three  primitive  segments  from  sagittal  section  of  human  embryo  of 
the  3rd  week.     Kollmann. 


THE   CONNECTIVE  TISSUES  AND   THE   SKELETAL   SYSTEM. 


133 


cells  become  more  widely  separated  from  one  another,  at  the  same  time 
assuming  oval  or  spindle  shapes  and  then  irregular  branching  forms  (Fig. 
106).  The  rest  of  the  mesoderm,  except  the  mesothelium,  also  undergoes  a 
similar  transformation  so  that  structurally  its  cells  are  indistinguishable  from 
those  derived  from  the  sclerotomes  and  cutis  plates. 

Thus  the  mesoderm  at  this  stage  is  composed  of  irregular,  branching 
cells,  with  a  relatively  large  amount  of  homogeneous  intercellular  substance 
filling  the  interstices.  The  branches,  or  protoplasmic  processes,  of  each 
cell  anastomose  freely  with  those  of  other  cells  in  the  immediate  vicinity. 


FIG.  1 06. — Mesenchymal  tissue  from  somatopleure  of  a  5  mm.  human  embryo. 
Mesothelium  is  shown  along  lower  border  of  figure. 

In  this  manner  a  syncytium  is  formed  to  which  the  term  mesenchyme  is  ap- 
plied (Fig.  106).  The  mesenchyme  itself  lacks  specialization,  being  what 
is  known  as  an  indifferent  tissue,  but  it  constitutes  the  structural  basis  upon 
which  all  the  connective  tissues  of  the  adult  body  are  built;  all  the  forms  of 
connective  tissue  (except  neuroglia)  develop  from  it. 

That  intercellularsttbstarice  is~  derived  originally  from  the  cell  can  scarcely 
be  denied.  All  the  cells  of  the  organism  are  derived  from  the  fertilized  ovum. 
As  soon  as  two  or  more  cells  are  formed  by  segmentation  of  the  ovum,  they  are 
either  simply  in  apposition  or  else  they  are  united  by  something  in  the  nature 
of  a  "cement"  substance  which  must  have  been  derived  from  the  cells  them- 
selves. In  the  mesenchymal  tissue  this  intercellular  ground  substance  is  a 
prominent  feature,  and  probably  represents  in  part  nutritive  materials  and 
in  part  the  products  of  cell  activity. 


134  TEXT-BOOK  OF  EMBRYOLOGY. 

Fibrils   and   Fibers.— The   least   differentiated   and   perhaps  the  least 

specialized  tissue  derivedjrpm  EQ^cn^TmBjsj^^|^l^?^5L-§5^  as  tnat 
found  in  the  lympbTnodes  and  spleen.  In  the  peripheral  part  of  the  cyto- 
plasm, or  exoplasm,  of  the  mesenchymal  cells  and  their  processes  there  arise 
delicate  fibrils,  often  extending  from  one  cell  to  another,  which  probably 


FIG.  107. — Fibril  forming  cells  from  fresh  subcutaneous  tissue  of  head  of  chick  embryo.     Boll. 

represent  specialized  parts  of  the  spongioplasm.  These  fibrils  maintain 
their  intracellular  position  instead  of  becoming  separated  from  the  parent 
cytoplasm,  so  that  the  reticular  tissue  retains  a  marked  resemblance  in 
form  to  the  original  mesenchyme. 


FIG.  108. — Connective  tissue  (mesenchymal)  cells  from  larval  salamander.     Flemming. 

The  first  step  in  the  development  of  the  true  fibrillar  forms  of  connective 
tissue  from  mesenchyme  is  the  formation  of  fibrils  and  fibers.  While  it  has 
been  held  by  some  investigators  that  the  fibrils  arise  in  and  from  the  homo- 
geneous intercellular  substance,  the  best  substantiated  view  is  that  they  arise 
within  and  from  the  cytoplasm  of  the  mesenchymal  cells  (Figs.  107  and  108). 
They  then  become  separated  from  the  cytoplasm  and  lie  free  in  the  " ground" 


THE   CONNECTIVE  TISSUES  AND   THE  SKELETAL  SYSTEM.  135 

substance  in  bundles  (fibers).  These  fibrillated  fibers  are  collaginous  in 
character.  Elastic  fibers,  while  not  fibrillated,  probably  have  a  similar 
origin.  This  first  step  in  development  gives  rise  to  a  loose,  delicate  tissue 
in  the  embryo,  known  as  embryonal  connective  tissue,  from  which  all  the 
adult  forms,  except  reticular  tissue,  develop. 

The  areolar  tissue  of  the  adult  retains  many  of  the  general  characters  of 
embryonal  connective  tissue.  The  fibers,  both  collaginous  and  elastic,  are 
loosely  arranged  and  extend  in  all  directions.  The  cells  (fibroblasts)  are 
fewer,  however,  and  while  they  are  characterized  by  irregular,  branching 
forms  it  is  not  known  whether  their  processes  anastomose. 


FIG.  109. — Longitudinal  section  of  developing  ligament  from  finger  of 
human  foetus  of  6  months.     Photograph. 

In  any  fibrous  tissue,  such  as  areolar,  or  the  denser  forms  (fascia,  tendons, 
ligaments),  the  structure  depends  upon  the  secondary  arrangement  of  the 
fibers  and  not  upon  any  peculiarity  of  origin.  In  all  these  forms  the  fibers 
have  the  same  origin,  but  in  the  denser  fascia,  tendons  and  ligaments  they 
become  arranged  in  parallel  lines  (Fig.  109). 

Adipose  Tissue. — Adipose  tissue  is  a  form  of  connective  tissue  in  which 
the  fatty  element  replaces  to  a  great  extent  the  cytoplasm  in  many  of  the 
embryonic  connective  tissue  cells.  It  always  develops  in  close  relation  to  blood 


136  TEXT-BOOK  OF  EMBRYOLOGY. 

vessels,  and  first  appears  in  the  axilla  and  groin  about  the  thirteenth  week. 
It  is  formed  in  other  places  at  later  periods,  even  during  adult  life,  but  the 
mode  of  development  is  always  the  same.  In  some  of  the  cells  in  the  neigh- 
borhood of  small  blood  vessels  minute  droplets  of  fat  are  deposited.  The 
origin  of  the  fat  is  not  known.  The  droplets  become  larger,  other  smaller  ones 
appear,  and  finally  all  of  them  coalesce  to  form  a  single  large  drop  which  practi- 
cally fills  the  cell.  The  result  of  this  is  that  the  remaining  cytoplasm  is  pushed 
outward  and  forms  a  sort  of  pellicle  around  the  fat.  The  nucleus  also  is 
crowded  outward  and  comes  to  lie  flattened  in  the  pellicle  of  cytoplasm  (Fig. 


Small  artery 

FIG.  no. — Developing  fat  from  subcutaneous  tissue  of  pig  embryo  5  inches  long.  Small 
artery  breaking  up  into  capillary  network'  groups  of  fat  cells  developing  in 
embryonic  connective  tissue 

in).  At  the  same  time  the  whole  fat  cell  increases  in  size  and  forms  a  relatively 
large  structure. 

Fat  cells  usually  develop  in  groups  or  masses  around  blood  vessels  (Fig. 
no).  The  neighboring  groups  gradually  enlarge  and  approach  each  other, 
but  do  not  fuse,  thus  leaving  more  or  less  fibrous  connective  tissue  between 
them,  which  constitutes  the  interlobular  tissue  seen  in  adult  adipose  tissue. 
Among  the  individual  cells  in  a  lobule  there  is  also  a  small  amount  of  fibrous 
tissue  present.  From  the  mode  of  development  a  small  artery  usually  affords 
the  blood  supply  for  each  lobule. 

Cartilage.— In  the  different  kinds  of  cartilage  the  matrix  probably  repre- 


THE   CONNECTIVE   TISSUES   AND   THE   SKELETAL  SYSTEM. 


137 


sents  a  modification  of  tne  "ground  substance"  of  the  original  embryonic 
tissue.  The  fibers  in  the  matrix  are  probably  derived  from  the  cells  in  the 
same  manner  as  the  fibers  in  the  fibrillar  forms  of  connective  tissue  (Fig.  112). 
Osseous  Tissue. — Here  again  the  basis  for  development  is  embryonic 
connective  tissue,  although  in  one  type  of  development  cartilage  precedes  the 
bone.  Two  types  of  ossification  are  recognized — intramembranous  and  intra- 
cartilaginous  or  endochondral.  Injin^minemb^ajious  ossification  calcium  salts 
are  deposited  in  ordmarv  embryonjc_  connective  tissue.  In  intracartilagi- 


Capillary 


Embryonic 
connective  tissue 


Arteriole 


FIG.  in. — Developing  fat  from  subcutaneous  tissue  of  pig  embryo  5  inches  long.  Fat  (stained 
black)  developing  in  embryonic  connective  tissue  cells.  At  the  right  are  five  individual  cells 
showing  stages  of  development  from  an  embryonic  cell  to  an  adult  fat  cell. 

nous  ossification  hyalin  cartilage  first  develops  in  the  same  general  shape  as 
the  future  bone  and  the  calcium  salts  are  afterward  deposited  within  the  mass  of 
cartilage.  It  is  customary  to  speak  also  of  another  type  of  ossification — sub- 
feriosteal — in  which  the  calcium  salts  are  deposited  under  the  periosteum. 


INTRAMEMBRANOUS  OSSIFICATION. 

This  is  the  type  of  ossification  by  which  many  of  the  flat  bones  of  the  skull 
and  face  are  formed.  The  region  in  which  these  bones  are  to  develop  consists 
of  embryonic  connective  tissue.  At  certain  points  in  this  region  bundles  of 
connective  tissue  fibers  become  impregnated  with  calcium  salts.  Such  areas  are 
known  as  calcification  centers.  In  each  of  these  areas  the  cells  increase  in  num- 
ber, the  tissue  becomes  very  vascular  and  some  of  the  cells,  becoming  more  or 
less  round  or  oval,  with  distinct  nuclei  and  a  considerable  amount  of  cytoplasm, 


138 


TEXT-BOOK  OF  EMBRYOLOGY. 


Ectoplasm  with 
"white"  fibers 


Ground 
substance 


Ectoplasm 


FiG.  112.- — Connective  tissue  cells  from  intervertebral  disk  of  calf  embryo;  showing  origin  of 
"white"  and  elastic  fibers  in  protoplasm  of  cells.  Ectoplasm  represents  a  modified  part 
of  the  protoplasm.  Hansen. 


Osteogenetio 
tissue 


FIG.  113. — Vertical  section  through  frontal  bone  of  human  foetus  of  4  months. 
(Intramembranous  ossification.)     Photograph. 


THE   CONNECTIVE  TISSUES   AND  THE  SKELETAL  SYSTEM.  139 

arrange  themselves  in  single,  fairly  regular  rows  along  the  bundles  of  calcined 
fibers.  The  differentiated  cells  are  known  as  osteoblasts  (bone  formers) ,  and  the 
whole  tissue  is  now  known  as  osteo genetic  tissue.  Under  the  influence  of  the  osteo- 
blasts a  thin  layer  of  calcium  salts  is  deposited  between  the  osteoblasts  and  the 
calcified  fibers.  In  this  way  the  first  true  bone  is  formed,  and  the  calcification 
center  becomes  an  ossification  center.  Successive  layers  or  lamellae  of  calcium 
salts  are  laid  down  and  some  of  the  osteoblasts  become  enclosed  between  the 
lamellae  to  form  the  bone  cells  (Figs.  113  and  1 14).  The  spaces  in  which  the  bone 
cells  lie  are  the  lacuna.  At  the  same  time  the  fibers  also  are  enclosed  within  the 
bone  and  give  it  its  characteristic  fibrous  structure  (Fig.  114). 

Such  a  process  results  in  the  formation  of  irregular,  anastomosing  trabeculae 
of  bone.     The  spaces  among  the  trabeculae  are  known  as  primary  marrow 

Osteogenetis 

tissue  Osteoclast  Lacunae 


Bone 


Calcified  fibers 

FIG.  114. — From  vertical  section  through  parietal  bone  of  human  foetus  of  4. months. 
Bone  cells  not  shown  in  lacunae,     (Intramenibranous  ossification.) 

spaces-  and  contain  osteogenetic  tissue  (Fig.  113).  This  type  of  bone,  consisting 
of  irregular,  anastomosing  trabeculae  and  enclosed  marrow  spaces,  is  known  as 
spongy  bone.  The  spongy  bone  thus  formed  is  covered  on-ats  outer  side  by  a 
layer  of  connective  tissue  which  from  its  position  is  called  the  periosteum 
(Fig.  113),  and  which  represents  a  part  of  the  original  embryonic  connective 
tissue  membrane  in  which  the  bone  was  laid  down.  During  its  development 
the  periosteum  becomes  an  exceedingly  dense  fibrous  membrane  which  is  closely 
applied  to  the  surface  of  the  bone. 

In  a  growing  embryo,  provision  must  be  made  for  increase  in  the  size  of  the 
cranial  cavity  to  accommodate  the  growing  brain.  This  is  accomplished  in 
the  following  manner :  On  the  inner  surface  of  the  newly  formed  bone,  large 
multinuclear  cells  appear,  which  are  known  as  osteoclasts  (bone  destroyers). 
The  osteoclasts  are  unusually  large  cells  with  a  large  number  of  nuclei  and 
abundant  cytoplasm,  and  in  sections  can  be  seen  lying  in  depressions  in  the 


140 


TEXT-BOOK  OF  EMBRYOLOGY. 


bone — Howslip's  lacuna  (Fig.  114).  Whether  they  are  the  specific  agents  in 
dissolution  of  bone  has  been  questioned  (Arey).  While  the  destruction  of 
bone  is  going  on  on  the  inner  surface,  new  bone  is  being  formed  on  the  outer 
surface,  especially  under  the  periosteum  where  the  osteoblasts  are  most 
numerous.  Thus  the  layer  of  bone  gradually  comes  to  lie  farther  and 
farther  out  and  the  cranial  cavity  is  enlarged.  So  long  as  the  cranial  cavity 


Cartilage 


Osteogenetic  tissue 


Intracartilaginous 
bone 

Subperiosteal 
bone 


Blood  vessels 


Periosteum 
(perichondrium) 


*  Ossification  center 


Calcification  zone 


FIG.  115. — Longitudinal  section  of  one  of  the  metatarsal  bones  of  a  sheep  embryo. 
(Intracartilaginous  ossification.) 

continues  to  enlarge  the  new  bone  is  of  the  spongy  variety,  but  toward  the  end 
of  development  the  trabeculae  become  thicker  and  finally  come  together  to 
form  the  compact  bone  characteristic  of  the  roof  of  the  skull.  The  fact  that 
the  new  bone  laid  down  during  the  enlargement  of  the  cranial  cavity  is  laid 
down  under  the  periosteum  has  led  to  the  term  subperiosteal  ossification. 
The  process  is  essentially  the  same  as  in  the  original  intramembranous 
ossification. 

INTRACARTILAGINOUS  OSSIFICATION. 

^  In  this  type  of  ossification  hyalin  cartilage  is  first  formed  in  a  shape  which 
^  corresponds  very  closely  to  the  shape  of  the  future  bone.  For  example,  the 
!  femur  is  first  represented  by  a  piece  of  hyalin  cartilage  which  develops  from 


THE   CONNECTIVE  TISSUES  AND   THE   SKELETAL  SYSTEM. 


141 


the  original  embryonic  connective  tissue.  On  the  surface  of  the  cartilage  a 
membrane  of  dense  fibrous  connective  tissue,  known  as  the  perichondrium, 
develops  (Fig.  115).  In  most  cases,  ossification  begins  about  the  middle 
of  the  piece  of  cartilage,  corresponding  to  the  middle  of  the  shaft  of  a  long 
bone  (Fig.  115).  The  cell  spaces  enlarge  and  in  some  cases  the  septa  of  matrix 
between  the  enlarged  spaces  break  down,  so  that  several  cells  may  lie  in  one 
space.  The  cell  spaces  radiate  from  a  common  center,  but  a  little  later  they 
come  to  lie  in  rows  parallel  with  the  long  axis  of  the  mass  of  cartilage.  During 
these  early  changes  lime  salts  are  deposited  in  the  matrix  of  the  cartilage  in 
this  region,  and  the  portion  so  involved  is  known  as  a  calcification  center. 

So  far  the  process  is  preparatory  to  actual  bone  formation.     Then  small 
blood  vessels  from  the  perichondrium  (periosteum)  grow  into   the  cartilage, 


Periosteal  bud 


Blood  vessel 


Cartilage 
cell  spaces 


/ 


Cartilage  cells 


wMM 


Cartilage  matrix 


Kmi&it 


Periosteum 
(Perichondrium) 


FIG.  116.  —  From  section  of  one  of  the  tarsal  bones  of  a  pig  embryo.     Showing  periosteal  bud 
pushing  into  the  cartilage  at  the  ossification  center.     (Intracartilaginous  ossification.) 


carrying  with  them  some  of  the  embryonic  connective  tissue.  These  little 
ingrowths  of  connective  tissue  and  blood  vessels  are  known  as  periosteal  buds 
(Fig.  1  1  6).  The  septa  between  the  enlarged  cartilage  cell  spaces  break  down 
still  further,  forming  still  larger  spaces  into  which  the  periosteal  buds  grow. 
Many  of  the  connective  tissue  cells  are  transformed  into  osteoblasts  —  oval  or 
round  cells  with  distinct  nuclei  and  a  considerable  amount  of  cytoplasm  —  and 
with  the  fibers  and  blood  vessels  constitute  osteogenetic  tissue  (Fig.  117).  The 
cartilage  cells  in  this  region  disintegrate  and  disappear,  and  the  cavity  formed 
by  the  coalescence  of  the  cell  spaces  constitutes  the  primary  marrow  cavity  (Fig. 
117).  From  the  primary  marrow  cavity  osteogenetic  tissue  pushes  in  both 
directions  toward  the  ends  of  the  cartilage.  The  transverse  septa  between  the 
enlarged  cartilage  cell  spaces  break  down,  leaving  a  few  longitudinal  septa 
which  form  the  walls  of  long  anastomosing  channels  which  are  continuous  with 


142 


TEXT-BOOK  OF  EMBRYOLOGY. 


the  primary  marrow  cavity.  The  osteoblasts  arrange  themselves  in  rows  along 
the  septa  of  calcined  cartilage  and  a  thin  layer  or  lamella  of  calcium  salts  is 
deposited  between  them  and  the  cartilage.  Successive  lamellae  are  deposited 
in  the  same  manner  and  some  of  the  osteoblasts  become  enclosed  to  form  bone 
cells  (Fig.  118).  The  cartilage  in  the  center  gradually  disappears.  This 
region  where  bone  formation  is  going  on  is  known  as  an  ossification  center  (Fig. 
115)  and  the  irregular  anastomosing  trabeculae  of  bone  with  the  enclosed  marrow 
spaces  constitute  primary  spongy  bone. 

From  this  time  on,  ossification  gradually  progresses  toward  each  end  of  the 
cartilage,  and  at  the  same  time  a  special  modification  of  the  cartilage  precedes 
it.  Nearest  the  ossification  center  the  cartilage  cell  spaces  become  enlarged  and 


Cartilage  cell  spaces 
(primary  marrow  space) 


Disintegrating 
cartilage  cells 


Cartilage  cell 
spaces 


Blood  vessel    — 


Trabecula 
of  cartilage 


Osteogenetic  tissue  in 
primary  marrow  space 

FIG.  117. — From  same  section  as  Fig.  153;  showing  osteogenetic  tissue  pushing  into  the  cartilage 
and  breaking  it  up  into  trabeculae.     (Intracartilaginous  ossification.) 

arranged  in  rows  and  contain  cartilage  cells  in  various  stages  of  disintegration. 
Some  of  the  septa  break  down,  leaving  larger,  irregular  spaces;  the  remaining 
septa  become  calcified  (Fig.  115).  Passing  away  from  the  center  of  ossifica- 
tion, there  is  less  enlargement  of  the  cell  spaces  and  they  have  a  tendency  to  be 
arranged  in  rows  transverse  to  the  long  axis  of  the  cartilage;  there  is  also  a  lesser 
degree  of  calcification.  The  region  of  modified  cartilage  at  each  end  of  the 
ossification  center  passes  over  gradually  into  ordinary  hyalin  cartilage  and  is 
known  as  the  calcification  zone.  It  always  precedes  the  formation  of  bone  as 
the  latter  process  moves  toward  the  end  of  the  cartilage  (Fig.  115). 

Along  with  the  type  of  ossification  just  described  subperiosteal  ossification 
also  occurs  (Fig.  115).  Beneath  the  periosteum  (perichondrium)  is  a  layer  of 
connective  tissue  the  cells  of  which  are  transformed  into  osteoblasts.  They 


THE  CONNECTIVE  TISSUES  AND  THE  SKELETAL  SYSTEM.  143 


deposit  layers  of  calcium  salts  on  the  surface  of  the  cartilage  in  the  same 
manner  as  around  the  trabeculae  inside  the  cartilage. 

The  transformation  of  the  spongy  bone  into  compact  bone  is  peculiar 
in  that  the  former  is  dissolved  and  then  replaced  by  new  bone.  Whether 
this  dissolution  occurs  through  the  agency  of  the  large  multinucleated  cells 
known  as  osteoclasts  is  not  certain.  By  the  process  of  dissolution  the  marrow 
spaces  are  increased  in  size  and  are  known  as  Haversian  spaces.  Within 
these  spaces  new  bone  is  then  deposited  layer  upon  layer,  under  the  influence 
of  the  osteoblasts,  until  the  Haversian  spaces  are  reduced  to  narrow  channels, 
the  Haversian  canals.  The  layers  of  bone  are  the  Haversian  lamella.  The 
interstitial  lamella  in  compact  bone  have  two  possible  origins.  They  may  be 


Blood  vessel 


Bone 


Cartilage 


Bone  cell 


Cartilage  cell  — 


Cartilage  cell  space 


Osteogenetic 
tissue 


Osteoblasts 


FIG.  1  1  8.  —  From  same  section  as  Fig.  115;  showing  bone  deposited  around  one  of  the 
trabeculae  of  cartilage.     (Intracartilaginous  ossification.) 

the  remnants  of  certain  lamellae  of  the  original  spongy  bone  which  were  not 
removed  in  the  enlargement  of  the  primary  marrow  spaces,  or  they  may  be 
parts  of  early  formed  Haversian  lamellae  which  were  later  more  or  less 
replaced  by  other  Haversian  lamellae. 

Carey,  in  his  recent  studies  on  certain  mechanical  phases  of  development, 
concludes  "  that  cartilage  and  bone  are  not  self  -differentia  ted,  nor  are  they 
self-crystallized  products,"  but  represent  "  cellular  responses  to  the  varying 
intensity  of  the  stresses  and  strains  produced  by  resistance  (pressure)  counter- 
acting the  growth"  of  the  skeleton  in  its  blastemal  stage,  that  is,  while  the 
cells  are  closely  compacted  prior  to  the  appearance  of  the  specific  tissue. 
In  his  analysis  of  the  femur,  Koch  has  concluded  that  the  "normal  external 
form  and  internal  architecture  of  the  human  femur  results  from  an  adaptation 
of  form  to  the  normal  static  demands,  or  normal  function  of  the  bone." 
It  would  appear  therefore  that  in  the  development  of  bone  mechanical  factors 


144  TEXT-BOOK  OF  EMBRYOLOGY. 

play  an  essential  part  not  only  in  the  formation  of  the  bone  itself  but  also  in 
the  establishment  of  its  form  and  internal  structure. 

GROWTH  OF  BONES. — The  way  in  which  the  cranial  cavity  enlarges  has  been 
described  on  page  139.  While  the  process  of  enlargement  is  going  on,  the 
individual  bones  increase  in  size  principally  by  the  addition  of  new  bone  along 
their  edges. 

Intracartilaginous  bones  grow  both  in  diameter  and  in  length.  It  has 
already  been  stated  that  the  primary  spongy  bone  formed  in  cartilage  is  dis- 
solved and  that  new  bone  is  deposited  under  the  periosteum.  This  naturally 
brings  about  an  enlargement  of  the  primary  marrow  cavity  and  at  the  same 
time  an  increase  in  the  diameter  of  the  bone  as  a  whole.  From  this  it  is  obvious 
that  the  compact  bone  of  the  shaft  of  a  long  bone  is  of  subperiosteal  origin,  the 
intracartilaginous  bone  having  been  completely  absorbed. 


A.  B 

FIG.  119. — Diagram  representing  growth  in  diameter  of  a  long  bone. 

from  Flour  ens. 

The  fact  that  the  osseous  tissue  bordering  the  marrow  cavity  is  absorbed  and  that  new 
bone  is  deposited  under  the  periosteum  can  be  quite  clearly  demonstrated.  A  young 
growing  animal  is  fed  for  a  few  weeks  on  madder,  which  colors  all  the  bone  formed  during  that 
time  a  distinct  red.  If  the  animal  is  then  killed  and  sections  made  of  the  long  bones,  the 
outer  part  of  the  latter  will  appear  a  distinct  red.  Another  growing  animal  is  fed  on  madder 
for  a  few  weeks,  then  allowed  to  live  a  few  weeks  longer  without  madder.  Then  if  it  is 
killed  and  sections  made  of  the  bones,  the  red  bone  is  found  to  be  covered  with  a  layer  of 
uncolored  bone  which  was  deposited  after  the  madder  feeding  had  been  stopped.  If  a 
young  growing  animal  is  fed  on  madder  for  a  time  and  then  allowed  to  live  long  enough 
without  madder,  the  red  bone  will  be  found  lining  the  marrow  cavity.  (See  Fig.  119.) 

Growth  in  length  of  the  long  bones  takes  place  in  a  different  manner.  The 
primary  center  of  ossification  is  situated  near  the  middle  of  the  piece  of  cartilage, 
and  ossification  proceeds  in  both  directions  toward  the  ends  of  the  cartilage  to 
produce  the  diaphysis  or  shaft  of  the  bone.  In  each  end  of  the  cartilage  there 
appears  a  secondary  center  from  which  ossification  proceeds  in  all  directions  to 
produce  the  epiphysis.  Between  the  shaft  and  epiphysis  a  disk  of  cartilage 
remains,  and  here,  so  long  as  the  bone  is  growing,  new  cartilage  continues  to  be 
formed.  At  the  same  time  new  bone  is  being  formed  in  the  new  cartilage, 


THE  CONNECTIVE  TISSUES  AND  THE  SKELETAL  SYSTEM.  145 

principally  in  the  part  next  the  shaft.  This  produces  an  elongation  of  the 
shaft,  the  two  epiphyses  being  carried  farther  and  farther  apart,  and  conse- 
quently a  lengthening  of  the  bone  as  a  whole.  When  the  bone  reaches  the 
required  length,  the  cartilage  disk  diminishes  and  finally  is  wholly  replaced  by 
bone,  being  represented  in  the  adult  only  by  the  epiphyseal  line.  (See  Fig.  120.) 
MARROW. — The  forerunner  of  marrow  is  the  osteogenetic  tissue  in  the  pri- 
mary marrow  spaces,  which  in  turn  is  derived  from  embryonic  connective  tissue 
(Fig.  117).  During  the  development  of  bone,  great  numbers  of  osteoblasts  are 


FIG.  1 20. — Longitudinal  section  from  head  of  femur  of  young  dog.  Photograph. 
The  head  of  the  femur  is  shown  in  the  upper  part  of  the  figure,  the  end  of  the  shaft  in  the  lower 
part.  Between  the  two  the  lighter  line  represents  the  cartilage  between  the  primary  center 
of  ossification  (shaft)  and  the  secondary  center  (epiphysis,  head),  and  marks  the  site  of  the 
epiphyseal  line.  The  lighter  portion  covering  the  head  represents  the  cartilage  bordering 
the  jomt  cavity. 

constantly  being  differentiated  from  the  connective  tissue  cells  and  many  of 
these  ultimately  become  bone  cells.  When  development  ceases,  osteoblasts 
cease  to  become  differentiated.  Marrow  is  one  of  the  chief  centers  of  blood 
cell  formation  in  later  foetal  life,  and  in  the  adult  is  normally  probably  the 
only  source  of  erythrocytes.  An  account  of  blood  cell  formation  will  be 
found  in  the  section  on  "Haemopoiesis."  The  myeloblasts,  which  are  prob- 
ably identical  with  or  at  least  closely  allied  to  the  primitive  blood  cells 
(haemoblasts),  by  acquiring  certain  types  of  granules  in  the  cytoplasm 
become  neutrophilic,  acidophilic  or  basophilic  myelocytes.  During  develop- 
ment two  types  of  giant-cells  (myeloplaxes)  appear  in  the  marrow.  Accord- 


146  TEXT-BOOK  OF   EMBRYOLOGY. 

ing  to  Jordan  one  of  these  is  haemogenic  and  the  other  osteolytic.  The 
former  originates  from  enlarged  hasmoblasts  and  may  be  regarded  as  repre- 
senting centers  of  intense  haemopoiesis,  giving  rise  to  erythrocytes.  The 
osteolytic  giant-cells  (osteoclasts)  arise  more  frequently  from  fused  portions 
of  the  marrow  reticulum,  less  often  from  fused  osteoblasts,  and  are  always 
multinucleated.  Arey  maintains  in  his  more  recent  work  that  the  so-called 
osteoclasts  usually  arise  by  fusion  of  old  and  basophilic  osteoblasts,  the 
cytoplasm  of  the  syncytial  mass  becoming  acidophilic.  Arey  also  holds 
that  this  type  of  giant-cell  is  not  a  specific  agent  in  bone  resorption.  In 
young  marrow  there  is  little  or  no  fat  present,  but  in  later  life  many  of  the 
connective  tissue  cells  are  transformed  into  fat  cells  (p.  136),  so  that  these 
form  the  greater  part  of  the  marrow.  Such  a  process  occurs  most  extensively 
in  the  shaft  of  the  long  bones  and  gives  rise  to  "yellow"  marrow.  In  the 
heads  of  the  long  bones,  in  the  ribs,  and  in  the  short  bones  the  marrow  retains 
its  earlier  character  and  is  known  as  "red"  marrow. 

THE  DEVELOPMENT  OF  THE  SKELETAL  SYSTEM. 
The  Axial  Skeleton. 

The  Notochord. — The  notochord  (chorda  dorsalis)  constitutes  the 
primitive  axial  skeleton  of  all  Vertebrates,  yet  it  differs  from  the  other  skeletal 
elements  in  that  it  is  a  derivative  of  the  entoderm.  In  man  it  is  merely  a  tran- 
sient structure  and  disappears  early  in  fcetal  life,  leaving  but  a  slight  trace  of 
itself  in  the  intervertebral  disks.  In  embryos  of  2-3  mm.  the  cells  of  the 


*  Ectoderm 
Mesoderm 


Entoderm 


FIG.  I2i.— From  transverse  section  of  human  embryo  with  8  pairs  of 
primitive  segments  (2.69  mm.).     Kollmann. 

entoderm  just  ventral  to  the  neural  groove  become  slightly  differentiated 
(Fig.  121)  and  then  form  a  groove  with  a  ventral  concavity.  The  groove  closes 
in,  becomes  constricted  from  the  parent  tissue  (entoderm)  and  lies  just  ventral  to 
the  neural  tube,  where  it  soon  becomes  surrounded  by  mesodermal  tissue.  This 
structure  is  the  notochord  and  constitutes  a  solid,  cylindrical  cord  of  cells 
extending  from  a  point  just  caudal  to  the  hypophysis  to  the  caudal  extremity  of 
the  embryonic  body.  In  embryos  of  17-20  mm.  the  mesodermal  tissue  around 
the  notochord  becomes  modified  to  form  the  chorda!  sheath.  On  account  of  its 
position  the  notochord  naturally  becomes  embedded  in  the  developing  vertebral 


THE   CONNECTIVE  TISSUES  AND   THE   SKELETAL  SYSTEM. 


147 


column,  extending  through  the  bodies  of  the  vertebrae  and  the  intervertebral 
disks.  The  cells  are  at  first  of  an  epithelial  nature  (Fig.  121),  but  those  within 
the  vertebral  bodies  become  vacuolated  and  broken  up  into  irregular,  multinu- 
clear  masses  which  then  disappear.  The  cord  is  thus  first  interrupted  in  the 
vertebrae,  leaving  only  the  segments  within  the  intervertebral  disks.  Later  these 
segments  also  undergo  degenerative  changes,  but  persist  as  the  so-called  pulpy 
nuclei. 

While  the  notochord  is  morphologically  the  forerunner  of  the  axial  skeleton, 
and  persists  as  a  whole  in  Amphioxus,  and  in  part  in  Fishes  and  Amphibia,  in 
the  higher  forms  it  is  almost  exclusively  an  embryonic  structure  with  little  or  no 
functional  significance.  It  differs  in  origin  from  the  true  skeletal  elements  and 
becomes  involved  with  them  only  to  disappear  as  they  develop. 


Spinal  nerve 


Myotome 


Perichordal  sheath 
Cleft  between  two 
vertebral  anlagen 

Intersegmental 

artery 

•Notochord 


Parts  of  two 
adjacent  sclerotomes 


FIG.  122. — Five  myotomes  and  sclerotomes  from  sagittal  section  of  human  embryo  of  5  mm.  Bardeen. 

Each  sclerotome  is  differentiated  into  a  looser  cephalic  part  and  a  denser  caudal  part,  the  two 

being  separated  by  a  cleft  (fissure  of  von  Ebner). 

The  Vertebrae. — The  changes  which  occur  in  the  ventro-medial  parts  of  the 
primitive  segments  to  form  the  sclerotomes  have  already  been  described.  At 
the  same  time  it  was  stated  that  the  vertebrae,  with  the  other  types  of  connective 
tissue  around  them,  were  derived  from  the  mesenchymal  tissue  of  the  sclerotomes 
(p.  131;  see  also  Fig.  104).  The  segmentally  arranged  masses  forming  the 
sclerotomes  are  separated  by  looser  tissue  in  which  the  intersegmental  arteries 
develop.  The  arteries  mark  the  boundaries  between  the  sclerotomes  (Fig.  122). 
About  the  third  week  of  development  the  caudal  part  of  each  sclerotome  con- 
denses to  form  a  more  compact  mass  of  tissue,  and  a  little  later  becomes 
separated  from  the  cephalic  part  by  a  small  cleft  (Fig.  123).  From  the  denser 
caudal  part  a  secondary  mass  of  tissue  grows  medially  and  meets  and  fuses  with 
its  fellow  of  the  opposite  side,  thus  enclosing  the  notochord.  The  medial  mass 


148 


TEXT-BOOK  OF  EMBRYOLOGY. 


thus  formed  may  be  considered  as  the  anlage  of  the  body  of  a  vertebra.  Another 
secondary  mass  also  grows  dorsally  between  the  myotome  and  the  spinal  cord, 
forming  the  anlage  of  the  -vertebral  arch.  A  third  mass  grows  ventro-laterally  to 
form  the  costal  process  (Figs.  124  and  125).  The  looser  tissue  of  the  cephalic 
part  of  each  sclerotome  also  sends  an  extension  medially  to  surround  the 
notochord,  and  fills  up  the  intervals  between  the  succeeding  denser  (caudal) 
parts.  The  looser  part  also  forms  a  sort  of  membrane  between  the  succeeding 
vertebral  arches.  The  tissue  between  the  denser  caudal  part  and  the  looser 
cephalic  part  of  each  sclerotome  is  destined  to  give  rise  to  an  intervertebral 
fibrocartilage.  While  the  denser  tissue  forming  the  caudal  part  of  each  sclero- 


Dermis 


Myotome 


Notochord 

Cleft 

Intersegmental  artery 

Perichordal  sheath 
Inter  vertebral  disk 
Interdiscal  membrane 


FIG.  123. — Six  myotomes  and  sclerotomes  from  sagittal  section  of  human  embryo  of  6  mm. 
Bardeen.     Compare  with  Fig.  160. 

tome  probably  gives  rise  to  the  greater  part  of  a  vertebra,  the  looser  tissue  of  the 
cephalic  part  is  also  involved  in  the  formation  of  the  cartilaginous  body,  as  will 
be  noted  again  in  the  following  paragraph.  The  peculiar  feature  of  the  process 
is  that  the  denser  caudal  part  of  a  sclerotome  becomes  associated  with  the  looser 
cephalic  part  of  the  next  succeeding  sclerotome,  so  that  each  vertebra  is  derived 
from  parts  of  two  adjacent  sclerotomes  and  not  from  a  single  sclerotome.  This 
naturally  brings  about  an  alternation  of  vertebra  and  myotomes  (Fig.  123). 

So  far  the  anlagen  of  the  vertebrae  are  in  the  so-called  blastemal  stage. 

Following  the  blastemal  stage  and  beginning  in  human  embryos  of  about  15 
mm.,  comes  the  cartilaginous  stage  in  which  the  mesenchymal  anlagen  of  the 
vertebrae  are  converted  into  embryonic  hyalin  cartilage.  In  the  body  of  each 
vertebra  a  center  of  chondrification  appears  in  the  looser  tissue  of  the  caudal 


THE   CONNECTIVE  TISSUES  AND   THE  SKELETAL  SYSTEM. 


149 


part  and  gradually  enlarges  and  involves  the  denser  cephalic  part.  It  is  to  be 
noted  that  the  denser  tissue  of  the  cephalic  part  of  a  vertebral  body  corresponds 
to  the  caudal  part  of  a  sclerotome.  Two  chondrification  centers  appear,  one  on 


Costal  process 


Aorta 


Stomach 


Arch  of 
vertebra 


Notochord 


Body  of 
vertebra 


Mesonephros 


Liver 


FIG.  124. — Transverse  section  (dorsal  part)  of  pig  embryo  of  14  mm.     Photograph. 

each  side  of  the  medial  line,  but  the  two  soon  fuse  around  the  notochord  to 
form  a  single  center.  In  addition  to  the  center  in  the  body  of  the  vertebra,  one 
also  appears  in  each  half  of  the  vertebral  arch,  and  one  in  each  costal  process 


Interdorsal  membrane 


Notochord 


Costal  process 
FIG,  125.— Models  of  three  vertebrae  in  the  blastemal  stage;  from  an  embryo  of  n  mm.     Bardeen. 

(Fig.  126).  All  these  centers  then  enlarge  and  unite  to  form  a  single  mass  of 
cartilage  which  corresponds  quite  accurately  in  shape  to  the  future  bony 
vertebra.  Processes  then  grow  out  from  the  vertebral  arch.  These  represent 


150 


TEXT-BOOK  OF  EMBRYOLOGY. 


the  transverse  and  articular  processes  (Fig.  127).  Each  half  of  a  vertebral 
arch  meets  its  fellow  of  the  opposite  side  dorsal  to  the  spinal  cord,  and  from 
the  point  of  meeting  the  spinous  process  grows  out.  The  costal  processes  do 


Costal  process 
(rib) 


Body  of 
vertebra 


Costal  process 
(rib) 


Aorta 


Pleural  cavity  Liver  CEsophagus  Lung 

FIG.  126. — Transverse  section  (dorsal  part)  of  pig  embryo  of  35  mm.     Photograph. 

not  retain  their  connection  with  the  body  of  the  vertebra,  but  break  away 
and  become  the  rib  cartilages,  as  will  be  noted  again  in  connection  with  the 
development  of  the  ribs. 

Following  the  cartilaginous  stage  is  the  stage  of  ossification  in  which  the 

Arch  of  vertebra 
Post,  articular 
process 

Transverse  process 


Anterior  articular  process 

FIG.  127. — Models  of  the  6th,  yth  and  8th  thoracic  vertebrae  of  an  embryo  of  33  mm. 

(dorsal  view).     Bardeen. 
On  the  right  the  cartilage  is  shown,  on  the  left  the  surrounding  fibrous  tissue. 

vertebrae  become  ossified  and  acquire  the  adult  condition.  Ossification  begins 
during  the  third  month  of  foetal  life  and  extends  over  a  long  period,  even  up  to 
the  age  of  twenty-five  years.  A  single  center  of  ossification  appears  in  the  body 


THE   CONNECTIVE  TISSUES  AND  THE  SKELETAL  SYSTEM. 


151 


of  each  vertebra,  and  following  this  a  center  in  each  half  of  the  vertebral  arch 
(Fig.  128).  Osseous  tissue  then  gradually  replaces  the  cartilage.  The  two 
halves  of  an  arch  fuse  dorsal  to  the  spinal  cord  during  the  first  year  of  post- 
natal life,  thus  completing  the  bony  arch.  The  arch  fuses  with  the  body  of  the 


Spinous  process 
Articular  process 
Rib 

Transverse  process 
Lat.  ossif.  center 

Med.  ossif.  center 

FIG.  128. — Thoracic  vertebra  and  ribs  of  human  embryo  of  55  mm.  (middle  of 

3rd  month).     Kollmanri's  A  Has. 
Cartilage  indicated  by  stippled  areas,  ossification  centers  by  irregular  black  lines. 

vertebra  between  the  third  and  eighth  years.  Thus  it  is  seen  that  the  process  of 
ossification  is  a  slow  one,  and  this  is  even  more  striking  when  one  considers  the 
formation  of  the  secondary  centers.  For  at  about  the  age  of  puberty  a  secondary 
center  appears  in  each  of  the  cartilages  that  cover  the  ends  of  the  vertebrae,  pro- 

Spinous  process 
Transverse  process 
Articular  process 


Body  of  vertebra 


Upper  epiphyseal 
plate 


FIG.  129. — Lumbar  vertebra  (lateral  view)  showing  secondary  centers  of  ossification.    Sappey. 

ducing  disks  of  bone — the  epiphyses.  A  secondary  center  also  appears  in  the 
cartilage  on  the  tip  of  each  spinous  process  and  transverse  process,  and  in  the 
lumbar  vertebrae  one  appears  also  on  the  tip  of  each  articular  process  (Fig.  120). 
The  epiphyses  unite  with  the  vertebrae  any  time  between  sixteen  and  twenty- 


152 


TEXT-BOOK  OF  EMBRYOLOGY. 


five  years.  About  the  twenty-fifth  year  the  sacral  vertebrae  unite  to  form  a 
single  mass  of  bone,  and  a  similar  union  also  takes  place  between  the  more  or 
less  rudimentary  coccygeal  vertebrae. 

While  the  general  plan  of  development  is  practically  the  same  in  all  the 
vertebrae,  there  are  a  few  noteworthy  modifications.  The  greatest  modification 
is  in  the  atlas  and  epistropheus  (axis).  The  entire  atlas  is  formed  from  the 
denser  caudal  part  of  a  sclerotome.  The  lateral  mass  and  the  posterior  (dorsal) 
arch  represent  the  vertebral  arch.  The  anterior  (ventral)  arch  represents  the 
hypochordal  bar,  a  plate  of  cartilage  which  develops  in  all  vertebrae  ventral  to 
the  notochord  but  disappears  in  all  except  the  atlas.  A  body  also  develops 
but  instead  of  forming  part  of  the  atlas  it  unites  with  the  body  of  the  epistro- 
pheus to  form  the  dens  (odontoid  process)  of  the  latter. 


FIG.  130. — Ventral  view  of  developing  sternum  of  human  embryo  of  30  mm. 
(beginning  of  3rd  month).     Ruge,  Kollmanris  Atlas. 

The  various  ligaments  of  the  vertebral  column  are  derived  from  the  embry- 
onic connective  tissue  surrounding  the  vertebras.  The  embryonic  connective 
tissue  in  the  clefts  separating  the  developing  vertebrae  is  transformed  into  the 
intervertebral  fibrocartilages. 

The  Ribs. — It  has  been  stated  in  a  previous  paragraph  that  the  costal  proc- 
esses arise  as  outgrowths  from  the  denser  caudal  parts  of  the  sclero tomes;  that 
they  grow  in  a  ventro-lateral  direction  and  consequently  are  at  first  connected 
with  and  are  parts  of  the  bodies  of  the  vertebrae  (Figs.  124  and  126).  These 
costal  processes  are  the  anlagen  of  the  ribs,  and  they  continue  to  grow  ventrally 
until  they  practically  encircle  the  body,  the  ventral  ends  of  a  number  of  them 
fusing  in  the  medial  line  to  form  the  sternum.  The  primary  junctions  between 
the  costal  processes  and  vertebrae  are  dissolved,  and  the  embryonic  connective 
tissue  in  this  region  gives  rise  to  the  costo-vertebral  ligaments.  The  dissolu- 
tion of  the  junctions  leaves  the  ribs  simply  articulating  with  the  vertebrae. 


THE   CONNECTIVE  TISSUES   AND   THE   SKELETAL  SYSTEM. 


153 


A  chondrification  center  appears  in  each  costal  process,  shortly  after  that  in 
the  body  of  the  vertebra,  and  from  this  point  the  formation  of  cartilage 
gradually  extends  throughout  the  entire  rib. 

Ossification  begins  during  the  third  month  at  a  center  which  is  situated  near 
the  angle  of  the  rib  (Fig.  128).  At  the  age  of  eight  to  fourteen  years  a  second- 
ary center  appears  in  each  capitulum  and  tuberculum  and  subsequently  fuses 
with  the  rest  of  the  rib  at  the  age  of  fourteen  to  twenty-five  years.  As  the 
tuberculum  develops,  the  transverse  process  of  the  corresponding  vertebra 
grows  ventrally  and  caudally  to  meet  it  and  form  the  articulation. 

The  ribs  reach  the  highest  degree  of  development  in  the  thoracic  region 
where  one  develops  on  each  side,  corresponding  to  each  vertebra.  The  first 
seven  or  eight  thoracic  ribs  extend  almost  to  the  mid- 
ventral  line  and  are  attached  to  the  sternum;  the  last  four 
or  five  become  successively  shorter  and  are  only  indirectly 
or  not  at  all  attached  to  the  sternum.  In  the  cervical 
region  the  ribs  do  not  reach  a  high  degree  of  development. 
Their  tips  simply  fuse  with  the  transverse  processes  of  the 
vertebrae  and  their  heads  with  the  bodies  of  the  vertebrae, 
leaving  a  space — the  foramen  transversarium — through 
which  the  vertebral  vessels  pass.  The  seventh  cervical  rib 
may,  however,  reach  a  fairly  high  degree  of  development. 
In  the  lumbar  region  also  the  ribs  are  reduced  to  small 
pieces  of  bone  which  are  firmly  united  with  the  transverse 
processes  and  form  the  accessory  processes.  In  the  sacral 
region  the  rudimentary  ribs  unite  to  form  the  lateral  part 
(pars  lateralis)  of  the  sacral  bone.  After  the  blastemal 
stage  there  are  no  indications  of  ribs  in  the  coccygeal  region. 
In  the  blastemal  stage,  however,  there  is  a  small  bit  of  tissue  FIG.  131.— Sternum  of 
which  probably  represents  the  anlage  of  a  rib,  but  soon 
fuses  with  the  transverse  process. 

The  Sternum. — The  sternum,  according  to  Hanson's 
recent  contribution,  originates  independently  of  the  ribs. 
On  each  side,  some  distance  from  the  midventral  line,  the 
sternal  band  or  bar  arises  as  a  mesenchymal  condensation  in  the  body 
wall.  These  bars  then  approach  the  midventral  line  and  fuse  with  each 
other  to  form  a  single  cartilaginous  structure.  Meanwhile  the  ventral 
ends  of  the  first  seven  ribs  extend  far  enough  to  come  into  contact  with  and 
join  the  sternal  bar  (Fig.  130).  Before  the  two  bars  have  united  a  medial 
unpaired  rudiment  appears  opposite  their  anterior  ends  to  form  the  pre- 
sternum  with  which  the  paired  rudiments  subsequently  unite.  The  pre- 
sternal  component,  with  which  the  clavicles  articulate,  probably  represents 
the  ventral  part  of  the  primitive  vertebrate  shoulder  girdle. 


12  year  old  child, 
showing  centers  of 
ossification.  Seven 
ribs  are  attached  on 
the  right  side,  8  on 
the  left.  Markowski, 
Kollmann's  Atlas. 


154 


TEXT-BOOK  OF  EMBRYOLOGY. 


Ossification  begins  in  the  sternum  about  the  end  of  the  fifth  month  of 
foetal  life.  In  the  cephalic  portion  two  unpaired  centers  appear;  caudal  to 
these  is  a  series  of  paired  centers  which  subsequently  fuse  across  the  mid- 
ventral  line.  (See  Fig.  131.)  The  paired  centers  perhaps  reflect  the  paired 
character  of  the  sternal  bars.  Sometimes,  however,  the  centers  appear  as  a 
single  series,  that  is,  with  no  indication  of  a  paired  character.  The  ossifica- 
tion of  the  most  cephalic  segment,  along  with  the  episternal  cartilages, 
produces  the  manubrium  sterni.  Ossification  of  the  following  six  or  seven 
segments  and  their  union  produce  the  corpus  sterni.  The  xyphoid  process 
appears  to  be  a  caudal  extension  of  the  corpus  sterni.  This  process  remains 


Olfactory  organ 
Hypophysis 
Visual  organ 

Prechordal  plate 

Auditory  organ 

Parachordal  plate 

Notochord 


Nasal  septum 

Olfactory  organ 
Hypophysis 
Visual  organ 

Prechordal  plate 
Auditory  organ 


Basal  (parachordal) 
plate 

Notochord 


FIG.  133. 


FIG.  132. 

FIG.  132. — Diagram  of  first  stage  in  the  development  of  the  cartilaginous 

primordial  cranium.     Wiedersheim. 
FIG.  133. — Diagram  of  later  stage  of  same.     VJ iedersheim. 

cartilaginous  for  a  long  period,  and  may  be  single,  perforated,  or  bifurcated, 
depending  upon  the  degree  of  fusion  between  the  two  primary  bars. 

The  Head  Skeleton. — Topographically  the  skeleton  of  the  head  appears 
as  the  cephalic  part  of  the  axial  skeleton.  Structurally  it  is  decidedly  different, 
for  it  is  adapted  to  different  conditions.  The  neural  tube  here  becomes  differ- 
entiated into  the  brain  with  its  many  and  dissimilar  parts.  In  connection  with 
the  brain  the  complicated  sense  organs  (nose,  eye  and  ear)  arise.  A  part  of 
the  alimentary  tract  and  portions  of  the  visceral  arches  are  also  inclosed 
within  the  head.  The  head  skeleton  is  specially  modified  to  accommodate 
these  highly  developed  organs,  and  becomes  extremely  complicated.  In 
general  the  skeleton  in  any  part  of  the  body  adapts  itself  to  the  other  structures 
and  not  the  other  structures  to  the  skeleton. 

The  anlage  of  the  skull  is  a  mass  of  embryonic  connective  tissue  which  sur- 


THE  CONNECTIVE  TISSUES  AND  THE  SKELETAL  SYSTEM. 


155 


rounds  the  cephalic  end  of  the  notochord,  extends  from  there  into  the  nasal 
region  and  also  extends  around  the  sides  and  dorsal  part  of  the  neural  tube 
(brain).  Unlike  the  anlage  of  the  vertebral  column,  the  anlage  of  the  skull 
shows  no  distinct  division  into  primitive  segments.  The  only  indications  of  a 
segmental  character  are  referred  to  in  a  succeeding  paragraph  (small  print, 

P-  157)- 

The  next  step  in  the  development  of  the  skull  is  the  appearance  of  cartilage 

in  certain  regions  of  the  embryonic  connective  tissue.  On  account  of  the  com- 
plicated arrangement  of  the  cartilage  in  the  human  skull,  it  is  best  to  consider 


Palatoquadrate 

Palatoquadrate 
Meckel's  cartilage 


Palatoquadrate 
Hypophysis 


Hyomandibular 
Post,  basal  fenestra 


Nasal  fossa 
Preorbital  process 


Roof  of  skull 
-  Marginal  bar 


Prechordal  plate 
Prootic  incisure 
Jugular  foramen 

j  Foramina  (VII  Narve) 
Prechordal  plate 

Notochord 
>Otic  (auditory)  capsule 

Synotic  tectum 


FIG.  134. — Primordial  cranium  of  Salmo  salar  (salmon)  embryo  of  25  mm.     Dorsal  view.     Gaupp 
Compare  with  Fig.  133  and  note  further  elaboration  of  parts  surrounding  the  sense  organs. 

first  its  more  simple  arrangement  in  the  lower  Vertebrates.  In  these  there  ap- 
pear in  the  embryonic  connective  tissue  around  the  cephalic  end  of  the  notochord 
two  bilaterally  symmetrical  pieces  of  cartilage,  which  extend  as  far  as  the 
hypophysis.  Then  two  other  bilaterally  symmetrical  pieces  appear,  extending 
from  the  hypophysis  to  the  nasal  region.  Subsequently  all  these  pieces  fuse 
into  a  single  mass  which  extends  from  the  cephalic  end  of  the  vertebral  column 
to  the  tip  of  the  nose,  enclosing  the  end  of  the  notochord  and,  to  a  certain  ex- 
tent, the  ear,  eye  and  olfactory  apparatus.  There  is  left,  however,  an  opening 
for  the  hypophysis.  From  this  mass  of  cartilage,  chondrification  extends  into 
the  embryonic  connective  tissue  along  the  sides  and  roof  of  the  cranial 


156 


TEXT-BOOK  OF  EMBRYOLOGY. 


cavity,  so  that  the  brain  and  sense  organs  are  practically  enclosed.  To  this 
capsule  the  term  cartilaginous  primordial  cranium  has  been  applied.  (See 
Figs.  132,  133,  134.) 

In  the  higher  Vertebrates,  chondrification  is  limited  to  the  basal  region  of  the 
skull,  while  the  side  walls  and  roof  are  formed  later  by  intramembranous  bone. 


Crista  galli 


Lamina  cribrosa 


Meckel's  cartilage 
Malleus 

Incus 


Int.  acoustic  pore 
Jugular  foramen 

Subarcuate  fossa 


Ala  magna  (sphenoid) 
Optic  foramen 

Ala  parva  (sphenoid] 

Setla  turcica 
Dorsum  sellae 


Foramina 
(VII  Nerve) 

Auditory 
capsule 


Foramen 


Foramen  (XII  Nerve) 


Large  occipital  foramen  Occipital 

(foramen  magnum)        (synotic  tectum) 

FIG.  135. — Dorsal  view  of  primordial  cranium  of  human  embryo  of  80  mm. 

(3rd  month).     Gaupp.  Hertwig. 

The  membrane  bones  of  the  roof  of  the  skull  have  been  removed.     Through  the  large  occipital 
foramen  can  be  seen  the  first  three  cervical  vertebrae. 

In  the  human  embryo  chondrification  occurs  first  in  the  occipital  and  sphenoidal 
regions,  and  then  gradually  extends  into  the  nasal  (ethmoidal)  region.  A  little 
later  it  spreads  somewhat  dorsally  in  the  occipital  and  sphenoidal  regions  to  form 
part  of  the  squamous  portion  of  the  occipital  and  the  wings  of  the  sphenoid.  At 
the  same  time  cartilage  develops  in  the  embryonic  connective  tissue  surround- 


THE   CONNECTIVE  TISSUES  AND   THE  SKELETAL  SYSTEM. 


157 


ing  the  internal  ear  to  form  the  periotic  capsule  whicn  subsequent!}  unites  with 
the  occipital  and  sphenoidal  cartilages.  The  pieces  of  cartilage  thus  formed  con- 
stitute the  chondrocranium. 

In  connection  with  the  development  of  the  caudal  part  of  the  occipital  cartilage  there  is 
an  interesting  feature  which  is  at  least  indicative  of  a  segmental  character.  In  some  of  the 
lower  Mammals  there  are  four  fairly  distinct  condensations  of  embryonic  connective  tissue 
just  cranial  to  the  first  cervical  vertebra,  corresponding  to  the  first  cervical  nerve  and  the 
three  roots  of  the  hypo  glossal.  These  condensations  bear  a  general  resemblance  to  the 
primitive  segments  and  indicate  the  existence  of  four  vertebrae  which  are  later  taken  up  into 
the  chondrocranium.  In  the  human  embryo  the  condensations  are  less  distinct,  but  the 
existence  of  a  first  cervical  and  a  three-rooted  hypoglossal  nerve  in  this  region  suggests  an 
original  segmental  character.  If  this  is  true,  then  the  base  of  the  human  skull  is  formed 
from  the  unsegmented  chondrocranium  plus  four  vertebrae  which  become  incorporated  in 
the  occipital  region. 


Optic  foramen 


Ala  magna  (sphenoid) 
\  ^^    Ala  parva  (sphenoid) 


Nasal  capsule 
Nasal  septum 

Maxilla 


Vomer 
Palate  bone 


Mandible 

Meckel's  cartilage 

Cricoid  cartilage 


\  Styloid  process 
Malleus   \    Cochlear  fenestra 
Foramen  (XII  Nerve) 


Thyreoid  cartilage 


FIG.  136. — Lateral  view  of  primordial  cranium  of  human  embryo  of  80  mm. 

(3rd  month).     Gaupp,  Hertwig. 

The  membrane  bones  of  the  roof  of  the  skull  have  been  removed.     Compare  with  FIG.  135.     The 
maxilla,  vomer,  palate,  and  mandible  are  membrane  bones. 

In  addition  to  the  chondrocranium,  other  cartilaginous  elements  enter  into 
the  formation  of  the  skull,  all  of  which  are  derived  from  the  visceral  arches. 
Not  all  the  arches,  however,  produce  cartilage;  for  in  the  maxillary  process  of 
the  first  arch,  which  forms  the  upper  boundary  of  the  mouth,  cartilage  does  not 
appear,  and  the  bones  which  later  develop  in  it  are  of  the  membranous  type. 
The  mandibular  process  of  the  first  arch  produces  a  rod  of  cartilage— Meckel's 
cartilage.  This  gives  rise,  at  its  proximal  end,  to  a  part  of  the  auditory  ossicles, 
but  the  cartilage  in  the  jaw  proper  soon  wholly  or  almost  wholly  disappears. 
The  cartilage  of  the  second  arch  becomes  connected  with  the  skull  in  the  region 


158 


TEXT-BOOK  OF  EMBRYOLOGY. 


of  the  periotic  capsule.     The   cartilages  of  the  other  three  arches  are  only 
indirectly  connected  with  the  skull  and  will  be  considered  later. 

Figs.  135  and  136  show  the  condition  of  the  chondrocranium  in  a  human 
embryo  of  80  mm.  (third  month) .  Although  at  first  glance  it  seems  exceedingly 
complicated,  a  careful  study  and  comparison  of  the  various  parts  will  aid  the 
student  in  his  comprehension  of  the  cartilaginous  foundation  upon  which  the 
skull  is  built. 

OSSIFICATION  OF  THE  CHONDROCRANIUM. 

In  the  human  fcetus  ossification  begins  in  the  occipital  region  during  the 
third  month.  Four  centers  appear  which  correspond  to  the  four  parts  of  the 
adult  occipital  bone  (Fig.  137).  (i)  An  unpaired  center  situated  ventral  to  the 
foramen  magnum.  From  this  center  ossification  proceeds  in  all  directions  to 


Interparietal 
(of  lower  forms) 


Squamous  part 
(intramemb.) 


Squamous 
part 


Kerkringius'  bone 


Squamous  part 
'(intracartilag.) 


•Lateral  part 


•Basilar  part 


FlG.  137. — Occipital  bone  of  human  embryo  of  21.5  cm.     Kollmann's  Atlas. 


form  the  pars  basilaris  (basioccipital).  (2  and  3)  Two  lateral  centers,  one 
on  each  side.  From  these,  ossification  proceeds  to  produce  the  partes  laterales 
(exoccipital)  which  bear  the  condyles.  (4)  A  center  dorsal  to  the  foramen 
magnum.  This  produces  the  pars  squamosa  (supraoccipital)  as  far  as  the  supe- 
rior nuchal  line.  Beyond  this  line  the  pars  squamosa  is  of  intramembranous 
origin.  (See  p.  160.)  At  birth  the  four  parts  are  still  separated  by  plates  of 
cartilage.  During  the  first  or  second  year  after  birth  the  partes  laterales 
unite  with  the  pars  squamosa,  and  about  the  seventh  year  the  pars  basilaris 
unites  with  the  rest  of  the  bone. 


THE   CONNECTIVE  TISSUES  AND  THE  SKELETAL  SYSTEM.  159 

In  the  sphenoidal  region  ossification  begins  at  a  number  of  centers  which, 
as  in  the  occipital  region,  correspond  generally  to  the  parts  of  the  adult  sphenoid 
bone  (Fig.  138).  (i  and  2)  About  the  ninth  week  an  ossification  center 
appears  on  each  side  in  the  cartilage  which  corresponds  to  the  ala  magna 
(alisphenoid).  (3  and  4)  About  the  twelfth  week  a  center  appears  on  each 
side  which  corresponds  to  the  ala  parva  (orbitosphenoid) .  (5  and  6)  A 
short  time  after  this  a  center  appears  on  each  side  of  the  medial  line  in  the 
basal  part  of  the  cartilage,  and  the  two  centers  subsequently  fuse  to  produce  the 
corpus  (basisphenoid) .  (7  and  8)  Lateral  to  each  basal  center,  another  center 
appears  which  represents  the  beginning  of  the  lingula.  (9  and  10)  Finally 
two  centers  appear  in  the  basal  part  of  the  cartilage,  in  front  of  the  other 
basal  centers,  and  then  fuse  to  form  the  presphenoid.  As  in  the  case  of  the  oc- 
cipital bone,  not  all  of  the  adult  sphenoid  is  of  intracartilaginous  origin;  for  the 

Ala  parva- 

Ala  magna 


Lingula-  ~^m         mtimzM      m^ Lingula 

Pterygoid 
process 

"^      ^/\    \  \  /     7V  7 

Corpus 
'  (basisphenoid) 

FIG.  138. — Sphenoid  bone  of  embryo  of  3^-4  months.     Sappey. 
The  parts  that  are  still  cartilaginous  are  represented  in  black. 

upper  anterior  angle  of  each  ala  magna  is  of  intramembranous  origin,  as  are  also 
the  medial  and  lateral  laminae  of  the  pterygoid  process.  The  pterygoid  hamulus, 
however,  is  formed  by  the  ossification  of  a  small  piece  of  cartilage  which  de- 
velops on  the  tip  of  the  medial  lamina.  The  fusion  of  these  various  parts  oc- 
curs at  different  times.  The  lateral  pterygoid  lamina  unites  with  the  alisphe- 
noid before  the  sixth  month  of  fcetal  life;  about  the  sixth  month  the  lingula  fuses 
with  the  basisphenoid,  and  the  presphenoid  with  the  orbitosphenoid.  The 
alisphenoid  and  medial  pterygoid  lamina  fuse  with  the  rest  of  the  bone  during 
the  first  year  after  birth.  The  union  of  the  basisphenoid  and  basioccipital 
usually  occurs  when  the  growth  of  the  individual  ceases,  though  the  two  bones 
may  remain  separate  throughout  life. 

In  the  region  of  the  periotic  capsule,  several  centers  of  ossification  appear  in 
the  cartilage  during  the  fifth  month.  During  the  sixth  month  these  centers 
unite  to  form  a  single  center  which  then  gradually  increases  to  form  the  pars 
petrosa  and  pars  mastoidea  of  the  adult  temporal  bone.  The  mastoid  process  is 


160  TEXT-BOOK  OF  EMBRYOLOGY. 

formed  after  birth  by  an  evagination  from  the  pars  petrosa,  and  is  lined  by  an 
evaginated  portion  of  the  mucosa  of  the  middle  ear.  The  other  parts  of  the 
temporal  bone  are  of  intramembranous  origin,  except  the  styloid  process  which 
represents  the  proximal  end  of  the  second  branchial  arch. 

In  the  ethmoidal  region,  conditions  become  more  complicated  on  account  of 
the  peculiarities  of  the  nasal  cavities,  and  on  account  of  the  fact  that  the  cartilage 
is  never  entirely  replaced  by  bone,  and  that  "membrane"  bones  also  enter  into 
more  intimate  relations  with  the  "cartilage"  bones.  The  ethmoidal  cartilage 
at  first  consists  of  a  medial  mass,  which  extends  from  the  presphenoid  region  to 
the  end  of  the  nasal  process,  and  of  a  lateral  mass  on  each  side,  which  is  situated 
lateral  to  the  nasal  pit  (Fig.  136).  Ossification  in  the  lateral  mass  on  each  side 
produces  the  ethmoidal  labyrinth  (lateral  mass  of  ethmoid).  It  is  perhaps  not 
quite  correct  to  say  that  ossification  produces  the  ethmoidal  labyrinth,  for  at 
first  there  is  only  a  mass  of  spongy  bone  with  no  indication  of  the  honey-combed 
structure  characteristic  of  the  adult.  The  latter  condition  is  produced  by  at 
certain  amount  of  dissolution  of  the  bone  and  the  growth  of  the  nasal  mucosa 
into  the  cavities  so  formed.  By  the  same  process  of  dissolution  and  ingrowth  of 
nasal  mucosa  the  superior,  middle  and  inferior  concha  (turbinated  bones)  are 
formed.  The  medial  mass  of  cartilage  begins  to  ossify  after  birth  and  then  only 
in  its  upper  (superior)  edge.  It  forms  the  lamina  perpendicular  is  and  crista 
galli  and  extends  into  the  nose  as  the  nasal  septum.  The  lower  (inferior)  edge 
remains  as  cartilage  until  the  vomer,  which  is  a  membrane  bone  (p.  194), 
develops,  after  which  it  is  partly  dissolved.  The  lamina  cribrosa  (cribriform 
plate)  is  formed  by  bony  trabeculae  which  extend  across  between  the  medial 
mass  and  the  lateral  masses  and  surround  the  bundles  of  fibers  of  the  olfactory 
nerve. 

MEMBRANE  'BONES  OF  THE  SKULL. 

Under  this  head  we  shall  consider  only  those  bones  which  develop  a 
from  the  visceral  arches,  those  which  involve  the  arches  being  considered  later. 
It  has  been  seen  that  by  far  the  greater  parts  of  the  bones  forming  the  base  of  th 
skull  are  of  intracartilaginous  origin.  On  the  other  hand,  those  forming  the 
sides  and  roof  of  the  skull  are  largely  of  intramembranous  origin.  In  the  case 
of  the  occipital  bone,  two  centers  of  ossification  appear  in  the  membrane  dorsal 
to  the  supraoccipital,  and  the  bone  so  formed  begins  to  unite  with  the  supra- 
occipital  during  the  third  month  of  fcetal  life.  At  birth  the  union  is  usually 
complete,  though  for  a  time  an  open  suture  may  persist  on  each  side.  The  bone 
derived  from  the  two  centers  forms  that  part  of  the  occipital  squama  which  is 
situated  above  the  superior  nuchal  line;  the  part  below  the  line  is  of  intracarti- 
laginous origin  (p.  190).  The  adult  occipital  is  thus  a  composite  bone,  partly 
of  intramembranous,  partly  of  intracartilaginous  origin. 


THE   CONNECTIVE  TISSUES   AND   THE   SKELETAL  SYSTEM. 


161 


The  temporal  is  also  a  composite  bone,  the  petrous  and  mastoid  parts 
and  the  styloid  process  being  of  intracartilaginous  origin,  while  the  temporal 
squama  and  the  tympanic  part  are  of  intramembranous  origin.  During  the 
eighth  week  of  foetal  life  a  center  of  ossification  appears  in  the  membrane  in  the 
temporal  region,  and  the  bone  formed  from  this  center  subsequently  unites 
with  the  petrous  part  and  becomes  the  temporal  squama.  Another  center  ap- 
pears in  the  membrane  to  the  outer  side  of  the  periotic  capsule  and  produces  a 
ring  of  bone  around  the  external  auditory  meatus,  which  fuses  with  the  petrous 


"Parietal 


Frontal 
fontanell^ 


Occipital 
xontanelle 


Occipital  -f 


Mastoid   - 
fontanelle 


Ocdipital 

Petrous 

Occipital 

Tympanic 

Styloid  process 

Stylohyoid  lig 

Hyoid  (greater  horn) 

Cricoid 


Frontal 


Sphenoidal 
fontanelle 


— f\-  Alisphenoid 

Zygomatic 
v~-  Maxilla 

Mandible 


Meckel's  cartilage 
Hyoid  (lesser  horn) 

Thyreoid 


FIG.  139. — Diagram  of  skull  of  new-born  child.     Combined  from  McMurrich  and  Kollmann. 
White  areas  represent  bones  of  intramembranous  origin;  dotted  areas  represent  bones  (not  derived 
from   branchial  arches)  of  intracartilaginous  origin;   black  areas   represent  derivatives  of 
branchial  arches. 


part  and  forms  the  tympanic  part  of  the  adult  bone.  It  gives  attachment  at  its 
inner  border  to  the  tympanic  membrane.  While  the  union  of  the  different 
parts  begins  during  fcetal  life,  it  is  usually  completed  after  birth. 

The  sphenoid  bone  is  also  composed  of  parts  which  have  different 
origins.  The  body,  small  wings  and  large  wings  are  of  intracartilaginous 
origin,  the  pterygoid  process  of  intramembranous  origin.  About  the  eighth 
week  of  development  a  center  of  ossification  appears  in  the  mesenchyme  in  the 
lateral  wall  of  the  posterior  part  of  the  nasal  cavity  and  gives  rise  to  the  medial 
pterygoid  lamina.  On  the  tip  of  the  latter  a  small  piece  of  cartilage  appears  in 


162  TEXT-BOOK  OF  EMBRYOLOGY. 

which  ossification  later  takes  place  to  form  the  pterygoid  hamulus  (p.  159). 
The  lateral  pterygoid  lamina  is  also  of  intramembranous  origin  and  fuses  with 
the  medial  lamina,  the  two  laminae  forming  the  pterygoid  process  which  subse- 
quently unites  with  the  body  of  the  sphenoid.  (See  Fig.  138.) 

In  the  ethmoidal  region,  only  the  vomer  is  of  intramembranous  origin.  An 
ossification  center  appears  in  the  embryonic  connective  tissue  on  each  side  of 
the  perpendicular  plate  (lamina  perpendicularis)  and  these  two  centers  produce 
two  thin  plates  of  bone  which  unite  at  their  lower  borders  and  invest  the  lower 
part  of  the  perpendicular  plate.  The  portion  of  the  latter  thus  invested 
undergoes  resorption. 

The  frontal  and  parietal  bones  are  purely  of  intramembranous  origin.  About 
the  eighth  week  two  centers  of  ossification,  one  on  each  side,  appear  for  the 
frontal.  The  bones  produced  by  these  centers  unite  in  the  medial  line  to  form 
the  single  adult  bone.  In  the  event  of  an  incomplete  union  an  open  suture 
remains — the  metopic  suture.  A  single  center  of  ossification  appears  for  each 
parietal  bone  at  about  the  same  time  as  those  for  the  frontal.  The  union  of 
the  bones  which  form  the  roof  and  the  greater  part  of  the  sides  of  the  skull  does 
not  occur  till  after  birth.  The  spaces  between  them  constitute  the  sutures  and 
fontanelles  so  obvious  in  new-born  children  (Fig.  139). 

A  single  center  of  ossification  appears  in  the  embryonic  connective  tissue 
for  each  zygomatic,  lachrymal  and  nasal  bone,  all  of  which  are  of  intramem- 
branous origin. 

BONES  DERIVED  FROM  THE  BRANCHIAL  ARCHES. 

The  first  branchial  arch  becomes  divided  into  two  portions.  One  of  these, 
the  maxillary  process,  is  destined  to  give  rise  to  the  upper  jaw  and  much  of  the 
upper  lip  and  face  region.  The  other,  the  mandibular  process,  is  destined  to 
give  rise  to  the  lower  jaw,  the  lower  lip  and  chin  region,  and  two  of  the  auditory 
ossicles.  The  angle  between  the  two  processes  corresponds  to  the  angle  of  the 
mouth,  and  the  cavity  enclosed  by  the  processes  is  the  forerunner  of  the  mouth 
and  nasal  cavities.  (See  Fig.  96,  also  p.  119.)  So  far  as  the  skeletal  elements 
are  concerned,  cartilage  develops  only  in  the  mandibular  process  where  it 
forms  a  slender  bar  or  rod  known  as  MeckeVs  cartilage.  Only  a  small  part  of 
this  becomes  ossified,  the  greater  portion  of  the  mandible  being  of  intramem- 
branous origin.  No  cartilage  develops  in  the  maxillary  process.  This 
probably  indicates  a  condensation  of  development  in  man  and  the  higher 
animals,  for  among  the  lower  animals  cartilage  precedes  the  bone.  In  man  the 
maxilla  and  palate  bone  also  are  of  intramembranous  origin. 

The  palate  bone  develops  from  a  single  center  of  ossification  which  appears 
at  the  side  of  the  nasal  cavity  in  embryos  of  about  18  mm.  This  center 


THE   CONNECTIVE  TISSUES  AND  THE  SKELETAL  SYSTEM.  163 

represents  the  perpendicular  part,  the  horizontal  part  appearing  in  embryos  of 
about  24  mm.  as  an  outgrowth  from  the  perpendicular  and  not  as  a  separate 
center  of  ossification.  The  orbital  and  sphenoidal  processes  also  represent  out- 
growths from  the  primary  center  and  appear  much  later. 

Opinions  regarding  the  development  of  the  maxilla  are  at  variance.  One 
view  is  that  it  arises  from  five  centers  of  ossification.  One  of  these  centers  gives 
rise  to  that  part  of  the  alveolar  border  which  bears  the  molar  and  premolar 
teeth;  a  second  center  forms  the  nasal  process  and  that  part  of  the  alveolar  bor- 
der which  bears  the  canine  tooth;  a  third  produces  the  part  which  bears  the 
incisor  teeth;  and  the  two  remaining  centers  give  rise  to  the  rest  of  the  bone. 
All  these  parts  effect  a  firm  union  at  an  early  stage,  with  the  exception  of  the 
part  bearing  the  incisor  teeth  which  remains  more  or  less  distinct  as  the  incisive 
bone  (premaxilla,  intermaxilla) .  Another  view  arising  from  recent  work  on 

Incisive  bone  Upper  lip 

(intermaxillary) 

I 


Primitive  choan* ^S^M  •T^  Lip  groovc 


Cut  surface         Palatine  processes 

FIG.  140. — Head  of  human  embryo  of  7  weeks.     His. 
Ventral  aspect  of  upper  jaw  region.     Lower  jaw  and  tongue  have  been  removed. 


human  embryos  is  that  there  are  primarily  only  two  ossification  centers;  one  of 
these  gives  rise  to  the  incisive  bone,  the  other  to  the  rest  of  the  maxilla  (Mall). 
These  centers  appear  at  the  end  of  the  sixth  week  (embryos  of  18  mm.); 

A  very  important  feature  in  the  development  of  the  maxilla  is  its  agency  in 
separating  the  nasal  cavity  from  the  mouth  cavity.  The  palatine  process  of  the 
bone  grows  medially  and  meets  and  fuses  with  its  fellow  of  the  opposite  side  in 
the  medial  line,  the  two  processes  together  thus  constituting  about  the  an- 
terior three-fourths  of  the  bony  part  of  the  hard  palate.  It  should  be  observed, 
however,  that  the  palatine  processes  do  not  meet  at  their  anterior  borders,  for 
the  incisive  bone  is  insinuated  between  them  (see  Figs.  140,  141). 


164  TEXT-BOOK  OF  EMBRYOLOGY. 

The  incisive  bone  is  probably  not  derived  from  the  maxillary  process  of  the  first  visceral 
arch,  but  from  the  fronto-nasal  process.  The  question  thus  arises  as  to  whether  it  is  derived 
from  both  the  middle  and  lateral  nasal  processes  or  only  from  the  middle.  According  to 
Kolliker's  view,  the  lateral  nasal  process  takes  no  part  in  the  formation  of  the  incisive  bone. 
It  is  derived  from  the  middle  process,  hence  genetically  it  is  a  single  bone  on  each  side. 
According  to  Albrecht's  view  the  incisive  bone  is  genetically  composed  of  two  parts,  one 
derived  from  the  lateral,  the  other  from  the  middle  nasal  process.  While  the  matter  is  not 
one  of  great  importance  merely  from  the  standpoint  of  development,  it  has  an  important 
bearing  on  the  question  of  certain  congenital  malformations,  e.g.,  hare  lip,  and  will  be 
discussed  further  under  that  head  (p.  180). 

In  the  mandibular  process  of  the  first  visceral  arch,  the  mandible  develops  as 
a  bone  which  is  partly  of  intramembranous  and  partly  of  intracartilaginous 
origin.  In  the  first  place  a  rod  of  cartilage,  known  as  MeckePs  cartilage, 
forms  the  core  of  the  mandibular  process  and  extends  from  the  distal  end  of  the 
process  to  the  temporal  region  of  the  skull,  where  it  passes  between  the  tympanic 


Medial  line  

^^  .      ^-^  Incisive  bone 

Canine  alveolus  m_ _™_™^™,,, „„_.,,„„„.„ 

Incisive  suture 


Molar  alveolus  f  timsigm  y8%"J^rm//w/i//'f?Mytf>  •KVT»  n ~  Palatine  process 


Palate  bone 
(horizontal  part) 

FIG.  141. — Ventral  aspect  of  hard  palate  of  human  embryo  of  80  mm.     Kollmann's  Atlas. 

bone  and  the  periotic  capsule  and  ends  in  the  tympanic  cavity  of  the  ear  (Fig. 
136).  During  the  sixth  week  of  foetal  life,  intramembranous  bone  begins  to 
develop  in  the  mandibular  process.  In  the  region  of  the  body  of  the  mandible 
the  bone  encloses  the  cartilage,  but  in  the  region  of  the  ramus  and  coronoid 
process  the  cartilage  lies  to  the  inner  side  of  the  bone.  Development  is  further 
complicated  by  the  appearance  of  cartilage  in  the  region  of  the  middle  incisor 
teeth  and  on  the  coronoid  and  condyloid  processes.  These  pieces  of  cartilage 
form  independently  of  Meckel's  cartilage  and  subsequently  are  replaced  by  the 
bone  which  constitutes  the  corresponding  parts  of  the  mandible.  The  part  of 
Meckel's  cartilage  enclosed  in  the  bone  disappears;  the  part  to  the  inner  side  of 
the  ramus  is  transformed  into  the  sphenomandibular  ligament.  (See  Fig.  142.) 
In  each  half  of  the  second  branchial  arch  a  rod  of  cartilage  develops,  which 
extends  from  the  ventro-medial  line  to  the  region  of  the  periotic  capsule.  The 


THE  CONNECTIVE  TISSUES  AND   THE  SKELETAL  SYSTEM.  165 

proximal  end  of  this  rod  is  then  replaced  by  bone  which  fuses  with  the  temporal 
bone  and  forms  the  styloid  process.  The  distal  (ventral)  end  is  replaced  by 
bone  which  forms  the  lesser  horn  of  the  hyoid  bone.  Between  the  styloid  proc- 
ess and  the  lesser  horn,  the  cartilage  is  transformed  into  the  stylohyoid  liga- 
ment (see  Figs.  139  and  142). 

In  each  half  of  the  third  branchial  arch  a  piece  of  cartilage  develops  and 
subsequently  is  replaced  by  bone  to  form  the  greater  horn  of  the  hyoid  bone. 
The  two  horns  become  connected  at  their  ventral  ends  by  the  body  of  the  hyoid 
bone  which  is  also  a  derivative  of  the  third  arch.  Later  the  lesser  horn  fuses 
with  the  greater  horn  to  bring  about  the  adult  condition  (Fig.  142). 

In  the  ventral  parts  of  the  fourth  and  fifth  arches  pieces  of  cartilage  develop 


Incus       Malleus 


Tympanic  ring 
Stylohyoid  lig. 

Cricoid  cartilage 


Thyreoid  cartilage     |  Meckel's  cartilage 

Hyoid  cartilage  (greater  horn) 

FIG.  142. — Lateral  dissection  of  head  of  human  fcetus,  showing  derivatives  of  branchial 
arches  in  natural  position.     Kollmann's  Atlas. 

and  form  the  skeletal  elements,  of  the  larynx.  A  more  detailed  account  of  these 
will  be  found  under  the  head  of  the  larynx. 

The  auditory  ossicles  are  also  derived  largely  from  the  branchial  arches,  the 
incus  and  malleus  being  derived  from  the  proximal  end  of  Meckel's  cartilage  (first 
arch) ,  the  stapes  having  a  double  origin  from  the  second  arch  and  the  embryonic 
connective  tissue  surrounding  the  periotic  capsule.  But  since  they  form  inte- 
gral parts  of  the  organ  of  hearing,  a  discussion  of  their  formation  is  best  in- 
cluded in  the  development  of  the  ear. 

The  accompanying  table  indicates  the  types  of  development  in  the  different 
bones  of  the  head  skeleton. 


166 


TEXT-BOOK  OF  EMBRYOLOGY. 


Bones 


Of  Intracartilaginous 
Origin 


Of  Intramembranous 
Origin 


Derived  from  Visceral 
Arches 


Occipitale. 


Pars  basilaris. 
Pars  lateralis. 
Squama  occipitalis  below 
sup.  nuchal  line. 


Squama  occipitalis  above 
sup.  nuchal  line. 


Temporale. 


Pars  mastoidea. 
Pars    petrosa,  with 
essus  sty  oideus. 


proc- 


Pars  tympanica. 
Squama  tempo ralis. 


Processus  styloideus  (sea 
arch). 


Sphenoidale. 


Corpus. 

Ala  parva. 

Ala  magna. 

Hamulus  pterygoideus. 


Processus  pterygoideus,  ex- 
cept hamulus  pterygoi- 
deus. 


Ethmoidale. 


Crista  galli. 
Lamina  cribrosa. 
Lamina  perpendicularis. 
Labyrinthus  ethmoidalis. 


Vomer. 


Vomer. 


Parietale. 


Parietale. 


Frontale. 


Frontale. 


Lacrimale. 


Lacrimale. 


Nasale. 


Nasale. 


Zygoma. 


Zygoma. 


Maxilla. 


Maxilla,  with  incisivum. 


Maxilla,except  incisivum(  ?) 
(first  arch). 


Palatinum. 


Palatinum. 


Palatinum. 


Mandibula. 


Processus    condyloideus, 

tip  of. 
Processus  coronoideus, 

tip  of. 
Corpus,  distal  end  of. 


Processus  condyloideus,  ex- 
cept tip. 

Processus  coronoideus,  ex- 
cept tip. 

Corpus,  except  distal  end. 

Ramus. 


Mandibula  (first  arch). 


Hyoideum. 


Hvoideum 


Cornu  majus  (third  arch). 
Cornu  minus  (second  arch). 
Corpus  (third  arch). 


Ossicula 
auditus. 


Incus. 

Malleus. 

Stapes,  except  basis  (?). 


Basis  stapedis. 


Incus  (first  arch). 
Malleus   (first  arch). 
Stapes,     except    basis 
(second  arch). 


The  Appendicular  Skeleton. 

The  growth  of  the  limb  buds  and  their  differentiation  into  arm,  forearm 
and  hand,  thigh,  leg  and  foot,  along  with  the  rotation  which  they  undergo  during 
development,  have  been  discussed  in  the  chapter  on  the  external  form  of  the 
body  (p.  121).  The  metameric  origin  of  the  muscles  of  the  extremities  is 


THE  CONNECTIVE  TISSUES  AND  THE  SKELETAL  SYSTEM. 


167 


discussed  in  the  chapter  on  the  muscular  system  (Chap.  XI).  It  has  been 
seen  that  the  greater  part  of  the  axial  skeleton  is  derived  from  the  sclerotomes, 
is  preformed  in  cartilage,  and  maintains  its  segmental  character  throughout  life. 
It  has  also  been  seen  that  the  head  skeleton  is  in  part  preformed  in  cartilage,  is  in 
part  of  intramembranous  origin,  and  shows  but  a  trace  of  segmental  character, 
and  that  only  in  the  occipital  region  at  a  very  early  stage.  The  appendicular 
skeleton  is  derived  wholly  from  the  embryonic  connective  tissue  which  forms  the 
cores  of  the  developing  extremities,  and  shows  no  trace  of  a  segmental  character. 
Here  also,  as  in  the  axial  skeleton,  three  stages  may  be  recognized — a  blastemal, 
a  cartilaginous  (Fig.  143),  and  a  final  osseous, 

Acromion       Coracoid  process 


Scapula 


Humerus 


Radius 

Metacarpal  I 

Large  multangular 
(trapezium) 

Navicular  (scaphoid) 
Lunate  (semilunar) 

Small  multangular 
(trapezoid) 

Metacarpal  IV 
Capitate  (os  magnum) 
Triquetral  (cuneiform) 
Hamatate  (unciform) 


Ulna 


FIG.  143. — Cartilages  of  left  upper  extremity  of  a  human  embryo  of  17  mm.    Hagen. 

In  the  region  of  the  shoulder  girdle  a  plate  of  cartilage  appears  in  the  em- 
bryonic connective  tissue  which  lies  among  the  developing  muscles  dorso-lateral 
to  the  thorax.  This  plate  of  cartilage  is  the  forerunner  of  the  scapula,  and  in 
general  resembles  it  in  shape.  During  the  eighth  week  of  fcetal  life  a  single 
center  of  ossification  appears  and  gives  rise  to  the  body  and  spine  of  the  scapula. 
After  birth  certain  accessory  centers  appear  and  produce  the  coracoid  process,  the 
supraglenoidal  tuberosity,  the  acromion  process,  and  the  inferior  angle  and  verte- 
bral margin  (Fig.  144).  Later  the  supraglenoidal  fuses  with  the  coracoid  and 
forms  part  of  the  wall  of  the  glenoid  cavity.  About  the  seventeenth  year  the 
single  center  formed  by  the  union  of  these  two  fuses  with  the  rest  of  the  scapula. 


168  TEXT-BOOK  OF  EMBRYOLOGY. 

At  the  age  of  twenty  to  twenty-five  years  all  the  other  accessory  centers  unite 
with  the  rest  of  the  scapula  to  form  the  adult  bone. 

There  are  two  views  concerning  the  development  of  the  clavicle:  one  that  it 
is  of  intracartilaginous  origin,  the  other  that  it  is  of  intramembranous  origin. 
Ossification  begins  during  the  sixth  week,  possibly  from  two  centers.  It  is  true 
that  the  cartilage  that  appears  around  the  centers  is  of  a  looser  character  than 
the  ordinary  embryonic  cartilage,  but  whether  the  centers  appear  in  cartilage 
seems  not  to  have  been  determined.  At  the  age  of  fifteen  to  twenty  years  a 
sort  of  secondary  center  appears  at  the  sternal  end  of  clavicle  and  fuses  with 
the  body  about  the  twenty-fifth  year. 

The  humerus,  radius  and  ulna  are  preformed  in  cartilage  (Fig.  143)  and 
develop  as  typical  long  bones.  Ossification  begins  in  each  during  the  seventh 


Bone 


Cartilage 


FiGc  144. — Scapula  of  new-born  child,  showing  primary  center  of  ossification,  and  cartilage 
(lighter  shading)  in  which  secondary  centers  appear.     Bonnet. 

week  at  a  single  center  and  proceeds  in  both  directions  to  form  the  shaft. 
During  the  first  four  years  after  birth  epiphyseal  centers  appear  for  the  head, 
greater  and  smaller  tubercles,  trochlea  and  epicondyles.  All  these  secondary 
centers  unite  with  the  shaft  of  the  humerus  when  the  growth  of  the  individual 
ceases.  In  the  case  of  the  radius  and  ulna  a  secondary  center  appears  at  each 
end  of  each  bone  to  form  the  epiphysis;  and  in  the  ulna  another  secondary 
center  appears  to  form  the  olecranon.  (For  the  growth  of  bones,  see  page  144) . 
The  carpal  bones  are  all  preformed  in  cartilage  (Fig.  143)  but  their  develop- 
ment is  somewhat  complicated  owing  to  the  fact  that  pieces  of  cartilage  appear 
which  subsequently  may  disappear,  or  ossify  and  become  incorporated  in  other 
bones.  Primarily  seven  distinct  pieces  of  cartilage  develop  and  become  ar- 
ranged transversely  in  two  rows;  these  represent  seven  of  the  carpal  bones. 
The  proximal  row  consists  of  three  large  pieces  which  are  the  forerunners  of  the 
navicular  (radial,  scaphoid),  lunate  (intermediate,  semilunar)  and  triquetral 


THE   CONNECTIVE  TISSUES  AND  THE  SKELETAL  SYSTEM. 


169 


(ulnar,  pyramidal,  cuneiform) .  The  distal  row  is  composed  of  four  elements 
which  are  the  forerunners  of  the  large  multangular  (trapezium),  small  multangu- 
lar (trapezoid),  capitate  (os  magnum),  and  hamatate  or  hooked  (unciform).  In 
addition  to  the  cartilages  mentioned,  several  others  also  appear  in  an  inconstant 
way  in  different  individuals.  Two  of  these  are  important.  One  appears  on 
the  ulnar  side  of  the  proximal  row  and  is  the  forerunner  of  the  pisiform;  the 
other  is  situated  between  the  two  rows  and  may  either  disappear  entirely  or  fuse 
with  the  navicular.  Ossification  does  not  begin  in  the  carpal  cartilages  until 
after  birth;  it  begins  in  the  hamatate  and  capitate  during  the  third  year,  in  the 


Metacarpals 


Large 
multangular 

Capitate 
Navicular 

Radius 


FIG.  145. — Skiagram  of  right  hand  of  5  year  old  girl.     (Courtesy  of  Dr.  Edward  Learning). 
The  ossification  centers  are  indicated  by  the  darker  areas. 

others  at  later  periods,  and  is  completed  only  when  the  growth  of  the  individ- 
ual ceases.  The  fact  that  the  hamatate  ossifies  from  two  centers  indicates 
that  it  is  probably  derived  phylogenetically  from  two  bones.  Comparative 
anatomy  teaches  that  the  accessory  cartilages  in  the  human  wrist  are  repre- 
sentatives of  structures  which  are  normally  present  in  the  lower  forms. 

The  metacarpals  and  phalanges  are  preformed  in  cartilages  which  correspond 
in  shape  to  the  adult  bones.  A  center  of  ossification  appears  in  each  cartilage 
and  produces  the  shaft  of  the  bone.  Only  one  epiphysis  develops  on  each 
metacarpal  and  phalanx.  In  each  metacarpal  it  develops  at  the  distal  end, 


170 


TEXT-BOOK  OF  EMBRYOLOGY. 


Dium 


Crural  nerve 


Pubic  bone  (cartilage) 

Obturator  nerve 
Ischium 

Ischiadic  nerve 


FIG.  146. — Cartilage  of  right  side  of  pelvic  girdle  of  a  human  embryo  of  13.6  mm. 

(5  weeks).     Peter  sen. 
The  numerals  indicate  the  vertebrae;  the  first  sacral  being  opposite  the  ilium. 


Ilium 


Crural  nerve 


Pubic  bone  (cartilage) 


Obturator  nerve 


Ischium 


Ischiadic  nerve 


FIG.  147.— Cartilage  of  right  side  of  pelvic  girdle  of  a  human  embryo  of  18.5  mm. 

(8  weeks).     Peter  sen. 

The  numerals  indicate  the  vertebras;  the  first  and  second  sacral  being  opposite  the  ilium 

Compare  with  Fig.  146. 


THE   CONNECTIVE  TISSUES  AND   THE  SKELETAL  SYSTEM.  171 

except  in  the  thumb  where  it  appears  at  the  proximal  end.     In  each  phalanx  it 
develops  at  the  proximal  end  (Fig.  145). 

The  skeletal  elements  of  the  lower  extremities,  including  the  pelvic  girdle,  are 
of  intracartilaginous  origin.     Each  hip  bone  (os  coxae,  innominate  bone)  is  pre- 
formed in  cartilage  which,  in  a  general  way,  resembles  in  shape  the  adult  bone. 
The  ventral  part  of  the  pubic  cartilage  does  not  at  first  join  the  ischial;  but  by  the 
eighth  week  the  junction  is  complete,  leaving  dorsal  to  it  the  obturator  foramen. 
In  the  earliest  stages  the  long  axis  of  the  cartilage  is  nearly  at  right  angles  to  the 
;  vertebral  column,  and  the  ilium  lies  close  to  the  fifth  lumbar  and  first  sacral 
|  vertebrae;  later  (eighth  week)  the  long  axis  lies  nearly  parallel  with  the  vertebral 
l  column  and  the  whole  cartilage  has  shifted  so  that  the  ilium  is  associated  with 
I  the  first  three  sacral  vertebrae  (Figs.  146  and  147). 


-Ischium 

Pubic  bone  ^       _  ,^^^^ 

•Acetabulum 


Ilium 


Cartilage 


FIG*  148  — Right  os  coxae  (innominate  bone)  of  new-born  child.     Bonnet. 
Bone  is  indicated  by  darker  areas/  cartilage  by  lighter  areas. 


Ossification  begins  at  three  centers  which  correspond  to  the  ilium,  ischium 
and  pubis;  the  center  for  the  ilium  appears  during  the  eighth  week,  the  centers 
j  for  the  ischium  and  pubis  several  weeks  later  (Fig.  148).     The  process  of  ossifi- 
:  cation  is  slow,  and  is  far  from  complete  at  the  time  of  birth,  for  at  that  time  the 
entire  crest  of  the  ilium,  the  bottom  of  the  acetabulum  and  all  the  region  ventral 
to  the  obturator  foramen  are  cartilaginous.     During  the  eighth  or  ninth  year 
the  ventral  parts  of  the  pubis  and  ischium  become  partly  ossified,  but  up  to  the 
time  of  puberty  the  pubis,  ischium  and  ilium  remain  separated  by  plates  of  car- 
tilage which  radiate  from  a  common  center  at  the  bottom  of  the  acetabulum. 
Soon  after  this,  the  three  bones  unite  to  form  the  single  os  coxae,  leaving  only  the 
crest  of  the  ilium,  the  pubic  tubercle  and  the  sciatic  tuber  (tuberosity  of  the 
;  ischium)  cartilaginous.     In  each  of  these  regions  an  accessory  ossification  cen- 


172 


TEXT-BOOK  OF  EMBRYOLOGY. 


ter  appears  and  finally  fuses  with  the  corresponding  bone  about  the  twenty- 
fourth  year. 

The  femur,  tibia  and  fibula  are  preformed  in  cartilage.  In  the  femur  a  center 
of  ossification  appears  about  the  end  of  the  sixth  week  and  gives  rise  to  the 
shaft;  similar  centers  appear  in  the  tibia  and  fibula  during  the  seventh  and 
eighth  week,  respectively.  In  the  femur  a  distal  epiphyseal  center  appears 
shortly  before  birth,  and  during  the  first  year  after  birth  a  proximal  center 
appears  for  the  head.  These  centers  do  not  unite  with  the  shaft  until  the  individ- 
ual ceases  to  grow.  The  great  and  lesser  trochanters  also  have  accessory  ossifica- 
tion centers.  In  the  tibia  the  center  of  ossification  for  the  proximal  epiphysis 
appears  about  the  time  of  birth,  the  one  for  the  distal  during  the  second  year.  In 


Fibula 


Calcane 


Cuboid 


Cuneiform  III 


Tibia 


Talus 

Navicular 

Cuneiform  I 
'Cuneiform  II 


Metatarsals  £--  /---'----  '- ' 

FIG.  149. — Diagram  of  cartilages  of  left  leg  and  foot  of  human  embryo  of  17  mm.     Hagen. 


the  fibula  the  epiphyseal  centers  appear  during  the  second  and  sixth  years  after 
birth.  The  cartilage  of  the  patella  appears  during  the  third  or  fourth  month 
of  foetal  life,  and  ossification  begins  two  or  three  years  after  birth. 

The  bones  of  the  tarsus,  like  those  of  the  carpus,  are  preformed  in  pieces  of 
cartilage  which  are  arranged  in  two  transverse  rows.  The  proximal  row  con- 
sists of  three  pieces,  one  at  the  end  of  the  tibia  (tibial),  one  at  the  end  of  the 
fibula  (fibular),  and  the  third  between  the  two  (intermedial) .  At  an  early  stage 
the  tibial  and  intermedial  fuse  to  form  a  single  piece  of  cartilage  which  corre- 
sponds to  the  talus  (astragalus)  bone.  The  fibular  cartilage  corresponds  to  the 
calcaneus  (os  calcis).  The  distal  row  is  composed  of  four  pieces  of  cartilage 
which  correspond  to  the  first  cuneiform  (internal),  second  cuneiform  (middle), 
third  cuneiform  (external),  and  cuboid  (Fig.  149).  Between  the  two  rows  is  a 


THE   CONNECTIVE  TISSUES  AND   THE   SKELETAL  SYSTEM. 


173 


piece  of  cartilage  which  corresponds  to  the  navicular  (scaphoid).  Ossification 
begins  relatively  late  in  the  metatarsals.  A  center  for  the  calcaneus  appears 
during  the  sixth  month  of  fcetal  life,  and  one  for  the  talus  shortly  before  birth. 
Centers  appear  in  the  cuboid  and  third  cuneiform  during  the  first  year  after 
birth,  and  in  the  first  cuneiform,  navicular  and  second  cuneiform  in  order  during 
the  third  and  fourth  years  (Figs.  150  and  151).  At  the  age  of  puberty  ossifica- 
tion is  nearly  complete  in  all  the  metatarsals.  In  the  talus  two  centers,  cor- 
responding to  the  tibial  and  intermedial,  appear,  but  soon  fuse  into  a  single 
center.  Occasionally  the  intermedial  remains  separate  and  forms  the  trigonum. 


Calcaneus  ~ 


FIG.  150. — Ossification  centers  in  foot  of  a  child  9  months  old.     Hasselwander. 

An  accessory  center  appears  in  the  calcaneus  at  the  insertion  of  the  tendon  of 
Achilles. 

;  The  metatarsals  and  phalanges  develop  in  a  manner  corresponding  to  the 
metacarpals  and  phalanges  (of  fingers).  Ossification  begins  in  the  metatarsals 
about  the  ninth  week,  in  the  first  row  of  (proximal)  phalanges  about  the 
thirteenth  week,  in  the  second  row  about  the  sixteenth  week  and  in  the  third 
row  (distal)  about  the  beginning  of  the  ninth  week.  Epiphyseal  centers  ap- 
pear from  the  second  to  the  eighth  year  after  birth. 

Development  of  Joints. 

The  embryonic  connective  tissue  from  which  the  connective  tissues,  includ- 
ing cartilage  and  bone,  are  developed,  at  first  forms  a  continuous  mass.  When 
cartilage  appears  it  may  form  a  continuous  mass,  as  in  the  chondrocranium,  or 


174 


TEXT-BOOK  OF  EMBRYOLOGY. 


it  may  form  a  number  of  distinct  and  separate  pieces,  as  in  the  vertebral  column, 
the  pieces  being  united  by  a  certain  amount  of  the  undifferentiated  embryonic 
connective  tissue. 

SYNARTHROSIS.  Syndesmosis. — When  ossification  begins  at  one  or  more 
centers,  either  in  cartilage  or  in  embryonic  connective  tissue,  the  centers  grad- 
ually enlarge  and  approach  each  other,  and  the  bone  so  formed  comes  in  contact 
with  the  bone  formed  in  neighboring  centers,  (a)  In  a  case  where  more  than  one 
center  appears  for  any  single  adult  bone,  they  may  come  in  contact  and  fuse  so 
completely  that  the  line  of  fusion  becomes  indistinguishable,  (b)  In  the  case  of 


Calcaneus 
(os  calcis) 


cuboid  —  -;-"€'* 


Metatarsal  V 


Epiphysis  of 
metatarsal  V 


Phalanx 


Talus  (astragalus) 


Cuneiform  II 


Cuneiform  I 

Epiphysis  of 
metatarsal  I 


. Metatarsal  I 


Epiphyses  of 
phalanges 


FIG.  151. — Skeleton  of  right  foot  of  a  boy  3  years  old,  showing  ossification  centers.     Toldt. 

adjacent  bones  the  fusion  may  not  be  so  complete;  that  is,  the  two  bones  may 
simply  articulate,  leaving  a  visible  line  of  junction  or  suture.  Such  joints  are 
immovable  and  are  represented  in  the  sutures  of  the  skull. 

Synchondrosis. — In  some  cases  a  small  amount  of  embryonic  connective 
tissue  remains  between  adjacent  bones,  (a)  In  time,  this  embryonic  connective 
tissue  gives  rise  to  cartilage  which  unites  the  bones  quite  firmly,  thus  producing 
a  practically  immovable  joint,  as  in  the  case  of  the  sacro-iliac  joint,  (b)  Or  the 
cells  in  the  center  of  the  cartilage  disintegrate  or  become  liquefied  so  that  a  small 
cavity  is  produced  (articular  cavity).  This  type  of  joint  makes  possible  a  slight 
degree  of  mobility  and  is  exemplified  by  the  symphysis  of  the  pubic  bones.  Such 
a  type  is  also  represented  by  the  joints  of  the  vertebral  column.  In  place  of 
cavities,  however,  are  the  pulpy  nuclei  which  are  remnants  of  the  notochord. 


THE   CONNECTIVE   TISSUES   AND   THE   SKELETAL  SYSTEM. 


175 


DIARTHROSIS. — Where  a  great  degree  of  mobility  is  necessary,  the  arrange- 
ment of  the  joint  is  different.  The  cells  in  the  central  part  of  the  embryonic 
connective  tissue  between  the  ends  of  adjacent  bones  (or  cartilages)  (Fig.  152) 
liquefy  so  that  a  relatively  large  cavity,  the  joint  cavity,  is  formed  (Fig.  153). 
The  liquefaction  of  the  connective  tissue  cells  may  also  extend  for  a  short  dis- 
tance along  the  sides  of  the  bones  so  that  the  joint  cavity  surrounds  the  ends 
of  the  bones  (Figs.  154  and  155).  The  origin  of  the  synovial fluid  is  not  known 

Humerus 


Radius 

FIG.  152. — Section  through  axilla  and  arm  of  a  human  embryo  of  26  mm.  (2  months).     Photograph. 
Note  the  mesenchymal  tissue  between  the  humerus  and  the  radius — the  site  of  the  elbow  joint. 

with  certainty,  but  it  is  probably  in  part  the  product  of  liquefaction  of  the  con- 
nective tissue  cells.  The  more  peripheral  part  of  the  connective  tissue  which 
encloses  the  joint  cavity  is  transformed  into  a  dense  fibrous  tissue,  the  joint 
capsule.  The  cells  lining  the  cavity  become  differentiated  into  oval  or  irregular 
cells,  among  which  is  a  considerable  amount  of  intercellular  substance.  By 
some  it  is  held  that  these  cells  form  a  continuous  single  layer  like  endothelium, 
but  the  most  recent  researches  tend  to  disprove  this.  The  cells  lining  the 


176 


TEXT-BOOK  OF  EMBRYOLOGY. 

Joint  cavity 


m%^-$^'&&m 

*  c        *•      .-      -   -       '  -    •  **  V««i    44k,    .  f     '  »    *    •-* 


FlG.  153. — Longitudinal  section  of  finger  of  human  embryo  of  26  mm.  (2  months),  showing  beginning 
of  joint  cavity  between  adjacent  ends  of  phalanges.  (Photograph  from  preparation  by 
Dr.  W.  C.  Clarke.) 


FlG  154. — From  longitudinal  section  of  finger  of  child  at  birth,  showing  developing  joint  cavit^ 
between  adjacent  ends  of  phalanges.  The  darker  portion  at  each  end  of  the  figure  indicates 
the  ossification  center  in  the  phalanx,  the  end  of  the  latter  (lighter  area)  being  yet  cartilagi- 
nous. The  dark  bands  at  each  side  of  the  joint  indicate  developing  ligaments.  Photograph. 


THE   CONNECTIVE   TISSUES   AND   THE  SKELETAL  SYSTEM. 


177 


cavity  are  the  most  highly  differentiated,  the  cell  bodies  being  large  and  ap- 
parently swollen,  and  there  is  gradually  less  differentiation  as  the  distance  from 
the  surface  increases,  until  finally  they  merge  with  the  ordinary  type  of  con- 
nective tissue  cells  of  the  joint  capsule  (Clarke).  The  more  mobile  joints  of 
the  body  are  all  representatives  of  this  type. 

Joint  cavity 


Synovial  membrane 

FIG.  155. — From  longitudinal  section  of  finger  of  child  at  birth,  showing  joint  cavity  and  synovial 
membrane  between  adjacent  ends  of  the  first  metacarpal  and  proximal  phalanx.  Other 
description  same  as  in  Fig.  154.  Photograph. 


Anomalies. 
THE  AXIAL  SKELETON. 


THE  VERTEBRAE. — The  number  of  cervical  vertebrae  in  man  is  remarkably 
constant.  Cases  where  the  number  is  but  six  are  extremely  rare.  The 
thoracic  vertebrae  may  vary  in  number  in  different  individuals  from  eleven  to 
thirteen,  twelve  being  the  usual  number.  The  lumbar  vertebrae  may  vary 
from  four  to  six,  five  being  the  usual  number.  The  sacral  vertebrae,  fused  in  the 
adult  to  form  the  sacrum,  are  usually  five  in  number,  sometimes  four,  sometimes 


178  TEXT-BOOK  OF  EMBRYOLOGV. 

six.  Occasionally  a  vertebra  between  the  lumbar  region  and  sacral  region — 
lumbo-sacral  vertebra — possesses  both  lumbar  and  sacral  characters,  one 
side  being  fused  with  the  sacrum,  the  other  side  having  a  free  transverse  process. 
Variation  occurs  frequently  in  the  coccygeal  vertebrae;  four  and  five  are  present 
with  about  equal  frequency,  more  rarely  there  are  only  three. 

The  total  number  of  true  (presacral)  vertebrae  may  be  diminished  by  one  or 
increased  by  one.  In  the  former  case  the  first  sacral  is  the  twenty-fourth  ver- 
tebra, and,  if  the  number  of  ribs  remains  normal,  there  are  only  four  lumbar 
vertebrae.  In  case  the  total  number  is  increased  by  one,  the  first  sacral  is  the 
twenty-sixth  vertebra,  and  there  are  twelve  thoracic  and  six  lumbar  or  thirteen 
thoracic  and  five  lumbar. 

From  these  facts  it  is  seen  that  variation  occurs  most  frequently  in  the  more 
caudal  portion  of  the  vertebral  column — in  the  lumbar,  sacral  and  coccygeal 
regions.  According  to  a  hypothesis  advanced  by  Rosenberg,  the  sacrum  in  the 
earlier  embryonic  stages  is  composed  of  a  more  caudal  set  of  vertebrae  than  those 
which  belong  to  it  in  the  adult,  and  during  development  lumbar  vertebrae  are 
converted  into  sacral  and  sacral  vertebrae  into  coccygeal.  In  other  words,  the 
hip  bone  moves  headward  during  development  and  finally  becomes  attached  to 
vertebrae  which  are  situated  more  cranially  than  those  with  which  it  was  pri- 
marily associated.  This  change  in  the  position  of  the  pelvic  attachment,  and  the 
corresponding  reduction  in  the  total  number  of  vertebrae,  during  the  develop- 
ment of  the  individual  (i.e.,  during  ontogenetic  development)  is  believed  to 
correspond  to  a  similar  change  in  position  during  the  evolution  of  the  race  (i.e., 
during  phylogenetic  development). 

According  to  Rosenberg,  variation  in  the  adult  is  due  largely  to  a  failure 
during  ontogeny  to  carry  the  processes  of  reduction  in  the  number  of  vertebrae 
as  far  as  they  are  usually  carried  in  the  race,  or  to  their  being  carried  beyond  this 
point. 

The  coccygeal  vertebrae  apparently  represent  remnants  of  the  more  exten- 
sively developed  caudal  vertebrae  in  lower  forms.  In  human  embryos  of  8  to 
16  mm.,  when  the  caudal  appendage  is  at  the  height  of  its  development,  there 
are  usually  seven  anlagen  of  coccygeal  vertebrae.  During  later  development  this 
number  becomes  reduced  by  fusion  of  the  more  distally  situated  anlagen  to  the 
smaller  number  in  the  adult.  This  process  of  reduction  varies  in  different  in- 
dividuals, so  that  five  or  four,  rarely  three,  coccygeal  vertebrae  may  be  the  result. 
In  cases  where  children  are  born  with  distinct  caudal  appendages  there  is  no 
good  evidence  that  the  number  of  coccygeal  vertebrae  is  increased,  although  the 
coccyx  may  extend  into  the  appendage. 

THE  RIBS. — Occasionally  in  the  adult  a  rib  is  present  on  one  side  or  on 
each  side  in  connection  with  the  seventh  cervical  vertebra  (cervical  rib),  or  in 
connection  with  the  first  lumbar  vertebra  (lumbar  rib) .  There  seems  to  be  no 


THE   CONNECTIVE   TISSUES  AND   THE  SKELETAL  SYSTEM.  179 

case  on  record  where  cervical  and  lumbar  ribs  are  present  in  the  same  individual. 
The  cervical  rib  may  vary  between  a  small  piece  of  bone  connected  with  the 
transverse  process  of  the  vertebra  and  a  well  developed  structure  long  enough  to 
reach  the  sternum.  There  are  also  great  variations  in  the  size  of  the  lumbar  rib. 
In  case  the  number  of  ribs  is  normal,  the  last  (twelfth)  may  be  rudimentary. 

The  eighth  costal  cartilage  not  infrequently  unites  with  the  sternum.  Oc- 
casionally the  seventh  costal  cartilage  fails  to  fuse  with  the  sternum,  owing  to 
the  shortening  of  the  latter,  but  meets  and  fuses  with  its  fellow  of  the  opposite 
side  in  the  midventral  line. 

The  above  mentioned  anomalies  can  be  referred  back  to  aberrant  develop- 
ment. Primarily  costal  processes  appear  in  connection  with  the  cervical,  lum- 
bar and  sacral  vertebrae.  Normally  these  processes  fuse  with  and  finally  form 
parts  of  the  vertebrae  (p.  153).  In  some  cases,  however,  the  seventh  cervical  or 
the  first  lumbar  processes  develop  more  fully  and  form  more  or  less  distinct  ribs. 

As  an  explanation  of  these  variations  in  the  number  of  ribs,  it  has  been  sug- 
gested that  there  is  a  tendency  toward  reduction  in  the  total  number  of  ribs,  and 
that  supernumerary  ribs  represent  the  result  of  a  failure  to  carry  the  reduction  as 
far  as  the  normal  number.  In  case  the  twelfth  rib  is  rudimentary,  the  reduction 
has  been  carried  beyond  the  normal  limit.  This  hypothesis  is  a  corollary  to  the 
hypothesis  regarding  the  variations  in  the  number  of  vertebrae.  (See  under 
"The  Vertebrae.") 

THE  STERNUM.— Certain  anomalous  conditions  of  the  sternum  can  also  be 
explained  by  reference  to  development.  The  condition  known  as  cleft  sternum, 
in  which  the  sternum  is  partially  or  wholly  divided  into  two  longitudinal  bars 
by  a  medial  fissure,  represents  the  result  of  a  failure  of  the  two  bars  to  unite  in 
the  midventral  line  (p.  153,  see  also  Fig.  130).  This  is  sometimes  associated 
with  ectopia  cordis  (p.  255).  The  xyphoid  process  may  also  be  bifurcated  or 
perforated,  according  to  the  degree  of  fusion  between  the  two  primary  bars 

(P-  I54)- 

Suprasternal  bones  may  be  present.  They  represent  the  ossified  episternal 
cartilages  which  have  failed  to  unite  with  the  manubrium  (p.  154).  Morpho- 
logically the  suprasternal  bones  possibly  represent  the  omosternum,  a  bone 
situated  cranially  to  the  manubrium  in  some  of  the  lower  Mammals. 

THE  HEAD  SKELETON. — The  skull  is  sometimes  decidedly  asymmetrical. 
Probably  no  skull  is  perfectly  symmetrical.  The  condition  which  most  fre- 
quently accompanies  the  irregular  forms  of  skulls  is  premature  synosteosis  or 
premature  closure  of  certain  sutures.  The  cranial  bones  increase  in  size  prin- 
cipally at  their  margins,  and  when  a  suture  is  prematurely  closed  the  growth  of 
the  skull  in  a  direction  at  right  angles  to  the  line  of  suture  is  interfered  with. 
Consequently  compensatory  growth  must  take  place  in  other  directions.  Thus 
if  the  sagittal  suture  is  prematurely  closed  and  transverse  growth  prevented, 


180  TEXT-BOOK  OF  EMBRYOLOGY. 

increase  occurs  in  the  vertical  and  longitudinal  directions.  This  results  in  the 
vault  of  the  skull  becoming  heightened  and  elongated,  like  an  inverted  skiff,  a 
condition  known  as  scaphocephaly.  After  premature  closure  of  the  coronal 
suture,  growth  takes  place  principally  upward  and  gives  rise  to  acrocephaly.  In 
case  only  one-half  the  coronal  or  lambdoidal  suture  is  closed,  the  growth  is 
oblique  and  results  in  plagiocephaly. 

A  suture — the  metopic  suture — sometimes  exists  in  the  medial  line  between 
the  two  halves  of  the  frontal  bone,  a  condition  known  as  metopism.  This  is  due 
to  an  imperfect  union  of  the  two  plates  of  bone  produced  by  the  two  centers  of 
ossification  in  the  frontal  region  (p.  162). 

Certain  malformations  in  the  face  region  and  in  the  roof  of  the  mouth  are 
brought  about  by  defective  fusion  or  complete  absence  of  fusion  between  certain 
structures  during  the  earlier  embryonic  stages.  The  maxillary  process  of  the 
first  branchial  arch  sometimes  fails  to  unite  with  the  middle  nasal  process 
(Kolliker's  view,  p.  164;  see  also  Fig.  98).  The  result  is  a  fissure  in  the 
upper  lip,  a  condition  known  as  hare  lip,  which  may  or  may  not  be  accompanied 
by  a  cleft  in  the  alveolar  process  of  the  maxilla,  extending  as  far  as  the  incisive 
(palatine)  foramen.  The  same  result  may  be  produced  by  a  defective  fusion 
between  the  middle  nasal  process  and  the  lateral  nasal  process  (Albrecht's  view, 
p.  164;  see  also  Fig.  98).  Hare  lip  may  be  either  unilateral  (single)  or  bilateral 
(double),  accordingly  as  defective  fusion  occurs  on  one  or  both  sides,  but  never 
medial. 

Occasionally  the  palatine  process  of  the  maxillary  process  fails  to  meet  not 
only  its  fellow  of  the  opposite  side,  but  also  the  vomer  (see  Fig.  141) .  The  result 
is  a  cleft  in  the  hard  palate,  a  condition  known  as  cleft  palate.  This  malforma- 
tion may  be  unilateral  or  bilateral,  but  not  medial.  Sometimes  the  cleft  extends 
into  the  soft  palate  where  it  occupies,  however,  a  medial  position. 

Cleft  palate  may  accompany  hare  lip,  or  either  may  exist  without  the  other, 
depending  upon  the  degree  of  fusion  between  the  processes  mentioned  above. 
In  bilateral  hare  lip,  with  or  without  cleft  palate,  the  incisive  (intermaxillary) 
bone  is  sometimes  pushed  forward  by  the  vomer  and  projects  beyond  the  surface 
of  the  face,  a  condition  known  as  "wolf's  snout." 

The  causes  underlying  the  origin  of  harelip  and  cleft  palate  are  obscure. 

THE  APPENDICULAR  SKELETON. 

THE  HUMERUS. — On  the  medial  side  of  the  humerus,  just  proximal  to  the 
medial  condyle,  there  is  not  infrequently  a  small  hook-like  process  directed 
distally — the  supracondyloid  process.  This  process  represents  a  portion  of  bone 
which  in  some  of  the  lower  mammals  (cat,  for  example)  joins  the  internal 
condyle  and  completes  the  supracondyloid  foramen,  through  which  the  median 
nerve  and  brachial  artery  pass. 


THE   CONNECTIVE  TISSUES  AND   THE  SKELETAL   SYSTEM.  181 

THE  CARPAL  BONES. — Occasionally  an  os  centrale  is  present  in  addition  to 
the  usual  carpal  bones.  It  is  situated  on  the  dorsal  side  of  the  wrist  between  the 
navicular,  capitate  and  small  multangulum.  In  the  embryo  an  additional  piece 
of  cartilage  is  of  constant  occurrence  in  this  location,  but  usually  disappears 
during  later  development;  in  cases  where  it  persists,  ossification  takes  place 
to  form  the  os  centrale.  In  some  of  the  apes  the  os  centrale  is  of  constant 
occurrence  in  the  adult. 

THE  FEMUR. — The  gluteal  tuberosity  (ridge)  sometimes  projects  like  a 
comb,  forming  the  so-called  third  trochanter,  a  structure  homologous  with  the 
third  trochanter  in  the  horse  and  some  other  mammals. 

THE  TARSAL  BONES. — Cases  have  been  recorded  in  which  the  total  number 
of  tarsal  bones  was  reduced,  owing  to  congenital  synosteosis  (fusion)  of  the 
calcaneus  (os  calcis)  and  scaphoid  (navicular),  of  the  talus  (astragalus)  and 
calcaneus,  or  of  the  talus  and  scaphoid.  Occasionally  an  additional  bone — the 
trigonum — is  present  at  the  back  of  the  talus.  In  the  embryo,  the  talus  ossifies 
from  two  centers  which  normally  fuse  at  an  early  stage  into  a  single  center. 
The  trigonum  probably  represents  a  bone  produced  by  one  of  the  centers  which 
has  remained  separate. 

POLYDACTYLY. — This  anomaly  consists  of  an  increase  in  the  number  of 
fingers  or  toes,  or  both.  Any  degree  of  variation  may  exist  from  a  supernum- 
erary finger  or  toe  to  a  double  complement  of  fingers  or  toes.  The  causes  under- 
lying the  origin  of  such  anomalies  are  not  clear.  Some  assign  the  supernumer- 
ary digits  to  the  category  of  pathological  growths  or  neoplasms,  linking  them 
with  partial  duplicate  formations.  Others  explain  the  extra  digits  on  the  ground 
of  atavism  or  reversion  to  an  ancestral  type.  The  latter  explanation  assumes 
an  ancestral  type  with  more  than  five  digits.  But  neither  zoology  nor  paleon- 
tology has  found  any  vertebrate  form,  above  the  Fishes,  which  normally  pos- 
sesses more  than  five  digits  on  each  extremity.  Consequently  one  must  refer  to 
the  Fishes  for  some  ancestral  type  to  explain  the  existence  of  more  than  five 
digits.  Going  back  so  far  in  phylogenetic  history,  no  certainty  whatever  can  be 
attached  to  the  origin  of  supernumerary  digits,  for  it  is  not  even  known  from 
what  fins  the  extremities  of  the  higher  forms  are  derived.  Still  another  view 
regarding  the  origin  of  supernumerary  digits  is  that  they  are  due  to  certain  ex- 
ternal influences  among  which  the  most  important  is  the  mechanical  impression 
of  amniotic  folds  or  bands.  This,  however,  could  not  be  the  sole  cause  of 
polydactylism,  since  such  malformations  are  common  in  amphibian  embryos 
where  no  amnion  is  present. 

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KEIBEL,  F.:  Zur  Entwickelungsgeschichte  der  Chorda  bei  Saugern.  Arch.f.  Anat. 
u.  PhysioL,  Anat.  Abth.,  1889. 

KEIBEL,  F.,  and  MALL,  F.  P.:  Manual  of  Human  Embryology,  Vol.  I,  1910.  Chap. 
XI. 

KJELLBERG,  K.:  Beitrage  zur  Entwickelungsgeschichte  des  Kiefergelenks.  Morph. 
Jahrbuch,  Bd.  XXXII,  1904. 

KOCH,  JOHN  C.:  The  Laws  of  Bone  Architecture.  American  Jour,  of  Anat.,  Vol.  XXI, 
No.  2,  1917. 

KOLLMANN,  J.:  Entwickelung  der  Chorda  dorsalis  bei  dem  Menschen.  Anat.  Anz., 
Bd.  V,  1890. 

KOLLMANN,  J.:  Lehrbuch  der  Entwickelungsgeschichte  des  Menschen.     Jena,  1898. 

KOLLMANN,  J.:  Handatlas  der  Entwickelungsgeschichte  des  Menschen.     Jena,  1907. 

MALL,  F.  P.:  The  Development  of  the  Connective  Tissues  from  the  Connective- 
tissue  Syncytium.  American  Jour,  of  Anat.,  Bd.  I,  1902. 

MALL,  F.  P. :  On  Ossification  Centers  in  Human  Embryos  less  than  One  Hundred  Days 
Old.  American  Jour,  of  Anat.,  Bd  V,  1906. 

McMuRRiCH,  J.  P.:  The  Development  of  the  Human  Body.     Philadelphia,    1919. 

PATERSON,  A.:  The  Sternum:  Its  Early  Development  and  Ossification  in  Man  and 
Mammals.  Jour,  of  Anat.  and  PhysioL,  Vol.  XXXV,  1901. 

PETERSEN,  H.:  Untersuchungen  zur  Entwickelung  des  menschlichen  Beckens.  Arch, 
f.  Anat.  u.  PhysioL,  Anat.  Abth.,  1893. 

RABL,  C.:  Theorie  des  Mesoderms.     Morph.  Jahrbuch,  Bd.  XV,  1889. 

ROSENBERG,  E.:  Ueber  die  Entwickelung  der  Wirbelsaule  und  das  Centrale  carpi  des 
Menschen.  Morph.  Jahrbuch,  Bd.  I,  1876. 

SCHAUINSLAND,  H.:  Die  Entwickelung  der  Wirbelsaule  nebst  Rippen  und  Brustbein. 
In  Hertwig's  Handbuch  der  vergleich.  u.  experiment.  Entwickelungslehre  der  Wirbeltiere, 
Bd.  Ill,  Teil  II,  1905. 

SPULER,  A.:  Beitrage  zur  Histologie  und  Histogenese  der  Binde-  und  Stutzsubstanz. 
Anat.  Hefte,  Heft  XXI,  1896. 


184  TEXT-BOOK  OF   EMBRYOLOGY. 

THILENIUS,  G.:  Untersuchungen  iiber  die  morphologische  Bedeutung  accessorischer 
Elemente  am  menschlichen  Carpus  (und  Tarsus).  Morph.  Arbeiten,  Bd.  V,  1896. 

THOMSON,  A.:  The  Sexual  Differences  of  the  Foetal  Pelvis.  Jour,  of  Anat.  and 
PhysioL,  Vol.  XXXIII,  1899. 

TORNIER,  G.:  Das  Entstehen  der  Gelenkformen.  Arch.  f.  Entw.-Mechanik,  Bd.  I, 
1895. 

WALDEYER,  W.:  Kittsubstanz  und  Grundsubstanz,  Epithel  und.Endothel.  Arch.  f. 
mik.  Anat.,  Bd.  LVII,  1900. 

WEISS,  A.:  Die  Entwickelung  der  Wirbelsaule  der  weissen  Ratte,  besonders  der  vorder- 
sten  Halswirbel.  Zeitschr.  f.  wissensch.  Zool.,  Bd.  LXIX,  1901. 

ZIMMERMANN,  K.:  Ueber  Kopfhohlenrudimente  beim  Menschen.  Arch./,  mik.  Anat., 
Bd.  LIII,  1899. 


CHAPTER  X. 

THE  DEVELOPMENT  OF  THE  VASCULAR  SYSTEM. 
THE  BLOOD  VASCULAR  SYSTEM. 

The  blood  vessels  constitute  such  an  extensive  and  complex  system  that 
it  is  obviously  beyond  the  scope  of  this  book  to  consider  the  entire  system  in 
detail.  Consequently  attention  must  be  directed  only  to  the  develop- 
ment of  the  main  channels,  including  the  heart,  and  to  the  principles  of 
vessel  formation. 


FIG.   156. — Surface  views  of  chick  blastoderms.     Ruckert,  Her  twig. 

a,  Blastoderm  with  primitive  streak  and  head  process;  showing  blood  islands  (dark  spots  in 

crescent-shaped  area  in  lower  part  of  figure). 

b,  Blastoderm  with   6   pairs  of  primitive  segments.     Reticulated  appearance  is  due  to  blood 

islands  (dark  spots)  and  to  developing  vessels,  the  entire  reticulated  area  being  the  area 
vasculosa. 

The  formation  of  blood  vessels  in  all  the  higher  vertebrates  including 
mammals  begins  in  the  opaque  area  of  the  blastoderm  (area  opaca)  while 
the  germ  layers  still  lie  flat.  Toward  the  end  of  the  first  day  of  incubation 
in  the  chick,  about  the  time  the  primitive  streak  reaches  the  height  of  its 

185 


186 


TEXT-BOOK  OF  EMBRYOLOGY. 


development,  the  peripheral  part  of  the  area  opaca  caudal  and  lateral  to  the 
primitive  streak  presents  a  mottled  appearance  (Fig.  1560).  This  indicates 
the  beginning  of  the  area  vasculosa,  which  subsequently  extends  forward  in 
the  peripheral  portion  of  the  opaque  area,  lateral  to  the  developing  body, 
and  becomes  reticulated  in  appearance  (Fig.  156^). 

Sections  of  the  blastoderm  show  that  the  mottled  surface  appearance  is 
due  to  clusters  of  cells  amidst  the  mesoderm,  known  as  blood  islands  (Fig. 
157).  These  are  composed  of  rounded  cells  which  have  developed  from  the 
branched  mesodermal  (mesenchymal)  cells,  and  are  situated  in  close  apposi- 
tion to  the  entoderm.  Subsequently,  when  the  coelom  appears  in  this  region, 
they  lie  in  the  visceral,  or  splanchnic,  layer  of  mesoderm  (Fig.  158). 


Ectoderm 


Mesoderm 


Entoderm 
(yolk  cells) 


Blood  island 


FIG.   157. — Section  of  blastoderm  (area  opaca)  of  chick  of  27  hours'  incubation.     Photograph. 

The  early  changes  that  occur  in  the  blood  islands  are  important  as  re- 
gards both  developing  vessels  and  blood  cells.  The  superficial  cells  of  an 
island  are  transformed  into  flat  cells  placed  edge  to  edge  which  surround 
the  remaining  rounded  cells.  The  flat  cells  constitute  the  endothelium  of  a 
primitive  blood  space,  while  the  cells  within  the  space  comprise  primitive 
blood  cells  (Fig.  158).  These  early  spaces  in  the  area  vasculosa  join  one 
another  and  become  continuous  to  form  a  net-work,  or  plexus,  of  channels 
to  which  is  due  the  reticulated  appearance  referred  to  above  (Fig.  1566). 
This  is  known  as  the  vitelline  plexus.  The  groups  of  primitive  blood  cells 
within  the  channels  will  be  considered  in  detail  in  a  subsequent  section 
(page  236). 

During    the    second    day    of   incubation    in    the    chick    the    peripheral 


THE  DEVELOPMENT  OF  THE  VASCULAR  SYSTEM. 


187 


channels  of  the  vascular  area  unite  to  form  a  vessel — the  sinus  terminalis — 
which  is  continuous  around  the  border  except  at  the  head  end  of  the  embryo 
(Fig.  159).  At  the  same  time  the  vascularization  of  the  visceral  layer  of 
mesoderm  gradually  extends  through  the  clear  area  of  the  blastoderm 
(area  pellucida)  toward  and  finally  into  the  embryonic  body.  Reaching 
the  region  just  lateral  to  the  notocord,  the  vessels  unite  longitudinally  in  the 
embryo  to  form  a  continuous  channel,  the  primitive  aorta,  which  thus  con- 
stitutes a  natural  selvage  to  the  vascular  area  on  each  side  of  the  blastoderm 
(Fig.  159).  Some  of  the  channels  of  the  vitelline  plexus  increase  in  size 
and  coalesce  to  form  a  large  trunk  which  is  a  branch  of  the  primitive  aorta 


Ccelom 


Parietal  mesoderm 


Ectoderm 


Visceral  mesoderm 


Blood  islands 


IG.  158. — Section  of  blastoderm  of  chick  of  42  hours'  incubation.  Photograph.  The  cells  of 
the  blood  islands  are  differentiated  into  primitive  blood  cells  and  the  endothelium  of 
the  vessels. 

on  each  side  and  leads  off  into  the  smaller  vessels  in  the  peripheral  part  of 
the  vascular  area.  This  trunk  is  known  as  the  vitelline,  or  omphalomesenteric, 
artery  and  is  at  first  located  near  the  caudal  end  of  the  embryo.  When  cir- 
culation is  established  through  contractions  of  the  heart  it  carries  blood 
from  the  aorta  to  the  surface  of  the  yolk  sac  (Fig.  159).  Other  channels  of 
the  vitelline  plexus  nearer  the  head  end  of  the  embryo  likewise  form  a  large 
trunk,  the  vitelline,  or  omphalomesenteric,  vein  which  collects  the  blood  from 
the  surface  of  the  yolk  sac  and  conveys  it  to  the  heart  (Fig.  159). 

So  long  as  the  germ  layers  lie  flat  the  two  primitive  aortae  remain  separate, 
but  with  the  ventral  flexion  and  fusion  of  the  germ  layers  to  form  the  tubular 
body  the  aortae  fuse  into  a  single  medial  vessel,  the  dorsal  aorta,  except  in 
the  cervical  region  where  the  two  original  vessels  persist  as  the  dorsal  aortic 
roots.  The  proximal  ends  of  the  vitelline  arteries  also  fuse  into  a  single 


188 


TEXT-BOOK  OF  EMBRYOLOGY. 


trunk,  the  two  vitelline  veins,  however,  remaining  separate.  In  each 
branchial  arch  on  each  side  a  vessel  develops  which  joins  with  the  corre- 
sponding dorsal  aortic  root.  These  vessels— the  aortic  arches — arise  from 
single  vessel  on  each  side  ventral  to  the  pharynx  which  is  known  as  the 
ventral  aortic  root.  The  two  ventral  aortic  roots  arise  from  a  single  medial 


Vitelline 
plexus 


FIG.  159. — Dorsal  surface  view  of  chick  embryo  with  18  segments,  including  the  area  vascuk 

Photograph,        X  15.     The  blood  vessels  were  injected  with  India  ink,  the  dark  blotch  ii 
the  upper  left  corner  indicating  some  ink  which  escaped  during  the  injection. 

"t-essel,  the  aortic  trunk,  or  truncus  arteriosus,  which  in  turn  is  a  continuatioi 
of  the  early  tubular  heart. 

The  heart,  having  developed  and  become  a  contractile  organ  in  the 
meantime,  receives  the  blood  in  its  caudal  end  through  the  vitelline  veins 
and  ejects  it  from  its  cephalic  end  through  the  aortic  trunk.  The  blood 
then  passes  through  the  aortic  arches  to  the  dorsal  aorta  whence  it  is  dis- 
tributed to  the  vitelline  plexus  by  the  vitelline  arteries.  The  blood  is 


THE  DEVELOPMENT  OF  THE  VASCULAR  SYSTEM. 


189 


collected  by  tributaries  of  the  vitelline  veins  and  carried  to  the  heart.  Thus 
the  vitelline  (yolk)  circulation  is  completed  (Fig.  160).  From  this  time  on, 
the  area  vasculosa  gradually  enlarges,  as  the  germ  layers  extend  farther  and 
farther  around  the  yolk,  until  it  eventually  surrounds  the  whole  yolk  mass. 
In  mammals,  as  in  the  chick,  the  vascular  rudiments  develop  first  in  the 
extraembryonic  portion  of  the  mesoderm  as  clusters  of  cells  which  give  the 
area  opaca  a  mottled  appearance  on  surface  view.  This  soon  changes  to  a 
reticulated  appearance  as  the  cell  clusters  give  rise  to  primitive  blood  spaces 
which  join  one  another  to  form  a  plexus  of  channels.  This  plexus  gradually 


Aortic  arches 


Heart 


Sinus  terminalis 


Ant.  cardinal 
vein 

Aorta 


Sinus 
venosus 


Right  vitelline  vein 

Right  vitelline  artery 


Duct  of  Cuviev 
Post,  cardinal  vein 
Left  vitelline  artery 


Left  vitelline  vein 


FIG.  1 60. — Diagram  of  the  vitelline  (yolk)  circulation  of  a  chick  embryo  at  the  end  of 
the  third  day  of  incubation.     Ventral  view.     Balfour. 

extends  across  the  area  pellucida  toward  the  embryo  and  terminates  in  a 
natural  selvage  as  the  primitive  aorta  on  each  side  of  the  median  line.  The 
vitelline  arteries  and  veins  are  formed  out  of  the  plexus  and,  with  the  heart, 
aortic  arches  and  dorsal  aorta  as  in  the  chick,  constitute  the  vitelline  cir- 
culatory system  (Fig.  161).  The  vascular  area  in  some  mammals  gradually 
enlarges  until  it  embraces  the  "entire  yolk  sac  (Fig.  162). 

It  is  seen  from  the  foregoing  account  that  the  earliest  circulation  is  asso- 
ciated with  the  yolk  sac.  In  animals  below  the  mammals,  where  a  large 
amount  of  yolk  is  present  in  the  sac,  the  vitelline  circulation  is  of  prime 


190 


TEXT-BOOK  OF  EMBRYOLOGY. 


FIG.  161 . — Surface  view  of  area  vasculosa  of  a  rabbit  embryo  of  1 1  days,     van  Beneden  and  Jidin. 
The  vessel  around  the  border  is  the  sinus  terminalis;  the  two  large  vessels  above  the  embryo  are 

the  vitelline  (omphalomesenteric)   veins ;    the    two    large  vessels  converging  below  the 

embryo  are  the  vitelline  (omphalomesenteric)  arteries. 


Dors,  aortic  root 
and  aortic  arches 


Ant.  cardinal  vein 


Chorionic  villi 

FIG.  162. — Human  embryo  of  3.2  mm.     His.     The  arrows  indicate  the  direction 

of  the  blood  current. 


THE  DEVELOPMENT  OF  THE  VASCULAR  SYSTEM. 


191 


importance  in  supplying  the  growing  embryo  with  nutritive  materials.  In 
mammals  the  vitelline  circulatory  system  develops  as  extensively  as  in  the 
lower  forms  but,  since  little  yolk  is  present,  does  not  assume  the  same  impor- 
tant role  of  carrying  food  supply;  yet  the  portions  of  the  vessels  inside  the  em- 
bryo, viz. :  the  heart,  aortic  arches,  aorta,  the  proximal  part  of  the  vitelline 
artery,  and  the  vitelline  veins,  form  parts  of  the  permanent  vascular  system. 
In  reptiles  and  birds  a  second  set  olyessels  develops  in  connection  with 
the  allantois  and  serves  to  carry  away  the  waste  products  of  the  body  and 
deposit  them  in  that  sac-like  structure.  Two  arteries,  one  on  each  side, 


Yolk  stalk 


Allantois 


Umbilical  artery 
Umbilical  vein 

Amnion 


Chorionic  villi 


FIG.  163, — Diagram  of  the  umbilical  vessels  in  the  belly  stalk  and  chorion.     Kollmann's  Atlas. 

arise  as  branches  of  the  dorsal  aorta  near  its  caudal  end  and  pass  out  of  the 
body  along  with  the  allantoic  duct  to  ramify  upon  the  surface  of  the  allantois. 
These  are  the  umbilical,  or  allantoic,  arteries.  The  blood  is  collected  and 
carried  back  by  the  umbilical  veins  which  pass  along  the 'allantoic  duct  to  the 
body  and  then  forward,  one  on  each  side,  through  the  somatic  layer  of 
mesoderm  to  join  the  ducts  of  Cuvier.  The  duct  of  Cuvier,  formed  on  each 
side  by  the  junction  of  the  anterior  and  posterior  cardinal  veins,  which  will 
be  considered  in  a  subsequent  section,  pour  their  blood  into  the  sinus  venosus. 
This  venous  trunk  is  formed  by  the  junction  of  the  ducts  of  Cuvier  with  -the 
vitelline  veins  and  empties  directly  into  the  heart. 


192 


TEXT-BOOK  OF  EMBRYOLOGY. 


In  mammals  in  general  the  allantois  is  a  rudimentary  structure  incapable 
of  receiving  the  total  waste  of  the  embryo.  The  umbilical  (allantoic) 
vessels  develop,  however,  as  in  reptiles  and  birds  but  become  associatec 
through  the  belly  stalk  with  the  placenta  which  establishes  communication 
between  the  embryo  and  the  mother  (Fig.  163).  The  vessels  within  the 
embryo  are  at  first  disposed  in  the  same  manner  as  in  the  lower  forms, 

Int.  carotid  artery 


Vertebral  artery 


Vitelline  vein 
Vitelline  artery 

Umbilical  vein 

Umbilical 

arteries 


Duct  of  Cuvier 


Post,  cardinal 
vein 


Aorta 


Post,  cardinal  vein 


FIG.   164. — Reconstruction  of  a  human  embryo  of   7   mm.     Mall. 

Arteries  represented  in  black.  A.V.,  Auditory  vesicle;  B,  bronchus;  L,  liver;  K,  anlage  o 
kidney;  T,  thyreoid  gland;  III-XII,  cranial  nerve  roots;  i,  2,  3,  4,  branchial  grooves;  i, 
8,  12,  5  (on  spinal  nerve  roots),  ist  and  8th  cervical,  i2th  dorsal,  5th  lumbar  spinal  nerv 
respectively.  Dotted  outlines  represent  limb  buds. 


the  umbilical  arteries  arising  from  the  caudal  portion  of  the  aorta  and  the 
umbilical  veins  passing  forward  in  the  ventro-lateral  body  wall  to  join  the 
ducts  of  Cuvier.  With  the  formation  of  the  umbilical  cord  the  two  umbilical 
veins  within  this  structure  fuse  into  a  single  vessel  (Fig.  164).  The  later 
changes  in  the  umbilical  veins  are  most  conveniently  considered  subsequently. 
In  mammals  in  general  the  umbilical  (allantoic)  circulatory  system 
performs  a  two-fold  function.  The  blood  carries  to  the  placenta  the  waste 


THE  DEVELOPMENT  OF  THE  VASCULAR  SYSTEM.  193 

products  of  the  embryo  for  deposition  in  the  maternal  circulation,  the  waste 
in  the  lower  forms  (reptiles  and  birds)  being  deposited  in  the  allantois. 
The  blood  carries  from  the  placenta  the  food  materials  derived  from  the 
maternal  circulation,  the  food  in  the  lower  forms  being  taken  from  the  yolk 
sac  and  conveyed  to  the  embryo  by  the  vitelline  vessels. 

Principles  of  Vasculogenesis. — Upon  the  thesis  that  tissues  in  general 
must  receive  materials  which  they  build  up  into  their  own  substances  and 
must  discharge  the  products  of  their  activities,  the  vascular  channels  of 
the  body  can  be  considered  as  structural  expressions  of  this  functional 
necessity.  For  instance,  a  muscle  which  acts  must  receive  materials  to 
compensate  it  for  its  loss  and  must  discharge  the  waste  products  that  result 
from  its  action,  and  the  blood  vessels  are  peculiarly  adapted  to  these  func- 
tions. The  lymph  vessels,  too,  similar  in  structure  to  the  blood  vessels, 
although  efferent  relative  to  the  tissues,  play  their  part  in  conveying  the 
products  of  metabolism. 

Much  controversy  has  arisen  over  the  actual  genesis,  or  origin,  of  blood 
vessels  and  lymphatics,  and  as  yet  the  opposing  views  have  not  been  recon- 
ciled. In  brief  there  are  two  views:  One  that  with  a  few  exceptions  every 
vessel  in  the  body  develops  as  a  sprout  from  another  vessel,  that  is,  the 
endothelium  arises  from  preexisting  endothelium  by  proliferation  of  its  own 
cells;  the  other  that  vessels  in  general  arise  in  situ,  that  is,  the  lumen  of  a 
vessel  represents  an  intercellular  tissue  space^or  several  such  spaces,  whose 
bordering  cells  have  been  transformed  into  the  characteristic  endothelial 
cells,  and  as  a  corollary,  the  continuity  of  a  given  vessel  results  from  the 
union  of  such  spaces.  According  to  the  latter  view,  the  whole  vascular 
system  represents  intercellular  tissue  spaces  which,  with  their  lining  of 
flattened  cells,  have  united  to  form  a  set  of  continuous  channels. 

In  the  case  of  either  view  it  is  recognized  that  the  first  vessels  appear 
in  the  opaque  area  of  the  blastoderm.  Here  the  blood  islands  originate  as 
clusters  of  cells  amidst  the  mesoderm,  differentiating  from  mesenchymal 
elements  in  close  approximation  to  the  entoderm  (Fig.  157).  The  superficial 
cells  of  the  clusters  are  then  transformed  into  flat  cells  placed  edge  to  edge 
to  form  the  endothelial  wall  of  a  primitive  blood  space.  These  blood 
spaces  join  one  another  and  thus  form  a  net-work  of  channels.  From  this 
point  in  development  the  two  views  diverge. 

The  evidence  adduced  in  favor  of  either  theory  is  too  great  in  volume 
to  set  down  here.  The  advocates  of  the  theory  of  sprouting  of  the  endo- 
thelium lay  stress  upon  the  evidence  of  injected  specimens.  By  injecting 
developing  blood  vessels  at  successive  stages  it  is  found  that  the  vascular 
field  gradually  becomes  larger,  and  the  inference  is  that  the  individual 
channels  are  extending  farther  and  farther  from  the  focus  of  origin  through 


194  TEXT-BOOK  OF  EMBRYOLOGY. 

proliferation  and  migration  of  the  endothelial  elements.  This  method,  of 
course,  would  demonstrate  vessels  only  so  far  as  the  lumina  are  continuous. 
Solid  cords  of  cells  which  extend  beyond  the  field  of  injection  are  interpreted 
as  cords  of  endothelial  cells  which  subsequently  acquire  lumina  and  become 
capillary  tubes.  If  this  theory  is  correct  then  the  vascularization  of  the 
area  pellucida  and  of  the  embryonic  body  would  be  effected  through  true 
outgrowths  of  the  original  endothelium  of  the  opaque  area.  Possible 
exceptions  to  this,  as  noted  above,  are  the  rudiments  of  the  heart,  the  aorta 
and  the  cardinal  veins  which  arise  in  situ  as  do  the  first  vascular  rudiments. 
Observations  upon  growing  vessels  in  living  embryos,  in  which  strands 
of  cells  were  seen  to  extend  from  the  endothelium  already  present,  have 
also  been  accepted  as  evidence  in  favor  of  this  view. 

The  evidence  afforded  by  injected  specimens  has  been  attacked  by  those 
who  believe  in  the  in  situ  origin  of  vessels,  on  the  ground  that  the  injection 
shows  only  vessels  with  continuous  lumina  and  does  not  prove  the  non- 
existence  of  isolated  vascular  rudiments  beyond  the  field  of  injection.  It  is 
claimed  that  the  vascular  field  becomes  more  extensive  through  the  gradual 
addition  of  such  isolated  spaces  to  the  channels  already  continuous,  in  the 
same  manner  that  the  primitive  blood  spaces  unite  to  form  a  network,  and 
the  claim  is  supported  by  demonstration  of  these  spaces  in  the  mesenchymal 
tissue  with  every  gradation  between  the  bordering  flattened  cells  (endo- 
thelium) and  the  branching  irregular  mesenchymal  cells.  The  actual 
formation  of  intercellular  spaces  with  flat  bordering  cells  and  their  union 
with  vascular  channels  have  been  observed  in  the  living  chick  blastoderm. 
Experimental  evidence  has  also  been  brought  to  bear  in  favor  of  the  view 
that  vessels  arise  in  situ.  The  area  opaca  was  entirely  removed  from  the 
chick  blastoderm  before  any  vascular  rudiments  had  appeared  in  the  area 
pellucida  and  the  blastoderm  was  then  allowed  to  develop  further;  it  was 
found  that  vascular  rudiments  appeared  both  in  the  area  pellucida  and 
embryonic  body  with  practically  the  same  disposition  as  in  the  normal 
embryo. 

The  concept  that  the  vascular  channels  are  structural  expressions  of  the 
functional  necessity  of  carrying  nutritive  materials  to  the  tissues  and  waste 
products  away  from  them  leads  to  consideration  of  such  factors  as  may  be 
involved  in  the  formation  of  vessels;  that  is,  factors  that  would  cause  plastic 
cells,  like  those  of  the  mesenchyme  in  which  the  earliest  and  simplest  vessels 
appear,  to  change  in  character  and  rearrange  themselves  to  form  capillary 
tubes.  In  a  mass  of  mesenchymal  tissue,  in  which  there  is  a  resemblance 
to  a  sponge  with  the  cellular  elements  representing  the  parenchyma  of  the 
sponge  and  the  intercellular  tissue  spaces  the  interstices,  the  products  of 
cell  activity  naturally  accumulate  in  the  intercellular  spaces.  Incident 


THE  DEVELOPMENT  OF  THE  VASCULAR  SYSTEM.  195 

to  this  accumulation,  pressure  would  be  exerted  upon  the  cells  bordering 
the  spaces.  Seeking  outlet  from  the  confines  of  the  spaces,  the  waste 
products  would  move,  or  flow,  and  cause  friction  against  the  cells  past 
which  they  flow.  Similarly,  pressure  and  friction  would  result  from  the 
movement  of  nutritive  materials  to  and  through  the  tissue.  The  plastic 
mesenchymal  cells,  reacting  to  these  mechanical  influences,  would  tend  to 
become  flat,  and  the  continued  operatic  of  the  factors  would  result  in  a 
smooth- walled  tube  in  which  the  movement  of  fluid  is  greatly  facilitated. 

The  reaction  of  the  irregular  mesenchymal  cells  to  the  mechanical  in- 
fluences of  pressure  and  friction  is,  of  course,  the  crux  of  the  question.  It 
has  been  shown  experimentally  that  cells  of  this  type  do  react  to  mechanical 
stimuli.  Smooth  non-irritating  foreign  bodies  have  been  imbedded  in  the 
loose  connective  tissue  of  an  animal  and  the  cells  in  contact  therewith  be- 
came flat  and  formed  a  mosaic  apparently  identical  with  simple  squamous 
epithelium  or  endothelium.  In  the  growth  of  mesenchymal  tissue  outside 
of  the  body  (in  vitro)  it  has  been  observed  that  the  cells  flatten  against 
foreign  substances  which  may  be  present. 

In  the  embryo  it  has  been  observed  that  where  blood  vessels  disappear, 
which  they  do  in  certain  regions,  the  endothelium  does  not  degenerate  but 
that  the  cells  assume  irregular  branching  forms.  This  would  indicate  that 
endothelium  comprises  merely  modified  mesenchymal  cells  and  that  upon 
removal  of  the  factors  incident  to  the  pressure  and  friction  of  blood  flow 
the  cells  reassume  the  indifferent  character  of  mesenchyme,  thus  reverting 
to  the  mesenchymal  type.  It  militates,  therefore,  against  the  view  that 
endothelium  is  a  specific  tissue. 

It  is  generally  recognized,  whether  or  not  the  endothelium  originates 
in  situ,  that  a  capillary  network  precedes  the  formation  of  larger  vessels. 
For  instance,  the  vitelline  plexus  of  capillaries  (p.  186)  antedates  any  of  the 
larger  vitelline  vessels  which  later  carry  blood  to  and  from  the  embryo. 
The  establishment  of  vascular  trunks  in  this  plexus  of  small  vessels  seems  to 
be  dependent  upon  the  same  mechanical  factors  that  were  considered  as 
operative  in  the  origin  of  vessels;  viz.:  pressure  and  friction.  If  the  volume 
of  blood  that  flows  through  a  given  capillary  network  at  a  given  rate  is  in- 
creased the  flow  will  naturally  follow  the  channels  that  offer  the  least  re- 
sistance, and  these  channels  will  increase  in  size  sufficiently  to  accommodate 
the  greater  volume.  A  few  channels,  or  perhaps  even  only  one,  will  form  the 
most  direct  course,  and  the  angles  in  the  course  will  be  still  further  reduced 
as  the  blood  stream  impinges  upon  the  walls  of  the  vessels.  In  this  manner 
a  large  vessel,  or  main  vascular  trunk,  is  established  and  the  remaining 
smaller  vessels  constitute  its  branches  or  tributaries.  A  rather  crude  analogy 
would  be  the  draining  of  a  swamp  in  which  a  small  rivulet,  once  gaming 


196  TEXT-BOOK  OF  EMBRYOLOGY. 

slight  supremacy  over  its  fellows,  would  gradually  cut  its  way  deeper  into 
the  soil  and  pursue  a  straighter  course,  with  the  result  that  the  other  rivulets 
would  flow  into  it  as  the  main  channel. 

The  concept  that  the  main  vascular  trunks  are  preceded  by  a  capillary 
plexus,  out  of  which  they  develop  in  response  to  certain  mechanical  stimuli, 
offers  a  simple  explanation  of  the  numerous  variations  found  in  the  vascular 
system.  In  the  incipient  stages  of  the  larger  vessels  but  slight  influences, 
due  to  variations  in  the  development  of  surrounding  structures,  would  be 
sufficient  to  deflect  their  courses  and  cause  them  to  occupy  positions  which 
do  not  accord  with  the  normal.  So  far  as  the  thickened  walls  of  the  larger 
vascular  channels  are  concerned,  they  may  be  regarded  as  structural  adapta- 
tions to  the  functions  they  perform.  For  example,  the  large  amount  of 
elastic  tissue  in  the  wall  of  the  aorta  and  other  large  arteries  tends  to  main- 
tain a  uniform  diameter  in  these  vessels  against  the  force  exerted  by  the 
blood  expelled  from  the  heart  at  each  contraction. 

The  Heart. — The  heart  has  a  peculiar  origin  in  that  it  arises  as  two  sep- 
arate parts  or  anlagen  which  unite  secondarily.  In  the  chick,  for  example, 
it  appears  during  the  first  day  of  incubation,  at  a  time  when  the  germ  layers 
are  still  flat.  The  ccelom  in  the  cephalic  region  becomes  dilated  to  form  the 
so-called  primitive  pericardial  cavity  (parietal  cavity),  and  at  the  same  time 
a  space  appears  on  each  side,  not  far  from  the  medial  line,  in  the  mesodermal 
layer  of  the  splanchnopleure  (Fig.  165).  These  spaces  at  first  are  filled  with 
a  gelatinous  substance  in  which  lie  a  few  isolated  cells.  These  cells  then 
take  on  the  appearance  of  endothelium  and  line  the  cavities,  and  the  meso- 
thelium  in  this  vicinity  is  changed  into  a  distinct,  thickened  layer  of  cells. 
Now  by  a  bending  ventrally  of  the  splanchnopleure  the  cavities  or  vessels 
are  carried  toward  the  mid  ventral  line  (Fig.  165).  The  bending  continues 
until  the  entoderm  of  each  side  meets  and  fuses  with  that  of  the  opposite 
side,  thus  closing  in  a  flat  cavity — the  fore-gut.  The  entoderm  ventral 
to  the  cavity  breaks  away  and  allows  the  medial  walls  of  the  two  endothelial 
tubes  to  come  in  contact.  These  walls  then  break  away  and  the  tubes  are 
united  in  the  midventral  line  to  form  a  single  tube  (Fig.  165),  which  extends 
longitudinally  for  some  distance  in  the  cervical  region  of  the  embryo.  The 
mesothelial  layers  of  opposite  sides  meet  dorsal  and  ventral  to  the  endo- 
thelial tube,  forming  the  dorsal  and  ventral  mesocardium  (Fig.  165).  In 
the  meantime  the  cephalic  end  of  the  tube  has  united  with  the  arterial  system, 
and  the  caudal  end  with  the  venous  system ;  and  in  a  short  time  the  dorsal 
and  ventral  mesocardia  disappear  and  leave  the  heart  suspended  by  its 
two  ends  in  the  primitive  pericardial  cavity.  The  conditions  at  this  point 
may  be  summarized  thus:  The  heart  is  a  double-walled  tube— the  inner  wall 
composed  of  endothelium  and  destined  to  become  the  endocardium,  the 


THE  DEVELOPMENT  OF  THE  VASCULAR  SYSTEM. 


197 


outer  wall  of  a  thicker  mesothelial  layer  and  destined  to  become  the  myo- 
cardium— the   two  walls  separated  by  a  considerable   space.     The  organ 
hangs,  as  it  were,  in  the  primitive  pericardial  cavity  (ccelom),  connected 
V 


Dors,  tnesocardivm 

card  cum 
t  hell  urn) 


fieri  ca.  ret. 
Cavity 


'EqdocardLury 
(Eydotfyetiury) 

FIG.  165. — Diagrams  showing  the  two  anlagen  of  the  heart  and  their  union  to  form  a  single 
structure;  made  from  camera  lucida  tracings  of  transverse  sections  of  chick  embryos. 
In  C  the  ventral  mesocardium  has  disappeared  (see  text). 

at  its  cephalic  end  with  the  ventral  aortic  trunk  and  at  its  caudal  end  with 
the  omphalomesenteric  veins. 

In  all  U.ammals  thus  far  studied  the  principle  of  development  in  the 
earlier  stages  is  essentially  the  same  as  in  the  chick.  The  double  origin 
of  the  heart  is  even  more  marked  because  of  the  relatively  late  closure,  of 


198 


TEXT-BOOK  OF  EMBRYOLOGY. 


the  fore-gut.     There  are  no  observations  on  the  origin  of  the  heart  in  human 
embryos,  but  it  is  reasonable  to  assume  that  it  has  the  same  double  origin 


Dorsal  aortic  root 


Gut  (pharynx) 


'ericardial 
cavity  (coelom) 


Endocardium 
(endothelium) 


Myocardium 


FIG.  166. — Transverse  section  of  a  human  embryo  of  2.69  mm.     von  Spee,  Kollmann's  Atlas. 


Oral  fossa 

Ventral  aortic 
trunk 


Ventricle 


Ant.  cardinal  vein 
Duct  of  Cuvier 
Umbilical  vein 


Ventricle 

Atrium 

Diaphragm 

Duct  of  Cuvier 

— -Liver 
"        -»Duct  of  liver 


FIG.  167. — Ventral  view  of  reconstruction  of  human  embryo  of  2.15  mm.     His. 

The  ventral  body  wall  has  been  removed.     The  vessels  (in  black)  at  the  sides  of  the  duct 

of  the  liver  are  the  omphalomesenteric  veins. 

as  in  other  Mammals,  although  in  embryos  of  2  to  3  mm.  the  organ  has 
already  become  a  single  tube  (Figs.  166  and  167).  At  this  stage  the  tube  is 
somewhat  coiled. 


THE  DEVP:LOPMENT  OF  THE  VASCULAR  SYSTEM. 


199 


While  the  double  origin  of  the  heart  is  characteristic  of  all  amniotic  Vertebrates 
(Reptiles,  Birds,  Mammals),  in  all  the  lower  forms  the  organ  arises  as  a  single  anlage.  In 
the  region  of  the  fore-gut  the  two  halves  of  the  ccelom  are  separated  by  a  ventral  mesentery 
which  extends  from  the  gut  to  the  ventral  body  wall,  and  which  is  composed  of  two  layers 
of  mesothelium  with  a  small  amount  of  mesenchyme  between  them.  In  the  mesenchyme 
a  cavity  appears  and  is  lined  by  a  single  layer  of  flat  (endothelial)  cells.  This  cavity 
extends  longitudinally  for  some  distance  in  the  cervical  region  and  with  its  endothelial 
and  mesothelial  walls  constitutes  the  simple  cylindrical  heart.  On  the  dorsal  side  it  is 
connected  with  the  gut  by  a  portion  of  the  mesentery  which  is  called  the  dorsal  meso- 
cardium;  on  the  ventral  side  it  is  connected  with  the  ventral  body  wall  by  the  ventral 
mesocardium  (Fig.  168).  Thus  the  heart  is  primarily  a  single  structure.  The  difference 
between  the  two  types  of  development  is  not  a  fundamental  one  but  simply  depends  upon 
the  difference  in  the  germ  layers.  In  the  lower  forms  the  germ  layers  are  closed  in  ven- 


Entoderm 
Mesoderm  (visceral) 


Heart 

Pericard.  cavity 
(coelom) 


Dorsal  mesocardium 

Endothelium 
'Mesoderm  (parietal) 
Ventral  mesocardium 
Ectoderm 


FIG.  1 68. — Ventral  part  of  transverse  section  through  the  heart  region  of  Salamandra 
maculosa  embryo  with  4  branchial  arches.     Rabl. 

trally  from  the  beginning,  and  the  heart  appears  in  a  medial  position.  In  the  higher 
forms  the  germ  layers  for  a  time  remain  spread  out  upon  the  surface  of  the  yolk  or  yolk 
sac,  and  the  heart  begins  to  develop  before  they  close  in  on  the  ventral  side  of  the  embryo. 
Consequently  the  heart  arises  in  two  parts  which  are  carried  ventrally  by  the  germ  layers 
and  unite  secondarily. 

The  further  development  of  the  heart  consists  of  various  changes  in  the 
shape  of  the  tube  and  in  the  structure  of  its  walls.  At  the  same  time  the  dila- 
tation of  the  ccelom  (primitive  pericardial  cavity)  in  the  cervical  region  is  of 
importance  in  affording  room  for  the  heart  to  grow.  In  the  chick,  for  ex- 
ample, the  tube  begins,  toward  the  end  of  the  first  day  of  incubation,  to 
bend  to  the  right;  during  the  second  day  it  continues  to  bend  and  assumes 
an  irregular  S-shape.  This  bending  process  has  not  been  observed  in 
human  embryos,  but  other  Mammals  show  the  same  process  as  the  chick. 
In  a  human  embryo  of  2.15  mm.  the  S-shaped  heart  is  present  (Fig.  167). 
The  venous  end,  into  which  the  omphalomesenteric  veins  open,  is  situated 
somewhat  to  the  left,  extends  cranially  a  snort  distance  and  then  passes 
over  into  the  ventricular  portion.  The  latter  turns  ventrally  and  extends 
obliquely  across  to  the  right  side,  then  bends  dorsally  and  cranially  to  join 
the  aortic  bjulb  which  in  turn  joins  the  ventral  aortic  trunk  in  the  medial 

- 


200  TEXT-BOOK  OF  EMBRYOLOGY. 

line.  The  endothelial  tube,  which  is  still  separated  from  the  muscular  wall 
by  a  considerable  space,  becomes  somewhat  constricted  at  its  junction  with 
the  aortic  bulb  to  form  the  so-called  f return  Halleri.  During  these  changes 
the  heart  as  a  whole  increases  in  diameter,  especially  the  ventricular  portion. 
Gradually  the  venous  end  of  the  heart  moves  cranially  and  in  embryos  of 


Vent,  aortic  trunk 


Ventricular 
portion 


FIG.  169. — Ventral  view  heart  of  human  embryo  of  4.2  mm.     His. 
The  atria  are  hidden  behind  the  ventricular  portion. 

4.2  mm.  lies  in  the  same  transverse  plane  as  the  ventricular  portion.  The 
latter  lies  transversely  across  the  body  (Fig.  169).  At  the  same  time  two 
e vagina tions  appear  on  the  venous  end,  which  represent  the  anlagen  of  the 
atria.  In  embryos  of  about  5  mm.  further  changes  have  occurred,  which  are 
represented  in  Fig.  170.  The  two  atrial  anlagen  are  larger  than  in  the 


Right  atrium  1 1;  j>  fflSML'' til  ,  Left  atrium 


Right  ventricle    if  './«•  Left  ventricle 


Interventricular  furrow 
FIG.  170. — Ventral  view  of  heart  of  human  embryo  of  5  mm.     His. 

preceding  stage  and  surround,  to  a  certain  extent,  the  proximal  end  of  the 
aortic  trunk.  As  they  enlarge  still  more  in  later  stages,  they  come  in  con- 
tact, their  medial  walls  almost  entirely  disappear,  and  they  form  a  single 
chamber.  The  ventricular  portion  of  the  heart  becomes  separated  into  a 
right  and  a  left  part  by  the  interventricular  furrow  (Fig.  1 70) ;  the  right  part 


THE  DEVELOPMENT  OF  THE  VASCULAR  SYSTEM. 


201 


is  the  anlage  of  the  right  ventricle,  the  left  part,  of  the  left  ventricle.  At  the 
same  time  the  atrial  portion  has  moved  still  farther  cranially  so  that  it  lies 
to  the  cranial  side  of  the  ventricular  portion.  The  venous  and  arterial 
ends  of  the  heart  have  thus  reversed  their  original  relative  positions.  At 
this  point  it  should  be  noted  that  the  atrial  end  of  the  heart  is  connected 
with  the  large  venous  trunk  formed  by  the  union  of  the  omphalomesenteric 
veins  and  the  ducts  of  Cuvier — the  sinus  venosus. 

During  the  changes  in  the  heart  as  a  whole,  certain  changes  also  occur  in 
the  endothelial  and  muscular  walls.  The  walls  of  the  atria  are  composed 
of  compact  plates  of  muscle  with  the  endothelium  closely  investing  the  inner 
surface.  The  walls  of  the  ventricular  portion,  on  the  other  hand,  become 
thicker  and  are  composed  of  an  outer  compact  layer  of  muscle  and  an  inner 
layer  made  up  of  trabeculae  which  are  closely  invested  by  the  endothelium. 


Septum  spurium 

Atrial  septum 
(septum  superius) 

Opening  of  sinus  venosus 


Right  atrium 
Left  atrium 
Atrio-ventricular  canal 


Right  ventricle 
Ventricular  septum 
Left  ventricle 


FIG.   171. — Dorsal  half  of  heart  (seen  from  ventral  side)  of  a  human  embryo  of  10  mm.     His. 


Everywhere  the  endothelium  is  closely  applied  to  the  inner  surface  of  the 
myocardium,  the  space  which  originally  existed  between  the  endothelium 
and  mesothelium  being  obliterated. 

The  embryonic  heart  in  Mammals  in  the  earlier  stages  resembles  that  of  the  adult  in 
the  lower  Vertebrates  (Fishes).  The  atrial  portion  receives  the  blood  from  the  body  veins 
and  conveys  it  to  the  ventricular  portion  which  in  turn  sends  it  out  through  the  arteries 
to  the  body.  The  circulation  is  a  single  one.  This  condition  changes  during  the  foetal 
life  of  Mammals  with  the  development  of  the  lungs.  The  same  transition  occurs  in  the 
ascending  scale  of  development  in  the  vertebrate  series  in  those  forms  in  which  gill  breath- 
ing is  replaced  by  lung  breathing.  The  change  consists  of  a  division  of  the  heart  and 
circulation,  so  that  the  single  circulation  becomes  a  double  circulation.  In  other  words, 
the  heart,  is  so  divided  that  the  lung  (pulmonary)  circulation  is  separated  from  the 
general  circulation  of  the  body.  This  division  first  appears  in  the  Dipnoi  (Lung  Fishes) 
and  Amphibians  in  which  gill  breathing  stops  and  lung  breathing  begins,  although  here 


202 


TEXT-BOOK  OF  EMBRYOLOGY. 


the  division  is  not  complete.      In  Reptiles  the  division  is  complete  except  for  a  small 
direct  communication  between  the  ventricles. 

Fig.  171  represents  the  dorsal  half  of  the  heart  at  a  stage  when  all  the 
chambers  are  in  open  communication,  and  shows  the  conditions  in  a  single 
circulation  but  with  the  beginning  of  a  separation.  The  atria  are  rather 
thin-walled  chambers,  the  ventricles  have  relatively  thick  walls.  Between 
the  atrial  and  ventricular  portion  is  a  canal — the  atrio-ventricular  canal— 
which  affords  a  free  passage  for  the  blood.  From  the  cephalic  side  of  the 
atrial  portion  a  ridge  projects  into  the  cavity.  This  ridge  represents  a 
remnant  of  the  original  medial  walls  of  the  two  atria  and  marks  the  begin- 
ning of  the  future  atrial  septum.  The  opening  of  the  sinus  venosus  is  seen 
on  the  dorsal  wall  of  the  right  atrium.  Primarily  both  atria  communicated 


Septum  superius  :" 
Sinus  venosus  — 


Valvulae  venosae  ... 

Right  atrium   -- 

Right  ventricle  • 

Ventricular  septum  ,. 


Foramen  ovale 

•  Atrial  septum 

; —   Left  atrium 

Atrio-ventricular  valves 

.  _  Atrio-ventricular  canals 
—  Left  ventricle 


FIG.  172. — Dorsal  half  of  heart  showing  chambers  and  septa.     (Semidiagrammatic.) 

Modified  from  Born. 

directly  with  the  sinus  venosus,but  in  the  course  of  development  the  open- 
ing of  the  latter  migrated  to  the  right  and  at  this  stage  is  found  in  the  wall 
of  the  right  atrium.  The  opening  is  guarded,  as  it  were,  by  a  lateral  and  a 
medial  fold  the  significance  of  which  will  be  described  later.  The  vetricular 
portion  also  shows  a  ridge  projecting  from  the  caudal  side,  which  corresponds 
to  the  interventricular  groove  and  represents  the  beginning  of  the  ventricular 
septum. 

The  Septa. — The  further  changes  are  largely  concerned  with  the  separa- 
tion of  the  heart  into  right  and  left  sides,  and  with  the  development  of  the 
valves.  The  atria  become  separated  by  the  further  growth  on  the  cephalic 
side,  of  the  ridge  which  has  already  been  mentioned  and  which  is  known  as 
the  septum  superius  (Figs.  171  and  172).  This  septum  grows  across  the 
cavity  of  the  atria  until  it  almost  reaches  the  atrio-ventricular  canal,  form- 
ing the  septum  atriorum.  A  portion  of  the  septum  then  breaks  away,  leav- 
ing the  two  atria  still  in  communication.  This  secondary  opening  is  the 


THE  DEVELOPMEN1  OF  THE  VASCULAR  SYSTEM. 


203 


foramen  ovale  which  persists  throughout  foetal  life,  but  closes  soon  after 
birth.     The  atrio-ventricular  canal  also  becomes  divided  into  two  passages 


Sinus  venosus 


Left  valvula  venosa 


Right  valvula  venosa 


Right  ventricle 


Right  atrio- 5 

ventricular  canal 


Right  ventricle 


Atrial  septum 

Pulmonary  vein 


—  Left  atrium 


Left  atrio- 
ventricular  canal 


Left  ventricle 


I  \ 

Interventricular  furrow  Ventricular  septum 

FIG.  173. — Dorsal  half  of  heart  (ventral  view)  of  rabbit  embryo  of  5.8  mm.     Born. 

by  a  ridge  from  the  dorsal  wall  and  one  from  the  ventral  wall  uniting  with 
each  other  and  finally  with  the  septum  atriorum  (Fig.  172).  Thus  the  two 
atria  would  be  completely  separated  if  it  were  not  for  the  foramen  ovale. 


Aortic  septum 


Interventricular  opening /_ 


Right  atrio-ventricu-       (. 
lar  orifice  "  ~~i 


Right  ventricle  -  ~c 
.•*?;/-.  \ 

'] 

Ventricular  septum  *-- 


Pulmonary  artery 


-  Aorta 


_.  Left  atrio-ventricular  orifice 


*>•»-  -  Left  ventricle 


FIG.  174. — Ventricles  and  proximal  ends  of  aorta  and  pulmonary  artery  of  a  7.5  mm.   human 
embryo.    Lower  walls  of  ventricles  have  been  removed.     Kollmann's  Atlas. 

During  the  separation  of  the  atria,  a  division  of  the  ventricular  portion 
of  the  heart  also  occurs.     On  the  caudal  side  of  the  ventricular  portion  a 


204  TEXT-BOOK  OF  EMBRYOLOGY. 

septum  appears  and  gradually  grows  across  the  cavity  forming  the  septum 
ventriculorum  (Figs.  171  and  172).  This  septum  is  situated  nearer  the  right 
side  and  is  indicated  on  the  outer  surface  by  a  groove  which  becomes  the 
sulcus  longitudinalis  anterior  and  posterior.  The  dorsal  edge  of  this  septum 
finally  fuses  with  the  septum  dividing  the  atrio-ventricular  canal,  but  for  a 
time  its  ventral  edge  remains  free,  leaving  an  opening  between  the  two 
ventricles  (Figs.  173  and  174). 

This  opening  then  becomes  closed  in  connection  with  the  division  of  the 
aortic  bulb  and  ventral  aortic  trunk.  On  the  inner  surface  of  the  aortic 
trunk,  at  a  point  where  the  branches  which  form  the  pulmonary  arteries 
arise,  two  ridges  appear,  grow  across  the  lumen  and  fuse  with  each  other, 
thus  dividing  the  vessel  into  two  channels.  This  partition — the  septum 
aorticum  (Fig.  175) — gradually  grows  toward  the  heart  through  the  aortic 
bulb  and  finally  unites  with  the  ventral  edge  of  the  ventricular  septum,  thus 
closing  the  opening  between  the  two  ventricles.  Corresponding  with  the 


FIG.  175. — Diagrams  representing  the  division  of  the  ventral  aortic  trunk  into  aorta  and 
pulmonary  artery  and  the  development  of  the  semilunar  valves.     Hochsietter. 

edges  of  the  septum  aorticum,  a  groove  appears  on  each  side  of  the  aortic 
trunk  and  gradually  grows  deeper  and  extends  toward  the  heart,  until  finally 
the  trunk  and  aortic  bulb  are  split  longitudinally  into  two  distinct  vessels, 
one  of  which  is  connected  with  the  right  ventricle  and  becomes  the  pulmonary 
artery,  the  other  with  the  left  ventricle  and  becomes  the  proximal  part  of  the 
aortic  arch  (Fig.  174).  The  result  of  the  formation  of  these  various  septa  is 
the  division  of  the  entire  heart  into  two  sides.  The  atrium  and  ventricle 
of  each  side  are  in  communication  through  the  atrio- ventricular  foramen,  the 
two  sides  are  in  communication  only  by  the  foramen  ovale  which  is  but  a 
temporary  opening. 

After  the  opening  of  the  sinus  venosus  is  shifted  to  the  right  atrium,  the 
left  atrium  for  a  short  period  has  no  vessels  opening  into  it.  As  soon,  how- 
ever, as  the  pulmonary  veins  develop,  they  form  a  permanent  union  with  the 
left  atrium  (Fig.  173).  At  first  two  veins  arise  from  each  lung,  which  unite 
to  form  a  single  vessel  on  each  side;  the  two  single  vessels  then  unite  to  form 
a  common  trunk  which  opens  into  the  left  atrium  on  the  cephalic  side.  As 


THE  DEVELOPMENT  OF  THE  VASCULAR  SYSTEM.  205 

development  proceeds,  the  wall  of  the  single  trunk  is  gradually  absorbed  in 
the  wall  of  the  atrium,  until  the  single  vessel  from  each  side  opens  separately. 
Absorption  continuing,  all  four  veins,  two  from  each  lung  finally  open 
separately.  This  is  the  condition  usually  found  in  the  adult.  A  partial 
failure  in  the  absorption  may  leave  one,  two,  or  three  vessels  opening  into 
the  atrium.  Such  variations  are  not  infrequently  met  with  in  the  pulmonary 
veins. 

The  Valves. — If  all  the  passageways  between  the  different  chambers  of 
the  heart  and  the  large  vascular  trunks  were  to  remain  free  and  clear,  there 
would  be  nothing  to  prevent  the  blood  from  flowing  contrary  to  its  proper 
course.  Consequently  five  sets  of  valves  develop  in  relation  to  these  orifices, 
and  are  so  arranged  that  they  direct  the  blood  in  a  certain  definite  direction. 
These  appear  (a)  at  the  openings  of  the  large  venous  trunks  into  the  right 
atrium,  (b)  at  the  opening  between  the  right  atrium  and  right  ventricle, 
(c)  at  the  opening  between  the  left  atrium  and  left  ventricle,  (d)  at  the 
opening  between  right  ventricle  and  pulmonary  artery  and  (e)  at  the  open- 
ing between  the  left  ventricle  and  aorta.  No  valves  develop  at  the  openings 
of  the  pulmonary  veins  into  the  left  atrium. 

(a)  The  sinus  venosus  (which  is  formed  by  the  union  of  the  large  body 
veins)  opens  into  the  right  atrium  on  its  cranial  side,  as  has  already  been 
mentioned  (p.  201).  By  a  process  of  absorption,  similar  to  that  in  the  case 
of  the  pulmonary  veins,  the  wall  of  the  sinus  is  taken  up  into  the  wall  of  the 
atrium.  The  result  is  that  the  vena  cava  superior,  vena  cava  inferior,  and 
sinus  coronarius  (a  remnant  of  the  left  duct  of  Cuvier)  open  separately  into 
the  atrium.  As  the  sinus  is  absorbed,  its  wall  forms  two  ridges  on  the 
inner  surface  of  the  atrium,  one  situated  at  the  right  of  the  opening  and  one 
at  the  left  (Figs.  172  and  173).  These  two  ridges — valvulce  venosce — are 
united  at  their  cranial  ends  with  the  septum  spurium  (Fig.  171),  a  ridge 
projecting  from  the  cephalic  wall  of  the  atrium.  The  septum  spurium 
probably  has  a  tendency  to  draw  the  two  valves  together  and  prevent  the 
blood  from  flowing  back  into  the  veins.  The  left  valve  and  the  septum 
spurium  later  atrophy  to  a  certain  extent  and  probably  unite  with  the  septum 
atriorum  to  form  part  of  the  limbus  fossce  ovalis  (Vieussenii) .  The  right 
valve  is  the  larger  and  in  addition  to  its  assistance  in  preventing  a  backward 
flow  of  blood  into  the  veins,  it  also  serves  to  direct  the  flow  toward  the 
foramen  o\;ale.  As  the  veins  come  to  open  separately,  the  cephalic  part 
of  the  right  valve  disappears;  the  greater  part  of  the  remainder  becomes 
the  valvula  Deuce  cavce  inferioris  (Eustachii)  and  during  fcetal  life  directs  the 
blood  toward  the  foramen  ovale.  In  the  adult  it  becomes  a  structure  of 
variable  size.  A  small  part  of  the  remainder  of  the  right  valve  forms  the  val- 
vula sinus  coronarii  (Thebesii)  which  guards  the  opening  of  the  coronary  sinus. 


206  TEXT-BOOK  OF   EMBRYOLOGY. 

(b)  and  (c)  The  valves  between  the  atrium  and  ventricle  on  each  side 
develop  for  the  most  part  from  the  walls  of  the  triangular  atrio-ventricular 
opening  (ostium  atrio-ventriculare) .  Elevations  or  folds  appear  on  the  rims 
of  the  openings  and  project  into  the  cavities  of  the  ventricles  where  they 
become  attached  to  the  muscle  trabeculae  of  the  ventricle  walls  (Figs.  176 
and  177).  On  the  right  side  three  of  these  folds  appear,  and  develop  into  the 
valvula  tricuspidalis  which  guards  the  right  atrio-ventricular  orifice.  On 
the  left  side  only  two  folds  appear,  and  these  become  the  valvula  biscuspidalis 
(mitralis)  which  guards  the  left  atrio-ventricular  orifice.  These  valves, 
which  are  at  first  muscular,  soon  change  into  dense  connective  tissue.  The 
muscle  trabeculae  to  which  they  are  attached  also  undergo  marked  changes. 
Some  become  condensed  at  the  ends  which  are  attached  to  the  valves  into 
slender  tendinous  cords — the  chorda  tendinece,  while  at  their  opposite  ends 


Muscle  trabeculae          , 

Trab6co!0  carneae 

FIG.  176. — Diagrams  representing  the  development  of  the  atrio-ventricular  valves,  chordae, 
tendineas,  and  papillary  muscles.     Gegenbaur. 

they  remain  muscular  as  the  Mm.  papillares;  others  remain  muscular  and 
lie  in  transverse  planes  in  the  ventricles,  or  fuse  with  the  more  compact 
part  of  the  muscular  wall,  or  form  irregular,  anastomosing  bands  and  con- 
stitute the  Irabecula  carnea  (Fig.  176). 

(d)  and  (e)  The  valves  of  the  pulmonary  artery  and  aorta  develop  at  the 
point  where  originally  the  endothelial  tube  was  constricted  to  form  the 
f return  Halleri  (p.  200)  where  the  ventricular  portion  of  the  heart  joined 
the  aortic  bulb.  Before  the  aortic  trunk  and  bulb  are  divided  into  the  aortic 
arch  and  pulmonary  artery,  four  protuberances  appear  in  the  lumen  (Fig. 
213).  The  septum  aorticum  then  divides  the  two  which  are  opposite  so  that 
each  vessel  receives  three  (Fig.  175).  These  then  become  concave  on  the 
side  away  from  the  heart,  in  a  manner  which  has  not  been  fully  determined, 
and  at  the  same  time  enlarge  so  that  they  close  the  lumen.  Those  in  the 
pulmonary  artery  are  known  as  the  valvula  semilunares  arteria  pulmonalis, 
those  in  the  aorta  as  the  valvula  semilunares  aorta. 

Changes  after  Birth. — The  migratory  changes  of  the  heart  from  its  origi- 
nal position  in  the  cervical  region  to  its  final  position  in  the  thorax  will  be  con- 


THE  DEVELOPMENT  OF  THE  VASCULAR  SYSTEM. 


207 


sidered  in  connection  with  the  development  of  the  pericardium  (Chap.  XIV). 
With  the  exception  of  the  septum  atriorum,  the  heart  acquires  during  fcetal 
life  practically  the  form  and  structure  characteristic  of  the  adult  (Fig. 
178).  So  long  as  the  individual  continues  to  grow,  the  heart,  generally 
speaking,  increases  in  size  accordingly.  This  increase  takes  place  by  in- 
tussusception in  the  endocardium  and  myocardium.  At  the  time  of  birth 
the  two  atria  are  in  communication  through  the  foramen  ovale  which  is 


Atrial  septum 


Right  atrium 

Right  atrio- 

ventricular 

(tricuspid)  valves 


Right  ventricle 


Ventricular 
septum 


Pericardial  cavity 


Dorsal  aortic  roots 


Amnioo 


Upper  limb  bud 


Left  atrium 


Left  atrio- 
ventricular 
(bicuspid)  valves 


Left  ventricle 


FIG.  177. — Transverse  section  of  pig  embryo  of  14  mm.     Photograph. 

simply  an  orifice  in  the  atrial  septum  (Fig.  179).  Thus  the  blood  which  is 
brought  to  the  right  atrium  by  the  body  veins  is  allowed  to  pass  directly 
into  the  left  atrium,  thence  to  the  left  ventricle,  and  thence  is  forced  out  to 
the  body  again  through  the  aorta.  A  certain  amount  of  blood  also  passes 
from  the  right  atrium  into  the  right  ventricle  and  thence  into  the  pulmonary 
artery;  but  this  blood  does  not  enter  the  lungs  but  passes  directly  into  the 
aorta  through  the  ductus  arteriosus  (Fig.  178).  After  birth  the  lungs  begin 


TEXT-BOOK  OF  EMBRYOLOGY. 


Innominate  artery 

Branches  of  right_  j 
pulmonary  artery"  ~ 

Arch  of  aorta 
Pulmonary  artery-  - 
Right  auricular  appendage — 


Left  carotid  artery 
Left  subclavian  artery 

Ductus  arteriosus 


__         Branches  of  left 
2      7  pulmonary  artery 


-"- Left  auricular  appendage 


—  Left  ventricle 


Right  ventricle  •. —  --S^i^.- -4~; 


Descending  aorta 


FIG.  178. — Ventral  view  of  heart  of  foetus  at  term.     Kollmann's  Atlas. 


Sup.  vena  cava- 


Right  atrium-     •Bj 


Inf.  vena  cava 


Right  ventricle A;  -ffe  V\'jU 


Inf.  vena  cava 


Pulmonary  veins 


Left  atrium 


Left  ventricle 


FIG.  179. — Dorsal  half  of  foetal  heart.     Bumm,  Kollmann's  Atlas. 


THE  DEVELOPMENT  OF  THE  VASCULAR  SYSTEM. 


209 


to  function  and  the  placental  blood  is  cut  off,  so  that  the  right  atrium  receives 
venous  blood  only  and  the  left  arterial  blood  only.  If  the  foramen  ovale  were 
to  persist  it  would  allow  a  mingling  of  venous  and  arterial  blood.  Con- 
sequently the  foramen  ovale  closes  soon  after  birth  and  the  two  currents  of 
blood  are  completely  separated.  At  the  same  time  the  ductus  arteriosus 
atrophies  and  becomes  the  ligamentum  arteriosum.  Consequently  there  is 
no  direct  communication  between  the  pulmonary  artery  and  aorta. 

Certain  features  of  development  have  an  important  bearing  on  the  theories  regarding 
the  physiology  of  the  heart,  particularly  on  the  theory  that  the  heart  is  an  automatic 
organ.  Whether  the  theory  that  the  heart  beats  automatically,  i.e.,  independently  of 
stimuli  from  the  nervous  system,  is  true  or  not,  it  is  a  fact  that  in  the  embryo  it  begins  to 
beat  before  any  nerve  cells  appear  in  it  and  before  any  nerve  fibers  are  connected  with  it. 
At  least  no  technic  has  yet  been  devised  by  which  it  is  possible  to  demonstrate  nerve  cells 
in,  or  fibers  connected  with  it,  at  the  time  when  it  begins  to  perform  its  characteristic 
function.  And,  furthermore,  at  the  time  when  the  heart  begins  to  beat,  no  heart  muscle 
cells  are  developed.  This  last  fact  seems  to  indicate  an  inherent  contractility  in  the 
mesothelial  cells  which  form  the  anlage  of  the  myocardium. 

The  Arteries. — The  simplest  condition  of  the  arterial  system,  following 
the  establishment  of  the  vitelline  and  allantoic  circulation  (p.  189  and  p. 


Dors,  aortic  root 


Vent,  aortic  root 


Vent,  aortic  trunk 


Dors,  aortic  root 


— • —  (Esophagus 

Trachea 

Pulmonary  artery 

FIG.   180. — From  reconstruction  of  aortic  arches  (i,  2,  3,  4,  6)  of  left  side  and  pharynx 

ot  a  5  mm.  human  embryo.     Tandler. 

I-IV,  Inner  branchial  grooves. 

191),  is  as  follows:  The  single  ventral  aortic  trunk  is  given  off  from  the 
cephalic  end  of  the  heart.  This  is  a  short  vessel,  soon  dividing  into  the 
two  vejntral  aortic  roots  which  pass  forward  beneath  the  pharynx  (Fig.  180). 
Each  ventral  aortic  root  gives  rise  to  branches  which  pass  dorsally,  one  in 
each  branchial  arch,  as  the  aortic  arches  to  unite  in  a  common  stem  along 
the  dorsal  wall  of  the  pharynx.  This  common  stem  is  the  dorsal  aortic 
root  (Fig.  1 80)  which  fuses  with  its  fellow  of  the  opposite  side  in  the  mid- 
dorsal  line  to  form  the  dorsal  aorta.  The  single  dorsal  aorta,  situated 
ventral  to  the  notochord,  extends  from  the  cervical  region  to  the  caudal 
end  of  the  embryo.  Somewhat  caudal  to  the  middle  of  the  embryo  a  branch 


to- 


210 


TEXT-BOOK  OF  EMBRYOLOGY. 


of  the  aorta  passes  ventrally  through  the  mesentery  as  the  vitelline  artery 
which  enters  the  umbilical  cord  (Fig.  164).  Still  farther  caudally  the 
paired  umbilical  (allantoic)  arteries  are  given  off  from  the  aorta  and  pass 
out  into  the  umbilical  cord  (Fig.  164). 

The  conditions  which  exist  at  this  stage  in  the  region  of  the  aortic  arches 
in  mammalian  embryos  are  indicative  of  the  conditions  which  persist  as  a 
whole  or  in  part  throughout  life  in  the  lowest  Vertebrates.  The  changes 
which  occur  in  Mammals,  however,  are  profound  and  the  adult  condition 
bears  no  resemblance  to  the  embryonic.  Yet  certain  features  in  the  adult 
are  intelligible  only  from  a  knowledge  of  their  development.  In  the  human 


Vent,  aortic  roots 


Subclavian  arteries 


Aorta 


FIG.  181. — Diagram  of  the  aortic  arches  of  a  Mammal.     Modified  from  Hochstetter. 

embryo  ,§ix  aortic  arches  appear  on  each  side.  The  first,  second,  third,  and 
fourth  pass  through  the  corresponding  branchial  arches.  The  fifth  arch, 
which  is  merely  a  loop  from  the  fourth,  seems  to  pass  through  the  fourth 
branchial  arch.  The  sixth  aortic  arch  passes  through  the  region  behind 
the  fourth  branchial.  All  these  arches  are  present  in  embryos  of  5  mm. 
(Fig.  180).  In  Fishes  and  larval  Amphibians,  where  the  branchial  arches 
develop  into  the  gills,  the  aortic  arches  are  broken  up  into  capillary  net- 
works which  ramify  in  the  gills,  and  the  ventral  aortic  root  becomes  the 
afferent  vessel,  the  dorsal  aortic  roots  the  efferent  vessels.  In  the  higher 
Vertebrates  and  in  man  the  aortic  arches  begin,  at  a  very  early  period,  to 


ef- 


THE  DEVELOPMENT  OF  THE  VASCULAR  SYSTEM. 


211 


undergo  changes;  some  disappear  and  others  become  portions  of  the  large 
arterial  trunks  which  leave  the  heart.  In  connection  with  the  following 
description,  constant  reference  to  Figs.  181  and  182  will  assist  the  student  in 
understanding  <he  changes. 

The  first  and  second  arches  soon  atrophy  and  disappear.  The  third 
arch  on  each  side  becomes  the  proximal  part  of  the  internal  carotid  artery, 
while  the  continuation  of  the  dorsal  aortic  root,  cranially  to  the  third  arch, 
becomes  its  more  distal  part.  The  continuation  of  the  ventral  a,ortic  root 
cranially  to  jthe_third,  jirch,  becomes  L  the  proximal 


Common  carotid  arteries 


Int.  carotid  artery  (right) 


Ext.  carotid  artery  (right) 


Int.  carotid  III 

Subclavian  IV 

V 

VI 

Innominate  artery 


Subclavian  artery  (right) 


Int.  carotid  artery  (left) 
Ext.  carotid  artery  (left) 


II 

III  Int.  carotid 

IV  Arch  of  aorta 
V 

VI  Ductus  arteriosus 

Pulmonary  artery 
Subclavian  artery  (left) 
Aorta 


FTG.  182. — Diagram  representing  the  changes  in  the  aortic  arches  of  a  Mammal. 
Compare  with  Fig.  181.    Modified  from  Hochstetter. 

artery,  while  the  portion  of  the  ventral  aortic  root  between  the  third  and 
fourth  arches  becomes  the  common  carotid  artery.  The  portion  of  the  dorsal 
aortic  root  between  the  third  and  fourth  arches  disappears.  The  fourth 
aortic  arch  on  the  left  side  enlarges  and  becomes  the  arch  of  the  aorta  (arcus 
aorta)  which  is  then  continued  caudally  through  the  left  dorsal  aortic  root 
into  the  dorsal  aorta.  On  the  right  side,  the  fourth  arch  becomes  the  proxi- 
mal part  of  the  subclavian  artery.  Since  the  third,  foutth,  fifth,  and  'sixth 
arches  really  leave  the  ventral  aortic  trunk  as  a  single  vessel,  it  will  be  seen 
that  these  changes  bring  it  about  that  the  common  carotid  and  subclavian 


212 


TEXT-BOOK  OF  EMBRYOLOGY. 


on  the  right  side  arise  by  a  common  stem,  the  innominate  artery,  which  in 
turn  is  a  branch  of  the  arch  of  the  aorta.  On  the  left  side,  for  the  same 
reason,  the  common  carotid  is  a  branch  of  the  arch  of  the  aorta.  The  fifth 
aortic  arch  from  the  beginning  is  rudimentary  and  disappears  very  early. 
The  sixth  arch  on  each  side  undergoes  wide  changes.  A  branch  from  each 
enters  the  corresponding  lung.  On  the  right  side  the  portion  of  the  sixth 
arch  between  the  branch  which  enters  the  lung  and  the  dorsal  aortic  root 
disappears,  as  does  also  that  portion  of  the  right  dorsal  aortic  root  between 
the  subclavian  artery  and  the  original  bifurcation  of  the  dorsal  aorta.  On 
the  left  side,  however,  that  portion  of  the  sixth  arch  between  the  branch 
which  enters  the  lung  and  the  dorsal  aortic  root  persists  until  birth  as  the 
ductus  arteriosus  (Botalli).  This  conveys  the, blood  from  the  right  ventricle 
to  the  aorta  until  the  lungs  become  functional  (Fig.  178);  it  then  atrophies 


V 


Int.  carotid  artery 


Vertebral  artery 


Segmental  cervical  artery 


\ - —    Pulmonary  artery 


FIG.  183. — Diagram  of  the  aortic  arches  (III,  IV,  VI)  and  segmental  cervical  arteries 
of  a  10  mm.  human  embryo.    His. 

and  becomes  the  ligamentum  arteriosum.  In  the  meantime  the  septum 
aorticum  has  divided  the  original  ventral  aortic  trunk  into  two  vessels  (see 
p.  204);  one  of  the  vessels  communicates  with  the  left  ventricle  and  is  the 
proximal  part  of  the  arch  of  the  aorta,  the  other  communicates  with  the  right 
ventricle  and  becomes  the  large  pulmonary  artery  (fig.  174). 

In  human  embryos  of  10  mm.  the  dorsal  aortic  root  on  each  side  gives  off 
several  lateral  branches — the  segmental  cervical  vessels  (Fig.  183).  The 
first  of  these  (first  cervical,  suboccipital),  which  arises  nearly  opposite  the 
fourth  aortic  arch,  is  a  companion,  as  it  were,  to  the  hypoglossal  nerve,  and J 
sends  a  branch  cranially  which  unites  with  its  fellow  of  the  opposite  side  in- 
side the  skull  to  form  the  basilar  artery.  The  basilar  artery  again  bifurcates 
and  each  branch  unites  with  the  corresponding  internal  carotid  by  means  of 
the  circulus  arteriosus  (Fig.  185).  The  other  segmental  cervical  vessels 
arise  from  the  aortic  root  at  intervals,  the  eighth  arising  near  the  point  of 


THE  DEVELOPMENT  OF  THE  VASCULAR  SYSTEM. 


213 


bifurcation  of  the  aorta.  In  a  short  time  a  longitudinal  anastomosis  appears 
between  these  segmental  arteries,  which  extends  as  far  as  the  seventh  (Fig. 
184).  The  proximal  ends  of  the  first  six  disappear,  and  the  longitudinal 


FIG.  184. — Diagram  illustrating  the  formation  of  the  vertebral  and  superior  intercostal  arteries. 
The  broken  lines  represent  the  portions  of  the  original  segmental  vessels  that  disappear. 
Modified  from  Hochstetter. 

vessel  forms  the  vertebral  artery  which  then  opens  into  the  aortic  root  through 
the  seventh  segmental  artery,  and  which  is  continued  cranially  as  the 
basilar  artery  (Fig.  185).  The  seventh  (it  is  held  by  some  to  be  the  sixth) 


Circulus  arteriosus 


Middle  cerebral 
artery 


Basilar  artery 
Int.  carotid  artery 


FIG.  185. — Brain  and  arteries  of  a  human  embrvo  of  o  mm.     M all. 


segmental  artery  becomes  the  subclavian,  and  consequently  the  vertebral 
opens  into  the  subclavian,  as  in  the  adult  (Fig.  184).  But  it  should  be 
borne  in  mind  that  the  right  subclavian  artery  is  more  than  equivalent  to 
the  left,  since  the  proximal  part  of  the  former  is  made  up  of  the  fourth 


214 


TEXT-BOOK  OF  EMBRYOLOGY. 


aortic  arch  and  a  part  of  the  aortic  root  (see  Figs.  181  and  182).  Further- 
more, changes  occur  in  the  position  of  the  heart  during  development,  which 
alter  the  relations  of  the  vessels.  The  heart  migrates  from  its  original 
position  in  the  cervical  region  into  the  thorax,  and  this  produces  an  elonga- 
tion of  the  carotid  arteries  and  an  apparent  shortening  of  the  arch  of  the 
aorta;  consequently  the  subclavian  artery  on  the  left  side  arises  relatively 
nearer  the  heart. 

The  arteries  of  the  brain  arise  as  branches  of  the  internal  carotid  and  circu- 
lus  arteriosus.  The  anterior  cerebral  artery  and  the  middle  cerebral  artery 
arise  primarily  from  a  common  stem  which  in  turn  is  a  branch  of  the  most 
cranial  part  of  the  internal  carotid  (Figs.  185  and  186).  The  posterior 
cerebral  artery  arises  as  a  branch  of  the  circulus  arteriosus  (Fig.  185). 


Post,  cerebral  vein 
(sup.  petrosal  sinus) 


irculus  arteriosus 
Transverse  sinus 

Basilar  artery 
Int.  jugular  vein 


Confluence  of  sinuses 

Inf.  sagittal  sinus 
Sup.  sagittal  sinus 
Post,  cerebral  artery 

Ant.  cerebral  artery 
Int.  carotid  artery 


FIG.  1 86. — Brain,  arteries  and  veins  of  a  human  embryo  of  33  mm.     Mall 

*  " '  .!.:."•  '•.' 

From  the  point  of  its  bifurcation  to  its  caudal  end  the  aorta  gives  off  | 
paired,  segmental  branches  which  accompany  the  segmental  nerves.  The 
last  (eighth)  cervical  branch  and  the  first  two  thoracic  branches  undergo  j 
longitudinal  anastomoses,  similar  to  those  between  the  first  seven  cervical,  | 
to  form  the  superior  intercostal  artery  (A.  intercostalis  suprema)  which  opens 
into  the  subclavian  (Fig.  184).  The  other  thoracic  branches  persist  as  the 
intercostal  arteries;  the  lumbar  branches  persist  as  the  lumbar  arteries.  At 
the  same  time  anastomoses  are  formed  between  the  distal  ends  of  the  inter- 
costal and  lumbar  arteries  in  the  ventro-lateral  region  of  the  body  wall, 
which  give  rise,  on  the  one  hand,  to  the  internal  mammary  artery  and,  on 
the  other  hand,  to  the  inferior  epigastric  artery.  Of  these  two  the  former 
opens  into  the  subclavian,  the  latter  into  the  external  iliac.  By  a  further 
anastomosis  the  distal  ends  of  the  internal  mammary  and  inferior  epigastric 
are  joined,  thus  forming  a  continuous  vessel  from  the  subclavian  to  the 
external  iliac  (Fig.  187).  It  is  interesting  to  note  that  while  originally  all 
the  lateral  branches  of  the  aorta  are  arranged  segmentally,  many  of  them 


THE  DEVELOPMENT  OF  1HE  VASCULAR  SYSTEM. 


215 


lose  their  segmental  character  and  are  replaced  or  supplemented  by  longi- 
tudinal vessels. 

In  addition  to  the  dorsal  segmental  branches  of  the  aorta,  which  have 
been  described,  other  branches  develop  which  carry  blood  to  the  viscera. 
A  number  of  these,  or  possibly  all,  are  also  primarily  segmental  vessels, 
although  they  lose  every  trace  of  their  segmental  character  during  develop- 
ment. The  first  of  the  visceral  branches  to  appear  is  the  omphalomesenteric 
artery  which  arises  from  the  ventral  side  of  the  aorta  and  which  has  been 
mentioned  in  connection  with  the  vitelline  circulation.  Originally  it  passes 


Int.  mammary  artery 


tof.  epigastric  artery 


Umbilical  artery 


Femoral  artery 


FIG.  187. — Diagram  of  human  embryo  of  13  mm.,  showing  the  mode  of  development 
of  the  internal  mammary  and  inferior  epigastric  arteries.     M all. 

out  through  the  mesentery  and  follows  the  yolk  stalk  to  ramify  on  the  surface 
of  the  yolk  sac.  But  since  the  yolk  sac  is  of  slight  importance,  the  distal 
part  of  the  artery  soon  disappears,  while  the  proximal  part  becomes  the 
superior  mesenteric  artery  (Fig.  188).  The  cceliac  artery  arises  from  the  ventral 
side  of  the  aorta  a  short  distance  cranially  to  the  omphalomesenteric  (Fig. 
1 88)  and  gives  rise  in  turn  to  the  gastric,  hepatic  and  splenic  arteries.  The 
inferior  mesenteric  artery  also  arises  from  the  ventral  side  of  the  aorta  some 
distance  caudal  to  the  omphalomesenteric  (Fig.  188).  In  the  early  stages 
these  visceral  arteries  arise  relatively  much  farther  cranially  than  in  the 


216 


TEXT-BOOK  OF  EMBRYOLOGY. 


adult.     During  development  they  gradually  migrate  caudally  to  their  normal 
positions. 

Other  branches  of  the  aorta  develop  in  connection  with  the  urinary  and 
genital  organs.  Several  lateral  branches  supply  the  mesonephroi,  but  when 
the  latter  atrophy  and  disappear  the  vessels  also  disappear.  A  periaortic 
plexus  of  vessels,  with  many  branches  from  the  aorta,  supplies  the  develop- 
ing kidneys  until  these  organs  reach  their  definitive  position,  when  one  of 
the  branches  on  each  side  enlarges  to  become  the  renal  artery.  The  de- 
veloping genital  glands  are  likewise  supplied  by  several  branches  from  the 
aorta.  Later  the  majority  of  these  vessels  disappear,  one  pair  only  per- 
sisting as  the  internal  spermatic  arteries  which  differ  in  accordance  with  the 


Cceliac  artery 


Sup.  mesenteric 
(vitelline)  artery 


Umbilical  artery 


Aorta 


Duodenum 


Inf.  mesenteric  artery 
Int.  iliac  artery 


FIG.  1 88. — Diagram  of  the  visceral  arteries  in  a  human  embryo  of  12.5  mm. 
Numerals  indicate  segmental  arteries. 


Tandler. 


sex  of  the  individual.  In  both  sexes  they  are  at  first  very  short;  in  the 
female,  as  the  ovaries  move  farther  into  the  pelvic  region,  they  become 
considerably  elongated  to  form  the  ovarian  arteries;  in  the  male,  with  the 
descent  of  the  testes,  they  become  very  much  elongated  to  form  the  testicular 
arteries. 

The  fifth  (or  fourth?)  pair  of  segmental  lumbar  arteries  primarily  gives 
rise  to  the  vessels  which  supply  the  lower  extremities,  viz.,  the  iliac  arteries. 
These  then  would  be  serially  homologous  to  the  subclavians.  But  certain 
changes  occur  in  this  region,  which  are  due  to  the  relations  of  the  umbilical 
arteries.  The  latter,  as  has  already  been  noted,  arise  as  paired  branches  of 
the  aorta  in  the  lumbar  region,  pass  ventrally  through  the  genital  cord 
(Chap.  XV)  and  then  follow  the  allantois  (urachus)  to  the  umbilical  cord. 


THE  DEVELOPMENT  OF  THE  VASCULAR  SYSTEM.  217 

During  foetal  life  they  carry  all  the  blood  that  passes  to  the  placenta.  At  an 
early  period  a  branch  from  each  iliac  artery  anastomoses  with  the  corre- 
sponding umbilical,  and  the  portion  of  the  umbilical  artery  between  the 
aorta  and  the  anastomosis  then  disappears.  This  makes  the  umbilical 
artery  a  branch  of  the  iliac;  and  the  blood  then  passes  from  the  aorta  into 
the  proximal  part  of  the  liiac  which  becomes  the  common  iliac  artery  of  the 
adult.  At  birth,  when  the  umbilical  cord  is  cut,  the  umbilical  arteries  no 
longer  carry  blood  to  the  placenta,  and  their  intraembryonic  portions, 
often  called  the  hypogastric  arteries,  persist  only  in  part;  their  proximal 
ends  persist  as  the  superior  vesical  arteries,  while  the  portions  which  accom- 
panied the  urachus  degenerate  to  form  the  lateral  umbilical  ligaments. 

So  far  as  a  complete  history  of  the  growth  of  the  arteries  of  the  extremities 
is  concerned,  knowledge  is  lacking.  The  facts  of  comparative  anatomy  and 
the  anomalies  which  occur  in  the  human  body  have  led  to  certain  conclusions 
which  have  been  largely  confirmed  by  embryological  observations;  but  much 
more  work  on  the  development  of  the  arteries  is  yet  necessary  to  complete 
their  history.  The  extremities  represent  outgrowths  from  several  segments 
oft  the  body,  the  nerve  supply  is  derived  from  several  segments,  and  the 
limb  buds  are  likewise  primarily  supplied  by  plexuses  of  vessels  arising  from 
several  branches  of  the  aorta.  In  the  upper  extremity  the  subclavian,  which 
represents  the  seventh  cervical  branch  of  the  aortic  root,  is  the  single  vessel 
which  eventually  develops  out  of  the  original  plexus.  In  the  lower  extremity 
the  common  iliac,  which  represents  the  fifth  lumbar  branch  of  the  aorta, 
is  the  single  vessel  which  develops  out  of  the  plexus  supplying  the  lower 
limb  bud. 

In  the  upper  extremity  the  subclavian  grows  as  a  single  vessel  to  the  wrist 
and  then  divides  into  branches  corresponding  to  the  fingers.  In  the  forearm 
it  lies  between  the  radius  and  ulna.  In  a  short  time  a  branch  is  given  off 
just  distal  to  the  elbow  and  accompanies  the  median  nerve.  As  this  branch 
increases,  the  original  vessel  in  the  forearm  diminishes  to  form  the  volar 
interosseous  artery;  and  at  the  same  time  the  branch  unites  again  with  the 
lower  end  of  the  interosseous,  takes  up  the  digital  branches  and  becomes 
the  chief  vessel  of  the  forearm  at  this  stage,  forming  the  median  artery. 
Later,  however,  it  diminishes  in  size  as  another  vessel  develops,  the  ulnar 
artery,  which  arises  a  short  distance  proximal  to  the  origin  of  the  median  and, 
passing  along  the  ulnar  side  of  the  forearm,  unites  with  the  median  to  form 
the  superficial  volar  arch.  From  the  artery  of  the  arm,  which  is  called  the 
brachial  artery,  a  branch  develops  about  the  middle  and  extends  distally 
along  the  radial  side  of  the  forearm.  A  little  later  another  branch  grows  out 
from  the  brachial  just  proximally  to  the  origin  of  the  ulnar  and  extends  across 
to,  and  anastomoses  with,  the  first  branch.  Then  the  portion  of  the  first 


218 


TEXT-BOOK  OF  EMBRYOLOGY. 


branch  between  its  point  of  origin  and  the  anastomosis  atrophies,  leaving 
only  a  small  vessel  which  goes  to  the  biceps  muscle.  The  second  branch 
and  the  remaining  part  of  the  first  branch  together  form  the  radial  artery 
(Fig.  189)  (McMurrich). 

In  the  lower  extremity  the  primary  artery  is  a  continuation  of  the  common 
iliac  which,  in  turn,  is  a  branch  of  the  aorta.  This  primary  vessel,  the  sciatic 
artery,  passes  distally  as  far  as  the  ankle.  Below  the  knee  it  gives  off  a  short 
branch  which  corresponds  to  the  proximal  part  of  the  anterior  tibial  artery. 
Just  above  the  ankle  it  gives  off  another  branch  which  corresponds  to  the 
distal  part  of  the  anterior  tibial.  As  will  be  seen,  these  two  parts  join  at  a 
later  period  to  form  a  continuous  vessel.  At  this  early  stage  the  external 


Brachial  artery1 


Superficial  radial  artery 

Median  artery 

Interosseous  artery  — 


Ulnar  artery 


Brachial  artery 


B 


Median  artery 

Interosseous  artery 

— •  Ulnar  artery 


Radial  artery 


FIG.  189. — Diagrams  showing  (A)  an  early  and  (£)  a  late  stage  in  the  development 
of  the  arteries  of  the  upper  extremity.     McMurrich. 

iliac  artery  is  but  a  small  branch  of  the  common  iliac;  but  it  gradually  in- 
creases in  size,  extends  farther  distally  in  the  thigh  as  the  femoral  artery 
and  unites  with  the  sciatic  near  the  knee.  Just  proximal  to  its  union  with 
the  sciatic  it  gives  off  a  branch  which  extends  distally  along  the  inner  side 
of  the  leg  to  the  plantar  surface  of  the  foot,  where  it  gives  off  the  digital 
branches.  This  vessel  is  the  saphenous  artery  in  the  embryo,  and  disappears 
in  part  during  further  development.  From  this  time  on,  the  femoral  and  its 
direct  continuation,  the  popliteal,  increase  in  size;  and  at  the  same  time  the 
sciatic  loses  its  primary  connection  and  becomes  much  reduced  to  form  the 
inferior  gluteal  artery.  The  direct  continuation  of  the  sciatic  in  the  leg,  which 
is  now  the  direct  continuation  of  the  popliteal,  becomes  reduced  to  form  the 


THE  DEVELOPMENT  OF  THE  VASCULAR  SYSTEM. 


219 


peroneal  artery.  The  branch  of  the  original  sciatic,  which  was  given  off  just 
below  the  knee,  unites  with  the  branch  which  was  given  off  just  above  the 
ankle  to  form  a  continuous  vessel,  the  anterior  tibial  artery.  A  new  branch 
arises  from  the  proximal  portion  of  the  peroneal,  extends  down  the  back  of 
the  leg,  and  unites  with  the  distal  part  of  the  embryonic  saphenous  to 
form  the  posterior  tibial  artery.  The  proximal  part  of  the  saphenous  then 
atrophies,  leaving  but  one  of  the  small  genu  branches  of  the  popliteal  (Fig. 
190)  (McMurrich). 


Femoral  artery  *—  4|  — 

!• 

1 

n 

Yv 

1 

-f 

Dors,  artery  of  foot  ^-  -  -U  _  - 

-----I 

n 

Ant.  tibial  artery 

| Peroneal  artery 

j Post,  tibial  artery 


"A  B 

FIG.  190. — Diagrams  showing  three  stages  in  the  development  of  the  arteries 
of  the  lower  extremity.     McMurrich. 

The  Veins. — The  changes  which  occur  during  the  development  of  the 
venous  system  are  so  complicated,  and  in  some  cases  so  varied,  that  the  scope 
of  this  book  permits  only  a  brief  outline  of  the  growth  of  the  more  important 
of  the  venous  trunks. 

Corresponding  to  the  arterial  system,  the  first  veins  to  appear  are  the 
omphalomesenteric  veins.  These  vessels,  which  carry  blood  from  the  yolk  sac 
to  the  heart,  arise  in  the  area  vasculosa,  enter  the  embryonic  body  at  the  sides 
of  the  yolk  stalk,  pass  cranially  along  the  intestinal  tract,  and  join  the  caudal 
end  of  the  heart  (Figs.  160,  162,  164  and  193).  Next  in  point  of  time  to  ap- 
pear are  the  umbilical  veins  which  carry  back  to  the  heart  the  blood  which 
has  been  carried  to  the  placenta  by  the  umbilical  arteries.  These  also  are 
paired  veins  within  the  embryo,  although  they  form  a  single  trunk  in  the 
umbilical  cord.  They  extend  cranially  on  each  side  through  the  ventro- 
lateral  part  of  the  body  wall  and  join  the  duct  of  Cuvier  (see  below)  in  the 
septum  transversum  (Figs.  163,  164  and  193).  Very  soon  after  the  appear- 
ance of  the  umbilical  veins  two  other  longitudinal  vessels  develop,  one  on 


220 


TEXT-BOOK  OF  EMBRYOLOGY. 


each  side  of  the  aorta.  In  the  cervical  region  they  lie  dorsal  to  the  branchia 
arches  and  are  called  the  anterior  cardinal  veins  (Figs.  162  and  193).  The 
more  caudal  parts  of  the  vessels  are  situated  in  the  region  of  the  developing 
mesonephros  and  are  called  the  posterior  cardinal  veins  (Figs.  162  and  193). 
At  a  point  about  opposite  the  heart  the  anterior  and  posterior  cardinals  on 
each  side  unite  to  form  a  single  vessel,  the  duct  ofCuvier,  which  turns  medially 
through  the  septum  transversum  and  opens  into  the  sinus  venosus  (Figs. 
162  and  178).  Thus  three  primary  sets  of  veins  are  formed  at  a  very  early 
stage  of  development:  (i)  The  omphalomesenteric  veins;  (2)  the  umbilical 
veins;  (3)  the  cardinal  veins. 

The  veins  of  the  head  and  neck  regions  are  derivatives  of  the  anterior 
cardinals.  The  proximal  parts  of  these  vessels  are  present  in  embryos  of 
3.2  mm.;  later  they  extend  cranially  along  the  ventro-lateral  surface  of  the 

N.V  N.VII  N.IX 


Mid.  cerebral  vein 


Sup.  cerebral  vein 


Inf.  cerebral  vein 


FIG.  i Q i. — Veins  of  the  head  of  a  9  mm.  human  embryo.     Mall. 

brain  on  the  medial  side  of  the  roots  of  the  cranial  nerves.  The  position 
relative  to  the  nerves  is  only  temporary,  however,  for  collaterals  arising  from 
the  veins  pass  to  the  lateral  side  of  the  nerves  and  enlarge  to  form  the  main 
channels.  The  original  channels  atrophy  except  in  the  region  of  the  trigemi- 
nal  nerves  where  they  still  remain  on  the  medial  side  of  the  nerves  as  the 
forerunners  of  the  cavernous  sinuses.  The  vessel  thus  formed  laterally  to  the 
cranial  nerves  (except  the  trigeminal)  on  each  side  of  the  brain  is  known  as 
the  lateral  vein  of  the  head  (vena  lateralis  capitis)  (Fig.  191.)  The  blood  is 
collected  from  the  brain  region  by  small  vessels  which  unite  to  form  three 
main  stems;  one  of  these,  the  superior  cerebral  vein,  opens  into  the  cranial  end 
of  the  cavernous  sinus;  another,  the  middle  cerebral  vein,  opens  into  the  op- 
posite end  of  the  cavernous  sinus;  and  the  third,  the  inferior  cerebral  vein^ 
opens  into  the  lateral  vein  of  the  head  behind  the  ear  vesicle  (Figs.  191  and 


THE  DEVELOPMENT  OF  THE  VASCULAR  SYSTEM. 


221 


1 86).  The  branches  of  the  superior  cerebral  vein  extend  over  the  cerebral 
hemispheres  and  unite  with  their  fellows  of  the  opposite  side  to  form  the 
superior  sagittal  sinus  which  lies  in  the  medial  line  (Figs.  186  and  192). 
The  superior  sagittal  sinus  is  at  first  naturally  drained  by  the  superior  cere- 
bral veins;  but  later,  as  the  cerebral  hemispheres  enlarge  and  extend  farther 
toward  the  mid-brain  region,  it  is  carried  back  and  joins  the  middle  cerebral 
vein;  still  later,  for  the  same  reason,  it  joins  the  inferior  cerebral  vein  (Fig. 
192,  A  and  B).  During  these  later  changes  the  connection  between  the 


MU.  cereb.  vein      Cotfl.  of  sff 

OUc  vesicle 


Ayt.  c*rd.  reiy      Sufi.  s*f. 
~0tic  reside 


/Let  veiy  o/ 


L*t.  veirj  o 


WJT 

CAK  si 9 us       Sufrcere, 


lyf.  cere  6.  vei 


CoijfLof  slijuses 


sinus     Sub,  C6re6.  Vein 

\.Viih)  '  ' 


ercb.vtin 


FIG.  192. — Diagrams  representing  four  stages  in  the  development  of  the  veins  of  the 
head  in  human  embryos.     Mall. 

superior  sagittal  sinus  and  the  superior  cerebral  vein  is  lost  (Fig.  192).  The 
middle  cerebral  vein  becomes  the  superior  petrosal  sinus  which  forms  a  com- 
munication between  the  cavernous  sinus  and  transverse  sinus.  The  trans- 
verse sinus  represents  the  channel  between  the  superior  sagittal  sinus  and  the 
cranial  end  of  the  cardinal  vein;  or  in  other  words,  its  cranial  portion  repre- 
sents the  connection  between  the  superior  sagittal  sinus  and  the  inferior 
cerebral  vein  while  its  caudal  portion  represents  the  inferior  cerebral  vein 
itself  (Fig.  192,  compare  C  and  D).  The  caudal  end  of  the  superior  sagittal 
sinus  becomes  dilated  to  form  the  confluence  of  the  sinuses  (confluens 


222 


TEXT-BOOK  OF  EMBRYOLOGY. 


sinuum).  From  the  latter  a  new  vessel  grows  out  to  form  the  straight  sinus, 
and  a  further  growth  from  the  straight  sinus  forms  the  large  vein  of  the 
cerebrum  (vein  of  Galen).  The  inferior  sagittal  sinus  also  represents  a  new 
outgrowth  at  the  point  of  junction  of  the  large  vein  of  the  cerebrum  and 
inferior  sagittal  sinus  (Fig.  192,  D).  During  the  course  of  development  the 
lateral  vein  of  the  head  gradually  atrophies  and  finally  disappears,  and  the 
inferior  petrosal  sinus  probably  represents  a  new  formation  which  extends 
from  the  cavernous  sinus  to  the  transverse  sinus  (Fig.  192,  C  and  D).  At 


Ant.  cardinal 
(int.  jugular) 


Omphalomesenteric 
(vitelline) 


Mesonephro 


Subcardinal 


•Iliac 


FIG.  193. — Diagram  of  the  venous  system  of  a  human  embryo  of  2.6  mm. 
Slightly  modified  from  Kollmann's  Atlas. 

the  point  where  the  inferior  petrosal  joins  the  transverse  sinus  the  latter 
passes  out  of  the  skull  through  the  jugular  foramen  to  become  the  internal 
jugular  vein  (anterior  cardinal).  (Mall.) 

As  stated  in  a  preceding  paragraph,  the  anterior  cardinal  veins  extend 
from  the  ducts  of  Cuvier  to  the  head  region,  passing  to  the  dorsal  side  of  the 
branchial  arches.  They  are  at  first  paired  and  symmetrical,  but,  since  the 
heart  is  situated  in  the  cervical  region,  are  comparatively  short  and  receive 
blood  from  the  cervical  region  through  segmental  branches  which  belong  only 


THE  DEVELOPMENT  OF  THE  VASCULAR  SYSTEM. 


223 


to  the  most  cranial  of  the  cervical  segments.  The  other  segmented  cervical 
I  veins,  including  the  subdavian  veins,  open  at  first  into  the  posterior  cardinals 
(Fig.  193).  Later,  however,  as  the  heart  recedes  into  the  thorax  the  anterior 
cardinal  veins  are  elongated  and  the  segmental  cervical  veins,  including  the 
subclavians,  come  to  open  into  them  (Fig.  195).  The  bilateral  symmetry  is 
then  broken  by  an  anastomosing  vessel  which  extends  obliquely  across  from  a 
point  on  the  left  cardinal  about  opposite  the  subclavian  to  a  point  nearer  the 
heart  on  the  right  subclavian  (Figs.  194,  B,  and  195).  The  portion  of  the  left 
cardinal  cranial  to  the  subclavian  becomes  the  left  internal  jugular  vein  which 


Ant.  cardinal 

Duct  of  Cuvier 
Subclavian 

Inf.  vena  cava 


Post,  cardinal 


Iliac 


..  Ant.  cardinal 
(int.  jugular) 

—  Ext.  jugular 


Subclavian 
Duct  of  Cuvier 

— •  Inf.  vena  cava 
-—Post,  cardinal 

— -  Post,  cardinal 
Subcardinal 


Iliac 


A  B 

FIG.  194. — Diagrams  of  two  stages  in  the  development  of  the  anterior  and  posterior  cardinal  veins, 
the  subcardinal  veins  (revehent  veins  of  the  primitive  kidney),  and  the  inferior  vena  cava. 
The  small  branches  of  the  cardinals  and  subcardinals  ramify  in  the  primitive  kidneys 
(mesonephroi).  Slightly  modified  from  Hochstetter. 

communciates  with  the  intracranial  sinuses.  The  anastomosis  itself  be- 
comes the  left  innominate  vein.  The  portion  of  the  left  cardinal  between  the 
subclavian  and  the  duct  of  Cuvier,  the  duct  of  Cuvier  itself,  and  the  left  horn 
of  the  sinus  venosus  together  form  the  coronary  sinus  (Fig.  196).  On  the 
right  side  the  more  distal  part  of  the  cardinal  becomes  the  internal  jugular 
vein;  the  portion  between  the  subclavian  and  the  anastomosis  (left  innomi- 
nate vein)  becomes  the  right  innominate  vein ;  and  the  common  stem  formed 
by  the  latter  and  the  left  innominate  constitutes  the  superior  vena  cava 
which  opens  into  the  right  atrium  (see  p.  205) .  The  external  jugular  vein 
on  each  side  appears  later  than  the  superior  cardinal  as  an  independent 


224 


TEXT-BOOK  OF  EMBRYOLOGY. 


vessel  which  comes  to  lie  parallel  to  the  internal  jugular  and  opens  into  it 
near  the  subclavian.  The  opening,  however,  shifts  to  the  subclavian, 
where  it  is  usually  found  in  the  adult  (Figs.  195  and  196). 

The  changes  which  occur  in  the  posterior  cardinal  veins  are  very  extensive 
and  result  in  conditions  which  bear  but  little  resemblance  to  those  in  the 
earlier  stages.  In  connection  with  these  changes  the  development  of  the 
inferior  vena  cava  must  be  considered.  The  posterior  cardinal  veins  appear 
very  early  as  paired,  bilaterally  symmetrical  vessels  which  extend  from  the 
duct  of  Cuvier  to  the  tail  region  and  are  situated  ventro-lateral  to  the  aorta 


Ext.  jugular  — 


Innominate  (right) 


Sup.  vena  cava M- — 


Post,  cardinal 

(azygos) 


Inf.  vena  cava X - 


Subcardinal """""""" 


Subcardinal 


^_  Ant.  cardinal 
(int.  jugular) 


•-  Subclavian 

-  -  Innominate  (left) 

Post,  cardinal 


Subcardinal 
(left  suprarenal) 


•  Ureter 


Iliac- 


FlG.  195, — Diagram  representing  a  stage  (later  than  Fig.  194)  in  the  development  of  the  superior 
vena  cava  and  the  inferior  vena  cava,  also  of  the  azygos  vein.     Hochstetter. 

(Fig.  193).  From  the  first  they  receive  blood  from  the  body  wall  through 
segmental  branches,  and  as  the  primitive  kidneys  (mesonephroi)  develop 
they  receive  blood  from  them  also,  as  well  as  from  the  mesentery.  They 
return  practically  all  the  blood  from  the  region  of  the  body  situated  caudal 
to  the  heart,  just  as  the  anterior  cardinals  return  the  blood  from  the  region 
of  the  body  situated  cranial  to  the  heart.  In  other  words,  the  two  sets  of 
cardinal  veins  are  the  body  veins  par  excellence  during  the  earlier  stages  of 
development.  While  the  anterior  set  persists  for  the  most  part  as  permanent 
vessels  and  increases  with  the  development  of  the  body,  the  posterior  set 


THE  DEVELOPMENT  OF  THE  VASCULAR  SYSTEM. 


225 


undergoes  regressive  changes,  its  function  being  taken  by  a  new  vessel — 
the  inferior  vena  cava. 

Not  long  after  the  appearance  of  the  posterior  cardinals,  another  pair  of 
longitudinal  veins  appears  in  the  medial  part  of  the  mesonephroi.  They 
increase  in  size  as  the  mesonephroi  increase  and  receive  blood  from  the 
latter.  They  also  communicate  with  the  cardinals  by  means  of  transverse 
channels  which,  however,  are  later  broken  up  as  the  mesonephroi  become 
more  complicated  in  structure.  These  vessels  are  known  as  the  subcardinal 
veins,  or  revehent  veins  of  the  primitive  kidneys  (Fig.  194,  A).  After 
they  have  attained  a  considerable  size,  a  large  anastomosis  is  formed  between 
them  ventral  to  the  aorta  and  just  caudal  to  the  omphalomesenteric  (superior 
mesenteric)  artery  (Tig.  "194,  B).  In  the  meantime,  a  branch  of  the  ductus 

"  C     ^A^C^^cr^^  (*L    fVM-A*-XX 

Int.  jugular 
(ant.  cardinal; 

Innominate  (right) 

Sup.  vena  cava**"** 


Azygos 
(post,  cardinal) 


•"'Ext.  jugular 
Subclavian 

Innominate  (left) 
—Coronary  sinus 


Accessory 
hemiazygos 


— Hemiazygos 


FIG.  196.  —  Diagram  of  final  stage  in  the  development  of  the  superior  vena  cava 
and  the  azygos  vein.  (Compare  with  Fig.  195.) 

venosus  (see  p.  229)  grows  caudally  through  the  dorsal  part  of  the  liver  and 
the  mesentery,  and  joins  the  right  subcardinal  vein  a  short  distance  cranial 
to  the  above  mentioned  anastomosis  (Fig.  194,  A  and  B).  This  branch 
forms  the  proximal  part  of  the  inferior  vena  cava.  At  the  same  time,  also, 
each  subcardinal  forms  a  direct  connection  with  the  corresponding  cardinal 
at  a  point  opposite  the  first  anastomosis;  consequently  the  inferior  vena 
cava,  the  subcardinals  and  the  cardinals  are  all  in  direct  communication 
(Fig.  194,  B).  Thus  two  ways  are  formed  by  which  the  blood  may  return 
to  the  heart:  It  may  return  via  the  cardinals  and  ducts  of  Cuvier,  and  via 
the  inferior  vena  cava.  (^W 


It  is  obvious  that  while  these  conditions  exist,  that  is,  while  the  mesonephros  is  func- 
tional, and  blood  is  carried  to  it  by  the  cardinal  veins  and  from  it  by  the  subcardinal  veins, 
there  is  a  true  renal  portal  system.  The  blood  from  the  body  walls  and  lower  extremities 


226 


TEXT-BOOK  OF  EMBRYOLOGY. 


is  collected  by  the  segmental  vessels  and  poured  into  the  cardinal  veins  and  is  then  dis- 
tributed in  the  mesonephros  by  smaller  channels  or  sinusoids  (Minot),  whence  it  is 
collected  and  carried  off  by  the  subcardinal  veins.  This  passage  of  blood  through  purely 
venous  channels  simulates  the  conditions  in  the  liver  where  there  is  a  true  hepatic  portal 
system. 

Frcm  this  time  on,  the  changes  are  largely  regressions  in  the  cardinal  and 
subcardinal  systems,  corresponding  to  the  atrophy  of  the  mesonephroi,  and 
rapid  increase  in  the  vena  cava  and  its  branches.  The  cranial  end  of  each 
cardinal  becomes  smaller;  the  left  loses  its  connection  with  both  the  vena  cava 
and  the  duct  of  Cuvier,  the  right  its  connection  with  the  vena  cava  only  (Fig. 


Aorta 


Post,  cardinal 

Mesonephric  duct' 

Omphalomesenteric    artery 
Right  umbilical  vei 

Intestine 


Post,  cardinal  vein 


Dorsal  mesentery 
.Ccelom 


'Left  umbilical  vein 


FIG.  197. — From  a  transverse  section  of  a  5  mm.  human  embryo,  at  the  level  of  the 
omphalomesenteric  (vitelline,  superior  mesenteric)  artery. 

ig6j.  Subsequent  changes  in  these  parts  of  the  cardinals  will  be  considered 
in  the  following  paragraph.  For  a  time  the  caudal  ends  of  the  two  cardinals 
are  of  equal  importance.  Later,  however,  the  right  becomes  larger,  while  the 
left  atrophies.  The  right  thus  becomes  a  direct  continuation  and  really  a 
part  of  the  vena  cava  (Figs.  195  and  198).  This  is  brought  about,  of  course, 
by  the  original  anastomosis  between  the  vena  cava  and  the  subcardinal  and 
cardinal.  On  the  left  side  the  anastomosis  persists  simply  as  the  proximal 
part  of  the  renal  vein  (Fig.  198);  on  the  right  side  the  renal  vein  is  a  new 
structure  which  develops  after  the  kidney  has  attained  practically  its  final 
position,  and  opens  into  the  vena  cava  secondarilv.  The  inferior  vena  cava 


THE  DEVELOPMENT  OF  THE  VASCULAR  SYSTEM. 


227 


itself  is  a  composite  vessel  derived  from  four  different  anlagen.  i.  The 
part  which  extends  from  the  ductus  venosus  to  the  right  subcardinal  is  of 
independent  origin.  2.  A  short  portion  is  derived  from  a  part  of  the  right 
subcardinal.  3.  Another  short  portion  is  derived  from  the  cross-anastomosis 
between  the  subcardinals  and  cardinals.  4.  The  caudal  end  is  a  derivative 
of  the  caudal  part  of  the  right  cardinal  (compare  Figs.  194,  195,  198.) 

Before  the  caudal  end  of  the  left  cardinal  vein  atrophies,  an  interesting 
and  important  change  occurs  in  the  relations  of  the  ureters  and  cardinals. 
Primarily  the  cardinal  veins  develop  to  the  ventral  side  of  the  ureters.  But 
later  a  collateral  of  each  cardinal  develops  to  the  dorsal  side  of  the  ureter. 
These  join  the  cardinal  cranial  and  caudal  to  the  ureter.  In  other  words,  a 


Inf.  vena  cava 


Suprarenal  gland    -f- 

Suprarenal  vein  (right) 


Renal  vein  (right)       f" 
\    •••' 


Int.  spermatic  (right)   — 
Ureter  — 


Inf.  vena  cava 
(right  post,  cardinal) 


Common  iliac  (right) 


Int.  vena  cava 

Suprarenal  gland 

r.- Suprarenal  vein  (lefU 

..]...  Kidney 

*- Renal  vein  (left) 

Int.  spermatic"(left) 
(post,  cardinal) 

%i Ureter 


Common  iliac  (left) 

Ext.  iliac 

'* -  Int.  iliac 

.-.,...,,  Common  iliac  (right) 

B 

FIG.  198. — Diagrams  representing  final  stages  in  the  development  of  the  inferior  vena  cava 
(compare  with  Fig.  195).     Slightly  modified  from  Hochstetter. 

venous  loop  is  formed  around  the  ureter  (Fig.  195).  The  ventral  arm  of  the 
loop  then  atrophies  and  disappears,  leaving  the  dorsal  arm  as  the  direct  part 
of  the  cardinal  vein.  On  the  right  side,  where  the  cardinal  persists  as  a 
portion  of  the  vena  cava,  the  latter  vessel  comes  to  lie  ventral  to  the  ureter 
(Fig.  198,  A).  On  the  left  side  the  cardinal  atrophies,  leaving  only  the  por- 
tion cranial  to  the  loop  as  the  proximal  end  of  the  internal  spermatic  (testicular 
or  ovarian )  vein  (Fig.  198,  B).  Since  on  the  left  side  the  original  anastomosis 
between  the  subcardinals  and  cardinals  persists  as  the  renal  vein,  the  left 
internal  spermatic  is  a  branch  of  the  renal.  The  right  internal  spermatic 
vein  probably  represents  a  branch  of  the  vena  cava  which  is  independent 
of  the  cardinal. 

In  the  cat  embryo  the  venous  loop  around  the  ureter  is  much  more 


228 


TEXT-BOOK  OF  EMBRYOLOGY. 


extensive  than  in  the  other  forms.  The  dorsal  arm  of  the  loop,  named  the 
supracardinal  vein,  extends  from  the  iliac  vein  to  the  original  anastomosis 
between  the  subcardinals  and  cardinals.  In  the  course  of  further  develop- 
ment the  supracardinals  approach  each  other  and  finally  fuse,  forming  a 
large  single  vessel  which  becomes  the  portion  of  vena  cava  caudal  to  the 
renal  veins.  In  this  event  the  portions  of  both  cardinals  forming  the  ventral 
arms  of  the  venous  loops  atrophy  and  disappear. 

Near  the  caudal  end  of  each  cardinal  vein  a  branch  arises  which  receives 
the  blood  from  the  corresponding  lower  extremity.  Then  a  transverse 
anastomosis  appears  between  the  two  cardinals  at  this  point  (Fig.  198,  A). 
Since  the  portion  of  the  left  cardinal  caudal  to  the  renal  vein  atrophies,  the 
anastomosis  itself  constitutes  the  left  common  iliac  vein  (Fig.  198,  B).  The 
right  common  iliac  is,  of  course,  the  original  branch  of  the  right  cardinal. 
As  the  iliacs  enlarge  they  form  the  two  great  branches  of  the  vena  cava. 


—Duct  of  Cuvieri 


Duct  of  Cu 


Right  umbilical  — I- 


Right  omphalomesenteric  "•• 


--"•Ductus  venosus 


Left  umbilical 


Left  omphalomesenteric 


FIG.  199. — Diagrams  illustrating  two  stages  in  the  transformation  of  the  omphalomesenteric 
and  umbilical  veins  in  the  liver.     Hochstetter. 

With  the  atrophy  of  the  mesonephroi,  the  subcardinal  veins  diminish  in 
size  and  finally  disappear  for  the  greater  part.  The  part  of  the  right  sub- 
cardinal  cranial  to  the  point  of  junction  with  the  vena  cava  disappears 
entirely.  The  portion  of  the  left  subcardinal  cranial  to  the  anastomosis 
between  the  two  subcardinals  becomes  much  reduced  in  size,  but  persists 
as  the  left  suprarenal  vein.  The  left  suprarenal  vein  is  thus  a  branch  of  the 
left  renal  vein,  since  the  latter  represents  the  anastomosis  itself  (Figs.  194, 
195,  198).  The  right  suprarenal  vein  probably  does  not  represent  a  per- 
sistent right  subcardinal,  but  is  a  new  vessel  opening  into  the  vena  cava. 
The  portion  of  each  subcardinal  caudal  to  the  anastomosis  probably  dis- 
appears entirely,  but  this  has  not  been  definitely  determined. 

The  observations  on  the  development  of  the  azygos  veins  in  the  human 
embryo  are  only  fragmentary.  In  the  rabbit  the  portions  of  the  posterior 
cardinal  veins  immediately  cranial  to  the  anastomosis  between  the  sub- 


THE  DEVELOPMENT  OF  THE  VASCULAR  SYSTEM.  229 

cardinals  and  cardinals,  that  is,  just  cranial  to  the  renal  veins,  disappear. 
The  more  cranial  portion  of  the  right  cardinal  persists  as  the  azygos  vein 
which  receives  the  intercostal  (segmental)  branches  and  opens  into  the 
superior  vena  cava.  An  oblique  anastomosis  is  formed,  dorsal  to  the  aorta, 
between  the  two  cardinals  (Fig.  195).  This  anastomosis  and  the  portion  of 
the  left  cardinal  caudal  to  it  together  form  the  hemiazygos  vein.  The  por- 
tion of  the  left  cardinal  cranial  to  the  anastomosis  loses  its  connection 
with  the  duct  of  Cuvier  (or  coronary  sinus)  and  becomes  the  accessory 
hemiazygos  vein  (Fig.  196).  The  ascending  lumbar  veins,  which  join  the 
azygos  and  hemiazygos,  probably  do  not  represent  persistent  parts  of  the 
caudal  ends  of  the  cardinals,  but  are  formed  by  longitudinal  anastomoses 
between  the  original  segmental  lumbar  veins. 

The  changes  which  occur  in  the  region  of  the  liver  are  of  much  im- 
portance and  result  in  conditions  which  bear  no  resemblance  to  the  primary 
ones.  As  has  already  been  noted,  the  omphalomesenteric  veins  enter  the 
body  at  the  umbilicus,  pass  cranially  along  the  intestine  and  open  into  the 
caudal  end  of  the  heart.  The  umbilical  veins,  which  appear  soon  after, 
enter  the  body  at  the  umbilicus  and  pass  cranially,  one  on  each  side,  in  the 
ventro-lateral  part  of  the  body  wall;  at  the  level  of  the  heart  they  turn 
mesially  through  the  septum  transversum  and  join  the  corresponding 
omphalomesenteric  veins  to  form  a  common  trunk  on  each  side,  into  which 
the  duct  of  Cuvier  then  opens  (Fig.  193).  When  the  liver  grows  out  as  an 
evagination  from  the  intestine,  it  comes  in  contact  with  the  proximal  ends 
of  the  omphalomesenteric  veins  and,  as  it  enlarges,  breaks  them  up  into 
numerous  smaller  channels  (Fig.  199). 

The  blood  then,  instead  of  having  a  direct  channel,  is  forced  to  flow 
through  these  smaller  channels  which  have  been  termed  sinusoids.  When 
the  liver  has  attained  a  considerable  size  a  more  direct  and  definite  channel 
is  formed,  which  extends  through  the  substance  of  the  liver  from  the  proximal 
end  of  the  right  omphalomesenteric  vein  obliquely  caudally  to  the  left 
omphalomesenteric  vein.  This  newly  formed  channel  is  the  ductus  venosus 
(Figs.  199  and  200).  In  the  meantime,  three  transverse  anastomoses  develop 
between  the  omphalomesenteric  veins  just  caudal  to  the  liver.  The  middle 
one  is  dorsal  to  the  intestine,  the  other  two  ventral,  so  that  the  intestine  is 
surrounded  by  two  venous  loops  or  rings  (Figs.  199  and  200).  At  the  same 
time  a  cross-anastomosis  develops  between  the  left  umbilical  vein,  which  is 
primarily  the  smaller,  and  the  corresponding  omphalomesenteric.  This 
anastomosis  joins  the  omphalomesenteric  at  about  the  point  where  the  latter 
joins  the  ductus  venosus,  so  that  it  seems  to  be  a  continuation  of  the  ductus 
venosus.  A  similar  cross-anastomosis  also  develops  between  the  right  um- 
bilical and  right  omphalomesenteric  (Figs.  199  and  200).  Thus  the  blood 


230 


TEXT-BOOK  OF  EMBRYOLOGY. 


that  is  brought  in  from  the  placenta  by  the  umbilical  veins  may  pass  through 
the  liver.  Then  the  portion  of  each  umbilical  between  the  anastomosis  and 
the  duct  of  Cuvier  atrophies  and  disappears  (Fig.  200).  The  remaining 
portion  of  the  left  umbilical,  which  was  originally  the  smaller,  gradually 
increases  in  size  and  finally  carries  all  the  blood  from  the  placenta.  The 
right  umbilical,  on  the  other  hand,  loses  its  connection  with  the  liver  and 
persists  only  as  a  small  vein  in  the  body  wall,  which  opens  into  the  left 
umbilical  vein  near  the  umbilical  cord  (Fig.  201).  Thus  there  is  the  peculiar 
phenomenon  of  a  vessel  carrying  blood  in  different  directions  at  different 
periods  of  its  history.  During  the  course  of  development  of  the  septum 


Oesophagus 


Ant.  cardinal 


Post,  cardinal 

Liver 
Right  umbilical 

Venous  ring 
Venous  ring 


Duct  of  Cuvier 
Left  umbilical 
Ductus  venosus 


Left  umbilical 


Omphalomesenteric 
Intestine 


FIG.  200. — Veins  in  the  liver  region  of  a  human  embryo  of  4  mm.     His,  Kollmann's  Atlas. 

transversum  and  diaphragm  the  left  umbilical  is  withdrawn  from  the  body 
wall  and  passes  directly  from  the  umbilicus  to  the  ventral  side  of  the  liver. 
During  fcetal  life  it  conveys  all  the  blood  from  the  placenta  to  the  liver.  A 
part  of  the  blood  is  distributed  in  the  liver,  a  part  is  carried  directly  to  the 
inferior  vena  cava  by  the  ductus  venosus  (Fig.  202).  After  birth'  the 
placental  blood  is  cut  off  and  the  umbilical  vein  degenerates  to  form 
the  round  ligament  of  the  liver. 

The  venous  rings  around  the  intestine  also  undergo  marked  changes. 
The  right  side  of  the  most  caudal  and  the  left  side  of  the  most  cranial  dis- 
appear; the  remaining  vessel  finally  loses  its  connection  with  the  ductus 
venosus  and  becomes  the  portal  vein  (Figs.  199,  200,  201  and  202).  The 


THE  DEVELOPMENT  OF  THE  VASCULAR  SYSTEM. 


231 


portal  vein  is  thus  a  derivative  of  the  omphalomesenterics.  After  birth, 
when  the  placental  blood  is  cut  off,  blood  is  distributed  in  the  liver  by 
branches  of  the  portal  vein,  which  represent  the  advehent  hepatic  veins; 
it  is  collected  again  by  branches  which  unite  to  form  the  revehent  hepatic 
veins,  or  hepatic  veins  proper,  and  the  latter  open  into  the  inferior  vena 
cava.  The  advehent  and  revehent  hepatic  veins  are  formed  by  the 
enlargement  of  some  of  the  original  sinusoids  (Figs.  199  and  201). 

Observations  on  the  development  of  the  veins  in  the  extremities  of  human 


Ant.  cardinal 
(int.  jugular) 


Post,  cardinal 


Sinus  venosus  and 
orifice  of  ductus  venosus 


Revehent  hepatic 


Advehent  hepatic 


Right  umbilical 


Omphalomesenteric 
(portal) 


Umbilical  vein 


Ant.  cardinal 
(int.  jugular) 


Post,  cardinal 
Bronchus 

Revehent  hepatic 
Advehent  hepatic 

Left  umbilical 
Umbilical  cord 


FIG,  201. — Veins  in  the  liver  region  of  a  human  embryo  of  10  mm.     Kollmann's  Atlas. 

embryos  are  so  fragmentary  that  it  seems  advisable  to  make  use  of  the  work 
that  has  been  done  on  the  rabbit.  In  the  upper  extremity  the  first  vein  to 
develop  is  the  primary  ulnar  vein  which  begins  in  the  radial  (cranial)  side  of 
the  extremity  near  its  proximal  end,  extends  distally  along  the  radial  border, 
thence  proximally  along  the  ulnar  (caudal)  border,  and  opens  into  the 
anterior  cardinal  vein  (internal  jugular)  near  the  duct  of  Cuvier  (Fig.  203). 
This  condition  is  present  in  rabbit  embryos  of  thirteen  days.  A  little  later  a 
second  vessel,  the  cephalic  vein,  appears  as  a  branch  of  the  external  jugular, 


232 


TEXT-BOOK  OF  EMBRYOLOGY. 


extends  along  the  radial  side  of  the  extremity  and  becomes  connected  with 
the  digital  veins  (Fig.  204).  When  the  digital  veins  are  taken  up  by  the 
cephalic,  the  distal  portion  of  the  primitive  ulnar  undergoes  regression. 
These  changes  have  taken  place  in  rabbit  embryos  of  fifteen  days,  and  for  a 
short  period  the  cephalic  vein  is  the  chief  vessel  of  the  extremity.  The 
primitive  ulnar  vein,  however,  develops  more  rapidly  than  the  cephalic  and, 


Heart- 


Inf.  vena  cava  —  •  - 


Ductus  venosus  -i- 


Left  lobe  of  liver-- 


Umbilical vein,- 


Umbilical  ring 


Hepatic  veins 


Right  lobe  of  liver 


Gall  bladder 


Portal  vein 
(omphalomesenteric; 


Intestine 


Inf.  vena  cava 


FIG.  202. — Veins  of  the  liver  (seen  from  below)  of  a  human  foetus  at  term      Kollmann's  Atlas. 


with  its  branches,  soon  becomes  the  chief  vessel;  the  portion  in  the  forearm 
gives  rise  to  either  the  ulnar  or  basilic  vein;  the  portion  in  the  arm  becomes 
the  brachial  vein  which  then  passes  over  into  the  axillary,  and  the  latter 
in  turn  passes  over  into  the  subclavian.  The  cephalic  vein  of  the  embryo 
persists  as  the  cephalic  of  the  adult,  and,  during  the  period  when  it  forms  the 
chief  vessel  of  the  extremity,  a  branch  arises  from  it  which  becomes  the  radial 
vein.  Primarily  the  cephalic  vein  opens  into  the  external  jugular,  but  later 


THE  DEVELOPMENT  OF  THE  VASCULAR  SYSTEM. 


233 


Arjt.  ca.rJ. 


a  new  connection  is  formed  with  the  axillary,  while  the  original  connection 

persists  as  the  j ugulocephalic  (Fig.  205). 

In  a  rabbit  embryo  of  ten  and  one-half  days  a  vein  follows  the  border  of 
the  lower  extremity  all  the  way  round,  connecting 
on  the  cranial  side  with  the  umbilical  and  on  the 
caudal  side  with  the  posterior  cardinal.  This  is  the 
primitive  fibular  vein,  and  from  its  course  is  homol- 
ogous with  the  primitive  ulnar  vein  of  the  upper 
extremity  (Fig.  203).  From  this  time  on,  how- 
ever, the  course  of  development  in  the  lower  ex- 
tremity differs  from  that  in  the  upper.  The  con- 
nection of  the  fibular  vein  with  the  umbilical  is 
soon  lost.  In  older  embryos  (fifteen  days)  two 
branches  of  the  fibular  vein  have  appeared;  one 
of  these,  the  anterior  tibial  vein,  begins  on  the 
embryo  of  14  days  (n  mm.),  dorsum  of  the  foot  and  extends  diagonally  proxi- 

Modified  from  Lewis.  ,,  .  «        ,»v    *         •         i 

mally,   to   open   into   the  fibular  in   the   caudal 

border;  the  other,  the  so-called  connecting  branch,  begins  as  twigs  in  the  ab- 
dominal wall  and  tibial  side  of  the  extremity  and  opens  into  the  fibular  just 
proximal  to  the  opening  of  the  anterior  tibial  (Fig.  204).  Later  the  distal 


•Bracljiit  veiq 
Ext.  njArqyarj 


FIG.  204.  FIG.  205. 

FIG.  204.— Diagram  of  the  veins  in  the  extremities  of  a  rabbit  embryo  of  14  days 

and  18  hours  (14.5  mm.).     Modified  from  Lewis. 

FIG.  205. — Diagram  of  the  veins  in  the  extremities  of  a  rabbit  embryo  of  17  days 
(21  mm.).     Modified  from  Lewis. 

part  of  the  primitive  fibular  is  broken  up  by  the  differentiation  of  the  digits 
(toes)  and  disappears  almost  up  to  the  point  of  junction  with  the  anterior 
tibial.  The  latter  enlarges  and  receives  the  digital  branches,  and  appears 


234 


TEXT-BOOK  OF  EMBRYOLOGY. 


as  a  continuation  of  the  proximal  part  of  the  primitive  fibular.  The  anterior 
tibial  and  primitive  fibular  together  thus  constitute  the  sciatic  vein  (Fig. 
205).  Another  vessel  appears  in  embryos  of  fifteen  days,  which  represents 
the  beginning  of  the  femoral  vein  and  opens  into  the  cardinal,  cranial  to  the 
opening  of  the  sciatic  (Fig.  205).  From  this  time  on  the  femoral,  with  its 
branches,  enlarges  at  the  expense  of  the  other  veins  and  becomes  the  principal 
vein  of  the  lower  extremity.  In  the  human  embryo  the  femoral  anastomoses 
with  the  sciatic  near  the  knee  and  the  proximal  portion  of  the  sciatic  then 
atrophies,  the  distal  portion  persisting  as  the  small  sephenous  vein.  The 


Sup.  vena  cava 
Lungs 

Right  atrium 

Right  ventricle 

Inf.  vena  cava 

Liver 

Ductus  venosus 

Placenta 

Inf.  vena  cava 

Umbilical  vein 
Umbilical  artery 


Ant.  part  of  body 


Carotid  and 
subclavian  arteries 


Ductus  arteri'osus 

Pulmonary  artery 
Left  ventricle 


Post,  part  of  body 


FIG.  206. — Diagram  illustrating  the  foetal  circulation.     Compare  with  Fig.  207. 

Modified  from  Kollmann. 

The  shading  represents  the  relative  impurity  of  the  blood  in  different  regions,  the 
darkest  shading  representing  the  most  impure  blood 

large  saphenous  vein  and  the  posterior  tibial  vein  possibly  are  derivatives  of 
the  femoral,  but  this  question  has  not  been  settled. 

CHANGES  IN  THE  CIRCULATION  AT  BIRTH. — During  fcetal  life  the  course  of 
the  blood  is  adapted  to  the  placental  circulation,  since  the  placenta  is  the 
only  means  by  which  the  blood  is  purified  and  from  which  the  foetus  derives 
its  nutriment.  The  pure  blood  from  the  placenta  passes  through  the  umbil- 
ical vein  to  the  liver;  there  a  part  of  it  is  distributed  to  the  liver  by  some  of 
the  advehent  veins,  is  collected  again  by  the  revehent  veins  and  poured  into 
the  inferior  vena  cava;  a  part  passes  directly  to  the  vena  cava  through  the 


THE  DEVELOPMENT  OF  THE  VASCULAR  SYSTEM. 


235 


ductus  venosus.  At  this  point  the  blood  acquires  some  impurity  from  the 
stream  brought  in  by  the  vena  cava  itself  and  the  portal  vein.  The  slightly 
impure  blood  then  flows  into  the  right  atrium,  is  directed  by  the  Eustachian 
valve  through  the  foramen  ovale  into  the  left  atrium,  thence  flows  into  the 
left  ventricle  and  is  forced  out  into  the  aorta.  A  part  of  the  blood  flows  on 
through  the  aorta,  a  part  is  carried  to  the  upper  extremities  and  head  and 
neck  regions  by  the  subclavian  and  carotid  arteries.  The  latter  part,  then 
becoming  impure,  is  carried  back  to  the  right  atrium  by  the  subclavian 


Sup.  vena  cava 
Lungs 

Pulmonary  veins 
Right  atrium 

Right  ventricle 
Inf.  vena  cava 

Hepatic  vein 
Liver 


Inf.  vena  cava 


Ant.  part  of  body 


Carotid  and 
subclavian  arteries 


Pulmonary  artery 


Left  ventricle 


Hepatic  artery 


Post,  part  of  body 


FIG.  207. — Diagram  illustrating  the  circulation  in  the  adult.     Compare  with  Fig;  206.     The 
shading  represents  the  relative  impurity  of  the  blood,  the  white  being  the  purest  blood. 

and  jugular  veins  and  superior  vena  cava;  from  the  right  atrium  the  greater 
portion  flows  into  the  right  ventricle  and  thence  is  forced  out  into  the  large 
pulmonary  artery.  But  since  the  lungs  are  non-functional,  this  blood  passes 
through  the  ductus  arteriosus  to  join  the  stream  in  the  aorta.  The  blood 
received  by  the  more  cranial  portion  of  the  foetus  is  but  slightly  impure, 
for  the  impure  blood  from  the  ductus  arteriosus  joins  the  aortic  stream  distal 
to  the  origin  of  tlie  subclavian  and  carotid  arteries.  This  accounts  for 
the  fact  that  the  more  cranial  portion  of  the  body  generally  is  better  devel- 
oped than  the  more  caudal  portion.  It  is  well  to  note  here  that  the  liver 


236  TEXT-BOOK  OF  EMBRYOLOGY. 

receives  purer  blood  than  any  other  part  of  the  body,  and  this  is  undoubtedly 
correlated  with  the  relatively  enormous  size  of  that  organ  in  the  foetus. 
The  rather  impure  blood  which  starts  through  the  dorsal  aorta  is  in  part 
distributed  to  the  viscera,  body  walls,  and  lower  extremities  by  the  visceral 
and  segmental  arteries,  and  thence  is  collected  by  the  branches  of  the  portal 
vein  and  inferior  vena  cava  to  be  returned  as  impure  blood  to  the  umbilical 
current  at  the  liver;  in  part  it  is  carried  by  the  umbilical  arteries  to  the  pla- 
centa, there  to  be  purified  and  collected  by  the  branches  of  the  umbilical 
vein  (see  Fig.  206). 

At  birth,  when  the  placental  circulation  is  cut  off,  the  proximal  end  of  the 
umbilical  vein  atrophies  to  form  the  round  ligament  of  the  liver;  the  ductus 
venosus  also  atrophies  and  becomes  merely  a  connective-tissue  cord  in  the 
liver.  The  hepatic  portal  circulation  is  still  maintained  by  the  portal  vein. 
The  foramen  ovale  is  closed  and  the  impure  blood  from  the  inferior  vena  cava 
as  well  as  that  from  the  superior,  passes  from  the  right  atrium  into  the  right 
ventricle  and  thence  is  forced  out  through  the  pulmonary  artery  to  the  lungs, 
which  at  this  time  become  functional,  and  is  returned  to  the  left  atrium  by  the 
pulmonary  veins.  The  ductus  arteriosus  atrophies  to  form  the  ligamentum 
arteriosum.  From  the  left  atrium  the  pure  blood  flows  into  the  left  ventricle, 
thence  is  forced  out  through  the  aorta  and  its  branches  to  all  parts  of  the 
body.  At  the  same  time  the  more  distal  portions  of  the  umbilical  arteries  in 
the  embryo  atrophy  to  form  the  lateral  umbilical  ligaments,  their  proximal 
portions  persisting  as  the  superior  vesical  arteries  (see  Fig.  207). 

Haemopoiesis — Histogenesis  of  the  Blood  Cells. 

Two  sharply  contrasting  views  are  held  regarding  the  origin  and  genetic 
relationships  of  the  different  kinds  of  blood  cells.  The  one  view,  expressed 
in  the  monophyletic  theory,  holds  that  there  is  differentiated  out  of  the  mesen- 
chyme  a  certain  type  of  cells — the  primitive  blood  cells,  or  haemoblasts — 
and  that  from  this  single  type  all  the  cells  of  the  blood  arise  through  proc- 
esses of  development  along  divergent  lines.  The  other  view,  expressed  in 
the  polyphyletic  theory,  holds  that  while  the  blood  cells  are  of  mesenchymal 
origin  the  red  cells  and  white  cells  have  a  dual  origin,  each  type  arising  from 
its  own  mother-cells;  and  further  that  perhaps  each  kind  of  white  cells  arises 
from  a  distinct  parent-cell.  The  recent  extensive  studies  of  the  problem 
have  yielded  evidence  that  turns  the  balance  at  present  in  favor  of  the  mono- 
phyletic theory,  and  the  following  account  is  based  in  the  main  upon  these 
studies,  particularly  those  of  Maximow  on  the  rabbit  and  Dantschakoff  on 
the  chick. 

The  sites  of  blood  formation,  or  haemopoiesis,  are  (i)  the  area  opaca 


THE  DEVELOPMENT  OF  THE  VASCULAR  SYSTEM 


237 


(yolk  sac),  (2)  the  body  mesenchyme,  including  the  endothelium  of  the  early 
blood-vessels,  (3)  the  liver  and  spleen,  (4)  bone  marrow,  and  (5)  the  lymph 
glands.  These  various  structures  are  functional  at  successive  periods  of 
development  of  the  embryo,  but  overlap  to  a  certain  extent,  the  marrow  and 
lymph  glands  being  probably  the  only  foci  of  origin  of  blood  cells  in  the  adult. 
In  the  area  opaca  blood-cell  development  is  initiated  in  the  formation  of 
the  blood  islands.  Some  of  the  mesenchymal  cells  become  less  irregular  in 
shape  by  retraction  of  their  protoplasmic  processes  and  isolation  from  the 
general  syncytium.  They  assume  amoeboid  properties  and  the  cytoplasm 


FIG.  208. — Mesenchyme  from  a  rabbit  embryo  at  the  time  of  beginning  blood  formation. 

Maximow. 

m,  Ordinary  mesenchyme  cells;  m',  mesenchyme  cell  in  mitosis;  /,  primitive  Wood  cell 

(primitive   lymphocyte). 

[uires  a  distinctly  basophilic  character  (Fig.  208).  These  then  represent 
primitive  blood  cells,  or  hcemoUasts.  Maximow  has  given  them  the  name 
primitive  lymphocytes,  or  lymphoblasts ,  regarding  them  as  the  common  an- 
cestors of  all  the  blood  cells.  Clusters  of  these  cells  constitute  the  blood 
islands  which  are  involved  in  the  development  of  the  primitive  blood  spaces, 
the  superficial  cells  being  transformed  into  endothelium  (see  p.  186)  and  the 
central  cells  remaining  as  primitive  lymphocytes.  Other  primitive  lympho- 
cytes also  differentiate  in  the  mesenchyme  outside  of  the  blood  spaces, 
afterward  probably  entering  the  vessels  by  virtue  of  their  amoeboid  properties. 


238 


TEXT-BOOK  OF  EMBRYOLOGY. 


There  is  a  view  that  both  the  blood  cells  and  the  endothelium  of  blood 
vessels  arise  from  certain  mesam&boid  cells  of  entodermal  origin,  which  are 
insinuated  between  the  entoderm  and  mesoderm  but  are  not  in  the  strict 
sense  constituents  of  the  latter,  and  which  collectively  have  been  called  the    | 
angioUast.     While  the  mesamceboid  cells  are  probably  identical  with  the   j 
primitive  lymphocytes,  the  idea  that  they  constitute  a  set  of  specific  rudi- 
ments of  entodermal  origin,  from  which  both  blood  cells  and  endothelium 
arise,  has  not  been  generally  accepted.     The  view,  however,  is  not  discord- 
ant with  the  monophyletic  concept  of  the  origin  of  blood  cells. 


FIG.  209. — Portion  of  a  blood  vessel  from  the  yolk  sac  of  a  rabbit  embryo,  showing  various 

stages  in  the  formation  of  erythrocytes.     Maximow. 
fl,  megaloblasts;  a',  megaloblast  in  mitosis;  b,  normoblasts;  b',  normoblast  in  mitosis;  c,  erythro- 

blasts;    d,   erythrocyte,    not   yet   discoid;   en,   endothelium;   /,    primitive   lymphocytes; 

k,  normoblast  recently  divided;  n,  shrunken  erythroblasts  (?);  n' ',  extruded  nucleus. 

The  primitive  lymphocytes  (of  Maximow),  constituting  the  parent  stem 
from  which  all  the  blood  cells  arise  according  to  the  monophyletic  theory, 
specialize  at  first  in  two  general  directions.  In  one  direction  the  specializa- 
tion leads  toward  the  erythrocytes,  or  red  blood  corpuscles,  and  in  the  other 
toward  the  leucocyte,  or  white  blood  cell,  series  including  the  myelocytes. 
In  the  former  case  the  lymphocytes  become  modified  in  that  the  cytoplasm 
becomes  less  basophilic  and  acquires  a  trace  of  haemoglobin;  the  nuclei  become 


THE  DEVELOPMENT  OF  THE  VASCULAR  SYSTEM. 


239 


somewhat  eccentric,  the  chromatin  network  a  little  denser  and  the  nucleoli 
less  conspicuous.  While  these  changes  are  in  progress  the  cells  multiply  by 
mitosis.  The  resulting  cells  are  termed  megaloblasts  (Fig.  209,  a).  These 
continue  to  multiply  by  mitosis,  the  cytoplasm  acquiring  more  haemoglobin 
and  the  nuclei  becoming  more  dense,  the  resulting  cells  being  somewhat 
smaller  and  known  as  normoblasts  (Fig.  209,  b) .  The  normoblasts,  still  divid- 
ing by  mitosis,  acquire  still  more  haemoglobin  and  become  erythroblasts  (Fig. 
209,  c).  These  lose  their  nuclei  and  thus  become  erythrocytes,  the  definitive 
red  blood  corpuscles.  The  manner  in  which  the  nuclei  are  lost  is  a  matter 
of  dispute.  Some  claim  it  is  absorbed  (karyolysis) ;  others  claim  it  is  extruded 

(karyorrhexis)  (Fig.  210);  recently  the 
observation  has  been  made  that  the 
nucleus  with  a  small  amount  of  sur- 
rounding cytoplasm  escapes  from  the  cell 
in  a  manner  resembling  constriction. 

In  the  specialization  leading  to  the 
white  blood  cell  series,  the  parent  stem 
cell  (primitive  lymphocyte)  proliferates 
by  mitosis  and  undergoes  certain  di- 
vergent changes  in  its  nucleus  and  cyto- 
plasm which  yield  the  characters  of  the 
various  kinds  of  leucocytes.  Some  of 
the  cells  become  polymorphonuclear  and 
acquire  neutrophile  granules  to  become 
neutrophile  leucocytes;  others  acquire 
acidophile  granules  as  acidophiles;  still 
others,  basophile  granules  as  basophiles. 
The  large  mononuclear  leucocytes,  with  the  transitional  forms  having  the 
horseshoe-shaped  nuclei,  possibly  represent  but  slightly  modified  primitive 
lymphocytes.  The  definitive  lymphocytes  are  probably  derived  from  the 
primitive  by  division  and  but  slight  changes  in  character.  Thus  the  vari- 
ous forms  of  white  blood  cells  would  not  represent  different  stages  in  a  series 
but  divergent  lines  of  specialization  from  a  parent  stem. 

As  mentioned  before,  the  various  blood  forming  organs  function  as  such 
at  successive  stages  of  development  of  the  embryo.  The  mesenchyme 
generally,  both  in  the  yolk  sac  and  in  the  body,  gives  rise  to  blood  cells  during 
the  earlier  stages  and  may  continue  to  do  so  until  relatively  late  in  embryonic 
life  as  has  been  demonstrated  in  the  chick.  It  is  interesting  to  note  in  this 
connection  that  in  certain  regions  endothelial  cells  may  also  be  transformed 
into  primitive  blood  cells.  In  the  earlier  stages  of  liver  development  active 
haemopoiesis  is  observed  in  the  sinusoids,  probably  partly  from  cells  carried  in 


FIG.  210. — Showing  the  escape  of  the  nuclei 
from  nucleated  red  blood  cells.  Howell. 

I,  2,  3,  4,  represent  stages  of  extrusion 
observed  in  living  cells;  a,  from  circulat- 
ing blood  of  adult  cat  after  bleeding  four 
times;  b,  from  young  kitten  after  bleed- 
ing; c,  from  90  mm.  cat  embryo;  others 
from  marrow  of  adult  cat. 


240 


TEXT-BOOK  OF  EMBRYOLOGY. 


by  the  blood  stream  and  partly  from  primitive  blood  cells  derived  from  the 
neighboring  mesenchyme  (Fig.  211).  This  function  ceases  in  the  liver  in  later 
embryonic  life.  The  formation  of  blood  cells  takes  place  in  the  developing 
spleen  but  erythrocyte  formation  ceases  after  birth,  although  following  severe 
haemorrhage  the  function  may  be  resumed  even  in  adult  life.  The  formation 
of  lymphocytes,  however,  goes  on  throughout  life  in  the  splenic  corpuscles. 


FlG.  2 1 1. — From  the  liver  of  a  rabbit  embryo,  showing  formation  of  red  blood  cells.     Maximow. 
a,  Megaloblasts;  a',  megaloblast  in  mitosis;  b,  normoblasts;  c.  erythroblasts;  en,  en',  en'',  endothe- 
Hal  cells;   h,  liver  cells;   /,  primitive  lymphocytes;   /',  primitive  lymphocyte  in  mitosis; 
«,  nucleus  being  extruded  from  small  erythroblast. 

The  lymph  glands  are  constant  sources  of  lymphocytes,  the  parent  cells  being 
the  large  mononuclear  cells  found  in  the  germinal  centers.  These  cells  are 
regarded  as  closely  allied  to  the  primitive  lymphocytes,  perhaps  even 
identical,  although  here  in  this  particular  environment  giving  rise  only  to  the 
lymphocyte  line. 

The  bone  marrow  is  an  important  source  of  blood  cells  in  the  embryo, 
and  in  the  adult  under  normal  conditions  is  regarded  as  the  only  source  of 


THE  DEVELOPMENT  OF  THE  VASCULAR  SYSTEM. 


241 


red  corpuscles.  The  parent  stem  cells,  here  called  myeloblasts,  are  recog- 
nizable in  the  form  of  large  mononuclear,  non-granular  cells,  with  the  general 
characters  of  primitive  lymphocytes,  which  give  rise  to  the  red  blood  cells 
through  clearly  distinguishable  megaloblast  and  normoblast  stages,  and  to 
the  various  forms  of  leucocytes  and  lymphocytes.  In  addition  the  parent 


W 


m 


f' 

/W 
/// 


tn 


** 

'"??  4tt  «-* 


•^V 

^m-- 


m  ^ 


^j» 


•~®  &&  i 


m1 


meg 
m 

I 


«' 
/ 

e' 

m 
/re' 

/n" 


FIG.  212. — From  a  section  of  red  marrow  from  the  femur  of  a  young  rabbit.     Schafer. 
e,  Erythrocy tes ;  er,  normoblasts;  e",  normoblast  in  mitosis;  /,  outlines  of  fat  cells;  ^,  polymor- 
phonuclear    leucocytes;    m,    neutroohile    myelocytes;    m',   myelocytes    in   mitosis;    m", 
eosinophile  myelocytes;  m'".  basophile  myelocytes. 

cells  also  give  rise  to  certain  other  cells  which  are  normally  confined  to  the 
marrow,  viz.,  the  myelocytes.  These  are  large  mononuclear  cells,  with 
vesicular  nuclei,  the  cytoplasm  containing  neutrophile,  acidophile,  or  baso- 
phile granules  similar  to  those  of  the  leucocyte  series  (Fig.  212).  The 
genetic  relationships  of  the  "giant"  cells,  or  myeloplaxes,  in  the  marrow  are 
not  clear.  The  myeloplaxes  are  large  masses  (30  to  100  micra  in  diameter) 


242 


TEXT-BOOK  OF  EMBRYOLOGY. 


of  homogeneous  or  finely  granular,  slightly  basophilic  cytoplasm  containing 
either  a  single  lobulated,  annular  nucleus  (megakaryocytes,  Fig.  212,  meg) 
or  many  nuclei  (polykaryocytes).  The  polykaryocytes  have  been  considered 
identical  with  the  osteoclasts,  which  may  represent  fused  osteoblasts,  but 
this  relationship  has  not  been  definitely  established.  Both  kinds  of  cells 
have  been  considered  as  derivatives  of  the  myeloblasts,  the  polykaryocytes 
being  later  stages  of  megakaryocytes. 

The  blood  platelets  are  now  regarded  by  some  authors  as  derivatives  of 
the  megakaryocytes;  pseudopodia  of  the  latter  breaking  off  and  gaining 
access  to  the  blood  stream.  By  others  they  are  not  believed  to  be  formed 
constituents  of  the  circulating  blood,  but  appear  only  after  shed  blood 
comes  in  contact  with  a  foreign  substance. 

The  accompanying  table,  which  is  a  tentative  graphic  scheme  of  the 
monophyletic  theory,  will  assist  the  student  in  tracing  the  lineage  of  the 
blood  cells. 

Primitive  lymphocyte  (Maximow) 
Primitive  blood  cell  —  Haemoblast 


Primitive 
blood  cell 


^Lymphocytes 


Polymorph 


Granular     Non-granular 

\  i\ 


Momonudear   \  Mononuclear 


Transitional     \  Transitional 


Neutrophile  Basophile      Basophile 
Acidophile     Neutrophile  Acidophile 
Acidophile     Neutrophile 


Megaloblast 
Normoblast 
Erythroblast 
Erythrocyte 

V 

Megaloblast 
etc. 


Primitive 
blood  cell 


Lymphocytes 


Myeloblast     Leucocyte  series 

/  I  \  (as  above) 

Neutrophile         Basophile 

"yyelocyte        \    myelocyte 

Acidophile 

myelocyte 


Primitive 

blood  cell 

etc. 


THE  LYMPH  VASCULAR  SYSTEM. 


A  controversy  has  arisen  over  the  origin  of  the  lymph  channels  and  their 
endothelium,  similar  to  the  one  that  arose  over  the  genesis  of  the  blood  vessels. 
There  are  therefore  two  main  views,  viz.:  (i)  that  the  endothelium  of  the 
lymph  vessels  arises  as  sprouts  from  the  endothelium  of  veins  and  continues 
to  grow  by  proliferation  and  migration  of  its  own  cells,  the  lymphatics  thus 


THE  DEVELOPMENT  OF  THE  VASCULAR  SYSTEM. 


243 


being  direct  derivatives  of  the  venous  channels;  (2)  that  the  lymph  vessels 
arise  in  situ  through  enlargement  and  coalescence  of  intercellular  tissue 
spaces,  the  mesenchymal  cells  bounding  these  spaces  becoming  flattened  and 
rearranged  to  form  the  endothelial  walls  of  the  vessels,  and,  as  a  corollary, 
that  the  junction  of  the  lymph  vessels  with  the  veins,  which  occurs  at  certain 
definite  points,  is  a  secondary  matter. 

Here  again  the  scope  of  the  work  does  not  permit  presentation  in  detail 


Ant.  cardinal  vein    I — -/~ 

^ 
Subclavian  vein    — 

/ 

Diaphragm 


Suprarenal  gland        /C~~ 

Mesonephros 

Kidney-- 


Ant, lymph  heart 

Deep  lymphatics 

of  arm 


Branches  to  heart 

r 

Branches  to  lung 
Aorta 

—  '  Branch  to  oesophagus 
•'Branches  to  stomach 
^Branch  to  duodenum 

•/•  Branches  to  mesenteric  plexus 
Cisterna  chyli 


Post,  lymph  heart 

Deep  lymphatics 
to  leg 

FIG.  213. — Diagram  showing  the  arrangement  of  the  lymphatic  vessels  in  a 
pig  embryo  of  40  mm.     Sdbin. 

of  the  evidence  adduced  in  favor  of  either  of  these  views.  The  advocates 
of  the  first  view  have  placed  much  dependence  upon  the  method  of  in- 
jection, which,  as  in  the  case  of  the  origin  of  blood  vessels,  has  been  met 
with  the  criticism  that  injection  shows  only  those  lymph  channels  with  con- 
tinuous lumina  and  leaves  undetermined  the  field  beyond  the  injected  area 
(see  page  194).  To  supplement  their  studies  by  the  injection  method,  the 
investigators  who  maintain  that  lymphatic  endothelium  grows  by  sprouting 
of  preexisting  endothelium  have  added  studies  on  living  tissues  in  which 
the  sprouting  phenomena  are  claimed  to  be  clearly  observable.  Those  who 


244 


TEXT-BOOK  OF  EMBRYOLOGY. 


maintain  that  the  lymphatics  and  their  endothelium  arise  in  situ  from 
intercellular  tissue  spaces  and  the  bordering  cells,  argue  that  the  same 
principles  underlie  the  formation  of  lymphatics  that  determine  blood-vessel 
development  and  that  it  has  been  shown  experimentally  that  blood  vessels 
develop  in  regions  which  have  been  entirely  cut  off  from  any  source  of  endo- 
thelium except  the  mesenchymal  cells 
in  situ  (see  page  194).  •  ;.-'• 

According  to  the  first  view  lym- 
phatic development  can  be  divided  into 
two  stages:  (i)  the  formation  of  isolated 
lymph  sacs,  derived  from  veins,  which 
become  united  into  a  system,  and  (2) 
the  peripheral  growth  of  lymph  vessels 
which  sprout  from  the  endothelium  of 
these  sacs  and  spread  through  the  body. 
(i)  The  first  sacs  appear,  one  on  each 
side,  along  the  jugular  (anterior  cardi- 
nal) veins.  The  branches  of  these  veins 
at  first  form  a  plexus;  a  portion  of  the 
plexus  becomes  cut  off  from  the  parent 
stems  and  lies  as  a  series  of  isolated 
spaces  in  the  mesenchyme ;  these  spaces 
then  enlarge  and  coalesce  to  form  an  en- 
dothelial-lined  sac — the  jugular  lymph 
sac  or  heart — which  afterward  joins  the 
jugular  vein  by  a  new  opening  (-Fig. 
213).  A  second  pair  of  sacs — the  pos- 
terior lymph  sacs  or  hearts — develops 
in  the  same  manner  from  the  more 
caudal  branches  of  the  posterior  cardi- 
nal veins  (Fig.  213).  Two  other  sac- 
like  structures  develop — the  cisterna 

chyli  and  retroperitoneal  sac — the  former  in  the  region  of  the  renal  veins 
and  the  latter  in  the  vicinity  of  the  suprarenal  bodies.  Through  the  longi- 
tudinal fusion  of  the  chain  of  sac-like  structures,  the  axial  lymphatic  drain- 
age line  of  the  body  is  established  (Fig.  213).  The  thoracic  duct  probably 
represents  the  fused  cisterna  chyli  and  jugular  lymph  hearts.  The  lymph 
hearts  in  the  avian  and  mammalian  embryo  become  relatively  smaller  as 
development  proceeds  until  in  the  adult  they  are  barely  discernible  as  slight 
dilatations  in  the  lymph  vessels.  The  cisterna  chyli,  however,  may  persist 
as  a  clearly  distinguishable  dilatation  at  the  caudal  end  of  the  thoracic  duct. 


FIG.  214. — Diagram  showing  network  of 
lymphatic  vessels  in  skin  of  pig  embryos. 
Sabin. 

Area  marked  A  shows  extent  of  network  in 
an  embryo  of  18  mm.;  B,  in  embryo  of 
20  mm.;  C,  in  embryo  of  30  mm.;  D,  in 
embryo  of  40  mm. 


THE  DEVELOPMENT  OF  THE  VASCULAR  SYSTEM. 


245 


(2)  The  peripheral  lymph  channels,  which  drain  into  the  thoracic  duct, 
represent  outgrowths  from  the  lymph  sacs.     From  the  jugular  sacs  sprouts 


oj 


' 


FIG.  215. — From  cross-sections  of  cat  embryos  in  successive  stages  (<z,  b,  c,  d)  of  development, 
in  the  region  of  the  jugular  lymph  sac;  diagrammatic  but  amply  supported  by  studies  of  serial 
sections  and  reconstructions.  Huntington. 

i,  Anterior  cardinal  vein;  2,  somatic  tributary  of  same;  4,  developing  blood  cells  in  the  mesen- 
chyme;  5,  mesenchymal  intercellular  spaces — rudiments  of  the  jugular  lymph  sac;  6,  rudi- 
merits  of  brachio-cephalic  venous  anastomosis;  7,  brachio-cephalic  venous  anastomosis;  8, 
haemophoric  lymphatic  plexus — forerunner  of  jugular  lymph  sac;  u,  thoracic  duct- 
'approach'  of  jugular  lymph  sac;  12,  rudiments  of  thoracic  duct;  13,  jugular  lymph  sac  pre- 
paring to  rejoin  vein  and  to  establish  secondary  connection  with  rudiments  of  thoracic 
duct  (12)  and  of  other  systemic  lymphatics  (14);  15,  jugular  lymph  sac,  which  has  re- 
joined vein  through  permanent  lymphatico-venous  tap  (16);  17,  thoracic  duct;  1 8,  jugular 
and  cephalic  systemic  lymphatics. 

invade  the  neck,  head,  shoulders,  and  finally  the  entire  upper  extremities 
and  upper  part  of  the  body  wall  (Fig.  214).  Similarly,  from  the  posterior 
lymph  hearts  sprouts  invade  the  lower  extremities  and  lower  portion  of  the 


246 


TEXT-BOOK  OF  EMBRYOLOGY. 


body  wall  (Fig.  214).  Outgrowths  from  the  original  axial  drainage  line  invade 
the  various  visceral  organs  (Fig.  213).  Thus  the  lymphatic  drainage  of  the 
body  is  effected  through  outgrowths  from  a  few  primary  centers  which 
represent  derivatives  of  the  venous  channels.  The  lymph  glands  are  second- 
ary foci  of  development  along  the  lymph  vessels  (see  page  249). 

The  view  that  lymphatics  arise  as  enlarged  isolated  intercellular  spaces 
in  the  mesenchymal  tissue  does  not  include  any  dispute  as  to  the  general 


FIG.  216. — From  a  photograph  (X  600)  of  a  cross-section  through  the  caudal  end  of    a  chick 

embryo   of    15    mm.,  showing   enlarged   mesenchymal  intercellular  spaces  as  rudiments 

of  the  posterior  lymph  sac.     West. 
3,  Coccygeal  vein;  6,  caudal  muscle  plate;  8,  isolated  enlarged  intercellular  spaces,  the  bounding 

cells  becoming  flattened;  9,  lateral  branch  of  coccygeal  vein;  10,  lymphatics  containing 

collections  of  developing  blood  cells. 

disposition  of  the  lymph  channels  in  the  body,  but  comprises  a  funda- 
mentally different  concept  of  the  origin  of  these  vessels.  Upon  a  long  and 
exhaustive  series  of  observations  on  closely  graded  series  of  embryos  of 
Fishes,  Amphibia,  Reptiles,  Birds,  and  Mammals  is  based  the  conclusion 
that  not  only  the  lymph  sacs  but  the  peripheral  lymphatics  as  well  originate 
independently  of  the  veins;  and  that  the  opening  of  the  main  lymphatic 
drainage  lines  into  the  jugular  or  subclavian  veins  near  their  junction, 


THE  DEVELOPMENT  OF  1HE  VASCULAR  SYSTEM. 


247 


and  into  the  inferior  vena  cava  and  renal  veins  (in  some  monkeys) ,  is  second* 
arily  established.  The  same  hydrodynamic  mechanical  factors  regarded 
as  operative  in  the  formation  of  blood  vessels,  viz.:  pressure  and  friction 
incident  to  blood  flow  (see  page  195),  are  considered  as  effective  likewise 
in  the  development  of  lymphatics.  Fundamentally,  therefore,  the  lymph 
vascular  system  from  the  viewpoint  of  development  differs  in  no  wise  from 
the  blood  vascular  system. 


•o-l 


FIG.  2 1 7.— Diagrams  showing  three  stages  (a,  b,  c)  in  the  development  of  the  thoracic  duct  in 
the  cat  embryo,  in  which  the  jugular  lymph  sac  has  established  two  permanent  venous 
connections  (8  and  9).  Huntington. 

i,  Anterior  cardinal  vein;  2,  duct  of  Cuvier;  3,  posterior  cardinal  vein;  4,  external  jugular- 
cephalic  vein;  5,  subclavian  vein;  6,  jugular  lymph  sac;  7,  thoracic  duct  'approach'  of 
lymph  sac;  8,  common  jugular  opening  of  lymph  sac;  9,  jugulo-subclavian  opening  of  lymph 
sac;  10,  rudiments  of  thoracic  duct;  n,  thoracic  duct. 

The  lymph  sacs,  both  jugular  and  posterior,  arise  through  enlargement 
and  confluence  of  mesenchymal  intercellular  spaces,  the  cells  bounding  the 
spaces  becoming  flattened  and  rearranged  to  form  endothelium.  In  the 
case  of  the  mammalian  (cat)  jugular  sac,  intercellular  spaces  in  the  region 
dorso-lateral  to  the  anterior  cardinal  vein  unite  into  an  intricate  plexus  of 
channels  which  then  opens  into  the  vein  (Fig.  215,  a  and  b).  Following 
this  the  components  of  the  plexus  enlarge  and  coalesce  to  form  the  sac, 
which  then  temporarily  severs  connection  with  the  vein  (Fig.  2 1 5,  c) .  Finally 
the  sac  effects  a  permanent  connection  with  the  vein  through  one  or  more 


248  TEXT-BOOK  OF  EMBRYOLOGY. 

openings  which  represent  the  lymphatico-venous  communications  of  the 
adult  (Fig.  215,  d).  In  the  case  of  the  posterior  sac,  intercellular  spaces 
dorsal  to  the  posterior  cardinal  vein  (Fig.  216,  8)  first  form  a  plexus  the 
components  of  which  then  unite  into  a  large  endothelial-lined  space  which 
opens  into  the  dorsal  tributaries  of  the  vein. 

The  thoracic  duct  also  arises  as  a  chain  of  isolated  endothelial-lined 
spaces  along  the  line  of  the  aorta.  These  unite  longitudinally  into  a  con- 
tinuous channel  which  joins  the  jugular  lymph  sac,  thus  forming  the  axial 
lymphatic  drainage  line  of  the  body  (Fig.  217,  a,  b,  c).  In  reptilian  embryos 
the  spaces  first  fuse  into  a  distinct  periaortic  plexus  out  of  which  the  thoracic 
duct  is  established.  In  the  avian  embryo  the  chain  of  spaces  follows  the 
general  line  of  the  aorta  but  does  not  become  so  intimately  associated  with 
the  great  arterial  trunk  as  in  reptiles.  In  the  mammalian  forms  rudiments 
of  the  thoracic  duct  follow  the  same  general  plan  of  development,  but  are 
associated  topographically  with  the  ventro-medial  tributaries  of  the  azygos 
veins.  These  tributaries  finally  become  detached  from  the  larger  venous 
trunks,  atrophy  and  disappear,  being  replaced  by  the  thoracic  duct. 

On  the  same  principles  laid  down  for  the  development  of  the  lymph  sacs 
and  thoracic  duct,  the  peripheral  lymphatics  also  are  developed.  In  all 
the  regions  of  the  body  not  immediately  drained  by  the  lymph  sacs  or 
thoracic  duct,  mesenchymal  intercellular  spaces  enlarge  and  coalesce,  the 
cells  bounding  the  coalesced  spaces  being  transformed  directly  into  endo- 
thelium;  the  spaces  unite  to  form  a  plexus  of  endothelial-lined  channels, 
and  in  this  plexus  certain  channels  increase  in  size  to  form  the  larger  lym- 
phatics which  converge  and  eventually  join  the  main  axial  drainage  line. 
Thus  the  lymphatic  drainage  of  the  entire  body  is  established. 

One  of  the  most  interesting  and  significant  phases  of  lymphatic  develop- 
ment, which  has  been  brought  out  through  recent  studies  of  the  problem,  is 
the  role  played  by  certain  early  lymph  channels  in  conveying  blood  cells  to 
the  general  circulation.  It  has  been  found  that,  in  the  region  subsequently 
occupied  by  the  lymph  sacs,  extensive  blood  cell  formation  (haemopoiesis) 
occurs  prior  to  the  formation  of  lymphatic  rudiments.  As  the  lymph  spaces 
appear  and  unite  into  a  plexus  the  developing  blood  cells  are  included  within 
them  (Fig.  215,  a  and  Fig.  216,  10).  When  the  lymphatic  plexus  joins 
the  veins  the  blood  cells  are  carried  into  the  general  circulation  (Fig.  215,  b). 
This  haemophoric  function  of  the  early  lymph  channels  is  especially  prominent 
in  the  case  of  the  thoracic  duct  in  the  chick.  Here  extensive  collections  of 
blood  cells  develop  in  the  mesenchymal  tissue  along  the  line  of  the  aorta 
and  become  included  within  the  rudiments  of  the  thoracic  duct  and  eventu- 
ally, when  the  latter  unites  with  the  jugular  lymph  sac,  are  carried  into  the 
veins  and  thus  enter  the  general  circulation.  After  these  early  lymphatics, 


THE  DEVELOPMENT  OF  THE  VASCULAR  SYSTEM. 


249 


which  transport  blood  cells  and  which  have  been  defined  as  haemophoric 
lymphatics,  or  veno-lymphatics,  fulfil  their  haemophoric  function  they  are 
retained  as  permanent  lymph  channels  in  the  general  lymphatic  organiza- 
tion. In  a  broader  interpretation,  the  haemophoric  function  of  certain 
lymph  vessels  during  ontogeny  is  particularly  significant  in  that  it  indicates 
essential  and  fundamental  similarity  of  lymphatic  vascular  development  to 
haemal  vascular  development. 


The  Lymph  Glands. 

The  lymph  glands  do  not  begin  to  develop  for  some  time  after  the  lym- 
phatic vessels,  since  there  are  no  indications  of  them  in  the  human  foetus 
until  the  latter  part  of  the  third  month  and  none  in  pig  embryos  until  thev 

Efferent  lymph,  ves. 


Blood  vessel 


•'. '' V  '  *  "  ""  *'*-'  :&"  V  >'  V'''V 


iH      K|rMarginalsi 

mmm-A 


•i*.'.:,V*:&v'  •.•;»;— Capsule 

S&W&fi?      ''i'> 

P^S     :'V{ 

^^,x-^a 

rtv    ,;  v* 


'      '.  /  'I  \  **~ ,"        '    fV 

Afferent       ^.,1. r •..;/'"'<"- ,r   ?'^^ 
lymph,  ves.        is,    »j  ,*;  •  ;j  ,\vW'l 

U         . j  >. ,   , 


FIG.  218. — From  a  section  through  the  axilla  of  a  human  embryo  of  125  mm.  (4-5  months), 
showing  an  early  stage  of  a  lymph  gland.     Kling. 

have  reached  a  length  of  30  mm.  While  it  is  definitely  settled  that  lymph 
glands  originate  in  very  close  relation  with  the  lymphatic  vessels,  certain 
points  in  their  later  development  need  further  study.  In  the  axilla  and 
groin,  for  example,  the  lymphatic  vessels  form  a  dense  network  in  the  meshes 
of  which  are  masses  of  connective  tissue.  These  masses  become  more 
cellular  and  with  the  surrounding  vessels  constitute  the  anlagen  of  lymph 
glands  (Fig.  218).  The  new  cells  which  appear  in  the  masses  are  lympho- 
cytes which  may  pass  through  the  walls  of  the  neighboring  blood  vessels  and 
lodge  here  or  may  be  derived  directly  from  connective  tissue  (mesenchymal) 
cells  in  situ.  Whatever  the  origin  of  the  lymphocytes  may  be,  they  have  the 
opportunity  here  to  divide  freely.  The  mass  becomes  still  more  cellular  and 
enlarges  at  the  expense  of  the  lymphatic  vessels  which  then  come  to  form  a 


250 


TEXT-BOOK  OF  EMBRYOLOGY. 


network  around  the  mass.  This  network  is  the  marginal  plexus,  and  it 
communicates  freely  with  the  neighboring  lymphatic  channels.  Within 
the  mass  of  cells  blood  vessels  are  present  from  the  beginning,  and  these 
are  destined  to  be  the  blood  vessels  of  the  lymph  gland,  and  the  point  of  their 
entrance  and  exit  marks  the  hilus.  Outside  of  the  marginal  plexus  the  con- 
nective tissue  condenses  to  form  the  capsule.  The  gland  at  this  stage  thus 
consists  of  a  central  compact  cellular  mass,  made  up  of  connective  tissue 
and  lymphocytes,  in  which  blood  vessels  ramify;  a  plexus  of  lymphatic 
channels  around  the  mass  which  communicate  with  the  neighboring  channels; 
and  around  the  whole  structure  a  capsule  of  connective  tissue  (Fig.  218). 
Further  development  consists  of  the  breaking  up  of  the  cell  mass  by 

Afferent  lymphatic  vessels 


Marginal  sinus 


Dense  lymph. 

tissue 


•Marginal  sinus  (plexus) 
Capsule 
Trabecula 
.Reticular  tissue 


Intermediary 
plexus 


Efferent  lymph,  vessel 


Blood  vessels 


FlG.  219.— Diagram  illustrating  a  stage  (later  than  Fig.  218)  in  the  development 
of  a  lymph  gland.     Stohr. 

iymj  hatic  channels  and  the  formation  of  the  follicles.  It  seems  probable 
that  branches  from  the  marginal  plexus  invade  the  cell  mass  principally 
from  an  area  around  the  hilus,  thus  breaking  it  up  into  smaller  irregular 
masses  or  cords.  At  the  side  opposite  the  hilus  the  invading  channels  are  less 
numerous,  leaving  larger  parts  of  the  mass  which  become  the  follicles  (nodules) 
of  the  cortex.  On  all  sides  the  invading  channels  communicate  with  the 
marginal  plexus  and  form  the  so-called  intermediary  plexus.  The  gland  as 
a  whole  enlarges  and  its  peripheral  part  pushes  outward  into  the  surrounding 
tissue.  Over  the  follicles  the  capsule  is  pushed  outward,  while  between  them 
it  remains  in  place  and  comes  to  dip  into  the  gland  as  the  trabeculcz.  The 
blood  vessels  tend  to  lie  in  the  trabeculae,  but  a  small  branch  probably 
passes  to  each  follicle.  In  the  follicles  themselves  the  lymphocytes  pro- 


THE  DEVELOPMENT  OF  THE  VASCULAR  SYSTEM. 


251 


liferate  and  the  central  part  of  each  follicle  becomes  a  germinal  center.  The 
connective  tissue  among  the  lymphatic  vessels  composing  the  marginal  plexus 
becomes  proportionately  less  as  the  vessels  enlarge  and  finally  exists  only  as 
strands  of  reticular  tissue  which,  naturally,  are  covered  by  the  endothelium ; 
thus  the  marginal  plexus  becomes  the  marginal  sinus.  The  intermediary 
sinus  is  formed  by  the  channels  which  originally  invaded  the  cell  mass.  The 
reticular  tissue  is  probably  composed  of  remnants  of  the  original  connective 
tissue.  All  the  channels  converge  at  the  hilus  to  form  the  efferent  lymphatic 
vessels  (Figs.  219  and  220). 

The   haemolymph  glands   are  probably  developed  in  much   the   same 


Afferent  lymph,  vessels 


Lymph  follicle 


Marginal 
plexus 


Intermediary, 
plexus 


Medullary  cord 


Trabecula 


Capsule  r.^s«^ 

Efferent  lymph,  vessels 

FIG.  220. — Diagram  illustrating  a  late  stage  in  the  development  of  a  lymph  gland. 
Compare  with  Fig.  219.     Stohr. 

manner  as  the  lymph  glands  except  that  in  the  former  the  sinuses  are  filled 
with  red  blood  cells. 

The  first  lymph  glands  to  develop  are  those  in  the  axilla,  in  the  inguinal 
region,  in  the  neck,  and  in  the  base  of  the  mesentery.  These  are  the  so-called 
primary  glands  and  develop  during  fcetal  life.  They  are  of  constant  occur- 
rence in  these  regions,  but  vary  in  number  in  different  individuals.  The 
secondary  lymph  glands  are  those  in  the  bend  of  the  elbow,  in  the  popliteal 
space,  in  the  mesentery,  and  around  the  aorta.  Some  of  these  develop  during 
foetal  life  and  some  later.  While  lymph  glands  are  of  constant  occurrence  in 
some  regions  throughout  life,  the  number  may  vary  at  different  times  in  any 
region;  and  there  may  also  be  variations  in  different  individuals.  Glands 
may  be  called  into  existence  at  any  time  during  life,  in  almost  any  region, 
as  the  result  of  exceptional  activity  of  some  organ,  or  in  pathological  con- 
ditions. Such  structures  are  known  as  tertiary  lymph  glands. 


252  TEXT-BOOK  OF  EMBRYOLOGY. 

The  origin  of  the  lymph  (plasma)  itself  is  probably  extremely  complex. 
At  one  time  it  was  considered  as  the  result  of  nitration  from  the  blood  plasma 
through  the  capillary  walls.  If  lymph  originates  in  this  way  the  nitration 
is  selective,  for  the  chemical  composition  of  the  lymph  differs  from  that  of 
the  blood  plasma.  In  all  probability  the  lymph  plasma  consists  of  blood 
plasma  which  has  escaped  through  the  vessel  walls  plus  the  products  of  cell 
activity  in  the  tissues. 

The  Spleen. 

Since  the  spleen  is  generally  considered  as  a  lymphatic  organ  and  since 
recent  researches  have  shown  that  its  structure  is  quite  comparable  to  that 
of  the  lymph  glands,  it  seems  advisable  to  consider  it  under  the  head  of  lym- 
phatic organs.  Its  ultimate  origin  is  not  yet  settled  and  the  details  of  its 
later  development  are  still  obscure.  The  same  difficulties  are  met  with  as  in 
the  case  of  the  origin  and  development  of  blood  cells,  for  it  is  known  that  the 
spleen  plays  a  part  in  the  formation  of  the  blood  cells.  Its  structure  differs 
from  that  of  the  lymph  glands  chiefly  in  that  it  possesses  no  distinct  lym- 
phatic sinuses;  but  it  does  possess  lymph  follicles  (splenic  corpuscles)  and 
densely  cellular  cords  (pulp  cords)  which  are  separated  by  cavernous  blood 
vessels  (cavernous  veins). 

For  some  time  the  spleen  was  considered  as  a  derivative  primarily  of  the 
mesenchyme  in  the  region  of  the  dorsal  mesogastrium.     More  recently, 
however,  investigators  have  taken  the  view  that  it  arises  partly,  or  possibly 
entirely,  from  the  mesothelium  (coelomic  epithelium)  of  the  dorsal  mesogas- 
trium.    In  human  embryos  during  the  fifth  week  the  anlage  of  the  spleen 
appears  as  an  elevation  on  the  left  (dorsal)  side  of  the  mesogastrium  (Fig. 
221).     This  elevation  is  produced  by  a  local  thickening  and  vascularization 
of   the   mesenchyme,    accompanied  by   a   thickening   of   the   mesothelium 
which  covers  it;  and,  furthermore,  the  mesothelium  is  not  so  distinctly 
marked  off  from  the  mesenchyme   as  in  other  regions.     Cells  from   the 
mesothelium  then  migrate  into  the  subjacent  mesenchyme  and  the  latter 
becomes  much  more  cellular  (Fig.  222).     The  migration  is  brief,  and  in 
embryos  of  about  forty-two  days  has  ceased,  and  the  mesothelium  is  again   1 
reduced  to  a  single  layer  of  cells.     The  elevation  becomes  larger  and  projects   ; 
into  the  body  cavity.     At  first  it  is  attached  to  the  mesentery  (mesogas- 
trium) by  a  broad,  thick  base,  but  as  development  proceeds  the  attachment  if 
becomes  relatively  smaller  and  finally  forms  only  a  narrow  band  of  tissue  'j 
through  which  the  blood  vessels  (splenic  artery  and  vein)  pass. 

Further  development  of  the  substance  of  the  spleen  consists  of  the  break- 
ing up  of  the  cellular  mesenchymal  tissue  by  blood  vessels  and  the  formation 
of  the  splenic  corpuscles.  The  connective  tissue  trabeculce,  as  well  as  the  jfj 


THE  DEVELOPMENT  OF  THE  VASCULAR  SYSTEM. 


253 


capsule  of  the  spleen  are  derived  from  the  original  mesenchymal  tissue.  The 
blood  vessels  become  dilated  in  parts  of  their  course  to  form  the  cavernous 
vessels  (cavernous  veins)  which  are  separated  by  the  pulp  cords.  The  con- 
nective (reticular)  tissue  of  the  pulp  cords  is  a  derivative  of  the  mesenchyme, 
as  are  also  the  various  types  of  cells  in  the  cords.  The  adventitia  of  the 
walls  of  some  of  the  small  arteries  becomes  infiltrated  with  lymphocytes  to 
form  the  splenic  corpuscles  (lymph  follicles). 

It  is  generally  recognized  that  during  foetal  life  the  spleen  is  a  hemato- 

Aorta 


Omental 
bursa 


Right  side 


Mesonephros 


Spleen 


Dorsal 

mesogastrium 
(greater  omentum) 


Abdominal  cavity 
(coelom) 


Stomach 
Left  side 


Bile  duct        Ventral  mesoRastrium 
(lesser  omentum) 

FIG.  221. — From  transverse  section  through  stomach  region  of  a  14 
pig  embryo.     Photograph. 


poietic  organ,  that  is,  both  leucocytes  and  nucleated  red  blood  cells  ai.e  pro- 
duced within  it.  Normally,  the  formation  of  erythrocytes  stops  at  or  soon 
after  birth.  In  severe  anaemia  or  in  pernicious  anaemia  in  postnatal  life, 
however,  the  presence  of  dividing  nucleated  red  blood  cells  suggests  a  return 
to  embryonic  conditions.  The  reticular  tissue  constitutes  the  source  of  these 
nucleated  forms  (erythroblasts) .  It  has  also  been  suggested  that  the  spleen 
acts  as  a  destroyer  of  worn-out  erythrocytes,  for  in  many  cases  apparent 
remnants  of  the  latter  have  been  observed  within  the  cytoplasm  of  the 


254  TEXT-BOOK  OF  EMBRYOLOGY. 

"  spleen  cells."  The  lymphocytes  proliferate  to  a  certain  extent  in  the  splenic 
corpuscles,  and  in  that  way,  at  least,  the  spleen  serves  as  a  base  of  supply  for 
leucocytes.  There  is  a  possible  suggestion  that  the  first  leucocytes  of  the 
spleen  have  their  origin  in  the  mesenchymal  cells  of  the  spleen  anlage.  This 
would  be  in  accord  with  the  observations  which  indicate  that  leucocytes  are 
derived  from  indifferent  mesenchyme  cells. 


Mesothelium        Anlage  of  spleen 


Mesenchyme 


FIG.  2  2  2. — From  section  through  dorsal  mesogastrium  (anlage  of  spleen)  of  a  chick  embryo 
of  3  days  and  21  hours  incubation.    Tonkofl. 

Glomus  Coccygeum. 

The  coccygeal  skein  (coccygeal  gland)  was  originally  considered  as  belong- 
ing to  the  same  category  as  the  suprarenal  glands,  but  the  latest  researches 
have  indicated  that  its  cells  do  not  possess  the  characteristic  chromamn 
reaction  and  that  it  belongs  rather  to  the  category  of  lymph  glands.  It 
develops  ventral  to  the  apex  of  the  coccyx  in  relation  with  branches  of  the 
middle  sacral  artery. 

Although  the  thymus  gland  becomes  a  lymphatic  structure  it  is  primarily 
derived  from  the  epithelium  (entoderm)  of  the  branchial  grooves  and  will  be 
considered  in  connection  with  the  development  of  the  alimentary  tract  (Chap. 
XII).  The  tonsils  also  will  be  considered  in  the  same  connection. 

Anomalies. 

ANOMALIES  OF  THE  HEART. 

ACARDIA. — The  malformation  known  as  acardia  occurs  in  the  case  of  twins 
that  have  but  one  chorion.  The  so-called  acardiac  condition  does  not 


THE  DEVELOPMENT  OF  THE  VASCULAR  SYSTEM.  255 

necessarily  imply  the  absence  of  the  heart  in  the  affected  twin,  for  the  latter 
may  develop  to  a  considerable  degree  and  possess  a  functionating  heart. 
On  the  other  hand,  the  affected  twin  may  be  only  an  amorphous  mass  of 
tissue  which  derives  its  total  blood  supply  through  the  agency  of  the  stronger 
twin's  heart.  Or  there  may  be  any  intermediate  form  between  these  two 
extremes.  The  point  is  that  the  acardiac  monster  (acardiacus)  derives  its 
blood  wholly  or  in  part  through  the  agency  of  the  stronger  heart.  A  further 
discussion  of  acardiac  monsters  and  their  possible  explanation  will  be  found 
in  Chap.  XX. 

DOUBLE  HEART. — But  one  or  two  Ceases  of  a  double  heart  in  a  single 
human  foetus  have  been  recorded.  In  some  of  the  lower  forms  (chick)  it 
occurs  more  frequently.  The  explanation  is  probably  to  be  found  in  the 
double  origin  of  the  heart  in  Amniotes  (p.  196). 

ANOMALOUS  POSITION  OF  THE  HEART. — Congenital  anomalies  in  the  posi- 
tion of  the  heart  are  rare.  Dextrocardia  (heart  on  the  right  side)  is  almost 
invariably  associated  with  changes  in  the  position  of  the  viscera  (see  trans- 
position of  the  viscera,  page  304) .  In  the  condition  known  as  ectopia  cordis, 
the  heart,  with  the  pericardium,  protrudes  through  a  cleft  in  the  ventral 
wall  of  the  thorax,  the  cleft  being  probably  due  to  an  imperfect  fusion  of  the 
two  sides  of  the  body  wall  in  that  particular  region. 

ANOMALIES  OF  THE  SEPTA. — The  most  frequent  anomaly  in  the  atrial 
septum  is  the  persistence  of  the  foramen  ovale.  The  entire  foramen  may 
remain  patent,  or,  as  is  more  frequently  the  case,  a  smaller  opening  may 
persist  between  the  ventral  (anterior)  border  of  the  foramen  and  the  valve  of 
the  latter  (p.  203). 

The  atrial  septum  may  be  wholly  lacking,  but  this  always  occurs  in  con- 
junction with  other  defects.  It  sometimes  happens  that  the  primary  atrial 
septum  (septum  superius),  which  grows  from  the  cephalic  side  of  the  common 
chamber,  fails  to  fuse  with  the  septum  of  the  atrio-ventricular  aperture  (p. 
203  and  Fig.  171). 

Defects  in  the  ventricular  septum  occur  less  frequently  than  in  the  atrial 
septum.  It  may  happen  that  the  cephalic  (upper)  border  of  the  ventricular 
septum  fails  to  fuse  with  the  septum  which  divides  the  aortic  trunk  and  bulb 
into  the  aorta  and  pulmonary  artery.  This  affects  the  cephalic  (upper)  part 
of  the  septum  sometimes  called  the  pars  membranacea  (p.  204  and  Fig.  174); 
and  since  the  defect  is  situated  near  the  opening  of  the  aorta  it  brings  about 
the  so-called  "origin  of  the  aorta  from  both  ventricles."  Stenosis  of  the 
pulmonary  artery  usually  accompanies  this  condition.  Rarely  is  there  a 
deficiency  in  the  caudal  (lower)  part  of  the  ventricular  septum.  Complete 
absence  of  the  ventricular  septum  may  occur,  and  along  with  it  also  an 
absence  of  the  atrial  septum,  so  that  the  heart  is  simply  two-chambered;  or 


256  TEXT-BOOK  OF  EMBRYOLOGY. 

the  single  ventricle  may  open  into  two  atria.     The  causes  of  these  defects  ] 
are  obscure. 

ANOMALIES  OF  THE  VALVES. — There  may  be  congenital  variations  in  the  j 
size  and  number  of  the  atrio-ventricular  valves,  depending  upon  abnormal 
position,  fusion,  or  division  of  the  pad-like  masses  from  which  the  valves  ! 
develop  (p.  206). 

There  may  be  also  a  greater  or  lesser  number  of  semilunar  valves  in  the  | 
aorta  and  pulmonary  artery.     This  irregularity  can  probably  be  referred 
back  to  an  atypical  division  of  the  aortic  trunk  and  bulb,  and  a  corresponding  \ 
atypical  division  of  the  protuberances  which  give  rise  to  the  valves  (p.. 206). 
Variations  in  the  valves  may  or  may  not  be  accompanied  by  functional  dis-  i 
turbances.     The  congenital  diminution  in  the  number  of  valves  should  be 
distinguished  from  the  acquired,  where  chronic  endocarditis  may  cause  a 
fusion. 

ANOMALIES  or  THE  LARGE  VASCULAR  TRUNKS. 

ANOMALIES  or  THE  ARTERIES. — There  may  be  a  transposition  of  the  aorta  \ 
and  pulmonary  artery.     This  results  from  an  anomalous  division  of  the  aortic 
trunk  and  bulb.     The  partition  develops  in  such  a  way  as  to  put  the  aorta  in 
communication  with  the  right  ventricle,  and  the  pulmonary  artery  with1  the  j 
left  ventricle  (p.  204).     Or  the  aorta  and  pulmonary  artery  may  remain  in  \ 
direct   communication   on   account   of   an   imperfect   development   of   the 
partition.     Rarely  the  two  vessels  remain  as  a  common  stem. 

Congenital  stenosis  (constriction)  of  the  pulmonary  artery  may  occur,  j 
accompanied  by  an  increase  in  the  size  of  the  aorta,  possibly  due  to  an  unequal  j 
division  of  the  aortic  trunk  and  bulb.     After  birth  little  or  no  blood  can  pass  \ 
to  the  lungs,  and  the  result  is  a  general  damming  (stasis)  of  the  venous  blood  ! 
with  marked  cyanosis.     This  is  at  least  one  explanation  of  the  so-called  "blue 
babies."    Less  frequently  there  is  a  stenosis  of  the  proximal  end  of  the  aorta, 
with  excessive  size  of  the  pulmonary  artery,  also  due  to  an  unequal  division 
of  the  aortic  trunk  and  bulb  (p.  204) .     These  stenoses  are  usually,  though  not 
always,  accompanied  by  defects  in  the  ventricular  septum. 

Persistence  of  the  ductus  arteriosus  may  occur  without  any  other  defect;  ;i 
but  usually  the  persistence  is  associated  with  anomalous  conditions  of  the 
aorta  and  pulmonary  artery. 

Occasionally  the  arch  of  the  aorta  is  found  on  the  right  side.  This  condi- 
tion is  due  to  the  persistence  of  the  fourth  aortic  arch  on  the  right  side  instead 
of  the  corresponding  arch  on  the  left  side;  this  is  the  normal  condition  in 
Birds.  Rarely  both  fourth  aortic  arches  persist,  which  results  in  a  double 
arch  of  the  aorta — the  normal  condition  in  Reptiles.  (Compare  Figs.  181 
and  182.) 


THE  DEVELOPMENT  OF  THE  VASCULAR  SYSTEM.  257 

The  dorsal  aorta,  particularly  the  abdominal  part,  is  occasionally  found  to 
consist  of  two  parallel,  imperfectly  separated  vessels — a  condition  known  as 
double  aorta.  This  anomaly  is  due  to  an  imperfect  fusion  of  the  two  primitive 
aortae  (p.  187  and  Fig.  165). 

Numerous  variations  are  met  with  in  the  larger  branches  of  the  aorta,, 
many  of  which  are  explained  by  referring  them  to  embryonic  conditions. 
Especially  noteworthy  are  the  branches  from  the  arch  of  the  aorta,  since  their 
development  is  so  closely  associated  with  the  changes  in  the  aortic  arches. 
The  normal  arrangement  passing  from  the  heart,  is  innominate  artery,  left 
common  carotid  artery,  left  subclavin  artery  (see  Fig.  182). 

1.  All  these  branches  may  be  collected  into  a  single  trunk  a  condition 
characteristic  of  the  horse. 

2.  Two  branches  may  arise  from  the  arch,     (a)  The  left  common  carotid 
unites  with  the  innominate,  and  the  left  subclavian  arises  separately.     This  is 
the  normal  arrangement  among  the  apes,  and  is  probably  the  most  common 
variation  in  man.     (b)  Very  rarely  there  are  two  innominate  arteries,  each 
formed  by  the  union  of  a  common  carotid  and  subclavian — a  condition  char- 
acteristic of  Birds. 

3.  Three  branches  may  arise  from  the  arch  but  in  a  manner  differing  from 
the  normal.     Each  subclavian  arises  separately  and  the  two  common  carotids 
are  united  into  a  single  vessel.     This  arrangement  is  found  in  some  of  the 
Cetacea. 

4.  Four  vessels  may  arise  from  the  arch,     (a)  These  are,  in  order,  in- 
nominate,  left   common   carotid,   left  vertebral,   left   subclavian.     (b)  Or 
the  order  may  be  right  common  carotid,  left  common  carotid,  left  subclavian, 
right  subclavian.     In  this  case  the  proximal  part  of  the  right  subclavian  rep- 
resents the  portion  of  the  right  dorsal  aortic  root  just  cranial  to  the  bifurca- 
tion; the  fourth  arch  on  the  right  side  disappears,     (c)  Or  very  rarely  the 
order  may  be  right  subclavian,  right  common  carotid,  left  common  carotid, 
left  subclavian. 

5.  Five  branches  of  the  arch  are  rare.     In  order  they  are  right  sub- 
clavian, right  vertebral,  right  common  carotid,  left  common  carotid,  left 
subclavian. 

6.  Very  rarely  there  are  six  branches  of  the  arch;  right  subclavian,  right 
vertebral,  right  .common  carotid,  left  common  carotid,  left  vertebral,  left 
subclavian. 

ANOMALIES  OF  THE  VEINS. — The  two  pulmonary  veins  on  each  side,  more 
frequently  those  on  the  left  side,  many  unite  into  a  common  trunk  before 
opening  into  the  atrium.  This  variation  is  probably  due  to  the  fact  that  the 
absorption  of  the  originally  single  pulmonary  trunk  into  the  wall  of  the 


258  TEXT-BOOK  OF  EMBRYOLOGY. 

atrium  does  not  proceed  far  enough  to  cause  all  four  of  the  pulmonary  veins 
to  open  separately  (see  p.  205) .  The  upper  (more  cephalic)  vein  on  the  right 
side  may  open  into  the  superior  vena  cava;  or  the  upper  vein  on  the  left  side 
may  open  into  the  left  innominate  vein.  A  possible  explanation  for  this  is 
that  the  pulmonary  veins  are  formed  after  the  heart  and  other  vessels  have 
developed  to  a  considerable  degree,  and  some  of  them  may  unite  with  the 
other  vessels  instead  of  with  the  atrium. 

Occasionally  two  superior  vena  cava  are  met  with.  In  this  case  the  right 
opens  into  the  right  atrium  in  the  normal  position;  the  left  opens  into  the 
right  atrium  through  the  coronary  sinus  which  naturally  is  much  enlarged. 
This  condition  represents  a  persistence  of  the  proximal  end  of  the  left 
anterior  cardinal  vein  and  the  left  duct  of  Cuvier,  and  is  the  normal  arrange- 
ment in  many  of  the  lower  Vertebrates.  Even  with  two  venae  cavae  there 
may  be  a  small  anastomosing  branch  in  the  position  of  the  left  innominate 
vein,  which  represents  the  normal  structure  in  the  Marsupials  (see  Figs. 
194  and  195  and  p.  223).  There  are  a  few  cases  on  record  of  a  single  left 
superior  vena  cava. 

The  inferior  vena  cava  is  also  subject  to  variations  which  represent  the 
abnormal  persistence  of  certain  embryonic  vessels.  Perhaps  the  most 
striking  of  these  variations  is  the  condition  known  as  double  inferior  vena 
cava.  There  may  be  two  parallel  vessels,  of  equal  or  unequal  size,  which 
unite  at  or  above  the  level  of  the  renal  veins.  This  condition  is  to  be  ex- 
plained by  the  persistence  of  parts  of  both  posterior  cardinal  veins.  It  is 
met  with  not  infrequently  among  the  lower  Mammals,  especially  the  Mar- 
supials (see  Figs.  195  and  198). 

Rarely  the  inferior  vena  cava  opens  into  the  superior,  and  in  this  case  the 
hepatic  veins  open  directly  into  the  right  atrium.  This  anomaly  probably 
represents  a  failure  of  the  absorption  of  the  sinus  venosus  into  the  wall  of  the 
atrium  (p.  205). 

A  left  renal  vein  may  open  into  the  left  common  iliac,  which  condition 
represents  a  persistence  of  the  more  caudal  part  of  the  left  posterior  cardinal 
(Fig.  198).  This  anomaly  is  rare. 

The  azygos  vein  occasionally  presents  variations  which  are  due  to  anoma- 
lous development.  All  the  intercostal  veins  on  the  left  side  may  be  collected 
into  a  vessel  which  opens  into  the  left  innominate  vein.  There  may  be  a 
single  median  azygos  vein;  or  there  may  be  a  transposition  of  the  azygos  vein. 
It  may  be  on  the  left  side  and  open  into  the  coronary  sinus  (normal  condi- 
tions in  the  sheep  and  a  few  other  Mammals).  The  latter  condition  repre- 
sents a  persistence  of  the  more  cephalic  part  of  the  left  posterior  cardinal 
vein  (see  Figs.  195  and  106). 


, 


THE   DEVELOPMENT  OF  THE  VASCULAR   SYSTEM.  259 

Space  does  not  permit  a  discussion  of  the  great  number  of  congenital 
variations  that  occur  in  the  smaller  blood  vessels,  both  arteries  and  veins. 
The  student  is  referred,  however,  to  the  more  extensive  text-books  of 
anatomy. 

References  for  Further  Study. 

BORN,  G.:  Beitrage  zur  Entwicklungsgeschichte  des  Saugetierherzens.  Archiv  f. 
mik.  Anat.  Bd.  XXXIII,  1899. 

BREMER,  J.  L.:  The  Origin  of  the  Renal  Artery  in  Mammals  and  Its  Anomalies. 
Am.  Jour,  of  Anat.,  Vol.  XVIII,  1915. 

CLARK,  E.  R.:  Further  Observations  on  Living  Growing  Lymphatics;  their  Relation 
to  Mesenchymal  Cells.  Am.  Jour,  of  Anat.,  Vol.  XIII  1911. 

CLARKE,  W.  C.:  Experimental  Mesothelium.     Anat.  Record,  Vol.  VIII,  1914. 

DANTSCHAKOFF,  W.:  Untersuchungen  iiber  die  Entwicklung  des  Blutes  und  Bindege- 
webes  bei  den  Vogeln.  Anat.  Hefte,  Bd.  XXXVII,  1908. 

DANCHAKOFF,  V.:  Origin  of  the  Blood  Cells.  Development  of  the  Haematopoietic 
Organs  and  Regeneration  of  the  Blood  Cells  from  the  Standpoint  of  the  Monophyletic 
School.  Anat.  Record,  Vol.  X,  No.  5,  1916. 

DANCHAKOFF,  VERA:  Cell  Potentialities  and  Differential  Factors  in  Relation  to 
Erythropoiesis.  Am.  Jour,  of  Anat.,  Vol.  XXIV,  1918. 

ETERNOD,  A.  C.  F.:  Premiers  stades  de  la  circulation  sanguine  dans  1'ceuf  et  embryon 
humain.  Anat.  Anz.,  Bd.  XV,  1899. 

EVANS,  H.  M.:  On  the  Earliest  Blood  Vessels  in  the  Anterior  Limb  Buds  of  Birds  and 
their  Relation  to  the  Primary  Subclavian  Artery.  Am.  Jour,  of  Anat.,  Vol.  IX,  1909. 

His,   W.:  Anatomic  menschlicher  Embryonen.    Leipzig,    1880-1885.     With   Atlas. 

HOCHSTETTER,  F.:  Die  Entwickelung  des  Blutgefasssystems.  In  Hertwig's  Handbuch 
der  vergleich.  und  experiment.  Entwickelungslehre.  Bd.  Ill,  Teil  II,  1901.  Contains  also 
extensive  bibliography. 

HOWELL,  W.  H.:  The  Life  History  of  the  Formed  Elements  of  the  Blood,  Especially 
the  Red  Blood-corpuscles.  Journal  of  Morph.,  Vol.  IV,  1890. 

HUNTINGTON,  G.  S.,  and  McCLURE,  C.  F.  W.:  Development  of  Postcava  and  Tribu- 
taries in  the  Domestic  Cat.  Am.  Jour,  of  Anat.,  Vol.  VI,  1907. 

J     HUNTINGTON,  G.  S.:  The  Phylogenetic  Relations  of  the  Lymphatic  and  Blood  Vas- 
cular Systems  in  Vetebrates.     Anat.  Record,  Vol.  IV,  1910. 

HUNTINGTON,  G.  S.:  The  Genetic  Principles  of  the  Development  of  the  Systemic 
Lymphatic  Vessels  in  the  Mammalian  Embryo.  Anat.  Record,  Vol.  IV,  1910. 

HUNTINGTON,  G.  S.:  The  Development  of  the  Lymphatic  System  in  Reptiles.  Anat. 
Record,  Vol.  V,  1911. 

HUNTINGTON,  G.  S.:  The  Anatomy  and  Development  of  the  Systemic  Lymphatic 
Vessels  in  the  Domestic  Cat.  Memoirs  of  the  Wistar  Institute  of  Anatomy  and  Biology, 
No.  i,  1911. 

HUNTINGTON,  G.  S.:  The  Development  of  the  Mammalian  Jugular  Lymph  Sac,  of  the 
Tributary  Primitive  Ulnar  Lymphatic  and  the  Thoracic  Ducts  from  the  Viewpoint  of 

recent  Investigations  of  Lymphatic  Ontogeny, Am.  Jour,  of  Anat.,  Vol.  XVI, 

No.  3,  1914. 

HUNTINGTON,  GEORGE  S.:  The  Morphology  of  the  Pulmonary  Artery  in  the 
Mammalia.  Anat.  Record,  Vol.  XVII,  1919. 


260  TEXT-BOOK  OF   EMBRYOLOGY. 

-  KLING,  C.  A.:  Studien  iiber  die  Entwicklung  der  Lymphdriisen  beim  Menschen. 
Archvo  f.  mik.  Anat.,  Ed.  LXIII,  1904. 

KOLLMANN,  J.:  Handatlas  der  Entwickelungsgeschichte  des  Menschen,  Bd.  II,  1907. 

LEHMAN,  H.:  On  the  Embryonic  History  of  the  Aortic  Arches  in  Mammals.  Anat. 
Am.,  Bd.  XXVI,  1905. 

LEWIS,  F.  T.:  The  Development  of  the  Vena  Cava  Inferior.     Am.  Jour,  of  Anat., 
Vol.  I,  1902. 
\J      LEWIS,  F.  T.:  The  Development  of  the  Veins  in  the  Limbs  of  Rabbit  Embryos.     Am. 

Jour,  of  Anat.  Vol.  V,  1906. 

»/        MALL,  F.  P.:  Development  of  the  Internal  Mammary  and  Deep  Epigastric  Arteries 
in  Man.     Johns  Hopkins  Hosp.  Bull.,  1898. 

MALL,  F.  P.:  On  the  Development  of  the  Blood  Vessels  of  the  Brain  in  the  Human 
Embryo.  Am.  Jour,  of  Anat.,  Vol.  IV,  1905. 

MALL,  F.  P.:  On  the  Development  of  the  Human  Heart.  Am.  Jour,  of  Anat.,  Vol. 
XIII,  1912. 

MAXIMOW,  A.:  Die  Friihesten  Entwicklungsstadien  der  Blut-  und  Bindegewebszellen 
beim  Saugetierembryo,  bis  zum  Anfang  der  Blutbildung  in  der  Leber.  Arch.  f.  mik. 
Anat.,  Bd.  LXXIII,  1909. 

MAXIMOW,  A.:  Lymphozyt  als  gemeinsame  Stammzelle  der  verschiedenen  Blutele- 
mente  in  der  embryonalen  Entwicklung  und  im  postfetalen  Leber  der  Saugetiere.  Folia 
Hdmatolog.,  Bd.  VIII,  1909. 

MAXIMOW,  A.:  Die  embryonale  Histogenese  des  Knochenmarks  der  Saugetiere. 
Arch.f.  mik.  Anat.,  Bd.  LXXVI,  1910. 

McCLURE,  C.  F.  W.:  The  Development  of  the  Lymphatic  System  in  Fishes  with 
Especial  Reference  to  its  Development  in  the  Trout.  Memoirs  of  the  Wistar  Institute  of 
Anatomy  and  Biology,  No.  4,  1915. 

McCLURE,  C.  F.  W.,  and  SILVESTER,  C.  F.:  A  Comparative  Study  of  theLymphati- 
co- Venous  Communications  in  Adult  Mammals.  Anat.  Record,  Vol.  Ill,  1909. 

MILLER,  A.  M.:  Histogenesis  and  Morphogenesis  of  the  Thoracic  Duct  in  the  Chick; 
Development  of  Blood  Cells  and  their  Passage  to  the  Blood  Stream  via  the  Thoracic 
Duct.  Am.  Jour,  of  Anat.,  Vol.  XV,  1913. 

MINOT,  C.  S.:  On  a  Hitherto  Unrecognized  Form  of  Blood  Circulation  without 
Capillaries  in  the  Organs  of  Vertebrata.  Proc.  Boston  Soc.  Nat.  Hist.,  Vol.  XXIX,  1900. 

REAGAN,  F.  P.:  Experimental  Studies  on  the  Origin  of  Vascular  Endothelium  and  of 
Erythrocytes.  Am.  Jour,  of  Anat.,  Vol.  XXI,  1917. 

ROSE,  C.:  Zur  Entwickelungsgeschichte  des  Saugetierherzens.  Morph.  Jahrbuch,  Bd. 
XV,  1889. 

RUCKERT,  J.,  and  MOLLIER,  S.:  Die  erste  Entstehung  der  Gefasse  und  des  Blutes  bei 
Wirbeltiere.  In  Hertwig's  Handbuch  der  vergleich  und  experiment.  Entwickelungslehre, 
Bd.  I,  Teil  I,  1906.  Contains  also  extensive  bibliography. 

SABIN,  F.  R. :  On  the  Origin  of  the  Lymphatic  System  from  the  Veins  and  the  Develop- 
ment of  the  Lymph  Hearts  and  Thoracic  Duct  in  the  Pig.  Am.  Jour,  of  Anat.,  Vol. 
I,  1902. 

SABIN,  F.  R.:  The  Origin  and  Development  of  the  Lymphatic  System.  The  Johns 
Hopkins  Hospital  Reports  Monographs,  New  Series,  No.  5,  1913. 

SALA,  L.:  Svilluppo  dei  cuori  linfatici  e  dei  dotti  toracici  nelP  embrione  di  polio. 
Ricerche  fatte  nel  laboratorio  de  anatomia  normale  della  R.  Universita  di  Roma,  Vol.  VII, 
1900. 


THE  DEVELOPMENT  OF  THE  VASCULAR  SYSTEM.  261 

SCAMMON,  R.  E.,  and  NORRIS,  E.  H.:  On  the  Time  of  the  Post-natal  Obliteration- of 
the  Foetal  Blood-passages  (Foramen  ovale,  Ductus  arteriosus,  Ductus  Venosus).  Anat. 
Record,  Vol.  XV,  1918. 

SCHULTE,  H.  VON  W.:  Early  Stages  of  Vasculogenesis  in  the  Cat  (Felis  domestica) 
with  Especial  Reference  to  the  Mesenchymal  Origin  of  Endothelium.  Memoirs  of  the 
Wistar  Institute  of  Anatomy  and  Biology,  No.  3,  1914. 

SCHULTE,  H.  VON  W.:  The  Fusion  of  the  Cardiac  Anlages  and  the  Formation  of  the 
Cardiac  Loop  in  the  Cat  (Felis  domestica).  Am.  Jour,  of  Anat.,  Vol.  XX,  1916. 

SENIOR,  H.  D.:  The  Development  of  the  Arteries  of  the  Human  Lower  Extremity. 
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STOCKARD,  CHAS.  R.:  The  Origin  of  Blood  and  Vascular  Endothelium  in  Embryos 
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Vol.  XVIII,  No.  2,  1915. 

STOERK,  O.:  Uber  die  Chromreaktion  der  Glandula  coccygea  und  die  Beziehung 
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STOHR,  P.:  Uber  die  Entwicklung  der  Darmlymphknotchen  und  uber  die  Riickbildung 
von  Darmdriisen.  Arch.  f.  mik.  Anat.,  Bd.  LI,  1898. 

STREETER,  GEORGE  L.:  The  Development  of  the  Venous  Sinuses  of  the  Dura  Mater  in 
the  Human  Embryo.  Am.  Jour,  of  Anat.,  Vol.  XVIII,  1915. 

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WRIGHT,  J.  H.:  The  Origin  and  Nature  of  the  Blood  Plates.  Boston  Med.  and  Surg. 
Jour.,  Vol.  CLIV,  1906. 


CHAPTER  XI 
THE  DEVELOPMENT  OF  THE  MUSCULAR  SYSTEM. 

Anatomy  and  Histology  show  that  there  are,  in  a  sense,  two  muscular 
systems  in  the  body,  and  Embryology  teaches  that  the  two  systems  have  dif- 
ferent origins. 

1.  The  skeletal  musculature. — This,  as  the  name  indicates,  is  closely  associated 
with  the  skeletal  system.     It  is  made  up  of  striated  muscle  fibers  arranged  to 
form  definite  bundles  or  muscles.     The  skeletal   musculature  is  under  the 
voluntary  control  of  the  central  nervous  system. 

2.  The  visceral  musculature. — This  is. found  in  connection  with  and  forms 
integral  parts  of  certain  organs.     It  is  made  up  of  two  different  kinds  of  fibers — • 
smooth  muscle  fibers  or  cells  and  striated  fibers  or  cells  (heart-muscle  cells). 
The  latter  are  found  only  in  the  wall  of  the  heart.     The  visceral  musculature  is 
involuntary,  being  under  the  control  of  the  sympathetic  nervous  system. 

Both  systems  are  derived  from  mesoderm  but  from  distinct  parts  of  the 
mesoderm.  Furthermore,  their  developmental  histories  are  quite  different,  as 
will  be  seen  in  the  following  paragraphs. 

THE  SKELETAL  MUSCULATURE. 

In  the  chapters  on  the  development  of  the  germ  layers  it  was  said  that 
throughout  the  length  of  the  body  region  of  the  embryo  the  mesoderm  on 
each  side  of  the  neural  tube  and  notochord  becomes  divided  into  a  definite 
number  of  segments — the  primitive  segments  or  mesodermic  somites  (Figs.  24, 
52,  51).  These  indicate  the  segmentation  of  the  body,  and  the  history  of  the 
greater  part  of  the  skeletal  musculature  dates  from  their  differentiation  from 
the  axial  mesoderm.  Thus  the  skeletal  musculature  is,  for  the  most  part, 
primarily  segmental  in  character. 

At  first  the  primitive  segments  are  composed  of  closely  packed,  epithelial- 
like  cells,  and  each  segment  contains  a  small  cavity  which  represents  a  portion 
of  the  coelom  (Fig.  103).  The  ventro-medial  parts  of  the  segments  become 
differentiated  to  form  the  sclerotomes  which  are  composed  of  more  loosely  ar- 
ranged cells  (Fig.  223),  and  which  are  destined  to  give  rise  to  the  vertebrae  and 
to  the  various  kinds  of  connective  tissue  in  their  neighborhood.  The  lateral 
parts  of  the  segments  become  differentiated  to  form  the  cutis  plates  which  are 
destined  to  give  rise  to  a  part  of  the  corium  of  the  skin.  The  remaining  portions 

262 


THE  DEVELOPMENT  OF  THE  MUSCULAR  SYSTEM. 


263 


of  the  segments  form  the  muscle  plates  or  myotomes  (Fig.  223),  from  which 
develop  by  far  the  greater  part,  at  least,  of  the  voluntary  striated  muscles. 

The  differentiation  of  the  parts  of  the  primitive  segments  begins  in  the  cervi- 
cal region  by  the  end  of  the  second  week,  and  then  gradually  proceeds  toward 
the  tail.  Three  myotomes  are  also  probably  formed  in  the  occipital  region. 
The  cells  of  the  myotomes  are  at  first  of  an  epithelial  character  (Fig.  105). 
Contractile  fibrils  appear  in  the  cells  and  the  latter  are  transformed  directly 
into  muscle  fibers.  (For  histogenesis  see  p.  276).  The  fibers  later  alter  their 
direction  in  accordance  with  the  particular  muscle  to  which  they  belong.  The 
muscle  tissue  first  formed  is  thus  segmented,  being  derived  from  the  segmen- 


Neural  crest 


Pronephros  --- 


Parietal  mesoderm 

Intestine 


limb  bud 


— -  Amnion 


Umbilical 
veio 


Visceral  mesoderm 


FIG.  223^— Transverse  section  of  human  embryo  of  the  3rd  week.     Scl.1,  Break  in  myotome  at 
point  where  sclerotome  is  closely  attached.     Kottmann. 


tally  arranged  myotomes,  but  as  development  proceeds  the  myotomes  undergo 
extensive  changes  by  which  the  segmental  character  is  lost  in  the  majority  of 
cases.  It  is  retained,  however,  in  a  few  instances,  such  for  example  as  the 
intercostal  muscles.  The  course  of  the  changes  which  obliterate  the  segmental 
character  of  the  myotomes  and  give  rise  to  the  various  muscles  has  not  been 
observed  in  all  cases.  But  since  a  nerve  belonging  to  any  particular  segment 
and  innervating  the  myotome  of  that  segment  always  innervates  the  muscles 
derived  from  that  myotome,  it  is  possible  to  learn  something  of  the  history  of 
the  myotomes  by  studying  the  innervation  of  the  muscles. 

From  a  consideration  of  what  is  known  concerning  the  individual  histories 


264  TEXT-BOOK  OF  EMBRYOLOGY. 

of  the  muscles  and  concerning  the  innervation  of  the  muscles,  certain  factors 
can  be  recognized,  to  one  or  more  of  which  the  changes  in  the  myotomes  may 
be  referred.  These  factors  are  as  follows: 

1.  Migration.- — The  myotomes  may  migrate  in  whole  or  in  part,  and  the 
muscles  derived  from  them  may  be  situated  far  beyond  their  limits.    For 
example,  the  latissimus  dorsi  is  derived  from  cervical  myotomes  but  ultimately 
becomes  attached  to  the  lumbar  vertebrae  and  to  the  crest  of  the  ilium.     To  this 
factor,  possibly  more  than  to  any  other,  is  due  the  loss  of  the  segmental  character 
in  the  musculature. 

2.  Fusion. — Portions  of  two  or  more  myotomes  may  fuse  to  form  one  muscle. 
For  example,  each  oblique  abdominal  muscle  is  derived  from  several  thoracic 
myotomes. 

3.  Longitudinal  Splitting. — Very  frequently  a  myotome  or  a  developing 
muscle  splits  longitudinally  into  two  or  more  portions.     The  sternohyoid  and 
the  omohyoid,  for  example,  are  formed  in  this  manner. 

4.  Tangential  Splitting. — A  developing  muscle  may  split  tangentially  into 
two  or  more  plates  or  layers.     The  two  oblique  and  the  transverse  abdominal 
muscles,  for  example,  are  formed  in  this  way. 

5.  Degeneration. — Myotomes  may  degenerate  as  a  whole  or  in  part  and  be 
converted  into  some  form  of  connective  tissue,  such  as  fascia,  ligament  or 
aponeurosis.     The   aponeuroses   of   the   transverse   and   oblique  abdominal 
muscles  are  probably  due  to  a  degeneration  of  portions  of  the  myotomes  from 
which  the  muscles  are  derived. 

6.  Change  of  Direction. — The  muscle  fibers  may  change  their  direction. 
As  a  matter  of  fact,  the  fibers  of  very  few  muscles  retain  their  original  direction. 

Muscles  of  the  Trunk. 

The  myotomes  are  at  first  arranged  serially  along  each  side  of  the  notochord  and 
spinal  cord  (compare  Fig.  2  24  with  Figs.  105  and  223).  By  the  end  of  the  second 
week  fourteen  myotomes  are  differentiated  in  the  human  embryo.  Differen- 
tiation continues  until,  by  the  end  of  the  fourth  week,  the  total  number— thirty- 
eight — is  present.  Of  the  thirty-eight,  three  are  occipital,  eight  cervical,  twelve 
thoracic,  five  lumbar,  five  sacral,  and  five  (or  six)  coccygeal.  The  occipital 
myotomes  are  transient  structures  that  appear  in  relation  with  the  hypoglossal 
(XII)  nerve.  The  cervical,  thoracic,  lumbar,  sacral  and  coccygeal  myotomes 
correspond  individually  to  the  spinal  nerves  (Fig.  224).  As  stated  on  page  148, 
the  myotomes  alternate  with  the  anlagen  of  the  vertebrae.  Consequently  in  the 
cervical  region  there  are  eight  myotomes,  corresponding  to  the  eight  cervical 
spinal  nerves,  and  only  seven  vertebrae.  The  myotomes  in  the  neck  and  body 
regions  are  destined  to  give  rise  to  the  dorsal  musculature,  to  the  thoraco- 


THE  DEVELOPMENT  OF  THE  MUSCULAR  SYSTEM. 


265 


abdominal  musculature,  to  a  part  of  the  muscles  of  the  neck,  and  to  the 
muscles  of  the  tail  region.  There  is  a  possibility  that  they  give  rise  also  to  the 
muscles  of  the  tongue. 

As  the  myotomes  continue  to  develop,  they  become  elongated  in  a  ventral 


FIG.  224. — Lateral  view  of  human  embryo  of  9  mm.  (4!  weeks).     Bardeen  and  Lewis. 

The  area  from  which  the  skin  has  been  removed  is  drawn  from  reconstructions.  The  myotomes 
have  fused  to  a  certain  extent,  so  that  segmentation  is  becoming  less  distinct.  Note  that  the 
myotomes  correspond  to  the  spinal  nerves.  The  developing  muscle  mass  (the  myotomes 
collectively)  extends  ventrally  in  the  body  wall  in  the  thoracic  region,  and  is  divided  by  a 
longitudinal  groove  into  two  parts — a  dorsal  and  a  ventro-lateral  (see  text). 

In  the  region  of  the  upper  extremity,  dense  masses  of  "  premuscle  "  tissue  are  represented  which 
later  form  the  muscles.  In  the  region  of  the  forearm  and  hand  the  "  premuscle  "  tissue  has 
been  removed  to  disclose  the  anlagen  of  the  skeletal  elements  (radius,  ulna,  and  hand  plate). 
In  the  region  of  the  lower  extremity  the  superficial  tissue  has  been  removed  to  disclose  the 
border  vien,  the  anlagen  of  the  os  coxae,  and  the  lumbo-sacral  nerve  plexus. 


direction.  Those  of  the  thoracic  region  extend  into  the  connective  tissue  of 
the  somatopleure,  or  in  other  words,  into  the  lateral  body  walls  (compare 
Figs.  224  and  225).  During  the  fifth  week  the  myotomes  give  rise  to  a  dorso- 
ventral  mass  of  developing  muscle  tissue,  in  which  the  segmental  character 


266 


TEXT-BOOK  OF  EMBRYOLOGY. 


Spinal  ganglion  .../'.'; 
Dorsal  musculature 


Ventro-laterai 
musculature   vfcv 


Vertebral  arch 
Dorsal  ramus  of 
spinal  nerve 


Segmental  artery 

Costal  process 

Lat.  branch  of 
spinal  nerve 

Vent,  branch  of 
spinal  nerve 


FlG.  225.— Diagrammatic  cross  section  through  the  sth-6th  thoracic  segments  of  a  human  embryo 
of  9  mm.  (4!  weeks).     Bardeen  and  Lewis. 


FIG.  226. — Drawing  from  a  reconstruction  of  the  region  of  the  lower  extremity  of  a  human  embryo 
of  9  mm.  (4^  weeks).  Bardeen  and  Lewis. 

The  visceral  organs  and  the  greater  part  of  the  left  body  wall  have  been  removed.  The  8th  thoracic 
to  the  5th  sacral  segments  are  shown.  On  the  right  side  of  the  body  the  costal  processes, 
the  spinal  nerves  (including  the  lumbo-sacral  plexus),  and  the  lower  extremity  are  shown. 
On  the  left  side  the  costal  processes,  the  spinal  nerves,  and  the  nth  and  i2th  thoracic  myo- 
tomes  are  represented.  Note  the  dorsal,  lateral,  and  sympathetic  branches  of  the  spinal 
nerves. 


THE  DEVELOPMENT  OF  THE  MUSCULAR  SYSTEM. 


267 


largely  disappears.     The  muscle  mass  then  becomes  divided  longitudinally 
into  two  parts,  (i)  a  dorsal  and  (2)  a  ventro-lateral  (Figs.  224,  225  and  226). 

1.  The  dorsal  part  is  destined  to  give  rise  to  those  dorsal  muscles  of  the 
trunk  that  are  not  associated  with  the  extremities,  and  is  innervated  by  the 
dorsal  rami  of  the  spinal  nerves  (Fig.  225). 

2.  The  ventro-lateral  part  again  divides  longitudinally  into  (a)  a  lateral 


"  • »    External  oblique 
-     *  External  intercostal 


}&'rS-'  •' >^  '.*"-...    v  Internal  intercostal 
'*•»...  "*  Internal  oblique 

.  .-„,        ,  •**  Transversalis 

ft  '.    ,  /  ""  Rectus 


Ventro-lateral 
musculature 


FIG.  227. — Diagrammatic  cross  section  through  the  6th~7th  thoracic  segments  of  a  human  embryo 
of  17  rnm.  (5^  weeks).     Bardeen  and  Lewis. 


and  (b) 
between 
(a) 


a  ventral  part,  although  the  line  of  division  is  not  so  distinct  as 
the  original  (i)  dorsal  and  (2)  ventro-lateral  parts  (Fig.  227). 
The  lateral  part  subdivides  tangentially  and  gives  rise  in  the  cervical 
region  to  the  longus  capitis,  longus  colli,  rectus  capitis  anterior,  to  the 
scaleni,  and  to  parts  of  the  trapezius  and  sternomastoideus  (Figs.  228 
and  229).  In  the  thoracic  region  it  gives  rise  to  the  intercostaks 
and  to  the  transversus  thoracis  (Figs.  227  and  230);  in  the  abdominal 
region  to  the  psoas,  quadratus  lumborum,  and  to  the  obliqui  and 
transversus  abdominis  (Figs.  229  and  230). 


268  TEXT-BOOK  OF  EMBRYOLOGY. 

(b)  The  ventral  part  gives  rise  in  the  cervical  region  to  the  sternohyoideus, 
omohyoidem,  sternothyreoideus  and  geniohyoideus.  In  the  abdominal 
region  the  ventral  part  gives  rise  to  the  r edits  abdominis  and  to  the 
pyramidalis  (Figs.  227  and  229).  In  the  thoracic  region  there  are  no 
muscles  derived  from  the  ventral  part,  corresponding  to  those  in  the 
abdominal  region.  This  is  probably  due  to  the  development  of  the 
sternum. 


FIG.  228. — Lateral  view  of  a  human  embryo  of  n  mm.  (about  5  weeks).  Bardeen  and  Lewis. 
The  area  from  which  the  skin  has  been  removed  is  drawn  from  reconstructions.  The  dorsal  mus- 
culature has  been  removed  from  the  region  of  the  upper  extremity,  exposing  the  4th  to  the 
8th  cervical  and  the  ist  to  the  3d  thoracic  vertebrae.  The  dorsal  musculature  has  likewise 
been  removed  from  the  5th  lumbar  and  first  three  sacral  segments.  Segmentation  is  practi- 
cally lost  in  the  dorsal  musculature  in  the  thoracic  region,  but  is  still  evident  in  the  lumbar, 
sacral  and  coccygeal  regions.  The  ventro-lateral  musculature  is  distinctly  separated  from  the 
dorsal,  and  is  beginning  to  differentiate  into  the  muscles  of  the  thorax  and  abdomen. 

The  ventro-lateral  portions  of  the  lumbar  myotomes  and  of  the  first  two 
sacral  myotomes,  corresponding  to  the  ventro-lateral  portions  of  the  thoracic 
myotomes,  apparently  do  not  take  part  in  the  production  of  muscles  which  be- 
long to  the  body  wall  proper.  It  is  even  questionable  whether  they  give  rise  to 
any  muscles  of  the  lower  extremities.  The  ventro-lateral  portions  of  the  third 


THE  DEVELOPMENT  OF  THE  MUSCULAR  SYSTEM. 


269 


and  fourth  sacral  myotomes  give  rise  to  the  levator  ani,  the  coccygeus,  the 
sphincter  ani  externus  and  the  perineal  muscles.  The  dorsal  parts  of  the  myo- 
tomes as  far  as  the  fifth  sacral  probably  give  rise  to  the  sacrospinalis  (Fig.  228). 
THE  DIAPHRAGM. — In  addition  to  certain  structures  which  are  considered 
in  connection  with  the  pericardium  (parietal  mesoderm,  mesocardium  and 
common  mesentery — Chapter  XIV),  two  myotomes  on  each  side  enter  into 


FIG.  229. — Drawing  from  a  reconstruction  of  a  human  embryo  of  20  mm.  (about  7  weeks). 

Bardeen  and  Lewis. 

The  superficial  tissues  have  been  removed  from  the  extremities,  the  body  wall,  and  the  back. 


the  formation  of  the  diaphragm.  These  are  the  third  and  fourth  cervical  myo- 
tomes, parts  of  which  grow  into  the  developing  diaphragm  in  the  earlier  stages 
when  it  is  situated  far  forward  in  the  cervical  region  (p.  346  and  Fig.  298),  and 
give  rise  to  its  muscular  elements. 

Muscles  of  the  Head. 

Primitive  segments  (mesodermic  somites)  are  not  clearly  demonstrable  in 
the  heads  of  human  embryos,  nor,  in  fact,  in  the  heads  of  any  of  the  higher 
Vertebrates.  In  some  of  the  lower  forms,  however,  they  are  very  distinct.  It 
seems  possible,  even  probable,  that  their  indistinctness  in  the  higher  animals 


270  TEXT-BOOK  OF  EMBRYOLOGY. 

is  due  to  an  abbreviation  or  condensation  in  the  development  of  the  head 
region.  Such  condensations  are  known  to  occur  in  the  development  of  other 
structures.  In  a  human  embryo  3.5  mm.  long,  three  structures,  resembling 
segments  have  been  seen  somewhat  caudal  to  the  region  .of  the  ootic  vesicle  on 


FIG.  230. — Drawing  from  a  reconstruction  of  the  right  side  of  a  human  embryo  of  20  mm.  (about 

7  weeks).  Bardeen  and  Lewis. 

The  left  body  wall  and  viscera  have  been  removed.  Note  especially  the  following  muscles:  The 
deltoid  and  biceps,  just  to  the  left  of  the  brachial  plexus  and  below  the  clavicle;  the  internal 
intercostals;  the  diaphragm,  attached  to  the  body  wall;  the  transverse  abdominal  and  the 
rectus  abdominis;  the  quadratus  lumborum,  just  to  the  right  of  the  transverse  abdominal; 
the  psoas,  cut  just  above  the  lumbo-sacral  plexus;  the  levator  ani,  running  obliquely  upward 
from  the  coccygeal  region. 


one  side.  On  the  other  side  there  were  seven  similar  but  smaller  structures. 
All  were  composed  of  epithelial-like  cells  surrounding  small  cavities. 
Whether  these  segment-like  structures  bear  any  relation  to  the  mesenchymal 
condensations  which  appear  regularly  in  the  occipital  region  (p.  157).  seems 
not  to  have  been  determined. 


THE  DEVELOPMENT  OF  THE  MUSCULAR  SYSTEM. 


271 


Although  the  transformation  of  head  segments  into  muscles  has  not  been 
followed  in  detail  in  mammalian  embryos,  it  may  be  inferred  from  the  study  of 
lower  forms  that  three  segments  are  involved  in  the  formation  of  the  eye  muscles. 
The  most  cephalic  (anterior)  segment  gives  rise  to  the  recti  superior,  inferior 
and  medialis  (internus)  and  to  the  obliquus  inferior,  all  of  which  are  innervated 
by  the  occulomotor  (III)  nerve.  The  next  segment  gives  rise  to  the  obliquus 
superior  which  is  innervated  by  the  pathetic  (IV)  nerve.  The  most  caudal 
segment  gives  rise  to  the  rectus  lateralis  (externus)  which  is  innervated  by  the 
abducens  (VI)  nerve. 

The  development  and  innervation  of  the  other  muscles  of  the  head  and"  of 
the  hyoid  musculature  present  certain  peculiarities  which  have  caused  these 
muscles  to  be  considered  as  more  closely  related  to  the  visceral  musculature 
than  to  the  myotomic  musculature.  In  the  first  place  they  are  derived  from. 


Eighth  cervical 
myotome 


Upper  limb 
bud 


Somatopleure 

Mesonephric 
duct 


FIG.  231. — Transverse  section  through  the  eighth  cervical  segment  of  a  human 
embryo  of  2.1  mm.     Lewis* 


the  branchial  arches  (hence  are  often  called  branchiomeric  muscles),  and  not 
directly  from  the  myotomes  of  the  neck  region.  This  places  them  in  closer 
relation  to  the  visceral  muscles,  although  they  are  structurally  and  functionally 
different  from  the  latter.  In  the  second  place  the  nerves  which  supply  them 
are  fundamentally  different  from  those  which  supply  the  myotomic  muscles 
(Chap.  XVII). 

The  first  branchial  arch  on  each  side  gives  rise  to  the  temporalis,  masseter 
and  pterygoidei,  to  the  mylohyoideus  and  digastricus  (venter  anterior)  and  to  the 
tensor  tympani  and  tensor  veli  palatini.  All  these  muscles  are  innervated  by  the 
trigeminal  (V)  nerve. 

The  second  arch,  which  is  often  called  the  hyoid  arch,  gives  rise  to  a  large 
sheet  of  myogenic  tissue  which  produces  many  of  the  facial  muscles,  such  as  the 


272  TEXT-BOOK  OF  EMBRYOLOGY. 

platysma  and  epicranius,  the  muscles  of  expression — quadratus  labii  superiority 
risorius,  triangularis ,  mentalis,  etc.;  also  two  muscles  connected  with  the  hyoid 
bone — digastricus  (venter  posterior)  and  stylohyoideus — and  the  stapedius  of  the 
middle  ear.  The  facial  (VII)  nerve  corresponds  to  the  second  arch  and  sup- 
plies all  these  muscles. 

The  glossopharyngeal  (IX)  nerve  corresponds  to  the  third  branchial  arch, 
and  this  fact  indicates  the  muscles  derived  from  that  arch.  Some,  at  least,  of 
the  constrictor  muscles  of  the  pharynx  are  derived  from  the  third  arch.  The 
stylo-pharyngeus  is  also  a  derivative  of  the  same  arch. 

The  vagus  (X)  nerve  is  associated  with  the  fourth  and  fifth  arches  and  con- 
sequently innervates  the  muscles  derived  from  these  arches,  viz.,  the  rest  of  the 
constrictors  of  the  pharynx  (see  above),  the  laryngeal  muscles  and  the  muscles 
of  the  soft  palate  (except  the  tensor  veli  palatini  which  is  derived  from  the  first 
arch  (p.  271).  The  glossopalatinus  and  chondroglossus  are  also  derived  from 
the  fourth  and  fifth  arches,  while  the  rest  of  the  extrinsic  muscles  of  the  tongue 
are  of  myotomic  origin. 

Two  other  muscles  are  probably  derived  in  part  from  the  branchial  arches, 
for  fibers  of  the  spinal  accessory  (XI)  nerve  afford  a  part  of  their  innervation. 
These  are  the  trapezius  and  the  sternomastoideus ,  the  remaining  parts  of  which 
are  of  myotomic  origin  (p.  267). 

Muscles  of  the  Extremities. 

The  question  as  to  whether  the  muscles  of  the  extremities  are  derivatives  of 
the  myotomes  or  of  the  mesenchymal  tissue  in  the  limb  buds  has  not  been 
settled.  In  some  of  the  lower  Vertebrates,  especially  in  some  of  the  Fishes,  it 
seems  to  have  been  pretty  clearly  demonstrated  that  bud-like  processes  from 
the  myotomes  grow  into  the  anlagen  of  the  extremities  (fins),  and  there  give 
rise  to  muscles.  In  other  lower  forms  no  such  buds  from  the  myotomes  have 
been  demonstrated,  but  the  muscles  are  apparently  derived  directly  from 
the  mesenchymal  tissue  in  the  anlagen  of  the  extremities.  In  the  higher  verte- 
brates, especially  in  Mammals,  no  distinct  myotome  buds  have  been  traced  into 
the  extremities.  Some  investigators  hold,  however,  that  instead  of  myotome 
buds  some  cells  from  the  myotomes — myoblasts — wander  into  the  limb  buds 
and  give  rise  to  muscles.  Other  investigators  are  inclined  to  the  view  that  the 
musculature  of  the  extremities  is  not  of  myotomic  origin,  but  that  it  is  derived 
from  the  mesenchymal  tissue  of  the  limb  buds. 

A  most  striking  feature  of  the  musculature  of  the  extremities  is  its  distinctly 
segmental  nerve  supply.  This,  of  course,  is  in  favor  of,  although  it  does  not 
prove,  its  myotomic  origin.  If  the  muscles  of  the  extremities  are  of  myotomic 
origin,  it  is  very  probable  that  several  myotomes  take  part  in  their  formation. 


THE  DEVELOPMENT  OF  THE  MUSCULAR  SYSTEM. 


273 


In  the  first  place  among  the  lower  Vertebrates  the  muscles  of  each  extremity  are 
derived  from  several  myotomes  and  are  innervated  by  segmental  nerves  cor- 
responding to  these  myotomes.  In  the  second  place  among  the  higher  Verte- 
brates, although  the  myotomic  origin  of  the  muscles  has  not  been  clearly  demon- 
strated, the  nerve  supply  in  each  extremity  comes  through  several  segmental 
spinal  nerves. 

Knowledge  concerning  the  development  of  the  individual  muscles  of  the  ex- 
tremities in  the  human  embryo  is  incomplete.  Especially  is  this  true  of  the 
muscles  of  the  lower  extremities. 

The  upper  limb  bud  first  appears  in  embryos  of  2-3  mm.  (during  the  third 
week)  as  a  slight  swelling  ventro-lateral  to  the  myotomes  in  the  lower  cervical 


Upper  limb  bud 


Border  vein 


M&    Somatopleure 


FIG.  232. — Transverse  section  through  the  eighth  cervical  segment  of  a  human 
embryo  of  4.5  mm.     Lewis. 

region  (Fig.  231;  see  also  Fig.  87).  The  swelling  gradually  enlarges  and  by 
the  time  the  embryo  has  reached  a  length  of  4-5  mm.  lies  opposite  the  last  four 
cervical  and  the  first  thoracic  myotomes.  At  this  time  it  is  filled  with  closely 
packed  mesenchymal  cells.  No  buds  from  the  myotomes  can  be  seen  extending 
into  the  mesenchyme  (Fig.  232). 

In  succeeding  stages  the  limb  bud  enlarges  still  more,  and  the  mesenchymal 
tissue  becomes  denser  (Figs.  233  and  234).  During  these  stages  no  growths, 
either  of  buds  or  of  individual  cells,  from  the  myotomes  are  apparent.  Some 
of  the  cervical  nerves,  however,  enter  the  limb  buds  (Fig.  234). 

Apparently  the  tissue  from  which  the  muscles,  as  well  as  the  skeletal  ele- 
ments, are  to  develop,  is  the  condensed  mesenchymal  tissue.  The  first  indica- 
tion of  differentiation  occurs  during  the  fourth  week  (embryo  of  about  8  mm.). 
The  central  portion  or  core  of  the  mesenchymal  mass  becomes  still  denser  to 
form  the  anlage  of  the  skeletal  elements  of  the  extremity.  The  tissue  of  the 


274 


TEXT-BOOK  OF  EMBRYOLOGY. 


core  shades  off  into  the  surrounding  tissue  of  a  lesser  density,  which  is  destined 
to  give  rise  to  the  muscles  and  which  is  known  as  the  premuscle  sheath. 

During  these  processes  of  differentiation  in  the  limb  bud  proper,  masses  of 
premuscle  tissue  have  also  become  differentiated  around  the  base  of  the  limb 
bud.  These  are  the  forerunners  of  certain  extrinsic  muscles  of  the  upper  ex- 
tremity, such  as  the  pectoralisj  levator  scapula,  trapezius,  latissimus  dorsi,  ser- 
ratus,  etc.  (Fig.  235;  compare  with  Fig.  236). 


Spinal  ganglion 


Intervertebral  disk 


Upper 
limb  bud 


-  Border  vein 


FIG.  233. 


-Transverse  section  through  the  8th  cervical  segment  of  a  human 
embryo  of  5  mm.     Lewis. 


By  the  end  of  the  fifth  week  the  premuscle  sheath  in  the  limb  bud  proper  be- 
comes more  or  less  differentiated  into  muscles  or  groups  of  muscles.  The 
differentiation  is  most  complete  at  the  proximal  end.  From  this  the  transition 
is  gradual  to  the  distal  end  where  the  premuscle  sheath  is  intact 

By  the  end  of  the  sixth  week  most  of  the  muscles  of  the  upper  extremity  are 
recognizable  (Figs.  236  and  237). 

By  the  end  of  the  seventh  week  practically  all  the  muscles  can  be  recognized 
and  are  composed  of  muscle  fibers. 

During  the  differentiation  of  the  muscles,  the  limb  bud  and  certain  ex- 
trinsic muscles  migrate  a  considerable  distance  caudally.  For  example,  the 


THE  DEVELOPMENT  OF  THE  MUSCULAR  SYSTEM. 


275 


pectoralis  and  latissimus  dorsi  migrate  from  the  base  of  the  arm  to  the  thoracic 
wall.  Their  nerves  are  naturally  pulled  with  them.  The  trapezius  muscle, 
which  originates  well  forward  in  the  cervical  region,  migrates  so  that  it  finally 
reaches  as  far  as  the  last  thoracic  vertebra.  The  sternomastoideus  also  origi- 
nates well  forward  in  the  cervical  region,  but  finally  extends  to  the  clavicle  and 
sternum.  The  migration  of  the  upper  extremity  causes  the  brachial  plexus  to 
have  a  caudal  inclination. 

The  lower  limb  buds  arise  very  soon  after  the  upper.     As  stated  on  page  115, 
the  upper  limbs  always  maintain  a  slight  advance  over  the  lower  in  develop- 


Spinal  ganglion 


Vertebral  arch 


8th  cerv.  myotome 

8th  cerv.  nerve 
6th,  7th  cerv.  nerves 
Condensed 
mesenchyme 


Intervertebral  disk 


Border 


Somatopleure 


FiG.  234. — Transverse  section  through  the  8th  cervical  segment  of  a  human 
embryo  of  7  mm.  (about  4  weeks).     Lewis. 


ment.  As  in  the  case  of  the  upper,  the  lower  limb  buds  appear  as  swellings  on 
the  ventro-lateral  surface  of  the  body,  opposite  the  fifth  lumbar  and  first  sacral 
myotomes.  The  interior  of  each  swelling  is  at  first  composed  of  closely  packed 
mesenchymal  tissue,  but  whether  any  part  of  the  myotomes  enters  it  is  question- 
able. At  all  events  several  spinal  nerves  do  enter  the  tissue  and  supply  the 
nro.3cles.  The  differentiation  of  a  central  core  as  the  anlage  of  the  skeleton,  and 
the  differentiation  of  the  surrounding  tissue  as  the  premuscle  sheath,  take  place 
in  the  same  manner  as  in  the  upper  extremity  (p.  274).  From  this  premuscle 
sheath  all  the  muscles  of  the  lower  extremity  are  developed. 


276 


TEXT-BOOK  OF  EMBRYOLOGY. 


Histogenesis  of  Striated  Voluntary  Muscle  Tissue. 

The  majority  of  the  striated  voluntary  muscles  of  the  body  are  derived  from 
the  myotomes.  Some  are  derived  from  the  mesenchymal  tissue  in  the  branchial 
arches,  some  possibly  from  the  mesenchymal  tissue  in  the  limb  buds.  Thf 
primitive  segments  are  at  first  composed  of  closely  arranged,  epithelial-like  cells 
that  radiate  from  a  small  centrally  placed  cavity  (Fig.  103).  The  cavity  repre- 
sents part  of  the  ccelom  and  from  this  point  of  view  it  can  be  said  that  the  muscle 
is  a  derivative  of  the  epithelial  lining  of  the  ccelom.  A  part  of  each  primitive 


t  r 

o>     a 

K>      CO 


Scapular 


Pectoral 


'Premuscle  " 


Border  vein 


5th  nerve 


renic  nerve 
Brachial  plexus 

Sympathetic 

Diaphragm 

Vertebra 


Hand  plate 


Lateral 
musculature 


4th  rib 


FIG.  235. — Drawing  from  a  reconstruction  of  the  upper  limb  region  of  a  human 

embryo  of  9  mm.  (4^  weeks) ;  ventral  view.     Lewis. 

Inf.  hy.,  infrahyoid;  Lev.  scap.,  levator  scapulae;  My.,  myotome  mass;  Rhom., 
rhomboid;   Trap.,  trapezius. 


segment  becomes  the  sclerotome  and  cutis  plate.     The  remaining  part  be- 
comes the  myotome  or  muscle  plate  (Fig.  $  23). 

The  cells  of  the  myotome  are  at  first  not  essentially  different  from  those  of 
the  rest  of  the  primitive  segment.  Soon,  however,  changes  take  place  in  them 
and  they  become  the  so-called  myoblasts  or  muscle-forming  cells,  which  are 
destined  to  give  rise  to  the  muscle  fibers.  Opinions  differ  as  to  the  manner  in 
which  the  myoblasts  produce  the  muscle  fibers.  It  was  once  thought  that  each 
myoblast  gave  rise  to  a  single  muscle  fiber  in  which  there  were  several  nuclei,  all 


THE  DEVELOPMENT  OF  THE  MUSCULAR  SYSTEM. 


277 


derived  from  the  original  myoblast  nucleus  by  mitotic  division.  It  was  also 
thought  that  the  muscle  fibrillae  represented  highly  modified  and  specialized 
parts  of  the  cytoplasm,  which  arranged  themselves  longitudinally  in  the  cell. 
Some  of  the  later  researches  indicate  that  a  muscle  fiber  represents  a  number  of 
myoblasts  fused  together.  This  explanation  is  not,  however,  accepted  by  all 


investigators. 


In  contrast  with  the  above,  there  is  a  quite  general  consensus  of  opinion  in 
regard  to  the  development  of  the  internal  structure  of  the  muscle  fiber.     In  the 


FlG.  236. — Lateral  view  of  a  reconstruction  of  the  muscles  of  the  upper  extremity  of  a  human 
embryo  of  16  mm.  (about  6  weeks).  Lewis. 

The  trapezius  is  the  large  muscle  arising  from  the  transverse  processes  of  the  vertebrae  (at  the  right 
of  the  figure)  and  converging  to  its  insertion  on  the  clavicle.  Just  below  the  insertion  of  the 
trapezius  is  the  deltoid,  which  partly  hides  the  subscapular  (on  the  right)  and  the  pectoralis 
major  (on  the  left).  Arising  beneath  the  deltoid  and  running  downward  to  the  elbow  is  the 
triceps.  To  the  right  of  the  triceps  is  the  teres  major  (composed  of  two  parts).  The  large 
sheet  of  muscle  extending  down  the  forearm  and  sending  divisions  to  the  ad,  3d,  4th  and  5th 
digits  is  the  extensor  communis  digitorum. 


cytoplasm  of  the  myoblasts  there  appear  granules  which  soon  arrange  them- 
selves in  parallel  rows  and  unite  to  form  slender  thread-like  fibrils  (Fig.  238). 
These  fibrils  are  at  first  confined  to  one  myoblast  area.  If  several  myoblasts 
fuse,  the  fibrils  probably  extend  in  a  short  time  from  one  myoblast  area  to 
another.  If  one  myoblast  produces  a  fiber,  the  fibrils  naturally  are  confined  to 
a  single  myoblast  area  throughout  development.  The  fibrils  are  usually 
formed  first  at  the  periphery  of  the  cell  and  later  in  the  interior  (Figs.  239 


278 


TEXT-BOOK  OF  EMBRYOLOGY. 


and  240.)    At  the  same  time  they  increase  in  number  by  longitudinal  splitting. 
The  cytoplasm  among  the  fibrils  becomes  the  sarcoplasm. 

After  the  granules  which  first  appear  unite  to  form  the  fibrils,  the  latter 


FIG.  237. — Medial  view  of  a  reconstruction  of  the  muscles  of  the  upper  extremity  of  a  human 
embryo  of  16  mm.  (about  6  weeks).  Lewis. 

The  muscle  arising  on  the  scapula  (at  the  left  of  the  figure)  and  passing  toward  the  right  is  the 
subscapular.  The  small  muscle  just  below  the  subscapular  is  the  teres  major;  below  the 
latter  and  hanging  downward  is  the  latissimus  dorsi.  Note  the  cut  end  of  the  pectoralis 
minor  just  to  the  right  of  the  narrow  portion  of  the  subscapular.  Running  from  this  cut  end 
toward  the  right  is  the  biceps.  The  muscle  at  the  lower  edge  of  the  figure  in  the  arm  region 
is  the  triceps.  In  the  forearm  region,  the  muscle  crossing  the  end  of  the  biceps  is  the  pro- 
nator  teres.  Below  the  pronator  teres,  extending  from  the  elbow  to  the  thumb  region  is  the 
flexor  carpi  radialis.  Below  the  latter  and  extending  to  a  point  opposite  the  thumb,  is  the 
palmaris  longus.  Beneath  the  palmaris  longus  and  dividing  into  branches  which  pass  to  the 
2d,  ad,  4th,  and  5th  digits  is  the  flexor  sublimis  digitorum.  The  muscle  passing  to  the 
thumb  is  the  flexor  longus  pollicis.  The  muscle  at  the  lower  border  of  the  figure  in  the  fore- 
arm region  is  the  flexor  carpi  ulnaris. 


FIG.  238. — Myoblasts  in  different  stages  of  development.     Godleivski. 

The  upper  cell  represents  a  myoblast  with  granular  cytoplasm  (from  sheep  embryo  of  13  mm) ;  the 
middle,  a  myoblast  with  fibrils  in  process  of  formation  (from  guinea-pig  embryo  of  10  mm.); 
the  lower,  a  myoblast  with  still  further  differentiated,  segmented  fibrils  (from  a  rabbit 
embryo  of  8.5  mm.). 

are  apparently  quite  homogeneous.     Later  they  become  differentiated  into  two 
distinct  substances  which  alternate  throughout  their  length  and  produce  the 


THE  DEVELOPMENT  OF  THE  MUSCULAR  SYSTEM. 


279 


characteristic  cross  striation.  The  nature  of  this  differentiation  is  not  known. 
One  investigator  holds  that  both  substances  are  derived  from  the  original 
granules  that  unite  to  form  the  fibrils,  alternate  granules  being  composed  of  like 
substance  and  united  by  delicate  strands  of  the  other  substance. 

While  the  fibrils  are  being  formed,  the  nuclei  of  the  myoblasts  undergo  rapid 
mitotic  division.  When  the  cells  are  about  filled  with  fibrils,  the  nuclei  migrate 
to  the  periphery  where  they  are  situated  in  the  fully  formed  fiber  (Fig.  278). 
Each  fiber  thus  possesses  a  number  of  nuclei,  whether  it  is  derived  from  one 
myoblast  or  from  several. 


»2Sfes  \\^^^<,  //  /   P'U^e^y  •v*3*£»-vl 


FIG.  240 

FIG.  239. — From  a  cross  section  of  developing  voluntary  striated  muscle  in  the  leg  of  a  pig  embryo 

of  45  mm.,  showing  fibril  bundles  at  the  periphery  of  the  cells.     MacCallum. 
FIG.  240. — From  a  cross  section  of  developing  voluntary  striated  muscle  in  the  leg  of  a  pig  embryo 

of  75  mm.,  showing  fibril  bundles  more  numerous  than  in  Fig.  239.     A,  Central  vesicular 

nucleus;  B,  peripheral  more  compact  nucleus.     MacCallum. 


For  some  time  at  least,  the  number  of  fibers  in  a  developing  muscle  increases 
by  division  of  those  already  formed.  This  process  would  produce  a  certain 
degree  of  enlargement  of  the  muscle  as  a  whole.  Later  the  increase  in  the 
number  of  fibers  ceases,  and  the  muscle  grows  by  enlargement  of  the  individual 
fibers.  It  is  not  certain  at  what  period  in  development  the  increase  in  the  num- 
ber of  fibers  ceases. 

In  many  muscles  development  is  further  complicated  by  a  retrograde  proc- 
ess—a degeneration  of  some  of  the  fibers.  This  occurs  quite  regularly  in  the 
extremities.  A  well  fibrillated  fiber  first  presents  a  homogeneous  appearance, 
then  becomes  vacuolated,  the  nuclei  disintegrate,  and  finally  the  whole 
structure  disappears.  Mesenchymal  (or  connective)  tissue  takes  its  place,  and 
the  remaining  fibers  are  thus  grouped  into  bundles  and  the  bundles  into 
muscles.  This  would  account  to  a  certain  extent  for  the  intermuscular  con- 


280 


TEXT-BOOK  OF  EMBRYOLOGY. 


nective  tissue,  the  perimysium  and  endomysium,  the  epimysium  being  derived 
from  the  mesenchymal  tissue  which  originally  surrounded  the  muscle. 

THE  VISCERAL  MUSCULATURE. 

The  visceral  musculature  is  derived  wholly  from  the  mesoderm,  but  not 
from  the  myotomes.  The  striated  involuntary  muscle  or  heart  muscle  is  de- 
rived from  the  mesothelial  lining  of  the  coelom,  the  smooth  muscle  from  the 
mesenchymal  tissue  in  various  regions  of  the  body.  The  heart  muscle  develops 
only  in  connection  with  the  heart  and  consequently  occurs  in  the  adult  only  in 
that  organ.  Smooth  muscle  develops  to  form  integral  parts  of  certain  structures 
such,  for  example,  as  the  alimentary  tube,  glands,  blood  vessels,  and  skin. 

Histogenesis  of  Heart  Muscle. 

When  the  simple  tubular  heart  is  first  formed,  the  splanchnopleure  projects 
into  the  ccelom  (primitive  pericardial  cavity)  along  each  side  (Fig.  165;  also  p. 
196).  The  mesothelium  covering  these  projections  is  destined  to  give  rise  to 


FIG.  24*r. — From  a  section  of  developing  heart  muscle  from  a  rabbit  embryo  of  9  mm.     Godlewski, 

a,  Cell  body  with  granules  arranged  in  series;  b,  cell  body  with  centrosome  and  attraction  sphere; 

c,  branching  fibril;  d,  fibrils  extending  through  several  cells. 

the  myocardium.  The  mesothelial  cells  which  are  at  first  closely  packed  to- 
gether with  but  little  intercellular  substance,  assume  irregular  branching  forms 
and  the  branches  anastomose  freely  (Fig.  241).  After  the  cells  become  loosely 
arranged,  they  again  become  closely  packed  to  form  a  compact  syncytium,  in- 
dividual cells  apparently  assuming  the  shape  of  heavy  bands  (Fig.  242).  Ir- 
regular transverse  bands  next  appear,  dividing  the  syncytium  into  the  so-called 


THE  DEVELOPMENT  OF  THE  MUSCULAR  SYSTEM. 


281 


heart  muscle  cells.  These  may  or  may  not  represent  the  original  cells  or 
myoblasts.  At  all  events  the  muscle  fibrils  are  continuous  across  the  lines. 
The  nuclei  proliferate  in  the  syncytium  but  remain  in  the  central  part  of  the 
bands  or  cells,  instead  of  migrating  to  the  periphery  as  in  striated  voluntary 
muscle. 

While  the  cells  are  still  loosely  arranged,  rows  of  granules  appear  in  the 
cytoplasm,  and  the  granules  in  each  row  unite  to  form  a  fibril  (Fig.  241).     The 

fibrils  are  at  first  confined  to  individual 
cell  areas,  but  as  the  cells  come  closer 
together  to  form  the  compact  syncytium, 
they  extend  through  several  cell  areas 
and  run  in  different  directions  (Fig.  242). 
As  development  proceeds  the  fibrils  be- 
come more  nearly  parallel  (Fig.  243). 
They  are  first  formed  in  the  peripheries 
of  the  cells,  but  later  also  in  the  interior, 
except  in  a  small  area  immediately  sur- 
rounding the  nucleus,  where  a  small 
amount  of  undifferentiated  cytoplasm 
remains.  The  latter  is  continuous 
with  the  cytoplasm  or  sarcoplasm 
among  the  fibrils.  As  in  voluntary 
seriated  muscle  the  fibrils  become  differ- 
entiated into  two  distinct  substances 
which  alternate  with  each  other,  thus 
producing  the  transverse  striation. 


IG.    242. — From   a  section   of    developing 
heart  muscle  in  a  rabbit  embryo  of  9  mm. 
Godlewski. 
The  cells  form  a  compact  syncytium. 


Histogenesis  of  Smooth  Muscle. 

The  mesenchymal  cells  which  are  destined  to  produce  smooth  muscle  cells 
are  not  grouped  into  any  particular  primitive  structures  like  the  mesodermic 
somites.  They  are  simply  scattered  through  the  general  mass  of  mesenchymal 
tissue  and,  like  other  mesenchymal  cells,  possess  irregular  branching  forms  and 
distinct  spherical  nuclei.  The  internal  changes  by  which  these  cells  are  con- 
verted into  muscle  cells  are  not  well  known.  The  contractile  elements — 
the  fibrillae — probably  represent  highly  modified  portions  of  the  original  cyto- 
plasm but  the  manner  in  which  the  cytoplasm  is  transformed  into  fibrillae  has 
not  been  determined.  The  external  changes  consist  essentially  in  an  elonga- 
tion of  the  irregular  mesenchymal  cells.  The  result  of  this  elongation  is  usually 
a  spindle-shaped  cell,  but  exceptionally  cells  forked  at  one  or  both  ends  are 
produced.  The  original  spherical  nucleus  also  shares  in  the  elongation  and 
becomes  rod-shaped. 


282  TEXT-BOOK  OF  EMBRYOLOGY. 

In  some  cases,  for  example  in  the  muscular  layers  of  the  gastrointestinal 
tract,  distinct  bands  or  sheets  of  smooth  muscle  are  formed  in  which  the  cells 
are  closely  packed  and  lie  approximately  parallel.  In  other  cases,  such  as  the 
mucosa  of  the  intestine  and  the  capsules  of  certain  glands,  the  muscle  cells 
develop  in  little  groups  or  as  isolated  cells. 

Anomalies. 

More  or  less  of  the  muscular  system  is  involved  in  some  of  the  gross  anoma- 
lies or  malformations  of  the  body.  For  example,  congenital  defects  in  the  cen- 
tral nervous  system  (anencephaly,  rachichisis,  etc.)  are  necessarily  accompanied 
by  atrophy  or  faulty  development  of  certain  parts  of  the  muscular  system.  In 
the  case  of  ventral  median  fissure  of  the  abdominal  wall  (gastroschisis) ,  the 


FIG.  243. — From  a  section  of  developing  heart  muscle  in  a  rabbit  embryo  of  10  mm.     Godlewski. 
The  fibrils  are  segmented,  indicating  the  beginning  of  the  cross  striation  characteristic  of  heart  muscle. 

abdominal  muscles  are  naturally  involved.  Such  anomalies  in  the  muscles  are, 
however,  secondary  to  the  other  malformations  and  are  not  due  to  primary 
defects  in  the  muscles  themselves. 

Many  of  the  minor  variations  in  the  muscular  system  occur  in  the  same 
form  or  in  similar  forms  in  different  individuals,  thus  indicating  their  relation  to 
a  fundamental  type.  Many  of  these  are  more  or  less  accurate  repetitions  of 
normal  structures  found  in  lower  animals.  Such  variations  are  probably 
rightly  attributed  to  hereditary  influences.  On  the  other  hand,  there  are  varia- 
tions which  cannot  be  referred  to  conditions  found  in  any  of  the  lower  animals. 
These  constitute  a  class  of  variations  which  must  be  accounted  for  upon  some 
other  basis  than  that  of  heredity.  As  pointed  out  in  the  chapter  on  Teratogene- 
sis  (Chap.  XX),  external  influences  undoubtedly  play  an  important  part  in  the 
production  of  anomalies  and  it  is  probable  that  similar  influences  act  upon  the 
development  of  the  muscular  system. 

The  scope  of  this  book  does  not  permit  a  description,  or  even  mention,  of  the 
great  number  of  variations  in  the  muscles.  A  few  are  described  here  as  ex- 


THE  DEVELOPMENT  OF  THE  MUSCULAR  SYSTEM.  283 

amples;  for  others  the  student  is  referred  to  the  more  extensive  text-books  of 
anatomy. 

EXTRINSIC  MUSCLES  OF  THE  UPPER  EXTREMITY. — The  trapezius  is  some- 
times attached  to  less  than  the  normal  number  of  thoracic  vertebrae.  Its 
occipital  attachment  may  be  wanting.  Occasionally  the  cervical  and  thoracic 
portions  are  more  or  less  separated  as  in  some  of  the  lower  animals. 

The  latissimus  dorsi  sometimes  arises  from  less  than  the  usual  number  of 
thoracic  vertebrae,  and  from  less  than  the  normal  number  of  ribs.  The  iliac 
origin  may  be  wanting. 

The  rhomboidei  vary  in  their  vertebral  and  scapular  attachments. 

The  number  of  the  vertebral  attachments  of  the  levator  scapulae  may  vary. 
A  small  part  of  the  muscle  is  sometimes  attached  to  the  occipital  bone. 

The  pectoralis  major  not  infrequently  varies  in  the  extent  of  its  attachment 
to  the  ribs  and  sternum. 

The  serrati  vary  in  their  attachment  to  the  ribs. 

The  above  mentioned  extrinsic  muscles  of  the  upper  extremity  vary  prin- 
cipally in  their  attachments.  Since  they  all  appear  well  forward  in  the  cervical 
region  in  the  embryo,  and,  along  with  the  extremity,  gradually  migrate  caudally 
before  acquiring  their  final  attachments,  it  is  not  unlikely  that  the  variations  in 
their  attachments  are  due  to  variations  in  the  extent  of  migration. 

This  serves  to  illustrate  a  factor  which  is  probably  important  in  producing 
variations  in  the  attachments  of  many  other  muscles.  As  stated  in  paragraph 
i,  on  page  264,  the  myo tomes  frequently  migrate  very  extensively  during 
their  transformation  into  muscles,  before  the  muscles  have  acquired  their  per- 
manent attachment.  Variations  in  the  extent  of  this  migration  would  naturally 
produce  variations  in  the  final  attachments  of  these  muscles. 

Other  factors  related  to  the  changes  in  the  myo  tomes,  such  as  fusion,  longi- 
tudinal and  tangential  splitting  (paragraphs  2,  3  and  4,  p.  264)  probably  also 
play  a  part  in  the  production  of  variations. 

A  greater  than  normal  degree  of  fusion  between  two  or  more  myotomes 
might  result  in  the  union  of  muscles  which  are  usually  separate;  a  less  than 
normal  degree  of  fusion  might  result  in  the  separation  of  parts  usually  united. 
Variations  in  the  splitting  of  myotomes  might  produce  similar  results. 

At  the  same  time,  however,  heredity  may  be  the  active  factor  in  some  cases 
where  abnormal  fusions  or  separations  between  muscles  or  parts  of  muscles 
produce  results  resembling  conditions  found  in  lower  animals. 

Reference  for  Further  Study. 

V  BARDEEN,  C.  R. :  The  Development  of  the  Musculature  of  the  Body  Wall  in  the  Pig, 
Including  its  Histogenesis  and  its  Relation  to  the  Myotomes  and  to  the  Skeleton  and  to  the 
Nervous  Apparatus.  Johns  Hopkins  Hospital  Reports,  Vol.  XI. 


284 


TEXT-BOOK  OF  EMBRYOLOGY. 


BARDEEN,  C.  R.,  and  LEWIS,  W.  H.:  Development  of  the  Limbs,  Body  Wall  and  Back 
in  Man.  American  Jour,  of  Anat.,  Vol.  I,  1901. 

BOLK,  L.:  Die  Segmentaldifferenzierung  des  menschlichen  Rumpfes  und  seiner  Extremi- 
taten.  Morph.  Jahrbuch,  Bd.  XXV,  1898. 

FUTAMURA,  R.:  Ueber  die  Entwickelung  der  Facialismuskulatur  des  Menschen. 
Anat.  Hefte,  XXX,  1906. 

GODLEWSKI,  E.:  Die  Entwickelung  des  Skelet-  und  Herzmuskelgewebes  der  Saugetiere. 
Arch.  f.  mik.  Anat.,  Bd.  LX,  1902. 

GRAFENBERG,  E.:  Die  Entwickelung  der  menschlichen  Beckenmuskulatur.  Anat. 
Hefte,  1904. 

HEIDENHAIN,  M.:  Structur  der  contractilen  Materie.  Ergebnisse  der  Anat.  u.  Entwick., 
Bd.  VIII,  1898. 

HEIDENHAIN,  M.:  Ueber  die  Structur  des  menschlichen  Herzmuskels.  Anal.  Anz., 
Bd.  XX,  1901. 

KASTNER,  S.:  Ueber  die  Bildung  von  animalen  Muskelfasern  aus  dem  Urwirbel. 
Arch.  f.  Anat.  u.  Physiol.,  Anat.  Abth.,  Suppl.,  1890. 

KEIBEL,  F.,  and  MALL,  F.  P.:  Manual  of  Human  Embryology,  Vol.  I,  1910. 

KOLLMANN,  J.:  Die  Rumpfsegmente  menschlicher  Embryonen  von  13-35  Urwirbeln. 
Arch.  f.  Anat.  u.  Physiol.,  Anat.  Abth.,  1891. 

LEWIS,  W.  H.:  The  Development  of  the  Arm  in  Man.  American  Jour,  of  Anat.y  Vol.  I, 
1902. 

MAURER,  F.:  Die  Entwickelung  des  Muskelsystems  und  der  elektrischen  Organe.  Also 
Bibliography.  In  Hertwig's  Handbuch  der  vergl.  u.  experiment.  Entwickelungslehre  der 
Wirbeltiere,  Bd.  Ill,  Teil  I,  1904. 

MACCALLUM,  J.  B.:  On  the  Histology  and  Histogenesis  of  the  Heart-muscle  Cell. 
Anat.  Anz.,  Bd.  XIII,  1897. 

MACCALLUM,  J.  B.:  On  the  Histogenesis  of  the  Striated  Muscle  Fiber  and  the  Growth  of 
the  Human  Sartorius  Muscle.  Johns  Hopkins  Hospital  Bulletin,  Vol.  IX,  1898. 

MALL,  F.  P. :  Development  of  the  Ventral  Abdominal  Walls  in  Man.  Jour,  of  Mor- 
phology, Vol.  XIV,  1898. 

McGiLL,  CAROLINE:  The  Histogenesis  of  Smooth  Muscle  in  the  Alimentary  Canal  and 
Respiratory  Tract  of  the  Pig.  Internal.  Monatsch.  Anat.  u.  Phys.,  Bd.  XXIV,  1907. 

McMuRRicn,  J.  P. :  The  Phylogeny  of  the  Forearm  Flexors.  American  Jour,  of  Anat., 
Vol.  II,  1903. 

McMuRRiCH,  J.  P.:  The  Phylogeny  of  the  Palmar  Musculature.  American  Jour,  oj 
Anat.,  Vol.  II,  1903. 

MCMURRICH,  J.  P.:  The  Phylogeny  of  the  Crural  Flexors.  American  Jour,  of  Anat., 
Vol.  IV,  1904. 

MCMURRICH,  J.  P.:  The  Phylogeny  of  the  Plantar  Musculature.     American  Jour,  oj 
Anat.,  Vol.  VI,  1907. 

POPOWSKY,  I.:  Zur  Entwickelungsgeschichte  der  Dammmuskulatur  beim  Menschen. 
Anat.  Hefte,  1899. 

SUTTON,  J.  B.:  Ligaments,  Their  Nature  and  Morphology.     London,  1897. 
ZIMMERMANN:  Ueber  die  Metamerie  des  Wirbeltierkopfes.     Verhandl.  d.  Anat.  Gesettsch. 
Jena,  1891. 


CHAPTER  XII. 


THE  DEVELOPMENT  OF  THE  ALIMENTARY  TUBE  AND 
APPENDED  ORGANS. 

The  embryonic  disk,  composed  of  the  three  germ  layers,  primarily  lies  flat 
upon  the  yolk  sac  (see  p.  107;  also  Fig.  75).  A  little  later  the  axial  portion  of 
the  embryo  is  indicated  by  the  primitive  streak,  the  neural  groove  (subsequently 
the  neural  tube),  the  notochord,  and  the  primitive  segments  (Fig.  71).  Then 
along  each  side  of  the  axial  portion  and  at  the  cephalic  and  caudal  ends,  the 


Neural  tube 


Oral  fossa 


_    Yolk  sac 


Hind-gut  _ 


Allantoic  duct 


Belly  stalk 


FIG.  244 . — Lateral  view  of  human  embryo  with  14  pairs  of  primitive  segments  (2.5  mm.) .     Kollntann. 

The  yolk  sac  has  been  cut  off.     The  fore-gut,  mid-gut  and  hind-gut,  as  indicated  in  the  figure, 

together  constitute  the  primitive  gut.     Compare  with  Fig.  245. 

germ  layers  bend  ventrally  and  medially  and  finally  meet  and  fuse  in  the  mid- 
ventral  line  (p.  109) .  The  portion  of  the  entoderm  ventral  to  the  notochord  is 
bent  into  a  tube  which,  for  the  most  part,  becomes  pinched  off  from  the  parent 
entoderm  and  is  suspended  in  the  embryonic  coelom  by  the  common  mesentery 
(Figs.  103  and  104).  This  entodermal  tube  is  the  primitive  gut.  At  first  it  ir> 
but  slightly  elongated  and  is  closed  at  both  ends.  On  the  ventral  side,  however^ 

285 


286 


TEXT-BOOK  OF  EMBRYOLOGY. 


it  opens  widely  into  the  yolk  sac  (Figs.  244  and  245).  The  primitive  gut,  there- 
fore, has  no  communication  with  the  exterior.  It  communicates  at  its  caudal 
end  with  the  central  canal  of  the  spinal  cord  through  the  neurenteric  canal  (Fig.  76; 
compare  with  77). 

As  development  proceeds,  this  simple  tube  elongates  rapidly  and  becomes 
differentiated  into  distinct  regions.  The  cephalic  end,  in  connection  with  the 
branchial  arches  and  grooves,  becomes  the  dilated  pharyngeal  region.  Caudal 


m  . 


|_     Oral  fossa 

jr — "Branchial  arch  I 

a—     Branchial  arch  II 

— "    Body  wall 
Ccelom 


Coelom 


Hind-gut 


Belly  stalk 


FlG.  245. — Ventral  view  of  human  embryo  of  2.4  mm.     His,  Kollmann. 

Note  the  opening  in  the  ventral  wall  of  the  gut.     This  indicates  the  communication  between  the 
gut  and  the  yolk  sac.     The  latter  has  been  removed.     Compare  with  Fig.  244. 

to  and  continuous  with  this,  is  the  short,  narrow  cesophageal  region  which  in 
turn  passes  over  into  the  slightly  dilated  stomach  region.  The  portion  of  the 
gut  caudal  to  the  stomach  is  the  intestinal  region.  During  the  differential 
changes,  the  communication  with  the  yolk  sac  becomes  relatively  smaller,  form- 
ing the  yolk  stalk  which  joins  the  intestinal  portion  a  short  distance  caudal  to  the 
stomach  (Figs.  246  and  247). 

The  Mouth. 

At  a  very  early  period  the  primary  fore-brain  region  bends  ventrally  almost 
at  a  right  angle  to  the  long  axis  of  the  body  to  form  the  naso-frontal  process. 


DEVELOPMENT  OF  THE  ALIMENTARY  TUBE  AND  APPENDED  ORGANS.       287 

As  the  first  branchial  arch  develops,  it  grows  ventrally  until  it  meets  and  fuses 
with  its  fellow  of  the  opposite  side  in  the  midventral  line,  thus  forming  the 
mandibular  process.  From  the  cephalic  side  of  the  first  arch  a  secondary  proc- 
ess— maxillary  process— develops  and  fills  in  the  space  between  the  arch  itself 
and  the  naso-frontal  process.  These  various  structures  thus  bound  a  distinct 
depression  on  the  ventral  side  of  the  head.  This  depression  is  the  oral  pit,  the 
forerunner  of  the  oral  and  nasal  cavities  (Fig.  245;  compare  with  Figs.  244 
and  85).  The  groove  in  the  midventral  line  between  the  mandibular  pro- 
cesses marks  the  symphysis  of  the  lower  jaws.  The  groove  on  each  side 


Epiglottis 

Tongue 
Hypophysis 


Larynx 


Lung 


... —  Stornaeh 


—    Pancreas 


/  — ;          -  ~— -^       I-, |  /       l 

Caudal  gut 

-  Mesonephric  duct 

Kidney  bud 
FIG.  246. — Alimentary  tube  of  a  human  embryo  of  4.1  mm.     His  Kollmann. 


between  the  maxillary  process  and  the  mandibular  process  marks  the  angle  of 
the  mouth.     The  groove  between  the  maxillary  process  and  the  naso-frontal 
process  is  the  naso-optic  furrow,  at  the  dorsal  end  of  which  the  eye  develops. 
The  bottom  of  the  oral  pit  is  formed  by  a  portion  of  the  ventral  body  wall, 
which  separates  the  oral  cavity  from  the  cephalic  end  of  the  gut,  and  which  is 
composed  of  ectoderm  and  entoderm,  with  a  small  amount  of  mesoderm  be- 
tween.    This  closing  plate,  the  pharyngeal  membrane,  which  is  still  present  in 
I  embryos  of  2.15  mm.,  soon  becomes  thinner  and  finally  breaks  away,  leaving 
I  the  oral  pit  and  the  gut  in  direct  communication  (Fig.  247).     Since  the  oral  pit 
,  is  lined  with  ectoderm,  the  epithelial  lining  of  the  mouth  or  oral  cavity  is  largely  of 


288 


TP:XT-BOOK  OF  EMBRYOLOGY. 


, 


l 


ectodermal  origin.  In  the  medial  line  of  the  roof  of  the  oral  cavity,  near  the 
pharyngeal  membrane,  the  epithelium  (ectoderm)  evaginates  to  form  Rathke's 
pocket.  This  comes  in  contact  with  an  evagination  from  the  floor  of  the  brain 
and  with  it  forms  the  pituitary  body. 

The  further  development  of  the  mouth  consists  of  an  elaboration  of  the 
structures  which  primarily  bound  the  oral  pit  and  the  growth  of  certain  new 
structures  such  as  the  teeth  and  the  tongue.  The  first  branchial  arch  fuses  with 
its  fellow  of  the  opposite  side  in  the  midventral  line  to  form  the  symphysis  of 
the  lower  jaws,  giving  rise  also  to  the  lower  lip  and  chin  region.  As  the  naso- 
frontal  process  continues  to  grow,  two  depressions  appear  on  its  ventral  border, 


Pharynx 


Hypophysis 


Branchial  arches 
(pharynx) 


Lung 


Liver 

H| Stomach 

t-""BH         Pancreas 

Common 
mesentery 

Mesonephros 
Allantoic  duct 

Hind-gut 

^-  x^sp^v 

Kidney  bud 
FIG.  247. — Sagittal  section  of  reconstruction  of  a  human  embryo  of  5  mm.     His,  Kollmann. 

one  on  each  side,  a  short  distance  from  the  medial  line.  These  depressions  are 
the  nasal  pits  which  indicate  the  beginning  of  the  external  openings  of  the  nasal 
passages.  The  part  between  the  nasal  pits  is  destined  to  give  rise  to  the  nasal 
septum  and  the  medial  part  of  the  upper  lip  (Fig.  98).  The  primary  oral 
cavity  is  divided  into  the  oral  cavity  proper  and  the  nasal  cavity  by  outgrowths 
from  the  maxillary  processes.  From  the  medial  side  of  each  maxillary  process 
a  plate-like  structure  grows  across  the  primary  oral  cavity  toward  the  medial 
line  (Fig.  140).  These  two  plates,  or  palatine  processes,  meet  and  fuse  with  the 
lower  part  of  the  nasal  septum  (Fig.  248) .  (For  further  details  of  this  fusion,  see 
page  121  and  page  163).  The  palatine  processes  thus  form  the  palate,  or  the 
roof  of  the  mouth,  which  separates  the  mouth  cavity  from  the  nasal  cavity.  The 
palate  does  not  extend  far  enough  backward,  however,  to  separate  the  posterior 


DEVELOPMENT  OF  THE  ALIMENTARY  TUBE  AND  APPENDED  ORGAN?.       289 


part  of  the  nasal  cavity  from  the  pharynx.  Thus  the  posterior  nares  and 
pharynx  are  left  in  communication.  Externally  the  maxillary  processes  extend 
medially,  separate  the  nasal  pits  from  the  oral  cavity,  and  form  the  lateral 
portions  of  the  upper  lip  (Fig.  99). 


Jacobson's  organ 
Inferior  concha 

Jacobson's  cartilage 


Palatine  process 


Nasal  septum 


Nasal  cavity 


Oral  cavity 


FIG.  248. — From  a  section  through  the  head  of  a  human  embryo  of  28  mm.,  showing  the  nasal 
septum,  the  nasal  cavities,  the  oral  cavity,  and  the  palatine  processes.     Peter. 

The  Tongue. — The  tongue  develops  from  three  separate  anlagen  which 
unite  secondarily.  In  embryos  of  about  3  mm.  a  slight  elevation  appears  on  the 
floor  of  the  pharynx  in  the  region  of  the  first  branchial  arch.  This  is  the 


Tuberculum  impar 


Root  of  tongue 


Inner  branchial 
groove  IV 


Crista  terminalis 


Lung 
FIG.  249. — Floor  of  the  pharyngeal  region  of  a  human  embryo  of  about  3  weeks.     His. 

tuberculum  impar ,  being,  as  the  name  indicates,  unpaired,  and  is  destined  to  give 
rise  to  the  tip  and  body  of  the  tongue  (Fig.  249) .  Soon  afterward  two  bilaterally 
symmetrical  elevations  appear  on  the  floor  of  the  pharynx,  which  are  destined  to 
give  rise  to  the  root  of  the  tongue  (Fig.  250).  These  paired  elevations,  arising 


290  TEXT-BOOK  OF  EMBRYOLOGY. 

in,  the  region  of  the  second  and  third  branchial  arches,  gradually  enlarge  and 
unite  with  each  other  and  with  the  tuberculum  impar,  leaving  between  the 
latter  and  themselves,  however,  a  V-shaped  groove  (Fig.  -251).  At  the  apex  of 
the  groove  there  is  a  depression — the  foramen  c&cum  lingua — which  is  the  ex- 
ternal opening  of  the  thyreoglossal  duct  (see  p.  301).  The  groove  later  disap- 
pears, but  its  position  is  indicated  in  the  adult  by  the  vallate  papillae. 

According  to  Hammar,  the  tuberculum  impar  is  a  transitory  structure  and  does  not 
give  rise  to  the  tip  and  body  of  the  tongue.  The  tip  and  body  are  derived  from  a  much 
more  extensive  elevation  in  the  floor  of  the  pharynx. 

The  tongue  as  a  whole  enlarges  and  grows  from  its  place  of  origin  toward 
the  entrance  to  the  primary  oral  cavity.  For  a  time  it  practically  fills  the  cavity. 
When  the  palate  develops  it  recedes  and  finally  comes  to  lie  on  the  floor  of  the 
oral  cavity  proper,  as  in  the  adult.  The  growth  of  the  tongue  involves  the 


Tuberculum  impar 

Root  of  tongue 
Epiglottis 


FlG,  250.  —Floor  of  pharyngeal  region  of  a  human  embryo  of  12.5  mm.     His. 

epithelial  lining  of  the  pharynx  and  oral  cavity  and  also  the  underlying  mesen- 
chymal  tissue.  The  latter  produces  the  connective  tissue  and  at  least  a  part  of 
the  intrinsic  muscle  fibers  of  the  tongue.  The  papillae  involve  the  epithelium 
and  connective  tissue,  while  the  glands  and  taste  buds  are  derived  from  the 
epithelium  alone. 

The  portion  of  the  lingualis  muscle  innervated  by  the  facial  (VII)  nerve  is  probably 
derived  from  the  mesenchymal  tissue  in  the  tongue  anlage.  The  rest  of  the  muscle  is 
innervated  by  fibers  from  the  hypoglossal  (XII)  nerve,  indicating  a  possible  derivation  from 
certain  rudimentary  segments  in  the  occipital  region  which  correspond  to  the  three  roots  of 
the  nerve.  This  would  make  it  appear  that  during  phylogenesis  a  part  of  the  lingualis 
muscle  has  grown  into  the  tongue  from  a  region  caudal  to  the  last  branchial  arch. 

The  lingual  papilla  begin  to  develop  during  the  third  month.  Their 
development  is  limited  to  the  dorsum  of  the  tongue  and  to  the  portion  derived 
from  the  tuberculum  impar.  In  other  regions  slight  elevations  may  appear,  but 
not  in  the  form  of  distinct  papillae.  The  fungijorm  and  filiform  papillae  appear 
as  pointed  elevations  in  the  connective  tissue,  which  push  their  way  into  the 
epithelium,  the  latter  at  the  same  time  being  raised  above  the  surface  over  these 


DEVELOPMENT  OF  THE  ALIMENTARY  TUBE  AND  APPENDED  ORGANS.       291 

points.  Gradually  the  little  masses  of  connective  tissue  assume  the  shapes 
characteristic  of  fungiform  or  filiform  papillae.  During  the  fifth  month 
the  epithelium  between  the  papillae  apparently  degenerates  to  some  extent, 
thus  leaving  them  projecting  still  farther  above  the  surface.  The  forma- 
tion of  papillae  probably  goes  on  for  some  time  after  birth,  since  at  birth  their 
form,  size,  number  and  arrangement  are  not  the  same  as  at  later  periods.  It  is 
an  interesting  fact  that  the  filiform  papillae  lose  many  of  their  taste  buds  after 
the  child  is  weaned. 

The  anlage  of  the  vallate  papillae  appears  as  a  ridge  along  the  V-shaped  line 
of  fusion  between  the  paired  and  unpaired  portions  of  the  tongue.  The  ridge  is 
apparently  formed  by  the  ingrowth  of  a  solid  mass  of  epithelium  along  each 
side,  although  the  connective  tissue  between  the  masses  may  grow  toward  the 
surface  to  some  extent.  Later  the  ridge  is  broken  up  into  the  individual  papillae 

Tuberculum  impar 

Root  of  tongue 


FIG.  251. — Dorsal  view  of  the  tongue  of  a  human  embryo  of  20  mm.     His,  Bonnet. 

by  the  ingrowth  of  the  epithelium  at  certain  points.  The  more  superficial  cells 
of  the  masses  then  degenerate,  thus  leaving  each  papilla  surrounded  by  a  trench 
and  wall. 

The  development  of  the  lingual  glands  is  confined  for  the  most  part  to  the 
root  and  inferior  surface  and  to  the  region  of  the  vallate  papillae.  The  glands 
begin  to  develop  during  the  fourth  month  as  solid  ingrowths  of  epithelium,  the 
mucous  glands  appearing  first,  the  serous  somewhat  later.  The  epithelial 
masses  acquire  lumina  and  grow  deeper  into  the  tongue,  where  they  usually 
branch  and  coil  to  form  the  secreting  portions.  The  latter  open  to  the  surface 
through  the  original  ingrowths  which  become  the  ducts.  Ebner's  glands 
develop  from  the  bottoms  of  the  trenches  around  the  vallate  papillae. 

The  Teeth. — The  development  of  the  teeth  involves  the  ectoderm  and 
mesoderm,  the  former  giving  rise  to  the  enamel,  the  latter  to  the  dentine  and 
pulp.  In  human  embryos  of  12-15  mm.  (thirty-four  to  forty  days),  before 
the  lip  groove  is  formed,  a  thickening  of  the  epithelium  (ectoderm)  takes  place 


292 


TEXT-BOOK  OF  EMBRYOLOGY. 


along  the  edges  of  the  processes  that  bound  the  slit-like  entrance  to  the  mouth. 
When  the  lip  groove  appears  (Fig.  140),  the  epithelial  thickening  comes  to  lie 
along  the  edge  of  the  jaw,  or  in  other  words,  along  the  edge  of  the  gums.  It 
then  grows  into  the  mesenchymal  tissue  (mesoderm)  of  the  jaw  obliquely  toward 
the  lingual  surface  to  form  the  dental  shelf.  A  little  later  the  dental  groove 
appears  on  the  edge  of  the  jaw,  along  the  line  where  the  ingrowth  of  epithelium 
took  place. 


-•—  Epithelium  of  mouth  cavity 


Outer 8 

enamel  cells 


Enamel  pulp  - 


Inner 
enamel  cells 


Dental  papilla 


Neck  of 
enamel  organ 


Germ  of 
permanent  tooth 


FlG.  252. — Section  of  developing  tooth  from  a  3!  months  human  fetus.     Szymonowicz. 

Note  the  portion  of  the  original  dental  shelf  connecting  the  developing  tooth  with  the 

epithelium  of  the  mouth  cavity. 


The  dental  shelf  is  at  first  of  uniform  thickness,  but  in  a  short  time  five 
enlargements  appear  in  it  in  each  upper  and  lower  jaw,  indicating  the  begin- 
nings of  the  milk  teeth.  When  the  embryo  reaches  a  length  of  40  mm.  (an  age  of 
eleven  to  twelve  weeks)  the  mesenchymal  tissue  on  one  side  of  these  enlargements 
(above  and  to  the  inner  side  in  the  upper  jaw,  below  and  to  the  inner  side  in  the 
lower  jaw)  becomes  condensed  and  pushes  its  way  into  the  epithelium.  Each  of 
these  mesenchymal  ingrowths  is  a  dental  papilla.  Thus  at  this  stage  the  anlage 
of  each  tooth  is  a  mass  of  epithelium  fitting  cap-like  over  a  mesenchymal  papilla. 
The  epithelium  is  the  forerunner  of  the  enamel  organ;  the  papilla  is  destined  to 
give  rise  to  the  dentine  and  pulp.  The  anlagen  are  connected  with  one  another 


DEVELOPMENT  OF  THE  ALIMENTARY  TUBE  AND  APPENDED  ORGANS.       293 


by  intermediate  portions  of   the  dental  shelf,  and  with  the  surface  by  the 
original  ingrowth  of  epithelium.  •  ^ 

THE  ENAMEL. — The  epithelial  cells  nearest  the  dental  papilla  become  high 
columnar  in  shape,  forming  a  single  layer.  Those  in  the  interior  of  the  mass 
become  separated  and  changed  into  irregular,  stellate,  anastomosing  cells,  with 
a  fluid  intercellular  substance,  constituting  the  enamel  pulp.  Those  farthest 
from  the  papilla  become  flattened  (Fig.  252 ;  compare  with  Fig.  253).  Calcifi- 
cation begins  in  the  basal  ends  of  the  columnar  cells,  or  in  the  ends  next  the 


Enamel 
Dentine          I      Enamel  prisms 


Odontoblasts 


7 wsww^l*     •'§          &      ^t%  ) 

iil^  y<v;17k  i 

x^JJ4 
^S*  ,    *      ;>  '^ 

S.:'SV'       '>•'   .V, 

••*-.  ^      '    *v ' 


Outer } 

I  enarnei 
f  cells 


—     Inner  J 


Enamel  pulp 


. ,  -  ;«• 

,  ,4' li 

7-«i.V*  ^ 

i/*.*v   *  «•' 

••  ^. '  *  *fe 

»'  '  i  *,  *"*-: 

-.0*^* 

tf\*i*3jK 


•4L 

^ 


m. 


Cuticle  ] 

I  of  enamel 
f  cells 

Basal  memb.  J 


FIG.  253. — Section  through  the  border  of  a  developing  tooth  of  a  new-born  puppy.     Bonnet. 

papilla,  and  in  the  intercellular  substance,  and  gradually  progresses  throughout 
the  cells,  the  latter  at  the  same  time  becoming  much  more  elongated.  Thus  the 
cells  are  transformed  into  enamel  prisms  which  are  held  together  by  the  calci- 
ned intercellular  substance  (Fig.  253). 

The  formation  of  enamel  begins  in  the  milk  teeth  toward  the  end  of  the 
fourth  month  and  probably  continues  until  the  teeth  break  through  the  gums. 
The  enamel  organ  at  first  surrounds  the  entire  developing  tooth  except  where 
the  papilla  joins  he  underlying  mesenchymal  tissue  (Fig.  252).  Later  the 
deeper  part  of  the  organ  disappears  as  such,  and  the  enamel  is  formed  only  on 
that  part  of  the  tooth  which  eventually  becomes  the  crown.  The  enamel  pulp 
increases  in  amount  for  a  time,  but  subsequently  disappears  as  the  tooth  grows 
into  it  (Fig.  254).  Its  function  is  not  fully  understood.  It  may  serve  as  a.  line 


294 


TEXT-BOOK  OF  EMBRYOLOGY. 


of  least  resistance  in  which  the  tooth  grows,  and  it  may  convey  nourishment 
to  the  enamel  cells,  the  enamel  organ  being  non-vascular. 

The  Dentine  and  Pulp. — At  first  the  dental  papilla  is  simply  a  condensation 
of  mesenchyme,  but  later  it  is  converted  into  a  sort  of  connective  tissue  pene- 
trated by  blood  vessels  and  nerves  (Fig.  254).  The  cells  nearest  the  enamel 
organ  become  columnar  and  arranged  in  a  single  layer,  with  the  nuclei 
toward  their  inner  ends.  The  outer  ends  are  blunt,  while  the  inner  ends  are 


Epith.  of  mouth  cavi+v 


Dental  sac 


Bone  of  jaw 


Blood  vessel 


Outer] 

f-  enamel  cells 
Inner ) 


Enamel. 
Dentine 
Odontoblasts 


Enamel  pulp 
(remnant) 


Papilla 
FIG.  254. — Longitudinal  section  of  a  developing  tooth  of  a  new-born  puppy.     Bonnet. 


continued  as  slender  processes  that  extend  into  the  pulp  and  probably 
with  other  cell  processes.     These  columnar  cells  are  the  odontoblasts ,  under  tl 
influence  of  which  the  lime  salts  of  the  dentine  are  deposited,  and  which  are  coi 
parable  with  the  osteoblasts  in  developing  bone. 

Toward  the  end  of  the  fourth  month  the  odontoblasts  form  a  membrane 
like  structure,  the  membrana  preformativa,  between  themselves  and  the  enamel. 
This  membrane  is  first  converted  into  dentine  by  the  deposition  of  lime  salts, 
after  which  the  process  of  calcification  progresses  from  the  enamel  toward  the 


DEVELOPMENT.  OF  THE  ALIMENTARY  TUBE  AND  APPENDED  ORGANS.       295 

pulp.  During  calcification  slender  processes  of  the  odontoblasts  remain  in  minute 
channels,  or  dentinal  canals,  forming  the  dentinal fibers  which  anastomose  with 
one  another  (Fig.  253).  In  the  peripheral  part  of  the  dentine  certain  areas 
apparently  fail  to  become  calcified  and  form  the  inter  globular  spaces.  The  same 
cells  that  are  originally  differentiated  from  the  mesenchyme  probably  persist 
throughout  development  as  the  odontoblasts  and  produce  the  entire  amount  of 
dentine  in  a  tooth.  Even  in  the  fully  formed  tooth  there  is  a  layer  of  odonto- 
blasts bearing  the  same  relation  to  the  dentine  and  pulp  as  in  the  developing 
tooth.  The  chief  difference  between  dentine  formation  and  bone  formation  is 
that  in  the  latter  the  osteoblasts  become  enclosed  to  form  bone  cells,  while  in 
the  former  the  odontoblasts  merely  leave  processes  enclosed  as  the  cell  bodies 
recede. 

The  pulp  of  the  tooth  is  of  course  derived  from  the  mesenchymal  tissue  in 
the  interior  of  the  dental  papilla  (compare  Figs.  252  and  254).  The  blood 
vessels  and  nerves  grow  in  from  the  underlying  connective  (mesenchymal)  tissue. 

At  an  early  stage  the  mesenchymal  tissue  around  the  anlage  of  the  tooth,  in- 
cluding the  enamel  organ,  condenses  to  form  a  sort  of  sheath,  the  dental  sac, 
which  is  later  ruptured  when  the  tooth  breaks  through  the  gum  (Fig.  254). 
The  cement  is  formed  around  the  root  of  the  tooth  from  the  tissue  of  the  dental 
sac  in  the  same  manner  as  subperiosteal  bone  is  formed  from  osteogenetic  tissue 
(p.  142).  In  fact,  cement  is  true  bone  without  Haversian  systems. 

The  milk  teeth,  which  are  the  first  to  develop  and  the  first  to  appear  above 
the  surface,  are  represented  by  the  medial  incisors,  lateral  incisors,  canines,  and 
molars,  to  the  number  of  ten  in  the  upper  and  ten  in  the  lower  jaw.  They  may 
be  indicated  graphically  thus: 

M.     C.     L.I.     M.I.      M.I.     L.I.     C.     M. 

10 


211                  I 

I 

I 

I 

2 

211                   I 

I 

I 

I 

2 

—  20 
10 


M.     C.     L.I.     M.I.     M.I.    L.I.     C.     M. 


In  describing  the  formation  of  the  dental  shelf,  it  was  noted  that  the  papillae 
of  the  milk  teeth  grow  into  corresponding  thickenings  of  the  epithelium  (p.  292). 
The  growth  takes  place  from  the  side,  thus  leaving  the  edge  of  the  shelf  free  to 
grow  farther  toward  the  lingual  side  of  the  jaw.  In  this  free  edge  other  tooth 
germs  arise,  which  mark  the  beginnings  of  the  permanent  teeth  (Fig.  252).  In 
addition  to  the  germs  that  correspond  in  position  to  the  milk  teeth,  three  others 
arise  in  each  jaw,  representing  the  true  molars  of  the  adult.  The  latter  arise  in  a 
part  of  the  dental  shelf  which  has  grown  toward  the  articulation  of  the  jaws 
without  coming  in  contact  with  the  surface  epithelium.  The  first  papilla  of 
the  permanent  dentition  to  appear  is  that  of  the  first  molar.  It  appears  im- 
mediately behind  the  second  milk  molar  at  a  time  when  the  milk  teeth  are  well 


296 


TEXT-BOOK  OF  EMBRYOLOGY. 


advanced  (embryos  of  180  mm.,  about  seventeen  weeks).  The  permanent 
incisors  and  canines  appear  about  the  twenty-fourth  week;  the  premolars,  which 
correspond  to  the  milk  molars,  about  the  twenty-ninth  week.  The  second 
molar  does  not  appear  till  after  birth  (six  months),  and  the  third  molar,  or 
wisdom  tooth,  begins  to  develop  about  the  fifth  year. 

The  formation  of  the  anlagen  of  the  permanent  teeth  and  the  development  of 
the  enamel,  dentine  and  pulp  take  place  in  precisely  the  same  manner  as  in  the 
milk  teeth.  The  true  molars  grow  out  through  the  gums  in  the  same  way  as 
the  milk  teeth.  Those  permanent  teeth  which  correspond  in  position  to  milk 
teeth  grow  under  the  latter,  exert  pressure  on  their  roots  and  thus  loosen  and 
finally  replace  them.  The  two  sets  of  teeth  may  be  graphically  represented 
thus: 
Upper  Jaw — Permanent, 

Upper  jaw — Milk, 

16 

S1  *-•*•-•.  -i.  j.  j-  j.  ^  ^ 

Lower  Jaw — Milk, 
Lower  Jaw — Permanent, 

Normally  all  the  epithelium  of  the  dental  shelf,  except  the  parts  directly  con- 
cerned in  the  development  of  the  teeth,  disappears  at  times  which  vary  in  differ- 
ent individuals.  Occasionally,  however,  remnants  of  this  epithelium  give  rise 
to  cystic  structures  (developmental  tooth  tumors) . 


M. 

Pm. 

M 

C. 

L.L 

II 

M. 

II 

I. 

M.I. 

L.I. 

II 

c. 

Pm. 

M. 

M 

II 
M. 

C. 

II 
L.I. 

% 

I." 

M.I. 

II 
L.I. 

C. 

1! 
M. 

3 

2 

i 

i 

i 

i 

i 

I 

2 

3 

3 

2 

i 

i 

i 

i 

i 

I 

2 

3 

M. 

C. 

L.I. 

M. 

I. 

M.I. 

L.I. 

c. 

M. 

M. 

II 
Pm. 

II 
C. 

A 

J. 

I. 

M11!. 

£ 

II 

c. 

r 

r 

n. 

I 

Subling.  gland 


Submax.  gland 


.Vi .  Tongue 

te 


Palatine  process 


Submax.  gland 


Lingual  nerve 
FIG.  255. — From  a  transverse  section  through  the  tongue  and  oral  cavity  of  a  mouse  embryo.    Goppert. 

The  Salivary  Glands. — The  anlage  of  the  submaxillary  gland  appears,  in 
embryos  of  10  to  12  mm.,  as  a  flange  of  epithelium  directed  ventrally  from 
the  portion  of  the  lingual  sulcus  just  caudal  to  the  crossing  of  the  lingual 
nerve.  The  flange  grows  into  the  mesenchyme  of  the  lower  jaw,  and  at  an 
early  period  becomes  triangular  with  its  longest  side  free  and  a  free  vertical 
caudal  border.  Cell  proliferation  begins  at  the  angle  of  union  of  the  two 
borders  and  gradually  progresses  cephalad  along  the  longest  border,  thus 
producing  a  solid  ridge-like  thickening  of  the  latter. 


DEVELOPMENT  OF  THE  ALIMENTARY  TUBE  AND  APPENDED  ORGANS.       297 

The  main  portion  of  the  gland  is  produced  by  a  sprouting  of  the  epithelium 
from  the  angle  of  union  of  the  two  free  borders  of  the  flange  and  grows  deep 
into  the  mesenchyme  along  the  mesial  side  of  the  ramus  of  the  mandible. 
The  sprouts  branch  repeatedly  in  the  course  of  their  development,  thus  laying 
the  foundation  for  the  division  of  the  gland  into  lobes  and  lobules. 

The  distal  end  of  the  duct  of  the  submaxillary  (Wharton's)  is  formed  from 
the  ridge-like  thickening  of  the  free  margin  of  the  flange  through  a  dissolu- 
tion of  the  greater  part  of  the  flange  between  the  lingual  sulcus  and  the 
thickened  margin  itself,  thus  freeing  this  portion  of  the  duct  from  the  sulcus. 
By  a  continuation  of  the  growth  which  produced  the  ridge  along  the  free 
border  of  the  original  flange  an  extension  of  this  same  ridge  is  produced  along 
the  bottom  of  the  lingual  sulcus  forward  toward  the  chin  region.  This  portion 
of  the  ridge  is  progressively  constricted  off  from  the  sulcus  from  cehind 
forward,  until  finally  the  attachment  of  the  duct  reaches  its  definitive  position 
at  the  side  of  the  frenulum  linguae. 

The  anlage  of  the  Bartolinian  element  of  the  suUingual  gland  appears  as 
a  smaller  flange  attached  to  the  lateral  border  of  the  submaxillary  flange  near 
the  crossing  of  the  lingual  nerve  and  prolonged  forward  by  an  interrupted 
crest  along  the  lingual  sulcus.  Its  later  development  is  similar  to  that  of  the 
submaxillary. 

A  small  medial  flange  also  on  the  submaxillary  flange  gives  rise  to  a  sprout 
in  much  the  same  manner  as  the  other  anlagen.  While  the  history  of  this 
anlage  is  not  complete  in  the  human  embryo,  it  probably  gives  rise  to  the 
anterior  lingual  gland  (gland  of  Bland  in  and  Nuhn).  The  alveolingual  ele- 
ments arise  from  a  keel  attached  to  the  alveolingual  sulcus  (the  groove 
between  the  floor  of  the  mouth  and  the  alveolar  process  of  the  lower  jaw). 

The  parotid  gland  originates  from  the  buccal  sulcus  in  essentially  the  same 
way  as  the  submaxillary  arises  from  the  lingual  sulcus.  The  anlage  then 
continues  to  grow  through  the  mesenchyme  of  the  cheek  across  the  masseter 
muscle,  the  distal  end  branching  freely  to  form  the  secreting  portion  of  the 
gland.  The  outgrowths  are  at  first  solid,  but  later  become  hollow,  the 
proximal  portion  of  the  original  outgrowth  forming  the  parotid  (Steno's) 
duct,  the  more  distal  portions  forming  the  smaller  ducts  and  terminal  tvbales. 

The  histogenetic  changes  in  the  salivary  glands  probably  continue  until  the 
child  takes  solid  food,  when  the  glands  become  of  greater  functional  importance. 
In  the  parotid  gland,  which  is  serous  in  man,  the  original,  undifferentiated 
epithelial  cells  undergo  changes  in  form  and  arrangement  so  that  by  the 
twenty-second  week  the  larger  ducts  are  lined  with  a  two-layered  epithelium, 
the  smaller  ducts  with  a  simple  cuboidal  epithelium,  and  the  terminal  tubules  with 
a  single  layer  of  high  columnar  cells.  The  two-layered  epithelium  in  the  larger 
ducts  persists.  The  ducts  lined  with  the  cuboidal  epithelium  become  the 


298 


TEXT-BOOK  OF  EMBRYOLOGY. 


socalled  intermediate  tubules,  the  cells  changing  to  a  flat  type.  The  high 
columnar  cells  of  the  terminal  tubules  become  the  serous  secreting  cells. 

Quite  similar  changes  also  occur  in  the  submaxillary,  but  in  foetuses  of 
eight  to  nine  months  the  crescents  of  Gianuzzi  appear  as  masses  of  darkly 
staining  cells  forming  the  ends  or  sides  of  the  terminal  tubules.  The  crescents 
at  first  border  on  the  lumina,  but  later,  probably  by  a  process  of  evagination, 
come  to  lie  on  the  surface  of  the  tubules. 

The  beginning  of  the  secretory  function  may  be  detected  by  a  diminution  in 
the  affinity  of  the  cells  for  stains. 

The  Pharynx. 

The  pharynx  develops  from  the  cephalic  end  of  the  primitive  gut.  This 
part  of  the  gut  is  primarily  of  uniform  diameter,  is  broadly  attached  by  meso- 1 
derm  to  the  dorsal  body  wall,  and  ends  blindly  (Fig.  247).  When  the  branchial 
arches  and  grooves  develop  in  this  (the  cervical)  region,  they  affect  the  gut  as 


Neural  tube 
(brain) 


Maxillary  process 
Mandibular  process 


-—  Notochord 


Bi      Branchial  arches  and 
»  '  grooves  (pharynx) 


Heart  - — 


Lung  groove 


FIG.  256.— Sagittal  section  through  the  head  of  a  human  embryo  of  4.2  mm.  (31-34  days).     Hi 
I 

well  as  the  periphery  of  the  body.     The  arches  form  ridges  on  the  surface  of  tl 
body  (Fig.  85)  and  at  the  same  time  form  ridges  on  the  wall  of  the  gut.     Th< 
grooves  form  pockets  which  alternate  with  the  arches  (Fig.  256).     The  pock< 
in  the  pharyngeal  cavity,  or  inner  branchial  grooves,  are  directed  outwai 
toward   corresponding  outer  branchial  grooves  (Fig.  249).     The  arches  ai 
covered  externally  with  ectoderm,  internally  with  entoderm,  and  are  filled  wit 
mesoderrih     Between  the  arches,  or  in  the  grooves,  the  ectoderm  and  entoden 
are  in  contact  or  nearly  so.     Thus  the  pharynx  is  not  surrounded  by  a  coeloi 
cavity. 


DEVELOPMENT  OF  THE  ALIMENTARY  TUBE  AND  APPENDED  ORGANS.        299 

Since  the  branchial  arches  develop  in  such  a  way  that  they  are  successively 
smaller  from  the  first  to  the  fourth,  the  pharyngeal  cavity  becomes  funnel- 
shaped  (Fig.  256).  It  also  becomes  somewhat  flattened  in  the  dorso- ventral 
direction,  and  in  the  earlier  stages  when  the  arches  and  grooves  are  fully  formed, 
-the  pharynx  constitutes  approximately  one-third  the  entire  gut  (Fig.  247). 
Primarily  the  pharyngeal  cavity  is  separated  from  the  oral  cavity  by  the  pharyn- 
geal membrane  (see  p.  287 ;  also  Fig.  244).  When  this  ruptures  and  disappears 
(during  the  fourth  week  ?)  the  two  cavities  are  in  open  communication.  What 
point  in  the  adult  represents  the  attachment  of  the  pharyngeal  membrane  is 
not  known;  but  the  glosso-  and  pharyngopalatine  arches  (pillars  of  the  fauces) 
are  usually  considered  as  the  boundary  between  the  mouth  and  pharynx.  The 
caudal  limit  of  the  pharynx  is  the  opening  of  the  larynx  (Figs.  247  and  256). 

Thus  in  the  early  stages  the  general  adult  character  of  the  pharynx  is  es- 
tablished. While  the  branchial  arches  and  grooves  undergo  profound  changes, 
the  pharyngeal  cavity  retains  the  same  relation  to  the  mouth  and  to  the  oeso- 
phagus and  respiratory  tract.  The  cavity  becomes  relatively  shorter,  however, 
and  the  alternating  ridges  and  pockets  in  its  walls  are  lost  as  the  arches  and 
grooves  are  transformed  into  other  structures.  The  metamorphosis  ojf  the 
arches  and  grooves  is  considered  elsewhere  (p.  118).  ^Lo^^""  ^-vJ^  f}~^ 

THE  TONSILS. — The  tonsils  arise  in  the  region  of  the  ventral  part  of  the  L- 
second  inner  branchial  groove.  During  the  third  month  the  epithelium 
(entoderm)  grows  into  the  underlying  connective  (mesenchymal)  tissue  in  the 
form  of  a  hollow  bud.  From  this,  secondary  buds  develop,  which  are  at  first 
solid,  but  later  (during  the  fourth  or  fifth  month)  become  hollow  by  a  disappear- 
ance of  the  central  cells  and  open  into  the  cavity  of  the  primary  bud,  thus  form- 
ing the  crypts.  Lymphoid  cells  wander  from  the  neighboring  blood  vessels,  or 
are  derived  directly  from  the'  epithelium-  (Retterer),  and  with  the  connective 
tissue  form  a  diffuse  lymphatic  tissue  under  the  epithelium  (Fig.  257).  By  the 
eighth  month  the  cells  become  more  numerous  in  places,  and  by  the  third 
month  after  birth  form  distinct  lymph  follicles  with  germinal  centers.  The 
formation  of  follicles  goes  on  slowly  and  is  probably  not  complete  until 
some  time  after  birth. 

The  Lingual  Tonsils. — The  lymphatic  tissue  of  the  tongue  develops  in  rela- 
tion to  the  lingual  glands.  During  the  eighth  month  lymphoid  infiltration 
occurs  around  the  ducts  of  the  glands,  and  the  connective  tissue  acquires  the 
reticular  character.  True  follicles  probably  do  not  appear  until  the  child  is  at 
least  five  years  old. 

The  Pharyngeal  Tonsils. — During  the  sixth  month  small  folds  appear  in  the 
mucous  membrane  of  the  roof  of  the  pharynx  and  become  diffusely  infiltrated 
with  lymphoid  cells.  This  occurs  first  in  the  posterior  part  of  the  roof,  but  later 
(seventh  or  eighth  month)  it  extends  forward  and  along  the  sides  of  the  naso- 


300 


TEXT-BOOK  OF  EMBRYOLOGY. 


pharygeal  cavity.  By  the  end  of  foetal  life  the  ridges  become  quite  large. 
Follicles  may  appear  before  birth  or  not  until  one  or  two  years  later.  After 
puberty  the  ridges  almost  completely  disappear,  but  the  adenoid  tissue  remains 
wholly  or  in  part. 

The  bursa  pharyngea  is  an  evagination  from  the  roof  of  the  pharynx  about 
the  upper  border  of  the  superior  constrictor  muscle,  and  is  apparent  in  em- 
bryos of  eleven  weeks.  It  probably  has  no  genetic  relation  to  the  hypophysis. 
Its  significance  is  not  known. 


b' 


FlG.  257. — Section  through  the  middle  of  the  developing  tonsil  of  a  human 

embryo  of  5  months.     Stohr. 

6,  Epithelial  buds  (secondary  outgrowths)  from  the  epithelium  lining  the  primary  crypt  (c) ; 
L,  lymphoid  infiltration  of  the  connective  (mesodermal)  tissue. 

THE  BRANCHIAL  EPITHELIAL  BODIES. 

THE  THYREOID  GLAND. — The  thyreoid  arises,  after  the  manner  of  ordinary 
glands,  as  an  evagination  from  the  epithelium  of  the  pharynx.  It  appears  in 
embryos  of  3  to  5  mm.  as  a  ventral  outgrowth  of  epithelium  in  the  floor  of  the 
pharynx,  at  the  point  where  the  tuberculum  impar  and  the  two  paired  anlagen 
of  the  tongue  join  (Fig.  258).  This  point  is  the  foramen  caecum  linguae  which 
has  already  been  mentioned  in  connection  with  the  development  of  the  tongue 
(p.  290) .  The  evagination  grows  into  the  mesodermal  tissue  in  the  ventral  wall 
of  the  neck,  and  forms  a  transverse  mass  of  epithelium.  The  latter  breaks  up 
into  irregular  cords  of  cells  which,  by  a  further  process  of  budding,  grow  cau  • 
dally  along  the  ventral  surface  of  the  larynx.  The  cords  of  cells  are  from  the 
first  surrounded  by  connective  tissue  and  later  also  become  surrounded  by  net- 
works of  capillaries  (Fig.  259).  They  ultimately  break  up  into  smaller  masses 
which  become  hollow  and  form  the  alveoli.  Colloid  secretion  begins  toward 
the  end  of  fcetal  life  or  soon  after  birth. 

As  the  gland  grows  toward  its  final  position  it  becomes  enlarged  laterally  into 
the  two  lateral  lobes,  which  remain  connected  by  the  isthmus  (Fig.  260).  The 
Pyramidal  process  represents  either  a  secondary  outgrowth  from  the  isthmus  or 
one  of  the  lobes,  or  a  remnant  of  the  original  connection  with  the  tongue,  that  is, 


DEVELOPMENT  OF  THE  ALIMENTARY  TUBE  AND  APPENDED  ORGANS.       301 


of  the  thyreoglossal  duct.  The  duct  usually  disappears  for  the  most  part,  but 
certain  structures  sometimes  found  in  the  adult  in  the  line  of  the  duct  are 
possibly  remnants  of  it.  They  have  been  variously  named,  according  to  their 
position,  accessory  thyreoid ,  suprahyoid,  and  prehyoid  glands  (Fig.  260). 

A  pair  of  structures,  appearing  first  in  embryos  of  8  to  10  mm.,  arise  as 
evaginations  from  the  ventral  ends  of  the  fourth  inner  branchial  grooves.  They 
grow  into  the  mesodermal  tissue  and  then  caudally  along  the  ventro-lateral  side 


Notochord 


Thymus 


Thyreoid 


Jugular  vein 
Vagus  nerve 


Carotid  artery 
Parathyreoid  (epith.  body) 

Thymus  (in.  br.  groove  III) 


Heart 


FIG.  258. — Transverse  section  through  the  region  of  the  3d  branchial  groove 

of  an  Echidna  embryo.     Maurer. 
i.=  Pharynx,  below  which  are  the  paired  anlagen  of  the  tongue. 

of  the  larynx,  where  they  come  into  close  relation  with  the  lateral  lobes  of  the 
thyreoid  (Fig.  260).  They  have  been  called  the  lateral  thyreoids,  and  acquire 
the  thyreoid  structure. 

Considerable  confusion  has  arisen  in  regard  to  the  lateral  thyreoids.  The  earlier  investi- 
gators held  that  they  were  derived  from  the  fourth  groove  and  united  with  the  medial  portion, 
which  appeared  at  the  foramen  caecum,  to  become  integral  parts  of  the  thyreoid.  Further 
researches  among  the  lower  Vertebrates  led  others  to  deny  that  the  thyreoid  arose  other 
than  as  a  medial  anlage,  and  that  the  so-called  lateral  thyreoids  in  the  embryo  were  the 
postbranchial  bodies  which  never  assumed  the  thyreoid  structure,  but  atrophied  and  dis- 
appeared. More  recently  it  has  been  thought  that,  although  the  postbranchial  bodies  do 
not  function  in  the  lower  Vertebrates,  they  may  in  the  higher  Mammals  and  man  unite  with 
the  medial  thyreoid  and  secrete  colloid. 

The  parathyreoids  or  epithelial  bodies  also  come  into  close  relation  with  the 
thyreoid.  They  arise  as  paired  evaginations  from  the  cephalic  sides  of  the  third  v 


302 


TEXT-BOOK  OF  EMBRYOLOGY. 


and  fourth  grooves,  dorsal  to  the  thymus  and  the  lateral  thyreoid  evaginations 
(Figs.  258  and  261).  As  the  thyreoid  grows  caudally  from  its  point  of  origin, 
these  bodies  come  to  lie  close  to  it  or  may  even  become  embedded  in  it  (Fig.  260). 
They  acquire  a  structure  which  resembles  that  of  the  suprarenal  gland  and  not 


Trachea 


Lateral  lobe 


Capillaries 
Isthmus 


FlG.  259. — Section  of  the  right  half  of  the  thyreoid  gland  of  a  pig  embryo  of  22.5  mm.     Born. 

yn 

)gl 

I 


Accessory  thyroeids 
(thyreoglossal  duct) 


Carotid  artery 


P.-th. 

Lat.  thyreoid 
(postbr.  body) 


Rignt  subclavian  artery 


Thymus 


Pyramidal  process 

Carotid  artery 
Lateral  thyreoid 
Isthmus 

Lumen  in  thymus 
» 

Left  subclavian  artery 


Arch  of  aorta 

FIG.  260. — Branchial  groove  derivatives  of  a  rabbit  embryo  of  16  mm.    P.-th.,  parathyreoid 
or  epithelial  body.     Verdun,  Bonnet. 

that  of  the  thyreoid.     Their  relation  to  the  latter  organ  seems  to  be  purely 
topographical. 

THE  THYMUS. — The  thymus  appears  in  embryos  of  about  6  mm.  as  an 
entodermal  evagination  from  the  ventral  part  of  the  third  branchial  groove  on 


DEVELOPMENT  OF  THE  ALIMENTARY  TUBE  AND  APPENDED  ORGANS.        303 

each  side  (Fig  258) .  The  outgrowths  are  at  first  hollow  and  communicate  with 
the  pharyngeal  cavity;  later  they  become  solid  and  (in  embryos  of  14  mm.)  lose 
their  connection  with  the  parent  epithelium.  They  elongate  and  grow  caudally 
in  the  mesodermal  tissue  until  (in  embryos  of  16  mm.)  their  caudal  ends  lie 
ventral  to  the  carotid  arteries  (Fig.  260).  In  embryos  of  29  mm.  their  caudal 
ends  rest  upon  the  cephalic  surface  of  the  pericardium,  their  cephalic  ends 
reaching  to  the  isthmus  of  the  thyreoid.  The  two  parts  eventually  fuse  to  a 
considerable  extent,  but  the  gland  as  a  whole  always  consists  of  two  distinct 
lobes. 

The  gland  continues  to  enlarge,  at  the  same  time  becoming  lobulated  by  the 
ingrowth  of  connective  tissue,  until  the  child  is  two  or  three  years  old.  At  this 
time  it  is  situated  in  the  anterior  mediastinum,  usually  in  the  medial  line.  After 
this  it  begins  to  atrophy  and  becomes  a  mass  of  fibrous  and  fatty  tissue  through 
the  growth  of  the  interlobular  septa  and  their  encroachment  upon  the  lobules. 
The  classical  view  that  the  thymus  begins  to  atrophy  after  the  second  or  third 
year  and  is  quite  degenerated  in  the  adult  has  recently  been  somewhat  offset 


Parathyreoid  1 
(epith.  bodies)  \    TV  _JJWW''     X'»  ^5}  $~  Thymus 

Lat.  thyreoid 
(postbr.  body) 

FIG   261. — Diagram  of  the  branchial  groove  derivatives  in  man.     Verdun. 

by  the  view  that  comparatively  slight  changes  take  place  in  it  until  puberty. 
According  to  the  latter  view,  degeneration  goes  on  after  puberty  at  a  rate  which 
varies  widely  in  different  individuals,  and  the  thymus  may  persist  as  a  functional 
organ  up  to  the  age  of  sixty  years. 

The  histo genesis  of  the  thymus  has  been  a  subject  of  much  study  and  con- 
troversy, not  only  in  regard  to  its  origin,  but  also  in  regard  to  its  change  from 
an  epithelial  to  a  lymphoid  structure  and  the  regressive  changes  in  the  latter. 
It  has  almost  certainly  been  proven  to  be  of  entodermal  origin.  It  is  at  first  an 
epithelial  mass  which  later  becomes  broken  up  into  lobules  by  the  ingrowth  of 
connective  tissue.  In  regard  to  the  histological  changes  which  it  undergoes, 
the  older  views  are  in  general  that  a  "  pseudomorphosis "  takes  place;  that  is, 
the  epithelial  elements  are  replaced  by  lymphoid  cells  which  wander  in  from 
the  neighboring  blood  vessels,  HassalFs  corpuscles  being  remnants  of  the 
epithelium.  Later  other  investigators  looked  upon  the  changes  as  a  "  transf or- 


304  TEXT-BOOK  OF  EMBRYOLOGY. 

mation,"  asserting  that  the  epithelial  cells  were  transformed  into  lymphoid 
cells  in  situ,  and  that  Hassall's  corpuscles  were  remnants  of  epithelium  and 
disintegrating  blood  vessels.  Some  went  even  so  far  as  to  assert  that 

the  thymus  was  the  first  place  of  origin  of 
the  leucocytes.  More  recent  researches 
furnish  very  strong  evidence  that  no  lymph- 
oid cells  are  derived  from  the  epithelial 
cells  (Maximow),  but  that  the  epithelium  is 
transformed  into  the  reticular  tissue  of  the 
thymus,  in  which  the  lymphoid  cells  undergo 
mitotic  division,  Hassall's  corpuscles  possibly 
representing  compressed  parts  of  the  reticu- 
lum  (Hammar)  (Fig.  262). 

THE    GLOMUS    CAROTICUM. — The  early 
formation  of  the  glomus  caroticum  (carotid 
FIG.   262.— Hassall's  corpuscle  from      gland)  has  not  been  observed  in  the  human 
ZftfO^Z**      embryo.       From     observations     on     lower 

animals  it  has  not  been  made  clear  whether 

it  is  derived  from  the  entoderm  of  a  branchial  groove  or  from  the  adventitia 
of  the  carotid  artery. 

The  (Esophagus  and  Stomach. 

THE  (ESOPHAGUS. — When  the  primitive  gut  becomes  differentiated  into* 
distinct  regions  (p.  286),  the  cesophageal  region  forms  a  comparatively  short: 
tube,  of  uniform  diameter,  extending  from  the  pharynx  to  the  stomach  (Fig.. 
247).  In  embryos  of  about  3  to  4  mm.  the  anlage  of  the  respiratory  system 
arises  from  the  cephalic  end  of  the  tube  (see  p.  330).  The  latter  is  lined  with 
entoderm  and  broadly  attached  to  the  dorsal  body  wall  by  mesoderm  (Fig.  247). 
During  later  stages  it  becomes  relatively  longer  as  the  heart  recedes  into  the1 
thorax  (p.  214),  but  maintains  its  uniform  diameter. 

Further  development  produces  no  marked  changes  in  the  relative  position; 
of  the  oesophagus.  It  remains  broadly  attached  to  the  dorsal  body  wall! 
throughout  the  life  of  the  individual.  In  other  words,  there  is  never  a  distinct! 
mesentery.  The  entoderm  gives  rise  to  the  epithelial  lining  and  the  glands,  the: 
surrounding  mesoderm  to  the  connective  tissue  and  muscular  coats. 

THE  STOMACH. — The  anlage  of  the  stomach  can  br  recognized  in  embryos 
of  about  5  mm.  as  a  slight  spindle-shaped  enlargement  of  the  primitive  gut  ai 
short  distance  cranial  to  the  yolk  stalk  (Fig.  246).  The  dilatation  goes  on  more;- 
rapidly  on  the  dorsal  than  on  the  ventral  side,  thus  producing  the  greater  and^ 
lesser  curvature  respectively.  The  greater  curvature  is  attached  to  the  dorsaU 
body  wall  by  the  dorsal  mesogastrium  which  is  a  part  of  the  common  mesentery.. 


EVELOPMENT  OF  THE  ALIMENTARY  TUBE  AND  APPENDED  ORGANS.       305 


The  lesser  curvature  is  connected  with  the  ventral  body  wall  by  the  ventral 
mesogastrium  (Fig.  263). 

In  further  development,  apart  from  histogenesis,  the  greater  curvature 
becomes  much  more  prominent  and  the  organ  as  a  whole  changes  its  position, 
the  latter  process  beginning  in  embryos  of  12  to  14  mm.  The  cephalic  (car- 
diac) end  moves  toward  the  left  side  of  the  body,  the  pyloric  end  toward  the 
right  At  the  same  time  the  stomach  rotates,  the  greater  curvature  turning 


Aorta 

j— •  Spleen 

I 

""  Dorsal  mesogastrium 

'"  Coeliac  artery 

•-  Pancreas 
Sup.  mesenteric  artery 


Ventral  mesogastrium  — — 


gK — ,  Cbmmon  mesentery 
f 

&^y-- —   Inf.  mesenteric  artery 

"""-•  Hind-gut  (rectum) 
FIG.  263. — Gastrointestinal  tract  and  mesenteries  of  a  human  embryo  of  6  weeks.     Toldt. 


Caecum 


caudally  from  its  dorsal  position  and  the  lesser  curvature  cranially  from  its 
ventral  position.  The  result  is  that  the  organ  comes  to  lie  in  an  approximately 
transverse  position  in  the  body,  with  the  cardiac  end  to  the  left,  the  pyloric  end 
to  the  right,  the  greater  curvature  directed  caudally,  and  the  lesser  curvature 
directed  cranially  (compare  Figs.  247  and  263  with  Figs.  276  and  304).* 

*  These  changes  may  be  more  easily  understood  if  the  student  will  hold  a  closed  book  in  the 
sagittal  plane  in  front  of  him,  with  the  back  of  the  book  toward,  and  the  open  edge  away  from  him. 
The  back  represents  the  greater  curvature,  the  open  edge  the  lesser  curvature.  The  upper  end  of 
the  book  represents  the  cardiac  end  of  the  stomach,  the  lower  end  the  pylorus.  Turn  the  upper 
(cardiac)  end  to  the  left,  the  lower  (pyloric)  end  to  the  right,  at  the  same  time  allowing  the  back  of 
the  book  (the  greater  curvature)  to  drop  downward  on  the  side  toward  the  body.  The  changes  in 
the  position  of  the  book  represent  the  changes  in  the  position  of  the  developing  stomach. 


306  TEXT-BOOK  OF  EMBRYOLOGY. 

It  is  obvious  that  the  lower  end  of  the  oesophagus  is  carried  toward  the  left 
side  of  the  body  with  the  cardiac  end  of  the  stomach,  and  at  the  same  time 
twisted  so  that  the  side  which  originally  faced  the  left  comes  to  face  ventrally. 
The  changes  in  the  mesentery  which  accompany  the  changes  in  the  stomach 
are  described  elsewhere  (p.  348) . 

The  torsion  of  the  stomach  also  produces  an  asymmetrical  condition  of  the 
vagi  nerves.  The  latter  reach  the  stomach  before  it  changes  its  position.  As 
the  changes  take  place,  the  left  nerve  is  carried  around  to  the  left  and  ventrally 
so  that  in  the  adult  it  passes  through  the  diaphragm  ventral  to  the  oesophagus 
and  extends  over  the  ventral  surface  of  the  stomach.  The  right  nerve  passes 
over  the  dorsal  surface  of  the  stomach. 

The  Intestine. 

When  the  primitive  gut  is  differentiated  into  recognizable  regions  (p.  286) 
the  intestinal  region  forms  a  simple  tube,  of  uniform  diameter,  extending  from 
the  stomach  to  the  caudal  end  of  the  embryo  where  it  ends  blindly.  The  yolk 
stalk  is  attached  to  the  intestine  a  short  distance  from  the  stomach.  Near  the 
caudal  end  the  allantoic  duct  arises  (p.  582).  The  lumen  of  the  yolk  stalk  and 
of  the  allantoic  duct  is  continuous  with  that  of  the  intestine  (Fig.  247).  In 
embryos  of  2  to  3  mm.  the  liver  anlage  arises  from  the  ventral  side  of  the 
intestine  near  the  stomach,  that  is,  from  that  part  of  the  intestine  which  is  to 
\\  become  the  duodenum.  In  embryos  of  3  to  4  mm.  the  pancreas  anlage  arises 
in  the  same  region,  in  part  from  the  liver  evagination  and  in  part  from  the  dorsal 
side  of  the  intestine  (Fig.  247). 

The  intestine  as  a  whole  is  suspended  in  the  abdominal  cavity  by  the  dorsal 
mesentery  which  is  attached  to  the  dorsal  body  wall  and  which  is  continuous 
with  the  dorsal  mesogastrium.  A  ventral  mesentery,  continuous  with  the 
ventral  mesogastrium,  is  present  only  at  the  cephalic  end  of  the  duodenum 
(Fig.  263). 

The  further  development  of  the  intestine,  apart  from  histogenesis,  consists 
very  largely  of  the  formation  of  loops  and  coils,  due  to  an  enormous  increase  in 
the  length  of  the  tube.  The  abdominal  cavity  at  the  same  time  enlarges  to 
accommodate  the  increased  bulk.  As  the  stomach  changes  its  position  (p.  305) , 
the  duodenum  comes  to  lie  obliquely  across  the  body  and  forms  a  curve  with  the 
concavity  directed  dorsally  (Fig.  263).  The  rest  of  the  intestine  forms  a  loop 
which  extends  ventrally  and  caudally  as  far  as  the  umbilicus.  The  arms  of  the 
loop  are  almost  parallel  and  the  cephalic  arm  lies  a  little  to  the  left  of  the  caudal. 
The  apex  of  the  loop  extends  into  the  umbilical  ccelom  and  is  attached  to  the  yolk 
stalk.  From  the  dorsal  end  of  the  caudal  arm  the  intestine  extends  directly 
to  the  caudal  end  of  the  body  (Fig.  263). 

Soon  after  the  loop  is  formed  a  small  evagination  appears  on  its  caudal  arm, 
not  far  from  the  apex.  This  is  the  anlage  of  the  c&cum  and  marks  the  bound- 


DEVELOPMENT  OF  THE  ALIMENTARY  TUBE  AND  APPENDED  ORGANS.       307 

ary  between  the  small  and  large  intestine  (Fig.  263).  At  this  stage,  therefore, 
all  the  great  divisions  of  the  intestinal  tract  are  distinguishable,  viz. :  the  duodenum 
with  the  ducts  of  the  liver  and  pancreas;  the  mesenterial  small  intestine  with  the 
yolk  stalk;  and  the  colon  extending  from  the  caecum  to  the  caudal  end.  There 
are,  however,  practically  no  differences  between  the  regions,  either  in  structure 
or  in  size. 

In  further  development  the  duodenum  comes  to  lie  more  nearly  transversely 
across  the  body,  thus  assuming  its  adult  position.  Its  mesentery  fuses  with  the 
peritoneum  of  the  dorsal  body  wall  and  the  duodenum  thus  becomes  a  fixed 
portion  of  the  intestinal  tract  (p.  350;  also  Fig.  301).  It  enlarges  a  little  more 


FIG.  2  64. — Reconstruction  of  the  liver  and  intestine  of  a  human  embryo  of  17  mm.     Mall. 

G.B.,  gall  bladder;  H.  V.,  hepatic  vein;  U.V.,  umbilical  vein;  i -6,  primary  bends  in  the  long 

intestinal  loop;  i  represents  the  duodenum. 


rapidly  than  the  rest  of  the  small  intestine  and  acquires  a  greater  diameter.  In 
embryos  of  12  to  13  mm.  the  lumen  becomes  obliterated  by  an  overgrowth  of  the 
mucous  membrane  caudal  to  the  ducts  of  the  liver  and  pancreas.  In  embryos 
of  about  15  mm.,  however,  the  lumen  reappears.  It  seems  difficult  to  find  a 
cause  for  this  peculiar  growth  of  the  mucosa. 

Very  shortly  after  the  formation  of  the  long  loop  in  the  intestine,  six  bends 
become  recognizable  in  the  portion  between  the  stomach  and  the  apex  of  the 
loop  (Fig.  264).  These  bends  later  form  distinct  loops  which  are  destined  to 
become  definite  parts  of  the  small  intestine.  The  first  loop  is  the  duodenum, 
the  development  of  which  has  already  been  considered,  and  which  maintains 
practically  its  original  position.  The  other  five  loops  continue  to  elongate  and 
form  secondary  loops,  all  of  which  push  their  way  into  the  umbilical  coelom 


308 


TEXT-BOOK  OF  EMBRYOLOGY. 


where  they  remain  until  the  embryo  reaches  a  length  of  40  mm.  (compare  Figs, 
265  and  266).  Then  they  return  very  quickly  to  the  abdominal  cavity  proper. 

After  their  return,  the  primary  loops,  with  the  secondary  loops  derived  from 
them,  come  to  occupy  fairly  constant  positions.  The  second  and  third  move 
to  the  left  upper  part  of  the  abdominal  cavity;  the  fourth  crosses  the  medial 
line  and  occupies  the  right  upper  part.  The  fifth  crosses  back  and  lies  in  the 
left  iliac  fossa;  the  sixth  lies  in  the  pelvis  and  lower  part  of  the  abdominal 
cavity  (Fig.  267). 

Certain  variations  may  occur  but  are  usually  not  considered  as  abnormal. 
The  most  frequent  variation  is  one  in  which  the  fourth  coil,  along  with  the 


FIG.  265.— Reconstruction  of  the  stomach  and  intestine  of  a  human  embryo  of  28  mm.     Matt. 

The  numbers  are  placed  on  the  coils  derived  from  the  primary  bends  as  shown  in 

Fig.  302;  i  represents  the  duodenum. 

second  and  third,  lies  on  the  left  side,  its  usual  position  on  the  right  being  oc- 
cupied by  the  ascending  colon.  Not  uncommonly  the  positions  of  the  fourth 
and  the  second  and  third  are  reversed.  Less  commonly  extra  loops  are  formed. 

Usually  the  proximal  part  of  the  yolk  stalk  disappears  during  foetal  life.  In 
a  few  cases,  however,  it  persists  as  a  blind  sac  of  variable  length,  known  as 
Meckel's  diverticulum  (see  also  p.  581). 

Even  before  the  loops  return  to  the  abdominal  cavity  the  colon  or  large 
intestine  increases  in  diameter  more  rapidly  than  the  small  intestine.  After 
the  return,  the  caecum  is  carried  across  to  the  right  side  and  comes  to  lie  just 
caudal  to  the  liver.  From  the  caecum  the  colon  extends  across  the  abdominal 


DEVELOPMENT  OF  THE  ALIMENTARY  TUBE  AND  APPENDED  ORGANS.       309 

cavity,  ventral  to  the  duodenum,  forming  the  transverse  colon.  It  then  de- 
scends on  the  left  side  as  the  descending  colon  which  passes  over  into  the  sigmoid 
colon  (Fig.  299).  The  transverse,  the  descending  and  the  sigmoid  portions  of 
the  colon  are  recognizable  in  the  third  month.  Up  to  the  time  of  birth  the 
sigmoid  portion  is  disproportionately  long;  after  birth  the  other  portions 


FIG.  266. — Drawing  from  a  reconstruction  of  a  human  embryo  of  24  mm.     Matt. 
The  intestinal  coils  lie  for  the  most  part  in  the  umbilical  coelom.     C,  caecum;  K,  kidney;  L,  liven 
S,  stomach;  S.  C.,  suprarenal  gland;  W,  mesonephros;  12,  twelfth  thoracic  nerve;  5,  fifth 
lumbar  nerve. 

grow  relatively  faster.  After  the  fourth  month  the  portion  to  which  the  caecum 
is  attached  grows  downward  in  the  right  side  of  the  abdominal  cavity,  thus  form- 
ing the  ascending  colon  (Fig.  304). 

The  caecum,  which  appears  in  very  early  stages  as  an  evagination  at  the 
junction  of  the  small  and  large  intestines,  for  a  time  continues  to  increase  uni- 
formly in  size.  Then  the  proximal  end  increases  more  rapidly  than  the  distal, 
and  forms  the  caecum  of  adult  anatomy.  The  distal  end,  failing  to  keep  pace 


310  TEXT-BOOK  OF  EMBRYOLOGY. 


in  development,   remains   more   slender   and  forms  the  'vermiform  appendix 
(Fig.  267). 

As  has  already  been  mentioned,  the  primitive  gut  ends  blindly  in  the  caudal 
end  of  the  embryo  (Fig.  246).  The  anal  opening  is  a  secondary  formation, 
On  the  ventral  side  of  the  caudal  end  of  the  body  there  is  formed  a  depression 
known  as  the  anal  pit.  The  mesoderm  at  the  bottom  of  the  pit  becomes  thin- 
ner until  the  ectoderm  comes  in  contact  with  the  entoderm  on  the  ventral  side 
of  the  gut,  thus  forming  the  anal  membrane.  The  area  of  contact  is  not  at  the 


FIG.  267. — Drawing  from  a  model  of  the  small  intestine  in  the  adult.     Ventral  view.     Mall. 

The  intestinal  coils  are  shown  in  the  usual  relative  position.     The  numbers  indicate  the  coils  derived 

from  the  primary  bends  in  the  foetus  as  shown  in  Figs.  264  and  265. 

extreme  end  of  the  gut,  but  a  short  distance  toward  the  allantoic  duct.     In  the 
meantime,  the  urogenital  ducts  come  to  open  into  that  portion  of  the  gut  which 
lies  just  cranial  to  the  anal  membrane.     The  gut  enlarges  in  this  region  to 
i/form  the  cloaca.    The  latter  becomes  separated  by  the  urorectal  fold  into  a 
portion,  the  rectum,  and  a  ventral  portion,  the  urogenital  sinus  (Figs.  323 
and  325).     At  about  the  time  of  separation  (embryos  of  about  14  mm.  or 
thirty-six  to  thirty-eight  days)  the  anal  membrane  ruptures  and  the  anal  open- 


DEVELOPMENT  OF  THE  ALIMENTARY  TUBE  AND  APPENDED  ORGANS.       311 


ing  is  formed.     The  portion  of  the  gut  caudal  to  the  anus,  known  as  the  caudal 
gut,  normally  disappears. 

Histogenesis  of  the  Gastrointestinal  Tract. 

The  wall  of  the  primitive  gut  is  composed  of  two  layers — the  entoderm  which 
lines  the  lumen,  and  the  splanchnic  mesoderm  which  borders  on  the  ccelom  or  body 
cavity.  While  the  germ  layers  are  still  flat,  the  entoderm  is  a  single  layer  of  flat 
cells  with  bulging  nuclei,  but  after  the  closure  of  the  gut  the  cells  become  col- 
umnar. The  splanchnic  mesoderm  is  composed  of  two  layers — the  mesothe- 
lium  bordering  on  the  ccelom,  the  cells  of  which  gradually  change  from  flat 


Mesentery 


Epithelium 


Stroma 


Mesothelium 


Long.  1 

^muscle 
Trans.  J 


FlG.  268. — Transverse  section  of  the  small  intestine  of  a  pig  embryo  of  32  mm.     Bonnet. 


to  rather  high,  and  a  number  of  indifferent,  branching  mesenchymal  cells 
lying  between  the  mesothelium  and  entoderm.  The  entoderm  is  destined  to 
give  rise  to  the  general  epithelial  lining  of  the  gastrointestinal  tract  and  to  all 
the  glands  connected  with  it.  The  mesothelium  around  the  gut  forms  a  part  of 
the  general  mesothelial  lining  of  the  ccelom,  its  cells  apparently  changing  back 
to  a  flat  type.  The  mesenchymal  tissue  is  destined  to  give  rise  to  all  the  con- 
nective tissue  and  smooth  muscle  of  the  tract.  The  circular  layer  of  muscle 
appears  first,  the  longitudinal  next,  both  appearing  during  the  third  and  fourth 
months,  and  last  of  all  the  muscularis  mucosae  (Fig.  268). 

THE  Mucous  MEMBRANE. — The  mucous  membrane  is  formed  by  the 
epithelium  (entoderm)  and  the  subjacent  mesenchymal  tissue.     In  its  develop- 


312  TEXT-BOOK  OF  EMBRYOLOGY. 

ment  there  are  two  factors  to  be  considered:  (i)  The  formation  of  folds  to  in- 
crease the  absorbing  surface  and  (2)  the  formation  of  secreting  organs  or  glands. 
As  to  the  relation  between  these  two  factors  there  is  a  difference  of  opinion. 
Some  hold  that  both  kinds  of  structures  are  the  result  of  the  same  formative 
process,  that  is,  that  the  glands  are  simply  the  depressions  or  pits  formed  by  the 
intersection  of  folds  at  various  angles,  and  that  the  folds  are  produced  primarily 
by  the  growth  of  the  epithelium  and  mesenchymal  tissue  into  the  lumen  of  the 
gut.  Others  maintain  that  although  the  folds  may  be  produced  by  the  growth 
of  the  epithelium  and  mesenchymal  tissue  into  the  lumen,  the  glands  arise  as 
independent  growths  of  the  epithelium  into  the  subjacent  tissue.  The  latter 

view  is  supported  by  the  fact  that  in 
some  Amphibia  the  glands  appear  before 
the  folds  (Fig.  269).  Recent  work  on 
Mammals  also  favors  this  view. 


r~  Subm. 

\  The  development  of  the  folds  and 

glands  begins  in  the  different  parts  of  the 
gastrointestinal  tract  at  different  times. 
It  begins  first  in  the  stomach,  then  in  the 

FIG.  260.  —  Section  through  the  wall  of  the       ,       ,  ,.  .  .  .  A. 

stomach  of  a  frog  embryo.    Ep.t  Epi-     duodenum,  then  in  the  colon,  and  then 


thelium,  with  glands;  s«fo».  submucosa;     in    the   jejunum   whence    it    progresses 

Muse.,  muscle  layer.     Ratner.  J  J 

slowly  into  the  ileum.  In  the  stomach 

it  is  uncertain  whether  the  crypts  and  glands  are  depressions  left  among 
projections  of  the  mucous  membrane,  or  the  glands  represent  evaginations  of 
the  epithelium  into  the  underlying  tissue.  In  the  case  of  the  large  intestine 
the  same  uncertainty  exists.  If  the  so-called  glands  are  depressions  among 
villous  projections  that  grow-in  to  the  lumen  of  the  intestine,  they  are  not  true 
glands  from  an  embryological  point  of  view. 

Studies  of  the  development  of  the  villi  in  the  human  small  intestine  have  led 
to  the  conclusion  that  they  are  formed  primarily  as  growths  of  the  mucosa  into 
the  lumen.  In  embryos  of  19  mm.  the  mucosa  of  the  cephalic  end  is  thrown 
into  a  number  of  longitudinal  folds  (Fig.  270).  These  then  develop  pro- 
gressively toward  the  caudal  end.  Beginning  in  embryos  of  50  to  60  mm.  the 
longitudinal  folds  become  broken  transversely  into  conical  structures,  the 
villi.  The  intestinal  crypts  (of  Lieberkiihn)  possibly  represent  outgrowths  of 
the  epithelium  from  the  bottoms  of  the  intervillous  spaces.'  The  duodenal 
(B  runner's)  glands  are  possibly  to  be  considered  as  a  continuation  of  the  pyloric 
glands  of  the  stomach.  They  apparently  grow  as  evaginations  from  the 
intervillous  crypts. 

The  epithelial  lining  of  the  gastrointestinal  tract  is  from  the  beginning  a 
single  layer  of  cells,  although  the  individual  cells  are  altered  in  shape  and 
structure  and  acquire  different  functions  in  different  regions.  There  is  still 


DEVELOPMENT  OF  THE  ALIMENTARY  TUBE  AND  APPENDED  ORGANS.       313 

some  dispute  as  to  whether  the  mucous  cells  are  continuously  being  derived 
from  the  other  epithelial  cells  or,  when  once  formed,  reproduce  themselves  by 
mitosis.  As  a  matter  of  fact,  mitosis  has  been  observed  in  the  mucous  cells  of 
the  stomach. 


FlG.  270. — From  a  reconstruction  of  the  small  intestine  of  a  human  embryo  of  28  mm.,  showing  the 
longitudinal  ridges  which  eventually  become  broken  transversely  to  form  the  villi.     Berry. 

THE  LYMPH  FOLLICLES. — In  the  development  of  the  lymph  follicles  in  the 
gastrointestinal  tract  the  same  question  arises  as  in  the  case  of  the  tonsils  and 
thymus.  Are  the  lymphoid  cells  of  mesodermal  or  of  entodermal  (epithelial) 


a 


FIG.  271. — Sections  through  the  wall  of  the  caecum  of  (a)  a  rabbit  2^  days  and  (b)  5  days  after 
birth,  showing  the  development  of  the  lymph  follicles.  /.  Lymphoid  infiltration  in  the  stroma; 
r,  wandering  cells  in  the  epithelium;  2,  lymphoid  cells  in  the  core  of  a  villus.  Stohr. 

origin?  Evidence  at  present  favors  the  mesodermal  origin.  In  the  case  of 
Peyer's  patches,  collections  of  lymphoid  cells  appear  near  the  blood  vessels  in 
the  stroma  and  neighboring  parts  of  the  submucosa.  These  increase  in  extent, 


314 


TEXT-BOOK  OF  EMBRYOLOGY. 


the  lymphoid  cells  dividing  actively,  and  grow  into  the  bases  of  some  of  the 
villi  and  deeper  into  the  submucosa  (Fig.  271).  Germinal  centers  appear  in 
many  of  the  follicles,  and  the  surrounding  stroma  becomes  densely  infiltrated 
with  the  lymphoid  cells.  Individual  follicles  may  develop,  in  the  manner 
described,  in  any  part  of  the  gastrointestinal  tract.  The  appendix  especially  is 
the  seat  of  extensive  lymphatic  tissue  formation.  It  is  stated  in  the  section  on 
the  lymphatic  system  that  lymph  glands  may  arise  at  any  time  in  any  region  as 
the  result  of  unusual  conditions  (p.  251),  and  this  also  holds  true  in  the  case  of 
lymph  follicles  in  the  digestive  tract. 

The  Development  of  the  Liver. 

The  liver  is  the  first  gland  of  the  digestive  tract  to  appear.  In  embryos  of 
about  3  mm.  a  longitudinal  ridge-like  evagination  develops  from  the  entoderm 
on  the  ventral  side  of  the  gut  a  short  distance  caudal  to  the  stomach,  that  is,  in 


Myotome 

Aorta 

Post,  cardinal  vein 


Upper  limb  bud 
Dorsal  mesentery 

Duodenum 
Liver 


Ccelom 

Omphalomesenteric  vein 
Umbilical  vein 

Heart 


FIG.  272. — Transverse  section  of  a  human  embryo  of  5  mm.,  showing  the  liver  evagination  and  the 
breaking  up  of  the  omphalomesenteric  veins  by  the  hepatic  cylinders.     Photograph. 

the  duodenal  portion  of  the  gut  (Figs.  247, 272,  273).  The  cephalic  part  of  the 
evagination  is  solid  and,  being  destined  to  give  rise  to  the  liver  proper,  is  called  the 
pars  hepatica.  The  caudal  part  is  hollow,  its  cavity  being  continuous  with  the 
lumen  of  the  gut,  and  is  destined  to  give  rise  to  the  gall  bladder,  whence  it  is 
called  the  pars  cystica.  Beginning  at  both  the  cephalic  and  caudal  ends,  the 
evagination  as  a  whole  becomes  constricted  from  the  gut  until  (in  embryos  of 
about  8  mm.)  its  only  connection  with  the  latter  is  a  narrow  cord  of  cells  which 


DEVELOPMENT  OF  THE  ALIMENTARY  TUBE  AND  APPENDED  ORGANS.       315 


is  the  anlage  of  the  ductus  choledochus.  The  pars  hepatica  by  this  time  has 
enlarged  considerably  and  remains  attached  to  the  ductus  choledochus  by  a 
short  cord  of  cells,  the  anlage  of  the  hepatic  duct.  The  pars  cystica  has  also 
become  larger,  its  distal  portion  being  somewhat  dilated,  and  is  connected  with 
the  ductus  choledochus  by  the  anlage  of  the  cystic  duct  (Figs.  274  and  275). 
The  pars  cystica  grows  into  the  ventral  mesentery  and  thus  becomes  sur- 
rounded by  mesodermal  tissue.  The  proximal  portion  continues  to  elongate  to 
form  the  cystic  duct  and  the  distal  portion  becomes  larger  and  more  dilated  to 
form  the  gall  bladder. 


D.  pan. 


,Du. 


V.  pan. 


D.ch. 


H.du. 


G.bl. 


FIG.  273. — From   a  model  of  the  duodenum  and  the  primary  evaginations  of  the 

liver  and  pancreas  in  a  5  mm.  sheep  embryo.     Stoss. 

D.pan.,  Dorsal  pancreas;  Du.,  duodenum;  D.  ch.,  ductus  choledochus;  G.  bl.,  gall 
bladder;  H.  du.,  hepatic  duct. 

The  pars  hepatica,  or  anlage  of  the  liver  proper,  also  grows  into  the  ventral 
lesentery,  thus  becoming  surrounded  by  mesodermal  tissue.  As  stated  in 
connection  with  the  development  of  the  diaphragm,  the  portion  of  the  mesen- 
tery into  which  the  liver  grows  is  involved  in  the  formation  of  the  septum 
trans versum  (p.  344).  Thus  the  developing  liver  becomes  enclosed  in  the 
septum  (Fig.  292).  The  mesodermal  tissue  gives  rise  to  the  fibrous  capsule  of 
Glisson  and  to  the  small  amount  of  connective  tissue  within  the  gland. 

Although  the  liver  develops  as  a  series  of  outgrowths  from  the  original 
evagination,  there  are  certain  features  in  its  development  which  distinguish  it 
from  glands  in  general.  The  outgrowths  come  in  contact  with  the  omphalomes- 
enteric  veins  which  are  situated  in  the  ventral  mesentery  (p.  229).  They  push 
their  way  into  and  through  the  veins,  breaking  them  up  into  smaller  channels 
(Fig.  272).  They  anastomose  freely  with  one  another,  and  the  veins  send  off 


316 


TEXT-BOOK  OF  EMBRYOLOGY. 


branches  which  circumvent  them.     Thus  there  is  formed  a  network  of  trabec 
ulse  of  liver  cells,  called  hepatic  cylinders,  the  meshes  of  which  are  filled  with  blood 
vessels.     Therefore  the  liver  is  distinguished  from  other  glands  in  general  in 


Stomach 


Left  hep. 
duct 


Right  hep. 
duct 


Gall     _J 
bladder 


Dors,  pancreas 


Vent,  pancreas 


Duodenum 


FIG.  274. — From  a  reconstruction  of  the  anlagen  of  the  liver  and  pancreas  and  a  part  of  the 
stomach  and  duodenum  of  a  human  embryo  of  4  weeks.     Felix. 

that  the  hepatic  cylinders,  which  are  comparable  with  the  smaller  ducts  and 
terminal  tubules  of  other  glands,  anastomose,  and  in  that  the  blood  vessels  are 
broken  up  by  the  growth  of  these  cylinders. 


Du. 
FIG.  275. — From  a  reconstruction  of  the  anlagen  of  the  liver  and  pancreas  and  the  stomach 

of  a  human  embryo  of  8  mm.     Hammar. 

D.P.,  Dorsal  pancreas;    Du.,  duodenum;    D.  F.,  ductus   venosus;    G.B.,  gall   bladder; 
R.I.,  right  lobe  of  liver;  S.t  stomach;  V.  P.,  ventral  pancreas. 

This  mode  of  development  establishes  what  is  known  as  a  sinusoidal  circulation,  which 
differs  from  the  ordinary  capillary  circulation.  The  sinusoids  are  produced  by  the  growth 
of  the  trabeculae  of  the  developing  organ  into  large  vessels  and  the  breaking  up  of  the  latter 


DEVELOPMENT  OF  THE  ALIMENTARY  TUBE  AND  APPENDED  ORGANS.       317 

into  smaller  vessels.  It  is  obvious  that  a  sinusoidal  circulation  is  purely  venous  or  purely 
arterial.  Furthermore,  development  of  this  nature  leaves  comparatively  little  connective 
tissue  within  the  gland,  another  feature  characteristic  of  the  liver. 

All  the  blood  carried  to  the  liver  by  the  omphalomesenteric  veins  must 
follow  the  tortuous  course  of  the  sinusoids  before  being  collected  again  and 
passed  on  to  the  heart.  When  the  umbilical  veins  come  into  connection  with 
the  liver  they  also  join  in  the  sinusoidal  circulation.  Subsequently,  however,  a 
more  direct  channel — the  ductus  venosus — is  established  and  persists  for  a 


Aorta 

tnf.  vena  cava 
Coelom 


Ductus 
choledochus 


Right  side 


Suprarenal  glands 
Mesonephros 


Dorsal  mesogastrium 
(greater  omentum) 

Stomach 

Ventral  mesogastrium 
(lesser  omentum ) 


Liver 


Left  side 


FIG.  276. — Tranverse  section  of  a  14  mm.  pig  embryo,  through  the  region  of  the  stomach. 
Photograph.     The  arrow  points  into  the  bursa  omentalis. 

short  time.  This  is  probably  due  to  the  large  volume  of  blood  brought  in  by 
the  umbilical  veins.  Finally  the  ductus  venosus  disappears  and  the  sinusoidal 
circulation  remains  as  the  permanent  form.  (For  the  development  of  the  veins 
in  the  liver  see  p.  228.) 

The  lobes  of  the  liver  develop  in  a  general  way  in  relation  to  the  great 
venous  trunks  which  at  one  time  or  another  pass  into  or  through  the  gland. 
The  anlage  of  the  organ  grows  into  the  ventral  mesentery,  subsequently  be- 
coming enclosed  in  the  septum  transversum.  In  so  doing  it  encounters  the 
omphalomesenteric  veins,  and  forms,  in  relation  to  the  latter,  two  Incompletely 
separated  parts  which  have  been  called  the  dorso-lateral  lobes.  When  the 
umbilical  veins  enter  the  liver  a  more  ventral,  medial  mass  is  formed.  This 
becomes  incompletely  separated  into  two  parts  which  give  rise  to  the  permanent 


318  TEXT-BOOK  OF  EMBRYOLOGY. 

right  and  left  lobes.  The  right  becomes  the  larger.  The  right  umbilical  vein 
loses  its  connection  with  the  liver  (p.  230).  After  birth  the  left,  which  lies  be- 
tween the  right  and  left  lobes,  degenerates  into  the  round  ligament  of  the  liver. 
The  other  lobes  arise  secondarily  as  outgrowths  from  the  right  primary  dorso- 
lateral  lobe,  the  caudate  (lobe  of  Spigelius)  from  its  inner  (medial)  surface, 
the  quadrate  from  its  dorsal  surface. 

The  liver  as  a  whole  grows  rapidly  and  by  the  second  month  is  relatively 
large.  During  the  third  month  it  fills  the  greater  part  of  the  abdominal  cavity. 
After  the  fifth  month  it  grows  less  rapidly  and  the  other  intraabdominal  organs 
overtake  it,  so  to  speak,  although  at  birth  it  forms  one-eighteenth  the  total 
weight  of  the  body.  After  birth  it  actually  diminishes  in  size.  The  right  lobe 
is  from  the  beginning  larger  than  the  left,  and  after  birth  the  predominance 
increases. 

Histogenesis  of  the  Liver. — The  hepatic  part  (pars  hepatica)  of  the 
liver  anlage  is  derived  from  the  entodermal  lining  of  the  gut  and  constitutes  a 
mass  of  cells  with  no  lumen.  From  this  mass,  solid  bud-like  evaginations  grow 
into  the  mesentery,  break  up  the  omphalomesenteric  veins  into  smaller  channels 
and  form  trabeculae,  or  hepatic  cylinders  (p.  316).  The  latter  anastomose 
freely  with  one  another  and  are  composed  of  polyhedral,  darkly  staining  cells 
with  vesicular  nuclei  (Fig.  277,  A).  Lumina  begin  to  appear  in  the  cylinders 
about  the  fourth  week  as  small  cavities  which  communicate  with  the  cavity  of 
the  gut. 

The  hepatic  cylinders  are  the  forerunners  of  the  hepatic  cords  or  cords  of 
liver  cells.  There  are  two  views  as  to  the  manner  of  transformation.  The 
older  view  is  that  the  cylinders  gradually  become  stretched,  the  number  of  cells 
in  cross-section  becoming  less  until  it  is  reduced  to  two.  Between  these  two 
lies  the  lumen  of  the  cord  or  the  so-called  "bile  capillary"  (Fig.  277,  B).  The 
other  view  is  that  branches  from  the  sinusoids  grow  into  the  cylinders  and  sub- 
divide them  into  hepatic  cords. 

As  stated  above,  the  hepatic  cylinders  are  at  first  composed  of  darkly  stain- 
ing, polyhedral  cells  with  vesicular  nuclei.  These  are  the  liver  cells  proper. 
Later  other  small  spherical  cells,  with  dense  nuclei,  appear  and  during  the 
fourth  month  become  very  numerous  (Fig.  277,  A).  From  this  time  on,  they 
grow  less  in  number  and  at  birth  have  practically  disappeared.  Earlier  investi- 
gators considered  them  as  developing  liver  cells.  Further  study  on  the  develop- 
ment of  the  blood,  however,  has  led  others  to  consider  them  as  erythroblasts 
(p.  239).  Since  they  are  inside  of  the  hepatic  cylinders,  they  either  wander  in 
from  the  intertrabecular  blood  vessels  or  lie  in  intratrabecular  vessels.  The 
latter  supposition  accords  with  the  view  that  the  cylinders  are  broken  up  into 
hepatic  cords  by  the  ingrowth  of  branches  from  the  sinusoids. 

The  development  of  the  lobules  of  the  liver,  producing  the  peculiar  relations 


DEVELOPMENT  OF  THE  ALIMENTARY  TUBE  AND  APPENDED  ORGANS.       319 

between  the  parenchyma  of  the  gland  and  the  blood  vessels,  has  not  been 
clearly  and  completely  demonstrated.  In  young  embryos  the  branches  of  the 
hepatic  veins  are  surrounded  by  comparatively  little  connective  tissue.  The 
branches  of  the  portal  vein  are  surrounded  by  a  considerable  amount  which 
subdivides  the  liver  into  lobules  but  not  in  the  same  manner  as  in  the  adult. 
The  trabeculae  possess  no  radial  character  and  there  are  several  so-called  central 
•veins  in  each  lobule.  The  changes  by  which  these  primary  lobules  are  sub- 
divided into  the  permanent  ones  do  not  take  place  until  after  birth.  The 
branches  of  the  portal  vein,  with  the  surrounding  connective  tissue,  invade  the 


FIG.  277. — Sections  of  the  liver  of  (^4)  a  human  foetus  of  6  months  and  (B)  a  child  of  4  years. 

Toldt  and  Zuckerhandl.  McMurrich. 
be,  Bile  "capillary";  e,  erythroblast;  he,  hepatic  cylinder  (in  A),  cord  of  liver  cells  (in  B). 

primary  lobules  and  divide  them  into  a  number  of  secondary  lobules,  corre- 
sponding to  the  original  number  of  central  veins.  At  the  same  time  the  hepatic 
cords  (which  have  been  formed  meanwhile)  become  arranged  radially  around 
the  central  veins  in  the  characteristic  manner.  The  hepatic  artery  grows  into 
the  liver  secondarily  and  its  branches  follow  the  course  of  the  branches  of  the 
portal  vein. 

Degeneration  of  the  liver  cells  occurs  in  the  region  of  the  left  triangular  liga- 
ment, the  gall  bladder  and  the  inferior  vena  cava.  The  bile  ducts  may,  how- 
ever, withstand  the  degenerative  processes  and  persist  as  the  vasa  aberrantia  of 
the  liver.  The  cause  of  the  degeneration  is  possibly  the  pressure  brought  to 
bear  by  other  organs. 

The  Development  of  the  Pancreas. 

The  epithelium  of  the  pancreas,  like  that  of  the  liver,  is  a  derivative  of  the 
entoderm.  It  arises  from  two  (or  three)  separate  anlagen,  one  dorsal  and  one 


320 


TEXT-BOOK  OF  EMBRYOLOGY. 


(or  two)  ventral.  The  dorsal  anlage  appears  first  as  a  ridge-like  evagination 
from  the  dorsal  wall  of  the  gut,  slightly  cranial  to  the  level  of  the  liver  (Figs.  273 
and  274).  It  appears  about  the  same  time  as  the  liver  or  a  little  later.  The 
mass  of  cells  grows  into  the  dorsal  mesentery  and  becomes  constricted  from 
the  parent  epithelium  except  for  a  thin  neck  which  becomes  the  duct  of 
Santorini  (Fig.  278).  A  little  later  two  other  diverticula  appear,  one  from  each 
side  of  the  common  bile  duct.  It  is  uncertain  whether  only  one  or  both  of  these 


Stomach 


Liver 


Cystic  duct 


Dorsal  pancreas 


Acces.  pancr. 
duct  (Santorini) 


Dorsal  pancreas 


Gall  bladder 

Ductus  choledochus 
Ventral  pancreas 


Dorsal  pancreas 

Acces.  pancr.  duct 
(Santorini) 


Duodenum 


Ductus  choledochos 


Liver 


Cystic  duct 


Gall  bladder 


Ventral  pancreas  with 
pancr.  duct  (Wirsung) 
FIG.  279. 

FIGS.  278  and  279. — From  models" of  the  developing  liver  and  pancreas  of  rabbit  embryos  of 
8  mm.  and  10  mm.,,  respectively,,     Both  seen  from  the  right  side.     Hammar,  Bonnet. 

take  part  in  the  formation  of  the  pancreas,  but  it  seems  most  probable  that  th< 
left  one  disappears  entirely.  The  right  diverticulum  continues  to  develop  and 
becomes  constricted  from  the  parent  epithelium,  leaving  only  a  thin  neck  which 
becomes  the  duct  of  Wirsung. 

The  smaller  ventral  pancreas  grows  to  the  right  and  then  dorsally  in  the 
mesentery  (Fig.  260),  passing  over  the  right  surface  of  the  portal  vein,  until  it 
meets  and  fuses  with  the  proximal  part  of  the  larger  dorsal  pancreas.  The 
fusion  takes  place  in  the  sixth  week,  and  the  two  anlagen  then  form  a  single 


DEVELOPMENT  OF  THE  ALIMENTARY  TUBE  AND  APPENDED  ORGANS.       321 

mass.  A  communication  is  established  between  the  two  ducts,  and  the  dorsal 
duct  (Santorini)  usually  disappears,  leaving  the  ventral  (Wirsung)  as  the  per- 
manent duct  opening  into  the  ductus  choledochus.  In  a  general  way  it  may  be 
said  that  the  ventral  anlage  gives  rise  to  the  head,  the  dorsal  anlage  to  the  body 
and  tail  of  the  pancreas  (compare  Figs.  278  and  279). 

As  the  pancreas  grows  into  the  dorsal  mesentery  it  comes  to  lie  in  the 
dorsal  mesogastrium  between  the  greater  curvature  of  the  stomach  and  the 
vertebral  column,  and  since  the  dorsal  mesogastrium  at  first  lies  in  the  medial 
sagittal  plane,  the  pancreas  is  similarly  situated.  After  the  sixth  week,  how- 
ever, as  the  stomach  changes  its  position  (p.  305) ,  the  pancreas  is  carried  along 


Inf.  vena  cava 


Coelom 

Dorsal  pancreas 

Portal  vein 

Ventral  'pancreas 

Ductus  choledochus 


Right  side 


Mesonephros 


Greater  omentum 
(dorsal  mesentery) 


Duodenum 


Liver 


Left  side 


FIG.  280. — From  a  transverse  section  through  the  region  of  the  duodenum  of  a  pig 
embryo  of  14  mm.     Photograph. 

with  the  mesogastrium  and  comes  to  lie  in  a  transverse  plane,  with  its  head  to 
the  right  and  embedded  in  the  bend  of  the  duodenum,  and  its  tail  reaching  to 
the  spleen  on  the  left.  The  organ  as  a  whole  is  at  first  movable  along  with  the 
mesentery,  but  when  it  assumes  its  transverse  position  it  lies  close  to  the  dorsal 
abdominal  wall.  The  mesentery  then  fuses  with  the  adjacent  peritoneum 
(see  p.  350),  and  the  pancreas  is  firmly  fixed. 

The  connective  tissue  of  the  pancreas  is  derived  from  the  mesodermal  tissue 
of  the  mesentery.  As  the  processes  or  buds  which  form  the  ducts  and  terminal 
tubules  grow  out  from  the  primary  masses,  they  penetrate  the  mesodermal 
tissue  and  are  surrounded  by  it.  Groups  of  tubules  form  lobes  and  lobules, 
and  the  entire  gland  is  surrounded  by  a  capsule  of  connective  tissue. 


322 


TEXT-BOOK  OF  EMBRYOLOGY. 


Histogenesis  of  the  Pancreas. — The  masses  of  entodermal  cells  forming 
the  anlagen  of  the  pancreas  develop  further  by  a  process  of  budding,  which 
goes  on  until  finally  a  compound  tubular  gland  is  produced.  According  to 


FIG.  281. — Sections  of  the  developing  pancreas  of  a  guinea-pig  embryo  of  12  mm.  (a); 

of  33  mm.  (&) ;  of  Torpedo  marmorata  (c) .     Hetty. 

ct  Capillaries;  Dg,  ducts;  Gz,  duct  cells;  Lz,  Langhans'   cells.     The  cells  in  c  show- 
distinct  zymogen  granules 

some  investigators  the  primary  evaginations  are  hollow,  their  lumina  beinj 
continuous  with  the  lumen  of  the  gut.  According  to  others  they  are  solid  al 
first  and  acquire  their  lumina  secondarily.  The  same  uncertainty  exists 
regard  to  the  later  outgrowths  or  buds. 


DEVELOPMENT  OF  THE  ALIMENTARY  TUBE  AND  APPENDED  ORGANS.       323 

The  early  entodermal  cells  proliferate,  and  the  resulting  cells  change  ac- 
cording to  their  position  in  the  gland.  Those  lining  the  larger  ducts  become 
high  columnar,  with  more  or  less  homogeneous  cytoplasm;  those  lining  the 
intermediate  (intercalated)  ducts  become  low;  those  lining  the  terminal  secret- 
ing tubules  become  pyramidal  and  more  highly  specialized,  and  also  acquire 
certain  constituents — the  zymogen  granules  (Fig.  281,  c) — which  vary  with  the 
functional  activities  of  the  gland.  The  centro-tubular  cells  in  the  terminal 
tubules  are  probably  to  be  explained  on  a  developmental  basis.  While  a  few 
maintain  that  they  are  "wandering"  cells,  it  is  quite  generally  accepted 
that  they  are  simply  continuations  of  the  flat  cells  lining  the  intermediate 
ducts,  the  result  being  that  the  cells  of  the  terminal  tubules  seem  to 
spread  out  over  the  ends  of  the  intermediate  ducts  in  the  form  of  cap-like 
structures. 

It  was  once  thought  that  the  islands  of  Langerhans  were  derived  from  the 
mesodermal  tissue.  Recently  it  has  been  pretty  clearly  demonstrated  that  they 
are  derived  from  entoderm.  In  guinea-pig  embryos  of  5  to  6  mm.,  at  a  time 
when  the  dorsal  pancreas  has  merely  begun  its  constriction  from  the  gut,  certain 
cells  in  the  mass  appear  darker  and  slightly  larger  than  the  others.  They  show 
darker  areas  of  cytoplasm  around  the  nuclei,  and  later  the  darker  areas  extend 
throughout  the  cells  and  the  nuclei  become  larger  and  more  vesicular.  When 
lumina  appear  in  the  outgrowths  or  buds,  these  cells  occupy  a  position  on  or  near 
the  surface  of  the  buds  (Fig.  281,  a).  In  further  development  they  tend  to  sepa- 
rate themselves  from  the  buds  and  collect  in  clumps  (Fig.  281,  b).  Capillaries 
then  penetrate  the  clumps  and  break  them  up  into  the  trabeculae  of  cells  char- 
acteristic of  the  islands  of  Langerhans  (Fig.  281,  c).  Studies  on  the  development 
of  the  islands  in  the  human  pancreas  indicate  a  similar  origin  and  mode  of 
development. 

Anomalies. 

One  of  the  most  striking  anomalies  of  the  organs  of  alimentation  is  found 
in  connection  with  a  more  general  anomalous  condition  known  as  transposition 
of  the  viscera  (situs  viscerum  inversus) .  The  transposition  may  be  so  complete 
that  the  minor  asymmetries  normally  present  on  the  two  sides  are  all  repeated 
in  reverse  order,  the  functions  of  the  organs  being  unimpaired.  As  regards  the 
alimentary  tract,  this  means  that  the  position  of  the  stomach  is  reversed  in  the 
abdominal  cavity;  that  the  duodenum  crosses  from  left  to  right;  that  the  various 
coils  of  the  jejunum  and  ileum  occupy  positions  opposite  to  the  normal;  that  the 
caecum  and  ascending  colon  are  situated  on  the  left  side  and  the  descending 
colon  on  the  right;  and  that  the  larger  lobe  of  the  liver  lies  on  the  left  side.  The 
other  visceral  organs  are  transposed  accordingly,  the  heart  being  inclined  to- 
ward the  right  side,  the  left  lung  consisting  of  three  lobes  and  the  right  of  two, 


324  TEXT-BOOK  OF  EMBRYOLOGY. 

the  left  kidney  being  lower  than  the  right,  etc.  Such  cases  are  not  uncommon, 
two  hundred  being  on  record. 

Various  theories  as  to  the  causes  of  transposition  of  the  organs  have  been 
advanced.  In  the  most  plausible  of  these  the  anomalous  condition  is  consid- 
ered as  due  to  the  influence  of  the  large  veins  in  the  embryo.  It  seems  best, 
therefore,  to  consider  first  the  transposition  of  the  heart  (dextrocardia,  referred 
to  on  page  255). 

After  the  tvvo  anlagen  unite  in  the  midventral  line,  the  heart  constitutes  a 
simple  straight  tube  which  lies  in  a  longitudinal  direction  in  the  primitive  peri- 
cardial  cavity,  and  which  is  joined  caudally  by  the  two  omphalomesenteric 
veins  and  cranially  by  the  ventral  aortic  trunk  (p.  197) .  Normally  the  left 
omphalomesenteric  vein  is  the*larger  and  pours  a  greater  quantity  of  blood  into 
the  heart  tube  than  the  right.  This  condition  is  regarded  as  the  primary  factor 
in  the  deflection  of  the  tube  toward  the  right  side  (p.  199;  also  Fig.  158).  If  the 
conditions  were  reversed,  that  is,  if  the  right  omphalomesenteric  vein  were  the 
larger  and  poured  the  greater  quantity  of  blood  into  the  heart  tube,  the  pri- 
mary bend  of  the  latter  would  be  toward  the  left  side.  Consequently  the  heart 
would  continue  to  develop  in  the  transposed  position  and  eventually  come  to 
lie  on  the  side  opposite  to  the  normal. 

Although  dextrocardia  is  very  frequently  associated  with  transposition  of 
the  abdominal  organs,  it  is  not  necessarily  so,  for  there  are  cases  of  the  latter  in 
which  the  heart  occupies  the  normal  position.  Consequently  it  seems  that 
further  influences  must  be  present  to  account  for  transposition  of  the  abdominal 
organs  when  the  thoracic  organs  are  normal.  A  number  of  investigators  have 
emphasized  the  importance  of  the  influence  of  the  large  venous  trunks  in  the 
abdominal  region,  especially  on  the  position  of 'the  liver  and  stomach. 

Primarily  the  omphalomesenteric  veins  pass  cranially  through  the  mesen- 
tery. Later  they  form  two  loops  or  rings  around  the  duodenum.  Then  the 
left  half  of  the  upper  ring  and  the  right  half  of  the  lower  disappear,  the  common 
venous  trunk  thus  following  a  spiral  course  around  the  duodenum  (p.  231 ;  also 
Fig.  201).  This  primary  relation  of  the  omphalomesenteric  vein  is  retained  in 
the  relation  of  the  portal  vein  to  the  duodenum.  The  stomach  lies  to  the  left 
of  the  portal  vein.  After  the  allantoic  (placental)  circulation  is  established  the 
umbilical  veins  pass  cranially  in  the  lateral  body  walls.  After  the  veins  come 
into  connection  with  the  liver,  the  right  atrophies  and  the  left  increases  in  size 
and  becomes  the  single  large  umbilical  vein  of  later  stages  (p.  230;  also  Fig.  202). 
The  right  lobe  of  the  liver  becomes  the  larger. 

If,  as  is  maintained  by  some  investigators,  the  usual  position  of  the  stomach 
and  liver  is  due  to  the  persistence  of  the  left  venous  trunks,  a  persistence  of  the 
right  venous  trunks  would  afford  a  plausible  explanation  of  the  transposition  of 
these  organs.  It  is  not  unreasonable  to  attribute  also  the  transposition  of  the 


DEVELOPMENT  OF  THE  ALIMENTARY  TUBE  AND  APPENDED  ORGANS.       325 

other  abdominal  organs  directly  or  indirectly  to  the  persistence  of  the  right 
venous  trunks.  Certainly  a  reversal  in  the  position  of  the  stomach  would 
cause  a  reversal  in  the  position  of  the  duodenum. 

If  these  conditions  are  the  real  ones,  the  fact  that  the  thoracic  organs  can  be 
transposed  without  a  transposition  of  the  abdominal  organs,  or  vice  versa, 
is  accounted  for.  The  primary  bend  of  the  heart  tube  occurs  at  a  very  early 
period,  before  the  changes  in  the  vessels  in  the  region  of  the  liver.  Conse- 
quently a  reversal  of  the  conditions  of  the  omphalomesenteric  at  a  very  early 
stage  only  would  be  likely  to  affect  the  heart.  The  principal  changes  in  size 
of  the  venous  trunks  in  the  abdominal  region  take  place  after  their  channels 
have  been  broken  up  in  the  liver.  In  other  words,  the  modifications  in  the  veins 
in  the  liver  occur  after  the  definite  relations  of  the  heart  have  been  established. 
Therefore  the  transposition  of  the  abdominal  organs  may  take  place  after  the 
heart  has  begun  to  develop  normally. 

THE  MOUTH. — Anomalies  in  the  mouth  region,  due  to  defective  fusion  of 
the  processes  that  bound  it,  have  been  considered  elsewhere  (p.  180). 

Anomalies  of  the  tongue  sometimes  arise  as  the  result  of  imperfect  develop- 
ment of  one  or  more  of  its  anlagen.  Imperfect  development  of  the  tuberculum 
impar  results  in  total  or  partial  lack  of  the  anterior  part.  Defects  in  the  root 
are  probably  due  to  imperfect  development  of  one  or  both  of  the  paired  anlagen 
(p.  289).  Malformations  of  the  lower  jaw  (micrognathus,  agnathus)  are 
usually  accompanied  by  malformations  of  the  tongue,  both  structures  being 
derived  largely  from  the  first  pair  of  branchial  arches. 

THE  PHARYNX. — The  pharynx  is  the  seat  of  cysts,  fistulae  and  diverticula 
which  have  been  considered  in  connection  with  the  anomalies  in  the  region  of 
the  branchial  arches  and  grooves  (Chap.  XX). 

The  thyreoid  gland  is  not  infrequently  the  seat  of  certain  anomalies  that 
arise  as  the  result  of  abnormal  development.  Persistent  portions  of  the  thyreo- 
glossal  duct,  the  upper  end  of  which  is  indicated  by  the  foramen  caecum  linguae, 
may  give  rise  to  cystic  structures  extending  to  the  region  of  the  hyoid  bone. 
Persistent  portions  of  the  duct  may  even  give  rise  to  accessory  thyreoid  (supra- 
hyoid,  prehyoid)  glands  (p.  301;  also  Fig.  260).  Considerable  variation  also 
exists  in  the  isthmus  and  lateral  lobes  of  the  thyreoid,  due  to  variation  in  the 
manner  of  development  of  the  medial  anlage. 

Impaired  development  of  the  thymus  gland  sometimes  leads  to  cysts  which 
come  to  lie  in  the  anterior  mediastinum. 

THE  (ESOPHAGUS. — Very  rarely  the  oesophagus  is  entirely  lacking,  being 
represented  by  a  mere  cord  of  tissue.  More  frequently  it  is  defective  in  certain 
parts.  Tne  atresia  may  begin  just  below  the  pharynx  or  just  above  the  stomach, 
the  intermediate  portion  being  composed  of  a  cord  of  fibrous  tissue.  Occasion- 
ally the  non-atretic  portion  opens  into  the  trachea.  Possibly  this  represents 


326  TEXT-BOOK  OF  EMBRYOLOGY. 

an  imperfect  separation  between  the  primitive  gut  and  the  anlage  of  the 
respiratory  system  (p.  330). 

THE  STOMACH. — Occasionally  the  stomach  is  smaller  than  the  normal.  It 
may  even  be  a  narrow  tube  resembling  the  other  portions  of  the  gut,  owing  to 
lack  of  dilatation.  Other  congenital  malformations,  apart  from  transposition 
(p.  323),  are  very  rare. 

THE  INTESTINES. — One  of  the  most  common  anomalies  is  the  persistence  of 
the  proximal  end  of  the  yolk  stalk,  forming  MeckeVs  diverticulum  (see  p.  581). 
This  usually  is  attached  to  the  ileum  about  three  feet  from  the  caecum.  In  ex- 
ceptional cases  it  retains  its  lumen  and,  when  the  stump  of  the  umbilical  cord 
disappears,  forms  a  congenital  umbilical  fistula.  Usually,  however,  the  diver- 
ticulum is  shorter  and  ends  blindly.  Occasionally  it  becomes  constricted  from 
the  intestine  and  forms  a  cystic  structure.  (See  also  Chap.  XX.) 

Congenital  stenosis  and  atresia  may  occur  in  different  regions  of  the  intestine, 
the  duodenum  being  the  most  common  site.  Normally  the  lumen  of  the 
duodenum  becomes  closed  for  a  brief  period  during  development  (p.  307) ,  and 
congenital  closure  of  the  lumen  may  represent  a  persistence  of  the  early  em- 
bryonic condition. 

A  conspicuous  malformation  is  the  persistence  of  the  cloaca.  The  septum 
which  normally  separates  the  latter  structure  into  rectum  and  urogenital  sinus 
fails  to  develop,  thus  leaving  a  common  cavity  (see  Figs.  323  and  324).  In 
addition  to  this  the  cloacal  membrane  may  fail  to  rupture  and  the  cloaca  be- 
come much  distended.  More  often  the  septum  develops  in  part,  leaving  only 
a  small  opening  between  the  rectum  and  urogenital  sinus.  After  the  latter 
undergoes  further  development,  the  rectum  comes  to  open  into  the  urethra  or 
bladder,  or  into  the  vagina  or  uterus. 

Atresia  of  the  anus  is  not  infrequently  met  with.  The  cloacal  (or  anal) 
membrane  fails  to  rupture  and  the  rectum  ends  blindly.  In  other  cases  the 
rectum  opens  into  the  urogenital  sinus,  as  described  in  the  preceding  paragraph. 
Occasionally  the  lumen  of  the  rectum  is  closed — atresia  recti — and  the  gut  ends 
blindly  some  distance  from  the  surface,  being  connected  with  the  anal  region  by 
a  cord  of  fibrous  tissue. 

Variations  in  the  position  of  the  intestinal  loops,  apart  from  transposition  (p. 
323),  are  of  frequent  occurrence.  It  is  not  customary  to  include  these  varia- 
tions among  malformations  (see  p.  308) .  The  caecum  (and  appendix)  and  colon 
present  some  striking  variations.  The  caecum  may  be  situated  high  up  in  the 
abdominal  cavity,  the  ascending  colon  being  absent.  Or  it  may  be  situated  at 
any  intermediate  point  between  that  and  its  usual  position  in  the  right  iliac 
fossa.  These  variations  are  due  to  different  degrees  of  development  of  the 
ascending  colon  (p.  309). 

THE  LIVER.— Congenital  malformations  of  the  liver  are  rare.     The  most 


DEVELOPMENT  OF  THE  ALIMENTARY  TUBE  AND  APPENDED  ORGANS.       327 

frequent,  apart  from  transposition,  include  anomalies  in  the  size  and  number  of 
lobes.  Accessory  lobes  may  occur  within  the  falciform  ligament.  One  case 
of  lack  of  development  of  the  gall  bladder  has  been  observed.  Stenosis  of  the 
bile  passages  is  occasionally  met  with. 

THE  PANCREAS. — Occasionally  accessory  glands  are  found  in  the  intesti- 
nal or  gastric  wall.  These  probably  represent  aberrant  portions  of  the  main 
gland,  and  may  give  rise  to  cystic  structures.  Very  recently,  however,  a 
number  of  intestinal  diverticula  have  been  observed  in  certain  mammalian 
embryos  and  also  in  human  embryos.  Although  the  history  of  these  unusual 
diverticula  has  not  been  traced,  their  presence  may  offer  a  clue  to  the  origin  of 
accessory  pancreatic  structures.  The  ducts  of  the  pancreas  are  subject  to 
distinct  variations,  which,  however,  are  not  usually  considered  as  anomalies. 
Not  infrequently  the  duct  of  the  dorsal  anlage  (duct  of  Santorini)  persists  and 
opens  directly  into  the  duodenum.  It  may  persist  along  with  the  duct  of  the 
ventral  anlage  (duct  of  Wirsung),  or  the  latter  may  disappear  (p.  321;  compare 
Figs.  2 78  and  279). 

References  for  Further  Study. 

BADERTSCHER,  J.  A. :  The  Development  of  the  Thymus  in  the  Pig.  I,  Morphogenesis. 
II,  Histogenesis.  Am.  Jour,  of  Anat.,  Vol.  XVII,  1915. 

BARDEEN,  C.  R.:  The  Critical  Period  in  the  Development  of  the  Intestines.  Am. 
Jour,  of  Anat.,  Vol.  XVI,  1914. 

BELL,  E.  T.:  The  Development  of  the  Thymus.  American  Jour,  of  Anat.,  Vol.  V, 
1906. 

BERRY,  J.  M.:  On  the  Development  of  the  Villi  of  the  Human  Intestine.  Anat.  Anz., 
Bd.  XVI,  1900. 

BONNET,  R.:  Lehrbuch  der  Entwickelungsgeschichte.     Berlin,  1907. 

BORN,  G.:  Ueber  die  Derivate  der  embryonalen  Schlundbogen  und  Schlundspalten  bei 
Saugetiere.  Arch.},  mik.  Anat.,  Bd.  XXII,  1883. 

BRACKET,  A. :  Die  Entwickelung  und  Histogenese  der  Leber  und  des  Pancreas.  Ergeb- 
nisse  der  Anat.  u.  Entwick.,  Bd.  VI,  1897. 

CHIEVITZ,  J.  C.:  Beitrage  zur  Entwickelungsgeschichte  der  Speicheldriisen.  Arch.  f. 
Anat.  u.  Physiol.,  Anat.  Abth.,  1885. 

CHORONSCHITZKY:  Die  Entstehung  der  Milz,  Leber,  Gallenblase,  Bauchspeicheldruse 
und  des  Pfortadersyssems  bei  den  verschiedenen  Abteilungen  der  Wirbeltiere.  Anat. 
Hefte,  Bd.  XIII,  1900. 

Fox,  H.:  The  Pharyngeal  Pouches  and  their  Derivatives  in  the  Mammalia.  Am. 
Jour,  of  Anat.,  Vol.  VIII,  No.  3,  1908. 

FUSARI,  R.:  Sur  les  phenomenes,  que  Ton  observe  dans  la  muqueuse  du  canal  digestif 
durant  le  developement  du  fcetus  humain.  Arch.  ital.  Biol.,  T.  XLII,  1904. 

GOPPERT,  E.:  Die  Entwickelung  des  Mundes  und  der  Mundhohle  mit  Driisen  und 
Zunge;  die  Entwickelung  der  Schwimmblase,  der  Lunge  und  des  Kehlkopfes  der  Wirbeltiere. 
In  Hertwig's  Handbuch  der  vergleich.  u.  experiment.  Entwickelungslehre  der  Wirbeltiere. 
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Leberentwickelung.  Arch.f.  Anat.  u.  Physiol.,  Anat.  Abth.,  1893. 

HAMMAR,  J.  A.:  Allgemeine  Morphologic  der  Schlundspalten  beim  Menschen.  Ent- 
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HAMMAR,  J.  A. :  Das  Schicksal  der  zweiten  Schlundspalte.  Zur  vergleichenden  Em- 
bryologie  und  Morphologic  der  Tonsille.  Arch.f.  mik.  Anat.,  Bd.  LXI,  1903. 

HELLY,  K.:  Studien  iiber  Langerhanssche  Inseln.  Arch.  f.  mik.  Anat.,  Bd.  LXVII, 
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HERTWIG,  O. :  Lehrbuch  der  Entwickehmgsgeschichte  der  Wirbeltiere  und  des  Men- 
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HENDRICKSON,  W.  F.:  The  Development  of  the  Bile  Capillaries  as  Revealed  by  Golgi's 
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DEVELOPMENT  OF  THE  ALIMENTARY  TUBE  AND  APPENDED  ORGANS.       329 

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XXXIII,  1897 


CHAPTER  Xin. 
THE  DEVELOPMENT  OF  THE  RESPIRATORY  SYSTEM. 

The  anlage  of  the  respiratory  system  appears  in  human  embryos  of  about 
3.2  mm.  A  hollow,  linear  evagination — the  lung  groove — develops  on  the 
ventral  side  of  the  oesophageal  portion  of  the  primitive  gut,  extending  caudally 
a  short  distance  from  the  region  of  the  fourth  inner  branchial  groove.  It  was 
once  thought  that  the  evagination  developed  along  practically  the  entire  length 
of  the  oesophagus  anlage,  but  more  recent  researches  seem  to  prove  that  it  is 
confined  to  the  cephalic  end.  The  lung  groove  soon  becomes  separated  from 


Pharynx 


Hypophysis 


Branchial  arches 
(pharynx) 


Lung 

Liver 

Stomach 
Pancreas 

Common 
mesentery 

Mesonephros 
Allantoic  duct 

Hind-gut 


Kidney  bud 
FIG.  282. — Sagittal  section  of  reconstruction  of  a  human  embryo  of  5  mm.     His,  Kollmann. 

the  gut  by  a  constriction  which  appears  at  the  caudal  end  and  gradually  pro- 
gresses forward.  Thus  there  is  formed  a  tube  which  lies  ventral  to  the  gut  and 
which  opens  upon  the  floor  of  the  latter  at  the  boundary  line  between  the 
oesophagus  and  pharynx  (Figs.  282  and  246). 

From  this  simple  tube  the  entire  respiratory  system  develops.  The 
cephalic  end  gives  rise  to  the  larynx,  the  opening  into  the  gut  being  the  aditus 
laryngis.  The  middle  portion  gives  rise  to  the  trachea.  Two  outgrowths  from 
the  caudal  end  of  the  tube,  which  appear  about  the  time  of  separation  from  the 

330 


THE  DEVELOPMENT  OF  THE  RESPIRATORY  SYSTEM.  331 

oesophagus,  develop  into  the  bronchi  and  their  continuations— the  lungs.  The 
epithelial  lining  of  the  system  is  of  course  derived  from  the  entoderm.  The 
various  kinds  of  connective  tissue  are  derived  from  the  mesoderm,  since  the 
anlage  grows  into  the  mesodermal  tissue  of  the  ventral  mesentery. 

The  Larynx. 

The  opening  from  the  gut  into  the  respiratory  tube  becomes  surrounded  by 
a  U-shaped  elevation — thefurcula — which  lies  in  the  floor  of  the  pharynx  with 
its  open  end  directed  caudally.  Toward  the  end  of  the  first  month  each 
side  of  the  opening  (aditus  laryngis)  becomes  elevated,  forming  the  arytenoid 
ridge.  From  each  of  these  a  secondary  elevation  arises,  forming  the  cunei- 
form ridge.  The  arytenoid  ridges  come  so  close  together  that  they  practically 
close  the  opening  except  at  its  cephalic  side  (Fig.  283).  Along  with  the  develop- 
ment of  these  ridges  the  apical  portion  of  the  furcula  becomes  a  distinct  trans- 


Tuberculum  impar 


L  Epiglottis 

j-  Aryepiglottic  ridge 

—  Arytenoid  ridge 

—  Cuneiform  ridge 

—  Aditus  laryngis 

Cuneiform  ridge 


FIG.  283. — From  a  reconstruction  of  the  larynx  of  a  human  embryo  of  28  days. 
Seen  from  above.     Kattius. 

verse  fold  at  the  cephalic  rim  of  the  opening.  This  fold  is  the  anlage  of  the 
epiglottis.  Laterally  the  epiglottic  fold  becomes  continuous  with  the  arytenoid 
ridges,  forming  the  ary epiglottic  ridges  (Fig.  283). 

During  the  fourth  month  a  groove-like  depression  appears  on  the  medial 
side  of  each  arytenoid  ridge,  gradually  becomes  deeper,  and  leaves  on  each  side 
of  it  a  fold  or  lip  which  bounds  the  opening.  The  external  lips — those  nearer 
;  the  pharynx — form  the  superior  or  false  vocal  cords;  the  internal  lips  form  the 
true  vocal  cords.  At  the  same  time  the  opening  into  the  larynx,  which  was 
closed  by  the  arytenoid  ridges,  is  reestablished.  The  depression  between  the 
vocal  cords  on  each  side  becomes  still  deeper  to  form  the  ventricle,  and  a  further 
outgrowth  from  the  ventricle  produces  the  appendage  of  ike  ventricle  (the  laryn- 
geal  pouch). 


332 


TEXT-BOOK  OF  EMBRYOLOGY. 


The  mesodermal  tissue  external  to  the  epithelium  (entoderm)  of  the  larynx 
gives  rise  to  the  various  kinds  of  connective  tissue  including  the  laryngeal 
cartilages.  By  the  end  of  the  fourth  week  condensations  appear  in  the  mesen- 
chymal  tissue,  which  are  the  forerunners  of  the  cartilages,  but  true  cartilage 
does  not  appear  until  the  seventh  week.  The  anlagen  of  the  thyreoid  cartilage 


Sup.  hy. 


Sup.  hy. 


Inf.  hy 


Thyr. 


A  B 

FIG.  284. — From  reconstructions  of  the  mesenchymal  condensations  which  represent  the  hyoid  and 
thyreoid  cartilages  in  an  embryo  of  40  days.  A,  Ventral  view;  B,  lateral  view  from  right. 
Kallius. 

Inf.hy.,  Inferior  (greater)  horn  of  hyoid;  Sup.hy.,  superior  (lesser)  horn  of  hyoid;  Thyr.,  thyreoid. 
The  portions  indicated  by  black  lines  represent  chondrification  centers. 

are  two  mesenchymal  plates,  one  on  each  side,  which  are  bilaterally  sym- 
metrical and  correspond  to  the  lateral  parts  of  the  adult  cartilage  (Fig.  284,  A). 
These  plates  gradually  grow  ventrally  and  unite  and  fuse  in  the  midventral 
line  (Fig.  285) .  Two  centers  of  chondrification  appear  in  each  plate  (Fig.  284,  A,) 


Pharynx 


Muscle 


Arytenoid  cartilage 


£&£-:i__  Thyreoid  cartilage 


Muscle 


Copula 


FIG.  285. — From  a  transverse  section  through  the  pharynx  and  larynx  of  a  human 
embryo  of  48  mm.     Nicolas. 

and  enlarge  until  the  entire  plate  is  converted  into  cartilage,  the  middle 
becoming  elastic  in  character,  the  rest  hyalin. 

Originally  the  cephalic  edge  of  each  thyreoid  plate  is  connected  with  the 
inferior  horn  of  the  hyoid  cartilage  (Fig.  284,  B).  This  connection  is  subse- 
quently lost,  but  a  remnant  of  the  connecting  cartilage  persists  as  the  triticeous 


THE  DEVELOPMENT  OF  THE  RESPIRATORY  SYSTEM.  333 

cartilage  in  the  lateral  hyothyreoid  ligament.  The  anlagen  of  the  arytenoid 
cartilages  develop  in  the  arytenoid  ridges  as  condensations  of  the  mesenchyme, 
which  later  are  converted  into  true  cartilage  (Fig.  285).  The  apex  and  vocal 
process  of  each  arytenoid  become  elastic,  the  main  body  becomes  hyalin. 
The  corniculate  cartilages  (cartilages  of  Santorini)  are  split  off  from  the  cephalic 
ends  of  the  arytenoids  and  are  of  the  elastic  variety.  The  cricoid  cartilage, 
like  the  others,  is  preceded  by  a  condensation  of  mesenchyme.  Chondrifica- 
tion  begins  on  each  side  and  then  progresses  around  dorsally  and  ventrally  until 
a  complete  hyalin  ring  is  formed.  From  its  developmental  resemblance  to  the 
tracheal  rings,  the  cricoid  is  sometimes  regarded  as  the  most  cephalic  of  that 
series.  The  epiglottic  cartilage  develops  in  the  epiglottic  ridge  as  two  sepa- 
rate pieces  which  subsequently  fuse.  It  is  of  the  elastic  variety.  The  cuneiform 
cartilages  (cartilages  of  Wrisberg)  are  split  off  from  the  two  pieces  of  the  epi- 
glottic, and  are  of  the  elastic  type. 

Attempts  have  been  made  to  determine  which  branchial  arches  are  represented  by  the 
laryngeal  cartilages.  It  seems  quite  definitely  settled  that  the  thyreoid  is  derived  in  part,  at 
least,  from  the  fourth  arch.  There  is  much  doubt  as  regards  the  others,  for  there  is  great 
difficulty  in  determining  their  derivation  in  the  human  embryo,  since  the  arches  disappear 
at  such  an  early  stage.  Furthermore,  some  of  these  cartilages  may  represent  arches  which 
are  present  in  lower  forms  but  do  not  appear  in  the  higher  Mammals. 

The  larynx  is  situated  much  farther  cranially  in  the  foetus  and  in  the  new- 
born child  than  in  the  adult.  In  a  five  months  fcetus  it  extends  into  the  naso- 
pharyngeal  cavity,  whence  it  migrates  caudally  to  its  adult  position.  The 
laryngeal  skeleton  becomes  ossified  during  postnatal  life.  Ossification  begins 
in  the  thyreoid  and  cricoid  cartilages  at  the  age  of  eighteen  to  twenty  years, 
and  in  the  arytenoids  a  few  years  later.  Three  centers  appear  in  the  thyreoid 
— one  on  each  side  near  the  inferior  cornu  and  one  in  the  medial  line  between 
the  two  wings.  In  the  cricoid,  ossification  begins  near  the  upper  border  on 
each  side,  in  the  arytenoids  at  the  lower  borders.  Ossification  usually  begins 
earlier  and  proceeds  more  rapidly  in  the  male  than  in  the  female. 

As  an  example  of  the  explanation  which  Embryology  offers  of  certain  peculiarities  of 
structure  in  the  adult,  the  case  of  the  recurrent  laryngeal  nerve  may  be  cited.  The  heart  and 
aortic  arches  are  primarily  situated  in  the  cervical  region.  At  that  time  a  branch  of  the 
vagus  on  each  side,  passes  behind  the  fourth  aortic  arch  to  reach  the  larynx.  As  the 
heart  and  arches  recede  into  the  thorax,  the  nerve  is  pulled  caudally  between  its  origin  and 
termination,  so  that  in  the  adult  the  left  nerve  bends  around  the  arch  of  the  aorta  and  the 
right  around  the  subclavian  artery. 

The  Trachea. 

The  portion  of  the  original  tube  between  the  larynx  and  the  two  caudal  out- 
growths which  form  the  bronchi  and  lungs,  develops  into  the  trachea.  It  lies 
ventral  to  the  oesophagus  and  is  surrounded  by  mesodermal  tissue  which  is 


334 


TEXT-BOOK  OF   EMBRYOLOGY. 


destined  to  give  rise  to  the  connective  tis.  'ie,  including  the  cartilage,  of  the 
adult  trachea  (Figs.  246  and  282).  The  development  of  the  tracheal  rings  is 
very  similar  to  that  of  the  laryngeal  cartilages.  During  the  eighth  or  ninth 
week  condensations  appear  in  the  mesenchyme,  which  are  later  transformed 
into  hyalin  cartilage.  The  rings  are  not  complete  but  remain  open  on  the 
dorsal  side.  At  birth  the  trachea  is  collapsed,  the  ventral  side  being  concave 
and  the  dorsal  ends  of  each  ring  being  in  contact  After  respiration  begins  it 
is  dilated  and  becomes  more  or  less  rigid.  Ossification  of  the  tracheal  rings 
begins  in  the  male  at  the  age  of  about  forty  years,  in  the  female  at  about  sixty. 
The  glands  of  the  trachea  represent  evaginations  from  the  epithelial  linings. 

The  Lungs. 

As  has  been  stated  (p.  330),  the  caudal  end  of  the  original  tube  evaginates 
to  form  two  hollow  buds  which  are  the  beginnings. of  the  two  lungs  (Fig.  286). 
The  evagination  takes  place  soon  after  or  even  along  with  the  separation  of  the 
lung  groove  from  the  gut.  The  right  bud  soon  gives  rise  to  three  secondary 


Aorta 


Upper  limb  bud 
(Esophagus 

Body  cavity 
Pericardial  cavity 


FIG.  286. — Transverse  section  of  a  14  mm.  pig  embryo,  at  the  level  of  the  upper  limb  buds, 
showing  especially  the  two  bronchi. 


buds,  the  forerunners  of  the  three  lobes  of  the  right  lung.  The  left  bud  gives 
rise  to  two  secondary  buds,  the  forerunners  of  the  two  lobes  of  the  left  lung 
(Fig.  287).  The  primary  buds  may  be  said  to  represent  the  two  bronchi  arising 
from  the  trachea,  the  five  secondary  buds  to  represent  the  bronchial  rami 
which  extend  into  the  five  lobes  of  the  lungs.  Successive  evaginations  from 
each  of  the  five  buds  take  place  and  form  an  extensive  arborization  for  each 
lobe  (Figs.  288  and  289). 


THE  DEVELOPMENT   OF  THE  RESPIRATORY  SYSTEM. 


335 


The  manner  in  which  the  bronchial  rami  branch  is  not  definitely  known. 
Some  maintain  that  the  branching  is  dichotomous,  that  is,  each  bud  gives  rise 
to  two  equal  buds  and  each  of  these  to  two  others,  and  so  on.  In  order  to  as- 
sume the  adult  form,  however,  one  of  the  buds  places  itself  in  line  with  the 
preceding  bud  or  bronchus  while  the  other  places  itself  as  a  lateral  outgrowth. 
Others  hold  that  the  growth  is  monopodial,  that  is,  that  the  original  bud  grows 
in  a  more  or  less  direct  line  and  the  others  develop  as  lateral  outgrowths.  When 


Upper  -ight  lobe 


Middle  right  lobe 


Trachea 


Upper  left  lobe 


Mesoderm 
(mesenchyme) 


Lower  right  lobe 

FIG.  287. — Anlage  of  lungs  of  a  human  embryo  of  4.3  mm.     His. 


the  evaginations  that  produce  the  bronchial  rami  are  completed,  each  terminal 
(respiratory)  bronchus  subdivides  into  three  to  six  narrow  tubules,  the  alveolar 
ducts.  The  latter  again  branch  into  several  wider  compartments,  the  atria, 
from  which  several  .air  sacs  are  given  off.  The  walls  of  the  air  sacs  are  evagi- 
nated  to  form  many  closely  set  air  cells  which  represent  the  ultimate  branches 
of  the  air  passages  of  the  lungs. 


Trachea 


Right  bronchus 


Left  bronchus 


Bronchial  ramus 


Mesoderm 
(mesenchyme) 


Bronchial  ramus' 

FIG.  288; — Anlage  of  lungs  of  a  human  embryo  of  8.5  mm.     His. 


While  there  is  a  general  tendency  toward  bilateral  symmetry  in  the  various 
sets  of  bronchial  rami,  the  lobes  of  the  lungs  are  asymmetrical.  This  asym- 
metry is  indicated  in  the  five  secondary  buds  that  arise  from  the  two  primary, 
since  three  arise  on  the  right  side  and  only  two  on  the  left.  The  three  on  the 
right  represent  the  upper,  middle  and  lower  lobes  of  the  right  lung  (Fig.  287). 
The  upper  is  known  as  the  eparterial  from  the  fact  that  its  bronchus  lies  dorsad 


336 


TEXT-BOOK  OF  EMBRYOLOGY. 


to  the  pulmonary  artery.  No  lobe  develops  on  the  left  side  corresponding  to 
the  upper  (eparterial)  on  the  right.  There  is  a  possibility  that  it  is  absent  in 
order  to  allow  the  arch  of  the  aorta  to  migrate  caudally  as  it  normally  does 
(see  p.  254).  One  of  the  larger  ventral  bronchial  rami  of  the  left  lung  is  ab- 
sent, owing  to  the  inclination  of  the  heart  toward  the  left  side;  but  as  a  compensa- 
tion the  corresponding  ramus  of  the  right  lung  develops  more  extensively 
and  projects  into  the  space  between  the  pericardium  and  diaphragm  as  the 
infracardiac  ramus. 

From  the  fact  that  the  anlage  of  the  respiratory  system  is  enclosed  within 
the  mesentery  between  the  gut  and  the  pericardial  cavity,  and  that  its  caudal  end 
becomes  enclosed  within  the  dorsal  edge  of  the  septum  transversum,  it  is  obvious 


Pulmonary  artery 


Right  bronchus 


Upper  right 
bronch.  ramus 


Middle  right 
Tbronch.  ramus 


Lower  right 
bronch.  ramus 

Mesoderm 
(mesenchyme) 


Trachea 


Left  bronchus 


Upper  left 
bronch.  ramus 

Lower  left  branch 
pulmonary  vein 


Lower  left 
bronch.  ramus 


FIG.  289. — Anlage  of  lungs  of  a  human  embryo  of  10.5  mm.     His, 


that  the  lungs  will  push  their  way  into  the  dorsal  parietal  recesses  or  pleural 
cavities  (Figs.  290  and  295).  The  way  in  which  the  lungs  and  pleural  cavities 
enlarge  and  separate  the  pericardium  from  the  body  wall  on  each  side  and  from 
the  diaphragm  is  described  on  page  346  (see  Figs.  296  and  297).  The  mesoder- 
mal  tissue  that  surrounds  the  primary  lung  buds  is  in  part  pushed  before  the 
numerous  outgrowths  and  in  part  remains  among  them  (Figs.  287,  288,  289). 
The  part  around  the  lungs,  with  its  covering  of  mesothelium,  comes  to  form  the 
visceral  layer  of  the  pleura  which  closely  invests  the  entire  surface  of  the  lungs 
and  dips  down  between  the  lobes.  At  the  roots  of  the  lungs  it  is  continuous 
with  the  parietal  layer  of  the  pleura  lining  the  inner  surface  of  the  pleural  cavi- 
ties. The  mesodermal  tissue  among  the  bronchi  and  their  terminations  gives 
rise  to  the  connective  tissue  that  separates  the  lobes  and  lobules  and  invests  all 
the  structures  in  the  interior  of  the  lungs.  This  connective  tissue  at  first  con- 


THE  DEVELOPMENT  OF  THE  RESPIRATORY  SYSTEM. 


337 


stitutes  a  large  part  of  the  lungs,  but  as  development  proceeds,  the  more 
rapid  growth  of  the  respiratory  parts  results  in  the  relatively  small  amount  of 
connective  tissue  characteristic  of  the  adult  lung. 

Changes  in  the  Lungs  at  Birth. — At  birth  the  lungs  undergo  rapid  and 
remarkable  changes  in  consequence  of  their  assuming  the  respiratory  function. 
These  changes  affect  their  size,  form,  position,  texture,  weight,  etc.,  and 
furnish  probably  the  only  certain  means  of  distinguishing  between  a  still-born 
child  and  one  that  has  breathed.  In  the  foetus  at  term  the  lungs  are  small, 
possess  rather  sharp  margins  and  lie  in  the  dorsal  part  of  the  pleural  cavities. 


Lungs 


Pleural  cavities 


Diaphragm 

FIG.  290. — Transverse  section  of  a  pig  embryo  of  35  mm.,  showing  the  developing  lungs  (bronchial 
rami  surrounded  by  mesoderm).  The  oesophagus  is  seen  between  the  two  lungs;  above  the 
oesophagus  is  the'  aorta.  The  dark  mass  in  the  lower  part  of  the  figure  is  the  liver. 
Photograph. 

After  respiration  they  enlarge,  fill  practically  the  entire  pleural  cavities  and 
naturally  become  more  rounded  at  their  margins.  The  introduction  of  air  into 
the  air  passages  converts  the  compact,  gland-like,  foetal  lung  into  a  loose, 
spongy  tissue.  The  specific  gravity  is  changed  from  1.056  to  0.342.  While 
there  is  a  gradual  increase  in  the  weight  of  the  lungs  during  development,  there 
is  a  very  sudden  increase  at  birth  when  the  blood  is  freely  admitted  to  them 
through  the  pulmonary  arteries.  The  weight  of  the  lungs  relative  to  that  of 
the  body  changes  from  about  i  to  70  before  birth,  to  about  i  to  35  or  40  after 
birth. 


338  TEXT-BOOK  OF  EMBRYOLOGY. 

Anomalies. 

THE  LARYNX. — The  larynx  may  be  excessively  large  or  unusually  small. 
Occasionally  the  epiglottic  cartilage  consists  of  two  pieces,  indicating  a  failure 
of  the  two  anlagen  to  fuse  (p.  332).  Similar  defects  may  occur  in  the  other 
cartilages  that  are  derived  from  more  than  one  anlage.  The  ventricle  on  either 
side  may  be  abnormally  large  with  an  exaggerated  appendage  (laryngeal 
pouch) .  This  condition  resembles  that  in  the  anthropoid  apes. 

THE  TRACHEA. — The  trachea  is  sometimes  absent,  in  which  case  the  bronchi 
arise  immediately  below  the  larynx,  indicating  a  failure  on  the  part  of  the 
original  tube  to  elongate.  The  trachea  may  be  abnormally  short.  Rarely 
there  is  a  direct  communication  between  the  trachea  and  oesophagus,  probably 
due  to  an  incomplete  separation  of  the  lung  groove  from  the  gut  (p.  330) .  The 
cartilaginous  rings  may  vary  in  number  as  a  result  of  abnormal  splittings  and 
fusions. 

THE  LUNGS. — Rarely  the  eparterial  bronchial  ramus  on  the  right  side 
arises  as  a  branch  of  the  trachea  and  not  as  a  branch  of  the  bronchus  (p.  335). 
This  condition  is  normal  in  certain  Mammals  (ox,  sheep) .  Rarely  an  eparterial 
bronchial  ramus  is  present  on  the  left  side,  thus  producing  a  third  lobe  for 
the  left  lung.  In  some  animals  an  eparterial  ramus  is  normally  present  on 
each  side,  the  larger  bronchial  rami  thus  being  bilaterally  symmetrical.  Varia- 
tion in  size  and  number  of  lobes  is  not  infrequent.  Supernumerary  or  acces- 
sory lobes,  formed  either  by  evaginations  from  the  original  anlage  or  by  in- 
dependent evaginations  from  the  gut,  are  met  with  in  rare  cases. 

Occasionally  some  portion  of  either  lung  is  defective.  The  bronchial  bud 
that  would  normally  give  rise  to  the  lung  tissue  in  that  region  fails  to  develop 
properly,  and  the  result  is  a  number  of  rami,  without  the  ultimate  terminations, 
surrounded  by  vascular  tissue.  The  rami  may  remain  normal  or.  may  become 
dilated  and  form  krge  bronchial  cysts. 

References  for  Further  Study. 

j  BONNET,  R.:  Lehrbuch  der  Entwickelungsgeschichte.  Berlin,  1907. 

FLINT,  J.  M.:  The  Development  of  the  Lungs.     American  Jour,  of  Anat.,  Vol.  VI,  1906. 

GOPPERT,  E.:  Die  Entwickelung  des  Mundes  und  der  Mundhohle  mit  Drusen  uud 
Zunge;  die  Entwickelung  der  Schwimmblase,  der  Lunge  und  des  KehlkopfesderWirbeltiere. 
In  Hertwig's  Handbuch  der  vergleich.  u.  experiment.  Entwickelungslehre  der  Wirbeltiere, 
Bd.  II,  Teil  I,  1902. 

HERTWIG,  O.:  Lehrbuch  der  Entwickelungsgeschichte  des  Menschen  und  der  Wirbel- 
tiere. Jena,  1906. 

His,  W.:  Zur  Bildungsgeschichte   der  Lungen  beim  menschlichen  Embryo.     Arch.  /. 
Anat.  u.  Physiol.,  Anat.  Abth.,  1887. 

KALLIUS,  E.:  Beitrage  zur  Entwickelungsgeschichte  des  Kehlkopfes.  Anat.  Hejte, 
Bd.  IX,  1897. 

KOLLMANN,  J.:  Lehrbuch  der  Entwickelungsgeschichte  des  Menschen.     Jena,  1898. 

KOLLMANN,  J.:  Handatlas  der  Entwickelungsgeschichte  des  Menschen.     Jena,  1907. 


THE  DEVELOPMENT  OF  THE   RESPIRATORY  SYSTEM.  339 

HUNTINGTON,  CEO.  S.:  A  Critique  of  the  Theories  of  Pulmonary  Evolution  in  the 
Mammalia.  Am.  Jour,  of  Anat.,  Vol.  XXVII,  No.  2,  1920. 

McMuRRiCH,  J.  P.:  The  Development  of  the  Human  Body.     Third  Ed.,  1907. 

PIERSOL,  G.  A.:  Teratology.  In  Wood's  Reference  Handbook  of  the  Medical  Sciences, 
Vol.  VII,  1904. 

SYMINGTON,  J.:  On  the  Relations  of  Larynx  and  Trachea  to  the  Vertebral  Column  in 
the  Foetus  and  Child.  Journ.  of  Anat.  and  Physiol.,  Vol.  IX. 


CHAPTER  XIV. 

THE  DEVELOPMENT  OF  THE  CCELOM  (PERICARDIAL 

PLEURAL  AND  PERITONEAL  CAVITIES),  THE 

PERICARDIUM,  PLEUROPERITONEUM, 

DIAPHRAGM,  AND  MESENTERIES. 

In  the  Chapter  on  the  development  of  the  germ  layers,  it  is  stated  that  the 
peripheral  part  of  the  mesoderm  splits  into  two  layers,  an  outer  or  parietal,  and 
an  inner  or  visceral  (Fig.  72;  see  also  p.  96).  The  parietal  layer  of  mesoderm 
and  the  ectoderm  constitute  the  somatopleure.  The  visceral  layer  and  the 
entoderm  constitute  the  splanchnopleure  (Fig.  72).  The  cleft  or  cavity 
that  appears  between  the  parietal  and  visceral  layers  is  the  c&lom  or  body 
cavity  and  is  lined  with  a  layer  of  flattened  mesodermal  cells  known  as  the 
mesothelium.  It  will  be  remembered  that  in  the  earlier  stages  of  development  a 
portion  of  the  embryonic  disk  becomes  constricted  off  from  the  yolk  sac  to  form 
the  simple  cylindrical  body  (p.  107) .  Along  each  side  of  the  axial  portion  of  the 
germ  disk,  and  also  at  its  cephalic  and  caudal  ends,  the  germ  layers  bend  ven- 
trally  and  then  medially  until  they  meet  and  fuse  in  the  midventral  line  (p.  109) . 
In  this  way  a  part  of  the  somatopleure  forms  the  lateral  and  ventral  portions  of 
the  body  wall  (Pig.  103).  At  the  same  time  the  axial  portion  of  the  entoderm  is 
bent  into  a  tube  which  is  closed  at  both  ends — the  primitive  gut — and  is  then 
pinched  off  from  the  rest  of  the  entoderm  except  at  one  point,  where  the  cavity 
of  the  gut  remains  in  communication  with  the  cavity  of  the  yolk  sac.  The 
splanchnic  mesoderm  adjacent  to  the  entoderm  on  each  side  comes  in  contact 
and  fuses  with  the  corresponding  portion  from  the  opposite  side,  thus  forming 
a  sheet  of  tissue  which  encloses  the  primitive  gut  and  also  forms  a  partition  be- 
tween the  two  parts  of  the  coelom.  This  sheet  of  tissue  is  the  common  mesentery 
and  is  attached  to  the  dorsal  and  ventral  body  walls  along  the  medial  line. 
The  portion  between  the  gut  and  the  dorsal  body  wall  is  the  dorsal  mesentery, 
the  portion  between  the  gut  and  the  ventral  body  wall  is  the  ventral  mesentery. 
Thus  the  gut  is  suspended  in  the  common  mesentery  (Figs.  197  and  282). 

When  portions  of  the  somatopleure  and  splanchnopleure  are  bent  ventrally 
the  coelom  between  the  portions  is  naturally  carried  with  them.  This  part  of 
the  coelom  thus  becomes  enclosed  within  the  cylindrical  body  and  constitutes 
the  intraembryonic  or  simply  the  embryonic  codom  (body  cavity  proper).  The 
part  of  the  ccelom  which,  while  the  germ  layers  were  still  flat,  was  situated  more 
peripherally  constitutes  the  extraembryonic  coelom  or  eococcdom  (extraembryonic 

340 


PERICARDIUM,  PLEUROPERITONEUM,  DIAPHRAGM   AND  MESENTERIES.      341 

body  cavity).  From  the  nature  of  the  bending  process,  the  embryonic  coelom 
is  divided  into  bilaterally  symmetrical  parts  by  the  common  mesentery  (Fig. 
197) .  These  two  simple  cavities  are  the  forerunners  of  all  the  serous  cavities  of 
the  body.  The  various  partitions  between  the  serous  cavities,  the  walls  of  the 
cavities  and  the  mesenteries  proper  are  all  derived  from  the  somatic  and 
splanchnic  mesoderm  with  its  covering  of  mesothelium. 

While  the  foregoing  would  represent  a  typical  case  of  early  ccelom  and 
mesentery  formation,  there  are  certain  modifications  and  peculiarities  in  the 
higher  Mammals  and  in  man.  In  all  cases  the  splitting  of  the  mesoderm  to 
form  the  coelom  proceeds  from  the  periphery  of  the  germ  disk  toward  the  axial 
portion  (p.  80) .  In  the  human  embryo  the  bending  ventrally  and  fusing  of  the 
germ  layers  to  form  the  cylindrical  body  begins  in  the  anterior  region  of  the 
disk  and  is  accomplished  there  before  the  splitting  of  the  mesoderm  is  com- 
pleted. The  peripheral  splitting  has  resulted  in  the  formation  of  the  exoccelom, 
but  at  the  time  when  the  ventral  fusion  of  the  germ  layers  takes  place,  the  split- 
ting has  not  extended  axially  to  a  sufficient  degree  to  form  the  intraembryonic 
crelom.  The  latter,  which  appears  later  in  this  region,  never  communicates 
laterally,  therefore,  with  the  exocoelom.  Caudal  to  this  region  the  coelom  is 
formed  as  in  the  typical  case.  The  more  anterior  part  of  the  coelom  on  each 
side  is  thus  primarily  a  pocket-like  cavity.  It  communicates  with  the  rest  of  the 
coelom  at  about  the  level  of  the  yolk  stalk.  In  the  region  of  the  fore-gut,  the 
future  oesophagus,  no  distinct  mesentery  is  formed,  but  the  fore-gut  remains 
broadly  attached  to  the  dorsal  body  wall.  A  ventral  mesentery  is  lacking  from 
a  point  just  cranial  to  the  yolk  stalk  to  the  caudal  end  of  the  gut.  There  are 
no  coelomic  cavities  in  the  branchial  arches,  the  ccelom  extending  only  to  the 
last  branchial  groove. 

In  very  young  human  embryos  the  primitive  segments  contain  small  cavities. 
These  cavities  soon  disappear,  being  filled  with  cells  from  the  surrounding, 
parts  of  the  segments.  Whether  they  represent  isolated  portions  of  the  coelom 
is  not  certain.  In  the  lower  Vertebrates,  the  cavities  of  the  primitive  segments 
regularly  communicate  with  the  ccelom,  and  in  the  sheep  the  cavities  of  the  first 
formed  segments  are  continuous  with  the  ccelom.  In  the  head  there  is  no 
cavity  analogous  to  the  coelom  in  the  body.  In  but  one  human  embryo  have 
any  cavities  in  the  head  resembling  those  of  the  primitive  segments  been 
observed  (see  p.  2  70) . 

The  Pericardial  Cavity,  Pleural  Cavities  and  Diaphragm. 

The  pericardial  and  pleural  cavities  and  diaphragm  are  so  closely  related  in 
their  development  that  they  must  be  considered  together.  In  the  region  just 
caudal  to  the  visceral  arches,  where  the  two  anlagen  of  the  heart  appear,  the 
embryonic  coelom  becomes  dilated  at  a  very  early  stage  to  form  the  primitive 
pericardial  cavity  (parietal  cavity  of  His).  After  the  two  anlagen  of  the  heart 


342 


TEXT-BOOK  OF  EMBRYOLOGY. 


unite  to  form  a  simple  tubular  structure  (p.  196:  also  Fig.  156),  the  latter  is 
suspended  in  the  cavity  by  a  mesentery  which  consists  of  a  dorsal  and  a  ventral 
part,  a  dorsal  and  a  ventral  mesocardium.  By  these  the  cavity  is  at  first  divided 
into  two  bilaterally  symmetrically  parts.  The  mesocardia  soon  disappear  and 
leave  the  heart  attached  only  to  the  large  vascular  trunks  which  suspend  it 
in  the  single  pericardial  cavity.  The  early  pericardial  cavity  is  simply  the 
cephalic  end  of  the  embryonic  ccelom  and  is  therefore  directly  continuous  with 
the  rest  of  the  ccelom.  As  mentioned  on  p.  341  it  does  not,  however,  at  any 
time  communicate  laterally  with  the  extraembryonic  ccelom. 

The  communication  between  the  pericardial  cavity  and  the  rest  of  the  em- 
bryonic ccelom  is  soon  partly  cut  off  by  the  development  of  a  transverse  fold 
- — the  septum  transversum.  This  septum  is  formed  in  close  relation  with  the 
omphalomesenteric  veins.  These  vessels  unite  in  the  sinus  venosus  at  the 
caudal  end  of  the  heart,  whence  they  diverge  in  the  splanchnic  mesoderm. 


am 


vom 


FIG.  291.  —  Transverse  sections  of  a  rabbit  embryo,  showing  how  the  omphalomesenteric  veins  (vom) 
push  outward  across  the  ccelom  and  fuse  with  the  lateral  body  wall,  forming  the  ductus 
pleuro-pericardiacus  (rp,  rpd)  ;  am,  amnion.  Ravn. 

They  are  thus  embedded  in  the  mesodermal  layer  of  the  splanchnopleure,  and  as 
the  latter  closes  in  from  either  side  to  form  the  gut,  the  vessels  form  ridge-like 
projections  into  the  ccelom.  As  the  vessels  increase  in  size,  the  ridges  become 
so  large  that  the  splanchnic  mesoderm  is  pushed  outward  against  the  parietal 
mesoderm  and  fuses  with  it  (Fig.  291).  Thus  a  partition  is  formed  on  each  side, 
which  is  attached  on  the  one  hand  to  the  mesentery  and  on  the  other  hand  to  the 
ventral  and  lateral  body  walls,  and  which  contains  the  omphalomesenteric  veins. 
It  is  obvious  that  these  partitions,  forming  the  septum  transversum,  close  the 
ventral  part  of  the  communication  between  the  pericardial  cavity  and  the  rest  of 
the  ccelom.  The  dorsal  part  of  the  communication  remains  open  on  each  side 
of  the  mesentery  as  the  ductus  pleuro-pericardiacus  (dorsal  parietal  recess  of  His) 
(Figs.  291  and  292). 

As  the  heart  develops  it  migrates  caudally,  and  by  corresponding  migration 
the  pericardial  cavity  draws  the  ventral  edge  of  the  septum  transversum  farther 
caudally,  so  that  the  cephalic  surface  of  the  latter  faces  ventrally  and  cranially. 


PERICARDIUM,  PLEUROPERITONEUM,  DIAPHRAGM  AND  MESENTERIES.     343 

In  other  words  the  septum  comes  to  lie  in  an  oblique  cranio-caudal  plane.  The 
pericardial  cavity  therefore  comes  to  lie  ventral  to  the  ductus  pleuro-pericardiaci. 
The  latter — one  on  each  side  of  the  mesentery — are  two  passages  which  com- 


Pericardial  cavity- 
Lateral  mesocardium 

Pericardium 

Septum  transversum 

Liver 

Ductus  choledochus 


Yolk  stalk  -M 


Ventral  aortic  trunk 
Dorsal  mesocardium 

Sinus  venosus 
Duct  of  Cuvier 

Left  umbilical  vein 
Left  omphalomes.  vein 
Ductus  pleuro-pericardiacus 

Stomach 
Peritoneal  cavity 


FIG.  292. — From  a  model  of  the  septum  transversum,  liver  etc.,  of  a  human  embryo 
of  3  mm.     His,  K oilman. 

municate  on  the  one  hand  with  the  pericardial  cavity  and  on  the  other  hand  with 
the  peritoneal  cavity,  while  they  themselves  form  the  cavities  into  which  the  lungs 
grow — the  pleural  cavities.  (Compare  Figs.  292,  293  and  294.) 


Pharynx 
Dorsal  mesocardium 


Ductus  pleuro- 
pericardiacus 


Aorta 


Ductus  pleuro 
pericardiacus 
Duct  of  Cuvier 


Heart 


^^^^^        Pericardial  cavity 

FIG.  293. — View  (in  perspective)  of  the  pericardial  cavity  and  ductus  pieurp-pericardiaci 
of  a  rabbit  embryo  of  9  days.     Ravn. 

The  pleural  cavities  also  become  separated  from  the  pericardial  cavity,  ap- 
parently through  the  agency  of  the  ducts  of  Cuvier.  The  anterior  and  posterior 
cardinal  veins  on  each  side  unite  to  form  the  duct  of  Cuvier  which  then  ext  *nds 


344 


TEXT-BOOK  OF  EMBRYOLOGY. 


from  the  body  wall  through  the  dorsal  free  edge  of  the  septum  transversum  to 
join  the  sinus  venosus  (Fig.  292).  This  free  edge  is  pushed  farther  and 
farther  into  the  ductus  pleuro-pericardiacus  (Fig.  293)  until  it  meets  and  fuses 


Dorsal  mesentery 


Pleural  cavity 


Lung 


Lateral  mesocardium -- 


Pericardial  cavity 


Lateral  mesocardium 


l\'~" —  Dorsal  mesocardium 
1— -,  Heart 


FIG.  294. — View  (in  perspective)  of  the  pericardial  and  pleural  cavities  of  a  human  embryo 

of  7.5  mm.     Kollmann. 

The  arrow  points  through  the  opening  which  forms  the  communication  between  the  pleural 
and  peritoneal  cavities,  and  which  is  eventually  closed  by  the  pleuro-peritoneal  membrane. 

with  the  mesentery  or  posterior  mediastinum.     This  process  thus  produces  a 
septum  between  each  pleural  cavity  and  the  pericardial  cavity. 

The  septum  transversum  early  acquires  still  more  complicated  relations 


Lung     g 


Pleuro-peritoneal  membrane 


Mesentery  of 
inf.  vena  cava  if 


Inferior  vena  cava  --- 
Mesonephros  ^M 


Lung 

Pleuro-peritoneal  membrane 
Mesentery 


P'euro-peritoneal  membrane 
CEsophagus 


Dorsal  mesogastrium 


FIG.  295. — Ventral  view  (in  perspective)  of  parts  of  the  lungs,  pleural  cavities,  peritoneal  cavity, 
and  the  pleuro-peritoneal  membranes  in  a  rat  embryo.     Ravn. 

from  the  fact  that  the  liver  grows  into  its  caudal  part  (Fig.  292) .  It  may,  for  this 
reason,  be  divided  into  a  caudal  part  in  which  the  liver  is  situated  and  which 
furnishes  the  fibrous  capsule  (of  Glisson)  and  the  connective  tissue  of  the  liver, 
and  a  cephalic  part  which  may  be  called  the  primary  diaphragm.  These  two 
parts  at  first  are  not  separate,  the  separation  taking  place  secondarily.  After 


PERICARDIUM,  PLEUROPERITONEUM,  DIAPHRAGM  AND  MESENTERIES.     345 

the  separation  between  the  pericardial  cavity  and  the  pleural  cavities,  the  latter 
for  a  time  remain  in  open  communication  with  the  rest  of  the  coelom  or  peritoneal 
cavity.  The  lungs,  as  they  develop,  grow  into  the  pleural  cavities  (Fig.  294) 
until  their  tips  finally  touch  the  cephalic  surface  of  the  liver.  At  this  point 
folds  grow  from  the  lateral  and  dorsal  body  walls  (Fig.  295)  and  unite  ventrally 
with  the  primary  diaphragm  and  medially  with  the  mesentery.  These  folds — 
the  pleuroperitoneal  membranes — separate  the  pleural  cavities  from  the  perit- 
oneal cavity  and  complete  the  diaphragm.  Thus  the  diaphragm,  from  the  stand- 


Lv.c. 


FIG.  297. 

FIG.  296. — Transverse  section  through  the  thoracic  region  of  a  rabbit  embryo  of  15  days.  Hochstetter. 
FIG.  297. — Transverse  section  through  the  thoracic  region  of  a  cat  embryo  of  25  mm.  Hochstetter. 
I.v.c..  Inferior  vena  cava;  Inf.-c.  1.,  infracardiac  lobe  of  lung;  L.,  lung;  Oe..  oesophagus;  PC.  cav.t 

pericardial  cavity;  PI.  cav.,  pleural  cavity;  Pl.-p.  m.,  pleuro- pericardial  membrane;  Pu.-h.  r., 

pulmo-hepatic  recess. 

point  of  development,  consists  of  two  parts :  a  ventral  part  which  is  the  cephalic 
portion  of  the  original  septum  transversum,  and  a  dorsal  part  which  develops 
later  from  the  body  wall  and  is  the  closing  membrane  between  the  peritoneal 
and  pleural  cavities.  The  musculature  of  the  diaphragm  is  considered  in  the 
chapter  on  the  muscular  system  (p.  269). 

While  the  foregoing  structures  are  being  formed,  decided  changes  take  place 
in  their  positions  and  relations.  At  first  the  heart  lies  far  forward  in  the  cervi- 
cal region  near  the  visceral  arches.  Later  it  migrates  caudally  and  the  pericardial 


346 


TEXT-BOOK  OF  EMBRYOLOGY. 


cavity  comes  to  occupy  much  of  the  ventral  part  of  the  thorax,  the  pericardium 
having  extensive  attachments  to  the  ventral  body  wall  and  to  the  cephalic  sur- 
face of  the  primary  diaphragm  (Fig.  292).  The  diaphragm  is  much  farther 
forward  than  in  the  adult  and  is  broadly  attached  to  the  cephalic  surface  of  the 
liver.  The  principal  changes  which  bring  about  the  adult  conditions  are  the 
growth  of  the  lungs,  the  separation  of  the  diaphragm  from  the  liver,  and  the 

caudal  migration  of  the  diaphragm  itself.  With 
the  development  of  the  lungs,  the  pleura!  cavities 
necessarily  enlarge  and  push  their  way  ventrally. 
In  so  doing  they  split  the  pericardium  away  from 
the  lateral  body  walls  and  likewise  from  the  dia- 
phragm (compare  Figs.  296  and  297).  Thus  the 
pericardial  cavity  comes  to  be  confined  more  and 
more  closely  to  the  medial  ventral  position.  The 
separation  of  the  liver  from  the  primary  diaphragm 
is  caused  by  changes  in  the  peritoneum  which  at 
first  covers  the  caudal,  lateral  and  ventral  surfaces 
of  the  liver.  The  cephalic  surface  of  the  liver,  as 
stated  above,  is  covered  by  the  primary  diaphragm 
itself.  The  peritoneum  is  reflected  from  the  surface 
of  the  liver  on  to  the  diaphragm,  and  at  the  line  of 
reflection  a  groove  appears  on  each  side,  extending 
from  the  midventral  line  around  as  far  as  the 
attachment  of  the  liver  to  the  diaphragm.  The; 
FIG.  298.— Diagram  showing  the  grooves  gradually  grow  deeper,  the  peritoneum 
rum^embry^T^K  Pushing  its  way,  as  a  flat  sac,  between  the  two 
stages.  Mall.  structures,  until  the  separation  is  almost  complete. 

The  positions  are  those  shown    ..„'';.,.,.  - 

in  embryos  of  Mall's  collection   There   is   left,    however,    an   area  of  attachment 
(except  KO,  which  is  a  10.2   betwe8n  the  liver  and  diaphragm,  over  which  the 

mm.  embryo  of  the  His  collec-  _  ^  . 

tion) ;  XII  being  an  embryo  of    peritoneum  is  reflected,  the  ligamentum  coronariunt 

2.1  mm.;   XVIII,  of  7  mm.;     7     .     , .         T       .,  TIT         ^i  «         i         i    r^ 

XIX.  of  5  mm.;  II,  of  7  mm.;   hepotis.     In  the  medial  line  there  is  also  left  a 
IX,  of  17  mm.;  XLIII,  of  15    broad  thin  lamella  which  is  attached  to  the  dia- 

mm.;   VI,  of  24  mm.      The  • 

numerals  on  the  right  indicate    phragm,  the  liver  and  the  ventral  body  wall.     This 

is  a  remnant  of  the  ventral  mesentery  and  forms 

the  ligamentum  suspensorium  (falciforme)  hepatis.  In  its  free  caudal  edge: 
is  embedded  the  ligamentum  teres  hepatis  which  is  closely  related  to  the! 
umbilical  vein  (see  p.  230).  The  diaphragm  itself,  during  its  development,, 
migrates  from  a  position  in  the  cervical  region,  where  the  septum  transversuin » 
first  appears,  to  its  final  position  opposite  the  last  thoracic  vertebrae.  During: 
the  migration  the  plane  of  direction  also  changes  several  times,  as  may  bftf 
seen  in  Fig.  298. 


PERICARDIUM,  PLEUROPERITONEUM,  DIAPHRAGM  AND  MESENTERIES. 

The  Pericardium  and  Pleura.— Since  the  pericardial  cavity  represents  a 
portion  of  the  original  ccelom,  the  lining  of  the  cavity  must  be  a  derivative  of 
either  the  parietal  or  the  visceral  layer  of  mesoderm  or  of  both.  The  common 
mesentery  in  which  the  heart  develops  is  derived  from  the  visceral  layer.  Con- 
sequently the  epicardium  is  a  derivative  of  the  visceral  mesoderm  (Fig.  165). 
The  pericardium  is  derived  from  three  regions  of  mesoderm.  The  greater 
part  is  derived  from  the  parietal  mesoderm,  since  the  body  wall  which  is  com- 
posed of  parietal  mesoderm  is  also  primarily  the  wall  of  the  pericardial  cavity. 
A  small  dorsal  portion  is  probably  derived  from  the  mesoderm  at  the  root  of  the 
dorsal  mesocardium  (Fig.  165).  The  septum  transversum  primarily  forms 
the  caudal  wall  of  the  pericardial  cavity,  and,  since  the  septum  is  a  derivative 
of  the  visceral  layer,  the  caudal  wall  is  derived  from  this  layer.  The  three 
portions  are,  of  course,  Continuous. 

The  lungs  first  appear  in  the  common  mesentery  as  an  evagination  from  the 
primitive  gut  (Fig.  282,  p.  330;.  As  they  develop  further  they  grow  into  the 
pleural  cavities,  pushing  a  part  of  the  mesentery  before  them.  This  part  of 
the  mesentery  thus  invests  the  lungs  and  forms  the  visceral  layer  of  the  pleura 
which  is  therefore  a  derivative  of  the  visceral  mesoderm.  The  parietal  layer  of 
the  pleura  is  a  derivative  of  the  parietal  mesoderm,  since  the  wall  of  the  pleural 
cavity  is  primarily  the  body  wall. 

The  lining  of  all  these  cavities  is  at  first  composed  of  mesothelium  and 
mesenchyme.  The  latter  is  transformed  into  the  delicate  connective  tissue  of 
the  serous  membranes,  and  the  mesothelium  becomes  the  mesothelium  of 
the  membranes. 

The  Omen  turn  and  Mesentery. 

From  the  septum  transversum  (or  diaphragm)  to  the  anus  the  gut  is  sus- 
pended in  the  ccelom  (or  abdominal  cavity)  by  means  of  the  dorsal  mesentery. 
This  is  attached  to  the  dorsal  body  wall  along  the  medial  line  and  lies  in  the 
medial  sagittal  plane  (Fig.  263 ;  compare  with  Fig.  197).     On  the  ventral  side  of 
the  gut  a  mesentery  is  lacking  from  the  anus  to  a  point  just  cranial  to  the  yolk 
;  stalk  (p.  341).     There  is,  however,  a  small  ventral  mesentery  extending  a  short 
j  distance  caudally  from  the  septum  transversum.     On  account  of  its  relation  to 
I  the  stomach  this  is  known  as  the  ventral  mesogastrium  (Fig.  263).     These  two 
|  sheets  of  tissue,  the  dorsal  and  ventral  mesenteries,  are  destined  to  give  rise  to 
;  the  omenta  and  mesenteries  of  the  adult.     Owing  to  the  enormous  elongation  of 
!  the  gut  and  its  extensive  coiling  in  the  abdominal  cavity,  the  primary  mesen- 
teries are  twisted  and  thrown  into  many  folds  which  enclose  certain  pockets  or 
i  bursae.     Furthermore,  certain  parts  of  the  gut  which  are  originally  free  and 
movable  become  attached  to  other  parts  and  to  the  body  walls  through  fusions 
of  certain  parts  of  the  mesentery  with  one  another  and  with  the  body  walls. 


348 


TEXT-BOOK  OF  EMBRYOLOGY. 


The  Greater  Omentum  and  Omental  Bursa. — A  small  part  of  the  gut 
caudal  to  the  diaphragm  is  destined  to  become  the  stomach,  and  the  portion  of 
the  mesentery  which  attaches  it  to  the  dorsal  body  wall  is  known  as  the  dorsal 
mesogastrium  (Fig.  263).  The  latter  is  inserted  along  the  greater  curvature  of 
the  stomach  and  lies  in  the  medial  sagittal  plane  so  long  as  the  stomach  lies  in 
this  plane.  When  the  stomach  turns  so  that  its  long  axis  lies  in  a  transverse 
direction  and  its  greater  curvature  is  directed  caudally  (p.  305),  the  dorsal 
mesogastrium  changes  its  position  accordingly.  From  its  attachment  along  the 
dorsal  body. wall  it  bends  to  the  left  and  then  ventrally  to  its  attachment  along 
the  greater  curvature  of  the  stomach.  Thus  a  sort  of  sac  is  formed  dorsal  to 
the  stomach  (Figs.  299  and  300).  This  sac  is  really  a  part  of  the  abdominal  or 


Stomach 


Stomach 


Duodenum 


Small 
intestine 

Yolk  stalk 


Rectum 


Yolk  stalk 


Rectum 


FlG.  299. 


FIG.  300. 


FIG.  299. — Diagram  of  the  gastrointestinal  tract  and  its  mesenteries 

at  an  early  stage.     Ventral  view.     Hertwig. 
FIG.  300. — Same  at  a  later  stage      Hertwig. 
The  arrow  points  into  the  bursa  omentalis. 

peritoneal  cavity  and  opens  toward  the  right  side.  The  ventral  wall  is  form( 
by  the  stomach,  the  dorsal  and  caudal  walls  by  the  mesogastrium.  The  cavity 
of  the  sac  is  the  omental  bursa  (bursa  omentalis) ;  the  mesogastrium  forms  the 
greater  omentum  (omentum  ma  jus) .  The  opening  from  the  bursa  into  the  general 
peritoneal  cavity  is  the  epiploic  foramen  (foramen  of  Winslow).  (Fig.  276.) 

From  the  third  month  on,  the  greater  omentum  becomes  larger  and  gradually 
extends  toward  the  ventral  abdominal  wall,  over  the  transverse  colon,  and  then 
caudally  between  the  body  wall  and  the  small  intestine  (Figs.  301  and  302). 
The  portion  between  the  body  wall  and  intestine  encloses  merely  a  flat  cavity 
continuous  with  the  larger  cavity  dorsal  to  the  stomach.  From  the  fourth 
month  on,  the  omentum  fuses  with  certain  other  structures  and  becomes  less 
free.  The  dorsal  lamella  fuses  with  the  dorsal  body  wall  on  the  left  side  and 


PERICARDIUM,  PLEUROPERITONEUM,  DIAPHRAGM  AND   MESENTERIES.      349 


with  the  transverse  mesocolon  and  transverse  colon  (Fig.  303).  During  the 
first  or  second  year  after  birth  the  two  lamellae  fuse  with  each  other  caudal 
to  the  transverse  colon  to  form  the  greater  omentum  of  adult  anatomy. 


Diaphragm 

Liver-. __ 
omentum.^ 

Pancreas-..  _ 
Bursa  omentalis 

Stomach 

Greater  omentum 

Duodenum 

Transverse  mesocolon 

Transverse  colon 

Mesentery  of 
small  intestine 

Small  intestine 


FIG. 301. 


Diaph. 


FIG.  302.  FIG.  303. 

FIGS.  301,  302  and  303. — Diagrams  showing  stages  in  the  development  of  the  bursa  omentalis,  the 
greater  omentum,  and  the  fusion  of  the  latter  with  the  transverse  mesocolon.  Diagrams 
represent  sagittal  sections.  For  explanation  of  lettering  in  Figs.  302  and  303  see  Fig.  301. 


' 


•  The  Lesser  Omentum. — It  has  already  been  noted  that  the  liver  grows  into 
the  caudal  portion  of  the  septum  transversum  (p.  344).  Since  the  ventral 
mesentery  in  the  abdominal  region,  or  the  ventral  mesogastrium,  is  primarily 


350  TEXT-BOOK  OF  EMBRYOLOGY. 

directly  continuous  with  the  septum  transversum,  it  is  later  attached  to  the 
liver.  In  other  words  it  passes  between  the  liver  and  the  lesser  curvature  of  the 
stomach  and  also  extends  along  the  duodenal  portion  of  the  gut  for  a  short 
distance  (Fig.  263).  As  the  stomach  turns  to  the  left  the  ventral  mesentery  is 
also  drawn  toward  the  left  and  comes  to  lie  almost  at  right  angles  to  the  sagittal 
plane  of  the  body,  forming  the  lesser  omentum  (omentum  minus)  or  the  hepato- 
gastric  and  hepatoduodenal  ligaments  of  the  adult  (Figs.  303  and  304). 

The  Mesenteries. — So  long  as  the  intestine  is  a  straight  tube,  the  dorsal 
mesentery  lies  in  the  medial  sagittal  plane,  its  dorsal  attachment  being  practi- 
cally of  the  same  length  as  its  ventral  (intestinal)  attachment.  As  development 
proceeds,  the  intestine  elongates  much  more  rapidly  than  the  abdominal  walls, 
and  the  intestinal  attachment  of  the  mesentery  elongates  accordingly.  When 
the  portion  of  the  intestine  to  which  the  yolk  stalk  is  attached  grows  out  into  the 
proximal  end  of  the  umbilical  cord  (p.  307) ,  the  corresponding  portion  of  the 
mesentery  is  drawn  out  with  it  (Fig.  263).  When  the  intestine  returns  to  the 
abdominal  cavity  and  forms  the  primary  loop,  with  the  caecum  to  the  right  side 
(p.  308),  its  mesenteric  attachment  is  carried  out  of  the  medial  sagittal  plane. 
This  results  in  a  funnel-shaped  twisting  of  the  mesentery  (Figs.  299  and  300). 
The  portion  of  the  mesentery  which  forms  the  funnel  is  destined  to  become  the 
mesentery  of  the  jejunum,  ileum,  and  ascending  and  transverse  colon,  and  is 
attached  to  the  dorsal  body  wall  at  the  apex  of  the  funnel  (Fig.  299,  300,  304). 
This  condition  is  reached  about  the  middle  of  the  fourth  month. 

Up  to  this  time  the  mesentery  and  intestine  are  freely  movable,  that  is,  they 
have  formed  no  secondary  attachments.  From  this  time  on,  as  the  intestine 
continues  to  elongate  and  forms  loops  and  coils,  the  mesentery  is  thrown  into 
folds,  and  certain  parts  of  it  fuse  with  other  parts  and  with  the  body  wall. 
Thus  certain  parts  of  the  intestine  become  less  free  or  less  movable  within  the 
abdominal  cavity. 

The  duodenum  changes  from  the  original  longitudinal  position  to  a  more 
nearly  transverse  position  and,  with  its  mesentery — the  mesoduodenum — fuses 
with  the  dorsal  body  wall,  thus  becoming  firmly  fixed.  Since  the  mesoduode- 
num fuses  with  the  body  wall,  the  duodenum  has  no  mesentery  in  the  adult. 
The  pancreas,  which  is  primarily  enclosed  within  the  mesoduodenum,  also 
becomes  firmly  attached  to  the  dorsal  body  wall  (compare  Figs.  301  and  302). 

The  mesentery  of  the  transverse  colon,  or  the  transverse  mesocolon,  which 
lies  across  the  body  ventral  to  the  duodenum  (Figs.  300  and  304),  fuses  with  the 
ventral  surface  of  the  latter  and  with  the  peritoneum  of  the  dorsal  body  wall. 
In  this  way  the  dorsal  attachment  of  the  transverse  mesocolon  is  changed  from 
its  original  sagittal  direction  to  a  transverse  direction  (Figs.  302  and  303).  The 
mesocolon  itself  forms  a  transverse  partition  which  divides  the  peritoneal  cavity 
into  two  parts,  an  upper  (or  cranial)  which  contains  the  stomach  and  liver,  and 


PERICARDIUM,  PLEUROPERITONEUM,  DIAPHRAGM  AND  MESENTERIES.      351 

a  lower  (or  caudal)  which  contains  the  rest  of  the  digestive  tube  except  the 
duodenum.  The  mesentery  of  the  duodenum  and  pancreas  changes  from  a 
serous  membrane  into  subserous  connective  tissue,  and  these  two  organs  as- 
sume the  retroperitoneal  position  characteristic  of  the  adult  (Fig.  301). 

The  mesentery  of  the  descending  colon,  or  the  descending  mesocolon,  lies  in 
the  left  side  of  the  abdominal  cavity,  in  contact  with  the  peritoneum  of  the  body 
wall  (see  Fig.  304).  It  usually  fuses  with  the  peritoneum,  and  the  descending 


Dors,  mesogastrium 


Lesser  omentum 
(hep.-gast.  lig.) 


Bile  duct 


Mesoduodenum        — 


Transv.  colon 


Spleen 


Duo.-jej.  flexure 

Desc.  colon 
Desc.  mesocolon 


Appendix 


Yolk  stalk 


Medial  line 

FIG.  304. — Gastrointestinal  tract  and  mesenteries  in  a  human  embryo.     The  arrow 
points  into  the  bursa  omentalis.     Kollmann. 


colon  thus  becomes  fixed.  After  the  ascending  colon  is  formed,  the  ascending 
mesocolon  usually  fuses  with  the  peritoneum  on  the  right  side  (see  Fig.  304).  In 
a  large  percentage  (possibly  25  per  cent.)  of  individuals,  the  fusion  between  the 
peritoneum  and  the  ascending  and  descending  mesocolon  is  incomplete  or 
wanting. 

The  sigmoid  mesocolon  bends  to  the  left  to  reach  the  sigmoid  colon,  but 
forms  no  secondary  attachments.  It  is  continuous  with  the  mesorectum  which 
maintains  its  original  sagittal  position.  A  sheet  of  tissue — the  mesoappendix — 
continuous  with  and  resembling  the  -mesentery,  is  attached  to  the  caecum  and 
vermiform  appendix  (Fig.  304).  It  probably  represents  a  drawn  out  portion  of 


352  TEXT-BOOK  OF  EMBRYOLOGY. 

the  original  common  mesentery,  since  the  caecum  and  appendix  together  are 
formed  as  an  evagination  from  the  primitive  gut. 

Normally  the  mesentery  of  the  small  intestine  forms  no  secondary  attach- 
ments, but  is  thrown  into  a  number  of  folds  which  correspond  to  the  coils  of  the 
intestine. 

The  secondary  attachments  of  the  greater  omentum  and  the  fusion  of  the 
two  lamellae  have  been  described  earlier  in  this  chapter  (p.  348) .  The  mesen- 
teries of  the  urogenital  organs  are  considered  in  connection  with  the  develop- 
ment of  those  organs  (Chapter  XV). 

The  Peritoneum. — The  thin  layer  of  tissue — composed  of  delicate  fibrous 
connective  tissue  and  mesothelium — which  lines  the  abdominal  cavity  and  is  re- 
flected over  the  various  omenta,  mesenteries  and  visceral  organs,  is  derived 
wholly  from  the  mesoderm.  The  lining  of  the  ccelom  is  composed  of  mesothe- 
lium and  mesenchyme.  The  latter  gives  rise  to  the  connective  tissue  of  the 
serous  membranes,  and  the  mesothelial  layer  becomes  the  mesothelium  of  these 
membranes. 

Anomalies. 

THE  PERICARDIUM. — Anomalous  conditions  of  the  pericardium  are  usually, 
although  not  necessarily,  associated  with  anomalies  of  the  heart.  They  may 
also  be  associated  with  defects  in  the  diaphragm.  Displacement  of  the  heart 
(ectopia  cordis)  is  accompanied  by  displacement  of  the  pericardium.  The 
heart  sometimes  protrudes  through  the  thoracic  wall,  and,  as  a  rule,  in  such  cases 
is  covered  by  the  protruding  pericardium.  In  extensive  cleft  of  the  thoracic 
wall  (thoracoschisis,  Chap.  XX)  the  pericardium  may  be  ruptured. 

THE  DIAPHRAGM. — The  most  common  malformation  of  the  diaphragm  is  a 
defect  in  its  dorsal  part,  occurring  much  more  frequently  on  the  left  than  on  the 
right  side.  The  defect  may  affect  but  a  small  portion  or  may  be  extensive,  the 
peritoneum  being  directly  continuous  with  the  parietal  layer  of  the  pleura. 
Such  defects  are  due  to  the  imperfect  development  of  the  pleuro-peritoneal  mem- 
brane which  normally  grows  from  the  dorso-lateral  part  of  the  body  wall  and 
fuses  with  the  edge  of  the  primary  diaphragm,  thus  separating  the  pleural  and 
and  peritoneal  cavities  (p.  345) .  The  most  conspicuous  result  of  defects  in  the 
dorsal  part  of  the  diaphragm  is  diaphragmatic  hernia,  in  which  parts  of  the 
stomach,  liver,  spleen  and  intestine  project  into  the  pleural  cavity,  either  free  or 
enclosed  in  a  peritoneal  sac.  Defects  in  the  ventral  part  of  the  diaphragm,  due 
to  imperfect  development  of  portions  of  the  septum  transversum,  are  not 
common, 

THE  MESENTERIES  AND  OMENTA. — Extensive  malformations  of  the  mesen- 
teries apparently  do  not  occur  without  extensive  malformations  of  the  digestive 
tract.  One  of  the  most  striking  anomalous  conditions  is  a  retained  embryonic 


f 

PERICARDIUM,  PLEUROPERITONEUM,  DIAPHRAGM   AND  MESENTERIES.      353 

simplicity  of  the  mesentery,  concurrent  with  corresponding  simplicity  in  the 
loops  and  coils  of  the  intestine.  In  this  anomaly  the  intestine  has  failed  to 
arrive  at  its  usual  complicated  condition  and  the  mesentery  has  not  undergone 
the  usual  processes  of  folding  and  fusion  (p.  350  et  seq.).  Minor  variations  in 
the  mesenteries  and  omenta  are  probably  due  largely  to  imperfect  fusion  of 
certain  parts  with  one  another  and  with  the  body  wall.  It  is  not  uncommon  to 
find  the  ascending  or  descending  colon,  or  both,  more  or  less  free  and  mov- 
able. This  condition  is  due  to  imperfect  fusion  of  the  mesocolon  with  the  body 
wall  (p.  351).  If  the  greater  omentum  is  wholly  or  partially  divided  into  sheets 
of  tissue,  the  two  primary  lamellae  have  failed  to  fuse  completely  (p.  349). 
This  divided  condition  is  normal  in  many  Mammals. 

References  for  Further  Study. 

•»ib 
BRACKET,  A.:  Recherches  sur  le  developpement  du  diaphragme  et  du  foie.    Jour,  de 

VAnat.  et  de  la  Physiol.,  T.  XXXII,  1895. 

BROMAN,  J.:  Die  Entwickelungsgeschichte  der  Bursa  omentalis  und  ahnlicher  Recess* 
bildungen  bei  den  Wirbeltieren.     Wiesbaden,  1904. 

BROMAN,  I.:  Ueber  die  Entwickelung  und  Bedeutung  der  Mesenterien  und  der  Korper- 
hohlen  bei  den  Wirbeltieren.     Ergebnisse  der  Anat.  u.  Entwick.,  Bd.  XV,  1906. 

BROSSIKE,  G.:  Ueber  intraabdominale  (retroperitoneale)  Hernien  und  Bauchfelltaschen, 
nebst  einer  Darstellung  der  Entwickelung  peritonealer  Formationen.     Berlin,  1891. 

HERTWIG,  O. :  Lehrbuch  der  Entwickelungsgeschichte  des  Menschen  und  der  Wirbeltiere. 
Jena,  1906. 

KEIBEL,  F.,  and  MALL,  F.  P.:  Manual  of  Human  Embryology,  Vol.  I,  1910. 

KLAATSCH:  Zur  Morphologic  der  Mesenterialbildungen  am  Darmkanal  der  Wirbeltiere. 
Morph.  Jahrbuch,  Bd.  XVIII,  1892. 

KOLLMANN,  J.:  Lehrbuch  der  Entwickelungsgeschichte  des  Menschen.     Jena,  1898. 

KOLLMANN,  J.:  Handatlas  der  Entwickelungsgeschichte  des  Menschen.     Bd.  II,  1907. 

MALL,  F.  P.:  Development  of  the  Human  Ccelom.    Jour,  of  Morphol.,  Vol.  XII,  1897. 

MALL,  F.  P.:  On  the  Development  of  the  Human  Diaphragm.  Johns  Hopkins 
Hospital  Bulletin,  Vol.  XII,  1901. 

PIERSOL.  G.  A.:  Teratology.  In  Wood's  Reference  Handbook  of  the  Medical  Sciences. 
1904. 

RAVN,  E.:  Ueber  die  Bildung  der  Scheidewand  zwischen  Brust-  und  Bauchhohle  in 
Saugetierembryonen.  Arch.  f.  Anat.  u.  Physiol.,  Anat.  Abth.,  1889. 

STRAHL  and  CARIUS:  Beitrage  zur  Entwickelungsgeschichte  des  Herzens  und  der 
Korperhohlen.  Arch.  /.  Anat.  u.  Physiol.,  Anat.  Abth.,  1889. 

SWAEN,  A.:  Recherches  sur  le  developpement  du  foie,  du  tube  digestif,  de  1'arriere- 
cavite  du  peritoine  et  du  mesentere.  Premiere  partie,  Lapin.  Jour,  de  VAnat.  et  de  la 
Physiol.,  T.  XXXIII,  1896.  Seconde  partie.  Embryons  humains.  T.  XXXIII,  1897. 

TOLDT,  C.:  Bau  und  Wachstumsveranderung  der  Gekrose  des  menschlichen  Darm- 
kanals.  Denkschr.  der  kais.  Akad.  Wissensch.  Wien.  Math.-Naturwissen.  Classe,  Bd 
XLI,  1879. 


CHAPTER  XV. 
THE  DEVELOPMENT  OF  THE  UROGENITAL  SYSTEM. 

No  other  system  in  the  body  presents  such  peculiarities  of  development  as 
the  urogenital  system.  In  the  first  place,  it  is  exceedingly  complicated  on  ac- 
count of  its  many  parts.  It  is  derived  from  both  mesoderm  (mesothelium  and 
mesenchyme)  and  entoderm.  The  urinary  portion  develops  into  a  great  com- 
plex of  ducts  for  the  carrying  off  of  waste  products.  The  genital  portion  in 
both  sexes  becomes  highly  specialized  for  the  production  and  carrying  off 
of  the  sexual  elements.  In  the  second  place,  instead  of  one  set  of  urinary  organs 
developing  and  persisting,  three  sets  develop  at  different  stages.  The  first 
set  (the  pronephroi)  disappears  in  part,  but  leaves  certain  structures  which  are 
used,  so  to  speak,  in  the  development  of  the  second.  The  second  set  (the  meso- 
nephroi)  disappears  for  the  most  part,  leaving,  however,  some  portions  which 
are  taken  up  in  the  development  of  the  genital  organs  and  other  portions  which 
persist  as  rudimentary  structures  in  the  adult.  The  third  set  (the  metanephroi 
or  kidneys)  develops  in  part  from  the  second  and  in  part  is  of  independent 
origin.  These  conditions"  afford  one  of  the  most  striking  examples  of  the  repe- 
tition of  the  phylogenetic  history  by  the  ontogenetic,  or,  in  other  words,  of  von 
Baer's  law  that  an  individual,  in  its  development,  has  a  tendency  to  repeat  its 
ancestral  history;  for  the  first  and  second  sets  of  urinary  organs  in  the  human 
embryo  represent  systems  that  are  permanent  in  the  lower  Vertebrates.  In  the 
third  place,  the  ducts  of  the  genital  organs  are  not  homologous  in  the  two  sexes. 
In  the  male  the  ducts  (deferent  duct,  duct  of  the  epididymis,  efferent  ductules) 
are  derived  from  the  second  set  of  urinary  organs;  in  the  female  they  (the 
oviducts)  are  derived  from  other  ducts  which  develop  in  the  second  set  of 
urinary  organs,  but  which  are  not  functionally  a  part  of  the  latter. 

THE  PRONEPHROS. 

The  pronephros,  with  the  pronephric  duct,  is  the  first  of  the  urinary  organs 
to  appear.  In  embryos  of  2-3  mm.  there  are  two  pronephric  tubules  on  each 
side,  situated  at  the  level  of  the  heart.  Although  their  mode  of  origin  has  not 
been  observed  in  the  human  embryo,  it  is  probable,  judging  from  observations 
on  lower  Vertebrates,  that  they  arise  as  evaginations  of  the  mesothelium.  The 
part  of  the  mesothelium  involved  is  that  adjacent  to  the  intermediate  cell  mass 
(Fig.  305) .  (The  intermediate  cell  mass  is  the  portion  of  the  mesoderm  interven- 
ing between  the  primitive  segments  and  the  unsegmented  parietal  and  visceral 

354 


THE  DEVELOPMENT  OF  THE  UROGENITAL  SYSTEM.  355 

layers;  p.  99.)  The  more  cephalic  of  the  two  tubules  becomes  hollow  and 
opens  into  the  ccelom;  the  more  caudal  is  merely  a  solid  cord  of  cells.  Neither 
tubule  forms  any  connection  with  the  pronephric  duct.  At  each  side  of  the  root 
of  the  mesentery  a  small  elevation,  which  projects  into  the  ccelom,  probably 
represents  a  rudimentary  glomerulus.  A  glomerulus  in  the  lower  Vertebrates, 
where  the  pronephros  develops  to  a  much  greater  degree  than  in  Mammals, 
contains  tortuous  vessels  derived  from  branches  of  the  aorta  (Fig.  306). 
The  mesonephros  (p.  359),  beginning  to  develop  almost  as  soon  as  the  pro- 
nephros and  in  the  same  relative  position,  forms  a  ridge  which  projects  into  the 
coelom.  The  pronephric  tubules  thus  become  embedded  in  the  mesonephric 
ridge. 

The  pronephric  duct  begins  to  develop  about  the  same  time  as  the  tubules. 
It  appears  as  a  longitudinal  ridge  on  the  outer  side  of  the  intermediate  cell  mass 

Sclerotome       Myotome 


Visceral 
mesoderm 


Pronephric 
tubule 

FIG.  305. — Transverse  section  of  a  dog  embryo  with  19  primitive  segments.     Bonnet. 
Section  taken  through  sixth  segment. 

at  the  level  of  the  heart  and  projects  into  the  space  between  the  mesoderm  and 
ectoderm.  The  ridge  is  at  first  solid  but  soon  acquires  a  lumen,  and  gradually 
extends  to  the  caudal  end  of  the  embryo  where  it  bends  medially  to  open  into 
the  gut.  The  origin  of  the  caudal  portion  of  the  duct  is  a  matter  of  dispute. 
It  comes  in  contact  and  fuses  with  the  ectoderm,  but  whether  in  the  higher  ani- 
mals the  fusion  is  secondary  or  signifies  a  derivation  from  the  ectoderm  has 
not  been  determined.  When  first  formed,  the  entire  duct  lies  on  the  outer  side 
of  the  intermediate  cell  mass,  but  later  becomes  embedded  in  the  mesonephric 
ridge. 

The  pronephric  tubules  are  but  transient  structures  and  have  no  functional 
significance  in  man  and  the  higher  Vertebrates.  The  ducts,  however,  remain 
and  become  the  ducts  of  the  second  set  of  urinary  organs,  the  mesonephroi. 

The  significance  of  the  pronephros  can  be  understood  only  by  reference  to  the  conditions 
in  the  lower  animals.  In  the  latter  the  pronephros  acquires  a  relatively  higher  degree  of  de« 


356  TEXT-BOOK  OF  EMBRYOLOGY. 

velopment  than  in  the  higher  forms.  The  tubules  are  segmentally  arranged  and  are  preset 
in  many  segments  of  the  body.  They  open  at  their  outer  ends  into  the  ducts,  and  at  their 
inner  ends  into  the  coelom  through  ciliated  funnel-shaped  mouths  or  nephrostomes.  Little 
masses  of  mesoderm,  containing  tortuous  vessels  derived  from  branches  of  the  aorta,  form 
glomeruli  which  project  into  the  ccelom.  Waste  products  are  removed  from  the  blood 
through  the  agency  of  the  glomeruli  and  are  collected  in  the  ccelom.  They  are  then  taken  up 
by  the  pronephric  tubules  and  carried  away  by  the  ducts.  In  some  of  the  Round  Worms 
there  is  not  even  a  longitudinal  duct,  but  the  tubules  open  directly  on  the  outer  surface  of 
the  body.  In  the  lowest  Fishes  all  the  tubules  on  each  side  open  into  a  longitudinal  duct 
which  opens  into  the  cloaca.  In  these  lower  forms  of  animal  life  the  pronephroi  constitute 
the  permanent  urinary  apparatus.  In  the  ascending  scale  the  mesonephroi  appear  (higher 


^:   u-j     r-k    ~Nch- 

Pron.  t. 


Glom. 


FIG.  306. — Diagram  of  the  pronephric  system  in  an  amphibian.     Bonnet. 

CceL,  Coelom;  Glom.,  glomerulus,  containing  ramifications  of  a  branch  of  the  aorta; 

Nch.,  notochord;  Pron.  t.,  pronephric  tubule. 

Fishes,  Amphibia)  and  assume  the  function  of  carrying  off  waste  products.  The  prone- 
phroi also  develop,  but  to  a  lesser  degree.  Still  higher  in  the  scale  (Reptiles,  Birds,  Mam- 
mals) the  kidneys  (metanephroi)  appear  and  the  mesonephroi  lose  their  functional  sig- 
nificance. But  even  in  the  very  highest  Mammals  the  pronephroi  appear,  in  a  very  rudimen- 
tary form,  in  each  individual  in  the  earliest  embryonic  stages,  thus  repeating  the  ancestral 
history. 

THE  MESONEPHROS.- 

The  mesonephroi,  which  constitute  the  second  set  of  urinary  organs,  appear 
in  embryos  of  2.6-3.0  mm.,  immediately  following  the  pronephroi.  They  be- 
gin to  develop  just  caudal  to  the  pronephric  tubules  and  in  the  same  relative 
position  as  the  latter,  that  is,  in  the  intermediate  cell  mass.  Condensations* 
appear  in  the  mesenchyme  and  become  more  or  less  tortuous.  At  their  inner 
ends  they  form  secondary  connections  with  the  mesothelium  and  at  their  outer 
ends  they  join  the  pronephric  duct  which  now  becomes  the  mesonephric  (or 
Wolffian)  duct.  The  cells  acquire  an  epithelial  character,  lumina  appear, 
and  the  tortuous  mesenchymal  condensations  thus  become  true  tubules.  Their 
connections  with  the  mesothelium  soon  disappear  (Fig.  307). 

*The  term  "  condensation "  is  here  used  to  mean  increased  density  of  tissue  due  mainly  to 
proliferation  of  cells. 


THE  DEVELOPMENT  OF  THE  UROGENITAL  SYSTEM. 


357 


After  the  tubules  are  formed,  other  condensations  of  the  mesenchyme  appear 
near  their  inner  ends.  A  branch  from  the  aorta  enters  each  condensation  and 
breaks  up  into  a  number  of  smaller  vessels  which  ramify  inside,  the  entire 
structure  thus  becoming  a  glomerulus.  Each  glomerulus  pushes  against  the 
corresponding  tubule,  the  latter  becoming  flattened  and  then  growing  around 
the  glomerulus.  In  this  way  the  glomerulus  becomes  surrounded  by  two  layers 
of  epithelium,  except  at  the  point  where  the  vessels  enter,  and  the  whole  structure 
—the  Malpighian  corpuscle — resembles  very  closely  a  renal  corpuscle  of  the  adult 

Roof        Spinal 

plate      ganglion       Amnion 


Floor  plate 
Notochord 

Aorta 
Glomerulus 

Mesentery 
Intestine 


Post,  cardinal  vein 


Mesonephric 
(Wolffian)  duct 


Blood  vessel 

Mesonephric 
(Wolffian)  ridge 


Coelorn 

Body  wall  with 
umbilical  vein 


FIG.  307. — From  a  transverse  section  of  a  sheep  embryo  of  21  days  (15  mm.), 
showing  the  developing  mesonephros.     Bonnet. 


kidney.  Waste  products  are  removed  from  the  blood  through  the  agency  of 
the  glomeruli  and  are  carried  to  the  ducts  by  the  mesonephric  tubules  (Fig.  307). 
The  tubules  themselves  increase  in  length  and  become  much  coiled.  Sec- 
ondary and  tertiary  tubules  also  develop  and  become  branches  of  the  primary. 
Whether  these  develop  from  condensations  of  the  mesenchyme  or  as  buds  from 
the  primary  tubules  has  not  been  determined.  Each  tubule  consists  of  two 
parts — (i)  a  dilated  part  around  the  glomerulus,  composed  of  large  flat  cells 
and  forming  Bowman's  capsule,  and  (2)  a  narrower  coiled  part  leading  from 


358 


TEXT-BOOK  OF  EMBRYOLOGY. 


the  glomerulus  to  the  duct  and  composed  of  smaller  cuboidal  cells  (Fig.  307). 
The  primary  mesonephric  tubules  are  arranged  segmentally,  one  appearing 
in  each  segment  as  far  back  as  the  pelvic  region.  Thus  the  intermediate  cell 
mass  may  be  considered  as  a  series  of  nephrotomes,  corresponding  to  the 
sclerotomes  and  myotomes.  The  segmental  character  is  soon  lost,  however, 
owing  to  the  inequality  of  growth  between  the  mesonephros  and  the  other  seg- 
mental structures,  and  to  the  development  of  the  secondary  and  tertiary  tubules. 
As  stated  above,  the  first  mesonephric  tubules  appear  immediately  caudal  to 


Hind-brain 
Branchial  groove  I 

Hea 
Intestine 

Mesonephros 

Coelom 

Lower  limb  bud 


Mid-brain 


Fore-brain 


Lung 

Genital  ridge 

Body  wall 
Genital  eminence 

Tail 


FIG.  308.— Human  embryo  of  5  weeks.     The  ventral  body  wall  has  been  removed 
to  disclose  the  mesonephroi.     Kollmann. 

the  pronephros  From  this  point  their  formation  gradually  progresses  in  a 
caudal  direction  as  far  as  the  pelvic  region.  By  the  further  development  of  the 
primary  and  by  the  addition  of  the  secondary  and  tertiary  tubules  and  the 
glomeruli,  the  mesonephros  as  a  whole  increases  in  size  and  forms  a  large 
structure  which  projects  into  the  ccelom  on  each  side  of  the  body,  forming  the 
so-called  mesonephric  or  Wolffian  ridge.  It  reaches  the  height  of  its  develop- 
ment in  the  human  embryo  about  the  fifth  or  sixth  week,  at  which  time  it  ex- 
tends from  the  region  of  the  heart  to  the  pelvic  region  (Fig.  308).  Each  organ 


THE  DEVELOPMENT  OF  THE  UROGENITAL  SYSTEM. 


359 


is  attached  to  the  dorsal  body  wall  by  a  distinct  mesentery  which,  at  its  cephalic 
end,  also  sends  off  a  band  to  the  diaphragm — the  diaphragmatic  ligament  of 
the  mesonephros.  The  peritoneum  is  reflected  over  the  surface  of  the  meso- 
nephros,  and  on  the  ventro-medial  side  the  mesothelium  becomes  thickened  to 
form  the  genital  ridge  (p.  374;  Figs.  276  and  308).  The  mesonephric  ducts  are 
embedded  in  the  lateral  parts  of  the  organs  and  extend  throughout  practically 
T  their  entire  length.  Since  the  ducts  are  identical  with  the  pronephric  ducts, 
they  open  at  first  into  the  caudal  end  of  the  gut,  or  cloaca  (p.  355;  Fig.  322). 
At  a  little  later  period,  when  the  urogenital  sinus  is  formed,  they  open  at  the 
junction  of  the  latter  with  the  bladder  (Fig.  325).  Still  later  they  open  into  the 


Appendage 
of  testicle 


Testicle 


Appendage  of  epididymis 


Mesonephric  duct 
'  (duct  of  epididymis) 


-  -Paradidymis 


...  Aberrant  ductule- 


Mullerian  duct 


Urogenital  sinus 

FIG.  309. — Diagram  representing  certain  persistent  portions  of  the  mesonephros 
in  the  male  (see  table).     Kottmann. 

sinus  itself  (p.  3  70) .  A  description  of  their  further  development  is  best  deferred 
to  the  section  on  the  male  genital  organs,  since  they  become  the  genital  ducts 
(p.  386). 

The  mesonephroi  function  as  urinary  organs  during  the  period  of  their 
existence  in  the  embryos  of  all  higher  Vertebrates.  Excretory  products  are  con- 
veyed directly  to  the  tubules  by  means  of  the  glomeruli  instead  of  being  de- 
posited in  the  ccelom  and  then  taken  up  by  the  tubules,  as  is  the  case  in  func- 
tional pronephroi  (p.  356).  The  main  excretory  ducts  are  the  same  as  in  the 
pronephroi.  Aside  from  the  vessels  in  the  glomeruli  the  mesonephroi  are  ex- 
ceedingly vascular  organs.  Large  and  small  branches  of  the  posterior  cardinal 
veins  ramify  among  the  tubules  (Figs.  276  and  194).  The  blood  undergoes 


360 


TEXT-BOOK  OF  EMBRYOLOGY. 


purifying  processes  in  its  close  contact  with  the  tubules  and  is  returned  to  the 
heart  by  the  posterior  cardinals,  or,  after  the  cephalic  ends  of  the  latter  atrophy, 
by  the  subcardinals  and  the  inferior  vena  cava  (see  p.  225;  also  Fig.  194,  B). 
There  is  thus  present  a  true  renal  portal  system,  similar  to  the  hepatic  portal 
system. 

Although  the  mesonephroi  become  large  functional  organs  during  the  earlier 
stages  of  development,  they  atrophy  and  disappear  for  the  most  part,  coinci- 
dently  with  the  appearance  and  development  of  the  kidneys.  The  degeneration 
begins  during  the  sixth  or  seventh  week  and  goes  on  rapidly  until,  by  the  end  of 
the  fourth  month,  little  remains  but  the  ducts  and  a  few  tubules.  The  degenera- 


o.  t.  a. 


Ovd. 


Epo.  1. 


Epo.  t. 


FIG.  310. — Diagram  representing  certain  persistent  portions  of  the  mesonephros 

in  the  female  (see  table). 

Epo.  /.,  Longitudinal  duct  of  the  epoophoron;  Epo.  t.,  transverse  ductules  of  the  epoophoron;  O.  t.  a.t 
ostium  abdominale  tubae;  Ovd.,  oviduct;  X  represents  a  small  duct  which,  if  present,  leads 
from  the  epoophoron  to  one  of  the  fimbriae  of  the  oviduct. 

live  processes  consist  of  (i)  an  ingrowth  of  connective  tissue  among  the  tubules, 
(2)  atrophy  of  the  epithelium  of  the  tubules,  and  (3)  atrophy  of  the  glomeruli, 
The  portions  which  remain  differ  in  the  two.  sexes,  and  since  the  remnants 
are  taken  up  in  the  formation  of  the  male  and  female  genital  organs  it  seems 
best  to  discuss  them  more  fully  under  those  heads  (pp.  383,386).  The  accom- 
panying table,  however,  will  give  a  clue  to  their  fate  (see  also  Figs.  309  and 
310).  A  more  comprehensive  table  will  be  found  on  p.  393. 

Male  Female 


Mesonephros 


j  Cephalic  part 


{  Caudal  part 


Duct  of  mesonephros 


(Efferent      ductules 
(vasa  efferentia) 

J  Paradidymis 
|  Vasa  aberrantia 
Deferent  duct 
Ejaculatory  duct 
Seminal  vesicles 


Epoophoron 


Paroophoron 


Gartner's  canals 


The  significance  of  the  mesonephroi,  which,  as  well  as  the  pronephroi,  are  present  in  the 
embryos  of  ail  higher  Vertebrates,  can  be  understood  only  by  referring  to  the  conditions  in  the 
lower  Vertebrates.  In  the  majority  of  the  Fishes  and  in  the  Amphibia  the  mesonephroi  con- 
stitute the  functional  urinary  organs  of  the  adult  and  possess  essentially  the  same  structure  35 


THE  DEVELOPMENT  OF  THE  UROGENITAL  SYSTEM 


361 


in  the  embryos  of  higher  forms.  Beginning  in  the  Reptiles  and  continuing  up  through  the 
series  of  Birds  and  Mammals,  another  set  of  urinary  organs — the  kidneys — develops.  The 
mesonephroi  also  develop  in  these  forms,  even  to  a  high  degree,  thus  repeating  the  ancestral 
history,  but  retain  their  original  function  only  in  the  earlier  embryonic  stages. 

THE  KIDNEY  (METANEPHROS). 

The  kidneys  are  the  third  set  of  urinary  organs  to  develop.  They  assume 
the  function  of  the  mesonephroi  as  the  latter  atrophy,  and  constitute  the  per- 
manent urinary  apparatus.  Each  kidney  is  derived  from  two  separate  anlagen 
which  unite  secondarily.  The  epithelium  of  the  ureter,  renal  pelvis,  and 
straight  renal  tubules  (collecting  tubules)  is  derived  from  the  mesonephric  duct 


Mesonephros 


Mesonephric  duct 


Metanephric  blastema 


Metanephric  blastema 
(inner  zone) 

Primitive  renal  pelvis 


Cloacal  membrane 


Urete 


FIG.  311. — From  a  reconstruction  of  the  anlage  of  the  kidney  (metanephros) ,  etc.,  of  a  human 
embryo  at  the  beginning  of  the  $th  week.     Schreiner. 

by  a  process  of  evagination.  The  convoluted  renal  tubules  and  glomeruli  are 
derived  directly  from  the  mesenchyme,  and  in  this  respect  resemble  the  meso- 
nephric tubules  and  glomeruli. 

The  Ureter,  Renal  Pelvis  and  Straight  Renal  Tubules.— During  the 
fourth  week  (in  embryos  of  about  5  mm.)  a  small,  hollow,  bud-like  evagination 
appears  on  the  dorsal  side  of  each  mesonephric  duct  near  its  opening  into  the 
cloaca.  The  evagination  continues  to  grow  dorsally  in  the  mesenchyme 
toward  the  vertebral  column,  and  at  the  same  time  becomes  differentiated 
into  two  parts,  a  narrow  stalk  and  a  dilated  terminal  portion.  The  stalk  is 
the  forerunner  of  the  ureter,  the  dilated  end  is  the  primitive  renal  pelvis  (Figs. 
311  and  313).  When  the  dilated  end  reaches  the  ventral  side  of  the  vertebral 


362 


TEXT-BOOK  OF  EMBRYOLOGY. 


column  it  turns  and  grows  cranially  between  the  latter  and  the  mesonephros. 
The  stalk  (or  ureter)  elongates  accordingly  (Fig.  312). 

About  the  fifth  week,  four  evaginations  from  the  primitive  renal  pelvis  appear 
— one  cephalic,  one  caudal  and  two  central  (Figs.  312  and  314) .  These  may  be 
considered  as  straight  renal  tubules  of  the  first  order.  The  distal  end  of  each 
then  enlarges  to  form  a  sort  of  ampulla,  and  from  each  ampulla  two  other 
evaginations  develop,  forming  tubules  of  the  second  order.  From  the  ampulla 
of  each  secondary  tubule  two  tertiary  tubules  grow  out;  and  this  process  con- 


Mesonephros 


Mesonephric  duct 


Junction  of  meson, 
duct  and  ureter 


Cephalic  evagination 

Metanephric  blastema 
Central  evaginations 


\ —  Caudal  evagination 


FIG.  312. — From  a  reconstruction  of  the  anlage  of  the  kidney,  etc.,  of  a  human 
embryo  of  11.5  mm.     Schreiner. 

tinues  in  a  similar  manner  until  twelve  or  thirteen  divisions  occur,  the  final 
divisions  occurring  during  the  fifth  month.  The  tubules  grow  into  the  mesen- 
chyme  which  surrounds  the  pelvis  and  which  forms  the  so-called  metanephric 
blastema,  or  nephro genie  tissue  (Fig.  313).  LcMju&*  &*oU/>) 

If  the  straight  tubules  were  to  remain  in  this  condition,  only  four  would  open 
directly  into  the  pelvis,  corresponding  with  the  four  primary  evaginations.  In 
the  adult,  however,  many  hundreds  open  into  the  pelvis;  consequently  extensive 
changes  of  the  early  condition  must  take  place.  These  changes  are  similar  to 


THE  DEVELOPMENT  OF  THE  UROGENITAL  SYSTEM. 

the  process  by  which  the  proximal  ends  of  some  of  the  blood  vessels  come  to  be 
included  in  the  wall  of  the  heart  (p.  214).  The  proximal  ends  of  the  tubules 
become  wider,  the  pelvis  swells  out,  and  the  walls  of  the  tubules  become  in- 
cluded in  the  wall  of  the  pelvis.  In  certain  parts  of  the  pelvic  wall  this  process 
goes  on  until  deep  bays — the  calyces — are  formed,  into  which  a  large  number  of 
tubules  open.  In  the  other  parts  of  the  wall  the  process  does  not  go  so  far,  thus 
leaving  promontories — the  renal  papilla — upon  which  larger  tubules  or  papil- 
lary ducts  open.  The  adult  renal  pelvis  thus  consists  of  the  primitive  pelvis  plus 
the  proximal  ends  of  the  straight  tubules. 


Metanephric 
blastema 


Primitive 
renal  pelvis 


Ureter 

Mesonephric  duct 
Intestine 

Bladder 


FIG.  313. — From  a  transverse  section  of  a  human  embryo  at  the  beginning  of  the  5th  week. 
The  plane  of  the  section  is  indicated  in  Fig.  311.     Schreiner. 


The  Convoluted  Renal  Tubules  and  Glomeruli.— As  stated  above, 
the  metanephric  blastema  or  nephrogenic  tissue  surrounds  the  renal  pelvis 
and  the  straight  tubules.  It  represents  a  condensation  of  the  mesenchyme  and  is 
destined  to  give  rise  to  the  convoluted  tubules  and  glomeruli.  The  cells  of  the 
blastema  in  the  region  of  the  ampullae  of  the  terminal  straight  tubules  acquire 
an  epithelial  character  and  become  arranged  in  solid  masses  (Fig.  315).  Each 
mass  unites  with  an  ampulla  and  acquires  a  lumen,  which  becomes  continuous 
with  the  lumen  of  the  straight  tubule,  then  elongates  and  forms  an  S-shaped 
structure  (Figs.  316  and  317).  The  loop  of  the  S  nearer  the  straight  tubules 
elongates  still  more  and  grows  toward  the  pelvis,  parallel  with  the  straight 


364  TEXT-BOOK  OF  EMBRYOLOGY. 

tubules,  to  form  Ifenle's  loop.  The  part  between  Henle's  loop  and  the  straight 
tubule  elongates  and  becomes  convoluted  to  form  the  proximal  part  of  a  con- 
voluted renal  tubule  (second  convoluted  tubule) .  The  part  between  the  distal 
end  and  Henle's  loop  elongates  and  becomes  convoluted  to  form  the  distal  part 
of  a  convoluted  renal  tubule  (first  convoluted  tubule)  (Figs.  318  and  319). 

To  avoid  confusion  it  may  be  well  to  call  attention  to  the  fact  that  what  has  here  been 
called  the  proximal  part  of  a  convoluted  tubule  corresponds  with  what  is  usually  described  as 
the  second  or  distal  convoluted  tubule,  and  that  the  distal  part  of  a  convoluted  tubule 
corresponds  with  the  first  or  proximal  convoluted  tubule.  In  histology  the  distal  and  proxi- 
mal convoluted  tubules  are  spoken  of  in  relation  to  the  renal  corpuscle,  but  in  development 
it  is  more  convenient  to  speak  of  the  terminal  part  of  a  tubule  as  its  distal  part. 


Caudal 
evagination 


Ureter 


FIG.  314. — From  a  model  of  the  primitive  renal  pelvis  and  the  evaginations  which  form  the  cephalic, 
central  and  caudal  straight  renal  tubules  of  the  fir~st  order.  Human  embryo  of  4!  months. 
Compare  with  Fig.  350.  Schreiner 

A  glomerulus  develops  in  connection  with  the  extreme  distal  end  of  a  con- 
voluted tubule  or,  in  other  words,  with  the  distal  loop  of  the  S  (p.  363).  There 
occurs  here  a  further  condensation  of  the  mesenchyme,  into  which  grows  a 
branch  from  the  renal  artery.  This,  as  the  afferent  vessel  of  the  glomerulus, 
breaks  up  into  several  arterioles,  each  of  which  gives  rise  to  a  tuft  of  capillaries. 
These  tufts  are  separated  from  one  another  by  somewhat  more  mesenchymal 
tissue  than  separates  the  capillaries  within  a  tuft.  The  tufts  with  the  asso- 
ciated mesenchymal  tissue  constitute  a  glomerulus,  and  it  is  the  mesenchymal 
septa  between  the  tufts  that  give  to  the  glomerulus  its  characteristic  lobula.ted 
appearance.  The  capillaries  of  each  tuft  empty  into  an  arteriole,  and  the 
several  arterioles  unite  to  form  the  efferent  vessel  of  the  glomerulus,  which  passes 
out  along  side  of  the  afferent  vessel.  The  renal  tubule  becomes  flattened  on  the 
side  next  the  condensation  of  the  mesenchyme,  and  as  the  glomerulus  develops, 
the  epithelium  of  the  tubule  grows  around  it  except  at  the  point  where  the  blood 


THE  DEVELOPMENT  OF  THE  UROGENITAL  SYSTEM. 


365 


vessels  enter  and  leave.  Thus  a  double  layer  of  epithelium  comes  to  surround 
the  glomerulus,  the  space  between  the  two  layers  being  the  extreme  distal  part 
of  the  lumen  of  a  renal  tubule.  The  inner  layer  is  closely  applied  to  the  surface 


Anlagen  of 
convoluted 
renal  tubules 


Renal  pelvis 


Capsule 


Anlage  of 

convoluted  renal  tubule 

Ampulla  of 
straight  renal  tubule 


FIG.  315. — Sagittal  section  of  the  anlage  of  the  left  kidney  in  a  rabbit  embryo  of  15  days.  Schreiner. 
The  straight  renal  tubules  (sections  of  which  are  shown)  are  embedded  in  the  metanephric  blastema. 

Condensations  of  the  latter  form  the  anlagen  of  the  convoluted  renal  tubules.     At  the  left 

of  the  figure  several  mesonephric  tubules  are  shown. 


Amp. 


Con.  r.  t. 


Met.  bl. 


Con.  r.  t. 


FIG.  316. — From  a  section  of  the  kidney  of  a  human  foetus  of  7  months.     Schreiner. 

Amp.,  Ampulla  of  a  straight  renal  tubule;  Con.  r.  t.,  anlagen  of  convoluted  renal  tubules,  above  and 

between  which  are  two  ampullae  (compare  Fig.  317);  met.  bl.,  metanephric  blastema. 

of  the  glomerulus  and  even  dips  down  into  the  latter  between  the  tufts.  The 
outer  layer  forms  Bowman's  capsule,  the  flat  epithelium  of  which  passes  over 
into  the  cuboidal  epithelium  of  the  "neck"  of  the  tubule,  and  this  in  turn  is 


366 


TEXT-BOOK  OF  EMBRYOLOGY. 


Prox.  convoluted  tubule 
Dist.  convoluted  tubule 
Henle's  loo 


FIG.  317, 


Ampulla  of  straight  tubule 


Henle's  loop 

Distal  part  of 
convoluted  tubule 


Bowman's  capsule 


Proximal  part  of 
convoluted  tubule 


Distal  part  of 
convoluted  tubule 


"Neck" 
Bowman's  capsule 


FIG.  318. 


Prox.  convoluted  tubule 
Dist.  convoluted  tubule 
Henle's  loop 


Prox.  convoluted  tubule 

Bowman's  capsule 

Straight  tubule 


Prox.  convoluted  tubule 
Dist.  convoluted  tubule 

Prox.  convoluted  tubule 

Dist.  Convoluted  tubule 
Bowman's  capsule 


Ascending     ~\ 

>•  arm  of  Henle's  loop 
Descending  J 


FIG.  319 

FIGS.  317,  318  and  319. — From  reconstructions  of  convoluted  renal  tubules  in  successive 
stages  of  development.     Stoerk. 


THE  DEVELOPMENT  OF  THE  UROGENITAL  SYSTEM.  367 


continuous  with  the  pyramidal  epithelium  of  the  distal  convoluted  tubule. 
The  entire  structure  is  a  renal  corpuscle.  The  formation  of  renal  corpuscles 
begins  in  embryos  of  30  mm.  and  continues  until  after  birth. 

The  Renal  Pyramids  and  Renal  Columns. — The  tubules  arising  from 
the  four  primary  evaginations  of  the  renal  pelvis  together  form  four  distinct 
groups  or  primary  renal  (Malpighian)  pyramids — one  cephalic,  one  caudal,  and 
two  central.  The  central  pyramids  are  crowded  in  between  the  end  pyramids, 
(cephalic  and  caudal)  and  do  not  develop  as  rapidly  as  the  latter  which  soon 
bend  around  toward  the  ureter,  thus  resulting  in  the  formation  of  the  convex 
side  of  the  kidney  and  a  depression  or  hilus  opposite  (compare  Figs.  314  and 
320).  Between  these  four  pyramids  the  mesenchyme  remains  for  some  time  as 

Primary  renal  pyramid 


Primary  renal  column 


Primary  renal  pyramid 


Primary  renal  column 


Ureter- 

1^     Primary  renal  pyramid 
FIG,  320. — Frontal  section  of  the  kidney  of  a  human  foetus  of  3!  months  (10  cm.).     Hauch. 

\  rather  distinct  septa,  forming  the  primary  renal  columns  (columns  of  Bertini) 
which  are  marked  by  corresponding  depressions  on  the  surface  of  the  kidney 
and  extend  to  the  renal  pelvis.  The  four  primary  pyramids  may  be  considered 
as  lobes  (Fig.  320).  It  should  also  be  stated  that  the  parts  of  the  tubules 
derived  from  the  mesenchyme  form  the  bases  of  the  renal  pyramids.  Be- 
tween the  groups  of  straight  tubules  derived  from  evaginations  of  the  second  or 
third  order  (see  p.  362)  there  #re  also  septa  of  mesenchyme  which  divide  each 
primary  pyramid  into  two  or  three  secondary  pyramids.  These  septa  may 
be  considered  as  secondary  renal  columns  (Fig.  321).  Thus  the  entire  kidney 
is  divided  into  from  eight  to  twelve  secondary  pyramids.  Tertiary  renal 
columns  then  divide  incompletely  the  secondary  pyramids  into  tertiary  pyra- 


368 


TEXT-BOOK  OF  EMBRYOLOGY. 


mids.     These  are  apparent  on  the  surface  of  the  kidney  and  constitute  the 
surface  tabulation,  but  are  not  clearly  denned  in  the  interior. 

The  formation  of  renal  papillae  (p.  363)  corresponds  to  the  formation  of 
pyramids  only  to  a  certain  point,  for  some  of  the  tertiary  pyramids  appear  only 
near  the  surface  and  consequently  do  not  have  corresponding  papillae.  This 
accounts  for  the  fact  that  frequently  the  number  of  pyramids  apparent  on  the 
surface  does  not  correspond  with  the  number  of  papillae.  The  surface  lobula- 
tion  is  very  plainly  marked  in  kidneys  up  to  and  for  a  short  time  after  birth.  It 
then  disappears  and  the  surface  becomes  smooth.  At  the  same  time  the  con- 
nective (mesenchymal)  tissue  of  the  renal  columns  is  largely  replaced  by  the 

Secondary 

renal 
column    Secondary 

renal 

pyramid       Secondary 
renal 
column 


Primary 

renal 
column 


FIG.  321. — Frontal  section  of  the  kidney  of  a  human  foetus  of  19  weeks  (17.5  cm.).     Hauch. 

epithelial  elements  of  the  gland  so  that  in  the  adult  kidney  the  columns  are  not 
clearly  denned. 

The  capsule  of  the  kidney  is  derived  from  the  mesenchyme  which  surroum 
the  anlage  of  the  organ  (Fig  315).  This  mesenchyme  is  transformed  into  fibroi 
connective  tissue  and  a  small  amount  of  smooth  muscle,  forming  a  layer  which 
closely  invests  the  kidney  and  dips  into  the  hilus  where  it  surrounds  the  blood 
vessels  and  the  end  of  the  ureter.  The  connective  tissue  and  muscle  of  the 
ureter  are  also  derived  from  the  mesenchyme. 

CORTEX  AND  MEDULLA. — As  the  convoluted  renal  tubules  develop  in  the 
metanephric  blastema  (p.  363),  they  form  a  cap-like  mass  around  the  group  of 


THE  DEVELOPMENT  OF  THE  UROGENITAL  SYSTEM.  369 

straight  tubules.  This  is  the  beginning  of  the  renal  cortex.  A  true  cortex, 
however,  can  be  spoken  of  only  after  the  appearance  of  the  glomeruli  (in 
embryos  of  30  mm.).  Its  peripheral  boundary  is  the  capsule,  and  the  renal 
corpuscles  nearest  the  pelvis  mark  its  inner  boundary.  The  mass  of  straight 
tubules  forms  the  bulk  of  the  medulla.  It  does  not  at  this  stage  contain  Henle's 
loops,  the  latter  developing  later  (during  the  fourth  month).  Both  cortex 
and  medulla  increase  until  the  kidney  reaches  its  adult  size.  The  cortex 
increases  relatively  faster  than  the  medulla  up  to  the  seventh  year;  after 
this  the  increase  is  practically  equal.  The  medullary  rays  are  probably 
secondary  formations,  being  formed  by  groups  of  straight  tubules  which 
grow  out  into  the  cortex;  later,  ascending  arms  of  Henle's  loops  are  added  to 
these  groups. 

Some  of  the  glomeruli  of  the  first  generation  are  much  larger  than  any 
found  in  the  adult.  In  some  of  the  lower  Mammals  these  "giant"  glomeruli 
disappear  and  it  is  probable  that  the  same  occurs  in  the  human  embryo.  Some 
of  the  tubules  also  degenerate  and  disappear.  The  cause  of  these  phenomena 
is  not  known. 

Changes  in  the  Position  of  the  Kidneys. — As  has  already  been  described 
(p.  361),  the  kidney  buds  first  grow  dorsally  from  the  mesonephric  ducts 
toward  the  vertebral  column.  They  then  grow  cranially,  with  a  corresponding 
elongation  of  the  ureters,  and  in  embryos  of  20  mm.  they  lie  for  the  most  part 
cranial  to  the  common  iliac  arteries.  This  migration  continues  until  the  time 
of  birth  when  the  cephalic  ends  of  both  kidneys  reach  the  eleventh  thoracic  ver- 
tebra. When  the  kidneys  begin  to  move  cranially  the  hilus  is  directed  caudally. 
Later  they  rotate  and  the  hilus  is  turned  toward  the  medial  sagittal  plane. 

Since  the  ureter,  renal  pelvis  and  straight  tubules  develop  from  the  mesonephric  ducts, 
and  since  the  convoluted  tubules  and  glomeruli  develop  directly  from  the  same  tissue  as  the 
mesonephric  tubules,  namely,  the  mesenchyme,  the  renal  tubules  may  be  said  to  represent 
the  third  generation  of  urinary  tubules.  But  no  definite  reason  for  the  appearance  of  the 
third  generation  can  be  given.  The  atrophy  of  the  mesonephroi  would,  of  course,  make 
necessary  the  compensatory  development  of  new  structures;  but  this  only  carries  the  problem 
a  step  further  back,  for  the  cause  of  the  atrophy  of  the  mesonephroi  is  not  clear.  In  regard 
to  this  atrophy,  however,  there  is  a  suggestion  of  a  cause  in  the  fact  that  in  the  Amphibia 
the  mesonephroi  are  in  part  used  for  conveying  the  sexual  elements,  which  leaves  the  meso- 
nephroi less  free  to  function  as  urinary  organs.  Possibly  the  loss  of  freedom  to  function  leads 
to  the  development  of  new  structures — the  kidneys — in  the  higher  forms  (Reptiles,  Birds 
and  Mammals).  In  these  forms  the  kidneys  assume  the  urinary  function  after  the  early 
embryonic  stages,  and  only  the  ducts  and  a  part  of  the  tubules  of  the  mesonephroi  persist  in 
the  male  to  convey  the  sexual  elements.  Thus  the  persistent  parts  of  the  mesonephroi  as- 
sume a  new  function  as  the  old  one  is  lost.  But,  on  the  other  hand,  complications  arise 
on  account  of  the  fact  that  in  the  female  the  sexual  products  are  carried  off  by  another  set 
of  ducts  (the  Miillerian  ducts),  which  develop  in  both  sexes  but  disappear  in  the  male, 
while  the  mesonephroi  and  their  ducts  disappear  almost  entirely. 


370 


TEXT-BOOK  OF  EMBRYOLOGY. 


THE  URINARY  BLADDER,  URETHRA  AND  UROGENITAL  SINUS. 

As  described  elsewhere,  the  allantois  appears  at  an  early  stage  as  an  evagi- 
nation  from  the  ventral  side  of  the  caudal  end  of  the  primitive  gut  (Fig.  244), 
grows  out  into  the  belly  stalk,  and  finally  becomes  enclosed  in  the  umbilical  cord 
(p.  582).  As  the  embryo  develops,  the  proximal  end  of  the  allantois  becomes 
elongated  to  form  a  stalk  or  duct  which  extends  from  the  caudal  end  of  the 
gut  to  the  umbilicus  (Fig.  247).  The  portion  of  the  gut  immediately  caudal  to 
the  attachment  of  the  allantoic  duct  becomes  dilated  to  form  the  cloaca  which 
at  first  is  a  blind  sac,  its  cavity  being  separated  from  the  outer  surface  of  the 
embryo  by  the  cloacal  membrane  (Fig.  322).  The  latter  is  composed  of  a  layer  of 
entoderm  and  a  layer  of  ectoderm,  with  a  thin  layer  of  mesoderm  between.  The 
cloaca  then  becomes  separated  into  two  parts— a  larger  ventral  part  which  forms 


Intestine        Kidney  bud 


Mesonephric  duct 

Urachus 

Cloaca 

Cloacal  membrane 


Caudal  gut  - — .- 

Notochord 

Neural  tube 


FIG.  322. — From  a  model  of  the  cloaca  and  the  surrounding  structures  in  a 
human  embryo  of  6.5  mm.     Keibel. 

the  uro genital  sinus  and  a  smaller  "dorsal  part  which  forms  the  rectum.  This 
Is  accomplished  by  a  fold  or  ridge  which  grows  from  the  lateral  wall  into  the 
lumen  and  meets  and  fuses  with  its  fellow  of  the  opposite  side.  The  fusion  be- 
gins at  the  cephalic  end,  in  the  angle  between  the  allantoic  duct  and  the  gut, 
and  gradually  proceeds  caudally  until  the  separation  is  complete  as  far  as  the 
cloacal  membrane.  The  mass  of  tissue  forming  the  partition  is  called  the  uro- 
rectalfold  (Fig.  323).  The  openings  of  the  mesonephric  ducts,  which  primarily 
were  situated  in  the  lateral  cloacal  wall  (p.  359),  are  situated  after  the  separation 
in  the  dorso-lateral  wall  of  the  ur-ogenital  sinus  (compare  Figs.  322,  323,324). 
During  the  separation  of  the  urogenital  sinus  from  the  rectum,  certain 
changes  take  place  in  the  proximal  ends  of  the  mesonephric  ducts  and  ureters. 
The  ends  of  the  ducts  become  dilated  and  are  gradually  taken  up  into  the  wall  of 
the  sinus.  This  process  of  absorption  continues  until  the  ends  of  the  ureters  are 
included,  with  the  result  that  the  ducts  and  ureters  open  separately,  the  latter 


THE  DEVELOPMENT  OF  THE  UROGENITAL  SYSTEM.  371 

slightly  cranial  and  lateral  to  the  former.  (Compare  Figs.  324  and  325.)  This 
condition  is  reached  in  embryos  of  12  to  14  mm.  The  point  at  which  these  two 
sets  of  ducts  open  marks  the  boundary  between  a  slightly  larger  cephalic  part 
of  the  sinus,  the  anlage  of  the  bladder,  and  a  smaller  caudal  part  which  becomes 
the  urethra  and  urogenital  sinus  (Fig.  325). 

After  the  second  month  the  bladder  becomes  larger  and  more  sac-like,  and 
the  openings  of  the  ureters  migrate  farther  cranially  to  their  final  position.  The 
lumen  of  the  bladder  is  at  first  continuous  with  the  lumen  of  the  allantoic  duct, 
but  the  duct  degenerates  into  a  solid  cord  of  cells,  the  urachus.  The  latter 
degenerates  still  further  and  finally  remains  only  as  the  middle  umbilical  liga- 

Urorectal  fold  Mesonephric  duct 

Kidney  bud. 

^^^K&mn^L       /•?*& 

Urachus 


Cloaca 
Urogenital  sinus  — 


-  Rectum 

Cloacal  membrane 


audal  gut 


FIG.  323.— From  a  model  of  the  cloacal  region  of  a  human  embryo  slightly  older  than 

that  shown  in  Fig.  322.     Keibel. 

The  arrow  points  to  the  developing  partition  (uro«ectal  fold)  between  the  rectum  and  urogenital 
sinus.  The  opening  of  the  mesonephric  duct  into  the  urogenital  sinus  is  indicated  by  a 
small  seeker. 

merit.  It  seems  quite  probable  that  the  bladder  is  derived  almost  wholly  from 
the  cloaca.  A  small  part  arises  from  the  inclusion  of  the  ends  of  the  mesoneph- 
ric ducts.  If  any  part  is  derived  from  the  allantoic  duct,  it  is  only  the  apex. 
After  the  bladder  begins  to  enlarge,  the  adjacent  portion  of  the  urogenital 
sinus  becomes  slightly  constricted.  This  marks  the  beginning  of  the  urethra. 
In  the  female  the  constricted  part  represents  practically  the  entire  urethra. 
In  the  male  it  represents  only  the  proximal  end,  the  other  portion  developing 
in  connection  with  the  penis  (p.  398).  The  urogenital  sinus  is  narrow  and 
tubular  at  its  junction  with  the  urethra;  more  distally  it  is  wider  and  is  shut  off 
from  the  exterior  by  the  cloacal  membrane.  After  the  embryo  reaches  a  length 
of  16  to  17  mm.,  the  membrane  ruptures  and  the  sinus  opens  on  the  surface* 


372 


TEXT-BOOK  OF  EMBRYOLOGY. 


The  narrow  part  of  the  sinus  is  gradually  taken  up  into  the  wider,  resulting  in 
the  formation  of  a  sort  of  -vestibule.  In  both  sexes  the  urethra  opens  into  the 
deeper  end  of  the  vestibule.  In  the  male  the  mesonephric  (seminiferous) 


Cloaca 
(undivided  portion) 


Cloacal  membrane 


Tail 


Mesonephric  ducts 


L   Coelom 


'—  Primitive  renal  pelvis 


Rectum 


FlG.  324. — From  a  reconstruction  of  the  caudal  end  of  a  human  embryo 
of  11.5  mm.  (4^  weeks).     Keibel. 


Umbilical  artery 
Bladder 


Symphysis  pubis- 
Urogenital  sin  us  - 


Genital  tubercle 
Urethra 


Anus 


Ovary 

__  Broad  ligament 
of  uterus 


I—  Mullerian  duct 

j 

»-•  Mesonephric  duct 

Ureter 


Recto-uterine 
excavation 


-    Rectum 


Tail 


FIG.  325. — From  a  reconstruction  of  the  caudal  end  of  a  human  embryo 

of  25  mm.  (8i-g  weeks).     Keibel. 
The  asterisk  (*)  indicates  the  urorectal  fold. 

ducts  open  near  the  external  orifice.     In  the  female  the  opening  of  the  develop- 
ing vagina  is  situated  on  the  dorsal  side  near  the  external  orifice. 

The  epithelium  of  the  prostate  gland  is  derived  by  evagination  from  the  proxi- 


THE  DEVELOPMENT  OF  THE  UROGENITAL  SYSTEM.  373 

mal  part  of  the  urethra.  The  first  evagination  appears  during  the  third  month. 
In  the  male  the  process  continues  to  form  a  rather  large  gland;  in  the  female  the 
structure  remains  in  a  rudimentary  condition.  During  the  fourth  month  two 
evaginations  arise  from  the  urethra  and  develop  into  the  bulbo-urethral 
(Cowper's)  glands  in  the  male,  into  the  larger  vestibular  (Bartholin's)  glands  in 
the  female. 

From  the  course  of  development  it  is  seen  that  the  epithelium  of  most  of  the 
bladder,  of  the  female  urethra  and  proximal  end  of  the  male  urethra,  of  the 


Germinal        JS^  ^  Stroma 

epithelium  — I  a         (mesenchyme) 

(mesothehum) 


FIG.  326. — Transverse  section  through  the  germinal  epithelium  of  a  pig  embryo  of  n  mm.   Nagel. 

The  larger  cells  in  the  epithelium  represent  the  sex  cells,  the  smaller  ones  the 

undifferentiated  mesothelial  cells. 

prostate,  of  the  urogenital  sinus,  and  of  the  bulbo-urethral  and  vestibular 
glands  is  of  entodermal  origin.  A  very  small  part  of  the  bladder  epithelium 
is  of  mesodermal  origin,  since  the  proximal  ends  of  the  mesonephric  ducts, 
which  are  mesodermal  derivatives,  are  taken  up  into  the  wall.  All  the  connec- 
tive tissue  and  smooth  muscle  associated  with  these  organs  are  derived  from 
the  mesoderm  (mesenchyme)  which  surrounds  the  anlagen. 

•     "       *  ^ 

THE  GENITAL  GLANDS. 
The  Germinal  Epithelium  and  Genital  Ridge. 

At  a  very  early  stage  in  the  formation  of  the  mesonephros,  a  narrow  strip 
of  mesothelium  extending  along  the  medial  surface  becomes  thicker  and  the 
cells  become  arranged  in  several  layers  (Figs.  276  and  308).  Two  kinds 
of  cells  can  be  recognized  in  this — (i)  small  cuboidal  cells  with  cytoplasm 
which  stains  rather  intensely,  and  (2)  larger  spherical  cells  with  clearer 


374  TEXT-BOOK  OF  EMBRYOLOGY. 

cytoplasm  and  large  vesicular  nuclei  (Fig.  326).  The  latter  are  the  sex  cells; 
and  the  whole  epithelial  (mesothelial)  band  is  known  as  the  germinal  epi- 
thelium. The  sex  cells  are  destined  to  give  rise  to  the  sexual  elements — in  the 
female  to  the  ova,  in  the  male  to  the  spermatozoa.  In  the  earlier  stages, 
however,  it  is  impossible  to  determine  whether  the  sex  cells  will  give  rise  to 
male  or  female  elements.  The  differentiation  of  sex  and  the  corresponding 
histological  differentiation  of  the  sex  cells  occur  at  a  later  period. 

In  his  earlier  work  on  the  ovary  and  testis  in  Mammals,  Allen  has  ob- 
served in  very  early  stages  (pig  embryos  of  6  mm.,  rabbit  embryos  of  13  days) 
certain  large  cells,  with  large  clear  nuclei,  in  the  mesenchymal  tissue  of  the 
mesentery,  outside  oj  the  genital  ridge.  In  his  investigation  of  the  chick, 
Swift  has  discerned  the  sex  cells  at  the  time  when  the  primitive  streak  and 
primitive  axis  are  being  formed.  They  are  located  in  the  entoderm  and  in 
the  space  between  entoderm  and  ectoderm  in  the  anterior  part  of  the  germ 
wall.  When  the  mesoderm  appears  in  this  region  the  sex  cells  enter  this 
layer,  then  enter  the  blood  vessels.  They  are  apparently  amoeboid.  By  the 
blood  stream  they  are  carried  to  all  parts  of  the  blastoderm  and  embryo. 
Later  the  cells  accumulate  in  the  vicinity  of  the  ccelomic  angle  and  finally 
enter  the  thickened  mesothelium  (germinal  epithelium)  of  the  genital  ridge. 

Beard,  Eigenmann,  Rabl,  Woods,  and  others,  have  described  sex  cells,  undoubtedly 
homologous  with  the  early  sex  cells  mentioned  above,  as  occurring  in  various  regions  of  the 
embryos  of  certain  Fishes.  These  investigators  also  assert  that  the  sex  cells  become 
specialized  and,  so  to  speak,  segregated  at  a  very  early  period  of  development,  even  at  the 
stage  of  blastomere  formation.  Beard  contends  that  the  early  differentiated  sex  (or  germ) 
cells  are  significant  in  the  origin  of  certain  teratomata  (see  Chapter  on  Teratogenesis). 

The  cells  of  the  germinal  epithelium  increase  in  number  by  mitotic  division 
and  the  sex  cells  continue  to  increase  in  number  by  proliferation  of  their  own 
members  since  there  are  no  intermediate  stages  between  the  two  types. 
The  germinal  epithelium  soon  becomes  separated  into  two  layers — (i)  a 
superficial  layer  which  retains  its  epithelial  character  and  contains  the  sex 
cells,  and  (2)  a  deeper  layer  composed  of  smaller  cells  which  resemble  those 
of  the  mesenchyme  and  which  give  rise  to  a  part,  at  least,  of  the  stroma  of  the 
genital  glands.  The  elevation  formed  by  these  two  layers  projects  into'  the 
body  cavity  from  the  medial  side  of  the  mesonephros  and  constitutes  the 
genital  ridge  (Fig.  308).  From  the  superficial  epithelial  layer,  columns  or 
cords  of  cells,  containing  some  of  the  sex  cells,  grow  into  the  underlying  tissue. 
This  ingrowth,  however,  does  not  occur  equally  in  all  parts  of  the  genital 
ridge,  for  three  fairly  distinct  regions  can  be  recognized.  In  the  cephalic  end 
comparatively  few  columns  appear,  but  these  few  grow  far  down  into  the 
underlying  tissue  and  constitute  the  rete  cords.  In  the  middle  region  a  greater 


THE  DEVELOPMENT  OF  THE   UROGENITAL   SYSTEM. 


375 


number  of  columns  grow  into  the  stroma,  forming  the  sex  cords.  In  the 
caudal  region  there  are  practically  no  columns.  At  first  the  line  of  demarka- 
tion  between  the  cell  columns  and  the  stroma  is  not  clearly  defined. 

The  changes  thus  far  described  are  common  to  both  sexes  and  are  completed 
during  the  fourth  or  fifth  week.  The  genital  ridges  or  anlagen  of  the  genital 
glands  constitute  "indifferent"  structures  which  later  become  differentiated  into 
either  ovaries  or  testicles. 


Differentiation  of  the  Genital  Glands. 

After  the  fourth  or  fifth  week,  certain  changes  occur  in  the  genital  ridges 
which  differ  accordingly  as  the  ridges  form  ovaries  or  testicles.  While  the 
differences  are  at  first  not  particularly  obvious,  there  are  four  which  become 
clearer  as  the  changes  progress,  (i)  If  the  ridge  is  to  become  a  testicle,  the 
;ells  of  the  surface  epithelium  become  arranged  in  a  single  layer  and  become 


Rete  cords 
(Rete  testis) 


Mesorchium 


Mesothelii 


Tunica 
albuginea 


>•  Mesonephros 


Sex  cords   -.  Mr^w.-^V'        Glomerulus 
(convoluted  semin- 
iferous tubules) 

FIG.  327.  —  Transverse  section  of  the  left  testicle  of  a  pig  embryo  of  62  mm. 


Bonnet. 


flat.     (2)  In  a  developing  testicle  a  layer  of  dense  connective  tissue  grows  be- 
tween the  surface  epithelium  and  the  sex  cords,  forming  the  tunica   albuginea. 

(3)  In  a  tes.ticle  there  also  appears  a  sharper  line  of  demarkation  between  the 
cell  columns  and  the  stroma,  and  the  latter  shows  a  more  extensive  growth. 

(4)  Another  feature  of  the  testicle  is  that  the  sex  cells  begin  to  be  less  con- 
spicuous and  do  not  increase  furth2r  in  size,  but  come  to  resemble  the  other 
epithelial  elements.     The  ovarian  characters  are  to  a  certain  extent  the  oppo- 
site.    (i)  The  surface  epithelium  does  not  become  flattened.     (2)  A  layer  of 
connective  tissue,  corresponding  to  the  albuginea  of  the  testicle,  grows  be- 


376 


TEXT-BOOK  OF  EMBRYOLOGY. 


tween  the  epithelium  and  the  deeper  parts,  but  is  of  a  looser  nature.  (3)  There 
is  a  less  sharp  line  of  demarkation  between  the  cell  columns  and  the  stroma. 
(4)  The  sex  cells  continue  to  increase  in  size  and  become  more  conspicuous. 
(Compare  Figs.  327  and  328.) 

During  these  processes  of  development,  the  anlage  of  each  genital  gland  be- 
comes more  or  less  constricted  from  the  mesonephros  and  finally  is  attached  only 
by  a  thin  sheet  of  tissue — the  mesovarium  in  the  female  or  the  mesorchium  in  the 


Oviduct 

(Ostium  abdom-  

inale  tubae) 


1-4 ,Epo6phoron 


A*^ 


Cortex -. 


y^\M 


*ti 


Ifff 


Medullary  cords 
(Medulla) 


?.Q     •     /       Rete  cords 
""'&&>• —  (Rete  ovarii) 


l|5m  •  iQi 

fefei^fV  ^-®| 

SN^v  (  >-^ 

*Si«**4*c':  *^  *  *-^j»»v.  /.;  \ 


'"^-i Mesonephroe 


rao  ^ 


Oviduct 
FIG.  328.  —  Longitudinal  section  of  the  ovary  of  a  cat  embryo  of  94  mm.    Semidiagrammatic.    Coert. 


male  (p.  389).     At  the  same  time  the  anlage  grows  more  rapidly  in  thickness 
than  in  length  and  assumes  an  oval  shape. 

The  Ovary.  —  As  stated  above,  a  layer  of  loose  connective  tissue,  correspond- 
ing to  the  albuginea  of  the  testicle,  grows  in  between  the  surface  epithelium  and 
the  cell  columns  (sex  cords)  and  effects  a  more  or  less  complete  separation. 
The  sex  cords  are  thus  pushed  farther  from  the  surface,  become  more  clearly 
marked  off  from  the  surrounding  stroma  and  constitute  the  so-called  medullary 
'cords.  The  cortex  of  the  ovary  at  this  stage  is  represented  only  by  the  surface 
(germinal)  epithelium,  which  is  composed  of  several  layers  of  cells  and  contains 


THE  DEVELOPMENT  OF  THE  UROGENITAL  SYSTEM.  377 

numerous  sex  cells  in  various  stages  of  differentiation  (Fig.  329).  The 
rete  cords  which  arise  in  the  cranial  end  of  the  "indifferent"  gland  (p.  374) 
come  to  lie  in  what  will  be  the  hilus  of  the  ovary.  The  ovary  may  thus  be 
said  to  be  composed  of  two  parts — (i)  the  rete  anlage  and  (2)  the  stratum  ger- 
minativum.  The  latter  is  subdivided  by  the  albuginea  into  (a)  medulla  and 
(b)  cortex. 

i .  The  rete  cords  develop  into  a  group  of  anastomosing  trabeculae  which  con- 
stitute the  rete  ovarii,  situated  in  the  hilus  but  nearer  the  cephalic  end  of  the 
gland  (Fig.  328).  They  are  the  homologues  of  the  rete  testis.  The  cells  com- 
posing them  are  smaller  and  darker  than  those  of  the  medullary  cords.  Sprouts 
grow  out  from  the  rete  cords  and  unite  with  the  medullary  cords  and  the  meso- 
nephric  tubules.  (The  same  process  occurs  in  the  testicle,  where  the  rete  cords 
give  rise  to  the  functional  rete  testis  and  straight  seminiferous  tubules.)  In 


Mesothelium 
(Germinal  epithelium) 


^¥&\W$£&jffi 


Mesovarium 

—  Rete  ovarii 

FIG.  329. — Transverse  section  of  the  ovary  of  a  fox  embryo.     Buhler  in  Hertwig's  Handbuch. 
The  large  clear  cells  are  the  primitive  ova. 

some  of  the  cords  lumina  appear  and  are  lined  with  irregular  epithelium. 
Such  a  condition  represents  the  height  of  their  development  in  the  ovary. 
From  this  time  on,  they  degenerate  and  finally  disappear.  The  time  of  their 
disappearance  varies  in  different  individuals;  they  usually  persist  until  birth, 
sometimes  until  puberty. 

Formerly  it  was  thought  that  the  rete  cords  were  derived  from  the  meso- 
nephric  tubules  and  entered  the  genital  glands  secondarily.  More  recent  re- 
searches have  demonstrated  quite  conclusively,  however,  that  they  are  deriva- 
tives of  the  germinal  epithelium  and  unite  with  the  mesonephric  tubules 

secondarily.  . ,  <Jb-  ^  - 

-jj\ 
2  (a).  The  medullary  cords  are  composed  of  small  epithelial  cells,  contain  a 

number  of  larger  sex  cells  or  primitive  ova,  and  are  surrounded  by  stroma 
(Figs.  329,  330).  They  are  connected  with  the  rete  cords  and  in  some  places 
with  the  germinal  epithelium.  During  foetal  life  they  give  rise  to  primary 
ovarian  (Graafian)  follicles;  later  they  degenerate  and  finally  disappear. 


378 


TEXT-BOOK  OF  EMBRYOLOGY. 


2(b).  The  cortex  of  the  ovary,  as  stated  above,  at  first  consists  of  several 
layers  of  small,  darkly  staining  cells,  among  which  are  many  large,  clearer  sex 
cells  or  primitive  ova  (Fig.  329).  From  the  epithelium,  masses  or  cords  of  cells 
grow  into  the  underlying  tissue,  carrying  with  them  some  of  the  primitive  ova. 
These  masses  are  known  as  Pfluger's  egg  cords.  In  some  cases  several  ova  are 
grouped  together,  forming  egg  nests  (Fig.  330).  The  epithelial  cells  are  the 
progenitors  of  the  follicular  cells  and  constantly  undergo  mitotic  division.  The 
primitive  ova,  on  the  other  hand,  increase  in  size  and  their  nuclei  show  distinct 
intranuclear  networks. 

The  egg  cords  become  separated  from  the  surface  epithelium  and  are 
broken  up  so  that  in  most  cases  a  single  ovum  is  surrounded  by  a  single  layer  of 


Germinal 
epithelium 


Cortex 


Medulla 


FIG.  330. — From  a  section  through  the  ovary  of  a  human  foetus  of  4  months.    Meyer-Ruegg,  Buhler. 
The  large  cells  are  the  primitive  ova. 

epithelial  cells.  This  constitutes  a  primary  Graafian  follicle.  Rarely  a  follicle 
contains  more  than  one  ovum.  In  the  case  of  the  egg  nests,  the  ova  may  become 
separated,  or  two  or  more  may  lie  in  one  follicle.  If  two  or  more  ova  are 
present  at  first  in  any  follicle,  usually  only  one  continues  to  develop  and  th( 
others  either  degenerate  or  are  used  as  nutritive  materials.  In  very  rare  cases, 
however,  two  ova  may  develop  in  a  single  follicle,  but  whether  they  reach 
maturity  or  not  is  uncertain.  The  formation  of  egg  cords  is  usually  com- 
pleted before  birth,  but  in  some  cases  may  continue  for  one  or  two  years  after 
birth.  During  the  processes  thus  far  described,  the  stroma  also  has  been  in- 
creasing, and  the  egg  cords  and  follicles  come  to  be  separated  by  a  considerable 
amount  of  connective  tissue.  The  germinal  epithelium  becomes  reduced  to  a 
single  layer  of  cuboidal  cells. 


THE  DEVELOPMENT  OF  THE  UROGENITAL  SYSTEM. 


379 


Each  primary  ovarian  follicle,  containing  a  primitive  ovum  (egg  cell,  sex  cell) , 
is  composed  of  a  single  layer  of  flat  or  cuboidal  cells,  plus  a  layer  of  stroma 
which  gives  rise  to  the  theca  folliculi.  As  the  ovum  continues  to  enlarge,  the 
follicular  cells  become  higher  and  arranged  in  a  radial  manner  (Fig.  331,  a) .  By 
proliferation,  the  follicular  cells  come  to  form  several  layers,  the  innermost 
layer  retaining  the  radial  character  and  forming  the  zona  radiata.  The  inner  or 
basal  ends  of  the  cells  of  the  zona  radiata  become  clear  to  form  the  zona  pellucida. 
In  the  latter,  radial  striations  appear  which  have  been  described  as  minute 


.    c  d 

FIG.  331. — Four  stages  in  the  development  of  the  ovarian  (Graafian)  follicle 

From  photographs  of  sections  of  a  cat's  ovary      Hertwig. 

The  ovum  is  not  shown  in  a,  b  and  c. 

channels  in  the  cells,  through  which  nutriment  may  pass  to  the  ovum.  After 
the  follicular  epithelium  has  become  several  layers  thick,  a  fluid  substance 
known  as  the  liquor  folliculi,  and  probably  derived  from  the  cells  themselves, 
comes  to  lie  in  little  pools  among  the  cells  (Fig.  33 1,  b  and  c ) .  While  the  follicle 
as  a  whole  enlarges,  these  pools  gradually  coalesce  and  form  a  single  large  pool 
which  fills  the  interior  of  the  follicle  (Fib.  331,  d).  Thus  the  epithelium  is 
crowded  out  toward  the  periphery  where  it  forms  a  layer  several  cells  in  thick- 
ness, known  as  the  stratum  granulosum.  The  ovum  itself,  with  the  zona  radiata 
and  some  other  surrounding  cells,  is  also  crowded  off  to  the  periphery  of  the 


380  TEXT-BOOK  OF  EMBRYOLOGY. 

follicle.     The  little  elevation  of  the  stratum  granulosum  in  which  the  ovum 
is  embedded  is  known  as  the  cumulus  ovigerus  or  germ  hill  (see  Fig.  i). 

The  primary  ovarian  follicles  at  first  lie  rather  near  the  surface  of  the  ovary, 
but  as  they  enlarge  and  as  the  ovary  enlarges  they  come  to  lie  deeper.  As  the 
follicle  approaches  maturity  it  increases  greatly  in  size  (5=*=  mm.)  and  finally 
extends  through  the  entire  thickness  of  the  cortex,  its  theca  touching  the  tunica 
albuginea. 

In  speaking  of  the  development  of  the  follicles,  it  must  be  remembered  that 
they  develop  slowly  and  do  not  reach  maturity  until  near  the  age  of  puberty,  and 
furthermore  that  one,  or  very  few  at  most,  reach  maturity  at  the  same  time.  In 
other  words,  when  one  follicle  has  reached  m  iturity  there  are  all  intermediate 
stages  of  development  between  this  and  the  primitive  follicles.  When  a  follicle 
reaches  maturity  it  ruptures  at  the  surface  of  the  ovary  and  the  ovum  is  set  free 
(p.  24).  The  ovum  itself  undergoes  certain  changes  by  which  the  somatic 
number  of  chromosomes  is  reduced  one-half  (p.  16).  It  then  unites  with  the 
mature  spermatozoon,  which  also  contains  one-half  the  somatic  number  of 
chromosomes,  and  forms  the  starting  point,  so  to  speak,  for  a  new  individual. 
At  this  point  the  processes  by  which  an  individual  is  carried  through  its  life 
period  from  its  beginning  as  a  fertilized  ovum  to  the  time  when  it  produces  the 
next  generation  of  mature  sexual  elements  are  ended.  The  developmental 
cycle  of  one  generation  is  complete. 

It  has  been  estimated  that  approximately  36,000  primitive  ova  appear  ii 
each  human  ovary.     Since,  as  a  rule,  only  one  ovum  escapes  from  the  ovary  at 
menstrual  period  or  between  two  succeeding  periods,  it  is  obvious  that  the  vast 
majority  of  these  never  reach  maturity.     They  probably  degenerate,  and,  as 
matter  of  fact,  atretic  follicles  may  be  found  in  an  ovary  at  any  time. 

CORPUS  LUTEUM. — After  the  rupture  of  the  mature  follicle  at  the  surface 
the  ovary  and  the  escape  of  the  ovum  and  liquor  folliculi,  blood  from  the  rup 
tured  vessels  fills  the  interior  of  the  follicle  and  forms  a  clot — the  corpus  hcemor- 
rhagicum.  The  cells  of  the  stratum  granulosum  proliferate  and ,  migrate  into 
the  clot  and  gradually  form  a  mass  which  replaces  the  blood.  It  is  held  by  some 
that  the  cells  are  derived  from  the  theca  folliculi.  Whatever  their  origin,  they 
become  infiltrated  with  a  fatty  substance  known  as  lutein.  Trabecuke  of 
connective  tissue  grow  into  the  mass  of  cells,  carrying  small  blood  vessels  with 
them.  The  (lutein)  cells  disintegrate  and  the  products  of  disintegration  are 
probably  carried  off  by  the  blood,  and  finally  the  entire  corpus  luteum  is  trans- 
formed into  a  mass  of  connective  tissue. 

Whether  the  escaped  ovum  is  fertilized  or  not  has  an  influence  upon  the 
development  of  the  corpus  luteum.  In  case  of  fertilization,  the  corpus  luteum 
becomes  quite  large,  increasing  in  size  up  to  the  fourth  month  of  pregnancy,  and 
then  degenerates.  In  case  the  ovum  is  not  fertilized,  the  corpus  luteum  re- 


THE  DEVELOPMENT  OF  THE  UROGENITAL  SYSTEM.  381 

mains  smaller.     In  both  cases,  however,  the  histological  changes  are  essentially 
the  same. 

The  Testicle. — The  processes  that  give  rise  to  the  "indifferent"  genital 
glands  have  been  described  (p.  373  et  seq.}.  It  has  also  been  stated  that  there 
appears  during  the  fourth  or  fifth  week  a  structure  that  forms  one  of  the  char- 
acteristic features  of  the  testicle.  This  is  a  layer  of  dense  connective  tissue 
which  develops  beneath  the  surface  epithelium  and  constitutes  the  tunica 
albuginea  (p.  375),  and  which  separates  the  surface  epithelium  from  the  sex 
cords  (Fig.  327) .  The  epithelium  becomes  reduced  to  a  single  layer  of  flat  cells, 
although  the  cells  on  the  tip  of  the  gland  usually  remain  high  until  after  birth. 
Naturally  this  epithelium  is  continuous  around  the  hilus  of  the  testicle  with  the 
epithelium  (mesothelium)  of  the  abdominal  cavity.  Within  the  gland  are  the 
sex  cords — the  progenitors  of  the  convoluted  seminiferous  tubules,  which  become 
quite  distinctly  marked  off  from  the  stroma  by  a  basement  membrane.  In  the 

Interstitial  cell  Sex  cell 

i 


t^ilfcM^ 

r  •  «  •_  •>  ~^  — . ...  j%j»1  __ 

&$  - "  •    ;         -t^*!^; 
•i^n^^^ai^ 

I.    t  vvv: ...    a-,--?V*-»  &*  «i-  -"**•  ~it~;"tja»--~~> 

'^®8lf@^ 


Mesothelium    Tunica  Supporting  cell 

albuginea  (of  Sertoli) 

FIG.  332. — From  a  section  of  the  testicle  of  a  human  foetus  of  35  mm.,  showing  a  developing 
convoluted  seminiferous  tubule.     Meyer-Ruegg,  Biihler. 

hilus  region  lie  the  rete  cords — the  progenitors  of  the  rete  testis  and  the  straight 
seminiferous  tubules  (Fig.  327) .  The  rete  cords  of  the  testicle  are  homologues  of 
the  rete  cords  of  the  ovary,  and  are  derivatives  of  the  germinal  epithelium  on  the 
cephalic  portion  of  the  "indifferent"  gland  (p.  374). 

The  sex  cords  at  first  are  solid  masses  composed  of  several  layers  of  cells. 
The  latter  are  of  two  kinds,  as  in  the  ovary — (i)  smaller,  darkly  staining  indiffer- 
ent cells,  and  (2)  larger,  clearer  sex  cells  (Fig.  332).  The  sex  cells  lose  their 
clearness  and  come  to  resemble  again  the  undifferentiated  epithelial  cells. 
They  represent  the  spermatogonia,  which  correspond  to  the  primitive  ova. 
The  spermatogonia  proliferate  very  rapidly  and  become  much  more  numerous 
than  the  epithelial  cells.  The  sex  cords  become  more  and  more  coiled  during 
development  and  anastomose  with  one  another  near  the  convex  surface 
of  the  testicle.  Beginning  after  birth  and  continuing  up  to  the  time  of 
puberty,  lumina  appear  in  them  by  displacement  of  the  central  cells,  and 


382  TEXT-BOOK  OF  EMBRYOLOGY 

they  thus  give  rise  to  the  convoluted  seminiferous  tubules.  The  supporting 
cells  (of  Sertoli)  are  probably  derived  from  the  undifferentiated  epithelial  cells. 

The  details  of  the  further  development  of  the  spermatogonia  to  form  the 
the  spermatozoa  have  been  described  in  the  Chapter  on  Maturation.  At  this 
point,  that  is,  with  the  formation  of  the  spermatozoon,  the  life  cycle  from  a 
mature  male  sexual  element  in  an  individual  to  a  mature  male  sexual  element 
in  an  individual  of  the  succeeding  generation  is  completed. 

The  rete  cords  constitute  an  anastomosing  network  of  solid  cords  of  small, 
darkly  staining  cells,  situated  in  the  hilus  region.  These  cords  later  acquire 
irregular  lumina,  which  are  lined  with  cubpidal  cells,  and  form  the  rete  testis. 
Evaginations  grow  out  from  the  rete  and  fuse  with  the  ends  of  the  convoluted 
tubules,  thus  forming  the  straight  tubules.  On  the  other  hand,  outgrowths 
from  the  rete  unite  with  the  tubules  in  the  cephalic  portion  of  the  mesonephros, 
so  that  a  direct  communication  is  established  between  the  convoluted  semi- 
niferous tubules  and  theinesonephric  tubules.  There  is  thus  formed  the  proxi- 
mal part  of  the  efferent  duct  system  of  the  testicle  (Fig.  327).  That  portion 
of  the  tunica  albuginea  in  which  the  rete  testis  lies,  becomes  somewhat  thickened 
to  form  the  mediastinum  testis. 

The  stroma  of  the  testicle  is  derived  for  the  most  part  from  the  mesenchyme 
of  the  "indifferent"  gland  or  genital  ridge.  Probably  a  smaller  part  is  derived 
from  the  germinal  epithelium  (see  p.  374)-  During  development,  however, 
the  glandular  elements  increase  more  rapidly  than  the  stroma,  so  that  in  the 
adult  they  predominate.  There  is  a  tendency  for  the  convoluted  tubules  to 
become  arranged  in  groups  which  are  separated  by  trabeculae  of  connective 
tissue  radiating  from  the  mediastinum.  The  interstitial  cells  of  the  stroma  are 
direct  derivatives  of  the  connective  tissue  cells  (Fig.  332). 

Determination  of  Sex. 

The  views  regarding  the  determination  of  sex  are  discussed  in  the  chapter 
on  Maturation  (page  21)  in  connection  with  the  question  of  Mendelian 
heredity. 


THE   DEVELOPMENT  OF  THE  UROGENITAL  SYSTEM. 


383 


The  Ducts  of  the  Genital  Glands  and  the  Atrophy  of  the 
Mesonephroi. 

In  the  Female. — Strictly  speaking,  the  ovaries  are  ductless  glands;  for 
neither  developmentally  nor  anatomically  are  the  ducts  which  convey  their 
specific  secretion  directly  connected  with  them.  Furthermore,  these  ducts  are 
in  part  transformed  into  certain  organs  for  the  reception  and  retention  of  both 
kinds  of  sexual  elements.  In  other  words,  the  ducts  in  part  become  specially 
modified  to  form  the  vagina  and  uterus,  of  which  the  latter  serves  as  an  organ 
of  maintenance  for  the  embryos  of  the  next  generation. 

The  ducts  originate  in  connection  with  the  mesonephroi,  and  are  known  at 
first  as  the  Mullerian  ducts.  They  appear  in  both  sexes  alike  but  persist  only  in 
the  female.  In  the  lower  Vertebrates  they  are  split  off  from  the  mesonephric 
ducts.  In  the  higher  forms,  however,  their  mode  of  origin  is  not  known  with 


Ureter 


Intestine 


Mesonephric  duct 


Liver. 


Genital  cord 

Mullerian  duct 

Left  umbilical  artery 

Bladder 


Right  umbilical  artery 


FIG.  333. — From  a  transverse  section  through  the  pelvic  region  of  a  human  embryo 
of  25  mm.  (8J-9  weeks).     Keibel. 

certainty,  but  the  present  evidence  favors  the  view  that  they  arise  independ- 
ently of  the  mesonephric  ducts.  They  appear  in  human  embryos  of  8-14  mm. 
The  mesothelium  on  the  lateral  surface  of  the  cephalic  end  of  each  mesonephros 
becomes  thickened  and  then  invaginates  or  dips  into  the  underlying  mesen- 
chyme.  By  proliferation  of  the  cells  at  its  tip,  the  invaginated  mass  grows 
caudally  as  a  duct  parallel  with  and  close  to  the  mesonephric  duct.  The  two 
ducts  come  to  be  embedded  in  a  ridge  which  at  the  cephalic  end  of  the  meso- 
nephros is  situated  laterally,  but  toward  the  caudal  end  bends  around  and  comes 
to  lie  ventrally.  Beyond  (caudal  to)  the  mesonephros  the  ridge  is  attached  to 
the  lateral  body  wall,  and  near  the  urogenital  sinus  it  meets  and  fuses  with  its 
fellow  of  the  opposite  side  (Fig.  333).  The  two  Mullerian  ducts,  contained 
in  the  ridges,  also  approach  each  other  and  fuse.  The  fusion  begins  in 
embryos  of  25  to  28  mm.  (end  of  second  month),  and  about  the  same  time  they 
open  into  the  dorsal  side  of  the  urogenital  sinus.  The  relations  of  the  Mullerian 


384 


TEXT-BOOK  OF  EMBRYOLOGY. 


and  mesonephric  ducts  are  different  in  different  parts  of  their  courses.  At  the 
cephalic  end  the  Miillerian  lies  dorsal  to  the  mesonephric,  but  farther  back  it 
runs  more  laterally,  then  ventrally,  and  finally  opens  into  the  urogenital  sinus 
on  the  medial  side  of  the  mesonephric  duct. 

THE  OVIDUCT. — The  single  part  of  each  Miillerian  duct  gives  rise  to  the 
oviduct.  The  opening  at  the  cephalic  end  remains  as  the  ostium  abdominale 
tuba,  which  from  the  beginning  communicates  directly  with  the  abdominal 
cavity  (ccelom)  and  never  becomes  connected  with  the  ovary  (Fig.  328).  The 
rim  of  the  opening  sends  from  three  to  five  projections  into  the  abdominal 
cavity  to  form  the  primary  fimbria.  Secondary  branches  grow  out  from  these 
and  form  the  numerous  fimbriae  of  the  adult  oviduct.  The  part  of  each 


Bladder 


Rectum 


Symphysis  pubis 


Cervix  uteri 


Labium  majus          I      Hymen 
Labium  minus 


Vagina 


FIG.  334. — Right  half  of  the  pelvic  region  of  a  female  human  foetus  of  7  months.     Nagel. 

Miillerian  duct  between  the  fimbriated  end  and  the  fused  caudal  end,  grows  in 
length  as  the  embryo  develops,  but  not  proportionately,  so  that  in  the  adult  the 
oviduct  is  relatively  shorter  than  in  the  embryo.  At  first  it  is  lined  with  simple 
cylindrical  epithelium,  but  later  the  cells  become  cuboidal,  and  during  the 
second  half  of  f  octal  life  acquire  distinct  cilia.  The  connective  tissue  and  muscle 
of  the  oviduct  are  derived  from  the  mesenchyme  that  primarily  surrounds  the 
Miillerian  duct. 

In  connection  with  one  of  the  fimbriae  of  the  oviduct  there  is  sometimes  found 
a  small  vesicle  lined  with  ciliated  epithelium,  forming  the  non-stalked  hydatid 
(of  Morgagni),  which  possibly  represents  the  extreme  cephalic  end  of  the 
Miillerian  duct  (Fig.  342).  In  this  case  the  permanent  ostium  of  the  tube 
would  be  of  secondary  origin. 


THE  DEVELOPMENT  OF  THE  UROGENITAL  SYSTEM. 


385 


THE  UTERUS  AND  VAGINA. — The  fused  caudal  ends  of  the  two  Mullerian 
ducts  form  the  anlage  of  the  uterus  and  vagina,  which  is  a  single  medial  tube 
opening  into  the  urogenital  sinus  (Fig.  325).  During  the  third  month  certain 
histological  changes  bring  about  a  differentiation  between  the  cephalic  end  or 
uterus  and  the  caudal  end  or  vagina.  The  simple  columnar  epithelium  of  the 
vaginal  portion  changes  to  stratified  squamous,  and  during  the  fourth  month 
the  lumen  becomes  closed.  Near  the  external  orifice  a  semicircular  fold  ap- 
pears, which  represents  the  hymen  (Fig.  334).  During  the  sixth  month  the 
lumen  reappears  by  a  breaking  down  of  the  central  cells.  The  epithelium  of 
the  uterus,  primarily  high  columnar,  becomes  lower  and  toward  the  end  of 
foetal  life  acquires  cilia.  Many  irregular  folds  appear  in  the  mucosa  of  the 
vagina,  a  smaller  number  in  the  uterus  (Fig.  334).  Some  of  the  folds  in  the 


Ovary 


Mesovarium 


Broad  ligament 
with  paroophoron 


Oviduct 


Mesosalpinx 
with  epoophoron. 


FIG.  335. — Transverse  section  through  the  ovary  and  broad  ligament  of  a  human 
foetus  of  3  months.     Nagel. 

uterus  constitute  the  regular  plica  palmata  of  the  cervix.  The  uterine  glands 
represent  evaginations  from  the  epithelial  lining.  They  do  not  begin  to  develop 
until  after  birth  (one  to  five  years),  and  their  development  is  usually  not  com- 
pleted  until  the  age  of  puberty. 

The  muscle  and  connective  tissue  of  the  walls  of  the  uterus  and  vagina  are 
derived  from  the  mesenchyme  which  surrounds  the  Mullerian  ducts.  The 
muscle  develops  relatively  late  (after  the  fourth  month  of  fcetal  life). 

ATROPHY  OF  THE  MESONEPHROI. — By  far  the  greater  part  of  each  meso- 
nephros  degenerates  and  disappears,  and  the  parts  that  do  persist  are  rudimentary 
and  possess  no  functional  significance.  The  cephalic  portion  leaves  ten  to 
twenty  coiled  tubules  which  terminate  blindly  at  one  end  and  at  the  other  end 
open  into  a  common  duct  that  represents  the  cephalic  end  of  the  mesonephric 
duct.  These  tubules  constitute  the  epoophoron  (parovarium,  organ  of  Rosen- 


386  TEXT-BOOK  OF  EMBRYOLOGY. 

miiller)  which  comes  to  lie  in  the  mesosalpinx  between  the  oviduct  and  the 
mesovarium,  and  later  in  the  mesentery  between  the  oviduct  and  the  ovary 
(Fig.  335).  At  the  height  of  their  development  the  tubules  are  lined  with 
columnar,  ciliated  epithelium.  The  rete  cords  of  the  ovary  (rete  ovarii,  p.  377) 
during  their  development  unite  with  the  tubules  in  the  cephalic  portion  of  the 
mesonephros,  but  later  disappear.  The  epoophoron  is  homologous  with  the 
tubules  of  the  head  of  the  epididymis  in  the  male. 

The  caudal  portion  of  the  mesonephros  leaves  a  few  tubular  remnants 
which  come  to  lie  in  the  broad  ligament  near  the  hilus  of  the  ovary.  These  con- 
stitute the  paroophoron  which  is  homologous  with  the  paradidymis  in  the  male 
(Fig.  335).  They  may  disappear  before  birth  or  may  persist  through  life. 

The  mesonephric  duct  also  leaves  certain  remnants  which  are  situated  (i)  in 
the  broad  ligament,  (2)  in  the  lateral  wall  of  the  uterus,  (3)  in  the  lateral  wall  of  the 
vagina,  and  (4)  in  the  tissue  lateral  to  the  external  genital  opening.  These  rem- 
nants are  known  as  the  canals  of  Gartner,  and  they  naturally  lie  in  the  course  of 
the  duct  in  the  embryo.  All  the  rudimentary  structures  derived  from  the 
mesonephroi  and  their  ducts  are  extremely  variable. 

In  the  Male. — In  the  male  all  the  efferent  ducts  of  the  genital  glands,  except 
the  rete  testis,  are  derived  from  the  mesonephroi  and  their  ducts.  As  described 
earlier  in  this  chapter  (p.  381) ,  the  rete  testis  acquires  a  connection  with  some  of 
the  tubules  in  the  cephalic  end  of  the  mesonephros  and  with  the  sex  cords  or 
anlagen  of  the  convoluted  and  straight  seminiferous  tubules  (see  Fig.  327). 
This  establishes  a  communication  between  the  seminiferous  tubules  and  the 
tubules  of  the  mesonephros.  Those  mesonephric  tubules  with  which  the  rete 
testis  unites  persist  as  the  efferent  ductules  (or  vasa  eff erentia) .  The  latter  form 
a  set  of  coiled  ducts  which  are  situated  in  the  head  of  the  epididymis  and  which 
open  into  the  cephalic  part  of  the  mesonephric  duct  (Fig.  309).  They  are 
homologous  with  the  epoophoron  in  the  female. 

The  next  succeeding  portion  of  the  mesonephric  duct  becomes  the  duct  of  the 
epididymis  which  in  its  tortuous  course  constitutes  the  bulk  of  the  body  and  tail 
of  the  epididymis  and  passes  over  into  the  caudal  portion  of  the  mesonephric 
duct.  The  latter  portion  becomes  the  deferent  duct  (vas  def erens) .  The  caudal 
end  of  the  deferent  duct  forms  the  ejaculatory  duct  which  opens  into  the  urogeni- 
tal  sinus.  The  seminal  vesicles  appear  during  the  third  month  as  lateral 
evaginations  from  the  ejaculatory  ducts. 

The  portions  of  the  mesonephros  not  involved  in  the  formation  of  the  duct 
system  of  the  testicle  atrophy  and  for  the  most  part  disappear.  They  leave 
certain  tubules,  however,  which  persist  as  rudimentary  structures  connected 
with  the  testicle.  In  the  cephalic  end,  some  of  the  tubules  persist  in  part  and 
come  to  lie  among  the  efferent  ductules,  being  either  attached  to  the  latter  or  un- 
connected, and  forming  the  appendage  of  the  epididymis.  The  caudal  part  of 


THE  DEVELOPMENT  OF  THE  UROGENITAL  SYSTEM. 


387 


the  mesonephros  leaves  a  few  tubules  which  come  to  lie  near  the  head  of  the  epi- 
didymis  and  form  the  paradidymis  (or  organ  of  Giraldes),  the  tubules  of  which 
are  lined  with  columnar,  ciliated  epithelium.  Near  the  transition  from  the 
duct  of  the  epididymis  to  the  deferent  duct  there  is  almost  invariably  a  tubule 
(sometimes  branched)  which  also  represents  a  remnant  of  the  mesonephros  and 
is  known  as  the  aberrant  ductule.  It  usually  opens  into  the  duct  of  the  epididy- 
mis, but  may  lie  free  in  the  tissue  around  it  (Fig.  309). 

ATROPHY  OF  THE  MULLERIAN  DUCTS. — These  ducts  persist  in  the  female 
and  become  the  oviducts,  uterus  and  vagina;  in  the  male  they  degenerate  and 
disappear  almost  entirely.  The  degeneration  begins  about  the  time  they  open 


Diaphragmatic 
ligament  of 
mesonephros 


Genital  gland 
Mesonephros 


Mesonephric  duct 


Urachus 


Mesonephric  duct 


Inguinal  ligament 


Umbilical  artery 
FIG.  336.— Urogenital  organs  in  a  human  embryo  of  17  mm.  (6  weeks).     Kollmann's  Alias. 

into  the  urogenital  sinus  (embryos  of  25  to  28  mm.) ;  by  the  time  the  embryo 
reaches  a  length  of  60  mm.  only  the  extreme  cephalic  end  and  the  caudal 
third  remain,  and  at  90  mm.  the  entire  duct  is  gone  except  the  extreme  ends. 
The  cephalic  end  persists  as  the  appendix  testis  (or  hydatid  of  Morgagni) 
(Figs.  309,  341).  The  caudal  end  persists  as  the  utriculus  prostaticus  (uterus 
masculinus). 

Changes  in  the  Positions  of  the  Genital  Glands  and  the  Development 

of  their  Ligaments. 

During  the  early  stages  of  development  the  genital  glands — testicles  or 
ovaries — are  situated  far  forward  in  the  abdominal  cavity.  During  the  eighth 
week  they  lie  opposite  the  lumbar  vertebrae.  During  the  succeeding  months, 
up  to  the  time  of  birth,  they  gradually  move  caudally  to  the  positions  they 


388 


TEXT-BOOK  OF  EMBRYOLOGY. 


occupy  in  the  adult.  This  migration  is  brought  about,  to  some  extent  at 
least,  by  the  influence  of  certain  bands  of  tissue  which  are  primarily  like 
mesenteries.  As  the  mesonephros  develops  and  projects  into  the  body  cavity. 


—Ureter 


Deferent  duct 

Inguinal  ligament 
(Gubernaculum  testis) 

Processus  vaginalis 
periton    ' 


Umbilical  cord 


FIG.  337. — From  a  dissection  of  the  pelvic  region  of  a  male  human  foetus  of  21  cm. 

Kollmann's  Atlas. 

it  comes  to  be  attached  along  the  dorsal  body  wall,  lateral  to  the  dorsal  mesen- 
tery, by  a  sheet  of  tissue  which  is  called  the  mesonephric  mesentery.  Cranial  to 
the  mesonephros,  this  mesentery  is  continued  as  the  diaphragmatic  ligament 


-Spermatic  cord 


Tunica  vaginalis 


Inguinal  ring 


^J___ Tunica  vaginalis 
communis 


Inguinal  cone 


Scrotum 


FIG.  338. — From  a  dissection  of  the  scrotal  region  of  a  human  foetus  of  25  cm. 
Kollmann's  Atlas. 

of  the  mesonephros,  which  as  the  name  indicates,  is  attached  to  the  diaphragm; 
caudally  it  is  continued  to  the  inguinal  region  as  the  inguinal  ligament  of  th< 


THE  DEVELOPMENT  OF  THE  UROGENITAL  SYSTEM. 


389 


mesonephros  (Fig.  336).  The  genital  gland  lies  on  the  medial  side  of  the 
mesonephros  and  is  attached  to  the  latter  by  a  sort  of  mesentery  which  becomes 
the  mesovarium  in  the  female  or  the  mesorchium  in  the  male.  The  cephalic 
portions  of  the  ducts  (Miillerian  and  mesonephric)  lie  close  together  in  a  ridge 
on  the  lateral  surface  of  the  mesonephros;  as  they  pass  caudally  they  extend 
around  to  the  ventral  surface  of  the  mesonephros  and  approach  the  medial  line, 
and  finally,  in  the  pelvic  region,  the  two  ridges  meet  and  fuse,  forming  the  so- 
called  genital  cord  (Fig.  333).  The  genital  cord  thus  contains  the  mesonephric 
and  Miillerian  ducts,  the  latter  fusing  to  form  a  single  tube  (the  anlage  of  the 
uterus  and  vagina,  p.  385).  It  also  contains  the  umbilical  arteries. 


Suprarenal  gland 


Kidney 


intestine 


Round  ligament 
Clnguinal  ligament) 


Umbilical  artery 


Umbilical  vein 


FIG.  339. — From  a  dissection  of  the  pelvic  region  of  a  female  human  foetus  of  7.5  cm. 

Kollmann's  Atlas. 

Such  a  condition  is  found  in  embryos  of  about  eight  weeks.  From  this 
time  on,  the  processes  of  development  follow  divergent  lines  in  the  two  sexes, 
the  differences  becoming  more  marked  from  month  to  month.  Certain  struc- 
tures persist  and  othersdisappear,  according  to  the  sex.  The  mesenteries  and 
ligaments  undergo  metamorphoses  and  the  genital  glands  migrate  caudally. 

Descent  of  the  Testicles. — As  the  mesonephros  atrophies,  its  mesentery 
and  the  mesentery  of  the  testicle  are  combined  to  form  a  single  band  of  tissue 
which,  of  course,  is  continuous  with  the  inguinal  ligament.  The  latter  now 
becomes  the  so-called  gub.ernaculum  testis  (Hunteri),  a  strong  band  or  cord 
composed  of  connective  tissue  and  smooth  muscle.  Its  cephalic  end  is  attached 
to  the  epididymis;  its  caudal  end  pierces  the  body  wall  in  the  inguinal  region  and 


390 


TEXT-BOOK  OF  EMBRYOLOGY. 


is  attached  to  the  corium  of  the  skin  (Fig.  337).  It  plays  an  important  part  in 
the  descent  of  the  testicle.  The  descent  is  brought  about  through  the  principle 
of  unequal  growth.  As  the  body  grows  in  length,  the  gubernaculum  grows 
much  less  rapidly  and,  since  the  caudal  end  of  the  latter  is  fixed,  the  natural 
result  is  the  drawing  downward  of  the  testicle.  This  takes  place  gradually, 
and  at  the  end  of  the  third  month  the  testicle  lies  in  the  false  pelvis;  at  the  end 
of  the  sixth  month  close  to  the  body  wall  at  the  inguinal  ring. 

During  the  third  month  a  second  factor  in  the  descent  of  the  testicle  appears. 
This  is  an  evagination  of  the  peritoneum  at  the  point  where  the  gubernaculum 
pierces  the  body  wall.  The  evagination  at  first  is  a  shallow  depression,  known 


Kidney 
Mullerian  duct 

Genital  gland 
Mesonephros 


Ureter 

Inguinal  ligament 

Mesonephric  duct 

Mullerian  duct 


Apex  of  bladder 


Bladder 


Opening  of  ureter 


Opening  of  mesonephric  duct 

Opening  of  Mullerian  ducts 

Rectum 

Urogenital  sinus 

Cloaca 

Genital  tubercle 

Genital  ridge 

Opening  of  cloaca 


FIG.  340. — Diagrammatic  representation  of  the  urogenital  organs  in  the  "  indifferent "  stage.  Hertwig. 


as  the  processus  vaginalis  peritonei,  but  continues  to  burrow  through  the  body 
wall  and  causes  an  elevation  in  the  skin  which  is  destined  to  become  one  side  of 
the  scrotum  (see  p.  396) .  The  opening  of  the  peritoneal  sac  into  the  body  cavity 
is  the  inguinal  ring.  In  its  descent  the  testicle  passes  through  the  inguinal  ring 
and  comes  to  lie  in  the  elevation  in  the  skin  or  scrotum  (ninth  month) .  Whether 
its  passage  into  the  scrotum  is  the  result  of  a  traction  by  the  gubernaculum  is 
not  certain.  The  inguinal  ring  then  closes  by  apposition  of  its  walls  and  the 
testicle  lies  in  a  closed  sac  which  has  been  pinched  off,  so  to  speak,  from  the  body 
cavity  (Fig.  338). 


THE  DEVELOPMENT  OF  THE  UROGENITAL  SYSTEM 


391 


Kidney 

Appendage  of  testicle 
(hydatid  of  Morgagni) 

Epididymis 

Testicle 

Paradidymis 

Deferent  duct 

Mullerian  duct 

Gubernaculum  testis 

Ureter 

Seminal  vesicle 
Deferent  duct 


Epididymis 
Testicle 

Gubernaculum  testis 


Kidney 


Hydatid 

Oviduct 
(fimbrias) 

Epoophoron 
Ovary 

Paroophoron 

Mesonephric  duct 

Oviduct 

Epoophoron 

Ovary 

Ovarian  ligament 

Uterus 
Round  ligament 


Vagina 


Apex  of  bladder 


Bladder 


Opening  of  ureter 


Urethra 

Opening  of  ejacul.  duct 

Prostate 


Urethra    Sinus  prostaticus 

FIG.  341. 


Apex  of  bladder 

Bladder 
Ureter 

Urethra 
Vestibulum  vaginae 


FIG.  342. 


FIG.  341. — Diagram  of  the  development  of  the  male  genital  organs  from  the 

"  indifferent "  anlagen.     Hertivig. 
FIG.  342. — Diagram  of  the  development  of  the  female  genital  organs  from  the 

"  indifferent "  anlagen.     Hertwig. 
lese  diagrams  should  be  compared  with  Fig.  340.    The  dotted  lines  represent  the  organs  in  the 
relative  positions  they  occupy  in  the  adult  (with  the  exception  of  the  Mullerian  duct  in  the 
male  and  the  mesonephric  duct  in  the  female,  which  ducts  disappear  for  the  most  part). 


392  TEXT-BOOK  OF  EMBRYOLOGY. 

Since  the  testicle  is  invested  by  peritoneum  from  the  beginning  of  its  develop- 
ment, it  must  be  understood  that  in  its  passage  into  the  scrotum  it  passes  along 
under  the  peritoneum.  Consequently  when  it  reaches  the  scrotum  it  is  sur- 
rounded by  a  double  layer  of  peritoneum,  the  tunica  vaginalis  propria. 

The  descent  of  the  testicle  also  produces  marked  changes  in  the  course  of 
the  deferent  duct.  Primarily  the  (mesonephric)  duct  extends  cranially  from 
the  urogenital  sinus  in  a  longitudinal  direction.  But  as  the  testicle  migrates, 
the  cephalic  end  of  the  duct  is  drawn  caudally  so  that  in  the  adult  the  deferent 
duct  extends  cranially  from  the  scrotum  to  the  ventral  side  of  the  urinary 
bladder  and  then  bends  caudally  again  to  open  into  the  urethra. 

Descent  of  the  Ovaries. — The  ovaries  undergo  a  change  of  position  cor- 
responding to  the  descent  of  the  testicles,  although  the  change  is  not  so  extensive. 
Primarily  the  Miillerian  and  mesonephric  ducts  lie  in  a  ridge  on  the  surface  of 
the  mesonephros  (p.  383).  As  the  mesonephros  and  its  duct  atrophy,  the  Miil- 
lerian duct  (oviduct)  comes  to  lie  in  a  fold,  the  mesosalpinx,  which  is  attached 
to  the  mesovarium  (Fig.  335) .  At  the  same  time  the  mesovarium  becomes  directly 
continuous  with  and  really  a  part  of  the  inguinal  ligament.  The  latter  cor- 
responds, of  course,  to  the  gubernaculum  testis,  and  plays  a  role  in  the  descent 
of  the  ovaries.  It  may  be  conveniently  divided  into  three  parts,  (i)  a  cephalic 
part  which  is  attached  to  the  hilus  of  the  ovary,  (2)  a  middle  part  which  ex- 
tends from  the  ovary  to  the  uterus,  forming  the  ovarian  ligament,  and  (3)  a  cau- 
dal part  which  extends  from  the  uterus  to  the  inguinal  region,  forming  the 
round  ligament  of  the  uterus  (Fig.  339).  The  round  ligament  pierces  the  body 
wall  and  is  attached  to  the  corium  of  the  skin.  At  the  point  where  it  passes 
through  the  body  wall  there  is  a  slight  evagination  of  the  peritoneum,  the 
diverticulum  of  Nuck,  which  corresponds  to  the  processus  vaginalis  peritonei 
in  the  male. 

The  ovaries  gradually  migrate  caudally  from  their  original  position  into  the 
false  pelvis  (third  month)  and  thence  into  the  true  pelvis  (at  birth) .  Obviously 
no  traction  can  be  exerted  upon  them  by  the  round  ligament  (or  caudal  part  of 
the  inguinal  ligament) ,  since  the  latter  extends  from  the  uterus  to  the  inguinal 
region.  Their  descent  into  the  pelvic  seems  to  be  due  to  the  unequal  growth 
of  the  ovarian  ligaments,  or  in  other  words,  to  the  fact  that  the  ovarian  liga- 
ments grow  proportionally  less  than  the  surrounding  parts.  During  their 
descent  the  ovaries  become  embedded  in  the  broad  ligaments  of  the  uterus, 
which  represent  further  development  of  the  peritoneal  folds  of  the  genital  cord. 
In  this  way  the  mesovarium  becomes  merged  with  the  broad  ligament. 

On  pages  390  and  391  are  three  diagrammatic  representations  of  the  changes 
that  take  place  in  the  genital  systems  of  the  two  sexes.  Fig.  340  represents 
the  "indifferent"  stage  in  which  all  the  embryonic  structures  are  present; 
Fig.  341  represents  the  changes  that  occur  in  the  male;  Fig.  342  represents  the 


THE  DEVELOPMENT  OF  THE  UROGENITAL  SYSTEM. 


393 


changes  that  occur  in  the  female.  A  careful  study  of  the  diagrams  will  assist 
the  student  materially  in  understanding  the  processes  of  development  which 
have  been  described  in  the  preceding  paragraphs. 

Below  is  a  table  that  is  meant  to  set  forth  briefly  the  various  structures 
which  belong  to  the  internal  genital  organs  in  the  two  sexes,  and  which  are 
derived  from  the  structures  in  the  "indifferent"  stage.  The  words  in  italics 
are  the  names  of  structures  that  persist  in  a  rudimentary  form. 


Indifferent 

Male 

Female 

Germinal  epithelium  (meso- 
i    ,  .      \  A                  x           -• 

Convoluted  seminiferous  tubules  1 
with  spermatozoa  J 

Ovarian   (Graafian)  follicles 
with  ova. 

Medullary  cords 

thehum)      ..... 

Straight  seminiferous  tubules  .    .   1 
Rete  testis  J 

Rete  cords. 

Part  of  stroma  of  testicle     .... 

Part  of  stroma  of  ovary. 

("  cephalic  part 
Mesonephros  -j 
[  caudal  part 

Efferent  ductules  (vasa  efferentia)  \ 
A  ppendage  of  epididymis     .    .    .   / 
Paradidymis  (organ  of  Giraldes)  1 
Aberrant  ductules  (vasa  aberrantia)  J 

Epoophoron,  transverse  duc- 
tules. 

Paroophoron. 

Duct  of  epididymis  (vas  epididy- 
midis)      

Vesicular     appendage     (of 
Morgagni)  (?) 

Mesonephric  duct     .... 

Deferent  duct  (vas  deferens)  .    . 
Ejaculatory  duct  

•  Epoophoron,       longitudinal 
duct. 

Seminal  vesic'e  

Gartner's  canals. 

Miillerian  duct  • 

Morgagni's  appendage  of  testicle  "1  . 
(hydatid  of  Morgagni)      .    .    .  J 

Fimbriae  of  oviduct 
Oviduct. 

Prostatic  utricle  (uterus  masculinus) 

Uterus. 
Vagina. 

Inguinal  ligament  of   meso-  " 
nephros  . 

Gubernaculum  testis  (Hunteri)  .    . 

f  Ovarian  ligament. 
1  Round  ligament  of  uterus 

Urogenital  sinus    • 

TT  QfU  „  f  prostatic  part  .    .    .    .   \ 
Urethra  \membranous  part    .    .  ) 
Prostate  

f  Urethra. 
\  Vestibule  of  vagina. 
Prostate. 

Bulbo-urethral  gland  (Cowpers) 

Larger  vestib  alar  gland  (Bar- 
tholin's. 

THE  EXTERNAL  GENITAL  ORGANS. 

In  addition  to  the  internal  organs  of  generation,  to  which  the  description  has 
thus  far  been  confined,  certain  other  structures  appear  on  the  outside  of  the 
body  to  form  the  external  genitalia.  In  the  case  of  these  also  there  is  an  "  indif- 
ferent" stage  from  which  the  courses  of  development  diverge  in  the  two  sexes. 

During  the  sixth  week  a  depression  appearing  on  the  ventral  surface  of  the 
caudal  end  of  the  body  indicates  the  position  of  the  cloacal  membrane  (p.  370). 
This  becomes  surrounded  by  a  slight  elevation,  produced  by  the  thickening 
of  the  mesoderm  which  is  known  as  the  genital  ridge  (Fig.  343).  The  cephalic 


394  TEXT-BOOK  OF  EMBRYOLOGY. 

side  of  the  ridge  becomes  raised  still  farther  above  the  surface,  forming  a  dis- 
tinct protrusion,  the  genital  tubercle.  The  tubercle  continues  to  increase  in 
size,  and  the  distal  end  forms  a  knob-like  enlargement.  Along  the  ventral  (or 
rather  caudal)  side  a  groove  appears,  which  extends  distally  as  far  as  the  base 
of  the  enlarged  end.  The  ridges  along  the  sides  of  the  groove  increase  in 
size  and  form  the  genital  folds.  In  the  meantime  a  second  pair  of  elevations 
appears  lateral  to  the  genital  folds  to  form  the  genital  swellings  (Fig.  344). 

After  the  cloacal  membrane  ruptures,  a  single  opening  is  produced  which 
leads  from  the  exterior  into  the  cloaca.  This  opening  is  then  separated  by  the 
further  growth  of  the  urorectal  fold  (p.  370)  into  the  opening  of  the  urogenital 
tract  and  the  anal  opening.  The  caudal  part  of  the  fold  then  enlarges  to  form 
the  perineal  body,  which  serves  to  push  the  anus  farther  away  from  the  genital 
ridges.  The  latter,  together  with  the  genital  tubercle  and  swellings,  all  of  which 
lie  in  the  immediate  vicinity  of  the  urogenital  opening,  constitute  the  anlagen 
of  the  external  genital  organs  (Fig.  345).  These  at  this  time  are  in  the 
"indifferent"  stage,  from  which  development  proceeds  in  one  of  two  directions, 
accordingly  as  the  embryo  is  a  male  or  a  female.  Up  to  the  fourth  month 
there  is  little  difference  between  the  structures  in  the  two  sexes.  After  this  the 
differences  become  more  and  more  obvious. 

In  the  female  the  changes  in  the  originally  "indifferent"  structures  are 
comparatively  slight.  The  genital  tubercle  grows  slowly  and  becomes  the 
clitoris.  The  enlarged  extremity  becomes  more  clearly  marked  off  from  the 
other  part  to  form  the  glans  clitoridis.  The  skin  covering  the  glans  is  converted 
by  a  process  of  folding  into  a  sort  of  prepuce.  The  genital  folds,  which 
bound  the  opening  of  the  urogenital  tract,  become  elongated  and  form  the 
labia  minora.  The  opening  of  the  urogenital  tract  is  the  vestibulum  vagina. 
The  genital  swellings  enlarge  still  more  than  the  genital  folds,  by  a  deposition 
of  a  considerable  mass  of  fat  in  the  mesenchyme,  and  become  the  labia  majora. 
The  latter  are  the  structures  (mentioned  on  p.  390)  which  mark  the  points 
at  which  the  inguinal  ligaments  of  the  mesonephroi  pierce  the  body  wall,  and 
are  homologous  with  the  scrotum  in  the  male  (Figs.  346  and  347). 

In  the  male  the  "indifferent"  anlagen  undergo  more  extensive  changes 
than  in  the  female.  The  genital  tubercle  continues  to  grow  more  rapidly  and 
forms  the  penis,  which  is  homologous  with  the  clitoris.  The  enlarged  extremity 
becomes  the  glans  penis,  and  an  extensive  folding  of  the  skin  over  the  glans 
forms  the  prepuce.  The  groove  on  the  caudal  or  lower  side  of  the  tubercle 
elongates  as  the  latter  elongates  and  becomes  deeper.  Finally  the  ridge  (or 
genital  fold)  on  each  side  of  the  groove  meets  and  fuses  with  its  fellow  of  the 
opposite  side,  thus  enclosing  within  the  penis  a  canal — the  penile  portion  of 
the  urethra.  The  groove  is  primarily  continuous  with  the  opening  of  the  uro- 
genital tract,  and  as  the  fusion  takes  place  the  penile  portion  forms  a  direct 


THE   DEVELOPMENT  OF  THE  UROGENITAL  SYSTEM.  395 

Umb.  c. 


Gen.  r. 


-  Gen.  tub. 


—  Gl.  p. 


Scr. 


Ug.s. 


343, 
Fi 


FIG.  347.  FIG.  348. 

FIGS.  381-386.  —  Stages  in  the  development  of  the  external  genital  organs.     Kollmann's  Atlas. 

indifferent  "  stage  —  embryo  of  17  mm.;  Fig.  344,  "  indifferent  "  stage  —  embryo  of  23  mm  ; 
g.  345,  "  indifferent  "  stage  —  embryo  of  29  mm.  (beginning  of  3d  month)  ;  Fig.  346,  female 
embryo  of  70  mm.  (n  weeks);  Fig.  347,  female  embryo  of  150  mm.  (16  weeks);  Fig.  348, 
male  embryo  of  145  mm.  (16  weeks). 

An.,  Anus;  CL,  clitoris;  Clo.and  gen.  /.,  cloaca  and  genital  folds;  Cl.  m.,  cloacal  membrane;  Ext.y 
lower  extremity;  Gen.  /.,  genital  folds;  Gen.  r.,  genital  ridge;  Gen.  sw.,  genital  swelling; 
Gen.  tub.,  genital  tubercle;  Gl.  p.,  glans  penis;  Lab.  ma.,  labium  majus;  Lab.  mi.,  labiura 
minus;  Ra.,  raphe  of  scrotum;  Scr.,  scrotum;  Ta.,  tail;  Ug.  s.,  urogenital  sinus;  Umb.  c^ 
umbilical  cord. 


396 


TEXT-BOOK  OF  EMBRYOLOGY. 


continuation  of  the  internal  (membranous  and  prostatic)  portion  of  the  urethra. 
The  genital  swellings  also  fuse  and  form  the  scrotum,  the  line  of  fusion  in  the 
medial  line  becoming  the  raphe  (Fig.  348) .  Primarily  the  inguinal  ligaments 
of  the  mesonephroi  are  attached  to  the  corium  of  the  skin  in  the  genital  swellings, 
and  as  the  testicles  descend  they  pass  through  the  inguinal  ring  into  the  scro- 
tum. In  a  sense  the  scrotum  represents  an  evagination  of  the  body  wall 

THE  DEVELOPMENT  OF  THE  SUPRARENAL  GLANDS. 

Although  the  suprarenal  glands  do  not  logically  come  under  the  head  of  the 
urogenital  system,  being  neither  functionally  nor  developmentally  a  part  of  the 
latter,  it  is  most  convenient  to  consider  them  in  this  chapter. 

In  Mammals  including  man.  these  glands  are  composed  of  two  parts  which 
can  be  differentiated  histologically  and  topographically — the  cortex  and 
medulla.  The  cortex  is  composed  of  trabeculae  and  spheroidal  masses  of  cells 

Phasochrome  cells 


Nerve  fibers 


Phaeochrome    Connective 
cells  tissue 


Sympathetic 
ganglion  cells 


FIG.  349. — Section  of  a  sympathetic  ganglion  in  the  cceliac  region  of  a  frog  (Rana  esculenta), 
showing  differentiating  phaeochrome  cells.     Giacomini. 


which  do  not  have  a  strong  affinity  for  the  ordinary  cytoplasmic  stains  am 
which  contain  granules  of  a  fat-like  substance  known  as  lipoid  granules.  Th( 
medulla  is  composed  of  irregularly  arranged  sympathetic  ganglion  cells  am 
other  granular  cells  which,  after  treatment  with  chrome  salts,  acquire  a  pea 
brownish  color.  The  brown  cells  are  known  as  chromaffin  (or  phaeochrome) 
cells  and  their  granules  as  chromaffin  (or  phaeochrome)  granules.  As  cort( 
and  medulla  are  distinct  anatomically,  they  are  also  distinct  developmentally, 
being  derived  from  two  distinct  and  different  parent  tissues  which  unite 
secondarily.  Furthermore,  it  is  an  interesting  fact  that  in  the  lower  Vertebrates 
(Fishes)  the  two  parts  remain  permanently  separate;  that  in  the  ascending 
scale  of  animal  life  (Amphibia,  Reptiles,  Birds)  they  become  more  closely 
associated;  and  that  finally  (in  Mammals)  they  unite  to  form  a  single  glandular 
structure.  In  Mammals  the  phylogenetic  history  is  repeated  with  remarkable 


THE  DEVELOPMENT  OF  THE  UROGENITAL  SYSTEM. 


397 


precision  during  the  development  of  an  individual :  The  two  parts  arise  sepa- 
rately, come  closer  together,  and  finally  unite. 

The  Cortical  Substance.— The  cortex  is  of  mesothelial  (mesodermal) 
origin.  In  embryos  of  five  to  six  mm.  the  mesothelium  at  the  level  of  the 
cephalic  third  of  the  mesonephros  proliferates  and  sends  buds  or  sprouts  into 
the  mesenchyme  at  each  side  of  the  root  of  the  dorsal  mesentery.  These 
sprouts  soon  lose  their  connection  with  the  parent  mesothelium  and  unite  with 
one  another  to  form  a  rather  compact  mass  of  epithelial-like  cells  ventro-lateral 
to  the  aorta  (Fig.  276).  Frequently  the  two  masses  fuse  across  the  medial  line 
ventral  to  the  aorta.  They  constitute  the  anlagen  of  the  cortical  substance  of 


Cortex  — 
Connective  tissue 

Medulla 
Cortex 


Cortex 


Medulla 
(Phaeochrome  cells) 


FIG.  350. — From  a  transverse  section  of  a  40  mm.  pig  embryo,  showing  the  growth  of  the  medullary 
substance  into  the  cortical  substance  of  the  suprarenal  gland.  The  vessel  in  the  center  of 
the  figure  is  the  aorta.  Wiesel. 

the  two  suprarenal  glands.  From  the  fact  that  in  the  lower  forms  they  remain 
separate  from  the  medullary  substance  and  lie  between  the  urinary  organs, 
they  are  known  as  the  inter  renal  organs. 

The  Medullary  Substance. — A  little  later  than  the  appearance  of  the 

cortical  anlage,  the  cells  of  some  of  the  developing  sympathetic  ganglia  become 

differentiated  into  two  types — (i)  the  so-called  sympathoblasts  which  develop  into 

j  sympathetic  ganglion  cells,  and  (2)  phaochromoblasts  which  are  destined  to  give 

|  rise  to  the  phaeochome  or  chromafiin  cells  (Fig.  349).     Hence  the  chromaffin 

i  cells  are  derivatives  of  the  ectoderm,  since  the  ganglia  are  of  ectodermal  origin. 

.  They  soon  become  more  or  less  separated  from  the  ganglia,  migrate  to  the 


398 


TEXT-BOOK  OF  EMBRYOLOGY. 


region  of  the  cortical  anlagen  and  then  penetrate  the  latter  in  cord-like  masses 
(Fig.  350).  Finally  these  masses  unite  in  the  interior  of  the  cortical  substance 
to  form  a  single  compact  mass  (Fig.  351) .  Along  with  the  phaeochrome  masses, 
sympathoblasts  also  are  carried  in  and  give  rise  to  the  sympathetic  ganglion  cells 
within  the  gland.  The  two  types  of  cells  together  constitute  the  medullary 
substance.  In  the  lower  forms  the  phaeochrome  masses  remain  separate  from 
the  cortical  substance  and  are  known  as  the  suprarenal  organs.  In  Mammals 
the  two  sets  of  organs  (interrenal  and  suprarenal)  unite  to  form  the  suprarenal 
gland. 


j       i 

Med.     Cor.     Cor.1 

FIG.  351. — Section  of  the  suprarenal  gland  of  a  119  mm.  pig  embryo.     Cor.,  Cortex;  Cor.*,  some 
cortical  substance  in  the  center  of  the  gland;  Med.,  medulla.     Wiesel. 

At  the  time  when  the  mesonephros  is  fully  developed,  the  cortical  substance 
forms  a  small  oval  body  near  its  cephalic  end.  During  the  union  of  the  cortex 
and  medulla  and  the  atrophy  of  the  mesonephros,  the  suprarenal  gland  becomes 
more  closely  associated  with  the  cephalic  end  of  the  kidney,  and  by  the  middle  of 
the  third  month  has  practically  reached  its  adult  position.  During  the  third 
month  and  the  first  half  of  the  fourth  month  the  glands  increase  in  size  and 
become  relatively  large  structures,  larger  in  fact  than  the  kidneys.  From  the 
fourth  month  on,  they  grow  proportionately  less  than  the  neighboring  organs, 
and  by  the  sixth  month  are  about  half  as  large  as  the  kidneys.  At  birth  the 
ratio  of  their  weight  to  that  of  the  kidneys  is  about  1:3;  in  the  adult  about  1 128. 

While  perhaps  in  a  normal  course  of  development  all  the  anlagen  are  united 
in  the  adult  suprarenal  gland,  it  is  not  unusual  to  find  accessory  structures  in 
various  places.  Some  of  these  consist  of  cortical  tissue  only  and  are  usually 


THE  DEVELOPMENT  OF  THE   UROGENITAL  SYSTEM. 


399 


found  in  or  near  the  capsule  of  the  gland.  Others  may  consist  of  both  cortical 
and  medullary  substances,  and  are  found  in  the  vicinity  of  or  embedded  in  the 
kidneys,  in  the  retroperitoneal  tissue  near  the  kidneys,  in  the  walls  of  neighbor- 
ing blood  vessels,  or  associated  with  the  internal  genital 
organs — in  the  rete  testis  or  epididymis,  or  in  the  broad 
ligament.  These  accessory  structures  may  arise  inde- 
pendently of  the  main  gland,  or  they  may  be  portions  of 
the  main  gland  which  were  separated  during  the  union 
of  the  different  anlagen  of  the  latter  and  were  carried 
away  in  the  descent  of  the  genital  glands. 

In  addition  to  the  chromamn  tissue  which  enters  into 
the  formation  of  the  main  gland  or  of  accessory  glands, 
there  are  other  small  masses  of  this  tissue  which  remain 
permanently  associated  with  some  of  the  prevertebral 
and  peripheral  sympathetic  ganglia. 

Recent  researches  have  shown  that  the  Carotid  Skein 
(glomus  caroticum,  intercarotid  ganglion,  carotid  gland), 
which  formerly  was  believed  to  be  a  derivative  of  the 
epithelial  lining  of  one  of  the  branchial  grooves,  is  of 
sympathetic  origin  and  that  the  cells  acquire  the  charac- 
teristic chromaffin  reaction.  These  facts  indicate  that 
it  is  closely  allied  with  the  medullary  substance  of  the  suprarenal  gland. 


FIG.  352.— Diagram  of 
the  developing  phaeo- 
chrome .  masses  in  a 
human  foetus  of  50* 
mm.  A,  Aorta;  N;. 
cortical  substance  (in- 
terrenal  gland) ;  U, 
ureter;  R,  rectum. 
Kohn. 


Anomalies. 

THE  KIDNEYS. — Rarely  is  there  congenital  absence  of  both  kidneys.  More 
often  there  is  a  high  degree  of  aplasia  in  both  organs  in  otherwise  well-developed 
children.  In  either  case  death  necessarily  soon  follows.  Not  infrequently  one 
kidney,  usually  the  left,  is  poorly  developed  or  absent  and  a  compensatory 
enlargement  of  the  other  exists.  Such  malformations  are  due  to  deficient 
development  of  the  organs,  but  the  causes  underlying  the  deficient  development 
are  obscure. 

One  of  the  most  common  malformations  is  the  abnormal  position  of  one  or 
both  kidneys  (ectopia  of  the  kidneys).  Usually  they  occupy  a  position  lower 
than  the  normal  in  the  abdominal  cavity,  which  indicates  that  they  have  failed, 
during  development,  to  migrate  forward  to  the  normal  limit  (see  p.  369).  Very 
rarely  one  or  both  organs  migrate  beyond  the  normal  limit,  in  which  case  they 
occupy  positions  cranial  to  the  normal. 

Not  infrequently  the  lower  ends  of  the  two  kidneys  are  fused  across  the 
medial  line,  giving  rise  to  the  so-called  "horseshoe  kidney."  Two  renal 
pelves  and  ureters  are  usually  present.  Occasionally  the  fusion  is  so  extensive 


400  TEXT-BOOK  OF  EMBRYOLOGY. 

that  a  single  flat  mass  is  formed.  This  occupies  a  medial  position  or  lies  at 
either  side  of  the  medial  line,  and  may  be  situated  at  the  normal  level  or  lower. 
The  renal  pelvis  may  be  single  or  double,  with  one  or  two  ureters.  In  cases  of 
double  ureters  and  pelves  it  seems  most  likely  that  the  anlagen  of  the  kidneys 
have  fused  secondarily,  that  is,  after  the  evagination  from  the  mesonephric 
ducts  (p.  361) .  In  cases  where  the  pelvis  and  ureter  are  single,  the  fusion  may 
have  occurred  secondarily,  although  there  is  the  possibility  that  only  a  single 
anlage  appeared. 

Occasionally  in  children  and  even  in  adults  the  kidneys  show  a  distinct 
lobulation.  This  is  due  to  the  persistence  of  the  lobulation  that  normally 
exists  in  the  foetus  (p.  367). 

The  kidney  may  be  more  or  less  movable  owing  to  laxity  of  the  surrounding 
tissue,  or  it  may  Refloating,  in  which  case  it  has  a  distinct  mesentery.  These 
cases  should  be  distinguished  from  those  in  which  similar  conditions  have  been 
acquired,  usually  as  the  result  of  trauma. 

Congenital  cysts  of  the  kidney  are  not  uncommon.  They  vary  in  size  and 
number,  sometimes  being  so  numerous  that  they  crowd  out  the  greater  part 
of  the  renal  tissue.  Rarely  they  are  so  large  and  numerous  that  the  affected 
organ  fills  a  large  part  of  the  abdominal  cavity,  resulting  in  serious  or  even 
fatal  disturbances  of  the  functions  of  other  organs.  There  are  three  views  con- 
cerning the  origin  of  these  cysts,  (i)  They  may  be  the  result  of  dilatation  of 
certain  renal  tubules  derived  from  the  nephrogenic  tissue,  which  failed  to  unite 
with  the  straight  tubules  (p.  363).  (2)  Inflammation  in  the  medulla  of  the 
foetal  kidney  may  effect  a  closure  of  the  lumina  of  some  of  the  tubules,  with 
subsequent  dilatation  of  the  portions  (tubules. or  renal  corpuscles)  that  are  cut 
off  from  communication  with  the  renal  pelvis.  (3)  Normally  some  of  the  renal 
corpuscles  and  tubules  degenerate  (p.  369),  and  the,cysts  may  arise  as  dilatations 
of  incompletely  degenerated  corpuscles  or  tubules  or  both.  While  these  views 
appear  reasonable,  none  of  them  has  been  proven.  All  three  views  express 
possibilities,  and  there  is  no  good  reason  for  believing  that  any  one  of  them 
expresses  the  only  possibility. 

THE  URETERS. — The  renal  pelvis  is  sometimes  absent,  the  calyces  uniting 
to  form  two  or  more  tubes  which  in  turn  unite  to  form  the  ureter.  This  prob- 
ably is  the  result  of  abnormal  branching  of  the  ureter  during  development  and 
the  failure  of  the  ends  of  the  branches  to  become  dilated.  Occasionally  the 
ureter  is  double  or  triple  throughout  the  whole  or  a  part  of  its  length.  The 
most  reasonable  explanation  of  two  or  three  complete  ureters  on  either  side  is 
that  two  or  three  separate  evaginations  arose  from  the  mesonephric  duct  (p. 
361.)  Where  the  tube  is  double  in  only  a  part  of  its  length,  an  abnormal 
branching  of  the  single  original  evagination  is  indicated. 
••'  Atresia  of  one  or  both  ureters  is  occasionally  met  with.  This  probably 


THE   DEVELOPMENT   OF  THE   UROGENITAL  SYSTEM.  401 

represents  a  secondary  constriction  after  the  ureter  is  formed  since  both  ex-ag- 
inations are  hollow  from  the  beginning  (p.  391),  but  the  cause  of  the  constric- 
tion is  not  understood.  The  atresia  results  in  dilatation  of  the  portion  of  the 
ureter  on  the  side  toward  the  kidney. 

Abnormal  situations  of  the  openings  are  sometimes  seen,  the  explanation 
of  which  is  to  be  found  in  the  relations  of  these  tubes  to  the  mesonephric  ducts, 
to  the  cloaca,  and  to  the  Miillerian  ducts.  In  the  male  the  ureters  may  open  into 
the  seminal  vesicles,  the  prostatic  urethra,  or  the  rectum.  If  one  recalls  that 
the  ureter  arises  as  an  evagination  from  the  mesonephric  duct  near  the  opening 
of  the  latter  into  the  cloaca  (p.  361),  that  the  cloaca  becomes  separated  into  a 
dorsal  part  (the  rectum)  and  a  ventral  part  (the  urogenital  sinus)  (p.  370),  and 
that  the  proximal  end  of  the  mesonephric  duct  is  so  far  taken  up  into  the  wall 
of  the  urogenital  sinus  (or  bladder)  that  the  ureter  opens  separately  (p.  370),  it  is 
readily  seen  that  any  interference  with  these  normal  processes  of  development 
will  result  in  abnormal  opening  of  the  ureter.  If  the  ureter  does  not  become 
separated  from  the  mesonephric  duct,  it  will  open  into  the  deferent  duct  (vas 
deferens),  the  latter  being  the  proximal  part  of  the  mesonephric  duct.  And 
since  the  seminal  vesicle  is  an  outgrowth  from  the  proximal  end  of  the  meso- 
nephric duct,  the  opening  of  the  ureter  is  likely  to  be  associated  with  the  vesicle^ 
If  the  separation  between  the  ureter  and  mesonephric  duct  is  complete,  but 
the  opening  of  the  ureter  does  not  migrate  cranially  on  the  wall  of  the  bladder, 
the  opening  comes  to  lie  in  the  wall  of  the  prostatic  urethra.  If  the  wall 
(urorectal  fold)  separating  the  urogenital  sinus  and  rectum  is  situated  too  far 
dorsally,  the  opening  of  the  ureter  comes  to  be  in  the  wall  of  the  rectum.  (Con- 
sult Figs.  322,  323,  324,  325.) 

In  the  female  the  ureters  may  open  into  the  urethra,  the  vagina,  or  the  uterus. 
The  explanation  of  the  opening  into  the  urethra  is  the  same  as  in  the  male 
(see  preceding  paragraph).  The  opening  into  the  genital  tract  is  probably  to 
be  explained  on  the  ground  that  the  ureters  fail  to  migrate  cranially  along 
the  wall  of  the  urogenital  sinus  to  the  bladder,  and  as  the  fused  ends  of  the 
Mtillerian  ducts  enlarge  to  form  the  uterus  and  vagina,  the  openings  of  the 
ureters  are  taken  up  into  their  walls. 

THE  BLADDER. — Absence  of  the  bladder  is  very  rare.  Abnormal  small- 
ness,  due  to  imperfect  dilatation  of  the  urogenital  sinus  (p.  371),  is  not  infre- 
quent. 

The  urachus,  which  represents  the  portion  of  the  allantoic  duct  between 
the  bladder  and  the  umbilicus  (p.  371),  not  infrequently  persists  as  a  whole  or 
in  part,  giving  rise  to  certain  anomalous  conditions  in  the  region  of  the  middle 
umbilical  ligament.  The  urachus  may  persist  as  a  complete  tube,  lined 
with  epithelium,  thus  forming  a  means  by  which  urine  can  escape  at  the 
umbilicus.  This  condition  is  usually  associated  with  obstruction  of  the 


402  TEXT-BOOK  OF  EMBRYOLOGY. 

urethra  and  is  known  as  uracho-vesical  fistula.  The  urachus  may  degenerate 
in  part,  leaving  disconnected  portions  which  frequently  become  dilated  to 
form  cysts. 

Vesical  fissure,  the  most  serious  malformation  of  the  bladder,  is  associated 
with  fissure  of  the  lower  abdominal  wall.  The  edges  of  the  cleft  in  the  bladder 
are  continuous  with  those  of  the  cleft  in  abdominal  wall,  the  integument  being 
continuous  with  the  lining  of  the  bladder.  In  some  cases  the  bladder  is 
everted  through  the  cleft,  and  the  cleft  may  even  be  so  extensive  as  to  involve 
the  external  and  internal  genital  organs.  Vesical  fissure  is  much  more  com- 
mon in  the  male  than  in  the  female.  No  very  satisfactory  explanation  of  this 
malformation  has  yet  been  given.  It  is  in  some  way  connected  with  imperfect 
formation  of  the  ventral  abdominal  wall  resulting  from  influences  acting  at  a 
very  early  period  of  development. 

THE  URETHRA  in  both  sexes  may  be  abnormally  small  or  abnormally  large 
or  partly  occluded,  owing  to  faulty  development  of  the  urogenital  sinus.  In 
the  male  the  penile  portion  also  may  be  malformed,  being  represented  merely 
by  a  furrow  on  the  lower  side  of  the  penis.  This  condition,  known  as  hypo- 
spadias,  is  due  to  the  incomplete  fusion  or  lack  of  fusion  between  the  genital  folds 
along  the  lower  side  of  the  genital  tubercle  (p.  394).  In  extreme  cases  the  de- 
fect may  involve  the  scrotum  and  extend  back  as  far  as  the  prostate  gland,  the 
two  halves  of  the  scrotum  being  separated.  Epispadias,  in  which  the  urethral 
cleft  extends  along  the  upper  side  of  the  penis  (or  the  clitoris)  is  rare,  and  is 
usually  associated  with  vesico-abdominal  fissure.  Its  mode  of  origin  is  not 
understood. 

THE  TESTICLES. — One  of  the  most  common  malformations  affecting  the 
male  genital  glands  is  the  condition  known  as  chryptorchism,  in  which  the 
glands,  instead  of  descending  into  the  scrotum,  are  retained  within  the  ab- 
dominal cavity.  One  or  both  testicles  may  be  affected.  They  may  occupy 
their  original  position  far  forward  in  the  abdominal  cavity  or  may  be  situated 
near  the  inguinal  canal,  or  may  lie  at  some  intermediate  point.  The  malposi- 
tion is  due  to  a  failure  in  the  normal  descent  into  the  scrotum  (p.  389).  The 
cause  of  the  failure  is  obscure.  Not  infrequently  the  ectopic  testicles  atrophy 
or  fail  to  develop  properly  at  puberty. 

Congenital  absence  of  one  or  both  testicles  is  rare.  More  frequently  the 
gland  or  efferent  system  of  ducts  is  defective  in  part,  owing  to  imperfect 
development.  In  case  of  absence  of  the  testicles  the  individual  is  small  and 
poorly  developed ;  when  the  glands  are  imperfectly  developed  the  individual  is 
effeminate. 

Cysts  which  are  sometimes  met  with  in  the  epididymis  are  possibly  due  t( 
dilatation  of  incompletely  degenerated  portions  of  the  mesonephric  tubules 
or  Mullerian  ducts.  Teratoid  tumors  and  chorio-epitheliomata  are  occasionally 


THE  DEVELOPMENT   OF  THE   UROGENITAL  SYSTEM.  '  403 

found  in  the  testicle.  For  a  further  discussion  of  these  see  chapter  on  Terato- 
genesis  (XX). 

THE  OVARIES. — Congenital  absence  of  both  ovaries  is  rare;  defective 
development  of  one  is  more  common.  Either  anomaly  may  occur  with  or 
without  defects  in  the  other  genital  organs.  Occasionally  the  ovaries  remain 
rudimentary,  their  function  as  egg-producing  organs  never  being  assumed. 
Malpositions,  due  to  partial  or  complete  failure  in  the  normal  descent  into 
the  pelvis  (p.  392),  are  not  infrequent.  Sometimes,  on  the  other  hand,  they 
descend  to  the  inguinal  canal  and  may  even  pass  through  the  latter  into  the 
labia  majora. 

Ovarian  cysts  occur  frequently.  Some  of  these  (follicular  cysts)  may  arise 
during,  postnatal  life  as  dilatations  of  Graafian  follicles.  Others  probably 
arise  during  foetal  life  in  the  same  manner.  Certain  other  forms  of  ovarian 
tumors,  known  as  cystadenomata,  are  possibly  to  be  considered  as  derivatives 
of  the  epithelium  of  the  medullary  cords  which  in  normal  cases  disappear 
entirely  (p.  377;  also  Fig.  328).  A  discussion  of  the  origin  of  teratoid  tumors  of 
the  ovary  will  be  found  in  the  chapter  on  Teratogenesis  (XX). 

THE  OVIDUCTS,  UTERUS  AND  VAGINA. — Absence  of  the  oviducts  is  usually 
associated  with  malformations  of  other  parts  of  the  genital  tract.  On  the  other 
hand,  normal  oviducts  may  be  present  in  conjunction  with  defective  uterus 
and  vagina.  Atresia  may  occur  at  the  uterine  or  fimbriated  end,  or  at  any 
intermediate  point. 

The  majority  of  the  malformations  of  the  uterus  and  vagina  can  be  at- 
tributed to  defective  processes  of  development  in  the  caudal  ends  of  the  Miiller- 
ian  ducts.  It  will  be  remembered  that  the  caudal  ends  of  these  ducts  normally 
fuse  to  form  a  single  medial  tube  which  opens  into  the  urogenital  sinus,  and 
which  constitutes  the  anlage  of  the  uterus  and  vagina  (p.  385;  Fig.  325).  It  is 
obvious  that  any  defect  in  this  fusion  will  result  in  some  degree  of  duplicity 
in  the  two  organs  in  question.  The  fusion  may  be  almost  complete,  the  result- 
ing abnormality  being  merely  a  small  pocket  which  forms,  at  each  side  of  the 
fundus,  a  continuation  of  the  cavity  of  the  uterus.  There  may  be  a  greater 
degree  of  imperfection  in  the  fusion,  resulting  in  a  partial  division  of  the  uterus 
into  two  horns — bicornuate  uterus.  The  wall  between  the  two  Mullerian  ducts 
may  remain  patent  in  the  entire  uterine  portion  of  the  tract,  thus  giving  rise 
to  a  bipartite  uterus.  If  the  wall  between  the  ducts  remains  intact  throughout 
both  uterine  and  vaginal  portions,  the  result  is  a  complete  division  of  the  utero- 
vaginal  tract — uterus  didelphys.  Occasionally  the  uterine  portion  of  one 
Mullerian  duct  may  fail  to  develop  properly  and  becomes  a  solid  cord,  resulting 
in  an  unicornuate  uterus. 

Not  infrequently  the  uterus  remains  rudimentary — infantile  uterus.  This 
anomaly  is  usually  accompanied  by  stenosis  of  the  vagina.  Stenosis  or  other 


404  TEXT-BOOK  OF  EMBRYOLOGY. 

defects  in  the  vagina  may  occur,  however,  when  the  uterus  is  normal.  In  rare 
instances  the  hymen  is  absent;  in  other  cases  it  closes  the  entrance  to  the  vagina 
• — a  condition  known  as  imperforate  hymen. 

Malformations  of  the  uterus  and  vagina  resulting  from  persistence  of  the 
cloaca  and  atresia  of  the  anus  are  mentioned  on  page  326. 

HERMAPHRODITISM. 

This  condition  implies  a  combination  of  the  male  and  female  sexual  organs 
in  one  individual,  accompanied  by  a  blending  ot  the  general  characteristics  of 
the  two  sexes  When  such  an  individual  possesses  both  ovary  and  testicle,  the 
condition  is  known  as  true  hermaphroditism ;  when  the  individual  possesses 
ovaries  or  testicles,  the  condition  is  known  as  false  hermaphroditism. 

TRUE  HERMAPHRODITISM. — The  presence  of  both  ovary  and  testicle  in  one 
individual  is  one  of  the  rarest  anomalies  in  man.  Furthermore,  one  or  both  of 
the  organs  are  sexually  immature.  Three  forms  can  be  recognized  (Klebs) : 

1.  Lateral  hermaphroditism,  in  which  an  ovary  is  present  on  one  side  and  a 
testicle  on  the  other; 

2.  Unilateral  hermaphroditism,  in  which  both  ovary  and  testicle  are  present 
on  one  side,  either  ovary  or  testicle,  or  neither,  on  the  other  side; 

3.  Bilateral  hermaphroditism,  in  which  both  ovary  and  testicle  are  present  on 
both  sides. 

In  all  these  cases  the  general  character  of  the  body  is  of  an  intermediate 
type,  sometimes  tending  toward  the  male,  sometimes  toward  the  female.  The 
external  genitalia  are  also  of  an  intermediate  type,  with  hypospadias,  small 
penis,  separate  scrotal  halves,  and  small  vaginal  orifice.  The  uterus  usually 
shows  some  degree  of  duplicity. 

FALSE  HERMAPHRODITISM. — In  this  type  of  hermaphroditism,  in  which 
either  ovaries  or  testicles  are  present  in  an  individual  with  mixed  general 
sexual  characteristics,  two  varieties  can  be  recognized : 

1.  Masculine  false  hermaphroditism,  the  more  common,  in  which  testicles  are 
present  but  the  external  genitalia  and  general  character  of  the  body  approximate 
the  female; 

2.  Feminine  false  hermaphroditism,  in  which  ovaries  are  present  but  other- 
wise male  characteristics  predominate. 

The  causes  underlying  the  origin  of  hermaphroditism  are  among  the  most 
obscure  in  teratogenesis.  It  is  well  known  that  up  to  the  fourth  or  fifth  week 
the  anlagen  of  the  sexual  glands  are  histologically  "indifferent,"  and  later  be- 
come differentiated  into  ovaries  or  testicles  (p.  375).  Since  the  secondary 
sexual  characteristics  are  dependent  upon  the  development  of  the  primary,  they 
also  are  brought  out  later.  If  the  "  indifferent "  glands  give  rise  to  both  ovaries 


THE  DEVELOPMENT  OF  THE  UROGENITAL   SYSTEM.  405 

and  testicles,  true  hermaphroditism  is  the  result;  if  they  give  rise  to  either 
ovaries  or  testicles  but  the  external  genitalia  and  general  characteristics 
develop  in  the  opposite  direction,  false  hermaphroditism  is  the  result.  Thus 
the  hermaphroditic  condition  is  potentially  present  in  every  individual 
during  the  earlier  stages  of  development ;  the  most  remarkable  fact  is  that  it 
is  not  more  common. 

References  for  Further  Study. 

ADAMI,  J.  G.:  The  Principles  of  Pathology.     Vol.  I,  1908. 

AICHEL,  O.:  Vergleichende  Entwickelungsgeschichte  und  Stammesgeschichte  der 
Nebennieren.  Arch.f.  mik  Anat.,  Bd.  LVI,  1900. 

ALLEN,  B.  M.:  The  Embryonic  Development  of  the  Ovary  and  Testis  in  Mammals. 
Am.  Jour,  of  Anat.,  Vol.  Ill,  1904. 

BEARD,  J.:  The  Germ-cells  of  Pristiurus.     Anat.  Anz.,  Bd.  XXI,  1902. 

BEARD,  J.:  The  Morphological  Continuity  of  the  Germ  Cells  in  Raja  batis.  Anat. 
Am.,  Bd.  XVIII,  1900. 

BREMER,  J.  L. :  The  Interrelation  of  the  Mesonephros,  Kidney  and  Placenta  in  differ- 
ent Classes  of  Mammals.  Am.  Jour,  of  Anat.,  Vol.  XIX,  1916. 

BONNET,  R.:  Lehrbuch  der  Entwickelungsgeschichte.      Berlin,  1907. 

CORNER,  G.  W.:  On  the  Origin  of  the  Corpus  Luteum  in  the  Sow  from  both 
Granulosa  and  Theca  Interna.  Am.  Jour,  of  Anat.,  Vol.  XXVI,  1919. 

EGGERTH,  A.  H.:  On  the  Anlage  of  the  Bulbo-urethral  (Cowper's)  and  Major  Vestibu- 
lar  (Bartholin's)  Glands  in  the  Human  Embryo.  Anat.  Record,  Vol.  IX,  1915. 

EIGENMANN,  C.  H.:  On  the  Precocious  Segregation  of  the  Sex-cells  of  Micrometrus 
aggregatus.  Jour,  of  MorphoL,  Vol.  V,  1891. 

FELIX,  W.:  Entwickelungsgeschichte  des  Excretions-systems.  Ergebnisse  der  Anat. 
u.  Entunck.,  Bd.  XIII,  1903. 

FELLX,  W.,  and  BUHLER,  A.:  Die  Entwickelung  der  Harn-  und  Geschlechtsorgane. 
In  Hertwig's  Handbuch  d.  vergleich.  u.  experiment.  Entwickelungslehre  der  Wirbeltiere, 
Bd.  III.  Teil  I,  1904. 

GAGE,  S.  P.:  A  Three  Weeks'  Human  Embryo,  with  Especial  Reference  to  the  Brain 
and  Nephric  System.  Am.  Jour,  of  Anat.,  Vol.  IV,  1905. 

GERHARDT,  U.:  Zur  Entwickelung  der  bleibenden  Nieren.  Arch.  f.  mik.  Anat.,  Bd. 
LVII,  1901 

HERTWIG,  O. :  Lehrbuch  der  Entwickelungsgeschichte  des  Menschen  und  der  Wirbel- 
tiere. Jena,  1906. 

HILL,  E.  C.:  On  the  Gross  Development  and  Vascularization  of  the  Testis.  Am. 
Jour,  of  Anat.,  Vol.  VI,  1907. 

HUBER,  G.  C. :  On  the  Development  and  Shape  of  the  Uriniferous  Tubules  of  Certain 
of  the  Higher  Mammals.  Am.  Jour,  of  Anat.,  Vol.  IV,  SuppL,  1905. 

KED3EL,  F.:  Zur  Entwickelungsgeschichte  des  menschlichen  Urogenitalapparatus. 
Arch.f.  Anat.  u.  Physiol.,  Anat.  Abth.,  1896 

KINGSBURY,  B.  F.:  The  Morphogenesis  of  the  Mammalian  Ovary:  Felis  domestica. 
Am.  Jour,  of  Anat.,  Vol.  XV,  1913. 

KOHN,  A.:  Das  chromaffine  Gewebe.     Ergebnisse  der  Anat.  u.  Enlwick.,  Bd.  XII,  1903. 

KOLLMAN,  J.    Lehrbuch  der  Entwickelungsgeschichte  des  Menschen.     Jena,   1898. 

KOLLMAN,  J.:  Handatlas  der  Entwickelungsgeschichte  des  Menschen.  Jena,  1907, 
Bd.  II. 


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MARCHAND,  F.:  Missbildimgen.  In  Eulenburg's  Real-Encyclopddie  der  gesammten 
HeUkunde,  Bd.  XV,  1897. 

McMuRRiCH,  J.  P.:  JThe  Development  of  the  Human  Body.     Philadelphia,  1919. 

MINOT,  C.  S.:  Laboratory  Text-book  of  Embryology.     Philadelphia,  1903. 

MORGAN,  T.  H.:  ,The  Cause  of  Gynandromorphism  in  Insects.  Am.  Naturalist, 
Vol.  XLI,  1907. 

NAGEL,  W.:  Ueber  die  Entwickelung  des  Urogenitalsystems  des  Menschen.  Arch.  f. 
Mik.  Anat.,  Bd.  XXXIV,  1889. 

NAGEL,  W.:  Ueber  die  Entwickelung  der  Urethra  und  des  Dammes  beim  Menschen. 
Arch.f.  mik.  Anat.,  Bd.  XL,  1892. 

NAGEL,  W.:  Ueber  die  Entwickelung  des  Uterus  und  der  Vagina  beim  Menschen. 
Arch.f.  mik.  Anat.,  Bd.  XXXVII,  1891. 

PIERSOL,  G.  A.:  Teratology.  In  Wood's  Reference  Handbook  of  the  Medical  Sciences, 
Vol.  VII,  1904. 

POHLMAN,  A.  G.:  The  Development  of  the  Cloaca  in  Human  Embryos.  Am.  Jour,  of 
Anat.,  Vol.  XII,  1911. 

POLL,  H.:  Die  Entwickelung  der  Nebennierensysteme.  In  Hertwig's  Handbuch  der 
vergleich.  u.  experiment.  Entwickelungslehre  der  Wirbeltiere,  Bd.  Ill,  Teil  I,  1905. 

POLL,  H.:  Die  Entwickelung  der  Nebennierensysteme.  In  Hertwig's  Handbuch  der 
vergleich.  u.  experiment.  Entwickelungslehre  der  Wirbeltiere,  Bd.  Ill,  Teil  I,  1905. 

RABL,  C.:  Ueber  die  Entwickelung  des  Urogenitalsystems  der  Selachier.  Morphol. 
Jahrbuch,  Bd.  XXIV,  1896.  Theorie  des  Mesoderms.  Ueber  die  erste  Entwickelung  der 
Keimdruse.  Morphol.  Jahrbuch,  Bd.  XXIV,  1896. 

SCHREINER,  H.  E.:  Ueber  die  Entwickelung  der  Amniotenniere.  Zeitschr.  /. 
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de  Biol.,  Paris,  Ser.  10,  T.  II,  1895. 

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TANDLER,  J.:  Ueber  Vornieren-Rudimente  beim  menschlichen  Embryo.  Anat. 
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WINIWARTER,  H.:  Recherches  sur  1'ovogenese  et  1'organogenese  de  1'ovaire  des 
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Anat.,  Vol.  I,  No.  3,  1902. 


CHAPTER  XVI. 
THE  DEVELOPMENT  OF  THE  INTEGUMENTARY  SYSTEM. 

The  integument  consists  of  the  skin  and  certain  accessory  structures.  The 
skin  is  composed  of  the  dermis  (or  corium)  and  the  epidermis.  The  accessory 
structures  comprise  the  hairs,  nails,  sudoriferous  glands,  sebaceous  glands,  and 
mammary  glands.  The  epidermis  (or  epithelial  layer)  and  all  the  accessory 
structures  are  derived  from  the  ectoderm;  the  dermis  is  mesodermal  in  its 
origin.  Other  appendages  of  the  skin — such  as  scales,  feathers,  claws,  hoofs, 
and  horns — which  are  found  only  in  the  lower  animals,  are  ectodermal 
derivatives  and  belong  in  the  same  class  as  the  accessory  structures  in  man. 

The  Skin. 

THE  EPIDERMIS. — The  embryonic  ectoderm  consists  primarily  of  a  single 
layer  of  cells  (Fig.  72).  During  the  latter  part  of  the  first  month,  the  single 
layer  gives  rise  to  two  layers,  of  which  the  outer  is  composed  of  irregular  flat 
cells  and  is  known  as  the  epitrichium  or  periderm,  the  inner  or  basal,  of  larger 
cuboidal  cells  which  are  the  progenitors  of  the  epidermal  cells  and  of  the  acces- 
sory structures.  The  epitrichial  cells  later  become  dome-shaped  and  acquire 
a  vesicular  structure,  the  nuclei  becoming  less  distinct.  They  persist  until  the 
middle  of  foetal  life  and  are  then  cast  off  and  mingle  with  the  secretion  of  the 
newly  formed  sebaceous  glands  as  a  constituent  of  the  vernix  caseosa  (see  p.  412) . 
The  epidermal  cells,  constantly  increasing  in  number,  soon  come  to  form  several 
layers  (4  to  6  in  the  sixth  month).  The  innermost  layer  rests  upon  the  base- 
ment membrane  and  is  composed  of  cuboidal  or  columnar  cells  rich  in  cytoplasm ; 
the  outer  layers  consist  of  irregular  cells  with  clearer  contents  and  less  distinct 
nuclei. 

As  development  proceeds,  the  basal  layer  gives  rise  to  several  layers  which, 
together  constitute  the  stratum  germinativum.  The  cells  of  the  innermost 
layers  are  constantly  proliferating  and  thus  forming  new  cells  which  are  pushed 
toward  the  surface.  During  the  seventh  month  keratohyalin  granules  appear 
in  two  or  three  layers  which  are  then  known  collectively  as  the  stratum  granu- 
losum.  The  clearer  cells  of  the  superficial  layers  undergo  a  process  of  de- 
generation by  which  their  contents  are  transformed  into  a  horny  substance, 
the  nuclei  becoming  fainter  and  finally  disappearing.  These  modified  or  degen- 
erated cells,  which  are  constantly  being  cast  off  and  replaced  by  others  from 

407 


408 


TEXT-BOOK  OF  EMBRYOLOGY. 


the  deeper  layers,  constitute  the  stratum  corneum  (Fig.  354).  In  the  thick 
epidermis,  on  the  palms  of  the  hands  and  the  soles  of  the  feet,  for  example,  a 
few  layers  of  cells  just  outside  of  the  stratum  granulosum  become  specially 
modified  (keratinized)  to  form  the  stratum  lucidum. 

THE  DERMIS.— In  the  first  month  the  dermis  is  represented  by  closely  ar- 
ranged, spindle-shaped  mesenchymal  (mesodermal)  cells  underlying  the 
epidermis,  and  is  separated  from  the  latter  by  a  delicate  basement  membrane. 
This  mesenchymal  tissue  gives  rise  to  fibrous  connective  tissue  which,  about 
the  third  month,  becomes  differentiated  into  two  layers— the  dermis  proper 
and  the  deeper  subcutaneous  tissue.  The  papillae  develop  as  little  projections 
of  the  dermis  which  grow  into  the  stratum  germinativum  of  the  epidermis. 
In  some  of  these,  many  blood  vessels  appear,  while  in  others  nerve  endings 


Eponychium 
Root  of  nail  1      Nail 


Sole  plate 


Phalanx  II 


Sweat  glands 


FlG.  353. — Longitudinal  section  through  the  end  of  the  middle  finger  of  a 
5  months  human  foetus.     Bonnet. 


(tactile  corpuscles  of  Meissner)  develop,  thus  giving  rise  to  vascular  and  nerve 
papillae.  Usually  a  considerable  amount  of  fat  develops  in  the  subcutaneous 
tissue.  Some  of  the  mesencnymal  cells  of  the  dermis  are  transformed  into 
smooth  muscle  cells  which  are  found  in  connection  with  the  hairs  (arrectores 
pilorum) ,  in  the  scrotum  (tunica  dartos) ,  and  in  the  nipples. 

The  dermis  has  generally  been  considered  as  a  derivative  of  the  cutis  plates 
(p.  131)  which,  with  the  myotomes,  constitute  the  outer  walls  of  the  primitive 
segments,  but  it  is  probable  that  the  outer  walls  of  the  segments  are  trans- 
formed wholly  into  muscle  tissue  (McMurrich). 

The  pigment  in  the  dermis  develops  in  the  form  of  granules  in  the  connect- 
ive tissue  cells;  that  in  the  epidermis  appears  as  granules  in  the  cells  of  the  deeper 
layers  (white  races)  or  of  all  the  layers  (dark  races).  Whether  the  pigment  in 
the  epidermis  arises  independently  or  is  carried  from  the  dermis  by  wandering 
cells  is  not  known. 


THE  DEVELOPMENT  OF  THE  INTEGUMENTARY  SYSTEM.  409 

The  Nails. 

The  nails  are  derivatives  of  the  epidermal  layer  of  the  ectoderm,  and  cor- 
respond morphologically  to  the  claws  and  hoofs  of  lower  animals.  The 
epidermis  on  the  end  of  each  finger  and  toe  forms  a  thickening,  known  as  the 
primitive  nail,  which  is  encircled  by  a  faint  groove  (Zander).  This  occurs 
about  the  ninth  week.  Later  the  nail  area  migrates  to  the  dorsal  side  of  the 
digit  and  becomes  somewhat  sunken  below  the  surface  of  the  surrounding 
epithelium  (Fig.  353).  These  observations  have  led  to  the  conclusion  that 
primarily  the  nails  in  man  occupied  positions  on  the  ends  of  the  digits,  cor- 
responding to  the  positions  of  the  claws  in  lower  forms.  Furthermore,  the  fact 
that  the  nails  (or  their  anlagen)  are  at  first  situated  on  the  ends  of  the  digits  and 
subsequently  migrate  dorsally  would  exolain  the  innervation  of  the  nail  region 
by  the  palmar  (and  plantar)  nerves. 


c^---  -  ~~zr  --  5 -z^ 
^£~+~2  -  Vs "'  -~-^ 


Strat.  corneum  "\ 

>  Epidermis 
Strat.  germinativum  J 


••V?«* —~- Hair  papilla 


\ 

Con.  tis.  follicle  l^-JflF*  *  1  *       x 

.-"'"3^^  N 


Hair  germ 


Hair  papilla  Connective  tissue 

follicle 

FIG.  354. — Vertical  section  of  the  skin  of  a  mouse  embryo  of  18  mm.,  showing 
early  hair  germs.     Maurer. 

After  the  dorsal  migration  of  the  nail  area,  the  epithelium  and  dermis  along, 
the  proximal  and  lateral  edges  become  still  more  elevated  to  form  the  nail  wall, 
the  furrow  between  the  latter  and  the  nail  being  the  nail  groove.  At  the  distal 
edge  of  the  nail  area,  the  epithelium  becomes  thickened  to  form  the  so-called 
sole  plate,  which  is  probably  homologous  with  the  more  highly  developed  sole 
plate  in  animals  with  hoofs  or  claws.  The  epithelium  of  the  nail  area  increases 
in  thickness,  and,  as  in  the  skin,  becomes  differentiated  into  three  layers 
(Fig.  353).  The  outer  layers  of  cells  become  transformed  into  the  stratum 
corneum.  The  cells  of  the  next  deeper  layers,  which  acquire  keratin  granules 
and  constitute  the  stratum  lucidum,  degenerate  and  give  rise  to  the  nail  sub- 
stance. Thus  the  nail  is  a  modified  portion  of  the  stratum  lucidum.  The 
layers  of  epithelium  beneath  the  nail  form  the  stratum  germinativum,  which, 
with  the  subjacent  dermis,  is  thrown  into  longitudinal  ridges. 


410  TEXT-BOOK  OF  EMBRYOLOGY. 

After  its  first  formation,  the  nail  is  covered  by  the  stratum  corneum  and 
the  epitrichium,  the  two  together  forming  the  eponychium.  The  epitrichium 
soon  disappears;  later  the  stratum  corneum  also  disappears  with  the  exception 
of  a  narrow  band  along  the  base  of  the  nail. 

The  formation  of  nail  substance  begins  during  the  third  or  fourth  month  in 
the  proximal  part  of  the  nail  area.  The  nail  grows  from  the  root  and  from  the 
under  surface  in  the  region  marked  by  the  whitish  color  (the  lunuld).  New 
keratinized  cells  are  added  from  the  subjacent  stratum  germinativum  and  be- 
come degenerated  to  form  new  nail  substance  which  takes  the  place  of  the  old  as 
the  latter  grows  distally. 

The  Hair. 

The  hairs,  like  the  nails,  are  derivatives  of  the  epidermal  layer  of  the  ecto- 
derm. In  embryos  of  about  three  months,  local  thickenings  of  the  epidermis 
appear  (beginning  in  the  region  of  the  forehead  and  eye-brows)  and  grow 
obliquely  into  the  underlying  dermis  in  the  form  of  solid  buds — the  hair  germs 
(Fig.  355,  I,  II).  As  the  buds  continue  to  elongate  they  become  club-shaped 
and  the  epithelium  at  the  end  of  each  molds  itself  over  a  little  portion  of  the 
dermis  in  which  the  cells  have  become  more  numerous  and  which  is  known  as 
the  hair  papilla  (Fig.  354). 

As  the  epidermal  bud  grows  deeper,  its  central  cells  become  spindle-shaped 
and  undergo  keratinization  to  form  the  beginning  of  the  hair  shaft;  the  peripheral 
layers  constitute  the  anlage  of  the  root  sheath  (Fig.  355,  III,  IV).  The  hair 
shaft  grows  from  its  basal  end,  new  keratinized  cells  being  added  from  the 
epithelium  nearest  the  papilla  as  the  older  cells  are  pushed  toward  the  surface 
of  the  skin.  The  surface  cells  of  the  hair  shaft  become  flattened  to  form  the 
cuticle  of  the  hair  (Fig.  355,  V).  The  hairs  appear  above  the  surface  about  the 
fifth  month.  Of  the  cells  of  the  root  sheath,  those  nearest  the  hair  become 
scale-like  to  form  the  cuticle  of  the  root  sheath;  the  next  few  layers  become 
modified  (keratinized)  to  form  Huxley's  and  Henle's  layers.  Outside  of  these 
is  the  stratum  germinativum,  the  basal  layer  of  which  is  composed  of  columnar 
cells  resting  upon  a  distinct  basement  membrane.  The  stratum  germinativum 
is  continued  over  the  tip  of  the  papilla,  where  its  cells  give  rise  to  new  cells  for 
the  hair  shaft  (Fig.  355,  V). 

The  connective  tissue  around  the  root  sheath  becomes  differentiated  into  an 
inner  highly  vascular  layer,  the  fibers  of  which  run  circularly,  and  an  outer 
layer,  the  fibers  of  which  extend  along  the  sheath.  The  two  layers  together  con- 
stitute the  connective  tissue  follicle. 

The  first  formed  hairs,  which  are  exceedingly  fine  and  silky,  develop  in  vast 
numbers  over  the  surface  of  the  embryonic  body  and  are  known  collectively  as 
the  lanugo.  This  growth  is  lost  (beginning  before  birth  and  continuing  during 


THE  DEVELOPMENT  OF  THE  INTEGUMENTARY  SYSTEM.  411 

the  first  and  second  years  after),  except  over  the  face,  and  is  replaced  by  coarser 
hairs.     These  in  turn  are  constantly  being  shed  during  the  life  of  the  individual 


'••;•**•-/ 

fltf 


Fl°.  355. — Five  stages  in  the  development  of  a  human  hair.     Stohr. 

te>  Papilla;  b,  arrector  pili  muscle;  c,  beginning  of  hair  shaft;  d,  point  where  hair  shaft  grows 
through  epidermis;  e,  anlage  of  sebaceous  gland;  /,  hair  germ;  g,  hair  shaft;  h,  Henle's 
layer;  i,  Huxley's  layer;  k,  cuticle  of  root  sheath;  /,  inner  root  sheath;  m,  outer  root  sheath 
in  tangential  section;  n,  outer  root  sheath;  o,  connective  tissue  follicle. 

and  replaced  by  new  ones.     The  new  hairs  probably  in  most  cases  develop  from 
the  old  follicles,  the  cells  over  the  old  papillae  proliferating  and  the  newly 


412  TEXT-BOOK  OF  EMBRYOLOGY. 

formed  hairs  growing  up  through  the  old  sheaths.  In  some  cases,  however,  new 
follicles  are  formed  directly  from  the  epidermis  and  dermis.  In  some  of  the 
lower  Mammals,  new  hair  germs  appear  as  outgrows  from  the  sheaths  of  old 
follicles,  thus  giving  rise  to  tufts  of  hair.  The  arrectores  pilorum  muscles  arise 
from  the  dermal  (mesenchymal)  cells  and  become  attached  to  the  follicles  below 
the  sebaceous  glands. 

The  Glands  of  the  Skin. 

THE  SEBACEOUS  GLANDS. — These  structures  usually  develop  in  connection 
with  hairs.  From  the  root  sheath  a  solid  bud  of  cells  grows  out  into  the  dermis 
(Fig.  355,  IV)  and  becomes  lobed.  The  central  cells  of  the  mass  undergo  fatty 
degeneration  and  the  products  of  degeneration  pass  to  the  surface  of  the  skin 
through  the  space  between  the  hair  and  its  root  sheath.  The  more  peripheral 
cells  proliferate  and  give  rise  to  new  central  cells  which  in  turn  are  transformed 
into  the  specific  secretion  of  the  gland,  the  whole  process  being  continuous.  On 
the  margins  of  the  lips,  on  the  labia  minora'aridon  the  glans  penis  and  prepuce, 
glands  similar  in  character  to  the  sebaceous  glands  arise  directly  from  the 
epidermis  independently  of  hairs. 

THE  SUDORIFEROUS  GLANDS. — The  sweat  glands  :begin  to  develop  during 
the  fifth  month  as  solid  cylindrical  growths  from  the  deeper  layers  of  the  epider- 
mis into  the  dermis  (Fig.  353).  Later  the  deeper  ends  of  the  cylinders  become 
coiled  and  lumina  appear.  The  lumina  do  not  at  first  open  upon  the  surface 
but  gradually  approach  it  as  the  deeper  epidermal  layers  replace  the  more 
superficial. 

THE  VERNIX  CASEOSA. — During  foetal  life'  the  secretion  of  the  sebaceous 
glands  becomes  mingled  with  the  cast-off  epitrichial  and  epidermal  cells  to  form 
the  whitish  oleaginous  substance  (sometimes  called  the  smegma  embryonum) 
that  covers  the  skin  of  the  new-born  child.  It  is  collected  especially  in  the 
axilla,  groin  and  folds  of  the  neck. 

THE  MAMMARY   GLANDS. 

In  embryos  of  six  to  seven  mm.,  or  even  less,  a  thickening  of  the  epidermis 
occurs  in  a  narrow  zone  along  the  ventro-lateral  surface  of  the  body  (Strahl). 
In  embryos  of  1 5  mm.  this  thickening,  known  as  the  milk  ridge,  extends  from  the 
upper  extremity  to  the  inguinal  region  (Kallius,  Schmidt).  Later  the  caudal 
end  of  the  ridge  disappears,  while  the  cephalic  portion  becomes  more  prominent. 
The  further  history  of  the  ridge  has  not  been  traced,  but  in  embryos  considerably 
older  the  anlage  of  each  gland  is  a  circular  thickening  of  the  epidermis  in  the 
thoracic  region,  projecting  into  the  underlying  dermis.  It  seems  most  probable 
that  this  local  thickening  represents  a  portion  of  the  original  ridge,  the  remainder 


THE  DEVELOPMENT  OF  THE  INTEGUMENTARY  SYSTEM. 


413 


having  disappeared.  Later  the  central  cells  of  the  epidermal  mass  become 
cornified  and  are  cast  off,  leaving  a  depression  in  the  skin  (Fig.  356).  In  em- 
bryos of  250  mm.  a  number  of  solid  secondary  buds  have  grown  out  (Fig.  357). 
These  resemble  the  anlagen  of  the  sweat  glands,  to  which  they  are  generally 
considered  as  closely  allied  (Hertwig,  Wiedersheim  and  others), and  represent 
the  excretory  ducts.  Continued  evaginations  from  the  terminal  parts  of  the 
excretory  ducts  form  the  lobular  ducts  and  acini.  The  acini,  however,  are 
scarcely  demonstrable  in  the  male,  and  not  even  in  the  female  until  pregnancy. 
Lumina  appear  by  a  separation  and  breaking  down  of  the  central  cells  of  the 
ducts  and  acini,  the  peripheral  cells  remaining  as  their  lining. 


Epitrichium 


Nipple 
depression 


Dermis 


Stratum 


Stratum 
germinativum 


Dermis 
(Areolar  zone) 


FIG.  356. — Vertical  section  through  the  anlage  of  the  mammary  gland  of 
a  human  foetus  of  16  cm.     Bonnet. 

Late  in  fretal  life,  or  sometimes  after  birth,  the  original  depressed  gland 
area  becomes  elevated  above  the  surface  to  form  the  nipple.  The  excretory 
ducts  (15  to  20  in  number)  which  at  first  opened  into  the  depression,  thus  come 
to  open  on  the  surface  of  the  nipple.  In  the  area  around  the  nipple — the 
areola — numerous  sudoriferous  and  sebaceous  glands  develop,  some  of  which 
come  to  open  into  the  lacteal  ducts.  Sometimes  rudimentary  hairs  appear. 
Other  glands — known  as  areolar  glands  (of  Montgomery) — resembling  rudi- 
mentary mammary  glands  also  develop  from  the  epidermis  of  the  areola. 

After  birth  the  mammary  glands  continue  to  grow  slowly  in  both  sexes  up  to 
the  time  of  puberty.  After  this  they  cease  to  grow  in  the  male,  and  then  atrophy. 
In  the  female,  growth  of  the  glandular  elements  goes  on,  but  very  slowly,  and 
usually  a  considerable  amount  of  fat  develops  in  the  surrounding  tissue, 
causing  the  enlargement  of  the  breasts. 

The  Mammary  Glands  of  Pregnancy. — Even  in  the  female,  as  stated  before, 
acini  are  scarcely  demonstrable  until  pregnancy.  The  mamma  consists 


414 


TEXT-BOOK  OF  EMBRYOLOGY. 


mostly  of  connective  tissue  and  fat,  with  scattered  groups  of  duct-like  tubules. 
During  pregnancy  the  tubules  give  rise  to  the  acini  by  a  process  of  evagination, 
the  cells  increasing  in  number  by  mitosis.  Toward  the  end  of  pregnancy  each 
excretory  duct  and  its  smaller  ducts  and  acini  form  a  distinct  lobe  with  a  rela- 
tively small  amount  of  connective  tissue.  The  epithelium  is  low  or  cuboidal, 
and  fat  begins  to  accumulate,  in  the  seventh  or  eighth  month,  as  droplets  in  the 
basal  parts  of  the  cells.  The  droplets  increase  in  number  and  in  size,  approach- 
ing the  inner  end  of  the  cell,  until  finally  the  cell  is  practically  filled.  At  the 
beginning  of  lactation  the  fat  escapes  into  the  lumen  of  the  acinus,  leaving  a  bit 
of  ragged  cytoplasm  with  a  nucleus.  This  regenerates  into  a  cell  capable  of 


Stroma 
(dermis) 


Stroma 
FIG.  357. — Vertical  section  of  the  anlage  of  the  mammary  gland  of  a  human  foetus  of  25  cm.    Nagel. 


further  activity;  and  it  is  probable  that  the  same  cell  may  become  filled  with 
fat  and  discharge  its  contents  several  times  during  lactation. 

During  pregnancy  and  lactation  the  acini  also  contain  leucocytes  which  have 
wandered  through  the  epithelium  from  the  surrounding  tissue.  These  contain 
fat  droplets  and  are  known  as  colostrum  corpuscles. 

At  the  end  of  lactation  the  acini  atrophy  and  disappear,  the  lobules  becoming 
masses  of  connective  tissue  and  fat,  which  contain  groups  of  duct-like  tubules 
and  which  are  so  closely  joined  with  one  another  that  they  are  indistinguishable 
as  lobules. 

Anomalies. 

ANOMALIES  OF  THE  SKIN. — The  epidermis  may  develop  to  an  abnormal  de- 
gree over  the  entire  surface  of  the  body,  forming  a  horny  layer  which  is  broken 
only  where  the  skin  is  folded  by  the  movement  of  the  members  of  the  body— 
a  condition  known  as  hyperkeratosis.  Or  the  abnormal  development  may  give 
rise  to  irregular  patches  of  thick  epithelium — ichthyosis.  In  either  case,  hairs 
and  sebaceous  glands  are  usually  absent  over  the  affected  areas. 


THE  DEVELOPMENT  OF  THE  INTEGUMENTARY  SYSTEM.  415 

Occasionally  pigment  develops  in  excess  over  larger  or  smaller  areas  of  the 
skin,  giving  rise  to  the  so-called  ncevi  pigmentosi.  In  some  cases,  on  the  other 
hand,  there  is  total  or  almost  total  lack  of  pigment  in  the  skin  and  hair  (usually 
accompanied  by  defective  pigmentation  of  the  iris,  chorioid  and  retina) — • 
a  condition  known  as  albinism.  There  are  also  instances  of  partial  albinism. 
The  influence  of  heredity  in  albinism  is  doubtful,  for  albinos  are  usually  the 
children  of  ordinary  parents. 

The  angiomata  (lymphangiomata,  haemangiomata)  found  in  the  skin  are  due 
to  dilated  lymphatic  or  blood  channels,  the  color  in  haemangiomata  being  due 
to  the  haemoglobin  in  the  blood. 

Dermoid  Cysts. — The  congenital  dermoid  cysts  not  infrequently  found  in  or 
under  the  skin  are  usually  situated  in  or  near  the  line  of  fusion  of  embryonic 
structures,  as  in  the  region  of  the  branchial  arches,  along  the  ventral  body 
wall  and  on  the  back.  During  the  fusion  of  adjacent  structures,  portions  of  the 
epidermis  become  constricted  from  the  parent  tissue  and  come  to  lie  in  the  der- 
mis,  where  they  continue  to  grow  and  produce  cystic  masses  and  sometimes 
give  rise  to  hairs  and  sebaceous  glands'.  This  type  of  dermoid  is  to  be  dis- 
tinguished from  that  found  for  example  in  the  ovary,  in  which  derivatives  of 
all  three  germ  layers  are  present  (see  Chap.  XX). 

ANOMALIES  OF  THE  EPIDERMAL  DERIVATIVES. — Occasionally  hair  develops 
in  profusion  over  areas  of  the  skin  that  naturally  possess  only  a  fine,  silky  growth, 
such,  for  example,  as  a  woman's  face.  Or  nearly  the  entire  body  may  be 
covered  by  an  unusual  amount  of  hair.  Such  conditions — known  as  hyper- 
trichosis — possibly  represent  the  persistence  and  continued  growth  of  the 
lanugo  (p.  410)  and  in  this  sense  are  to  be  regarded  as  the  result  of  arrested 
development  (Unna,  Brandt).  Congenital  absence  of  the  hair  (hypotrichosis, 
alopecia)  is  a  rare  anomaly  and  is  usually  accompanied  by  defective  develop- 
ment of  the  teeth  and  nails. 

Sebaceous  cysts,  generally  regarded  as  due  to  accumulation  of  secretion 
in  the  sebaceous  glands,  sometimes  probably  represent  remnants  of  displaced 
pieces  of  epidermis  apart  from  the  hairs  (Chiari) . 

Supernumerary  mammary  glands  (hypermastid)  and  nipples  (hyperthelia]  are 
not  infrequently  present  in  both  males  and  females.  They  are  usually  situated 
below  the  normal  mammae  (rarely  in  the  axillary  region),  in  a  line  drawn  from 
the  axilla  to  the  groin,  and  probably  represent  persistent  and  abnormally  de- 
\  veloped  portions  of  the  milk  ridge  (see  p.  412).  In  very  rare  cases  a  super- 
numerary gland  develops  in  some  other  region  (even  on  the  thigh).  If  the 
mammary  glands  are  morphologically  allied  to  the  sweat  glands  (p.  413),  these 
misplaced  mammae  are  suggestive  of  anomalous  development  of  some  of  the 
sweat  gland  anlagen. 


416 


TEXT-BOOK  OF  EMBRYOLOGY. 


References  for  Further  Study. 


BROUHA:  Recherches  sur  les  di verses  phases  du  developpement  et  de  Pactivite  de  la 
mammelle.     Arch,  de  Biol.,  T.  XXI,  1905. 

BONNET,  R. :  Die  Mammarorgane  im  Lichte  der  Ontogenie  und  Phylogenie.     Ergebnisse 
d.  Anat.  u.  Entwick.,  Bd.  II,  1892;  Bd.  VII,  1898. 

KALLIUS,  E. :  Ein  Fall  von  Milchleiste  bei  einem  menschlichen  Embryo.     Anat.  Hefte, 
Bd.  VIII,  1897. 

KEIBEL,  F.,  and  MALL,  F.  P.:  Manual  of  Human  Embryology,  Vol.  I,  1910. 

KRAUSE,   W.:  Die   Entwickelung  der  Haut  und   ihrer   Nebenorgane.     In   Hertwig's 
Handbuch  d.  vergleich.  u.  experiment.  Entwick  elungslehre  der  Wirbeltiere,  Bd.  II,  Teil  I,  1902. 

OKAMURA,  T.:  Ueber  die  Entwickelung  des  Nagels  beim  Menschen.     Arch.  f.  Der- 
matol.  u.  Syphilol.,  Bd.  XXV,  1900. 

PIERSOL,  G.  A. :  Teratology.     In  Wood's  Reference  Handbook  of  the  Medical  Sciences, 
Vol.  VII,  1904. 

SCHMIDT,  H.:   Ueber    normale   H.yperthelie  menschlicher   Embryonen   und   tiber    die 
erste  Anlage  der  menschlichen  MilchdrUsen  uberhaupt.      Morphol.  Arbeiten,  Bd.  XVII,  1897. 

SCHULTZE,  O.:  Ueber  die  erste  Anlage  des  MilchdrUsen  Apparates.     Anat.  Anz.}  Bd. 
VIII,  1892. 

STOHR,    P.:  Entwiokelungsgeschichte   des    menschlichen    Wollhaares.     Anat.    Hefte, 
Bd.  XXIII,  1903. 

STRAHL,  H.:  Die  erste  Entwickelung  der  Mammarorgane  beim  Menschen.     Verhandl. 
d.  Anat.  Gesellsch.,  Bd.  XII,  1898. 

ZANDER,  R.:  Bie  friihesten  Stadien  der  Nagelentwickelung  und   ihre  Beziehungen  zu 
den  Digitalnerven.     Arch.  f.  Anat.  u.  PhysioL,  Anat.  Abth.,  1884. 


CHAPTER  XVII. 
THE  NERVOUS  SYSTEM. 

BY  OLIVER  S.   STRONG. 

GENERAL  CONSIDERATIONS. 

There  are  certain  features  of  the  nervous  system  in  general  and  particularly 
of  the  vertebrate  nervous  system,  the  comprehension  of  which  makes  the 
processes  of  development  of  the  nervous  system  in  man  more  intelligible. 
First,  the  nervous  systems  of  the  lower  Vertebrates  are  in  many  respects- 
simpler  than  those  of  higher  forms  and  their  variations  throw  light  upon  the- 
causes  which  determine  neural  structures.  Second,  as  the  nervous  systems  of 
all  Vertebrates  develop  from  the  same  germ  plasm,  there  are  resemblances 
between  certain  features  of  both  the  embryonic  and  adult  systems  of  lower 
vertebrates  and  certain  developmental  stages  in  the  higher.  Certain  struc- 
tures met  with  in  lower  adult  forms  may  be  regarded  as  representing  stages 
of  arrested  development — although  specialized  and  aberrant  in  many  respects 
— of  structures  found  in  higher  forms.  Vestigial  structures  in  the  developing 
nervous  systems  of  higher  forms  may  be  regarded  as  recurring  developmental 
necessities  in  the  attainment  of  the  adult  form. 

Stated  in  the  most  general  terms,  coordination  of  bodily  activities  in  response 
to  both  external  and  internal  conditions  is  the  biological  significance  of  the 
nervous  system.  This  implies  a  transmission  of  some  form  of  change  from  one 
part  to  another  or,  in  other  words,  conduction.  This  functional  necessity  is 
shown  structurally  in  the  elongated  form  of  the  histological  elements  of  the 
nervous  system.  That  such  changes  habitually  pass  along  each  element  or 
neurone  in  some  one  direction  seems  to  find  a  natural  structural  expression  in 
the  receptive  body  and  dendrites  of  the  neurone,  and  in  its  long  transmitting 
axone. 

It  is  also  evident  that  coordination  can  only  be  performed  by  a  transmission 
of  a  change  from  some  given  structure  either  back  to  that  structure  or  to  some 
other  structure  to  cause  a  responsive  change.  We  thus  have  not  only  in  the 
vertebrate,  but  at  a  very  early  stage  in  the  invertebrate  nervous  system,  a  dif- 
ferentiation into  afferent  and  efferent  components,  the  two  together  usually 
being  termed  the  peripheral  nervous  system.  The  histological  elements  of  these 
components  are  the  afferent  and  efferent  peripheral  neurones.  All  structures 
which  are  so  affected  as  to  transmit  the  change  to  the  afferent  peripheral  neu- 

417 


418 


TEXT-BOOK  OF  EMBRYOLOGY. 


rones  may  be  conveniently  termed  receptors,  those  structures  affected  by  the 
efferent  peripheral  neurones  may  be  termed  effectors  (Sherrington).  Receptors 
include  various  "sensory"  structures  whose  principal  function  appears  to  be 
to  limit  to  some  particular  kind  of  stimulus  the  changes  affecting  the  afferent 
nervous  elements  connected  with.  them.  Effectors  include  various  structures 
(muscles,  glandular  epithelia)  whose  activities  are  influenced  by  the  nervous 
system  (Fig.  358).  A  primitive  nervous  mechanism,  thus  composed  of  (i) 
afferent  peripheral  neurones  which  transmit  the  stimulus  from  a  receptor  to 
(2)  efferent  peripheral  neurones  which  in  turn  transmit  the  stimulus  to  an 
effector,  is  a  simple,  two-neurone  reflex  arc  (Fig.  358). 

At  the  same  time  these  neurones,  as  they  increase  in  number,  are  obviously 
brought  into  relation  with  each  other  with  more  economy  of  space  by  having 


Receptor 


Eftectoi 


FIG.  358. — A  two-neurone  reflex  arc  in  a  Vertebrate,     gg..  Ganglion,     van  Gehuchten. 


common  meeting  places.  This,  together  with  the  factor  noted  below,  leads  to 
the  concentration  of  an  originally  diffuse  nervous  system,  spread  out  principally 
in  connection  with  the  outer  (ectodermal)  surface,  into  a  more  centralized 
(ganglionic)  type  of  nervous  system,  which  at  the  same  time  has  in  part  re- 
treated from  the  surface  layer  (ectoderm)  from  which  it  was  originally  derived 

(Fig.  359)- 

Furthermore,  when  we  consider  the  great  number  of  receptors  and  effectors 
in  even  simple  forms,  it  is  apparent  that  for  effective  coordination  there  must  be 
a  considerable  degree  of  complexity  of  association  between  the  afferent  and 
efferent  neurones.  These  associations  may  be  to  some  extent  accomplished  by 
various  branches  of  the  afferent  and  efferent  neurones  coming  directly  into 
various  relations  with  each  other,  but  it  is  also  evident  that  when  a  certain 


THE  NERVOUS  SYSTEM. 


419 


degree  of  complexity  is  reached,  such  an  arrangement  would  necessitate  an 
extraordinary  number  of  afferent  and  efferent  neurones  or  an  extraordinary 
development  of  branches  of  each  where  they  connect.  Accordingly  we  find  a 
second  category  of  neurones,  the  intermediate  or  central  neurones  which  mediate 


Lumbncus 


Nereis 


Vertebrata 


FIG.  359. — Illustrating  the  withdrawal  from  the  surface  of  the  bodies 
of  the  afferent  peripheral  neurones.     After  Retzius. 

between  the  afferent  and  efferent  peripheral  neurones.  These  central  neurones, 
together  with  portions  of  peripheral  neurones  in  immediate  relation  with  them, 
form,  in  all  fairly  well  differentiated  nervous  systems,  including  those  of  all 
Vertebrates,  the  central  as  distinguished  from  the  peripheral  nervous  system. 


FIG.  360. — A  three-neurone  reflex  arc.     van  Gehuchten. 
Afferent  peripheral  neurone;  2,  intermediate  or  central  neurone;  3,  efferent  peripheral  neurones. 

The  change  or  stimulus  would  now  pass  from  receptor  through  (i)  afferent 
peripheral  neurones,  (2)  intermediate  neurones,  (3)  efferent  peripheral  neu- 
rones to  effector.  This  arrangement  constitutes  a  three-neurone  reflex  arc 


420 


TEXT-BOOK  OF  EMBRYOLOGY. 


(Fig.  360),  and  is  evidently  capable  of  complicated  combinations  which  may 
be  further  increased  in  complexity  by  the  intercalation  in  the  arc  of  other 
intermediate  neurones.  Finally,  in  the  central  nervous  system  certain  struc- 
tures consisting  of  intermediate  neurones  are  developed  which  represent  the 
mechanisms  for  certain  coordinations  of  the  highest  order.  Such  are  the 
higher  coordinating  centers  (suprasegmental  structures  of  Adolf  Meyer). 

As  a  result  of  the  preceding,  it  follows  that  in  seeking  the  explanation  for 
various  nervous  structures  there  must  always  be  kept  in  mind,  first,  their  correla- 
tion with  peripheral  structures  and,  second,  the  degree  of  development  of  the 
central  coordinating  mechanism  represented  by  the  intermediate  or  central 
'  neurones.  The  most  important  features  common  to  the  nervous  systems  of 
all  Vertebrates  owe  their  uniformity  either  to  a  corresponding  uniformity  in 
the  peripheral  receptors  and  effectors,  or  to  a  uniformity  in  the  coordinations  of 
the  stimuli  received  and  given  put  by  the  central  nervous  system.  Variations 
in  structure  are  due  to  variations  of  either  the  peripheral  or  central  factor  above 
mentioned.  In  the  lower  Vertebrates  the  former  factor  plays  a  relatively  more 
important  part  than  in  the  higher  Vertebrates,  the  central  apparatus  being 
simpler;  while  in  the  development  of  the  higher  vertebrate  nervous  systems  the 
dominating  factor  is  the  increasing  complexity  of  the  central  mechanism.  The 
superiority  of  the  nervous  system  of  man  does  not  consist,  in  the  main,  of  supe- 
riority in  sense  organs  or  motor  apparatus,  but  in  the  enormous  development  of 
the  intermediate  neurone  system. 

GENERAL  PLAN  OF  THE  VERTEBRATE  NERVOUS  SYSTEM. 

The.  Vertebrate  is  an  elongated  bilaterally  symmetrical  animal  progressing 
in  a  definite  direction,  primitively  perhaps  by  alternating  lateral  contractions 
performed  by  a  segmented  lateral  musculature.  Associated  with  these  char- 
acteristics are  the  bilateral  character  of  the  nervous  system  and  its  transverse 
segmentation,  shown  by  its  series  of  nerves,  a  pair  to  each  muscle  segment. 
The  definite  direction  of  progression  involves  a  differentiation  of  the  forward 
extremity  of  the  animal,  such  as  the  location  there  of.  the  mouth  and  respiratory 
apparatus  and  the  development  there  of  specialized  sense  organs,  the  nose,  eye, 
ear,  lateral  line  organs,  and  taste  buds,  which  increase  the  range  of  stimuli 
received  by  the  animal  and  thereby  render  possible  a  greater  range  of  responsive 
activities  in  obtaining  food  and  in  reproduction.  As  a  natural  outgrowth 
of  these  specializations,  the  highest  development  of  the  central  coordinating 
mechanism  also  takes  place  at  the  forward  end  or  head.  This  concentration 
and  development  of  various  mechanisms  in  the  anterior  end  is  usually  termed 
cephalizatian,  and  is  a  tendency  exhibited  also  by  various  groups  of  Inverte- 
brates in  which  the  same  general  conditions  are  present. 

The  typical  vertebrate  nervous  system,  then,  consists  of  a  bilateral  central 


THE  NERVOUS  SYSTEM.  421 


nervous  system  connected  by  means  of  a  series  of  segmental  nerves  with  per- 
ipheral structures  (receptors  and  effectors)  and  exhibiting  at  its  anterior  ex- 
tremity a  higher  development  and  specialization  in  both  its  peripheral  and 
central  parts. 

The  general  features  of  the  typical  vertebrate  nervous  system  are  best 
revealed  by  a  brief  examination  of  certain  stages  in  its  development. 

The  entire  nervous  system,  except  the  olfactory  epithelium  and  parts  of 
certain  ganglia  (see  p.  422),  is  derived  ontogenetically  from  an  elongated  plate 
of  thickened  ectoderm,  the  neural  plate.  This  plate  extends  longitudinally  in 
the  axis  of  the  developing  embryo,  its  position  being  usually  first  indicated 
externally  by  a  median  groove,  the  neural  groove  (Fig.  372),  the  edges  of  the 
plate  being  elevated  into  the  neural  folds  (Fig.  373).  The  neural  folds  are 
continuous  around  the  cephalic  end  of  the  plate,  but  diverge  at  the  caudal 
end,  enclosing  between  them  in  this  region  the  blastopore.  Even  at  this  stage, 
the  neural  plate  is  usually  broader  at  its  cephalic  end,  thereby  indicating  already 
the  future  differentiation  into  brain  and  spinal  cord  (Fig.  375).  The  neural 
folds  now  become  more  and  more  elevated  (Fig.  374),  presumably  due  in 
part  to  the  growth  of  the  whole  neural  plate,  and  finally  meet  dorsally  and  fuse, 
thus  forming  the  neural  tube  (Figs.  52  and  391).  The  fusion  of  the  lips  of  the 
neural  plate  to  form  the  neural  tube  usually  begins  somewhere  in  the  middle 
region  of  the  plate  and  thence  proceeds  both  forward  and  backward  (Fig.  83). 
The  last  point  to  close  anteriorly  is  usually  considered  as  marking  the  cephalic 
extremity  of  the  neural  tube,  and  is  called  the  anterior  neuropore. 

Even  before  the  neural  plate  closes  to  form  the  tube,  there  is  often  a  differen- 
tiation of  cells  along  each  edge,  forming  an  intermediate  zone  between  the 
neural  plate  and  the  non-neural  ectoderm  (Fig.  391).  As  the  neural  plate 
becomes  folded  dorsally  into  the  neural  tube  these  two  zones  are  naturally 
brought  together  at  the  point  of  fusion  of  the  dorsal  lips  of  the  neural  plate. 
The  two  zones  thus  brought  together  are  not  included  in  the  wall  of  the  neural 
tube,  but  form  a  paired  or  unpaired  ridge  of  cells  lying  along  its  dorsal  surface. 
This  ridge  of  cells  is  called  the  neural  crest  (Fig.  391).  Later,  each  half  of  the 
neural  crest  separates  from  the  other  half  and  from  the  neural  tube  and  passes 
ventrally  down  along  the  sides  of  the  tube,  at  the  same  time  becoming  trans- 
versely divided  into  blocks  of  cells  (Tig.  396).  These  masses  of  cells  are  the 
rudiments  of  the  cerebrospinal  ganglia  and  differentiate  into  the  afferent  per- 
ipheral neurones,  and  into  some  at  least  of  the  efferent  peripheral  visceral  neu- 
rones (sympathetic)  as  well  as  some  other  accessory  structures  (see  pp  459 
to  464).  The  peripheral  processes  of  these  ganglion  cells  (afferent  peripheral 
nerve  fibers)  pass  to  the  receptors,  the  central  processes  (afferent  root  fibers)  enter 
the  dorsal  part  of  the  nerve  tube  (Fig.  392).  In  the  case  of  the  special  sense 
organs  there  is  an  interesting  tendency  on  the  part  of  portions  of  the  neural 


422 


TEXT-BOOK  OF  EMBRYOLOGY. 


tube,  either  evaginations  (optic  vesicles,  olfactory  bulbs),  or  ganglia,  to  fuse 
with  ectodermal  thickenings  (placodes)  at  the  site  of  the  future  sense  organs. 
There  appear  to  be  often  two  series  of  ganglionic  placodes  in  the  head,  a 
dorsal  (supr abranchial)  series  and  a  ventral  (epibranchial)  series,  the  latter 
being  often  known  as  gill  cleft  organs.  The  former  appear  to  be  especially 
connected  with  the  development  of  the  acustico-lateral  system,  the  latter  prob- 
ably with  the  gustatory  (see  p.  432)-  (Fig-  361).  The  bodies  of  the  efferent 


Neural  crest  cells 


Suprabranchial  placode 

Mesoderm 

Epibranchial  placode, 
Rudiment  of  nerve  - 


Notochord 


Preoral  gut 


FIG.  361. — Transverse  section  through  the  head  of  a  7  day  Ammocoetes  in  the  region 
of  the  trigeminal  ganglion,     von  Kupffer. 

neurones  (except  the  sympathetic)  remain  in  the  neural  tube,  lying  in  its 
ventral  half,  and  send  their  axones  out  as  the  efferent  peripheral  nerve  fibers  to 
the  effectors. 

The  formation  of  the  neural  plate  and  its  closure  into  a  tube  are  the  em- 
bryological  expression  of  the  above  noted  tendency  of  highly  specialized  neural 
structures  to  concentrate  and  withdraw  from  the  surface  (p.  418).  The  same 
is  true  of  the  less  highly  specialized  placodes,  in  which  this  process  is  not  carried 
so  far.  The  neural  plate  may  thus  be  regarded  as  the  oldest  placode.  The 
afferent  peripheral  neurones  would  naturally  originate  from  the  borders  of  this 
plate,  such  portions  being  the  last  to  separate  from  the  non-neural  ectoderm 
or  outer  surface.  They  may  be  regarded  as  the  youngest  portions,  phylc 
genetically,  of  the  plate,  and  there  seems  to  be  some  variation  among  Chordate< 
as  to  the  degree  of  inclusion  of  the  afferent  peripheral  neurones  in  the  plat* 

In  the  neural  tube  thus  formed,  there  can  be  distinguished  four  longitudii 


THE  NERVOUS  SYSTEM. 


423 


plates  or  zones :    A  ventral  median  plate  (floor  plate},  a  dorsal  median  plate  (roof 
plate),  where  the  fusion  occurred,  and  two  lateral  plates  (e.g.,  Fig.  404). 

Two  points  are  to  be  noted :  First,  that  the  neural  plate  is  a  bilateral  struc- 
ture and  the  future  development  of  the  tube  will  naturally  take  place  principally 
in  the  side  walls  or  lateral  plates  of  the  formed  tube;  second,  that  the  primary 
connection  between  the  two  side  walls  is  the  ventral  median  plate,  the  dorsal 
median  plate  having  been  produced  by  a  secondary  fusion.  This  being  the 
case,  the  ventral  connection  between  the  two  lateral  plates  will  naturally  be 
more  extensive  and  possibly  more  primitive  than  the  dorsal.  The  ventral  and 
dorsal  median  plates  do  not  usually  develop  nervous  tissue,  but  bands  of  vertical 
elongated  ependyma  cells.  In  places  the  roof  plate  expands  into  thin  mem- 
branes which  are  covered  with  vascular  mesodermal  tissue  forming  chorioid 
plexuses,  such  as  the  chorioid  plexuses  of  the  lateral,  third  and  fourth  ventricles 
(Fig.  3  70). 


;.,'  „.,.    FIG.  362. — Scheme  of  a  median  sagittal  section  through  a  vertebrate  brain  before 

the  closure  of  the  neuropore.     von  Kupffer. 

A.,  Archencephalon;  D.,  deuterencephalon;  Ms.,  medulla  spinalis  (spinal  cord);  cd.,  notochord; 
en.,  neuronteric  canal;  ek.}  ectoderm;  en.,  entodernv  /.,  infundibulum;  np.,  neuropore;  pv.t 
ventral  cephalic  fold;  //>.,  tuberculum  posterius. 

It  has  already  been  seen  that  even  at  its  first  appearance  the  neural  plate 
exhibits  a  differentiation  into  an  anterior  expanded  part,  the  brain,  and  a 
posterior  narrower  part,  the  spinal  cord.  After  closure,  in  many  Vertebrates  at 
least,  a  three-fold  division  can  be  made  out:  (i)  A  caudal  part  of  the  neural 
tube,  the  spinal  cord,  which  gradually  expands  cranially  into  (2)  the  caudal  part 
)f  the  brain  (deuterencephalon,  v.  Kupffer)  (Fig.  362).  These  two  parts  lie 
ibove  the  notochord  and  all  the  typical  cerebrospinal  nerves  are  connected 
with  them.  (3)  Cranially,  at  the  anterior  end  of  the  notochord,  the  brain  wall 
expands  ventrally  forming  the  third  portion  (archencephalon) .  At  the  forward 
extremity  is  seen  the  anterior  neuropore.  The  deuterencephalon  is  thus  an 
epichordal  part  of  the  brain,  while  the  archencephalon  is  prechordal.  At  the 
boundary  between  the  two  is  a  ventral  infolding  of  the  brain  wall — the  ventral 
cephalic  fold  (plica  encephali  ventralis).  At  this  stage  the  brain  resembles  that 
of  Amphioxus  in  many  respects.  From  each  side  wall  of  the  archencephalon 


424 


TEXT-BOOK  OF  EMBRYOLOGY. 


an  evagination  appears,  the  optic  vesicle  (Fig.  376)  which  develops  into  the 
retina  and  optic  nerve. 

In  the  next  stage  (Fig.  363),  there  is  a  tendency  for  the  neural  tube  to  bend 
ventrally  around  the  anterior  end  of  the  notochord.  This  bending  is  the 
cephalic  flexure.  At  the  same  time  the  dorsal  wall  above  the  cephalic  fold  be- 
comes expanded  and  is  marked  off  from  that  part  of  the  dorsal  wall  lying 
caudally  by  a  transverse  constriction,  the  rhombo-mesencephalic  fol d,  and  from 
the  part  of  the  dorsal  wall  lying  cranially  by  another  transverse  fold  at  the 
site  of  the  future  posterior  commissure.  The  middle  part  of  the  brain,  the 
roof  of  which  is  thus  marked  off,  is  the  mid-brain  or  mesencephalon.  Its 
floor  is  the  middle  projecting  part  of  the  ventral  cephalic  fold.  The  cephalic 
expansion  of  the  brain,  practically  the  former  archencephalon,  is  now  the 


FIG.  363. — Scheme  of  a  median  sagittal  section  through  a  vertebrate  brain  after  the  formation 

of  the  three  primary  brain  expansions,     von  Kupffer. 
P..  prosencephalon;  M.,  mesencephalon;  R.,  rhombencephalon ;  Ms.,  spinal  cord;  cw.,  chiasma  emi- 
nence; /.,  infundibulum;  It.,  lamina  terminalis;    pv.,  ventral  cephalic  fold;  pn.,  processus 
neuroporicus;  pr.,  rhombo-mesencephalic  fold;  r.1,  unpairecTolfactory  placode;  ro.,  recessus 
(prae-?)  opticus;  tp.,  tuberculum  posterius. 

fore-brain  or  prosencephalon  and  the  caudal  expansion,  is  the  rhombic  brain  or 
rhombencephalon. 

These  three  primary  brain  expansions  ("  vesicles  "),  the  fore-brain,  mid- 
brain  and  rhombic  brain,  are  constant  throughout  the  Vertebrates.  Beginning 
at  the  location  of  the  former  neuropore  (processus  neuroporicus)  and  passing 
caudally  along  the  floor  of  the  fore-brain  we  have  the  lamina  terminalis  or  end- 
wall  of  the  brain,  containing  a  thickening  which  indicates  the  site  of  the  future 
anterior  (cerebral)  commissure,  next  the  recessus  praopticus,  then  another  thick- 
ening, the  chiasma  eminence,  and  finally  a  diverticulum,  the  recessus  postopticus 
and  infundibulum  (Fig.  363). 

At  a  later  stage  (Fig.  364),  there  appear  two  evaginations  in  the  roof  of  the 
fore-brain,  the  anterior  epiphysis  or  paraphysis  and  the  posterior  epiphysis  or 
epiphysis  proper  (pineal  body).  Immediately  caudal  to  the  paraphysis  is  a 
transverse  infolding  of  the  brain  roof,  the  velum  transversum.  The  line  aa 


THE  NERVOUS  SYSTEM. 


425 


(Fig.  364)  extending  from  this  fold  to  the  optic  recess  indicates  the  location  of  a 
fold  in  the  side  walls  in  some  forms  and  is  taken  by  some  as  the  boundary  be- 
tween two  subdivisions  of  the  fore-brain,  the  end-brain  or  telenccphalon  and  the 
inter-brain  or  diencephalon.  Cranial  to  the  epiphysis  proper,  is  a  commissure 
in 'the  dorsal  wall  (commissura  habenularis)  connecting  two  structures  which 
develop  in  the  crests  of  the  side  walls,  the  ganglia  habenula. 

From  the  dorsal  part  of  the  telencephalon  is  developed  the  pallium.  The 
ventral  anterior  part  evaginates  toward  the  olfactory  pit,  its  end  receiving  the 
olfactory  fibers.  This  region  is  often  termed  the  rhinencephalon.  Thickenings 
of  the  basal  lateral  walls  of  the  telencephalon  form  the  corpora  striata. 


FIG.  364. — Scheme  of  a  median  sagittal  section  through  a  vertebrate  brain  showing 

the  five-fold  division  of  the  brain,     von  Kupffer. 

TM  Telencephalon;  D.}  diencephalon;  M.,  mesencephalon;  Mt.,  metencephalon;  M/.,  myelence- 
phalon;  c.,  cerebellum;  cc.,  cerebellar  commissure;  ch.,  habenular  commissure;  cp.,  posterior 
commissure;  cw.,  chiasma  eminence;  e.,  epiphysis;  e*.,  paraphysis;  /.,  infundibulum;  lt.t 
lamina  terminalis;  pn.,  processus  neuroporicus;  pr.,  rhombo-mesencephalic  fold;  pv.,  ventral 
cephalic  fold;  ro.t  recessus  (prae-)  opticus;  si.,  sulcus  intraencephalicus  posterior;  tp.,  tuber- 
culum  posterius.  The  lines  aa.,  dd  and  ff  indicate  the  boundaries  between  four  divisions. 

The  roof  of  the  mesencephalon  finally  develops  the  "optic  lobes."     The 
dckened  part  of  the  roof  lying  immediately  caudal  to  the  rhombo-mesen- 
cephalic fold  develops  into  the  cerebellum.     The  part  of  the  tube  of  which  this 
forms  the  roof  is  often  called  the  hind-brain  or  metencephalon,  while  the  rest  of  the 
lombencephalon  is  then  termed  the  after-brain  or  myelencephalon.     The  roof  of 
i  is  portion,  which  has  become  very  thin  in  the  course  of  its  development,  forms 
epithelial  part  of  the  tela  chorioidea  of  the  fourth  ventricle.     The  con- 
•icted  portion  of  the  tube  between  the  rhombic  brairv  and  mid-brain  is  the 
\thmus. 

The  above  subdivisions  of  the  three  primary  expansions  into  five  parts 
(end-,  inter-,  mid-,  hind-  and  after-brains),  especially  the  subdivisions  of  the 
rhombic  brain,  do  not  have  the  morphological  value  of  the  three  primary 


426 


TEXT-BOOK  OF  EMBRYOLOGY. 


divisions  but  have  a  certain  value  for  descriptive  purposes.  The  cavities  of 
the  brain  are  the  ventricles  and  their  connecting  passages,  namely,  the  third 
ventricle  of  the  diencephalon  and  the  fourth  ventricle  of  the  rhombencephalon, 
the  two  being  connected  by  the  mid-brain  cavity  (aquceductus  Sylvii).  The 
telencephalon  usually  develops  a  more  or  less  paired  character,  its  cavities 
being  then  paired  diverticula  of  the  unpaired  fore-brain  cavity  and  known  as 
the  lateral  ventricles. 

Before  the  closure  of  the  brain  part  of  the  neural  tube,  transverse  constric- 
tions appear  across  the  neural  plate.     The  transverse  rings  into  which  the 


FIG.  365. — Chick  embryos;  i,  of  22  hours'  incubation;   2,  of  24  hours;  3,  of  25^  hours;  4,  of  26 

hours,  showing  respectively  2,  5,  6,  and  7  primitive  segments.     Hill. 

cp.,  Caudal  limit  of  fore-brain ;  fr.,  caudal  limit  of  mid -brain;  u.}  first  primitive  segment; 
ps.}  primitive  streak;  i-n,  neuromeres. 


tube,  when  completed,  is  thus  divided  are  known  as  neuromeres.  They  are 
held  to  represent  a  primitive  segmentation  of  the  head,  similar,  perhaps,  to 
that  exhibited  by  the  spinal  nerves  and  segmental  somatic  musculature  (primi- 
tive segments)  of  the  trunk.  The  neuromeres  may  appear  before  the  head 
somites.  To  what  extent  they  correspond  to  the  somites  or  to  the  visceral 
segmentation  (p.  430)  and  also  to  the  cranial  nerves  is  a  matter  of  dispute. 
Concerning  their  number  there  have  been  various  views,  the  evidence  inclining 
to  three  in  the  fore-brain,  two  in  the  mid-brain  and  six  in  the  rhombic  brain 
(Fig.  365).  Their  presence  and  number  are  most  in  doubt  in  the  cephalic  end 
of  the  tube,  the  highly  modified  prosencephalon. 


THE  NERVOUS  SYSTEM.  427 

The  general  features  of  the  vertebrate  nervous  system  which  especially 
illuminate  conditions  met  with  in  the  human  nervous  system  are  the  following: 
(i)  The  correlation  between  the  peripheral  structures  (receptors  and  effectors) 
and  the  nervous  system.  (2)  The  distinction  between  the  epichordal  and  pre- 
chordal  portions  of  the  brain.  The  latter  (fore-brain)  is,  in  accordance  with  its 
anterior  position  (comp.  p.  420),  the  most  highly  modified  part  of  the  neural 
tube.  (3)  The  distinction  between  the  segmented  and  suprasegmental  parts 
of  the  brain  (Adolf  Meyer).*  The  segmental  part  of  the  brain  is  that  portion 
in  more  immediate  connection  with  peripheral  segmental  structures.  Its  epi- 
chordal part  is  spinal-like  and  most  clearly  segmental.  Its  prechordal  part, 
both  as  to  its  peripheral  and  central  portions,  is  so  highly  modified  that  its 
segmental  character  is  more  obscure.  It  and  the  rest  of  the  prechordal  brain 
are  most  conveniently  treated  together  as  fore-brain.  The  suprasegmentai 
parts  of  the  brain,  or  higher  coordinating  centers,  are  the  cerebellum,  mid- 
brain  roof  and  the  pallium  (cerebral  hemispheres).  Their  general  functional 
significance  has  been  mentioned  (p.  420).  Some  of  their  general  structural 
characteristics  are :  First,  that  they  are  each  expansions  of  the  dorso-lateral 
walls  of  the  neural  tube;  second,  that  in  them  the  neurone  bodies  are  placed 
externally  and  in  layers  (cortex),  the  nerve  fibers  (white  matter)  lying  within; 
third,  that  each  appears  to  have  originally  had  an  especially  close  relation  with 
some  one  of  the  three  great  sense  organs  of  the  head,  the  olfactory,  visual  or 
acustico-lateral  system;  fourth,  that  each  is  connected  with  the  rest  of  the  brain 
by  bundles  of  centripetal  and  centrifugal  fibers,  and  often  there  are  specialized 
groups  of  neurone  bodies  in  other  parts  of  the  brain  for  the  origin  or  recep- 
tion of  such  bundles.  Each  higher  center  has  also  its  own  system  of  association 
neurones. 

It  will  accordingly  be  most  convenient  to  consider :  (i)  the  spinal  cord,  (2) 
the  segmental  part  of  the  epichordal  brain,  (3)  the  cerebellum,  (4)  the  mid- 
brain  roof,  (5)  the  prosencephalon. 

Spinal  Cord  and  Nerves. 

As  already  brought  out,  there  are  two  principal  morphological  differences 
between  the  afferent  and  efferent  peripheral  neurones.  First,  the  neurone 
bodies  of  the  former  are  located  outside  the  neural  tube,  while  the  neurone 
bodies  of  the  latter  lie  within  the  walls  of  the  neural  tube.  Second,  the  afferent 

*  This  distinction  apparently  ignores  the  fact  that  the  primitive  neuromeric  segmentation  of  the 
neural  tube  involves  its  dorsal  as  well  as  its  ventral  walls  and  thus  "suprasegmental"  as  well  as  "seg- 
mental "  structures  were  originally  segmental.  This  may  be  granted,  but  while  the  demonstration 
of  the  primitive  segmentation  of  the  neural  tube  may  be  valuable  as  showing  the  primitive  mechan- 
ism which  has  undergone  later  modifications,  the  importance  of  such  later  modifications  renders  the 
above  distinction  necessary.  The  main  significance  of  the  nervous  system  is  its  associative  character 
and  its  progressive  development  is  not  as  a  segmental,  but  as  a  more  and  more  highly  developed 
associating  mechanism. 


428 


TEXT-BOOK  OF  EMBRYOLOGY. 


nerves  enter  the  dorsal  part  of  the  lateral  walls  of  the  tube,  while  the  efferent 
nerves  leave  the  ventral  part  of  the  lateral  walls,  their  neurone  bodies  lying  in 
this  ventral  part.  The  effect  of  this  upon  the  structural  arrangements  within 
the  tube  is  the  production  in  the  tube  of  two  columns  of  neurone  bodies,  a  dorsal 
gray  column  for  the  reception  of  the  dorsal  or  afferent  roots  and  a  ventral, 
gray  column  containing  the  efferent  neurone  bodies. 

Another  important  differentiation  arises  apparently  from  the  important 
physiological  difference  in  general  character  between  the  activities  of  what  may 


FIG.  366. — Transverse  section  through  the  body  of  a  typical  Vertebrate,  showing  the  peripheral 

(segmental)  nervous  apparatus.     Froriep. 
Small  dots,  afferent    visceral    neurones;    coarse  dots,  afferent   somatic   neurones;    dashes,  efferent 

visceral  (ventral  root  and  sympathetic)  neurones;  lines,  efferent  somatic  neurones. 
Darm,  gut;    Ggl.  spin.,  spinal  ganglion;    Ggl.  vert.,  vertebral  sympathetic  ganglion;    Ggl.  mesent., 

mesenteric  sympathetic  ganglion.    The  peripheral  sympathetic  ganglionic  plexuses  (Auer- 

bach   and  Meissner)  are  not  shown.     Muse.,  muscle;    Rad.  dors.,  dorsal  root;    Rad.  vent., 

ventral  root;  R.  comm.,  white  ramus  communicans. 
Two  sympathetic  neurones  are  represented  as  intercalated  in  the  visceral  efferent  pathway.     It 

doubtful  if  there  should  be  more  than  one. 

be  termed  the  internal  (visceral  or  splanchnic)  and  the  external  (somatic)  struc- 
tures. Internal  activities  are  to  a  certain  extent  independent  of  activities 
which  have  to  do  more  with  the  reactions  of  the  organism  to  the  external  world, 
and  consequently  their  nervous  mechanisms  have  a  more  or  less  independent 
character,  forming  what  is  often  called  the  autonomic  (sympathetic)  system. 
This  independence  is  exhibited  structurally  by  the  intercalation  in  the  per- 
ipheral pathway  of  additional  neurones,  whose  bodies  form  visceral  ganglia 


THE  NERVOUS  SYSTEM.  429 


connected  in  various  ways  among  themselves  and  probably  having  their  own 
reflex  arcs  or  plexuses.  These  ganglia  are  nevertheless  to  some  extent  under 
the  control  of  the  efferent  neurones  of  the  central  nervous  system,  some  of 
which  send  their  axones  to  such  ganglia  (Fig.  366).  There  are  thus  in  the 
central  nervous  system  two  categories  of  efferent  peripheral  neurones,  those 
innervating  visceral  structures  "via  sympathetic  ganglia  and  those  innervating 
somatic  structures.  The  b'odies  of  the  somatic  efferent  neurones  are  located 
in  the  ventral  gray  matter  of  the  nerve  tube,  while  the  bodies  of  the  splanchnic 
efferent  neurones  are  believed  to  occupy  more  central  and  lateral  positions  in 
the  lower  half  of  the  gray  matter  of  the  neural  tube  (Fig.  366).  It  is  uncer- 
tain whether  there  are  similar  afferent  splanchnic  neurones  in  the  sympathetic 
ganglia,  and  thus  distinct  from  those  in  the  spinal  ganglia,  or  whether  these  all 
lie  in  the  spinal  ganglia  and  are  consequently  not  fully  differentiated  from  the 
somatic  afferent  neurones. 

The  muscular  segmentation  of  the  trunk  has  already  been  mentioned  and 
also  the  corresponding  segmental  arrangement  of  the  spinal  nerves.  Local 
extensions  of  this  musculature  and  of  its  overlying  cutaneous  surface  in  the 
form  of  fins  and  limbs  cause  corresponding  increase  in  the  size  of  those  seg- 
ments of  the  cord  innervating  them.  This  is  due  to  the  increased  number  of 
afferent  fibers  and  consequent  increase  in  the  dorsal  white  columns  and  in  the 
receptive  dorsal  gray  columns,  also  to  the  increase  in  the  number  of  efferent 
peripheral  neurones  whose  bodies  occupy  the  ventral  gray  column  (e.g.,  cervi- 
cal and  lumbar  enlargements).  (Compare  also  the  differentiation  in  the 
cervical  cord  and  lower  medulla  of  the  columns  and  nuclei  of  Goll  for  the 
lower  extremities  and  those  of  Burdach  for  the  upper  extremities). 

In  general,  the  intermediate  neurones  of  the  cord  fall  into  two  categories; 
intersegmental  (ground  bundles),  connecting  cord  segments,  and  those  send- 
ing long  ascending  bundles  to  suprasegmental  structures  (see  pp.  442  and  443.) 

The  Epichordal  Segmental  Brain  and  Nerves. 

The  principal  peripheral  structures  which  exert  a  determining  influence  on 
the  structure  of  the  epichordal  brain  are:  The  mouth,  the  respiratory  apparatus 
(gills  and  later  lungs),  and  two  specialized  sensory  somatic  structures,  the 
acustico-lateral  system  and  the  optic  apparatus. 

In  the  gills  we  have  essentially  a  series  of  vertical  clefts  forming  communica- 
tions between  the  pharynx  and  the  exterior,  the  intervals  between  the  clefts 
being  the  gill  arches.  The  musculature  of  the  gill  arches  is  morphologically 
splanchnic  (pp.  272  and  280).  The  gill  or  branchial  musculature  is  in  closer 
relations  with  stimuli  from  the  external  world  than  is  the  visceral  musculature 
of  the  body.  As  a  result  of  this  the  former  is  not  of  the  smooth  involuntary 


430  TEXT-BOOK  OF  EMBRYOLOGY. 


type,  like  the  visceral  musculature  of  the  body,  but  is  of  the  striated  voluntary 
type,  like  the  somatic  musculature.  The  branchial  receptors  are  naturally 
visceral  in  character  and  there  is  also  in  this  region  a  series  of  specialized 
visceral  receptors,  the  end  buds  of  the  gustatory  system.  The  development  of 
this  whole  specialized  visceral  apparatus  in  this  region  of  the  head  has  appar- 
ently caused  a  corresponding  reduction  of  the  somatic  musculature. 

The  musculature  of  the  mouth  is  also  splanchnic,  the  mouth  itself  being- 
regarded  by  many  morphologists  as  a  modified  pair  of  gill  clefts  which  has  re- 
placed an  older  mouth  lying  further  forward  in  the  region  of  the  hypophysis. 
The  existence  of  this  series  of  gill  clefts  has  naturally  caused  a  branchiomeric 
pir  splanchnic  segmentation  of  the  musculature  of  this  region  as  opposed  to  the 
somatic  muscular  segmentation  seen  in  the  trunk.  Whether  these  two  kinds 
of  segmentation  correspond  in  this  region  is  uncertain.  (In  this  connection  see 
Fig.  390  and  p.  466.) 

In  the  acustico-lateral  system  three  parts  may  be  distinguished :  (i)  a  remark- 
able series  of  cutaneous  sense  organs,  extending  in  lines  over  the  head  and  body 
and  known  as  the  lateral  line  organs;  (2)  the  vestibule,  including  the  semicircu- 
lar canals;  (3)  the  cochlea  (organ  of  hearing  proper — Cor ti's  organ) .  In  the 
higher  Vertebrates,  the  lateral  line  organs  have  disappeared,  owing  to  a  change 
from  a  water  to  a  land  habitat;  the  labyrinth  has  remained  unchanged,  and 
the  cochlea  has  undergone  a  much  higher  development  and  specialization. 

Regarding  the  optic  apparatus,  it  is  sufficient  to  point  out  here  that  its  motor 
part,  the  eye  muscles,  is  usually  taken  to  represent  the  sole  remaining  somatic 
musculature  belonging  to  the  head  proper. 

The  peripheral  nerves  of  the  epichordal  part  of  the  brain  have  fundamen- 
tally the  same  arrangements  as  the  spinal  nerves,  namely,  the  peripheral  af- 
ferent neurone  bodies  are  separate  from  the  nerve  tube,  forming  ganglia,  while 
the  bodies  of  the  efferent  neurones  are  located  centrally  in  the  morphologically 
ventral  portions  of  the  lateral  walls  of  the  nerve  tube.  There  are,  however, 
important  differences,  clearly  correlated  with  the  peripheral  differentiations  and 
specializations  outlined  above,  and  affecting  the  afferent  and  efferent  nerves. 

First  to  be  considered  is  the  afferent-  part  of  the  trigeminus  (Figs.  367  and 
368).  The  peripheral  branches  of  the  ganglion  (semilunar  or  Gasserian 
ganglion)  of  this  nerve  innervate  that  part  of  the  external  (somatic)  surfaces  of 
the  head  (skin  and  stomodaeal  epithelium)  which  have  not  been  encroached 
upon  by  the  spinal  afferent  nerves.  This  nerve  is  accordingly  more  strictly 
comparable  with  the  afferent  spinal  nerves.  The  central  processes  of  the 
semilunar  ganglion  cells,  after  entering  the  brain,  form  a  separate  descending 
bundle,  the  spinal  V.  It  is  interesting  to  note  that  the  terminal  nucleus  of 
this  bundle  of  fibers  is  the  morphological  continuation  in  the  brain  of  the 
dorsal  gray  column  of  the  cord.  The  extensiveness  of  the  area  innervated  by 


THE  NERVOUS  SYSTEM. 


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the  trigeminus  may  be  partly  due  to  disappearance  or  specialization  of  anterior 
somatic  nerves  and  also  to  the  growth  of  the  head. 

The  organs  of  the  lateral  line  are  innervated  by  a  quite  distinct  system  of 
ganglionated  afferent  nerves  whose  central  connections  are  nearly  identical  with 
those  of  the  acoustic  (Fig.  367).  With  the  disappearance  of  the  lateral  line 
organs  and  the  specialization  of  the  cochlear  part  of  the  ear  vesicle,  there  is  a 
disappearance  of  the  lateral  line  nerves  (comp.  Figs.  367  and  368)  and  a  well- 
marked  division  of  the  acoustic  nerve  into  vestibular  and  cochlear  portions, 
the  former  innervating  the  older  vestibule-semicircular  canal  portion,  the  latter, 
the  more  recent  cochlea.  Centrally,  the  vestibular  nerve  forms  also  a  descend- 
ing bundle  of  fibers  and  has  its  own  more  or  less  specialized  terminal  nuclei. 
The  latter  is  also  true  of  the  cochlear  nerve. 

The  afferent  portions  of  the  facial,  glossopharyhgeal  and  vagus  nerves  in- 
nervate the  splanchnic  receptors  of  the  pharyngeal  and  branchial  surfaces  as 
well  as  of  a  large  part  of  the  viscera.  The  facial,  glossopharyngeal  and  vagus 
also  innervate  the  specialized  splanchnic  receptors,  the  gustatory  system  men- 
tioned above.  This  system  of  taste  buds  has  a  very  extensive  development  in 
certain  lower  Vertebrates,  especially  the  Bony  Fishes.  In  the  latter  the 
system  of  nerves  innervating  these  structures  is  naturally  much  more  extensive 
and  its  central  terminations  and  nuclei  cause  important  modifications  of  the 
medulla.  In  Mammals  the  remnants  of  this  system  are  represented  by  the 
*  taste  buds  in  the  mouth,  the  nerves  innervating  them  being  the  chorda  tympani 
branch  of  the  facial  and  the  lingual  branch  of  the  glossopharyngeal  (Fig.  368). 
The  central  branches  of  the  ganglia  of  these  three  nerves,  after  entering  the 
brain,  form  a  descending  bundle  of  fibers,  the  tractus  solitarius  (or  communis). 

The  somatic  musculature  of  the  head,  as  above  mentioned,  is  usually  taken 
to  be  represented  by  the  eye  muscles  and,  later,  the  tongue  muscles.  The 
tongue  is  one  of  the  newer  structures,  rising  in  importance  with  the  change  to 
a  land  habitat,  and  its  muscles  are  probably  an  invasion  from  the  neck  region 
caudal  to  the  branchial  arches  (p.  290).  The  eye  muscles  are  innervated  by 
the  III,  IV  and  VI  cranial  nerves,  the  tongue  muscles  by  the  XII  which  is  a 
more  recent  addition  to  the  cranial  nerves.  All  of  these  nerves  are  charac- 
terized by  having  their  neurone  bodies  located  in  the  most  medial  (morpholog- 
ically most  ventral)  portions  of  the  lateral  brain  walls,  and  they  all,  except  the 
IV,  emerge  near  the  mid- ventral  line.  In  these  respects  they  resemble  the 
major  or  somatic  part  of  the  ventral  spinal  roots.  (For  illustration  see  Figs. 
389,  367  and  368). 

The  splanchnic  musculature  of  the  jaws  and  the  branchial  arches  is  inner- 
vated by  the  efferent  portions  of  the  V,  VII,  IX,  X  (and  XI).  The  neurone 
bodies  or  nuclei  of  origin  of  these  nerves  lie  more  laterally  than  those  of  the  III, 
IV,  VI  and  XII,  and  their  axones  also  leave  the  nerve  tube  more  laterally 


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434  TEXT-BOOK  OF  EMBRYOLOGY. 

along  with  the  incoming  afferent  fibres.  These  nerves  all  exhibit  a  character- 
istic segmental  arrangement  corresponding  to  that  of  the  gill  clefts.  The 
VII,  IX,  and  the  various  nerves  making  up  the  X,  divide  dorsal  to  the  cor- 
responding gill  clefts  into  prebranchial  and  postbranchial  branches,  also 
giving  off  suprabranchial  branches.  The  efferent  element,  or  component, 
forms  a  part  of  each  postbranchial  branch.  These  relations  are  shown  clearly 
in  the  accompanying  diagrams  (Figs.  367  and  368).  Part  of  the  vagus  also 
innervates  the  viscera  and  this  nerve  is  thus  divisible  into  branchial  and  visceral 
portions. 

Two  peculiarities  may  be  noted  in  regard  to  these  splanchnic  nerves :  First, 
that  the  afferent  portions  have  ganglia  resembling  those  of  the  spinal  nerves; 
second,  that  the  branchial  efferent  portions  consist  simply  of  one  neurone 
proceeding  all  the  way  from  the  nerve  tube  to  the  muscle  innervated,  thus 
resembling  the  somatic  rather  than  the  visceral  nerves  of  the  trunk.  As  al- 
ready noted  (p.  429),  these  nerves  regulate  activities  somatic  in  character  but 
involving  splanchnic  structures.  It  is  thus  seen  that  the  dominating  factor  is 
functional  rather  than  morphological — present  functional  necessities  modify 
those  of  the  past. 

With  the  change  from  a  water  to  a  land  habitat  and  the  accompanying 
disappearance  of  gills  and  appearance  of  lungs,  we  have  various  suppressions 
and  modifications  of  the  branchial  musculature  (Fig.  368).  There  are  two 
striking  specializations  of  the  branchial  musculature.  One  is  the  origin  of 
the  facial  (mimetic)  musculature  in  the  highest  Vertebrates.  This  is  derived 
from  the  muscles  of  the  hyoid  arch,  innervated  naturally  by  extensions  of  the 
facial  nerve.  The  other  is  a  specialization  of  muscles,  probably  of  the  caudal 
branchial  arches,  into  cervico-cranial  muscles  (head-movement),  innervated  by 
what  may  be  considered  a  caudal  extension  of  the  vagus  nerve,  namely,  the 
spinal  accessory  (p.  466).  The  splanchnic  laryngeal  musculature  and  its 
nerves  show  a  certain  degree  of  specialization  (sound-production)  in  higher 
forms.  The  efferent  V  is  naturally  a  large  constant  nerve,  in  correlation  with 
the  uniformly  developed  jaw  musculature  in  all  jaw-bearing  (gnathostome) 
Vertebrates  (Figs.  367  and  368).  These  various  changes  in  peripheral 
structures  are  thus  due  either  to  environmental  influences  or  to  developments 
within  the  central  nervous  system  (p.  420).  One  of  the  most  important  en- 
vironmental influences  is  the  change  from  a  water  to  a  land  habitat.  The 
influence  of  the  central  nervous  system  is  shown  in  the  further  development 
and  specialization  of  a  number  of  peripheral  structures  as  motor  "instru- 
ments" of  suprasegmental  mechanisms. 

The  effects,  then,  of  the  peripheral  arrangements  upon  the  arrangements 
within  the  neural  tube  are:  (i)  The  formation  of  separate  tracts  and  terminal 
nuclei  for  (a)  the  unspecialized  somatic  afferent  V  nerve  (spinal  V  and  posterior 


THE  NERVOUS  SYSTEM. 


435 


horn) ;  (b)  the  specialized  somatic  vestibular  nerve  (descending  or  spinal  VIII 
and  various  terminal  nuclei)  and  also  the  cochlear  nerve  and  its  various  termi- 
nal nuclei;  (c)  the  splanchnic  afferent  nerves  (tractus  solitarius  and  its 
terminal  nuclei).  (2)  The  separation  of  the  efferent  neurone  bodies  lying  in  the 
neural  tube  into  two  main  longitudinal  series  of  nuclei  (a)  the  somatic  efferent 
nuclei,  occupying  a  more  medial  position,  their  axones  emerging  from  the  neural 
tube  as  medial  ventral  nerve  roots;  (b)  the  splanchnic  efferent  nuclei  occupying 
a  more  lateral  position,  their  axones  emerging  laterally  and  forming  mixed 
roots  with  the  incoming  afferent  fibers  (Fig  369). 


FIG.  369 — Diagram  of  a  transverse  section  through  the  lower  human  medulla  showing  the  origin  of 
the  X  and  XII  cranial  nerves.     Schafer. 

gy  Ganglion  cell  of  afferent  vagus  sending  central  arm  (root  fiber)  to  solitary  tract  (/.  s.)  and  col- 
lateral to  the  nucleus  of  the  solitary  tract  (/.  5.  n.).  It  is  not  certain  that  the  axones  of  the 
cells  of  this  terminal  nucleus  take  the  course  indicated  in  the  figure,  n.  amb.,  nucleus  am- 
biguus  and  d.  n,  X,  dorsal  efferent  nucleus  of  the  vagus,  both  of  which  send  out  axones  as  the 
efferent  root  fibers  of  the  vagus.  These  two  represent  the  lateral  or  splanchnic  efferent  nuclei 
of  this  region,  n.  XII,  nucleus  of  the  hypoglossus  the  axones  of  which  pass  out  medially  as 
efferent  root  fibers  of  the  XII.  This  nucleus  represents  the  medial  or  somatic  efferent  nuclei 
of  this  region.  /.  s..  tractus  solitarius  or  descending  roots  of  vagus,  glossopharyngeus  and 
facial;  d.  V.,  descending  spinal  root  of  the  trigeminus;  r.,  restiform  body;  o.,  inferior  olivary 
nucleus  (''olive");  pyr..  pyramid. 

The  intermediate  neurones  of  the  epichordal  segmental  brain,  as  well  as 
of  the  cord,  fall  into  two  general  systems.  One  of  these  is  the  system  of 
inter  segmental  neurones,  connecting  various  segments  of  the  segmental  brain 
and  cord.  This  system  may  be  collectively  termed  the  ground  bundles  (of  the 
cord)  and  reticular  formation  (of  the  brain).  These  neurones  may  be  regarded 
as  not  only  furnishing  the  various  reflex  communications  between  the  afferent 
and  efferent  cerebrospinal  peripheral  neurones,  but  as  also  forming  a  system 
upon  which  the  descending  neurones  from  the  higher  coordinating  centers 
(suprasegmental  structures)  act,  before  the  efferent  peripheral  neurones  are 
reached.  This  system  may  thus  be  regarded  in  general  as  more  closely  associ- 


436  TEXT-BOOK  OF  EMBRYOLOGY. 

ated  with  the  efferent  than  with  the  afferent  peripheral  neurones.  Certain 
tracts  in  this  system  and  their  nuclei  of  origin  have  reached  a  considerable 
degree  of  differentiation,  due  principally  to  association  with  higher  centers. 
Among  these  differentiated  reticulo-spinal  tracts  may  be  mentioned  the  medial 
longitudinal  fasciculus,  the  rubro-spinal  tract,  and  the  various  tracts  from 
Deiters'  nucleus.  The  other  system  consists  of  nuclei  which  are  associated 
with  the  afferent  axones  as  their  terminal  nuclei,  the  axones  of  which  form  long 
afferent  tracts  to  suprasegmental  structures.  Especially  well-marked  differ- 
entiations of  nuclei  and  tracts  of  this  system  are  usually  due  both  to  its  con- 
nections with  peripheral  structures  and  with  the  higher  centers.  The  principal 
afferent  suprasegmental  tracts  to  the  cerebellum  are  mentioned  below  (p.  436). 
Those  to  mid-brain  roof  and  (via  added  neurones)  to  pallium  are  the  medial 
fillet  or  lemniscus  from  the  nuclei  of  the  columns  of  Goll  and  Burdach,  the 
lateral  lemniscus  from  the  cochlear  terminal  nuclei  and  other  ascending  tracts 
from  terminal  nuclei  of  peripheral  afferent  neurones. 

The  Cerebellum. 

The  other  great  factor  (see  p.  420)  affecting  the  structure  of  the  epichordal 
brain  is  the  development  in  it  of  two  higher  coordinating  centers  or  supraseg- 
mental structures,  the  cerebellum  and  optic  lobes.  The  cerebellum  is  a  develop- 
ment of  the  dorsal  part  of  the  lateral  walls  of  the  tube  just  caudal  to  the  isthmus 
and  was  probably  primarily  developed  in  correlation  with  the  acustico-lateral 
system,  especially  with  the  lateral  line  and  vestibulo-semicircular  canal 
portions  (p.  430).  Due  probably  to  the  fact  that  it  is  thus  an  important 
"equilibrating"  mechanism,  the  cerebellum  has  acquired  other  important  con- 
nections besides  its  original  ones  with  the  acustico-lateral  system.  In  the 
vertebrate  series  it  is  especially  developed  in  all  active  balancing  forms  (Fig.  370). 
In  Mammals  it  has  acquired  important  connections  with  the  greatly  enlarged 
pallium  (cerebral  hemispheres),  in  accordance  with  its  general  regulative  in- 
fluence (static  and  tonic)  upon  motor  reactions.  The  great  development  of  the 
cerebellum  has  profoundly  modified  the  anatomical  arrangements  of  the  rest  of 
the  brain  and  cord,  owing  to  its  numerous  and  massive  connections.  The  fol- 
lowing important  masses  of  gray  matter  and  fiber  bundles  may  be  mentioned  as 
cerebellar  afferent  connections:  Clarke's  column  cells,  and  other  cells  in  the 
cord,  and  the  spino-cerebellar  tracts;  the  lateral  nuclei,  inferior  olives  and  the 
restiform  body  in  the  medulla;  part  of  the  pes  pedunculi,  the  pontile  nuclei  and 
middle  peduncle  of  the  cerebellum.  The  superior  cerebellar  peduncle  to  the 
red  nucleus,  together  with  tracts  to  Deiter's  nucleus,  belong  to  the  cerebellar 
efferent  connections.  The  cortico-pontile  portion  of  the  pes,  the  pontile  nuclei 
and  the  middle  peduncle  represent  the  most  recently  developed  cerebral  con- 
nections (comp.  pp.  440-442  and  Fig.  371). 


THE  NERVOUS  SYSTEM.  437 

The  Mid-brain  Roof. 

This  expansion  of  the  dorsal  part  of  the  neural  tube  constitutes  a  higher 
coordinating  center  for  impulses  received  by  various  somatic  nerves — spinal, 
cochlear  and  optic.  Owing  to  its  being,  in  all  forms  below  Mammals,  the 
principal  visual  center,  the  optic  part  (optic  lobes)  varies  in  proportion  to  the 
development  of  the  eye,  animals  with  poorly  developed  eyes  having  small  optic 
lobes.  In  Mammals,  the  optic  part  (anterior  corpora  quadrigemina  or  col- 
liculi)  is  relatively  less  important,  owing  to  a  taking  over  of  a  portion  of  its 
coordinating  functions  by  the  neopallium  (pp.  440,  442) ,  but  the  cochlear  part 
(posterior  corpora  quadrigemina  or  colliculi)  has  increased  in  importance, 
owing  to  the  rise  of  the  cochlear  organ  (organ  of  Corti).  The  centripetal  and 
centrifugal  connections  of  the  mid-brain  roof  are  not  so  massive  or  extensive 
and  consequently  do  not  modify  the  other  parts  of  the  brain  and  cord  as  pro- 
foundly as  do  those  of  the  cerebellum.  It  sends  descending  tracts  to  after- 
brain  and  cord  segments. 

The  Prosencephalon. 

The  division  of  this  part  of  the  brain  into  the  telencephalon  and  diencephalon 
has  already  been  indicated  (p.  425).  In  the  diencephalon  may  be  noted  (i)  the 
absence  of  the  notochord  ventral  to  the  brain,  thereby  permitting  a  ventral  ex- 
pansion of  the  brain  walls,  the  hypothalamus,  associated  with  an  organ  not 
well  understood,  the  hypophysis;  (2)  certain  more  or  less  vestigial  structures, 
such  as  the  pineal  eyes  (epiphyses),  and  other  primitive  structures,  such  as 
the  ganglia  habenulae,  in  the  dorsal  part,  this  dorsal  portion  being  collectively 
termed  the  epithalamus;  (3)  nuclei  in  (i)  and  (2)  connected  with  olfactory 
and  gustatory  tracts;  (4)  receptive  nuclei  for  the  optic  tract  and  the  cochlear 
path  from  the  posterior  colliculus;  (5)  receptive  nuclei  for  secondary  tracts  from 
the  end  stations  of  more  caudal  somatic  ganglia  (nuclei  of  Go  11  and  Burdach 
and  medial  lemniscus).  The  last  two  (4  and  5)  constitute  the  thalamus  and 
increase  in  importance  in  the  higher  Vertebrates  (see  p.  440,  Fig.  371). 

In  the  telencephalon  there  may  be  roughly  distinguished  an  anterior  and  basal 
part,  the  rhinencephalon,  in  especially  intimate  relations  with  the  olfactory  nerve; 
a  thickening  of  the  basal  wall,  the  corpus  striatum ;  and  a  thinner- walled  dorsal 
part,  the  pallium.  The  latter  may  be  regarded  in  a  sense  as  a  dorsal  develop- 
ment of  the  corpus  striatum  and  first  appears  as  a  distinct  structure  in  the 
Amphibia. 

The  peripheral  or  segmental  apparatus  which  are  connected  with  the  pros- 
encephalon  are  the  highly  modified  optic  and  olfactory  organs.  While  the  optic 
apparatus  primarily  originates  from  the  prechordal  brain,  in  the  lower  Verte- 
brates its  highest  coordinating  center,  as  mentioned  above,  lies  partly  in  the 


438  TEXT-BOOK  OF  EMBRYOLOGY. 

epichordal  portion  (optic  lobes).  It  is  possible  that  this  connection  is  secon- 
dary and  contingent  upon  two  functional  necessities,  the  importance  of  cor- 
relation with  stimuli  coming  via  more  caudal  nerves  (cochlear  and  spinal 
nerves) ,  and  the  innervation  of  its  motor  apparatus  by  epichordal  nerves,  the 
III,  IV  and  VI.  With  the  development  of  the  neopallium  in  Mammals  (see  p. 
447)  and  the  consequent  projection  of  visual  stimuli  upon  it,  the  lower  pre- 
chordal  (thalamic)  centers  form  part  of  the  newer  pathway  to  the  neopallium 
and  thus  increase  in  importance,  while  the  optic  lobes  recede,  assuming  the 
position  of  a  reflex  center,  especially  for  the  visual  motor  apparatus. 

The  olfactory  nerves  enter  the  anterior  extremity  of  the  brain  and  are  con- 
nected by  secondary  and  tertiary  tracts  with  regions  lying  more  caudally,  where 
in  some  cases  the  olfactory  stimuli  are  associated  with  gustatory  and  probably 
with  visual  stimuli.  One  of  these  regions  is  the  hypothalamus  which  receives 
both  olfactory  and  gustatory  tracts  (Herrick) .  More  dorsal  olfactory  pathways 
pass  to  the  epithalamus.  Both  epithalamus  and  hypothalamus  give  rise  to  de- 
scending systems  which  doubtless  ultimately  reach  efferent  nuclei.  In  fact,  this 
part  of  the  brain  presents,  apparently,  a  complicated  primitive  mechanism  for 
the  correlation  especially  of  olfactory  and  gustatory  stimuli,  also  to  some  extent 
of  visual  stimuli  and  stimuli  via  the  trigeminal  nerve,  the  whole  forming  a  sort 
of  oral  sense,  probably  controlling  the  feeding  activities  (Edinger). 

The  next  factor  in  the  further  development  of  this  part  of  the  brain  is  the 
rise  in  importance  of  the  pallium  upon  which  at  first  are  projected  mainly 
olfactory  stimuli  (Fig.  370). 

A  further  and  still  more  extensive  development  of  the  pallium  arises  when 
other  kinds  of  stimuli  are  projected  to  a  considerable  extent  upon  it,  thus  giving 
rise  to  a  distinction  between  the  older  olfactory  pallium  (archipallium)  and  the 
newer  non-olfactory  pallium  (neopallium} .  The  latter  appears  first  in  the  lateral 
dorsal  portion  of  the  pallial  wall  and  by  its  subsequent  development  the  archi- 
pallial  wall  is  rolled  inward  upon  the  mesial  surface  of  the  hemispheres. 
Further  changes  consist  in  the  extension  caudally  of  this  portion  pari  passu  with 
the  extension  caudally  of  the  neopallium  and  then  the  practical  obliteration 
of  its  middle  portion  by  the  great  neopallial  commissure,  the  corpus  callosum 
(Fig.  370,  G  and  H). 

In  addition  to  the  increasing  projection  of  stimuli  from  all  parts  of  the  body 
upon  the  neopallium  and  the  consequent  increase  in  centripetal  fiber  termina- 
tions and  in  centrifugal  neurone  bodies  lying  in  its  walls,  a  second  factor  in 
the  development  of  the  neopallium  is  the  enormous  increase  of  its  association 
neurones.  It  is  the  latter  feature  which  especially  distinguishes  the  human 
from  other  mammalian  brains. 

The  biological  significance  of  these  changes  lies  in  the  fact  that  there  is  thus 
produced  a  mechanism  not  only  for  the  association  of  all  kinds  of  stimuli,  but 


THE  NERVOUS  SYSTEM. 


439 


G    OUNITHORHYNCHOS 


FIG.  370. — A-F  (Edinger)  are  sagittal  sections  showing  structures  lying  in  the  median  line  and  also 
paired  structures  (e.g.,  pallium)  lying  to  one  side  of  the  median  line.  The  cerebellum  is 
black.  It  is  doubtful  whether  the  membranous  roof  in  A  indicated  as  pallium  is  strictly 
homologous  with  that  structure  in  other  forms,  In  B,  Pallium  indicates  prepallial  structures. 

Aq.  SyL,  Aquseductus  Sylvii;  Basis  mesen.,  basis  mesencephali;  Bulb,  olf.,  bulbus  olfactorius;  Corp. 
striat.,  corpus  striatum;  Epiph.,  epiphysis;  G.  h.,  ganglion  habenulae;  Hyp.,  hypophysis; 
Infund.,  infundibulum;  Lam.  t.,  lamina  terminalis;  Lob.  elect.,  lobus  electricus;  L.  vagi, 
lobus  vagi;  L.  opt.,  mid-brain  roof;  Med.  obi.,  medulla  oblongata;  Opt.,  optic  nerve;  Pl.chor., 
plexus  chorioideus;  Rec.  inf.,  recessus  infundibuli;  Rec.  mam.,  recessus  mammillaris;  Saccus 
vase.,  saccus  vasculosus;  Sp.  c.,  spinal  cord;  ventr.,  ventricle;  v.  m.  a.,  velum  medullare 
anterius;  v.m.  p.,  velum  medullare  posterius. 

G  and  H  show  the  mesial  surface  of  the  cerebral  hemispheres  in  a  low  (G)  and  high  (H)  Mammal. 
G.  Elliot  Smith,  Edinger,  slightly  modified. 

The  exposed  gray  matter  of  the  olfactory  regions  is  shaded,  the  darker  shade  indicating  the  archi- 
pallium  (preterminal  area  and  hippocampal  formation),  the  lighter  shade  indicating  the 
rhinencephalon,  which  consists  of  the  anterior  and  the  posterior  (principally  pyriform)  olfactory 


440  TEXT-BOOK  OF  EMBRYOLOGY. 

also  for  very  complex  coordinations  between  these  stimuli.  In  this  way  an 
extensive  symbolization  and  formulation  of  individual  experience  (memory, 
language,  etc.)  can  take  place.  The  formulated  experience  of  one  generation 
can  be  immediately  transmitted  (by  education  in  the  broad  sense  of  the  term) 
to  the  plastic  late-developing  neopallia  of  the  next  generation.  In  this 
way  a  racial  experience  may  be  rapidly  built  up  without  the  direct  inter- 
vention of  the  slow  processes  of  heredity  and  natural  selection  and  each  gen- 
eration profit  by  the  accumulated  experience  of  past  generations  to  a  much 
greater  extent.  The  nervous  mechanism,  the  pallium,  is  provided  by  in- 
heritance; experience  is  not  inherited  but  "  learned."  The  pallial  associative 
mechanisms  are  continuously  modified  by  their  activities,  thus  affecting  the 
character  of  subsequent  pallial  reactions  (associative  memory).  Such  reac- 
tions are  usually  termed  psychical  or  conscious,  as  distinguished  from  the 
reflex  reactions  of  other  parts  of  the  nervous  system. 

In  the  course  of  these  developments  the  pallium  or  cerebral  hemispheres 
have  enormously  increased  in  size  until  in  man  they  overlap  all  the  other  parts 
of  the  brain.  Naturally  the  extensive  connections  of  the  neopallium  with  the 
rest  of  the  brain  have  profoundly  modified  the  latter.  Among  the  new  struc- 
tures which  have  on  this  account  been  added  to  the  older  structures  of  the  rest  of 
the  brain,  the  following  may  be  mentioned:  (i)  The  centripetal  connections  of 
the  neopallium,  consisting  mainly  of  what  are  usually  termed  the  thalamic  radi- 
ations. These  consist  essentially  of  a  system  of  neurones  passing  from  the 
above  mentioned  termini  in  the  thalamus  of  general  somatic,  acoustic  and  optic 
ascending  systems  to  certain  areas  in  the  cerebral  hemispheres.  In  this  system 
we  can  distinguish  (a)  the  continuation  of  the  fillet  (general  somatic)  to  the  cen- 
tral region  (somaesthetic  area)  of  each  hemisphere;  (b)  the  optic  radiation  from 
the  lower  thalamic  optic  center  (lateral  geniculate  body)  to  the  calcarine 
(visual)  area  of  the  hemisphere;  (c)  the  acoustic  radiation  from  the  medial 
geniculate  body  of  the  thalamus  to  the  upper  temporal  region  (auditory  area) 
of  the  hemisphere.  Associated  with  these  last  two  connections  are  the  increase 

lobes.  In  Amphibia  and  Reptiles  the  hippocampal  formation  includes  all  or  nearly  all  of  the 
mesial  surface.  As  the  early  neopallium  appears  in  the  lateral  hemisphere  walls,  the  neo- 
pallial  commissural  fibers  first  pass  across  the  median  line  in  the  ventral  or  anterior  com- 
missure. With  the  increase  of  the  neopallium  and  its  extension  on  the  mesial  hemisphere 
walls,  its  commissural  fibers  pass  across  more  dorsally  via  the  archipallial  or  fornix  com- 
missure (psalterium)  forming  the  neopallial  commissure  or  corpus  callosum,  the  great  de- 
velopment of  which  nearly  obliterates  the  anterior  hippocampal  formation. 

Com.  ant.,  Anterior  commissure;  corp.  callosum,  corpus  callosum;  Fimbr.,  fimbria;  Fiss.  hippo- 
campi, hippocampal  fissure;  Lam.  t.,  lamina  terminalis;  Lob.  olf.  ant.,  anterior  olfactory  lobe; 
Lob.  pyrfformis  pyriform  lobe;  Psalt.,  psalterium  (fornix  commissure);  Sept.  pell.,  septum 
pellucidum;  Tuo.  olf.,  tuberculum  olfactorium.  Only  a  part  of  the  gray  (cortex)  of  the  hip- 
pocampal formation  appears,  as  the  gyrus  dentatus,  on  the  mesial  surface;  the  remainder  forms 
an  eminence,  the  cornu  Ammonis,  on  the  ventricular  surface.  This  invagination  is  indicated 
extenu'lyby  the  hippocampal  fissure.  The  exposed  fiber  bundle  forming  the  edge  of  this 
formation  (fimbria)  passes  forward  (fornix  and  its  commissure)  and  thence  descends,  as  the 
anterior  pillar  of  the  fornix,  behind  the  anterior  commissure.  The  anterior  pillar  is  partly 
indicated  by  a  few  lines  in  this  region  in  the  figure. 


THE  NERVOUS  SYSTEM. 
i    S_P_H. 


441 


FIG.  371. — Principal  afferent  and  efferent  suprasegmental  pathways  (excepting  the  archipallial  con 
nections,  the  efferent  connections  of  the  mid- brain  roof  and  the  olivo-cerebellar  connections) 
Neopallial  connections  are  indicated  by  broken  lines.  Intersegmental  connections  are  omitted 
Some  peripheral  elements  are  indicated.  Each  neurone  group  (nucleus  and  fasciculus)  is  in 
dicated  by  one  or  several  individual  neurones.  Decussations  of  tracts  are  indicated  by  an  X 

etc.,  Acoustic   radiation,  from  medial  gemculate  body  to  temporal  lobe;  Z>r.  conj.,  brachium  con- 


442  TEXT-BOOK  OF  EMBRYOLOGY. 

of  the  geniculate  bodies  and  the  diminution  of  the  mid-brain  in  importance 
already  alluded  to  (p.  437).  (2)  The  centrifugal  connections  consisting  of  (a) 
the  pyramids  passing  from  the  precentral  area  of  each  hemisphere  to  various 
lower  efferent  neurones,  or  neurones  affecting  the  latter,  and  forming  part  of  the 
internal  capsule  and  pes  pedunculi ;  (b)  fibers  from  various  parts  of  the  hemis- 
phere, forming  the  greater  part  of  the  rest  of  the  internal  capsule  and  pes,  and 
terminating  principally  in  the  pontile  nuclei  whence  a  continuation  of  this 
system  (the  fibers  of  the  middle  peduncle),  passes  to  the  cerebellar  hemisphere. 
The  great  increase  in  size  of  the  cerebellar  hemispheres,  of  the  contained 
nuclei  dentati,  and  probably  of  the  superior  cerebellar  peduncles  are  further 
effects  of  this  new  connection,  which  has  already  been  alluded  to  (see  Cere- 
bellum, p.  436)  >  (Fig-  371-) 

Another  important  effect  of  the  development  of  the  pallium  is  the  assump- 
tion by  man  of  the  upright  position,  due  both  to  the  specialization  of  the 
hand  to  execute  pallial  coordinations  and  its  consequent  release  from  locomo- 
tion, and  also  to  the  overhanging  of  the  eyes  by  the  enlarged  cranium.  The 
great  increase  of  cerebellar  connections  may  be  partly  due  to  the  new 
problems  of  equilibrium  connected  with  the  upright  position. 

GENERAL  DEVELOPMENT  OF  THE  HUMAN  NERVOUS  SYSTEM  DURING 

THE  FIRST  MONTH. 

One  of  the  earliest  stages  in  the  development  of  the  human  nervous  system 
is  shown  in  the  2  mm.  embryo  of  about  two  weeks  (Fig.  372).  This  shows 
the  stage  of  the  open  neural  groove.  The  appearance  of  a  transverse  section 
of  the  neural  plate,  groove  and  folds,  in  other  forms,  is  shown  in  Figs.  373 
and  374. 

The  neural  folds  now  become  more  and  more  elevated  and  finally  meet,  thus 
forming  the  neural  tube  as  previously  described  (p.  421).  The  fusion  of  the 
neural  folds  begins  in  the  middle  region  and  thence  extends  cranially  and  cau- 

junctivum  (superior  cerebellar  peduncle);  brack,  pon.,  brachium  ponds  (middle  cerebellar 
peduncle);  b.q.  i.,  brachium  quadrigeminum  inferias  (a  link  in  the  cochlear  pathway) ;  c. g. I., 
lateral  or  external  geniculate  body;  c.  g.  m.,  medial  or  internal  geniculate  body;  c.  quad.,  cor- 
pora quadrigemina;  f.cort.-sp.,  cortico-spinal  fasciculus  (pyramidal  tract);/. c.  p.-f.  frontal 
cortico-pontile  fasciculus  (from  frontal  lobe);  f.c.-p.t.,  temporal  cortico-pontile  fasciculus 
(from  temporal  lobe);  f.c.-p.o.,  occipital  cortico-pontile  fasciculus  (from  occipital  lobe); 
f.ctm.f  fasciculus  cuneatus  (column  of  Burdach);  f.grac.,  fasciculus  gracilis  (column  of 
Goll) ;  /.  s.-t.,  tract  from  cord  to  mid-brain  roof  and  thalamus  (sometimes  included  in  Gowers* 
tract);  f.sp.-c.d.,  dorsal  spino-cerebellar  fasciculus  (tract  of  Flechsig);  f.sp.-c.v.,  ventral 
spino-cerebellar  fasciculus  (tract  of  Gowers,  location  of  cells  in  cord  uncertain) ;  lem.  lot., 
lateral  lemniscus  or  lateral  fillet;  lemniscus*-med.,  medial  lemniscus  or  fillet  (the  part  to  the 
thalamus  is  mainly  a  neopallial  acquisition);  n.coch.,  cochlear  nerve;  n.  cun.,  (terminal) 
nucleus  of  the  column  of  Burdach;  n.grac.,  nucleus  of  the  column  of  Goll;  n.dent.,  nucleus 
dentatus;  n.  opt.,  optic  nerve;  n.r.,  nucleus  ruber  (red  nucleus);  pes  ped.,  pes  pedunculi 
(crusta);  pulv.  thai.,  pulvinar  thalami;  pyr.,  pyramid;  rod.  ant.,  ventral  spinal  root;  rod.  post,. 
dorsal  spinal  root;  rod.  opt.,  optic  radiation  (from  lateral  geniculate  body,  and  pulvinar  (?), 
to  calcarine  region);  somaes.,  bundles  from  thalamus  to  postcentral  region  of  neopallium; 
s p. gang.,  spinal  ganglion;  ihal.,  thalamus. 


THE  NERVOUS  SYSTEM. 


443 


dally.  The  stage  of  partial  closure  of  the  neural  tube  is  shown  in  Eternod's 
figure  of  a  human  embryo  of  2.1  mm.  (Fig.  375,  b).  This  order  of  closure  in- 
dicates, to  some  extent,  the  order  of  subsequent  histological  development;  the 
extreme  caudal  and  cephalic  extremities  are  more  backward  than  the  parts 
which  close  first.  The  last  point  to  close  anteriorly  marks,  as  stated  previously 
(p.  42 1),  the  cephalic  extremity  of  the  neural  tube  and  is  the  anterior  neuropore. 
As  indicated  in  Eternod's  embryo,  the  anterior  end  of  the  neural  plate  is  broader 
even  before  its  closure;  thus  when  the  tube  is  completed  its  anterior  end  is  more 
expanded.  This  expansion  is  the  future  brain,  the  narrower  caudal  portion 


Yolk  sac 


Amnion 


Neural  groove 


FlG.  372. — Dorsal  view  of  human  embryo,  two  millimeters  in  length,  with  yolk 

von  Spee,  Kollmann. 
The  amnion  is  opened  dorsally. 


being  the  future  spinal  cord.  Before  the  closure  of  the  brain  part  of  the  tube 
the  beginnings  of  the  three  primary  brain  vesicles  are  also  indicated  (Fig.  84). 
At  this  stage  the  neural  plate  shows  no  differentiation  into  nervous  and  sup- 
porting elements.  The  neural  tube  is  composed  of  the  two  lateral  walls  and 
the  median  roof  and  floor  plates  (comp.  p.  423)  (Figs.  307  and  404). 

The  appearance  of  the  anterior  end  of  the  neural  tube  with  the  closure  com- 
pleted, except  the  anterior  and  posterior  neuropores,  is  shown  in  the  model  of 
one  half  of  the  tube.  The  external  appearance  and  also  the  inner  surfaces  are 
shown  in  Figs.  376  and  377.  At  this  stage  the  cephalic  flexure  (see  p.  424)  is 
already  quite  pronounced,  the  cephalic  end  of  the  brain  tube  being  bent  ven- 


444 


TEXT-BOOK  OF  EMBRYOLOGY. 


trally  at  about  a  right  angle  to  the  longitudinal  axis  of  the  remaining  portion  of 
the  tube.  This  bending  begins  before  the  closure  of  the  cephalic  part  of  the 
neural  tube  (Fig.  84).  From  each  side  of  the  brain  near  the  cephalic  ex- 
tremity is  an  evagination  of  the  brain  wall,  the  beginning  of  the  optic  vesicles. 


Neural 

fold 


Ectoderm 


Mesoderm 


x       Chorda  anlage  Entoderm 

FIG.  3  73 . — Transverse  section  through  dorsal  part  of  embryo  of  frog  (Rana  f usca) . 
x,  Groove  indicating  evagination  to  form  mesoderm. 


Ziegler. 


The  process  of  evagination  and  consequently  the  location  of  the  vesicle  begins 
before  the  closure  of  the  tube. 

Dorsal  and  anterior  to  the  optic  vesicles  can  be  seen  a  slight  unpaired  pro- 
trusion of  the  dorsal  wall,  the  beginning  of  the  pallium.     The  area  basal  to  it  and 


Prim.     Intermed. 
seg.      cell  mass 


Parietal  and 
visceral  mesoderm 


Ectoderm 
(epidermis) 


Chordal       Prim, 
plate         aorta 


Ccelom         Entoderm       Blood  vessels 
FIG.  374. — Transverse  section  of  dog  embryo  with  ten  pairs  of  primitive  segments.     Bonnet. 

extending  a  short  distance  into  the  anterior  wall  of  the  optic  vesicle  is  the  site  of 
the  future  corpus  striatum  (Figs.  376  and  377). 

Caudal  to  the  pallium  and  separated  from  it  by  a  slight  constriction  (in- 
dicated best  by  the  ridge  on  the  inner  wall)  is  another  protrusion  of  the  dorsal 
wall,  the  roof  of  the  diencephalon.  Still  further  caudally  and  separated  from  the 


THE  NERVOUS  SYSTEM. 


445 


roof  of  the  diencephalon  by  another  slight  constriction  is  another  expansion  of 
the  dorsal  wall,  the  roof  of  the  mid-brain  or  of  the  mesencephalon  which  arches 
over  the  cephalic  flexure.  It  is  separated  by  another  constriction  (plica 
rhombo-mesencephalicd)  from  the  rhombic  brain  or  rhombencephalon,  which  latter 
tapers  into  the  cord.  A  ventral  bulging  of  the  rhombencephalon  indicates  the 
future  pans  region  (Figs.  376  and  377). 


Heart 


Ant.  entrance  to 
prim,  gut  (Ant. 
"Dannpforte") 


Post,  entrance  to 

prim,  gut  (Post.  : 

"Darmpforte") 


Cerebral  plate 


Amnion 


Yolk  sac 
(cut  edge) 


Yolk  sac   


Belly  stalk 


FIG.  375.— (a)  Ventral  view;  (&)  dorsal  view  of  human  embryo  with  8  pairs  of  primitive 

segments  (2.11  mm.).     Eternod.    From  models  by  Ziegler. 

In  b  the  amnion  has  been  removed,  merely  the  cut  edge  showing;  in  a  the  yolk  sac  has 

been  removed. 


Even  at  this  early  stage  the  cavity  of  the  caudal  part  of  the  rhombencephalon 
is  expanded  dorsally  due  to  an  expansion  of  the  roof  plate,  which  forms  only  the 
narrow  dorsal  median  part  of  the  rest  of  the  tube.  This  expansion  reaches  its 
maximum  about  opposite  the  auditory  vesicle. 

The  principal  changes  in  form  during  the  next  two  weeks  are  the  following 
(Figs.  378  and  434):  The  cephalic  flexure  becomes  still  more  pronounced  so 
that  the  anterior  end  of  the  neural  tube  is  folded  back  upon  the  ventral  side  of 
the  rest  01  the  brain,  an  effect  probably  enhanced  by  the  expansion  of  the 


446 


TEXT-BOOK  OF  EMBRYOLOGY. 


FIG.  376. — Lateral  view  of  the  outside  of  a  model  of  the  brain  of  a  human 
embryo  two  weeks  old.     His. 


Diencephalon 


Pallium 


Mesencephalon 


Rhombq- 
mesencephalic  fcld 


Rtiombencephalon 


Neuropore 
Corpus  striatum 
P.  f. 
Optic  evagination 


Ventral  cephalic  told 
(Seesel's  pocket) 


Pons  region 


»  377* — Lateral  view  of  inner  side  of  the  same  model  shown  in  Fig.  414.    ffiS, 
P.f.  is  the  ridge  corresponding  to  the  peduncular  furrow  on  the  outer  side. 


THE  NERVOUS  SYSTEM.  447 

ventral  wall  of  the  anterior  portion  (Figi  378  and  434).  In  the  space  thus 
enclosed  the  dorsum  sellae  is  subsequently  formed.  Associated  with  this 
increase  of  the  cephalic  flexure  is  an  increased  prominence  of  the  mid-brain 
roof.  The  pontine  flexure  has  begun,  there  being  now  a  bending  of  the  whole 
tube  in  the  pons  region,  the  concavity  of  the  bend  being  dorsal.  At  the  same 
time  there  is  a  corresponding  tendency  for  the  roof  of  the  rhombencephalon  to 
become  shorter  and  wider.  There  is  also  a  further  thinning  of  the  above 
mentioned  expanded  portion  of  the  roof  plate  in  this  region,  and  associated 
with  this  a  thrusting  of  the  thick  lateral  walls  outward  at  the  top  so  that  they 
come  to  lie  almost  flat  instead  of  vertically  as  in  the  cord.  From  the  cord 
to  the  place  of  greatest  width  above  mentioned,  this  dorsal  thrusting  apart 


FIG.  378. — Profile  view  of  a  model  of  the  brain  of  a  human  embryo  during  the  third  week.    His. 
A,  Optic  vesicle;  A.v.,  auditory  vesicle;  Br,  pons  region;  H,  pallium;  Hh.  cerebellum;  /,  isthmus; 
M,  mid-brain;  AT  and  Rf,  medulla;  NK,  cervical  flexure;  Pm,  mammillary  region;  Tr,  in-' 
fundibulum;  Z,  inter-brain  or  diencephalon. 

of  the  lateral  rhombic  walls  obviously  becomes  more  and  more  pronounced. 
In  front  of  this  region  of  greatest  width,  the  roof  plate  becomes  narrower  and 
the  dorsal  parts  of  the  walls  (alar  plates)  form  the  rudiment  of  the  cerebellum, 
the  rest  of  the  rhombic  brain  forming  the  medulla  oblongata.  Each  lateral 
wall  of  the  rhombic  brain  is  now  divided  into  a  dorsal  longitudinal  zone  or 
plate  (alar  plate)  and  a  ventral  zone  or  plate  (basal  plate)  by  a  longitudinal 
furrow  along  its  inner  surface,  the  sulcus  limitans.  A  study  of  the  external 
appearances  and  transverse  sections  of  this  part  of  the  brain  tube  will  make 
these  relations  clear  (Figs.  418,  398  to  401  and  489).  Neuromeres  are  also 
present  at  this  stage  (see  p.  459).  In  the  meantime  the  neural  tube  has  also 
become  bent  ventrally  at  the  junction  of  the  brain  and  cord,  forming  the  cervical 


448  TEXT-BOOK  OF  EMBRYOLOGY. 

flexure.  The  pallium  has  increased  in  size  and  now  forms  a  considerable 
prominence  on  the  brain  tube.  Its  boundaries  are  also  much  more  clearly 
marked  off  (see  Fig.  433).  On  the  inner  side  of  the  tube,  the  area  below 
the  bulging  of  the  pallium  is  the  corpus  striatum.  Externally,  just  below  the 
bulging,  we  have  the  region  where  the  olfactory  lobes  are  differentiated.  The 
proximal  part  of  the  optic  evagination  has  become  longer  and  narrower.  The 
ventral  expansion  of  the  diencephalon  is  the  hypothalamus,  the  portion  of  the 
diencephalon  dorsal  to  the  latter  being  the  thalamus.  Two  slight  protrusions 
of  the  ventral  wall  of  the  hypothalamus  have  appeared;  the  caudal  one  is  the 
mammillary  region,  the  anterior  one  the  infundibulum.  The  cavity  of  the 
diencephalon  (third  ventricle)  is  connected  by  the  mid-brain  cavity  (iter  or 
aqu&ductus  Svlvii)  with  the  rhombic  brain  cavity  or  iourth  ventricle. 

HISTOGENESIS  OF  THE  NERVOUS  SYSTEM. 

The  neural  plate  is  at  first  a  simple  columnar  epithelium.  The  various 
processes  by  which  this  is  converted  into  the  fully  formed  nervous  system  are : 
(i)  cell  proliferation;  (2)  cell  migration;  (3)  cell  differentiation.  These  proc- 
esses are  not  entirely  successive  in  point  of  time,  but  overlap  each  other.  Cell 
division  is  present  from  the  first,  increases  to  a  certain  period  in  development 
and  then  practically  ceases;  cell  migration  is  partly  a  necessary  concomitant  and 
resultant  of  cell  division,  and  cell  differentiation  is  in  part  due  to  the  growth  of 
the  cytoplasm  and  is  in  part  a  result  of  environmental  differences  produced  by 
these  processes.  In  development  the  following  stages  may  be  distinguished : 

(i)  Stage  of  indifferent  epithelium;  (2)  appearance  of  nerve  elements 
(neurones)  and  resulting  differentiation  into  supporting  and  nerve  elements; 
(3)  growth  of  neurones  and  resulting  differentiation  and  development  of  (a) 
peripheral  neurones,  (b)  lower  intermediate  or  intersegmental  neurones,  (c) 
neurones  of  higher  centers  and  neurone  groups  in  connection  with  them  (supra- 
segmental  neurones).  These  stages  do  not  occur  simultaneously  throughout  the 
whole  neural  tube,  some  parts  being  more  backward  in  development  than  others 
(p.  443) .  In  general  the  spinal  cord  and  epichordal  segmental  brain  are  most 
advanced  in  development.  Furthermore,  the  ventral  part  of  the  brain  tube 
precedes  the  dorsal.  The  most  backward  part  of  the  whole  neural  tube  is  the 
pallium. 

The  various  phases  of  /^^-differentiation  of  the  neurone  are  (i)  the 
development  of  the  axone  and,  later,  of  its  branches;  (2)  the  growth  of  the 
dendrites;  (3)  the  formation  of  accessory  coverings  or  sheaths,  the  neurilemma 
and  the  myelin  (medullary)  sheath.  The  principal  internal  differentiations 
are  (i)  the  appearance  of  the  neurofibrils;  (2)  the  chromophilic  bodies  of 
Nissl;  (3)  pigment.  These  latter  may  all  be  regarded  as  products  of  the 
nucleus  and  undifferentiated  cytoplasm  of  the  nerve-cell. 


THE  NERVOUS  SYSTEM.  449 

Epithelial  Stage.     Development  of  Neuroglia. 

From  the  very  first,  the  neural  plate  exhibits  dividing  cells  similar  to  those 
seen  in  the  non-neural  ectoderm.  The  cell  divisions  are  indirect  and  the 
mitoses  are  confined  to  the  outer  part  of  the  ectoderm,  occurring  between  the 
outer  ends  of  the  resting  epithelial  cells  (Fig.  370).  These  dividing  cells  have 
been  termed  by  His  germinal  cells.  When  the  neural  tube  is  formed,  the 
mitoses  are  still  confined  to  the  outer,  now  the  luminal,  surface,  this  being  a 
general  phenomenon  in  developing  epithelial  tubular  structures.  As  a  result 
the  daughter  nuclei  migrate  away  from  the  lumen. 

In  the  most  advanced  parts  of  the  neural  tube  (see  p.  438),  the  mitoses  in- 
crease in  number  up  to  about  the  fourth  to  sixth  week  of  development,  and  then 
diminish  anc1  finally  nearly  disappear  about  at  the  end  of  two  months.  At 
about  the  time  the  blood  vessels  penetrate  the  tube,  the  mitoses  are  no  longer 
entirely  confined  to  the  proximity  of  the  lumen. 

As  a  result  of  proliferation,  the  epithelial  wall  very  early  assumes  the  ap- 
.  pearance  of  a  stratified  epithelium — at  least  there  are  several  strata  of  nuclei. 
There  are  at  this  stage  in  many  forms  two  layers,  an  outer  or  marginal  layer, 
free  of  nuclei,  and  an  inner  or  nuclear  layer  (Figs.  380  and  381).  In  a  human 
embryo,  however,  of  about  two  weeks  this  division  into  layers  is  yet  hardly 
evident,  though  there  are  several  strata  of  nuclei.  Apparently  these  layers  are 
not  well-marked  until  the  radial  arrangement  of  the  myelospongium,  as 
described  below,  has  become  more  pronounced. 

Accompanying  the  above  changes,  changes  also  manifest  themselves  in  the 
character  of  the  cells.  At  about  the  time  of  the  closure  of  the  neural  tube,  the 
cell  boundaries  become  indistinct  and  finally  practically  obliterated,  thus  form- 
ing a  syncytium,  the  myelospongium.  At  the  same  time,  the  syncytium  becomes 
very  alveolar  in  structure  and  a  general  spongioplasmic  reticulum  is  formed  (Figs. 
380  and  381)  by  the  anastomosing  denser  strands  (trabeculae)  of  protoplasm. 
At  a  very  early  stage  (two  weeks),  these  trabeculae  unite  along  the  inner  and 
outer  walls  of  the  neural  tube  forming  internal  and  external  limiting  mem- 
branes. The  nuclei  of  the  neural  tube  have  at  first  an  irregular  arrangement 
in  the  reticulum,  at  least  in  the  human  embryo.  This  is  followed  by  a  more 
radial  arrangement  of  both  nuclei  and  protoplasmic  filaments  (Fig  382),  form- 
ing nucleated  radial  masses  of  protoplasm — the  sponglioblasts  (Figs.  381  to 
384).  There  is  some  dispute  as  to  the  loss,  complete  or  incomplete,  of  identity 
of  the  epithelial  cells  in  the  formation  of  the  spongioblasts.  According  to 
Hardesty,  they  are  formed  by  a  collapse  of  the  epithelial  cells  and  a  rearrange- 
ment of  their  denser  parts  into  axial  filaments.  The  radial  arrangement  does 
not  extend  into  the  outer  part  of  the  neural  tube  which,  retaining  its  irregular 
reticular  character,  is  now  non-nucleated  in  the  human  embryo  and  forms  the 


450 


TEXT-BOOK  OF  EMBRYOLOGY, 


a 


FIG.  382. 


FIG.  379. — From  the  neural  tube  of  an  embryo  rabbit  shortly  before  the  closure  of  the  tube,  g,  Germi- 
nal or  dividing  cell;  w,  peripheral  zone,  position  of  the  later  marginal  layer.  His. 

FIG.  380. — Pig  of  5  mm.,  unflexed.  Just  after  closure  of  the  neural  tube.  Segment  of  a  vertical 
section  of  the  lateral  wall  of  the  tube,  g,  Germinal  cells;  m,  beginning  of  marginal  layer; 
mli,  internal  limiting  membrane;  r,  radial  columns  of  protoplasm.  The  resting  nuclei  lie  in 
the  inner  or  nuclear  layer.  Hardesty. 


THE  NERVOUS  SYSTEM. 


451 


marginal  layer.  The  increase  in  the  thickness  and  circumference  of  the  walls 
of  the  tube  and  the  resulting  tensions  may  be  a  factor  in  this  arrangement 
of  the  protoplasmic  filaments.  At  the  boundary  between  the  marginal  and 
nuclear  layers  the  reticulum  appears  to  be  especially  dense. 

"With  the  further  increase  and  development  of  the  nervous  elements  (see 
p.  455)  the  radial  arrangement  of  the  spongioblasts  noted  above  becomes  more 
and  more  obliterated.  As  shown  by  Golgi  preparations,  in  their  migration  from 
the  lumen  (Fig.  384)  the  spongioblasts  lose  their  connection  with  the  lumen, 


ep     mil 


cs 


FIG.  383, — Hardesty.  Combination  drawing  from  sections  of  pig  of  15  mm.  The  upper  part  is 
from  a  section  of  the  same  stage  as  the  lower  but  stained  by  the  Golgi  method.  By  migra- 
tion and  differentiation  the  mantle  layer  has  been  formed.  The  cells  remaining  near  the 
lumen  form  the  ependyma  layer  (ep.).  b,  Boundary  between  mantle  and  marginal  layers; 
ep,  ependyma;  mli  and  mle,  internal  and  external  limiting  membranes;  mv,  differently 
arranged  mid-ventral  portion  of  the  marginal  layer;  r,  radial  filaments;  cs,  connective  tissue 
syncytium. 


their  peripheral  processes  become  abbreviated  and  disappear,  and  they  finally 
differentiate  into  the  irregular  branching  neuroglia  cells  (Fig.  385).  According 
to  Hardesty,  there  is  simply  a  general  nucleated  mass  which  changes  form 
pari  passu  with  changes  in  the  enclosed .  differentiating  nervous  elements, 
finally  assuming  shapes  dependent  upon  the  character  of  the  spaces  between 
the  formed  nervous  elements.  An  exception  to  this  is  a  layer  of  nucleated 
elements  which  remain  next  the  lumen  and  form  the  ependyma  cells  which  still 

FIG.  381. — Pig  of   7  mm.,  unflexed.     Segment  from  the  ventro-lateral  wall  of  the  neural  tube; 

gy  Germinal     cells;     mli,  internal    limiting    membrane;    mle,  external   limiting  membrane 

-  radial,  axial  filaments  of  the  syncytial  protoplasm;  p,  beginning  of  pia  mater.     Hardesty. 
FIG.  382. — Pig  of  10  mm.,  "  crown-rump  "  measurement.     Segment  from  lateral  wall  of  neural  tube. 

&,  boundary  between    nuclear    layer  and    marginal  layer  (m).     Other   references   same   as 

in  381.    Hardesty. 
a  indicates  the  zone  in  which  the  dividing  cells  are  located.     Later,  it  is  composed  of  the  inner  ends 

of  the  ependyma  cells  (column  layer  of  His}. 


452 


TEXT-BOOK  OF  EMBRYOLOGY. 


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THE  NERVOUS  SYSTEM. 


453 


send  radial  extensions  into  the  wall  of  the  neural  tube  (Figs.  383  and  384). 
These  cells  develop  cilia  projecting  into  the  lumen. 

A  still  later  differentiation  in  the  supporting  elements  of  the  tube  is  the  ap- 
pearance of  neuroglia  fibers — a  product  of  the  spongioblastic  protoplasm,  but 
differing  from  it  chemically  (Fig.  385).  The  exact  relation  of  these  neuroglia 
fibers  to  the  nucleated  neuroglia  cells  in  the  adult  is  a  matter  of  dispute. 


FIG.  385. — Hardesty  Combination  drawing  from  transverse  sections  of  the  spinal  cord  of  20  cm. 
pi-*.  Showing  the  first  appearance  of  neuroglia  fibers,  a,  Neuroglia  cell  as  shown  by  the 
Benda  method  of  staining;  a',  similar  cell  by  the  Golgi  method;  b  and  br,  non-nucleated 
masses;  d,  free  nuclei;  e  and/,  differentiating  neuroglia  fibers;  s,  "seal-ring"  cells,  envelop- 
ing myelinating  nerve-fibers. 

With  the  penetration  of  blood  vessels  into  the  neural  tube  a  certain  amount  of 
mesodermal  tissue  is  brought  in.  How  much  of  the  supporting  tissue  of  the 
nervous  system  is  derived  from  the  mesoderm  is  uncertain,  but  it  is  most 
probable  that  it  is  relatively  small  in  amount  and  is  confined  principally  to  the 
connective  tissue  of  the  walls  of  the  blood  vessels. 

Early  Differentiation  of  the  Nerve  Elements. 

It  has  been  seen  that  some  of  the  actively  dividing  cells  (germinal  cells)  at 
first  simply  increase  the  ordinary  epithelial  elements  of  the  tube  which  in  turn 
form  the  myelospongium,  the  spongioblasts  and  finally  the  ependyma  and  the 
neuroglia.  Other  daughter  cells  produced  by  the  division  of  the  germinal  cells 


454 


TEXT-BOOK  OF  EMBRYOLOGY. 


differentiate  into  nerve  cells  as  described  below.  Still  others  probably  migrate 
outward  as  indifferent  cells,  which  later  proliferate  and  form  cells  which  differ- 
entiate into  neuroglia  and  nerve  cells. 

According  to  recent  researches  (Cajal),  by  means  of  the  silver  stain  of  Cajal 
the  first  indication  of  the  differentiation  of  cells  into  nerve  cells  is  the  appear- 
ance of  neurofibrils  in  the  cytoplasm  of  cells  near  the  lumen. '  The  part  of  the 
cell  in  which  the  neurofibrils  first  appear  is  called  the  fibrillogenous  zone 
(Held)  and  is  usually  in  the  side  furthest  from  the  lumen.  The  cells  in  which 
these  appear  are  apparently  without  processes,  and  are  accordingly  termed 
apolar  cells  (Cajal).  (Fig.  386.) 


FIG.  386. — Section  through  the  wall  of  the  fore-brain  vesicle  of  a  chick  embryo  of  3  J  days.     Cajal. 

A,  b  arid  c,  Differentiating  nerve  cells  in  apolar  stage,  the  neurofibrils  are  black;  a,  cell  in  a  stage 
transitional  to  the  bipolar  stage;  5,  bipolar  cells;  c  (at  lower  right  corner),  cone  of  "growth" 
of  developing  axone;  e,  tangential  axone.  The  cells  in  the  bipolar  stage  have  migrated  out 
ward,  but  the  neuroblast  or  mantle  layer  has  not  yet  been  differentiated. 


The  next  step  in  the  development  of  many,  but  probably  not  all,  of  these  cells 
is  their  transformation  into  bipolar  cells  by  the  outgrowth  of  two  neurofibrillar 
processes,  one  directed  toward  the  lumen,  the  other,  usually  thicker,  toward  the 
periphery,  the  cell  body  at  the  same  time  beginning  to  migrate  outward  (Fig.  386). 
This  bipolar  stage  may  be  regarded  as  conditioned  to  some  extent  by  the  radial 
arrangement  of  the  other  elements,  due  in  turn  partly  to  the  original  epithelial 
structure  and  partly,  possibly,  to  tensions  produced  by  the  growth  of  the  tube. 
It  is  also  interesting  as  recalling  conditions  in  sensory  epithelia  and  in  the 
cerebrospinal  ganglia.  The  bipolar  stage  is  most  common  probably  in  those 
parts  where  the  elements  show  a  radial  arrangement  in  the  adult.  Such  are  the 
layered  cortices  of  the  mid-brain  and  pallium.  Nerve  cells  maintaining  a  con- 
nection, by  central  processes,  with  the  luminal  wall  have  been  described  in  lower 
Vertebrates.  This  connection  may  be  explained  as  due  to  a  persistence  of  the 
central  processes  of  cells  in  the  bipolar  stage. 


THE  NERVOUS  SYSTEM. 


455 


The  next  stage  is  a  monopolar  stage  produced  by  the  atrophy  of  the  luminal 
process.  Cells  in  this  stage  are  the  neuroblasts  of  His,  the  peripheral  processes 
being  the  developing  axones  (Fig.  387).  As  seen  in  ordinary  stains,  the  above 
differentiation  of  the  neuroblasts  is  marked  by  a  corresponding  differentiation 
of  the  nuclear  layer  into  an  inner  layer  retaining  its  previous  characteristic  radial 
arrangement,  and  an  outer  layer  characterized  by  fewer  nuclei  more  irregularly 
arranged.  The  latter  layer  is  the  mantle,  or  neurone  layer  (Fig.  404) .  There 
are  now  three  layers:  (i)  inner  (nuclear),  (2)  mantle  (neurone)  and  (3)  marginal. 
The  mantle  layer  is  thus  produced  by  the  migration  and  differentiation  of  cells 
into  neuroblasts.  While  this  process  may  begin  near  the  lumen  (apolar  nerve 


FIG.  387. — Dorsal  portion  of  the  lumbar  cord  of  a  chick  embryo  of  three  days.     Cafal. 
A,  B,  Cells  in  the  apolar  stage  with  fibrillogenous  zones;  B  shows  transition  to  the  bipolar  stage; 
E,  further  advanced  bipolar  cell;  G,  cells  in  monopolar  stage  or  neuroblasts  of  His;  a,  giant 
cone  of  growth.     These  cells  have  migrated  to  the  outer  part  of  the  nuclear  layer,  thereby 
forming  the  beginning  of  the  mantle  layer. 

cell  of  Cajal)  and  progress  as  the  cell  has  moved  somewhat  further  away  (bipolar 
stage) ,  the  monopolar  stage  is  probably  reached  only  when  such  cells  form  a  part 
of  the  mantle  layer.  In  other  words,  the  mantle  layer  is  created  by  the  migra- 
tion to  a  certain  location  and  differentiation  to  a  certain  stage  of  the  primitive 
nerve  cells.  The  mantle  layer,  as  previously  stated,  probably  also  contains 
indifferent  cells  which  may  by  further  proliferation  and  subsequent  differentia- 
tion become  either  glia  or  nerve  cells.  *  The  looser  arrangement  of  the  cells  of  the 
mantle  layer  is  probably  in  some  measure  due  to  the  growth  of  the  dendrites  which 
appear  soon  after  the  axones.  It  may  be  also  due  to  the  beginning  vascularization 
of  the  tissues  with  resulting  transudates  (His)  which  usually,  however,  begins 
somewhat  later.  The  association  in  time  of  vascularization  and  further  growth 

*  It  is  an  open  question  as  to  how  late  in  development  these  "  extraventricular  "  cell-divisions,  in- 
volving "  indifferent "  cells,  may  occur.  The  neuroglia  cells,  however,  like  other  supporting  elements, 
preserve  this  capacity  of  division  indefinitely,  as  shown  by  the  increase  in  neuroglia  cells  in  patho- 
logical conditions. 


456  TEXT-BOOK  OF  EMBRYOLOGY. 

of  neurocytoplasm  (dendrites)  is  significant.  When  the  cell-proliferation  near 
the  lumen  has  ceased,  the  supply  of  new  cells  ceases,  and  as  the  cells  of  the 
inner  layer  continue  to  differentiate  into  cells  of  the  mantle  layer,  the  inner 
layer,  being  no  longer  replenished  from  within,  is  reduced  to  the  single  layer  of 
cells  which  remain  behind  as  ependyma  cells  (p.  451). 

-•  -^ 

Differentiation  of  the  Peripheral  Neurones  of  Cord  and 
Epichordal  Segmental  Brain. 

Efferent  Peripheral  Neurones.  The  differentiation  of  a  mantle  or 
neurone  layer  from  the  outer  part  of  the  original  nuclear  layer  is  practically 
universal  throughout  the  whole  neural  tube.  It  appears  first  and  is  conse- 
quently most  advanced,  however,  in  the  ventral  part  of  the  lateral  walls  of  the 
cord  and  epichordal  brain.  The  axones  of  neuroblasts  occupying  the  basal  plate 
of  this  region  of  the  neural  tube  grow  out  through  the  external  limiting  mem- 


FIG.  388. — Ventral  part  of  wall  of  lumbar  cord  of  7o-hour  duck  embryo,  showing  efferent  root 

fibers  first  emerging  from  cord  (combined  from  two  sections) .     Cajal. 
A,  Spinal  cord;  B,  perimedullary  space;  C,  meningeal  membrane;  a,  b,  cones  of  radially  directed 

axones;  c,  d,  cones  of  transversely  directed  axones;  Z>,  bifurcated  cone;  E,F,  cones  crossing 

perimedullary  space;  G,  aberrant  cones. 

brane  and  emerge  as  the  efferent  ventral  root  fibers.  The  appearance  of  these 
early  root  fibers  in  the  duck  is  shown  in  Fig.  388.  The  process  is  similar  in 
the  human  embryo  and  begins  about  the  third  week.  The  neurones  thus 
differentiated  are  the  efferent  peripheral  neurones. 

In  some  forms,  at  least,  cells  appear  to  migrate  out  from  the  tube  along  with 
the  efferent  root  fibers.  Their  fate  is  not  certain,  but  they  probably  either 
metamorphose  into  the  neurilemma  cells  or  possibly  form  part  of  the  sympa- 
thetic ganglia  (see  p.  492).  In  general  the  questions  affecting  the  differentiation 


THE  NERVOUS  SYSTEM. 


457 


of  the  efferent  fibers  are  the  same  as  for  the  afferent  and  are  further  dealt 
with  later  (pp.  462-465). 

The  majority  of  the  efferent  root  fibers  pass  to  the  differentiating  somatic 
muscles  which  they  innervate,  forming  specialized  terminal  arborizations  (the 
motor  end  plates).  The  fibers  to  the  dorsal  musculature  form,  together  with 
the  afferent  fibers  (p.  460),  the  dorsal  branch  of  the  peripheral  spinal  nerve; 
others  form  part  of  the  ventral  branch  which  sends  a  branch  mesially  toward 
the  aorta.  Some  of  the  fibers  of  the  mesial  branch  take  a  longitudinal  course. 
This  mesial  branch  is  the  white  ramus  communicans  and  terminates  in  the 
various  sympathetic  ganglia  which  are  later  formed  along  its  course  (p.  461). 


IG.  389. — Diagram  (lateral  view)  of  the  brain  of  a  10.2  mm.  human  embryo  (during  the  fifth  week), 

showing  the  roots  of  the  cranial  nerves.     His. 
Ill,  Oculomotor;  IV,  Trochlear;  V,  Trigeminus  (m,  efferent  root,  s,  afferent  root) ;  VI,  Abducens; 
VII,  Facial;  VIII,  Acoustic  (c,  cochlear  part,  vt  vestibular  part);  IX,  Glossopharyiigeus; 
X,  Vagus;  XI,  Spinal  accessory;  XII,  Hypoglossus.     ot.,  Auditory  vesicle;  Rh.l.,  rhombic 
lip.     The  two  series  of  efferent  roots  (medial  and  lateral)  are  clearly  shown. 


[Comp.  Figs.  225,  227,  394  and  36^.)  The  fibers  to  the  sympathetic  ganglia 
ire  the  visceral  (splanchnic)  fibers  of  the  ventral  root.  There  are  a  few  other 
fibers  which  grow  dorsally  from  neuroblasts  in  the  ventro-lateral  walls  of  the 
cord  and  thence  out  via  the  dorsal  root  (Fig.  392).  They  also  are  probably 
visceral. 

In  the  cord  the  splanchnic  fibers,  with  the  exception  above  noted,  issue  with 
the  somatic  fibers  in  a  common  ventral  root.  In  the  epichordal  segmental  brain, 
however,  there  is  a  differentiation  of  the  efferent  neuroblasts  of  the  basal  plate 
into  two  series  of  nuclei,  a  medial  and  a  lateral.  The  medial  series  consists  of 


458 


TEXT-BOOK  OF  EMBRYOLOGY. 


the  nuclei  of  the  XII,  VI,  IV  and  III  cranial  nerves,  and  their  axones  grow 
out  as  medial  ventral  root  fibers  (except  the  IV)  (Fig.  389)  to  the  differenti- 
ating muscles  of  the  tongue  and  eyeball  which  they  respectively  innervate. 
These  muscles  are  probably  somatic  and  their  nerves  are  the  somatic  efferent 
cranial  nerves  corresponding  with  the  greater  part  of  the  fibers  of  the  ventral 
roots  of  the  cord  (compare  p.  432).  The  lateral  series  consists  of  the  nuclei  of 
the  efferent  portions  of  the  roots  of  the  XI,  X,  IX,  VII  and  V  cranial  nerves 
and  their  axones  grow  out  as  lateral  roots  (Fig.  389)  to  the  differentiating 
striated  branchial  (splanchnic)  muscles  (sternocleidomastoideus,  trapezius, 


N.trigem.  (motor) 
•••N.trigeni.(3ensJ 
N.facialis 

—'-'••-  N.acusticus 
N.abdueens 

N.  glossopharyng. 

—N.  vagus 


N.hypoglossus 


FIG.  390. — Diagram  of  the  floor  of  the  4th  ventricle  of  a  10  mm.  human  embryo,  illustrating  the 
rhombic  grooves  and  their  relations  to  the  cranial  nerves.  The  point  of  attachment  of  the 
acoustic  and  the  sensory  root  of  the  trigeminal  nerve  is  shown  by  dotted  circles;  the  motor 
nuclei  are  represented  by  heavy  dots.  Streeter. 

pharynx,  larynx,  face  and  jaw)  and  also  to  muscles  of  the  viscera  (via  sympa- 
thetic?). The  lateral  nuclei  and  their  roots  are  thus  splanchnic.  (Cf.  pp. 
302-3,  462,  464.)  Their  root  fibers,  with  the  incoming  afferent  fibers,  form  the 
mixed  roots  of  these  nerves.  The  positions  of  these  various  nuclei  and  their 
roots  are  clearly  indicated  in  Figs.  389,  398-401,  409  and  413  and  require  no 
further  description.  Additional  details  are  mentioned  in  connection  with 
the  afferent  cranial  nerves.  In  the  region  of  the  vagus  nerve,  there  are 
differentiated  two  series  of  lateral  nuclei,  a  ventro-lateral  (nucleus  ambiguus  X) 
and  a  dorso-lateral  (dorsal  efferent  nucleus  X)  (comp.  Fig.  369).  Fig.  414 


11; 


THE  NERVOUS  SYSTEM. 


459 


apparently  indicates  the  beginning  of  this  differentiation.  The  significance 
of  the  dorso-lateral  nucleus  is  uncertain.  It  possibly  sends  fibers  to  the 
sympathetic  system. 

At  about  this  period  six  transverse  rhombic  grooves  are  plainly  marked  in 
the  floor  of  the  fourth  ventricle,  standing  in  relation  with  the  nerves  of  this 
region  (Fig.  390).  They  are  ordinarily  regarded  as  neuromeric,  but  the  above 
relation  would  indicate  that  they  have  primarily  a  branchiomeric  character 
(Streeter).  It  will  be  noticed  that  each  of  the  three  main  ganglionic  masses 
of  this  region  (p.  465)  corresponds  to  two  of  the  grooves.  (Comp.  p.  435). 

The  further  development  of  the  efferent  neurones  exhibits  phases  common 
to  many  other  nerve-cells  with  a  large  amount  of  cytoplasm  (somatochrome 
cells).  The  further  development  of  the  neurofibrils  of  cell  body  and  dendrites 


Neural  cvest 


— Ectoderm 

A 

Neural 
plate 


Ectoderm 


V 


Neural  crest ( 

C 

•^Primitive 
segment 


FIG.  391. — Three  stages  in  the  closure  of  the  neural  tube  and  formatiqn  of  the  neural  crest  (spinal 
ganglion  rudiment).  From  transverse  sections  of  a  human  embryo  of  2.5  mm.  (13  pairs  of 
primitive  segments,  14-16  days),  -von  Lenhossek. 

is,  according  to  some  observations,  at  first  confined  to  the  peripheral  portions, 
leaving  a  clear  zone  in  the  vicinity  of  the  nucleus.  The  chromophilic  sub- 
stance first  appears  as  distinct  granules  about  the  end  of  the  second  month, 
there  being  apparently  a  diffuse  chromophilic  substance  present  before  this 
period.  The  chromophilic  granules  also  are  first  differentiated  in  the  per- 
ipheral portions  of  the  cell.  A  still  later  differentiation  is  the  pigment,  which 
probably  does  not  appear  till  after  birth.  This  increases  greatly  in  amount 
in  later  years  and  is  then  an  indication  of  senility  of  the  nerve-cell. 

Afferent  Peripheral  and  Sympathetic  Neurones. — It  has  already  been 
mentioned  (p.  421)  that  in  the  closure  of  the  neural  tube  certain  cells  forming 
an  intermediate  band  between  the  borders  of  the  neural  plate  and  the  non- 
neural  ectoderm  are  brought  together  by  the  fusion  of  the  lips  of  the  plate 


460 


TEXT-BOOK  OF  EMBRYOLOGY. 


and  form  a  ridge  on  the  dorsal  surface  of  the  neural  tube,  this  ridge  being 
known  as  the  neural  crest  (Fig.  391). 

In  the  SPINAL  CORD,  at  three  weeks,  the  neural  crest  has  separated  from  the 
cord  and  split  into  two  longitudinal  bands.  The  ventral  border  of  each  band 
shows  a  transverse  segmentation  into  rounded  clumps  of  cells,  forming  the 
rudiments  of  the  spinal  ganglia  which  later  become  completely  separated.  The 
efferent  roots  have  begun  to  develop  but  the  afferent  roots  appear  later  (fourth 
week,  Fig.  396).  The  cells  composing  these  rudiments  are  polyhedral 
or  oval  rather  than  columnar  and  proliferation  still  proceeds  among  them 
A  differentiation  of  these  cells  soon  begins.  Some,  usually  larger  cells 


/C 


1M: 
.*    '/*'»    f^F^      * i<     *.    •'* 

&!•'*••• 

FIG.  392. — Part  of  a  transverse  section  through  the  cord  and  spinal  ganglion  of  a  56-hour  chick 

embryo  (combined  from  two  sections).     Cajal. 
A,  Efferent  cell  of  dorsal  root;  B,  cone  of  growth  of  central  process  (afferent  dorsal  root  fiber)  of 

spinal  ganglion  cell;  C,  bifurcation  of  afferent  root  fibers  in  cord,  forming  beginning  of  dorsal 

funiculus  or  dorsal  white  column  of  cord. 

begin  to  assume  a  bipolar  shape.  Their  central  processes  grow  toward  the 
dorsal  part  of  the  lateral  walls  (alar  plate)  of  the  neural  tube  which  they  enter 
(Fig.  392),  becoming  afferent  (dorsal)  root  fibers.  These  fibers  enter  the  mar- 
ginal layer  and  there  divide  (Figs.  392  and  403)  into  ascending  and  descend- 
ing longitudinal  arms  which  constitute  the  beginning  of  the  dorsal  (posterior) 
juniculus  of  the  cord.  The  peripheral  processes  of  the  developing  ganglion 
cells  grow  toward  the  periphery,  uniting  with  the  ventral  root  and  forming 
with  it  the  various  branches  of  the  peripheral  spinal  nerve  (compare  Figs. 
225>  227,394  and  366).  Other  peripheral  branches  pass  as  a  part  of  the 
white  ramus  communicans  to  the  sympathetic  ganglia  through  which  they 


THE  NERVOUS  SYSTEM. 


461 


proceed  to  the  visceral  receptors.  These  latter  fibers  are  thus  visceral  afferent 
fibers. 

It  is  now  known  that  the  spinal  ganglion  is  a  much  more  complicated  struc- 
ture and  has  more  forms  of  nerve  cells  than  was  formerly  realized.  The  dif- 
ferentiation into  these  various  types  has  not  yet  been  fully  observed.  The 
bipolar  cells,  however,  become  unipolar  in  the  manner  shown  in  Fig.  393. 
The  cell  body  first  becomes  eccentrically  placed  with  reference  to  the  two  proc- 
esses and  then,  as  it  were,  retracts  from  them,  remaining  connected  with  them 
by  a  single  process.  This  change  may  economize  space. 

According  to  most  authorities,  many  of  the  cells  of  the  neural  crest  do  not 
cease  their  migration  by  forming  spinal  ganglia,  but  undifferentiated  cells 


FIG.  393. — Section  of  spinal  ganglion  of  1 2-day  chick  embryo.     Cajal. 
Showing  various  stages  of  the  change  from  the  bipolar  to  the  unipolar  condition.     A,B,  Unipolar 
cells;  C,  D,  F,  G,  cells  in  transitional  stage;  E,  bipolar  cell;  H,  immature  cell.     The  neuro- 
fibrils  are  well  shown. 

wander  still  further  ventralward  and  form,  probably  also  undergoing  still 
further  proliferation,  the  rudiments  of  the  various  sympathetic  ganglia,  becom- 
ing subsequently  differentiated  into  the  sympathetic  cells.  By  this  migration 
there  is  first  formed  a  longitudinal  column  of  cells  ventral  to  the  spinal  ganglia 
(Fig.  395)  and,  later,  in  relation  with  the  white  communicating  rami  (Fig. 
394).  This  column  becomes  segmented  (seventh  week),  forming  ultimately 
the  ganglia  of  the  vertebral  sympathetic  chain.  In  the  meanwhile,  the 
cells  of  the  column  proliferate  in  places,  forming  rudiments  which,  by  migra- 
tion and  further  differentiation,  form  the  ganglia  of  the  various  prevertebral 
sympathetic  plexuses  (cardiac,  cceliac,  pelvic,  etc.).  Further  migrations  lead  to 
the  formation  of  the  ganglia  of  the  peripheral  plexuses  (Auerbach,  Meissner, 


462 


TEXT-BOOK  OF  EMBRYOLOGY. 


etc.).  All  these  ganglia,  probably,  are  innervated  by  fibers  from  the  white 
ramus,  along  whose  course  they  apparently  migrated.  The  axones  of  their 
cells  pass  to  visceral  structures  either  in  the  same  segment  or,  via  the  longi- 
tudinal chain,  to  those  of  other  segments.  Some  also  join  the  branches  of 
the  peripheral  spinal  nerves  (gray  ramus}.  Fibers  of  the  white  ramus  also  pass 
longitudinally  in  the  chain  to  vertebral  ganglia  of  other  segments.  The 
possibility  previously  mentioned  (p.  456)  of  a  contribution  to  the  sympa- 
thetic ganglia  by  cells  migrating  out  along  with  the  ventral  roots  must  be  kept  in 
mind.  It  would  seem  a  priori  more  probable  that  these  latter  would  furnish 
the  efferent  sympathetic  cells,  but  the  efferent  cells  predominate  in  the  sym- 


Spinal  cord 

Spinal  ganglion 


Ventral  root 


Mixed  spinal  nerve  -- 
Myotome  — 


Sympathetic  ganglion 


FIG.  394. — From  a  transverse  section  of  a  chick  embryo  of  4!  days.     Neumayer. 


pathetic  and  must  thus  be  regarded  as  derived  partly  or  wholly  from  the 
neural  crest  which  furnishes  at  least  the  major  part  of  all  the  sympathetic 
cells. 

It  seems  probable  that  not  all  the  cells  of  the  neural  crest  form  nerve  cells, 
but  some,  usually  smaller  cells,  become  closely  applied  to  the  spinal  ganglion 
cells,  forming  amphicytes,  while  others  (lemmocytes)  wander  out  along  the  nerve 
fibers  and  become  the  neurilemma  cells,  forming  the  neurilemma.  These  cells 
in  this  case  would  be  quite  strictly  comparable  to  the  glia  cells  of  the  neural 
tube.  According  to  another  view,  the  neurilemma  cells  are  of  mesodermal 
origin.  While  this  point  cannot  be  considered  entirely  determined,  it  seems 
fairly  certain  that  in  some  types  at  least  the  former  view  is  correct,  removal  of 
the  neural  crest  having  resulted  in  the  formation  of  efferent  nerves  without 


THE  NERVOUS  SYSTEM.  463 

neurilemma  cells  (Harrison).  The  modification  into  neurilemma  cells  seems 
to  be  accomplished  by  their  enveloping  the  axones  and  becoming  closely 
applied  to  them. 

The  peripheral  nerve  grows  toward  the  periphery  as  a  bundle  of  fibers  which  forms,  as 
seen  in  many  stains,  a  common  fibrillated  mass,  dividing  at  its  extremity  into  the  develop- 
ing branches  of  the  nerve.  The  lemmocytes  closely  envelop  each  of  these  growing  tips, 
but  proximally  only  envelop  the  main  nerve  trunk  (Bardeen).  The  final  clear  separation  of 


Notochord 


Spinal  ganglion  rudiment 


Sympathetic  ganglion  rudiment 


FIG.  395. — From  a  transverse  section  through  a  shark  (Scyllium)  embryo  of  15  mm.,  showing  the 

origin  of  the  sympathetic  ganglion.     Onodi. 

In  mammals  the  cells  are  more  scattered  and  their  origin  from  the  spinal  ganglion 
rudiment  not  so  clear. 

the  fibrillated  mass  into  the  individual  nerve  fibers  is  accomplished,  according  to  Gurwitsch, 
by  these  accompanying  cells  forming  septa  within  the  mass  and  finally  enveloping  each 
axone  as  its  neurilejnma  sheath.  Growth  in  bundles  appears  to  be  characteristic  also  of  the 
axones  (tracts  and  fasciculi)  of  many  neurone  groups  in  the  central  nervous  system. 

Owing  to  the  presence  of  these  migrating  cells  as  well  as  of  mesodermal  cells, 
the  peripheral  nerves  in  their  earlier  stages  appear  cellular  in  character;  later  the 
fibrous  elements  predominate,  the  nuclei  becoming  more  scattered  and  changing 
into  the  flatter  nuclei  characteristic  of  the  neurilemma  (Fig.  394).  According  to 
one  view  (Balfour;,  the  nerve  fibers  themselves  are  differentiated  from  the  cyto- 


464  TEXT-BOOK  OF  EMBRYOLOGY. 

plasm  of  these  cell-strings  and  are  thus  multicellular  structures.  Still  another 
view  is  that  of  Hensen,  according  to  which  the  fibers  are  a  differentiation  in 
situ  from  preexisting  syncytial  bridges  uniting  the  parts  connected  subsequently 
by  the  formed  nerve  fibers.  This  differentiation  may  not  be  primarily  con- 
nected with  the  neuroblasts  (Apathy,  Paton) .  An  intermediate  view  between 
this  and  the  outgrowth  view  of  His  is  that  of  Held,  according  to  which  the 
neurofibrillar  substance  is  an  outgrowth  from  the  neuroblast  body,  or  at  least  a 
differentiation  proceeding  from  that  body,  but  always  within  the  preexisting 
cellular  bridges  of  Hensen.  The  differentiating  fiber  is  thus  always  intracel- 
lular  instead  of  intercellular  as  according  to  the  His-Cajal  view.  The  experi- 
ments of  Harrison  above  alluded  to,  in  which  the  accompanying  migrating  cells 
were  eliminated  and  naked  axones  (axis-cylinders)  nevertheless  developed,  ap- 
parently disposes  of  the  cell-string  theory  of  Balfour.  The  growth  of  the 
fibers  in  the  marginal  layer  of  the  central  nervous  system  is  also  unfavorable  to 
this  theory.  The  apparently  proven  capacity  of  growing  axones  to  find  their 
way  through  foreign  tissues  (aberrant  regenerating  nerve  fibers,  Cajal), 
through  ventricular  fluid  (Cajal),  and  even  through  serum  (Harrison)  seems  to 
throw  the  weight  of  evidence  in  favor  of  the  view  of  His.  The  latter  is  the 
view  adopted  in  this  description,  though  many  of  the  most  important  facts  of 
development  are  not  perhaps  entirely  irreconcilable  with  any  of  these  views. 
The  general  conception  of  the  neurone  is  affected  by  these  questions  and  the 
related  question  of  anastomoses  between  the  nervous  elements,  whether  present 
at  all,  and  if  present,  whether  primary  or  secondarily  acquired. 

From  the  above  it  would  seem  that  the  cells  of  the  neural  crest  have  the 
capacity  of  differentiating  into  afferent  neurones,  efferent  (sympathetic)  neurones 
and  supporting  cells.  Other  cells  of  the  neural  crest  differentiate  into  the 
chromafnne  cells  of  the  suprarenal  glands  and  similar  structures  (p.  396). 

There  are  several  views  as  to  the  development  of  the  myelin  sheath.  Ac- 
cording to  one  view  (Vignal),  it  is  a  product  of  the  neurilemma  cells,  being 
formed  in  a  manner  analogous  to  the  formation  of  fat  by  fat  cells.  Accord- 
ing to  Wlassak,  the  various  substances  composing  the  myelin  (fat,  lecithin 
and  protagon)  are  first  found  in  the  central  nervous  system  in  the  protoplasm 
of  the  spongioblasts,  their  probable  original  source  being  the  blood  of  the 
meningeal  blood  vessels.  Later,  the  myelin  is  laid  down  around  the  axones, 
appearing  first  as  drops  or  granules.  The  same  process  takes  place  in  the 
peripheral  nervous  system.  The  supporting  elements  of  the  nervous  system 
thus  would  have  a  chemical  as  well  as  a  mechanical  function.  Another  view 
(Gurwitsch)  is  that  the  myelin  is  a  product  of  the  axone  and  is,  at  its  first 
appearance,  quite  distinct  from  the  neurilemma  cells. 

As  the  appearance  of  the  myelin  sheath  is  a  final  stage  in  the  development  of  the  neurone, 
the  various  neurone  systems  would  naturally  becorr0  Trwelinated  in  about  the  same  sequence 


THE  NERVOUS  SYSTEM.  465 

in  which  their  axones  develop.  This  is  probably  true  in  a  general  way,  but  the  development 
of  both  axones  and  sheaths  requires  further  study  before  any  law  can  be  exactly  formulated. 
Coarse  fibers  apparently  become  medullated  early,  the  sheaths  of  such  fibers  being  usually 
thicker. 

Although-  the  myelin  sheath  is  apparently  an  accessory  structure,  its  formation  is  of 
great  importance,  not  only  from  the  above  reason,  but  also  because  its  appearance  possibly 
indicates  the  assumption  by  the  neurone  of  its  capacity  for  the  precise  performance  of  its 
final  functions.  The  functional  significance  of  the  myelin  sheath  is  not,  however,  entirely 
clear.  Its  importance  is  enhanced  by  the  fact  that  its  integrity  depends  upon  the  integrity 
of  its  neurone  and  that  we  possess  precise  stains  for  demonstrating  both  its  normal  and 
abnormal  conditions. 

In  the  region  of  the  RHOMBENCEPHALON,  the  neural  crest  very  early  exhibits 
a  division  into  three  masses:  a  glossopharyngeo-vago-accessorius,  an  acustico- 
facialis,  and  a  trigeminus.  These  masses  soon  become  separated  from  each 
other  and  from  the  neural  tube,  the  glossopharyngeus  also  showing  a  partial 
separation  from  the  vago-accessorius  mass  (Fig.  396). 

The  vago-accessorius  group,  at  about  three  weeks,  is  a  mass  of  cells  much 
larger  at  the  cranial  end  and  continuous  by  a  narrow  band  of  irregular  cells 
with  the  spinal  neural  crest.  The  cranial  end  of  the  mass  shows  a  partial 
division  into  a  dorsal  and  ventral  part.  The  former  becomes  the  ganglion  of 
the  vagus  root,  the  latter  the  ganglion  of  the  trunk  (nodosum).  The  glosso- 
pharyngeus mass  likewise  shows  a  division  into  a  dorsal  group  of  cells,  the 
future  ganglion  of  the  root  and  a  ventral  group,  the  future  ganglion  of  the 
trunk  (petrosum).  The  two  ventral  groups  are  associated  with  epidermal 
thickenings  (placodes),  but  it  is  doubtful  whether  any  ganglion  cells  are 
derived  from  the  thickenings.  These  thickenings  probably  represent  the 
thickenings  associated  in  water-inhabiting  Vertebrates  with  the  development  of 
certain  sense  organs,  either  lateral  line  or  epibranchial  (see  p.  422).  At  this 
stage  there  are  no  afferent  fibers,  the  cells  not  yet  being  differentiated  into 
neurones.  Some  fibers  found  among  the  cells  are  efferent  (see  p.  458).  The 
glossopharyngeus  cells  lie  in  the  region  of  the  third  branchial  arch,  the  vagus 
in  the  region  of  the  fourth. 

During  the  fourth  and  fifth  weeks  the  processes  of  the  cells  begin  to  develop 
(Fig.  396),  and  the  cell  masses  finally  become  definite  ganglia  with  afferent  root 
fibers  passing  into  the  neural  tube  and  peripheral  processes  passing  outward, 
forming,  with  the  associated  efferent  fibers,  the  peripheral  branches  of  the  nerves 
in  question  (Fig.  397).  The  root  and  trunk  ganglia  of  the  vagus  and  glosso- 
pharyngeus, respectively,  are  also  now  connected  by  fiber  bundles  instead  of 
cellular  strands.  At  the  same  time  there  is  a  diminution  of  cells  in  the  caudal 
part  of  the  vago-accessorius  group,  this  part  finally  being  composed  almost  ex- 
clusively of  efferent  fibers  emerging  from  the  lateral  surface  of  the  medulla  and 
cord.  A  few  groups  of  cells  (accessory  root  ganglia)  persist,  however,  and  develop 


466 


TEXT-BOOK  OF  EMBRYOLOGY. 


into  ganglion  cells,  some  being  found  there  at  birth  (Streeter) .  This  would  in- 
dicate the  presence  of  a  small  and  hitherto  undetected  afferent  element  in  the 
spinal  accessory  nerve,  which  is  usually  regarded  as  purely  efferent.  The  spinal 
accessory  nerves  are  thus  identical  with  the  vagus  in  their  early  development 
and  consist  at  first  of  a  homologous  series  of  efferent  roots  and  ganglia.  This 


;x-x-x/  gang,  crest. 


Opthal  dlv. 
Supmax.div. 
N.matticatorius. 
Inf.  max.d/V. 


D.I. 


FIG.  396.— ^-From  a  reconstruction  of  the  peripheral  nerves  in  a  human  embryo  of 

4  weeks  (6.9  mm.).     Streeter. 

UI-XII,  III  to  XII  cranial  nerves;  C.I,  D.  /,,  L.I.,  5. /.,  ist  cervical,  ist  dorsal,  ist  lumbar,  and 
ist  sacral  nerves,  respectively;  i,  2,  3,  branchial  arches;  Ot.  v.,  auditory  vesicle;  IX-X-XI 
gang,  crest,  ganglionic  or  neural  crest  of  IX,  X  and  XI  cranial  nerves.  Fiber  masses  are 
represented  by  fine  lines,  ganglion  cell  masses  by  dots. 

indicates  that  the  spinal  accessory  might  be  regarded  as  a  specialized  part 
of  the  vagus  extending  caudally  into  the  cord  (Streeter)  (see  p.  434)  •  * 

From  this  point  on,  the  further  development  of  the  efferent  fibers  of  the  X 
and  XI  nerves  and  of  the  peripheral  processes  of  their  ganglia  is  the  further 

*  According  to  another  view  (Bremer) ,  the  spinal  accessory  nuclei  and  roots  are  to  be  regarded  as 
representing  a  specialization  of  lateral  nuclei  of  the  ventral  gray  column  of  the  cord  whose  root  fibers 
pass  in  the  dorsal  branches  of  the  spinal  nerves  to  the  dorsal  trunk  musculature  (p.  45  7  >  comp.  Fig. 
366).  According  to  this  view,  the  muscles  innervated  by  the  XI  would  be  somatic.  The  possible 
pomology  of  the  lateral  efferent  nuclei  and  roots  of  the  medulla  with  those  dorsal  root  fibers  of  the 
cord  which  arise  from  cells  in  the  ventral  gray  column  (p.  457  and  Fig.  392)  may  be  mentioned  in 
this  connection. 


THE  NERVOUS  SYSTEM. 


467 


growth  of  the  various  branches  of  these  nerves  and  their  connection  with  the 
differentiating  structures  innervated  by  them.  At  the  same  time  there  is  an  in- 
creasing concentration  of  the  cells,  thereby  forming  more  definite  ganglionic 


Gang,  acusticum 
Gang,  semilunare  n.V 


Vesicula  auditiva 

Gang.  radicisn.IX 


Gang,  petrosum 


Gang,  radicis  nJC 


N,  frontalis- 


N.  mandibularis 
Gang,  geniculatum 
N.  chorda  tympani 


/Gang.  Proriep 


x*N.  hypoglossus- 


Gang,  nodos.      r 
t> 

-  N.  desc.  cerv. 
Rami  hyoid. 
(Ansa  hypoglossi) 

_-.N.  musculocutan. 

---N.  axillaris 
~~N.  phrenicus 
--N.  medianus 

— N.  radialis 

--- N.  ulnaris 


-ITb. 


Tubus  digest. 


N.  femoralis 
N.  obturatorius 


R.  posterio 

R.  terminalis  lateralis 
R.  terminalis  anterior 
Mesonephros 
Nn.  ilioing.  et  hypogastr. 


FIG  307— Lateral  view  of  a  reconstruction  of  a  10  mm.  human  embryo,  showing  the  origin  and 
distribution  of  the  peripheral  nerves.  The  ganglionic  masses  are  represented  by  darker  and 
the  fiber  bundles  by  lighter  shading.  For  purposes  of  orientation  the  diaphragm  and  some 
of  the  viscera  are  shown.  The  arm  and  leg  are  represented  by  transparent  masses  into  the 
substance  of  which  the  nerve  branches  mav  be  followed.  Streeter. 


468 


TEXT-BOOK  OF  EMBRYOLOGY. 


masses.  The  changes  taking  place  are  similar  to  those  exhibited  in  the 
differentiation  of  the  spinal  nerves  (p.  460),  The  central  relations  of  the 
nerves  of  this  region  of  the  medulla  are  shown  in  Fig.  398.  (Comp.  Fig  369). 
The  glossopharyngeus  at  the  same  time  develops  its  branches,  most  of  the 
peripheral  fibers  running  in  the  third  arch  (lingual  branch).  Somewhat  later 
(i  2  to  14  mm.  embryo)  another  bundle  (tympanic  branch)  (Fig.  397)  passes  for- 
ward to  the  second  arch.  This  forms  the  typical  branchiomeric  arrangement 
in  which  there  is  a  forking  of  the  nerve  into  prebranchial  and  postbranchial 
branches,  the  latter  being  larger  and  containing  the  efferent  element  (see  p.  434 
and  Fig.  367). 


Roof  plate 

Alar  plate 
Fourth  ventricle 


Tractus  solitarius  -  - 
(in  marginal  layer) 


Efferent  nu.  N.  X. 
Nucleus  N.  XII.    - 

Ganglion  N.  X.     _  1 


Sulcus  limitans 


~    Inner  layer 


Mantle  layer 


of  basal 
plate 


~  Ventro-lat.  column 
(in  marginal  layer) 

-  Floor  plate 


FIG.  398. — Transverse  section  through  the  rhombic  brain  of  a  10.2  mm.  human  embryo  (during  the 
fifth  week).     X,  Vagus;  XII,  Hypoglossus.     His. 

While  the  ganglia  of  the  facialis  and  acusticus  are  derived  from  the  same 
mass  of  cells  (p.  465,  Fig.  396)  and  are  later  still  in  very  close  apposition,  it  must 
be  remembered  that  they  are  totally  different  in  character.  At  four  weeks  they 
are  differentiated  from  each  other  (Fig.  399).  The  relations  of  the  two  ganglia 
are  shown  in  Figs.  397  and  399.  It  is  probable  that  the  ganglion  of  the  facial 
(geniculate  ganglion)  shows  an  early  differentiation  into  dorsal  and  ventral 
parts  similar  to  the  ganglia  of  the  IX,  and  X,  and  also  has  associated  placodes. 
The  peripheral  branches  of  the  cells  of  the  geniculate  ganglion  develop  into  the 
great  superficial  petrosal  and  chorda  tympani.  Both  of  these  nerves  enter  into 
secondary  relations  with  the  V.  There  is  some  doubt  as  to  whether  the  chorda 
is  a  prebranchial  or  postbranchial  nerve  (Fig.  397;  also  compare  p.  432  and 
Figs.  367  and  368^ 


THE  NERVOUS  SYSTEM. 


469 


The  VII,  XX  and  X  are,  as  already  mentioned,  branchial  (splanchnic) 
nerves  and  the  central  processes  of  their  ganglia  ail  have  a  common  destina- 
tion; they  grow  into  the  lateral  surface  of  the  medulla  oblongata,  enter  the 
marginal  layer  of  the  alar  plate,  and  there  bend  caudally,  forming  a  comrion 
descending  bundle  of  fibers  in  the  marginal  layer,  the  tractm  solita.ius 
(Figs.  398  and  432;  see  also  pp.  432,  435). 

The  acoustic  ganglionic  mass  is  elongated  at  an  early  stage,  and  is  in  <  on- 
r.ection  with  an  ectodermal  thickening  (placode)  which  gives  rise  to  the  acoi  stic 


Roof  plate 


--  Alar  plate 

--   Sulcus  limitans 

-     Basal  plate 

Floor  plate 

FIG.  399. — Transverse  section  through  the  acoustic  region  of  the  rhombic  brain  of  a  10.2  mm.  human 
embryo.  VI,  Abducens  and  its  nucleus;  VII  G.g.,  geniculate  ganglion;  VIII G.  c.,  cochlear 
ganglion  of  acoustic  nerve;  VIIIG.v.,  vestibular  ganglion  of  VIII  nerve.  His. 

receptors  (p.  558).  From  the  upper  part  of  the  mass  a  bundle  of  peripheral 
processes  forms  a  branch  which  subsequently  innervates  the  ampullae  of  the 
superior  and  lateral  semicircular  canals  and  the  utricle,  while  from  the  lower 
part  a  branch  develops  to  the  ampulla  of  the  posterior  canal  and  to  the  saccule. 
The  nerve  and  ganglion  (ganglion  of  Scarpa]  is  thus  at  first  vestibular  and  at 
this  stage  the  cochlear  part  of  the  ear  vesicle  is  not  indicated  as  a  separate  out- 
growth. As  the  lower  border  of  the  vesicle  grows  out  into  the  cochlea,  the 
lower  border  of  the  ganglion  becomes  thickened  and  develops  into  the  cochlear 
ganglion  (the  ganglion  spirale).  It  will  be  recalled  that  the  vestibular  part  of 


470 


TEXT-BOOK  OF  EMBRYOLOGY. 


the  ear  is  the  older  part  phylogenetically,  the  cochlea  being  a  more  recent  special- 
ized diverticulum  of  the  older  structure.    (See  p.  552  and  Figs  464  and  465.) 

The  central  processes  of  the  acoustic  ganglionic  mass  first  develop  from  the 
upper  part,  forming  the  vestibular  nerve  root  which  enters  the  marginal  layer  of 
the  medulla.  A  portion  at  least  of  its  fibers  bends  caudally,  forming  a  de- 
scending tract.  The  central  processes  of  the  cells  of  the  cochlear  ganglion, 
forming  the  cochlear  nerve  root,  pass  dorsally,  cross  the  vestibular  ganglion  and 
enter  the  medulla  dorsal  and  lateral  to  the  vestibular  root  fibers  (Fig.  399). 

Roof  plate 


FIG.  400. — Transverse  section  through  the  rhombic  brain  in  the  region  of  the  trigeminus  (V)  nerve 
of  a  10.2  mm.  human  embryo.  a.W.,  Spinal  V;  G.G.,  Gasserian  ganglion;  V.m.,  efferent 
root  of  V  nerve.  His. 

The  trigeminus  is  the  most  anterior  of  the  ganglionic  masses  (Fig.  396). 
Embryological  evidence  has  been  brought  to  show  that  it  consists  of  two  or 
more  nerves  which  subsequently  fuse.  Placodes  have  also  been  described. 
It  is  possible  that  such  placodes  represent  those  belonging  to  the  most  anterior 
division  of  the  lateral  line  system  in  lower  forms,  and  probably  in  this  case 
would  not  properly  belong  to  the  V  (comp.  Fig.  367).  From  the  ganglionic 
mass  (Gasserian  or  semilunar  ganglion)  the  three  principal  branches — oph- 
thalmic, maxillary  and  mandibular — are  formed,  the  two  latter  passing  into  the 


THE  NERVOUS  SYSTEM. 


471 


Roof  plate 


FIG.  401.— Transverse  section  through  the  trigeminal  region  of  the  rhombic  brain  of  a  10.2  mm. 
human  embryo,  a.  W.,  Spinal  V;  V.  s.,  Gasserian  ganglion;  V.  m.,  part  of  efferent  root  of 
V  nerve.  His. 


FIG.  402.     Part  of  a  transverse  section  through  the  rhombic  brain  of  a  chick  embryo  toward  the 

fourth  day,  showing  the  trigeminal  roots.     Cajal. 
Aj  part  of  the  efferent  (masticator)  nucleus  of  the  V;  B,  efferent  root  of  the  V;  C,  bipolar  cells  of 

the  Gasserian  ganglion;  D,  beginning  of  descending  tract  (spinal  V)  formed  by  the  central 

Drocesses  of  C. 


472  TEXT-BOOK  OF  EMBRYOLOGY. 

maxillary  process  and  mandibular  arch,  respectively  (Fig  397).  The  central 
processes,  forming  the  afferent  root  (portio  major}  of  the  V,  enter  the  marginal 
layer  of  the  alar  plate  of  the  rhombencephalon  and  form  a  descending  bundle, 
the  spinal  V  (Figs.  400,  401,  402  and  432). 

The  trigeminus  exhibits  its  spinal-like  character  in  the  behavior  of  its 
visceral  portion  (comp.  p.  461).  Cells  of  the  ganglionic  mass  migrate  further 
peripherally  and  form  sympathetic  ganglia  (ciliary,  otic,  sphenopalatine  (?) 
submaxillary(?)  ).  As  in  the  cord,  the  question  has  arisen  whether  efferent 
roots  may  not  also  contribute  a  portion.  Cells  have  been  described  as  migrat- 
ing with  the  oculomotor  root  fibers  and  forming  part  of  the  ciliary  ganglion 
(Carpenter). 

Besides  those  already  described  (cerebrospinal,  sympathetic),  the  only 
other  peripheral  neurones  of  the  nervous  system  are  connected  with  the  PROS- 
ENCEPHALON  and  are  a  part  of  the  eye  and  nose.  The  visual  receptors  (rods 
and  cones)  and  peripheral  afferent  neurones  (bipolar  cells)  appear  to  be  repre- 
sented by  portions  of  the  retina  and  are  described  elsewhere  (Chap.  XVIII). 

In  the  nose  there  is  first  a  placode  (p.  422)  from  which  neuroblasts  develop. 
Some  of  these  migrate  toward  the  neural  tube  and  probably  differentiate  into 
lemmocytes,  a  few  becoming  ganglion  cells.*  The  majority  of  the  neuroblasts 
remain  in  the  olfactory  epithelium,  sending  their  axones  (fila  olfactoria)  into 
the  olfactory  bulb,  the  peripheral  afferent  olfactory  neurones  thus  apparently 
displaying  the  primitive  ectodermal  location  of  afferent  peripheral  neurones 
(p.  418  and  Fig.  359).  (Comp.  p.  551.) 

Development  of  the  Lower  (Intersegmental)  Intermediate  Neurones. 

It  has  already  been  seen  hoW,  by  migration  and  by  differentiation  of  the  cells 
during  migration,  the  nucleated  layer  comprising  the  greater  part  of  the  thick- 
ness of  the  wall  of  the  neural  tube  is  differentiated  into  two  layers — an  inner 
nucleated  layer  retaining  its  earlier  characteristics,  and  an  outer  nucleated 
(mantle)  layer,  composed  largely  of  the  differentiating  neuroblasts  and 
characterized  in  ordinary  staining  by  more  widely  separated  nuclei.  It  has 
also  been  seen  that  this  differentiation  takes  place  earlier  and  more  rapidly  at 
first  in  the  ventral  part  of  the  lateral  walls  (basal  plate) ,  and  that  the  first  cells  to 
migrate  and  differentiate  are  those  whose  axones  grow  out  through  the  neural 
wall  and  pass  out  as  the  ventral  root  fibers. 

Not  much  lat^r  than  the  above  differentiation  of  the  efferent  peripheral 
neurones,  axones  of  other  neuroblasts  also  grow  toward  the  periphery  of  the 
tube  but  do  not  pass  beyond  its  wall.  Such  neuroblasts  become  intermediate 

*  The  latter  are  probably  transient,  but  possibly  in  some  forms  persist  as  the  ganglion  cells  of  the 
nervus  terminalis  of  Pinkus. 


THE  NERVOUS  SYSTEM. 


473 


neurones  (p.  419).  The  migrating  bodies  of  these  neuroblasts  are  checked  at 
the  inner  boundary  of  the  marginal  layer,  but  their  growing  axones  enter  the 
marginal  layer  and  there,  apparently  on  account  of  their  inability  to  penetrate 
the  external  limiting  membrane,  turn  cranially  or  caudally,  or  bifurcate,  and 
form  longitudinal  ascending  and  descending  fibers.  These  longitudinal  fibers 
constitute  a  part  of  the  future  white  columns  (see  p.  477),  and  their  cells  are 
therefore  often  called  column  cells.  Many  axones  from  such  cells  in  all  parts 
of  the  lateral  walls  (heteromeric  or  commissural  column  cells)  pursue  a  ven- 
tral course  through  the  mantle  layer,  ar^ning  around  near  the  periphery  and 


FIG.  403. — Part  of  a  section  through  the  lumbar  spinal  cord  of  a  76-hour  chick,  embryo.     Cajal. 
A,  Ventral  root;  B,  spinal  ganglion;  C,  bifurcation  of  dorsal  root  fibers  forming  beginning  of  dorsal 
funiculus;  a,  b,  c,  neuroblasts  showing  various    stages  of  differentiation    into   intermediate 
neurones,  some,  at  least,  (c)  becoming  heteromeric  column  cells;  d,  efferent  neurone. 


crossing  the  floor  plate,  ventral  to  the  lumen,  to  become  longitudinal  ascending 
and  descending  fibers  in  the  marginal  zone  of  the  opposite  side.  These  early 
decussating  axones  form,  in  the  cord,  the  beginning  of  the  anterior  commissure 
(Fig.  403).  Other  neuroblasts,  the  axones  of  which  do  not  cross  the  median 
line,  become  tautomeric  column  cells. 

It  is  about  this  time  that  the  afferent  root  fibers  enter  the  marginal  layer  of 
the  dorsal  part  (alar  plate)  of  the  lateral  wall  and  form  in  the  marginal  layer 
various  bundles  of  longitudinal  fibers  above  described  (dorsal  funiculus, 
•actus  solitarius,  descending  vestibular,  and  spinal  V)  (Figs  403, 404,  398,  399, 


474  TEXT-BOOK  OF  EMBRYOLOGY. 

401,  402  and  432).  In  the  cord  the  ascending  arms  grow  to  a  greater  length 
than  the  descending.  In  the  rhombic  brain  the  reverse  is  usually  the  case. 

The  longitudinal  fibers  of  the  afferent  roots  and  of  the  intermediate  neurones 
thus  form  an  external  layer  occupying  the  marginal  layer  of  the  neural  tube. 
This  is  the  beginning  of  the  differentiation  into  white  and  gray  matter,  i.e., 
into  that  part  of  the  neural  tube  containing  only  the  axones  of  the  neurones 
and  into  that  part  containing  the  cell  bodies  and  the  beginnings  and  termina- 
tions of  the  axones.  The  terminations  of  axones  are  formed  by  a  turning  of 
the  longitudinal  fibers  into  the  mantle  layer  or  gray  matter  to  form  there 
terminal  arborizations.  Later,  the  longitudinal  fibers  develop  branches  (col- 
laterals) which  also  pass  into  the  gray  matter.  The  differentiation  of  the 
white  matter  is  completed  several  months  later  by  the  myelination  of  the 
nerve  fibers. 

The  longitudinal  axones  of  intermediate  neurones  which  are  formed  at  this 
period  in  the  cord  and  epichordal  brain  are  located  ventrally  near  the  median 
line.  These  medial  tracts  occupy  the  position  of  the  future  medial  longitu- 
dinal fasciculi,  the  reticulo-spinal  and  ventral  ground  bundles,  and  may  be 
regarded  on  both  comparative  anatomical  and  embryological  grounds  as  a 
primitive  system  of  long  and  short  ascending  and  descending  tracts  mediating 
between  cerebrospinal  afferent  and  efferent  peripheral  neurones,  and  not 
having  at  this  period  connections  with  the  higher  centers.  Other  more  lateral 
tracts  of  this  character  are  formed  somewhat  later,  the  whole  forming  the 
beginning  of  the  reticular  formation  +  ventro-lateral  ground  bundle  system 
(compare  Figs.  404,  411, 414  and  416). 

While  merging  more  or  less  imperceptibly  into  the  following  stages,  it  may 
in  a  general  way  be  said  that  at  this  stage  of  development  there  is  differentiated 
what  might  be  termed  the  primary  and  probably  the  oldest  coordinating  mech- 
anism of  the  nervous  system,  most  clearly  segmental  in  character  and  having 
general  features  common  not  only  to  all  Vertebrates,  but  to  many  Invertebrates. 
It  is  characterized  by  afferent  and  efferent  peripheral  neurones  arranged  seg- 
mentally  and  connected  longitudinally  in  the  central  nervous  system  by  crossed 
and  uncrossed  intersegmental  intermediate  neurones.  (Compare  pp.  435  and 
436) .  At  the  anterior  end  of  this  part  of  the  nervous  system  (epichordal  segmen- 
tal brain)  there  are  also  exhibited  differentiations  due  to  fundamental  vertebrate 
differentiations  in  the  peripheral  receptive  and  effective  apparatus.  Some  of 
these  are:  (i)  The  differentiation  of  the  splanchnic  (visceral)  receptive  and 
motor  apparatus,  giving  rise  in  the  nervous  system  to  (a)  a  separate  system  of 
afferent  root  fibers  (tractus  solitarius)  including  the  more  specialized  gustatory 
apparatus;  (b)  a  distinct  series  of  lateral  efferent  nuclei.  (2)  The  concentra- 
tion of  the  non-specialized  somat'c  afferent  innervation  into  one  nerve  (tri- 


THE  NERVOUS  SYSTEM.  475 

geminus  and  its  central  continuation,  the  spinal  V).  (3)  The  specialized 
somatic  sense  organ,  the  ear,  with  its  older  vestibular  and  newer  cochlear 
divisions  with  central  continuations  of  its  nerves,  including  a  vestibular 
descending  tract. 

These  differentiations  of  the  peripheral  afferent  apparatus  lead  to  the  later 
formation  of  special  terminal  nuclei  for  their  central  continuations  and  second- 
ary tracts  from  these  nuclei  to  suprasegmental  structures  (p.  436,  Fig.  371). 

The  peripheral  and  intermediate  neurones  of  the  more  highly  modified 
cranial  end  of  the  tube,  or  FORE-BRAIN,  appear  to  lag  behind  in  development, 
but  in  its  basal  part  the  neuroblasts  are  beginning  to  be  differentiated  (fifth 
week) .  In  the  development  of  the  eye,  the  brain  wall  is  evaginated,  carrying 
with  it  the  future  retina  comprising,  apparently,  the  sensory  epithelial  cells  or 
receptors  (rods  and  cones),  the  afferent  peripheral  neurones  (bipolar  cells  of 
retina)  and  the  receptive  or  primary  intermediate  neurones  (ganglion  cells  of 
retina  and  optic  nerve).  The  histogenesis  of  these  elements  is  dealt  with 
elsewhere,  but  it  may  be  pointed  out  here  that  the  axones  of  the  ganglion 
cells  of  the  retina  grow  toward  the  inner  side  of  the  optic  cup  (away  from 
the  original  luminal  surface),  pass  thence  in  the  marginal  layer  of  the  optic 
stalk,  undergo  a  partial  ventral  decussation  (optic  chiasma)  in  the  floor  plate, 
and  terminate  in  certain  thalamic  nuclei  (lateral  geniculate  bodies)  and  in  the 
roof  of  the  mid-brain.  The  so-called  optic  nerve  is  thus  obviously  a  central, 
secondary  tract.  The  development  of  this  tract  does  not  apparently  take  place 
until  a  later  period  than  the  differentiation  of  the  earlier  secondary  tracts  of  the 
cord  and  rhombic  brain  (after  the  sixth  week) . 

In  the  case  of  the  olfactory  organ,  it  has  already  been  seen  that  the  peripheral 
neurones  develop  at  first  apart  from  the  neural  tube  and  send  their  axones 
into  the  olfactory  bulb.  The  latter  is  an  evagination  of  the  neural  tube 
which  receives  the  olfactory  fibers,  thereby  constituting  a  complicated  terminal 
nucleus  for  the  latter.  The  axones  of  bulb  cells  (the  mitral  cells)  which  pass 
along  the  stalk  of  the  bulb  are  thus  the  secondary  tract  of  this  system.  Many 
of  them  decussate  in  the  anterior  commissure.  Secondary  (and  tertiary) 
olfactory  tracts  find  their  way  to  caudal  parts  of  the  rhinencephalon  and  to 
hypothalamus,  thalamus  and  epithalamus,  forming,  with  other  tracts,  a  highly 
modified  prechordal  intersegmental  mechanism  (p.  537).  Other  olfactory  tracts 
proceed  to  the  suprasegmental  archipallium  which  develops  efferent  bundles 
to  the  segmental  brain. 

The  embryological  development  of  the  peripheral  apparatus,  especially 
of  its  receptive  portions,  as  shown  by  the  various  separate  ganglionic  rudiments 
(Fig.  396)  and  placodes,  exhibits  a  segmental  character  which,  though  not 
in  all  respects  primitive,  is  of  practical  value.  These  segments  are  (Adolf 
Meyer) :  (i)  The  olfactory  apparatus,  nose,  without  efferent  elements.  (2) 


476  TEXT-BOOK  OF  EMBRYOLOGY. 

The  visual  apparatus,  eye,  with  the  eye-moving  III  and  IV  mid-brain  nerves 
as  its  efferent  portion.  (3)  The  general  sensory  apparatus  of  the  surfaces  of 
the  head  and  mouth,  the  afferent  trigeminus,  with  the  jaw-moving  efferent 
trigeminus.  (4)  The  auditory  (and  vestibular)  apparatus,  the  ear  (VIII 
nerve),  with  the  VI  (turning  the  eye  to  the  source  of  sound)  and  VII  (ear  and 
face  muscles)  efferent  nerves.  In  the  latter,  the  original  ear-moving  appa- 
ratus has  been  replaced  largely,  in  man,  by  the  muscles  of  expression.  (5) 
The  visceral  segment  (IX,  X,  and  XII  nerves),  not  indicated  externally  in 
forms  without  gills.  The  afferent  portion  is  concerned  with  taste  and  visceral 
stimuli,  the  efferent  with  tasting,  swallowing,  sound-production  and  other 
visceral  functions.  Overlapping  with  other  segments  is  due  to  its  visceral  as 
opposed  their  somatic  character.  The  apparent  dislocation  shown  by  the 
abducens  is  due  to  its  common  use  by  more  than  one  segment. 

Caudal  to  this  is  the  mechanism  for  head  movement  (N.  XI) ,  its  afferent 
portion  being  the  upper  spinal  nerves.  Following  this,  there  is  the  segmental 
series  of  spinal  nerves  which  in  places  shows  a  tendency  to  fuse  (plexuses)  into 
larger  segments  (phrenic  segment,  limb  segments) .  All  such  modifications  are 
expressions  of  more  recent  functional  adjustments  modifying  preexisting  ones. 

These  segments  may  be  regarded  as  a  series  of  reflex  arcs,  each  one  of 
which  may  have  a  certain  amount  of  physiological  independence  but  which 
are  associated  by  intersegmental  neurones.  The  latter  class  of  intermediate 
neurones  probably  effects  certain  groupings  of  various  efferent  neurones,  fur- 
nishing mechanisms  which  secure  harmonious  responses  of  groups  of  effectors 
involved  in  certain  definite  reactions  (e.g.,  limb-movements,  associated  eye 
movements).  These  effector-associating  mechanisms  may  be  acted  on  di- 
rectly (reflex)  by  afferent  neurones  or  by  the  efferent  arms  of  suprasegmental 
mechanisms. 

Superadded  to  this  segmental  apparatus  are  the  suprasegmental  mechan- 
isms which  develop  later,  the  pallium  being  the  last  to  be  completed.  These 
receive  bundles  from  the  segmental  nervous  system  and  send  descending 
bundles  to  the  intersegmental  neurones  (pp.427,  435  and  436  and  Fig.  371). 

FURTHER  DIFFERENTIATION  OF  THE  NEURAL  TUBE. 
The  Spinal  Cord. 

From  this  time  on,  differences  of  structure  between  cord  and  epichordal 
segmental  brain  become  more  marked  and  make  it  more  convenient  to  treat 
their  later  development  separately.  The  ventral  half  of  the  cord  for  a  con- 
siderable period  maintains  its  lead  in  development.  At  four  weeks  (Fig.  404) 
this  lead  is  not  so  pronounced  as  in  the  immediately  following  period.  At 
this  stage  it  will  be  noticed  that  the  lumen  is  narrower  in  the  ventral  part, 


THE  NERVOUS  SYSTEM. 


477 


as  if  due  to  the  greater  thickening  of  the  ventral  walls  (basal  plates).  The 
increase  of  the  mantle  layer  (gray)  of  the  basal  plate  marks  the  beginning  of 
the  ventral  (anterior)  gray  column  or  horn.  The  increase  in  the  basal  plate 
may  be  partly  due  to  neuroblasts  migrating  from  the  alar  plate.  These 
would  be  intermediate  neurones.  The  development  of  the  mantle  layer  at 
the  expense  of  the  inner  layer,  due  to  differentiation  and  migration  of  the  cells 
of  the  latter,  is  well  shown,  but  is  more  marked  in  the  following  stages. 

As  already  mentioned,  the  axones  of  the  heteromeric  cells,  many  of  which 
lie  in  the  dorsal  half  of  the  lateral  walls,  after  decussating  (anterior  commit- 


Beginning  of 
dorsa.  >:uniculus  \/ 

Dorsal  root5/f 
Mantle  layer'' 


Meningeal 
'   membrane 


Ventral  root 
r.eurcblasts 
of  mantle  layer) 


FIG.  404. — Half  of  a  transverse  section  of  the  spinal  cord  of  a  4  weeks,  (6.9  mm.)  human  embryo. 
Dp,  Roof  plate;  Bp,  floor  plate.     His. 

sure),  form  longitudinal  fibers  in  the  marginal  layer  along  the  ventral  surface 
of  the  opposite  side,  mostly  mesial  to  the  emerging  ventral  roots  (Fig.  4°4)« 
These  longitudinal  fibers  are  the  beginning  of  the  ventral  (anterior)  white  columns 
or  funiculi  of  the  cord.  The  sides  of  the  tube  between  the  dorsal  and  ventral 
roots  contain  at  first  only  a  few  longitudinal  fibers — the  beginning  of  the  ventro- 
lateral  juniculi.  Their  number  soon  rapidly  increases,  the  fibers  apparently 
coming  from  ventrally  located  tautomeric  cells.  The  dorsal  root  fibers,  as 
stated  before  (p.  460),  form  small  round  bundles  in  the  marginal  layer  of  the 
dorsal  halves  (Fig.  404).  This  is  the  beginning  of  the  dorsal  (posterior)  white 
columns  or  funiculi,. 


478 


TEXT-BOOK  OF  EMBRYOLOGY. 


At  four  weeks  there  are  blood  vessels  in  the  mesodermal  tissue  surrounding 
the  neural  tube.  Branches  of  these  soon  penetrate  the  tube  itself. 

From  its  first  appearance  in  the  cord  as  an  oval  bundle,  during  the  fourth 
week,  the  dorsal  funiculus  steadily  increases  in  size,  forming  a  "root  zone"  in 
the  marginal  layer  of  the  dorsal  half,  but  not  reaching  the  roof  plate  (Fig.  405). 
This  increase  in  size  is  probably  produced  in  part  by  the  addition  on  its 
inner  side  of  overlapping  ascending  arms  of  dorsal  root  fibers  from  lower 


Partly  differentiated  mantle  layer 


Mantle  layer 

Dorsal  funiculus 
(post,  white  column)    -  -,,. 


Dorsal  root  ^. 

Marginal  furrow-y^J 
Dorsal  spinal  artery 

Arcuate  fibers  — fc- 


Cylinder  furrow--/ 


•;^?^:£pi^      / 
?}i1i!mS^ 


Lateral  gray 
column  (lat.  horn) 


^. 


'Ssp.-SVoKlW^ 


Bp 


•.':'--'A-£(/20 

.<   'v'.  o3.  $°  *>"•»?>.  c 

.   "  ©   r»CP.iOQ    o  ,t>'v .'?e  "  0  ^  -c  c'  C 
.^^rv>0^^>,.^ 

f'lljii1 

Meningeal— i     '''  ^bSc?oM  o;^'--  O^y-^r  '»*Mt\^1  \ 
membrane     1  ^--^^Vo^  °^  '       ^°  «  ^^V?3  U 
"• «;  %*o^«  ^  >i  e  =%>  'd<fo°'^:  2%  -We,  cjl-rA' 

l^S^iti 

\v''-'   -'-••'4-  .  <?•.   C\. •-.-,  Oo°       '^  "   -'. ' 

\  ',  ••;•••••'  -';-;y  •     °0°o0?:"-  >• 
Ventral  root ^NJ/^C'  /.•'.•'  :f/  •'.'...' 


FIG.  405. — Half  of  a  transverse  section  of  the  spinal  cord  of  a  4^  weeks  (lo.gmm.)  human  embryo.  His. 
A.s.,  Artery  in  ventral  longitudinal  sulcus;  A.sp.a.,  ventral  (anterior)  spinal  artery;  Bp,  floor  plate; 
Dp,  roof  plate;  7. 1.,  inner  layer.     The  faint  inner  outline  is  the  outline  of  the  cord  proper. 


cord  segments.  The  mantle  layer  of  this  part  contains  an  increasing  number 
of  cells  forming  curved  or  arcuate  fibers.  (Fig.  405.)  The  increase  in  the 
mantle  cells  of  the  dorsal  part  marks  the  beginning  of  the  dorsal  (posterior) 
gray  column  or  horn  (terminal  nucleus  of  the  dorsal  root  fibers) .  Later,  other 
cells  become  differentiated  from  the  inner  layer  which  do  not  apparently  form 
arcuate  fibers  (Fig  405)  and  which  subsequently  become  part  of  the  posterior 
horn.  It  is  possible  that  the  axones  of  some  of  these  cells  form  the  compara- 


THE  NERVOUS  SYSTEM. 


479 


lively  small  ground  bundles  of  the  dorsal  funiculus.  During  this  period 
of  development  of  the  dorsal  portions  of  the  lateral  walls  the  latter  have  ap- 
proached each  other,  reducing  the  dorsal  part  of  the  lumen  to  a  slit.  The 
roof  plate  has  undergone  a  slight  infolding  (Fig.  406).  Ventral  to  the  dorsal 
roots  there  is  a  groove  running  along  each  side  of  the  cord  (marginal  furrow  of 
His).  At  four  and  one-half  weeks  the  number  of  fibers  of  the  ventro-lateral 
funiculus  has  greatly  increased  and  another  groove  has  appeared  parallel  and 
ventral  to  the  marginal  furrow  and  forming  the  dorsal  boundary  of  the  ventro- 


Intermediate  plate 
Central  canal  • 


Floor  plate  -  -^ 


Vent.  long,  sulcus 


Dors,  funiculus 

Dors,  gray  column  (post,  horn) 

Dors,  root 
Marginal  furrow 
Cylinder  furrow 


-  Lat.  gray  column  (lat.  horn) 
^i^/-/-  •  Ventro-lat.  funiculus 

Vent,  gray  column  (ant.  horn) 
^ Vent,  root 


Vent,  funiculus 
(ant.  white  column) 


Vent.  sp.  artery 

FIG.  406. — Half  of  a  transverse  section  of  the  spinal  cord  of  a  human  embryo 
of  18.5  mm.  (7^  weeks).     His. 

lateral  funiculus  (cylinder  furrow  of  His)  (Figs.  405  and  406).  The  portion 
of  the  lateral  wall  lying  between  these  two  grooves  or  furrows  forms  an 
intermediate  plate  which  contains  few  fibers  in  its  marginal  layer  at  this 
period,  and  is  thus  backward  in  development.  Grooves  appear  on  the  luminal 
wall,  apparently  corresponding  approximately  to  the  outer  grooves. 

The  further  growth  of  the  dorsal  funiculi  and  the  concomitant  growth 
of  the  associated  gray  matter,  i.e.,  of  the  cells  of  the  adjoining  mantle  layer, 
proceed  until  we  have  the  conditions  shown  in  Figs.  406  and  407.  At  the 
same  time  there  is  a  further  approximation  of  the  dorsal  portions  of  the  lateral 


480 


TEXT-BOOK  OF  EMBRYOLOGY. 


walls  so  that  the  widest  part  of  the  lumen  is  further  ventral.  At  about  eight 
weeks  the  portion  of  the  wall  near  the  median  line,  which  has  formed  a  ridge 
by  the  apposition  of  the  two  inner  layers  and  the  roof  plate  (Fig.  406  Y),  and  is 
uncovered  as  yet  with  fibers,  differentiates  a  marginal  layer  (eight  and  one-half 
weeks,  Fig.  407)  into  which  fibers  grow  forming,  on  each  side,  in  the  upper 
part  of  the  cord,  the  column  of  Goll  or  fasciculus  gracilis  (Fig.  408).  Many 
of  these  fibers,  at  least,  are  the  ascending  arms  of  caudal  dorsal  root  fibers, 
which  are  thus  added  mesially  to  the  continuations  of  upper  cord  roots.  It  will 


Rudiment  of  funiculus  gracilis 


Dorsal  funiculus  (cuneatus) 


Intermediate  plate 


Central  canal 


Floor  plate  -  - 


Vent.  long,  sulcus 


Dors,  gray  column 

Dors,  root 
Marginal  furrow 
Cylinder  furrow 

Lat.  gray  column 


-  -  Ventro-lat.  funiculus 


^^.y//. Vent,  gray  column 


Vent,  root 
Vent,  funiculus 


Vent.  sp.  art. 

FIG.  407. — Half  of  a  transverse  section  of  the  spinal  cord  of  a  human  embryo  of 
24  mm.  (8 1  weeks).     His. 

be  noted  that  there  is  now  a  massive  dorsal  gray  column  and  that  the  original 
oval  bundle  has  extended  around  on  the  mesial  side  of  this  gray  column. 

While  these  changes  are  taking  place,  the  dorsal  portions  of  the  lateral  walls 
have  fused,  probably  beginning  at  the  most  dorsal  part,  thus  forming  the  dorsal 
septum.  This  may  be  accompanied  by  a  certain  amount  of  rolling  in  from  the 
dorsal  part  indicated  by  the  direction  of  the  ependyma  cells  (Fig.  408).  The 
growth  of  the  ventral  funiculi  and  gray  columns  results  in  the  appearance 
and  subsequent  increasing  depth  of  the.  ventral  longitudinal  fissure.  The  cord 
now  resembles  the  adult  cord  in  many  features,  having  well-marked  white*  and 


*The  term  "white"  column  is  used  for  convenience, 
their  fibers  become  myelinated  during  the  sixth  month. 


The  funiculi  do  not  become  "white"  until 


THE  NERVOUS  SYSTEM. 


481 


gray  columns,  but  contains  a  disproportionately  small  amount  of  fibers.  A 
further  and  later  change  consists  in  a  rolling  inward,  as  it  were,  of  the  dorsal 
gray  column  so  that  it  becomes  separated  from  the  ventral  gray  column,  and 
that  portion  of  it  formerly  facing  dorsally  comes  to  face  more  mesially,  the  roots 
entering  more  dorsally.  This  change  may  be  due  partly  to  the  development 
of  the  intermediate  plate  which  has  in  the  meantime  taken  place.  In  this 
plate  axones  of  tautomeric  cells  have  begun  to  form  the  limiting  layer  of  the 
lateral  funiculus.  From  the  cells  of  the  intermediate  plate  are  formed  the 
neck  of  the  dorsal  gray  column,  also  the  cells  of  Clarke's  column  and  the 

Funiculus  gracilis 


Dors,  funiculus  (cuneatus) 
Dors,  gray  column 
Dors,  root 

Marginal  furrow 
Intermed.  plate 
Cylinder  furrow 


2f'V  •  -  Lat.  gray  column 

il/ /-  -  -  Ventro-lat.  funiculus 
Vent,  gray  column 

Vent,  root 

Vent,  funiculus 
Vent.  sp.  artery 
FIG.  408. — Half  of  a  transverse  section  of  the  spinal  cord  of  a  human  foetus  of  about  3  months.    His* 

processus  reticularis.  In  the  course  of  these  developments,  the  ventro-lateral 
ground  bundles,  formed  primarily  by  heteromeric  and  tautomeric  cord  cells, 
receives  various  accessions.  These  are  first  the  long  descending  inter- 
segmental  tracts  from  epichordal  brain  nuclei  in  the  formatio  reticularis 
which  as  they  proceed  down  the  cord  naturally  overlap  externally  the  ground 
bundles  already  formed  there.  They  include  the  medial  longitudinal  fasciculi; 
tracts  from  Deiters1  nuclei  and  the  rubro-spinal  tracts  which  occupy  the  ventro- 
lateral  funiculi  external  to  the  ground  bundles.  In  the  lateral  funiculi  there 
are  also  added  the  ascending  tracts  from  cord  nuclei  to  suprasegmental  structures. 


Vent.  long,  sulcus  --  — 


482  TEXT-BOOK  OF  EMBRYOLOGY. 

These  are  the  dorsal  spino-cerebellar  tracts  from  Clarke's  columns,  ventral  spino- 
cerebellar  tracts,  and  tracts  to  mid-brain  roof  and  thalamus  (spino-tectal  and 
thalamic).  Finally  (fifth  month)  the  descending  tracts  from  the  pallium  are 
added,  the  direct  and  crossed  cor tico- spinal  (pallio- spinal  or  pyramidal]  tracts, 
the  latter  being  thrust,  as  it  were,  into  the  lateral  funiculus. 

The  development  of  the  cord,  then,  is  produced  by  (i)  the  proliferation  of 
the  epithelial  cells  and  the  formation  of  the  nuclear  and  marginal  layers;  (2) 
the  multiplication,  differentiation  and  growth  of  the  neuroblasts  (mantle  layer) ; 
(3)  the  development  of  the  ventral  roots;  (4)  formation  of  the  funiculi  (white 
columns  when  myelinated)  by  the  growth  into  the  marginal  layer  of  (a)  dorsal 
root  fibers  of  the  cord,  the  ascending  arms  of  which  overlap  those  root  fibres 
entering  higher  cord  segments,  (b)  cord  neuroblasts  forming  intersegmental 
(ground  bundle)  tracts  next  to  the  gray  matter,  (c)  descending  intersegmental 
tracts  from  the  segmental  brain,  representing  continuations  principally  of  cere- 
bellar  efferent  tracts,  (d)  afferent  suprasegmental  tracts  from  cord  nuclei, 
(e)  descending  pallio-spinal  tracts.  In  addition  to  this,  there  are  general 
factors  of  growth,  such  as  increasing  vascularization,  increasing  amount  of 
neurone  cytoplasm  (especially  dendrites) ,  increased  size  of  axones  and,  finally, 
the  acquisition  by  the  latter  of  myelin  sheaths. 

The  vertebral  column  grows  faster  in  length  than  the  inclosed  spinal  cord. 
The  result  of  this  is  that  the  caudal  spinal  nerves  making  their  exit  through  the 
intervertebral  foramina  are,  so  to  speak,  dragged  caudalward  and  instead  of 
proceeding  outward  at  right  angle  to  the  cord,  pass  caudally  to  reach  their 
foramina.  The  leash  of  nerve  roots  thus  formed,  lying  within  the  caudal  part 
of  the  vertebral  column,  constitutes  the  cauda  equina.  The  coverings  of  the 
cord  retain  their  original  connections  at  the  caudal  end  of  the  vertebral  canal 
and  form  a  prolongation  of  the  cord  membranes  enclosing  the  thin,  terminal 
part  of  the  cord,  the  filum  terminate. 

The  Epichordal  Segmental  Brain. 

In  the  fifth  week,  the  walls  of  the  rhombencephalon  are  comparatively  thin. 
In  the  caudal  region  of  the  medulla  oblongata  (p.  447) ,  the  dorsal  part  of  each 
lateral  wall  is  upright  and  is  bent  at  a  considerable  angle  with  the  ventral 
part  (basal  plate),  the  groove  on  the  inner  surface  between  the  two  being  the 
sulcus  limitans.  The  roof  of  this  region  is  formed  by  the  thin  expanded  roof 
plate  (Figs.  398-401). 

Anterior  to  this,  the  roof  plate  is  not  expanded,  the  alar  plates  almost 
meeting  in  the  mid-dorsal  line.  This  thicker  part  of  the  roof  is  the  rudiment 
of  the  cerebellum.  Its  caudal  edges  are  attached  to  the  expanded  roof  plate  (see 
P-  495) 


THE  NERVOUS  SYSTEM.  483 

In  front  of  the  cerebellum  the  tube  is  narrower  and  is  compressed  laterally. 
This  part  is  the  isthmus  (Fig.  409) .  Anterior  to  this,  the  roof  plate  and  alar 
plates  expand  into  the  mid-brain  roof,  the  basal  and  floor  plates  forming  the 
basal  part  of  the  mid-brain. 

Certain  gross  changes  which  from  now  on  take  place  in  the  medulla  may 
conveniently  be  noted  here.  At  about  this  time  (fifth  week)  the  outer  borders 
of  the  alar  plate  become  folded  outward  and  then  downward,  being  thus  turned 
back  on  the  plate  itself  (Figs.  414  and  378).  This  fold  is  called  the  primary 
rhombic  lip,  and  is  most  marked  along  the  caudal  border  of '  the  cerebellum. 
The  folds  of  the  lip  then  fuse,  forming  a  rounded  eminence  composing  the  border 
of  the  alar  plate  to  which  the  roof  plate  is  attached  laterally.  Subsequently, 
the  attachment  to  the  roof  plate  is  shifted  dorsally  in  the  medulla,  caudally  in 


D.  IV 


M.I. 


— Nu.  IV. 


FIG.  409.— Transverse  section  through  the  isthmus  of  a  10.2  mm.  human  embryo.     D.IV,  Decussa- 
tion  of  trochlear  nerve;  M.  L,  marginal  layer;  Nu.  IV,  nucleus  trochlear  nerve,     ^s. 

the  cerebellum.  The  portion  of  this  lip  which  thins  off  into  the  roof  plate  is  the 
tania  of  the  medulla  and  the  posterior  velum  and  taenia  of  the  cerebellum.  The 
thin  roof  plate  itself  becomes  tbe  epithelial  part  of  the  tela  chorioidea  of  the 
fourth  ventricle.  At  the  caudal  apex  of  the  fourth  ventricle  a  fusion  of  the 
lips  of  the  opposite  sides  forms  the  obex. 

A  further  complication  is  due  to  the  increasing  pontine  flexure  by  which  the 
dorsal  walls  of  the  tube  are  brought  close  together  (Fig.  410).  The  transverse 
fold  of  the  tela  thus  produced  is  the  chorioid  fold.  At  about  the  same  time 
lateral  pocketings  outward  of  the  dorsal  walls  occur  just  caudal  to  the  cere- 
bellum which  contain  portions  of  the  chorioid  fold.  These  are  the  lateral 
recesses.  By  further  growth  and  vascularization,  the  mesodermal  part  of  the 
chorioid  fold  forms  the  chorioid  plexus  of  the  fourth  ventricle  (metaplexus). 
Finally,  in  the  human  brain  an  aperture  appears  in  the  caudal  portion  of 
the  roof  of  the  ventricle— the  foramen  of  Magendie  (metapore) ;  and,  according 
to  many  authorities,  one  also  occurs  in  the  roof  of  each  of  the  lateral  recesses 


484 


TEXT-BOOK  OF  p;M BRYOLOGY. 


— the  foramina  of  Luschka.  The  roof  of  the  fourth  ventricle,  where  present, 
is  thus  composed  of  an  inner  ependymal  epithelium — the  expanded  roof  plate 
of  the  neural  tube — and  an  outer  mesodermal  covering  containing  blood  vessels. 
Other  gross  changes  chiefly  involve  the  basal  plate.  At  the  beginning  of  the 
fifth  week  this  does  not  much  exceed  the  alar  plate  in  thickness  and  is  separated 
from  the  opposite  basal  plate  by  an  inner  median  sulcus  (Fig.  414).  The  basal 
plate  now  increases  in  thickness  and  thereby  both  deepens  the  sulcus  and  con- 
tributes to  a  flattening  out  of  the  lateral  walls,  so  that  all  portions  by  the  sixth 
week  lie  approximately  in  the  same  horizontal  plane  (Fig.  416).  Later,  the 
floor  plate  increases  in  thickness  more  rapidly  and  the  sulcus  becomes  shallower 
(eight  weeks)  (Fig.  417).  The  band  of  vertical  ependyma  fibers  passing  through 


Mesencephaion 


Epiphysis 
Diencephalon 


Isthmus 

- .  Cerebellum 
Transverse  fold 
Rhombic  lip 


Olfactory  lobe 
Optic  stalk  — 

/        !         \         I- 

Infundibulum         Hypophysis          Basilar  artery 
FIG,  410. — Lateral  view  of  a  model  of  the  brain  of  a  7^  weeks'  (18.5  mm.)  human  embryo.    His. 


it  is  the  septum  medulla.  It  is  bounded  on  each  side  by  a  vertical  extension  of 
the  marginal  layer  which  for  convenience  will  be  referred  to  as  the  septal 
marginal  layer  (Figs.  415,  416  and  417). 

The  histological  condition  of  this  part  of  the  tube  at  the  beginning  of  five 
weeks  has  already  been  described.  The  lateral  walls  consist  of  an  inner  layer 
of  closely  packed  cells,  of  a  mantle  layer  consisting  of  efferent  neurones  and  a 
simple  system  of  intermediate  neurones,  and  an  outer  marginal  layer  containing 
the  longitudinal  bundles  of  incoming  afferent  roots  and  longitudinal  axones  of 
intermediate  neurones  (see  p.  474).  It  has  been  seen  that  this  condition  has 
been  brought  about  by  the  proliferation  of  cells  near  the  tube  cavity,  which 
migrate  outward,  at  the  same  time  many  of  them  differentiating  into  neuro- 
blasts  and  nerve  cells  and  thereby  forming  the  mantle  layer.  As  in  the  cord, 
the  basal  plate  takes  the  lead  and  thus  at  first  outstrips  the  alar  plate,  as  shown 


THE  NERVOUS  SYSTEM.  485 

in  its  greater  thickness  above  mentioned.  This  process  likewise  terminates 
sooner  in  the  basal  plate,  few  cell  divisions  being  present  there  at  seven  weeks. 
At  about  the  end  of  the  fifth  week  (see  p.  489)  the  alar  plate  begins  to  develop 
very  rapidly.  Its  period  of  proliferation  is  about  terminated  at  the  end  of  the 
second  month.  When  the  cell  proliferation  near  the  ventricle  has  ceased, 
the  inner  layer  is  reduced  by  outward  migration  to  a  single  layer  of  epend]  ma 
cells  (compare  pp.  455  and  456). 

While  the  efferent  nuclei  continue  to  develop  and  the  central  continuations 
of  the  afferent  neurones  continue  to  grow  in  length,  the  principal  differential  ipns 
now  taking  place  in  the  rhombic  brain  are  those  affecting  the  intermediate 
neurone  systems. 

The  first  of  these  to  be  considered  is  the  further  differentiation  of  the  system 
of  intersegmental  neurones  (p.  435).  The  earlier  development  of  this  system 
has  been  seen  to  involve  especially  the  basal  plate  and  the  further  development 
of  the  latter  leads  to  the  complete  differentiation  of  the  formatio  reticularis 
which  especially  represents  this  system  in  the  epichordal  brain.  It  has  already 
been  seen  (p.  474)  that  many  of  the  intermediate  neurones  representing  the 
beginning  of  this  system  seem  to  be  at  first  heteromeric  and  form  an  internal 
arcuate  system  of  fibers  similar  to  those  seen  in  the  cord  (pp.  473,477).  They 
increase  in  number  toward  the  median  line  and  are  especially  numerous  in  the 
basal  plate,  where  they,  together  with  the  medial  efferent  neurones  (XII  and 
VI  cranial  nerves) ,  form  an  eminence  of  the  mantle  layer  corresponding  to  the 
ventral  gray  column  of  the  cord  (Fig.  411).  Many  of  the  axones  of  these  cells 
of  the  arcuate  system  cross  the  septum  medullae,  thus  marking  the  beginning  of 
the  raphe,  and  form  on  each  side  a  longitudinal  bundle  in  the  septal  marginal 
layer  (Fig.  411  .  These  longitudinal  bundles  correspond  to  the  first  formation 
of  the  ventral  funiculi  of  the  cord.  They  must  not,  of  course,  be  confused 
with  the  pyramids  which  appear  much  later.  Whether  these  longitudinal 
bundles  are  also  partly  formed  of  axones  of  tautomeric  cells  is  uncertain. 
Later,  as  the  anterior  horn  swellings  grow  and  the  depth  of  the  septum 
medullae  and  of  the  septal  marginal  layers  increases  (compare  p.  484),  more 
longitudinal  fibers  appear  in  the  latter,  the  new  ones  apparently  being  added 
ventrally.  Others  also  appear  more  laterally  in  the  marginal  layer  (Figs.  415, 
416  and  417).  (Compare  cord,  p.  477-)  At  this  time,  also,  fibers  enter  the 
marginal  layer  bordering  the  surface  (as  distinguished  from  the  septal),  pass 
along  parallel  with  the  surface,  cross  the  septum,  and  proceed  to  various  parts 
of  the  marginal  layer  of  the  opposite  side.  These  fibers  are  the  first  external 
arcuate  fibers  as  opposed  to  the  prec  eding  internal  arcuate  fibers  which  traverse 
the  mantle  layer  (gray)  in  the  arcuate  part  of  their  course  (Fig.  415). 

The  majority  of  the  longitudinal  fibers  entering  the  septal  marginal  layers 
during  the  second  month  occupy  approximately  the  position  of  the  future 


486 


TEXT-BOOK  OF  EMBRYOLOGY. 


mesial  formatio  reticularis  alba  (white  reticular  formation)  and  correspond  in 
position  to  the  fibers  of  the  medial  longitudinal  fasciculi  and  reticulo-spinal 
tracts  in  the  adult  medulla,  representing  probably  the  same  system  as  the 
medial  part  of  the  ventro-lateral  funiculi  of  the  cord  (medial  longitudinal 
fasciculi,  reticulo-spinal  and  ventro-medial  ground  bundles  of  the  cord).  The 
medial  longitudinal  fasciculi  are  in  part  descending  fibers  from  higher  levels 
described  later. 


Tsenia 


Marginal  layer 


Tractus  solitarius 


N.  X. 
(Medullary  XI) 

Internal  arcuate  fibers 

(in  beginning  gray 

reticular  formation) 


N.  XII 


Alar  plate 


Sulcus  limitans 


Basal  plate 


Ventral  funiculus  Floor  plate 

(beginning  of  form,  retic.  alba) 

FIG.  411. — Half  of  a  transverse  section  of  the  medulla  of  a  10.2  mm.  human  embryo.     His. 

In  the  basal  plate,  between  the  medial  and  lateral  efferent  nuclei,  there  are, 
even  at  the  beginning  of  the  fifth  week,  not  only  the  efferent  neurones  and  the 
heteromeric  (commissural)  neurones  already  mentioned,  but  other  neuroblasts 
whose  axones  have  a  radial  direction,  i.e.,  toward  the  periphery.  (Figs.  411 
and  414.)  The  interlacing  of  these  with  the  arcuate  fibers  forms  the  first 
indication  of  the  formatio  reticularis  grisea  (gray  reticular  formation).  Later, 
longitudinal  fibers  are  present  here,  giving  rise  to  a  condition  more  fully 
corresponding  to  that  in  the  adult,  analogous  also  to  the  condition  in  the 
lateral  funiculi  of  the  cord,  especially  in  the  processus  reticularis. 


THE  NERVOUS  SYSTEM. 


487 


In  the  region  of  the  auditory  segment  an  important  neurone  group  appears 
which  is  possibly  a  differentiation  of  the  extreme  dorso-lateral  portion  of  the 
basal  plate.  This  is  Deiters'  nucleus,  which  apparently  receives  vestibular 
and  cerebellar  fibers  and  sends  uncrossed  descending  bundles  along  the  outer 
lateral  part  of  the  reticular  formation  and  also  ascending  and  descending  crossed 
and  uncrossed  fibers  along  its  outer  mesial  portion  (part  of  the  medial  longi- 
tudinal fasciculus) .  This  nucleus  thus  represents,  apparently,  like  the  nucleus 
ruber  and  nucleus  of  Darkschewitsch  (below),  a  differentiated  portion  of  the 
intersegmental  neurones  in  especial  connection  with  suprasegmental  efferent 
fibers  which  thereby  act  on  many  brain  and  cord  segments. 

The  great  development  of  the  reticular  formation  here  and  caudally  possibly 
causes  a  ventro-lateral  displacement  of  the  contained  nucleus  ambiguus  and 
efferent  facial  nucleus  and  consequently  the  arched  or  hook-shaped  course  of 


Genu  facialis 


forward 


© 


m«d.sulcus 


medsulcus 


medsiilcus 

A  B  c 

FIG.  412. — Diagram  illustrating  the  development  of  the  genu  of  the  facial  nerve  in  the  human 
embryo.  The  drawings  show  the  right  facial  nerve  and  its  nucleus  of  origin,  in  three  stages: 
the  youngest,  A,  being  a  10  mm.  embryo,  and  the  oldest,  C,  a  new-born  child.  The  relative 
position  of  the  abducens  (VI)  nerve  is  represented  in  outline;  its  nerve  trunk  is  not  shown,  as 
the  structures  represented  are  seen  from  above.  Streeter. 

their  root  fibers  as  seen  in  transverse  section  (Streeter) .  At  the  same  time,  the 
nucleus  of  the  VI,  which  originally  was  caudal  to  the  VII,  migrates  cranially, 
carrying  the  facial  efferent  roots  with  it.  This  gives  rise  to  the  genu  facialis 
(Streeter,  Fig.  412). 

In  the  mid-brain  (Fig.  413),  what  appears  to  represent  the  basal  plate 
forms  an  eminence,  the  tegmental  swelling.  Later  there  is  differentiated  from 
this  the  reticular  formation  of  this  region,  containing  various  nuclei  and 
traversed  by  radial,  longitudinal  and  arcuate  fibers,  many  of  the  latter  arising 
from  the  later  differentiating  dorsal  portions  (corpora  quadrigemina)  of  the 
lateral  mid-brain  walls.  An  important  neurone  group  of  the  reticular  forma- 
tion system  which  appears  in  this  region  is  the  nucleus  of  Darkschewitsch.  Its 
descending  axones  form  a  part  of  the  medial  longitudinal  fasciculus  and 
probably  appear  at  the  end  of  the  first  month.  The  nucleus  ruber  is  probably 
differentiated  from  the  forward  extremity  of  the  tegmental  swelling  which  over- 
laps into  a  prechordal  region  (Fig.  425).  Its  axones  (crossing  as  ForeVs  decus- 
sation  and  forming  the  rubro-spinal  tract)  probably  develop  early.  This 


488 


TEXT-BOOK  OF  EMBRYOLOGY. 


neurone  group  apparently  owes  its  great  development  principally  to  its  close 
association  with  the  cerebellum.  These  two  long  descending  intersegmental 
tracts  as  they  grow  downward  envelop  the  differentiating  reticular  formation 
of  more  caudal  regions  of  brain  (and  cord)  and  thereby  come  to  occupy  an 
external  position  in  the  fully  differentiated  reticular  formation. 

The  reticular  formation  is  thus  composed  of  a  gray  portion  containing  the 
neurone  bodies  and  shorter  tracts  and  a  white  portion  composed  of  the  longer 
tracts.  Axones  from  certain  nuclei  (especially  N.  ruber,  N.  of  Darkschewitsch 
and  N.  of  Deiters)  form  long,  principally  descending,  tracts  which  envelop  the 
gray  reticular  formation  mesially  (medial  longitudinal  fasciculus  including 
fibers  from  nuclei  of  Darkschewitsch  and  Deiters  as  well  as  other  reticulo- 
spinal  fibers)  and  laterally  (rubro-spinal,  lateral  uncrossed  tract  from  Deiters* 


Alar  plate 


Marginal  layer 
%m_ Nucleus  N.  Ill 


Root  fibers  N.  Ill 


FIG.  413. — Transverse  section  through  the  mid-brain  of  a  10.2  mm.  human  embryo.     His. 


nucleus  and  other  reticulo-spinal  fibers)  and  constitute  the  white  reticular 
formation.  These  long  tracts  descend  to  the  cord  and  there  similarly  envelop 
its  ventro- lateral  ground  bundles. 

While  the  above  differentiation  of  the  reticular  formation  has  been  taking 
place,  changes  in  the  alar  plate  have  begun  which  lead  to  the  formation  of 
terminal  nuclei  of  peripheral  afferent  nerves,  as  well  as  terminal  nuclei  of  other 
tracts,  all  of  which  send  fiber  bundles  to  suprasegmental  structures. 

The  formation  of  the  receptive  nuclei  of  the  afferent  nerves  of  peripheral 
(segmental)  structures  is  complicated  by  the  fact  that  the  central  continuations 
of  the  peripheral  afferent  nerves  are  not  confined  to  their  own  respective  seg- 
ments but  form  longitudinal  tracts  which  continue  to  grow  upward  (columns  of 
Goll  and  Burdach)  or  downward  (descending  solitary,  vestibular  and  trigeminal 
tracts)  passing  into  other  segments  and  overlapping  externally  structures 
already  in  process  of  formation  there.  In  each  segment,  then,  the  terminal 
nuclei  of  the  afferent  nerves  of  that  segment  must  be  distinguished  from  the 


THE  NERVOUS  SYSTEM.  489 

terminal  nuclei  of  afferent  elements  from  other  segments.  The  latter  are 
external  or  added  to  the  former  and  are  differentiated  from  additional  prolifer- 
ations of  neuroblasts  of  the  alar  plate.  In  addition  to  these  nuclei,  there  are 
certain  nuclei  forming  links  between  the  two  great  suprasegmental  structures, 
the  pallium  and  cerebellum.  These  nuclei  are  the  olive*  and  pons  nudei, 
both  of  which  form  afferent  cerebellar  bundles  and  which  are  differentiatec.  by 
still  further  proliferations  and  migrations  of  alar  plate  neuroblasts. 

It  has  already  been  seen  that  the  afferent  peripheral  nerves  (IX  and  X) 
of  the  visceral  segment  form  (together  with  descending  fibers  of  the  VII)  the 
tractus  solitarius.  This  is  at  first  (5th  week)  short,  but  in  six  weeks  has  rea<  :hed 
the  cord.  The  terminal  nucleus  of  the  tractus  solitarius  is  differentiated  irom 
the  neuroblasts  of  the  medial  portion  of  the  alar  plate.  The  course  of  the 
axones  of  this  nucleus  is  not  known.  Judging  from  comparative  anatomical 
grounds,  they  would  not  follow  the  fillet  pathway  (C.  J.  Herrick).  The  most 
caudal  part  of  this  nucleus  is  the  nucleus  commissuralis  at  the  lower  apex  of  the 
fourth  ventricle. 

The  formation  of  the  other  terminal  nuclei  lying  in  the  region  of  this  seg- 
ment is  begun  by  the  further  developments  of  the  alar  plate  already  alluded 
to.  These  are  initiated  by  an  expansion  and  consequent  folding  of  its  border 
(formation  of  the  rhombic  lip,  p.  483).  followed  by  further  cell-proliferation, 
leading  to  fusion  of  these  folds  and  copious  formation  of  neuroblasts  in  this 
region.  These  neuroblasts  represent  fresh  accessions  to  the  neuroblasts 
already  formed  in  the  mantle  layer  of  the  more  medial  part  of  the  alar  plate. 
This  latest  development  of  the  border  portions  of  the  alar  plate  is  the  last  step 
in  the  progressive  development  of  the  neural  tube  from  the  medial  portion 
(basal  plate)  to  the  lateral  (dorsal)  border  of  the  lateral  walls  of  the  tube 
where  further  development  ceases  at  the  attachment  to  the  roof  plate  (taenia). 
(Fig.  414.) 

Many  of  the  neuroblasts  of  the  rhombic  lip  region  migrate  ventrally.t 
Some  of  those  from  the  medial  part  of  the  swelling  produced  by  the  fusion  of 
the  rhombic  lip  folds  (p.  483,  migrate  along  the  inner  side  of  the  tractus  soli- 
tarius, while  those  from  the  lateral  part  of  the  swelling  pass  outside  the  tractus, 
which  becomes  thereby  enclosed  in  the  mantle  layer  (Fig.  415).  Many  of  these 
neuroblasts  continue  their  journey,  passing  along  the  outer  side  of  the  differ- 


*  This  is  conjectural.  The  origin  of  fibers  to  the  inferior  olivary  nuclei  is  not  known.  The 
most  conspicuous  tract  to  the  olive  is  von  Bechterew's  central  tegmenlal  trad.  Purely  a  priori  con- 
siderations might  be  adduced  in  favor  of  this  being  considered  a  descending  tract  from  thalamic 
nuclei  which  in  turn  receive  pallio-thalamic  fibers.  It  may,  however,  arise  from  lower  optic  centers. 

fit  is,  perhaps,  an  open  -question  whether  the  formation  of  the  lip  is  a  fundamental  feature  in 
this  last  proliferation  and  invasion  of  neuroblasts  from  the  border  of  the  alar  plate.  The  promi- 
nence of  the  rhombic  lip  in  man  is  the  early  embryological  expression  of  the  future  great  develop- 
ment of  parts  subsequently  formed  from  this  portion  of  the  neural  wall,  especially  the  cerebellum 
and  neurone  groups  in  connection  with  it. 


490 


TEXT-BOOK  OF  EMBRYOLOGY. 


entiating  formatio  reticularis,  until  they  are  arrested  at  the  septal  marginal  layer 
(Figs.  416  and  417). 

From  these  neuroblasts  which  remain  in  situ  near  the  dorsal  border  are  de- 
veloped the  nucleus  gracilis  and  nucleus  cuneatus.  The  axones  of  these  nuclei 
form  internal  arcuate  fibers  which  decussate  and  form  a  bundle  of  longitudinal 
fibers  in  the  opposite  septal  marginal  layer  ventral  to  the  reticularis  alba. 
This  tract  is  the  medial  fillet  whose  fibers  appear  during  the  second  month 
and  is  one  of  the  afferent  paths  to  suprasegmental  structures  (mid-brain  roof 


Inner  rhombic  furrow 

Rhombic  lip 
Outer  rhombic  furrow 
Alar  plate 
^  Sulcus  limitans 

Tractus  solitarius 
Inner  layer 

N.  X  (medullary  XI) 
Mantle  layer 
Marginal  layer 

Basal  plate 

Beginning  of  gray 
reticular  formation 


Floor  plate  F.r.a.  N.  XII  Internal  arcuate  fibers 

(forming  septum  medullae) 

FIG.  414. — Half  of  a  transverse  section  of  the  medulla  of  a  9.1  mm.  human  embryo 

(during  the  fifth  week).     His. 
The  arrow  is  in  the  inner  median  sulcus.     F.  r.  a.,  beginning  of  white  reticular  formation. 

and  pallium).  Other  neuroblasts,  which  probably  migrate  further,  form  the 
substantia  gelatinosa  of  Rolando.  Axones  of  this  group  also  form  tracts  repre- 
senting afferent  paths  to  suprasegmental  structures  (pallium).  Neuroblasts 
which  migrate  further  form,  as  already  mentioned,  afferent  cerebellar  con- 
nections. Those  migrating  to  the  septal  marginal  layer  form  there  an 
L-shaped  mass  mesial  to  the  root  fibers  of  the  XII  cranial  nerve  (Fig.  417). 
This  is  the  medial  accessory  olive.  Fresh  groups  of  neuroblasts,  added  laterally 
to  these  in  streaks,  form  the  inferior  olivary  nucleus,  while  others  which  have  not 
advanced  so  far  form  the  lateral  nucleus.  Axones  of  the  olivary  neuroblasts 


THE  NERVOUS  SYSTEM. 


491 


(olivo-cerebellar  fibers)  pass  across  the  median  line  (seventh  or  eighth  week)  to 
the  opposite  dorsal  border  where  they,  together  with  axones  from  the  lateral 
nuclei  and  the  continuation  from  the  cord  of  Flechsig's  tract,  form  (end  of 
the  second  month)  the  bulk  of  the  restiform  body  (Fig.  417).  At  three  months 
the  olives  have  acquired  their  characteristic  folded  appearance. 

Owing  to  the  later  development  and  ventral  migration  of  the  alar  plate 
neuroblasts,  there  are  thus  formed  the  various  nuclei  which  lie  external  to  the 
reticular  formation  in  the  adult.  The  continuations  of  ascending  spinal  cord 


Outer  part  of  rhombic 
lip  migration 

Inner  part  of  r.  1.  mig. 
Inner  layer 
Tractus  solitarius 
Marginal  layer 
Mantle  layer 

Ext.  arcuate  fibers 
Int.  arcuate  fibers 


Septum      Beginning  white        N.  XII      Gray  reticular 
medullae    reticular  formation  formation 

FIG.  415. — Half  of  a  transverse  section  of  the  medulla  of  a  10.5  mm.  human  embryo 
(end  of  fifth  week).     His. 


tracts  (Flechsig  and  Gowers)  occupy  the  most  external  position  on  the  lateral  sur- 
face, and  other  cord  continuations  (medial  fillets)  the  most  external  mesial 
positions.  Later,  however  (fifth  month),  there  is  added  ventral  to  the  fillets 
the  descending  cortico-spinal  fibers  (pyramids).  Their  decussation  takes 
place  at  the  cervical  flexure. 

By  the  external  accessions  from  the  alar  plate  above  described,  forming 
terminal  nuclei  of  overlapping  tracts  from  above  (especially  the  nucleus  of 
the  spinal  V) ,  the  tractus  solitarius  becomes  buried,  as  it  were,  hence  its  deep 
position  in  the  adult.  The  great  development  of  the  reticular  formation 
may  contribute  to  this  result.  As  the  trigeminus  is  the  most  cephalic  rhombic 


492 


TEXT-BOOK  OF  EMBRYOLOGY. 


segment,  its  descending  fibers  are  not  overlapped  by  fibers  from  above  and 
therefore  occupy  the  most  external  position  of  all  these  descending  peripheral 
systems. 

Mantle  layer 

\ 


Inner  layer        Gray  ret.  form 


F.r.a. 


Rhombic  lip  migration  | 

Ext.  arc.  fib.  in  marg.  layer       N.  XII        F.r.a. v.        Septum  medullas 

FIG.  416. — Half  of  a  transverse  section  through  the  medulla  of  a  13.6  mm.  human  embryo 

(beginning  of  sixth  week).     His. 

F.  r.  a.,  Beginning  of  white  reticular  formation  in  dorsal  part  of  septal  marginal  layer. 
Another  bundle  has  formed  more  ventrally  (F.  r.  a.  v.) . 


Inner  layer 


Roof  plate 


Tractus  solitarius 


Formatio  reticularis 
grisea 

Formatio  reticularis  alba 


N.  XII 


Rhomic  lip 


Restiform 
body 


' *  Spinal  V 

Neuroblasts  from  alar  plate 
Marginal  layer 


Neuroblasts  from  alar  plate 
(Rudiment  of  accessory  olive) 


FIG.  417. — Transverse  section  through  the  medulla  of  an  8  weeks'  human  embryo.     His. 

The  terminal  nuclei  belonging  to  the  auditory  (acustico-facialis-abducens) 
segment  are  those  of  the  vestibular  and  cochlear  portions  of  the  VIII  nerve. 


THE  NERVOUS  SYSTEM.  493 

The  development  of  these  nuclei  is  not  fully  known,  but  they  are  derived  from 
the  alar  plate,  except  possibly  Deiters'  nucleus  (see  p.  487),  the  nuclei  of  the 
later  formed  cochlear  nerve  occupying  the  more  external  position.  The  ves- 
tibular  nuclei  apparently  send  axones  both  to  cerebellum  and  reticular  formation. 
The  cerebellum  itself  may  be  regarded  as  primitively  a  receptive  vestibular 
structure  (p.  436)  and  probably  receives  vestibular  root  fibers.  The  axones 
of  the  cochlear  nuclei  pass  across  the  median  line,  along  the  ventral  border  of 
the  reticular  formation  (second  half  of  second  month),  forming  the  trapez'um. 
On  the  lateral  boundary  of  the  opposite  reticular  formation  they  ascend,  form- 
ing the  lateral  fillet,  to  the  suprasegmental  posterior  corpus  quadrigeminum. 
Accessions  are  received  from  the  superior  olive,  in  which  some  of  the  trapezium 
fibers  terminate. 

The  alar  plate  of  this  segment  also  forms  the  substantia  gelatinosa  and  the 
anterior  portions  of  the  olivary  nuclei  in  this  region.  The  various  remaining 
tracts  assume  the  same  positions  as  further  caudally. 

Later,  the  pyramids  are  added  ventrally  to  the  fillet,  and  the  great  develop- 
ment of  the  pons  leads  to  it's  covering  the  ventral  surface  of  part  of  this  region. 
Owing  to  the  late  development  of  the  pons  and  pyramids,  the  trapezium  is  thus 
uncovered  and  lies  on  the  ventral  surface  of  the  rhombic  brain  during  the  third 
month.  It  is  permanently  uncovered  in  the  dog  and  cat. 

In  the  trigeminus  segment,  the  terminal  nucleus  of  the  afferent  portion  of 
this  nerve  is  probably  similarly  formed  from  the  alar  plate.  Its  axones  decus- 
sate, probably  joining  the  fillet,  and  proceed  to  the  thalamus,  which  is  connected 
with  the  pallium.  Descending  axones  from  cells  in  the  mid-brain  roof  form 
part  of  the  trigeminus  known  as  its  descending  or  mesencephalic  root.  The 
view  has  been  advanced  (Meyer,  Johnston)  that  these  are  afferent  neurones 
equivalent  to  certain  dorsal  horn  cells  found  in  some  adult  and  embryonic 
Vertebrates  and  representing  >spinal  ganglion  cells  which  have  become  included 
in  the  neural  tube  instead  of  becoming  detached  with  the  rest  of  the  neural  crest 
(compare  p.  422). 

In  front  of  the  lateral  recess  another  extensive  development  of  the  alar  plate 
occurs,  evidenced  by  the  large  rhombic  lip  of  this  region.  The  neuroblasts 
thus  differentiated  form  the  enormously  developed  pontile  nuclei  whose  axones 
pass  across  the  median  line  (fifth  month)  to  the  opposite  cerebellar  hemisphere, 
forming  the  middle  cerebellar  peduncle  or  brachium  pontis.  The  pons  extends 
over  the  ventral  surface  of  the  cephalic  part  of  the  medulla  and  over  the  ventral 
surface  of  part  of  the  mid-brain.  It  receives  fibres  from  various  parts  of  the 
neopallium,  which  form  a  great  part  of  the  pes  pedunculi  or  crusta.  A  still 
greater  development  of  the  alar  plate  forms  the  cerebellum. 

In  the  mid-brain  region,  the  reticular  formation  already  described  (p.  487) 
is  enveloped  ventrally  and  laterally  by  the  upward  extension  of  the  medial  and 


494  TEXT-BOOK  OF  EMBRYOLOGY. 

lateral  fillets,  the  whole  comprising  the  tegmentum.  Ventral  to  this  are  added 
later  the  pons  and  the  descending  cortico-pontile,  cortico-bulbar  and  cortico- 
spinal  bundles  forming  here  the  pes  pedunculi  or  crusta  (probably  during  the 
fifth  month). 

The  alar  plate  of  the  mid-brain  region  forms  the  corpora  quadrigemina 
(mid-brain  roof). 

The  further  changes  in  the  gross  morphology  of  the  medulla  are  due  mainly 
to  further  growth  of  structures  already  present.  The  nuclei  of  the  dorsal  col- 
umns by  their  increase  cause  the  swellings  on  the  surface  of  the  medulla  known 
as  the  clava  and  cuneus,  and  likewise  by  their  increase  in  size  cause  a  secondary 
dorsal  closing  in  of  the  caudal  apex  of  the  fourth  ventricle  which  formerly 
extended  to  the  cervical  flexure.  The  tuber culum  of  Rolando  is  produced  by  the 
growth  of  the  terminal  nucleus  of  the  spinal  V,  and  the  restiform  body  largely 
by  the  development  of  the  afferent  cerebellar  fibers  (Fig.  419). 

The  growth  of  the  olivary  nuclei  produces  the  swellings  known  as  the 
olives.  The  above  mentioned  accession  of  the  descending  cerebrospinal  tracts 
to  the  ventral  surface  is  indicated  by  the  pyramids. 

In  the  floor  of  the  ventricle  there  is  a  longitudinal  ridge  each  side  of  the 
median  line  occupied  by  swellings  produced  by  the  nucleus  of  the  XII  and, 
further  forward,  the  nucleus  of  the  VI,  together  with  other  nuclei  (intercalatus, 
funiculus  teres  and  incertus,  Streeter)  which  are  not  well  understood.  The 
furrow  forming  the  lateral  boundary  of  this  area  is  usually  taken  to  be  the 
representative  of  the  sulcus  limitans  and  consequently  the  area  in  question 
would  be  the  basal  plate.  Lateral  to  it  is  a  triangular  area  with  depressed 
edges — the  ala  cinerea.  It  represents  a  region  where  portions  of  the  vago- 
glossopharyngeal  nuclei  (dorsal  efferent  and  terminal  nuclei  of  fasciculus 
solitarius)  lie  near  the  surface.  Possibly  a  secondary  invasion  by  surrounding 
more  recently  differentiated  nuclei  may  account  for  their  apparent  partial 
retreat  from  the  surface.  It  is  possible  that  the  ala  cinerea  may  be  regarded 
not  so  much  as  a  part  of  the  alar  plate,  but  that  it — or  rather  the  branchial 
nuclei  involved  in  its  formation — represents  an  independent  intermediate  region 
corresponding  to  the  intermediate  region  in  the  cord  (J.  T.  Wilson).  The 
remaining  portion  of  the  alar  plate,  in  -the  floor,  is  apparently  represented 
principally  by  the  acoustic,  especially  the  vestibular,  field. 

In  the  development  of  the  segmental  brain  there  are  thus  the  following 
overlapping  stages:  (i)  The  differentiation  of  the  inner,  mantle  and  marginal 
layers.  (2)  The  primary  neural  apparatus,  consisting  of  (a)  the  peripheral 
segmental  neurones,  the  central  processes  of  the  afferent  neurones  entering  the 
alar  or  receptive  plate,  the  efferent  neurone  bodies  forming  two  main  series 
of  nuclei  in  the  basal  plate,  and  (b)  intersegmental  neurones  composing  the 
reticular  formation  in  which  the  long  tracts  occupy  external  positions.  (3) 


THE  NERVOUS  SYSTEM. 


495 


The  further  differentiation,  from  the  alar  plate,  of  terminal  nuclei  for  the 
afferent  peripheral  segmental  neurones,  the  axones  of  the  terminal  nuclei 
forming  afferent  tracts  to  suprasegmental  structures.  These  tracts  and  other 
later  forming  afferent  suprasegmental  tracts  with  their  nuclei  are  laid  down 
external  to  the.  reticular  formation.  (4)  Formation  of  efferent  (chiefly  thala- 
mic(?)  mid-brain  and  cerebellar)  suprasegmental  tracts  which  act  upon  the 
intersegmental  neurones  or  reticular  formation.  (5)  Accession  at  a  late  stage 
of  development  of  a  descending  system  of  fibres  from  the  neopallium.  These 
lie  ventral  to  the  preceding  structures. 


The  Cerebellum. 

It  has  already  been  pointed  out  that  at  an  early  period  (three  weeks)  the 
anterior  boundaries  of  the  thin  expanded  roof  plate  of  the  rhombic  brain  form 
two  lines  converging  anteriorly  to  the  median  line  where 
the  roof  plate  is  represented  by  the  usual  narrow  portion 
connecting  the  two  alar  plates  (Fig.  418).  It  has  also 
been  pointed  out  that  the  pontine  flexure  produces  on  the 
dorsal  surface  a  deep  transverse  fold  in  this  thin  roof,  into 
which  vascular  tissue  grows  later  forming  the  chorioid 
plexus  (Fig.  410).  At  this  stage,  the  continuations  of  the 
alar  plates  of  the  medulla  form  two  transverse  bands 
which,  when  viewed  laterally,  are  vertical  to  the  general 
longitudinal  axis  of  this  part  of  the  brain  (Fig.  448).  At 
the  same  time,  the  rhombic  lips  are  formed  along  the 
caudal  border  of  these  bands  and  the  latter  become 
musm  thickened  into  the  two  rudiments  of  the  cerebellum,  a 

H  IB  considerable  portion  of  which  may  be  derived  from  the 

I:  fj«  lips.     These    rudiments    are    thus    two  transverse  and 

vertical  swellings  and  are  connected  across  the  median 
line  by  the  roof  plate.     The  attachment  (taenia)   of  the 

FIG    418.— Dorsal  view         .  , 

alar  plate  of  this  region  to  the  roof  plate  of  the  fourth 
ventricle  is  at  first  along  its  caudal  edge.  Later,  by  the 
folding  back  and  fusion  of  this  border  to  form  the  rhom- 
bic lips,  the  attachment  is  carried  forward.  Still  later, 
by  the  growth  of  the  cerebellar  rudiment,  it  is  rolled 
backward  and  under,  as  described  below.  The  rudi- 
ments subsequently  fuse  across  the  median  line,  thus 
forming  externally  a  single  transverse  structure,  but  internally  a  paired  dorsal 
median  projection  of  the  lumen  marks  the  location  of  the  uniting  roof  plate 
(comp.  Fig.  420). 


ric  418. — Dorsal  view 
of  that  part  of  the 
brain  caudal  to  the 
cephalic  flexure 
(human  embryo  of  3d 
week,  2.15  mm.).  Hh. 
Cerebellum;  /,  isth- 
mus; M,  mid-brain; 
Rf,  Nh,  med  ulla. 
Compare  with  Fig. 
416.  His. 


496 


TEXT-BOOK  OF  EMBRYOLOGY. 


While  the  structure  thus  formed  expands  enormously  in  a  lateral  direction, 
in  its  subsequent  development  its  greatest  growth  is  in  a  longitudinal  direction. 
The  effect  of  this  is  that  the  continuations  of  the  cerebellum  forward  (velum 
•medullare  anterius)  and  backward  (velum  medullare  posterius)  into  the  adjoining, 
brain  walls  of  the  isthmus  and  medulla  are  comparatively  fixed  points  and  are 
completely  overlapped  by  the  spreading  cerebellum,  producing  an  appearance 
in  sagittal  section  as  though  they  were  rolled  in  under  the  latter  structure  (comp. 
Fig.  370,  F).  Another  result  of  this  longitudinal  growth  is  the  formation  of  fis- 
sures running  across  the  organ,  transversely  to  the  longitudinal  brain  axis. 
First,  lateral  incisures  separate  two  caudal  lateral  portions,  the  flocculi  (Fig. 
419),  the  median  continuation  of  which,  the  nodule,  is  finally  rolled  in  on 
the  under  side  of  the  cerebellum  as  explained  above.  Another  transverse  fissure, 
the  primary  fissure,  beginning  in  the  median  part  and  extending  laterally,  sepa- 

Cerebellar  hemisphere 


Taenia 


Tuberculum  cuneatum  - 

Clava-""' 

Tuberculum  cinereum  (Rolando) 


-—  Vermis 

Eminentia  teres 

Taenia 

Fasciculus  gracilis  (Goll) 
Fasciculus  cuneatus  (Burdach) 


FIG.  419. — Dorsal  view  of  the  cerebellum  and  medulla  of  a  5  months'  human  fetus.     Kollmann. 

rates  an  anterior  lobe  from  a  middle  lobe,  the  former  comprising  the  future  lin- 
gula,  centralis  and  culmen  and  their  lateral  extensions.  The  anterior  portion 
is  rolled  forward  under  the  anterior  part  of  the  cerebellum.  Another  trans- 
verse fissure  next  appears  in  the  median  part  (secondary  fissure}  which  later  ex- 
tends (peritonsillar)  to  the  floccular  incisure,  and  thereby  completes  the  de- 
marcation of  a  posterior  lobe,  including  not  only  the  flocculus  and  nodule,  but 
also  the  tonsilla  and  uvula,  which  are  also  rolled  backward  and  under.  The 
result  of  this  transverse  fissuration  would  be  the  production  of  a  cerebellum 
resembling  that  of  certain  forms  below  Mammals  where  the  cerebellum  is  well 
developed  (Selachians,  Birds).  A  complicating  factor,  however,  is  the  great 
growth  of  certain  lateral  portions  of  the  middle  lobe,  forming  the  future  cere- 
bellar  hemispheres  (Fig.  419),  which  causes  also  a  lateral  overlapping  and  rolling 
inward  of  adjoining  parts.  This  growth  is  the  chief  factor  in  the  division 
of  the  cerebellum  into  vermis  and  hemispheres  and  is  correlated  with  the  devel- 
opment of  the  neopallium  (p.  436  and  Fig.  371). 


THE  NERVOUS  SYSTEM.  497 

The  early  histological  development  of  the  cerebellum  has  been  most  closely 
studied  in  Bony  Fishes  (Schaper)  and  there  is  every  reason  to  suppose  that 
the  processes  taking  place  in  the  human  cerebellum  are  essentially  the  same.  In 
that  part  of  the  alar  plate  forming  the  rudiment  above  described,  the  cells  pro- 
liferate, forming  first  a  nuclear  layer  with  the  dividing  cells  along  its  ventricular 
surface,  and  a  non-nucleated  outer  or  marginal  layer.  Later,  owing  to  begin- 
ning migration  and  differentiation,  there  is  formed  the  usual  mantle  layer, 
representing  a  differentiation  of  part  of  the  original  nuclear  layer  and  thereby 
forming  the  three  layers :  an  inner,  a  mantle  and  a  marginal.  The  outer  cells 
of  the  mantle  layer  increase  in  size  and  differentiate  into  the  cells  of  Purkinje, 
snaller  cells  within  forming  the  granular  layer.  The  earliest  stage  of  differ- 
entiation of  the  Purkinje  cells  has  not  been  accurately  described,  but  the  axones 


FIG.  420. — Diagram  representing  the  differentiation  and  migration  of  the  cerebellar  cells  in  a  teleost 
The  arrows  indicate  the  migration  of  cells  from  the  borders  of  the  cerebellar  rudiment  into 
the  marginal  layer;  these  cells  probably  all  differentiate  into  nerve  cells.  Clear  circles,  indif 
ferent  cells;  circles  with  dots,  neuroglia  cells  (except  in  marginal  layer);  shaded  cells,  epithelia* 
cells;  circles  with  crosses,  epithelial  cells  in  mitosis  (germinal  cells);  black  cells,  neuroblasts;  Z* 
lateral  recess;  M,  median  furrow,  above  which  is  roof  plate;  R,  floor  of  4th  ventricle  (IV), 
Schaper. 

of  the  neuroblasts  evidently  proceed  (end  of  fifth  month)  toward  the  ventricular 
surface  instead  of  entering  the  marginal  layer.  In  this  way  the  fibrous  layer 
(white  matter)  comes  to  lie  within  instead  of  on  the  outer  surface  as  in  the  cord, 
and,  to  some  extent,  in  the  medulla.  There  is  thus  formed  the  outer  gray  matter 
or  cortex.  The  axones  of  the  Purkinje  cells  form  the  great  bulk  of  the  centrifu- 
gal fibers  of  the  cerebellar  cortex.  The  marginal  layer  becomes  ultimately 
the  outer  or  molecular  (plexiform)  layer  of  the  adult  cerebellum. 

It  has  been  seen  that  in  the  other  parts  of  the  tube  development  begins  in 
the  medial  parts  of  the  lateral  plates  and  thence  advances  toward  their  dorsal 
borders,  which  actively  develop  after  the  corresponding  stages  have  ceased  in 
the  medial  portions.  The  same  is  true  of  the  cerebellar  rudiment.  In  this, 
the  edges  which  border  on  the  thin  roof  plate,  i.e.,  those  parts  adjoining  the 
lateral  recesses,  the  main  roof  of  the  fourth  ventricle  and  the  roof  plate  inter- 
posed between  the  two  original  lateral  cerebellar  rudiments,  are  the  last  to  pro- 


498 


TEXT-BOOK  OF  EMB.RYOLOGY. 


liferate.  The  cells  thus  formed  spread  into  the  marginal  layer  of  the  earlier 
developed  parts  and  by  further  proliferation  form  a  nucleated  layer  of  consider- 
able thickness  (Fig.  420).  This  complication  is  apparently  essentially  similar 
to  that  described  above  in  the  development  of  the  medulla.  From  the  cells  of 
this  invasion  are  formed  a  part,  at  least,  of  the  granule  cells,  as  well  as  the  basket 
cells  and  other  cells  which  remain  in  the  marginal  (molecular)  layer.  These 
are  all  association  cells  of  the  cerebellum. 

The  cerebellum  reaches  its  full  histological  development  very  late;  after 
birth  in  many  Mammals.     These  last  postnatal  stages  of  development  naturally 


FIG.  421. — Scheme  showing  the  various  stages  of  position  and  form  in  the  differentiation  of  granule 
cells  from  the  outer  granular  layer.  Cajal. 

A,  Layer  of  undifferentiated  cells;  B,  layer  of  cells  in  horizontal  bipolar  stage;  C,  partly  formed 
molecular  (plexiform)  layer;  D,  granular  layer;  b,  beginning  differentiation  of  granule  cells; 
c,  cells  in  mo  no  polar  stage;  d,  cells  in  bipolar  stage;  e,f,  beginning  of  descending  dendrite 
and  of  unipolarization  of  cell;  g,h,  i,  different  stages  of  unipolarization  or  formation  of  single 
process  connecting  with  the  original  two  processes;  j,  cell  showing  differentiating  and  com- 
pleted dendrites;  k,  fully  formed  granule  cell. 

involve  principally  those  cells  proliferated  last  and  which  lie  in  the  mar- 
ginal layer.  These  have  been  studied  by  means  of  the  Golgi  method  in 
new-born  Mammals  by  Cajal  and  others.  The  majority  of  these  cells  form 
granule  cells  by  means  of  a  progressive  migration  and  differentiation,  as  shown 
in  the  accompanying  Fig.  421.  Each  cell  first  develops  a  single  horizontal 
process,  then  another,  thus  becoming  a  horizontal  bipolar  cell.  Following  this, 
the  cell  body  migrates  past  the  Purkinje  cells  into  the  granular  layer,  remaining 
in  connection  with  the  original  processes  by  a  single  process.  There  are  thus 
formed  the  axone  of  the  granule  cell  with  its  bifurcation  into  two  horizontal  pro- 
cesses, the  parallel  fibers  of  the  molecular  layer.  This  mode  of  formation  is  thus 


THE  NERVOUS  SYSTEM. 


499 


similar  to  the  unipolarization  of  the  cerebrospinal  ganglion  cell.  The  dendrites 
begin  to  be  formed  during  the  migration,  branch  when  the  cell  body  reaches  the 
granular  layer  and  there  finally  attain  the  adult  form.  Other  undifferentiated 
cells  in  the  marginal  layer  send  out  horizontal  processes  the  collaterals  of  which 
envelop  the  Purkinje  cell  bodies,  and  form  the  baskets.  The  place  vacated,  so  to 
speak,  by  the  migrating  granules,  is  filled  at  the  same  time  by  the  developing 
dendrites  of  the  Purkinje  cells.  These  at  first  show  no  regularity  of  branching, 
but  subsequently  differentiate  into  the  definite  branches  of  the  adult  condition, 
at  the  same  time  advancing  toward  the  periphery  (Fig.  422).  When  they 


FIG.  422. — Section  through  cerebellar  cortex  of  a  dog  a  few  days  after  birth,  showing  the  partial 
development  of  the  dendrites  of  two  cells  of  Purkinje.  Cajal. 

A,  external  limiting  membrane;  B,  external  (embryonic)  granule  layer;  C,  partly  formed  molecular 
(plexiform)  layer;  D,  granular  layer;  a,  body  of  cell  of  Purkinje;  &,  its  axone;  c,  and  d,  col- 
laterals with  terminal  arborizations  (e). 

reach  this,  the  migration  of  the  granules  is  completed  and  the  molecular  layer 
is  definitely  formed.  This  condition,  evidenced  by  the  disappearance  of  the 
outer  granular  layer,  is  usually  reached  in  Mammals  within  two  months  after 
birth,  but  in  man  not  until  the  sixth  or  seventh  year.  There  are  observations 
indicating  that  animals  possessing  completely  developed  powers  of  locomotion 
and  balancing  at  birth  have  more  completely  differentiated  cerebella  at  that 
time.  The  axones  of  the  Purkinje  cells  form  many  embryonic  collaterals  which 
are  afterward  reduced  in  number. 

Of  the  centripetal  fibers  to  the  cerebellum,  those  from  the  inferior  olives 
cross  the  median  line  of  the  medulla  about  the  seventh  or  eighth  week,  and 
thence  advance  to  the  vermis,  reaching  their  final  destination  during  the  third 


500  TEXT-BOOK  OF  EMBRYOLOGY. 

month.  The  fibers  from  the  pontile  nuclei  (middle  peduncle)  do  not  develop 
until  considerably  later  (end  of  the  fourth  month),  the  time  of  their  reaching 
their  destination  in  the  cerebellar  hemispheres  not  being  definitely  known. 
Many  at  least  of  the  centripetal  fibers  do  not  reach  their  full  development  in 
Mammals  till  birth  or  after.  Some  of  these  fibers  (climbing  fibers)  form  arbor- 
izations around  the  inferior  (axone)  surface  of  the  Purkinje  cell  bodies  and 
later  creep  upward,  enveloping  the  upper  surface  instead,  and  finally  the  den- 
dritic branches.  Other  centripetal  fibers  (mossy  fibers)  ramifying  in  the 
granular  layer  are  varicose  fibers,  at  first  otherwise  smooth.  From  the  vari- 
cosities  a  number  of  branches  are  given  off  which  later  become  abbreviated  and 
modified  into  the  shorter  processes  of  the  adult  condition.  This  final  differ- 
entiation occurs  simultaneously  with  the  final  differentiation  of  the  dendrites 
of  the  granule  cells  with  which  they  come  into  connection.  The  glia  elements 
apparently  develop  in  a  manner  essentially  similar  to  their  development  else- 
where. 

The  development  of  the  internal  nuclei  of  the  cerebellum  has  not  been 
thoroughly  investigated.  The  nucleus  dentatus  is  well  developed  at  the  end 
of  the  sixth  foetal  month.  Eminences  passing  forward  and  ventrally  along 
the  sides  of  the  isthmus  are  the  earliest  indications  of  the  superior  peduncles* 
formed  later  by  the  axones  of  the  cells  of  these  nuclei. 

Corpora  Quadrigemina. 

The  mid-brain  roof  is  an  expansion  of  the  alar  plate  of  the  mid-brain. 
Later  this  differentiates  into  the  anterior  and  posterior  corpora  quadrigemina. 
In  the  former,  by  the  usual  ventricular  mitoses  (germinal  cells),  a  nuclear 
layer  is  formed  with  a  non-nucleated  marginal  layer  external  to  it  which  becomes 
the  outer  or  zonal  layer.  Still  later  the  neuroblast  or  mantle  layer  is  differen- 
tiated, there  being  an  unusually  thick  inner  layer.  The  further  development 
has  not  been  closely  studied  in  man.  Owing  to  the  diminished  importance 
of  the  anterior  corpora  quadrigemina  (p.  437)  the  neuroblasts  do  not  differ- 
entiate into  the  well  marked  "spread  out"  layers  characteristic  of  the  optic 
lobes  of  many  Vertebrates.  This  is  probably  due  to  a  lack  of  development  of 
their  association  neurones. 

The  fibers  of  the  optic  tracts  grow  toward  the  anterior  corpora  quadrigemina 
in  the  marginal  layer  forming  the  anterior  brachia.  When  they  reach  the 
anterior  corpora  quadrigemina,  they  leave  the  marginal  layer  and  penetrate 
the  gray  matter  forming  the  most  external  fiber  layer.  The  medial  (and  some 
lateral)  lemniscus  fibers  enter  more  deeply  than  the  optic.  Neuroblast  axones 
grow  toward  the  ventricle,  turn  internally  to  the  lemniscus  fibers,  cross  (Mey- 
nert's  decussation) ,  and  proceed  as  the  predorsal  tracts  to  the  segmental  brain 
and  cord,  lying  ventral  to  the  medial  longitudinal  fasciculi. 


THE  NERVOUS  SYSTEM.  501 

The  Diencephalon. 

The  stage  of  development  of  the  diencephalon  at  four  weeks  has  already 
been  mentioned  (p.  448).  (Figs.  423,  433  and  434.)  In  the  lateral  walls  the 
principal  feature  is  the  presence  of  a  furrow,  the  sulcus  hypothalamicus,  which 
beg:ns  ventrally  as  an  extension  of  the  optic  recess  and  extends  dorsally  and 
caudally  toward  the  mid-brain.  A  branch  of  it  extends  to  the  posterior  part 
of  the  foramen  of  Monro.  This  is  the  sulcus  Monroi.  The  sulcus  hypothala- 
micus  is  sometimes  regarded  as  the  representative  in  this  region  of  the  sulcus 
limitans.  It  is  doubtful  whether  it  has  the  same  morphological  value  as  the 
latter.  Such  a  comparison  is  seen  a  priori  to  be  difficult  when  it  is  considered 
that  this  region  is  in  the  most  highly  modified  part  of  the  brain  tube,  lacking 


Ma. 


FIG.  423^ — Transverse  section  through  the  diencephalon  of  a  5  weeks'  human  embryo.  Dp.,  Roof 
plate;  Ma.,  mammillary  recess;  P.s.  hypothalamus;  S.M.,  sulcus  hypothalamicus;  Th., 
thalamus.  His. 

motor  peripheral  apparatus,  and  that  it  is  also  the  end  region  of  the  tube  where 
all  longitudinal  divisions  would  naturally  merge.  The  sulcus  deepens  till  the 
end  of  the  second  month  (Fig.  429).  Later  it  becomes  shallower,  but  appears 
to  persist  till  adult  life.  The  region  of  the  diencephalon  ventral  to  the  sulcus, 
as  already  mentioned,  is  termed  the  pars  subthalamica  or  hypothalamus.  The 
ventral  part  of  the  optic  stalk  forms  a  transverse  groove  in  the  floor,  the  pre- 
optic  recess,  caudal  to  which  is  a  ridge  or  fold,  the  chiasma  swelling,  in  which  the 
fibers  of  the  optic  chiasma  later  appear.*  Caudal  to  this  is  the  recess  or  invagi- 
nation  of  the  floor,  representing  the  postoptic  recess  and  the  beginning  of  the 
infundibulum  (Figs.  424  and  425) .  Its  extremity  later  becomes  extended  into  the 
infundibular  process,  the  posterior  part  of  which  in  the  fifth  week  comes  into 
contact  with  the  hypophyseal  (Rathke's)  pouch.  This  is  a  structure  formed 

*  According  to  Johnston,  the  chiasma  is  formed  in  front  of  the  optic  recess  which  would  then  be 
represented  by  the  postoptic  recess.  In  this  case  the  chiasma  would  be  regarded  as  falling  in  the 
region  of  the  telencephalon  instead  of  forming  the  optic  part  of  the  hypothalamus  (comp.  Figs.  364 
and  433). 


502 


TEXT-BOOK  OF  EMBRYOLOGY. 


from  the  stomodaeal  epithelium  and  is  connected  with  the  latter  by  a  stalk. 
The  pouch,  which  is  at  first  a  flat  structure,  develops  two  horns  which  envelop 


Ant.  corp.  quad.    Pineal  Anterior 

(ant.    colliculus)    region          brachium 


Pallium 

Ant.  ^ 

>  olfact.  lobe 
Post.  J 

Optic  stalk 
Hypophyseal  pouch 


Mammillary    Lateral         Tuber 
region        geniculate    cinereum 
body 

FIG.  424. — Lateral  view  of  a  model  of  the  brain  of  a  10.2  mm.  human  embryo 
(middle  of  5th  week).     His. 

the  infundibulum.  The  cavity  of  the  end  of  the  infundibular  process  becomes 
nearly  shut  off  from  the  rest  of  the  infundibular  cavity.  The  process  penetrates 
the  upper  part  of  the  pouch  and  then  bending  reaches  its  posterior  surface  and 

Diencephalon        Thalamus  Pineal  region 


Pallium 

Foramen  of  Monro 

Sulcus  hypothal- 
amicus 

Ant.  olfact.  lobe 

Post,  olfact.  lobe 

Lamina  terminalis 

Corpus  striatum 


Mesencephalon 
Tegmental  swelling 

Mammillary  region 
Hypothalamus 
Tuber  cinereum 


Recessus      Hypophyseal      Recessus 
(prae?)  opticus        pouch  infundibuli 

FIG.  425. — Median  view  of  the  right  half  of  a  model  of  the  brain  of  a  10.2  mm.  human  embryo 
(middle  of  5th  week).     Compare  Fig.  424.     His. 

ends  blindly.     In  the  second  half  of  the  second  month  epithelial  sprouts,  which 
become  very  vascular,  begin  to  appear,  first  in  the  lateral  parts  of  the  pouch, 


THE  NERVOUS  SYSTEM.  503 

next  the  brain,  and  then  extending  through  the  pouch  and  finally  nearly  oblit- 
erating its  cavity  (third  month).  The  shape  of  the  organ  (the  hypophysis) 
formed  by  the  union  of  these  two  parts  is  subsequently  changed  by  its  relations 
to  surrounding  parts.  Its  posterior  lobe  is  derived  from  the  infundibular  por- 
tion, its  anterior  lobe  from  the  pouch. 

An  expansion  of  the  floor  of  the  brain  caudal  to  the  infundibulum  has  been 
mentioned  as  the  mammillary  region.  Subsequently  there  is  formed  from  its 
cephalic  part  another  evagination,  the  tuber  cinereum.  The  mammillary  region 
forms  the  mammillary  bodies.  The  region  caudal  to  the  mammillary  region 
later  receives  many  blood  vessels,  thereby  becoming  the  posterior  perforated 
space. 

At  the  end  of  the  fourth  week  the  roof  plate  of  the  diencephalon  is  smooth. 
At  about  this  time  the  greater  part  of  the  roof  expands,  forming  a  median 
longitudinal  ridge  (Fig.  426).  This  ridge,  which  remains  epithelial  throughout 
life,  is  broader  at  its  anterior  end  where  it  passes  between  the  beginning  pallial 
hemispheres.  As  the  roof  plate  expands  further,  the  anterior  part  is  next 
thrown  into  longitudinal  folds.  The  ridge  forms  the  epithelial  lining  of  the 
tela  chorioidea  of  the  third  ventricle  (diatela).  By  further  growth  and  vas- 
cularization  of  its  mesodermal  covering  at  the  beginning  of  the  third  month, 
there  is  formed  the  chorioid  plexus  of  the  third  ventricle  (diaplexus).  Lateral 
extensions  of  the  tela  form  the  chorioid  plexuses  of  the  lateral  ventricles  (see 
p.  5 17) .  In  the  fifth  week  a  protrusion  appears  at  the  caudal  end  of  the  median 
ridge  which  is  the  beginning  of  the  epiphysis.  Soon  after  this,  the  furrow  which 
forms  its  caudal  boundary  extends  forward  along  the  upper  part  of  the  sides  of 
the  walls,  marking  off  a  fold  which  is  the  lateral  continuation  of  the  median 
protrusion.  From  the  median  protrusion  is  later  formed  the  pineal  body, 
while  from  the  lateral  folds  are  formed  the  pineal  stalk,  and  in  front  the 
habenula,  with  its  contained  nucleus  (ganglion)  habenulce,  and  the  stria 
medullaris.  Still  further  caudally,  the  anterior  part  of  the  mid-brain  forms 
a  horseshoe-shaped  fold  the  arms  of  which  extend  forward  over  the  dien- 
cephalon, ventral  to  the  pineal  folds.  The  median  part  of  this  fold  forms  the 
anterior  corpora  quadrigemina.  From  its  lateral  extensions  are  formed  the 
anterior  brachia  of  the  anterior  corpora  quadrigemina,  the  pulmnar  and  the 
lateral  and  medial  geniculate  bodies,  all  of  which  (pulvinar  ?)  later  receive  optic 
fibers.  The  transverse  furrow  which  forms  the  boundary  between  the  rudi- 
ments of  the  pineal  body  and  of  the  anterior  corpora  quadrigemina  marks  the 
location  of  the  future  posterior  commissure  (Figs.  426,  427  and  428). 

The  part  of  the  roof  anterior  to  the  pineal  fold,  as  already  stated,  forms  the 
tela  chorioidea  of  the  third  ventricle.  Certain  folds  appear  in  it,  however, 
which  are  more  clearly  indicated  in  later  stages  of  embryonic  development 
than  in  the  adult  and  which  probably  represent  structures  already  mentioned 


504 


TEXT-BOOK  OF  EMBRYOLOGY. 


as  common  to  the  vertebrate  brain  ("cushion"  of  the  epiphysis,  velum  trans- 
versum,  paraphysis?)    (p.  424  and  Fig.  364). 

From  the  above  it  is  evident  that  at  the  close  of  the  fifth  week  the  rudiments 
of  the  various  parts  of  the  diencephalon  are  already  well  marked.  These 
rudiments  are  principally  indicated  by  foldings  of  the  walls,  there  being  no  very 
strongly  marked  differences  of  thickness  except  the  early  differentiation  between 
the  median  and  lateral  plates.  From  this  time  on,  both  general  and  local 

Lamina  terminalis 


Cavity  of  ant.  olfact.  lobe 

Anterior  arcuate  fissure 

Cavity  of  post,  olfact.  lobe 

Chorioid  fold 

Hippocampal  fissure 


Lateral  geniculate  body 


Pineal  region 


Ant.  corp.  quad.  (ant.  colliculus) 
(extending  forward 
into  ant.  brachium) 


Angulus  praethalamicus 


(a)  (b) 
(c) 


Corpus  striatum 


Roof  plate  of  diencephalon 


FIG.  426. — Dorsal  view  of  a  model  of  the  brain  of  a  13.6  mm.  human  embryo  (beginning  of  6th 
week).  The  dorsal  part  of  the  pallium  on  each  side  has  been  removed.  Compare  with 
Figs.  427  and  428 .  His. 

thickenings  of  the  lateral  walls  occur.  This  indicates  a  rapid  proliferation 
of  the  cells,  especially  a  differentiation  of  the  nerve  cells  and  consequent  forma- 
tion of  masses  of  gray  and  white  matter.  Another  factor  affecting  the  dien- 
cephalon is  the  subsequent  growth  backward  over  it  of  the  cerebral 
hemispheres. 

During  the  second  month,  the  lateral  walls  become  thickened,  forming 
a  prominence  on  the  inner  surface  of  each  side.  This  reduces  much  of  the 
cavity  of  the  third  ventricle  to  a  cleft  and  in  the  third  or  fourth  month  a  fusion  of 


THE  NERVOUS  SYSTEM. 


505 


a  portion  of  these  two  projections  takes  place,  forming  the  commissura  mollis 
or  massa  intermedia.     The  condition  at  this  stage  is  shown  in  Fig.  429.     Later 


Ant.  corp.  quad. 


Diencephalon 


Tegmental 
swelling 

Mammillary 
body 

Tuber 
cinereum 


Pallium 


Beginning  of 
fossa  Sy»vii 

Ant'  "I  olfact. 
Post.jlobe 


Optic  stalk 


Infundibulum       Hypophyseal  pouch. 

FIG.  427. — Lateral  view  of  the  model  of  the  brain  of  a  13.6  mm.  human  embryo  (beginning  of  6th 
week).     F,  Beginning  of  frontal  lobe;  T,  beginning  of  temporal  lobe.     His. 

this  protrusion  thrusts  the  lateral  structures  above  described  (the  pulvinar, 
geniculate  bodies  and  brachia)  to  the  side,  the  cavity  of  the  lateral  geniculate 

Eplthalnnius  (Corpus  pfneale)  Mctathalamus  (Corpora  genlculata) 


Thalanuis 


Fissura 
chorioidea 


Pallium 


Rhiuencephalon 

Corpus  striatu 
Sulcns  hypothalainicus 

Hypothal 
Chiasma 


Corpora  quaclrigemina 


..Pedunculus  cerebrJ 


FlG.  428. — From  a  model  of  the  brain  of  a  13.6  mm.  human  embryo,  right  half, 
seen  from  the  left  side.     His,  Spalt'eholz, 

body  being  obliterated.     The  prominence  itself  extends  to  the  tegmental  swell- 
ing (see  Figs.  4  2 9-30)  and  there  thus  arises  the  possibility  of  direct  connections 


506 


TEXT-BOOK  OF  EMBRYOLOGY. 


between  these  two  structures.     There  can,  then,  be  distinguished  in  the  dien- 
cephalon  three  regions,  a  hypothalamic  region,  as  already  described,  an  epithala- 


Hippocampal 
fissure 


Chorioid  fissure 
Angulus  prjethalamicu 

Foramen  of  Mon 

Ant.  arcuate  fissure 

Preterminal  area 

Ant.  olfact.  lobe 

Olfactory  nerve 

Post,  olfact.  lobe 


Hypothalamic  region 
Mammillary  region 


Lamina  terminalis 


FIG.  429. — Median  sagittal  section  of  the  brain  of  a  7^  weeks'  human  embryo.  Aq.  S.,  Aquaeductus 
Sylvii;  C.  c.,  fold  between  mid-  and  interbrain;  C.m.,  commissura  mollis;  C.  s.,  corpus  stri- 
atum;  H.  b.,  tegmental  swelling;  R.g.,  geniculate  recess;  R.  i.,  recessus  infundibuli;  R.  o., 
recessus  (prae-?)  opticus;  S.h.,  habenular  evagination;  5.  M.}  sulcus  hypothalamicus;  S.p., 
pineal  evagination;  T.  T.,  thalamus.  His. 

mic  region  comprising  the  pineal  body,  ganglia  habenulae  and  related  structures, 
and  finally  the  thalamus  proper.     In  the  latter,  the  geniculate  bodies  already 


Epitbalamus  (Corpus  p!ueale» 

Met  a  thalamus 
(Corpora  geniculaia) 


Corpus  striatum  \ . 


Rhinenceplialon   ^ 
Pars  optica  hypothalami     /'  / 
Chiasma  opticum'  y' 
Hypophysis'' 

Pars  maraillaris  bypothalami* 

Pons  [Varolfl- 


Corpora  quadrigrmlna 


•  Pedunculus  ceiebri 


Cerebellimi 
Fossa  rhomboidea 


Medulla  oblongata 


FIG.  430. — Brain  of  a  human  foetus 'in  the  3d  month,  right  half,  seen  from  the  left.     His,  Spalteholz, 


mentioned  constitute  a  metathalamic  portion,  while  the  portion  derived  from 
the  thickened  part,  which  is  continuous  anteriorly  with  the  corpus  striatum, 


THE  NERVOUS  SYSTEM. 


507 


differentiates  various  nuclei,  especially  those  which  receive  the  general  somatic 
sensory  fibers  (medial  lemniscus  or  fillet),  and  other  nuclei  in  relation  to  definite 
centers  of  the  pallium.  The  thalamus  is  thus  strongly  developed,  owing  to  its 
containing  the  nuclei  which  receive  the  general  sensory  (ventro-lateral  nuclei), 
acoustic  (medial  geniculate  bodies),  and  optic  (lateral  geniculate  bodies) 
systems  of  fibers  and  which  in  turn  send  fibers  (thalamic  radiations)  to  the  pallium. 
These  thalamic  nuclei  do  not  receive  fibers  probably  until  after  the  middle  of  the. 
second  month.  About  this  time  the  thalamic  radiations  begin  to  be  formed 
from  the  thalamic  nuclei  and  grow  toward  the  corpus  striatum  which  they  reach 
toward  the  end  of  the  second  month.  With  the  first  appearance  of  the  coi  tical 


TbaJamus 


Bbinencephalon 

Recessus  opticus 

Chiasma  opticnm 
Recessus  infundibuli 

Infundibulum 

Pedunculus  cerebri 


Velum  medal- 
lare  antenu» 


Cerebellum 
Ventriculus  quartus 
-      .  Meduua  oblongata 
on\ 


FIG.  431.— Adult  human  brain,  right  half,  seen  from  the  left,  partly  schematic.     Spalteholz. 


layer  of  the  developing  neopallium  (see  p.  512)  they  penetrate  the  corpus  stria- 
tum and  pass  to  the  cortex,  forming  the  beginning  of  the  internal  capsule,  and 
corona  radiata.  It  has  already  been  pointed  out  (p.  437)  that  the  great  develop- 
ment of  the  thalamus  and  its  radiations  is  more  recent  phylogenetically  and  is 
due  to  the  newly  acquired  connections  with  the  neopallium. 

Before  the  development  of  these  neopallial  connections,  other  tracts  have 
begun  to  appear  which  represent  older  epithalamic  and  hypothalamic  connec- 
tions existing  practically  throughout  the  Vertebrates  (pp.  437  and  438) .  Some 
of  the  hypothalamic  connections  are  the  mammillo-tegmental  fasciculus  which 
appears  early  in  the  second  month,  the  thalamomammillary  fasciculus 
(Vicq  d'Azyr's  bundle),  which  appears  later,  and  the  bundles  from  the  rhinen- 
cephalon  (p.  475)  and  archipallium  (columns  of  the  jornioc,  middle  of  fourth 
month,  p.  521).  In  the  hypothalamic  region  is  also  differentiated  the  corpus 


508 


TEXT-BOOK  OF  EMBRYOLOGY. 


Luysii,  connected  by  fiber  bundles  with  the  corpus  striatum  and  tegmentum. 
Epithalamic  connections  are  represented  by  bundles  from  anterior  olfactory 
regions  (stria  medullaris,  seventh  week),  by  the  commissure,  habenularis,  and  by 
bundles  to  caudal  regions  (fasciculus  retroflexus  of  Meynert  to  the  interpedun- 
cular  ganglion,  middle  of  second  month),  (pp.  437  and  475.)  The  posterior 
commissure  fibers  are  formed  early  in  the  second  month  in  the  fold  between 
•  mid-  and  inter-brain  (Fig.  429).  (Fig.  432)- 


01. 


FIG.  432. — Construction  of  the  brain  of  a  19  mm.  human  embryo  (7^  weeks),  showing  the  stage  of 
development  of  some  of  the  principal  fiber-systems.  His. 

C.C.,  posterior  commissure;  F.  s.,  tractus  solitarius;  F.  t.,  fasciculus  spinalis  trigemini  (spinal  V); 
K,  nuclei  of  dorsa!  funiculi  of  cord;  L.,  medial  longitudinal  fasciculus;  M.,  fasciculus  retro- 
flexus of  Meynert;  Ma.,  mammillary  bundle;  n.  i.,  nervus  intermedius;  O.,  olive;  Ol.,  olfactory 
nerve;  S.,  fillet;  St.,  stria  medullaris  thalami;  T.,  thalamic  radiation;  T.  o.,  tractus  opticus; 
V,  Gasserian  ganglion;  VII,  facial  nerve  and  geniculate  ganglion;  VIII,  ganglia  of  acoustic 
nerve;  IX,  N.  glossopharyngeus;  X,  N.  vagus. 


The  Telencephalon  (Rhinencephalon,  Corpora  Striata  and  Pallium) . 

To  understand  the  development  of  this  part  of  the  brain  it  is  necessary  to 
keep  firmly  in  mind  certain  relations  which  are  laid  down  at  a  comparatively 
early  stage.  Some  of  these  relations  are  shown  in  the  diagram  of  the  inner  sur- 
face of  a  model  of  a  brain  of  four  weeks.  At  this  stage  the  pallium  is  unpaired, 
i.e.,  there  is  no  median  furrow  separating  the  two  halves  of  the  pallial  expansion. 
The  various  boundaries  of  the  pallium  in  one  side  are  (i)  the  median  line  uniting 


THE  NERVOUS  SYSTEM. 


509 


the  two  halves  of  the  pallial  expansion  (Fig.  433,  be) ;  (2)  the  boundary  line  or 
line  of  union  with  the  thalamus  lying  caudally  (pallio-thalamic  boundary) 
(Fig-  433>  cd) ;  (3)  the  boundary  between  pallium  and  corpus  striatum  (strio- 
pallial  boundary)  (Fig.  433,  bd) .  The  boundaries  of  the  future  corpus  striatum 
are  (i)  the  median  (Fig.  433,  ab),  (2)  the  strio-pallial  (Fig.  433,  bd),  (3)  the 
strio-thalamic  or  peduncular  (Fig.  433,  de)  and  (4)  the  strio-hypothalamic  (Fig. 
433,  a<0-  The  internal  prominence  which  is  the  rudiment  of  the  corpus 
striatum,  has  three  limbs  or  crura,  (i)  a  ridge  proceeding  forward  (anterior 
crus),  which  corresponds  externally  to  the  furrow  (external  rhinal  furrow) 
foiming  the  lateral  boundary  of  the  anterior  olfactory  lobe,  (2)  a  middle  crus 


Thalamus 


Prosenccphalon 
(Fore  -brain) 


Rhinencephalotr-- 
Corpus  stria 


Pars  optica  liypothalam 
Pars  niainillaris  hypothalami    .. 
Pens  [Varolif 


Pars  ven  trails  - 
Sulcus  limitiins- 


Corpora  quadrigemfaa 


(-.-..  Peduiiculus  cerebri 

Brachium  conjunctivum 
and  velam  medullare 

auterius 


/Rhomb- 
4nceprialon 
'••'"  (Lozenge- shaped 
.brain) 

Cerebellum 


FIG.  433. — From  a  model  of  the  brain  of  a  human  embryo  at  the  end  of  the  first  month,  right 
half,  seen  from  the  left.     His,  Spalteholz. 


corresponding  to  the  constriction  separating  the  two  olfactory  lobes,  and  (3)  a 
posterior  crus  corresponding  to  the  posterior  boundary  of  the  posterior  olfactory 
lobe.  This  latter  is  merged  with  the  earlier  furrow  separating  the  telencephalon 
from  the  thalamus  and  hypothalamus  (peduncular  furrow).  What  may  be 
called  the  main  body  of  the  corpus  striatum,  from  which  these  limbs  radiate, 
soon  becomes  expressed  externally  by  a  shallow  depression  in  the  lateral  sur- 
face of  the  hemispheres  immediately  dorsal  to  the  olfactory  lobes.  This 
depression  is  the  first  indication  of  the  fossa  Sylvii  (Fig.  427). 

The  boundaries  of  the  pallial  hemisphere  above  indicated  are  identical 
with  the  boundaries  of  the  future  foramen  of  Monro. 

The  median  lamina  uniting  the  two  halves  of  the  pallium  and  the  two  corpora 
striata  may  be  termed  the  lamina  terminalis  and  represents  the  roof  plate  and 
floor  plate  of  this  region.  The  point  of  meeting  of  the  roof  plate  and  floca 


510 


TEXT-BOOK  OF  EMBRYOLOGY. 


plate  at  the  end  of  the  tube  is  often  taken  to  be  at  the  recessus  neuroporicus ; 
and  the  lamina  terminalis  or  end  wall  of  the  neural  tube,  more  strictly  speaking, 
is  limited  to  the  median  wall  ventral  to  this  point.  Here  it  will  be  understood 
as  including  the  median  wall  to  the  point  where  the  pa'llio-thalamic  boundary 
begins,  marked  later  |py  the  angulus  prathalamicus  of  His  (see  p.  517  and  Fig. 
442). 

Rhinencephalon.— The  term  rhinencephalon  is  a  convenient  one  for 
those  basal  structures  of  the  fore-brain  which  are  in  most  intimate  connection 
with  the  olfactory  nerve.  The  term  has  been  extended  by  some  to  include 
the  pallial  olfactory  structures.  For  descriptive  purposes  it  is  here  used  in 
the  more  limited  sense. 

At  the  fourth  week,  as  already  indicated  (p.  5 16 .  Fig.  434) ,  there  is  a  slight  longi- 
tudinal furrow  on  the  external  surface,  marking  the  ventral  limit  of  the  pallial 


FIG.  434. — Lateral  view  of  outside  of  brain  shown  in  Fig.  433.     His. 


eminence.  The  part  of  the  brain  ventral  to  this  furrow  is  the  rhinencephalon, 
Somewhat  later  the  latter  becomes  better  marked  off,  the  fissure  forming  its 
boundary  on  the  lateral  surface  being  the  external  rhinal  fissure  (Fig.  424). 
Later  the  mesial  side  is  also  marked  off  by  an  extension  of  the  fissure  around 
on  the  mesial  side  (medial  rhinal  fissure)  and  also  by  a  notch,  the  incisura 
prima,  a  continuation  of  which  later  ascends  along  the  middle  part  of  the 
median  surface  of  the  hemispheres  and  is  known  as  the  (interior  arcuate  fissure 
(fissura  prima  of  His).  (Fig.  442.)  The  existence  of  a  fissura  prima  in  early 
stages,  however,  is  doubtful.  At  about  this  time,  the  rhinencephalon  shows  a 
beginning  division  into  anterior  and  posterior  portions,  the  anterior  and  posterior 
olfactory  lobes,  the  whole  structure  assuming  a  bean-shape  (comp.  p.  512) 
(Fig.  427).  On  the  lateral  surface  immediately  above  this  constriction  is  the 
beginning  concavity  in  the  lateral  surface  of  the  hemispheres  which  marks  the 


THE  NERVOUS  SYSTEM. 


511 


earliest  appearance  of  the  fossa  Sylvii.  The  external  rhinal  fissure,  as  it 
becomes  more  pronounced,  may  be  regarded  as  an  extension  forward  of  the 
fossa  (anterior  crus  of  the  corpus  striatum) .  On  the  mesial  surface  the  incisura 
prima  marks  this  constriction.  With  the  further  curvature  of  the  hemispheres, 
the  anterior  lobe  becomes  bent  back  under  the  posterior  (third  month),  but 
later  is  again  directed  forward.  It  contains  a  diverticulum  of  the  fore-brain 
"cavity.  The  cavity  of  the  posterior  lobe  is  not  so  well  marked  off  and  is 
bounded  by  the  corpus  striatum  and  the  inward  projection  of  the  incisura 
prima.  (Figs.  424,  425,  427,  428  and  442.) 

The  olfactory  nerve  at  the  end  of  five  weeks  has  reached  the  anterior  lobe 
on  its  ventral  and  posterior  side.  The  lobe  develops  into  the  receptive  centei  5  for 
the  nerve — the  olfactory  bulb;  into  the  stalk  in  which  the  secondary  olfactory 


Gyrus  olfact.  medialis 

Gyrus  olfact.  medius 

Gyrus  diagonalis 


Cerebellum 


Insula 

Gyrus  olfact.  lat. 

Gyrus  ambiens 
Gyrus  semilunaris 


Olive 


FIG.  435. — Ventral  view  of  the  brain  of  human  foetus  at  the  beginning  of  the  4th  month.  Kollmann. 

tract  proceeds;  and  also  into  a  triangular  area  where  the  tract  divides — the 
trigonum.  The  posterior  olfactory  lobe  develops  into  the  anterior  perforated 
space  and  an  eminence  known  as  the  lobus  pyriformis  which  becomes  reduced 
later  (comp.  Fig.  3  70,  G  and  H).  From  it  is  developed  the  gyms  olfactorius  later- 
alis,  connected  with  the  lateral  division  of  the  olfactory  tract  and  thegyri  ambiens 
and  semilunaris  (Fig.  435).  On  the  mesial  wall,  the  posterior  lobe  is  especially 
connected  with  the  region  between  the  anterior  arcuate  fissure  and  the  lamina 
terminalis  (trapezoid  area  of  His,  parolfactory  or  preterminal  area  of  G.  Elliot 
Smith)  (Fig.  442).  Part  of  this  mesial  region  represents  the  anterior  portion 
of  the  archipallium  (comp.  Fig.  370,  G  and  H  and  p.  482). 

Corpora  Striata  and  Pallium. — The  leading  feature  of  the  development 
of  this  part  of  the  brain  is  the  great  expansion  of  the  pallial  hemispheres.  That 
part  of  the  brain  wall  marked  externally  by  the  fossa  Sylvii  and  internally  by  the 
body  of  the  corpus  striatum,  and  especially  that  part  where  the  corpus  striatum 


512  TEXT-HOOK  OF  EMBRYOLOGY. 

is  continuous  with  the  thalamus  (peduncular  part) ,  may  be  considered  as  a  fixed 
point  from  which  the  pallial  walls  expand  in  all  directions,  anteriorly,  dorsally 
and  posteriorly,  i.e.,  in  both  transverse  and  longitudinal  directions.  At  first, 
this  expansion  causes  the  pallial  hemispheres  to  assume  a  bean-shape  with  the 
hilum  at  the  fixed  point  (Fig.  427).  The  anterior  end  curves  downward  and 
forms  the  frontal  lobe  with  its  enclosed  cavity  (anterior  horn  of  the  lateral  ven- 
tricle). The  posterior  end  curves  downward  caudally  and  forms  the  temporal 
lobe  with  the  descending  horn  of  the  lateral  ventricle.  At  the  same  time,  owing 
to  the  great  expansion  in  a  transverse  plane  of  each  pallial  eminence,  the 
median  lamina  uniting  them  (Figs.  425  and  426)  not  sharing  in  this  growth, 
there  are  formed  the  hemispheres  with  their  cavities,  the  lateral  ventricles,  and 
the  great  longitudinal  fissure  between  the  hemispheres.  Later,  vascular 
mesodermal  tissue  fills  this  fissure,  forming  the  falx  cerebri.  The  paired 
cavities  of  the  pallium  are  connected  with  the  unpaired  end-brain  cavity  (aula) 
by  the  foramina  of  Monro,  the  boundaries  of  which  are  the  same  as  those  of  the 
pallium  described  above  (p.  508). 

At  first  the  walls  of  the  telencephalon,  like  those  of  other  parts  of  the  tube, 
are  epithelial  in  character  and  nearly  uniform  in  thickness.  By  proliferation 
there  is  formed  a  several-layered  epithelium  differentiated  into  an  inner 
nuclear  layer  and  an  outer  marginal  layer.  Later  a  mantle  layer  is  differen- 
tiated. The  hemispheres  are  late  in  development  and  until  the  end  of  the 
second  month  the  walls  are  thin  and  simply  show  the  above  three  layers. 
Toward  the  end  of  the  first  month  a  greater  activity  in  cell  proliferation  takes 
place  in  the  basal  portion  of  the  telencephalon  which  thickens  into  the  corpus 
striatum.  At  eight  weeks  there  first  appears  on  the  external  surface  of  the 
corpus  striatum,  a  cortical  layer  of  cells  lying  next  the  marginal  layer  and  sepa- 
rated from  the  inner  layer  by  an  intermediate  layer  comparatively  free  of  cells 
and  known  as  the  fibrous  or  medullary  layer  (see  p.  524).  The  differentiation 
thus  begun  extends  gradually  around  the  circumference  of  the  hemispheres 
until  the  mesial  surface  is  reached.  This  differentiation  permanently  ceases 
at  the  medial  pallial  margin.  The  cortical  layer  does  not  extend  as  far  as 
the  medullary  layer,  thus  leaving  an  uncovered  medullary  layer  on  the  mesial 
hemisphere  wall.  As  a  result  of  this,  there  is  in  this  region,  passing  toward 
the  median  line,  (i)  a  region  covered  with  a  cortical  layer  (limbus  corticalis 
of  His);  (2)  an  uncovered  medullary  layer  (limbus  medullaris);  (3)  a  fibrous 
transitional  zone  (the  t&nia)  passing  into  (4)  a  membranous  zone,  the  roof 
plate. 

This  process  resembles  that  taking  place  in  other  parts  of  the  neural  tube, 
in  which  there  is  the  same  progressive  development  from  the  ventral  portion 
of  the  lateral  wall  to  the  dorsal  border  of  the  same,  where  the  latter  passes  into 
the  roof  plate  which  is  either  ependymal  or  expanded  into  a  thin  membrane. 


THE  NERVOUS  SYSTEM.  513 

The  longitudinal  growth  of  the  hemispheres  naturally  affects  the  form  of  a 
number  of  its  structures.  As  already  mentioned,  this  growth  consists  in  an 
elongation  around  a  fixed  point,  which  may  be  regarded  as  located  on  its  ven- 
tral border,  the  result  of  this  being  a  curving  down  in  front  and  behind  this 
point.  This  is  especially  marked  in  the  caudal  half  which  thereby  becomes 
curled  first  ventrally  and  then  forward,  thus  forming  a  spiral.  This  growth  in 
length  is  interstitial,  i.  e.,  due  to  expansion  of  the  intermediate  parts,  and  pari 
passu  with  it  there  is  an  elongation  not  only  of  the  corpus  striatum  and 
structures  in  the  mesial  hemisphere  wall  (hippocampal  formation,  corpus  callo- 
sum,  chorioid  plexus  of  lateral  ventricle),  but  also  of  adjacent  thalamic  struc- 
tures (stria  terminalis  or  semicircularis) ,  as  described  later. 


R.i 


FIG.  436. — View  of  the  inside  of  the  lateral  wall  of  anterior  part  of  fore-brain.     Human  embryo 

of  about  4^  weeks.     His. 

C,  Corpus  striatum;  H,  pallium;  h.  R,  posterior  olfactory  lobe;  L,  lamina  terminalis;  O,  re- 
cessus  (prae-?)  opticus;  R.  i.,  recessus  infundibuli;  S.  M..  sulcus  hypothalamicus;  St,  hypo- 
thalamus;  T,  thalamus;  v.  R.,  anterior  olfactory  lobe. 

The  early  divisions  of  the  corpus  striatum  have  been  mentioned,  and  also 
the  relations  of  its  parts  with  the  rhinencephalon.  The  anterior  end  of  the 
corpus  striatum  at  this  period  and  later  shows  a  longitudinal  division  into 
three  portions,  a  lateral,  a  middle  and  a  medial,  due  to  the  original  division 
into  three  limbs  described  above  (p.  508).  (Figs.  436,  437,  and  438.)  With 
the  elongation  backward  of  the  hemisphere  the  corpus  striatum  also  becomes- 
elongated,  being  drawn  out  and  curled  around  the  peduncle  or  stalk  of  the 
hemisphere  and  forming  a  thickening  along  the  elongated  wall.  This  caudal 
prolongation  of  the  striatum  is  its  cauda  (tail)  and  extends  to  the  tip  of  the  in- 
ferior horn  (Figs.  437  and  438).  The  medial  portion  of  the  corpus  striatum 
forms  a  triangular  projection  (Figs.  426  and  428)  the  edge  of  which  is  directed 
toward  the  foramen  of  Monro. 


514 


TEXT-BOOK  OF  EMBRYOLOGY. 


i;;The   stalk   of   the  hemisphere  has  already  been  mentioned  as  including 
that  part  where  corpus  striatum  and  thalamus  meet.     In  this  region,  according 


v.ttl.. 


FIG.  437. — View  of  inside  of  the  lateral  wall  of  lateral  ventricle  of  a  human  foetus  at  beginning 

of  third  month.     His. 

Bb,  bulbus  olfactorius;  C.  L,  lateral  limb  of  corpus  striatum;  C.m.,  medial  segment  (consisting  of 
the  middle  and  inner  limbs)  of  the  corpus  striatum.  The  furrow  between  these  two  parts 
opens  into  the  anterior  olfactory  lobe;  hRl.,  posterior  olfactory  lobe;  L./.,  frontal  lobe;  L. o.y 
occipital  lobe;  Og.}  olfactory  nerve;  R.  i.,  recessus  infundibuli;  R.  o.,  recessus  (prae-?)  opticus; 
St.,  stalk  of  hemisphere  (strio-thalamic  junction);  V.I.,  lateral  ventricle;  v.Rl.+Bb,  anterior 
olfactory  lobe. 

to  some,  there  is  a,  fusion  of  the  striatum,  the  medial  wall  of  the  hemisphere  and 
the  anterior  part  of  the  thalamus.     According  to  others,  the  increase  in  bulk  of 


Medial  wall 


Chorioid  plexus  of 
lateral  ventricle 


Lamina  terminalis — 9 

Taenia  thalami — \ 
Thalamus 

Habenula 

Trigonum  subpineale 
Cerebellum 

Myelencephalon 


Lateral  ventricle 
audate  nucleus  (head) 

Medial  wall 
Caudate  nucleus  (tail) 
Pineal  body 
Median  sulcus 


Mesencephalon 
Fourth  ventricle 


FIG.  438. — Dorsal  view  of  the  brain  of  a  3  months'  (45  mm.)  human  foetus.    The  dorsal  part  of  each 
cerebral  hemisphere  has  been  removed.     Kollmann. 

this  region  is  produced  by  a  simple  thickening  of  the  walls,  thus  causing  a  flat- 
tening out  or  shallowing  of  the  grooves  marking  the  junctions  of  striatum  and 


THE  NERVOUS  SYSTEM. 


515 


FIG.  439. — i,  2  and  3,  Schematic  horizontal  sections  through  human  embryonic  fore-brains  at  dif- 
ferent stages  of  development;  4,  vertical  section  through  fore-brain  at  about  same  stage  as  i. 
Goldstein. 

a,  That  part  of  the  lateral  ventricle  lying  between  the  corpus  striatum  and  the  junction  of  medial 
hemisphere  wall  and  thalamus  (leading  into  the  inferior  horn);  b,  furrow  or  trough  between 
mesial  hemisphere  wall  and  thalamus,  produced  by  backward  extension  of  hemisphere;  c.  /., 
internal  capsule;  P.M.,  foramen  of  Monro;  &,  external  surface  at  junction  of  mesial  hemi- 
sphere wall  and  thalamus;  Str.,  corpus  striatum;  Th.,  thalamus;  U,  place  where  mesial  hemi- 
sphere wall  continues  into  the  thalamus  wall  (junction  of  hemisphere  wall  and  thalamus)  ; 
U1,  place  where  mesial  hemisphere  wall  is  continuous  with  lateral  hemisphere  wall. 

In  I,  owing  to  the  thickening  of  U  and  growth  of  the  corpus  striatum,  these  two  are  brought 
into  apposition,  as  indicated  by  the  dotted  lines  on  the  right,  and  apparently  fuse,  obliterating 
a  and  producing  the  condition  shown  in  2  and  3.  In  2  and  3  the  position  of  the  former 
space  a  is  indicated  by  the  dotted  lines  a — a'  By  comparison  with  4,  it  will  be  seen  that  this 
obliteration  by  apparent  fusion  is  actually  produced  by  a  filling  up  from  the  bottom  of  a  (in- 
dicated faintly  by  dotted  lines  on  the  right  in  4).  The  thickening  of  thfe  walls  at  this  region 
also  produces  a  shallowing  of  b  (indicated  by  dotted  lines  on  the  right  in  i).  The  principal 
cause  of  this  general  thickening  is  the  passage  of  the  fibers  of  the  thalamic  radiation  to  the 
hemispheres  and,  later,  of  fibers  from  hemisphere  to  pes,  forming  the  internal  capsule  (4,  2 
and  3). 


516  TEXT-BOOK  OF  EMBRYOLOGY. 

thalamus  on  the  ventricular  surface,  and  between  medial  hemisphere  wall  and 
thalamus  externally  (Fig,  439).  The  effect  is  much  the  same  whether  accom 
plished  by  apposition  and  fusion  or  by  interstitial  thickening,  massive  con- 
nections being  formed  which  consist  mainly  of  fibers  connecting  hemispheres 
and  thalamus,  the  foramen  of  Monro  at  the  same  time  being  changed  in  form 
to  a  slit.  From  the  metathalamic  region  the  fibers  of  the  optic  and  acoustic 
pathways  grow  forward  into  the  hemispheres  (see  also  p.  507) .  entering  more 
caudally  and  forming  the  retro-  and  sublenticular  portions  of  the  internal  capsule 
(comp.  p.  507).  That  part  of  the  thalamic  radiation  from  the  anterior  portion 
of  the  thalamus  (fillet  pathway)  also  forms  a  part  of  the  internal  capsule  as 
described  on  p.  507.  Later,  the  internal  capsule  is  completed  by  the  growth 


Medial  wall 


Caudate  nucleus-  f  _alr  ^Rlb!""  ~  Chorioid  fissure 

Internal  capsule  ~—f  ^Bfe  9^ M-esencephalon 

Lentiform  nucleus 

Lateral  wall       ,  _,_ __         _^ 

Pedunculus  cerebri 


Chiasma  « 

Recessus  infundibuli 

Myelencephalon 


FIG.  440. — Lateral  view  of 'the  brain  of  a  3  months'  (42  mm.)  human  foetus.     The  lateral  wall  of 
the  left  cerebral  hemisphere  has  been  removed.     His,  Kollmann. 

from  the  pallium  of  descending  fibers  from  the  neopallial  cortex,  through 
the  striatum  to  the  pes.  By  these  various  traversing  fibers  the  striatum  is 
divided  into  the  nucleus  lenticularis  or  lentiformis  and  the  nucleus  caudatus. 
The  posterior  arm  of  the  internal  capsule  is  formed  by  fibers  passing  between 
and  thus  separating  thalamus  and  lenticularis  (Figs.  439  and  440). 

THE  ARCHIPALLIUM. 

During  the  fifth  week,  following  the  stage  shown  in  Figs.  433  and  434, 
the  pal  Hal  evaginations  or  hemispheres  have  become  much  more  pronounced 
and  consequently  the  foramina  of  Monro  much  better  defined.  A  comparison 
will  show  that  the  boundaries  of  the  foramen  of  Monro  are  essentially  unaltered. 
Anteriorly  it  is  bounded  by  the  medial  wall  connecting  the  two  hemispheres, 
posteriorly  by  the  boundary  between  pallium  and  thalamus,  ventrally  by  the 
corpus  striatum  and  junction  of  it  and  thalamus  (Figs.  425  and  441). 


THE  NERVOUS  SYSTEM. 


517 


At  the  beginning  of  the  sixth  week  the  foramen  of  Monro  has  changed  some- 
what in  shape.  The  pallio-thalamic  part  of  its  boundary  passes  forward  and 
forms  the  above-mentioned  (p.  5 10)  acute  angle  (angulus  praethalamicus)  with 
that  part  of  the  wall  uniting  the  two  hemispheres  (lamina  terminalis).  The 
latter  wall  descends  to  the  region  of  the  optic  recess.  The  inferior  part  of  the 
foramen  is  partly  closed  by  the  medial  part  of  the  corpus  striatum  as  already 
described.  (Comp.  Figs.  441,  426  and  428.)  In  the  ependymal  mesial  wall 
of  the  hemispheres  just  below  the  taenia,  described  above,  there  arises  a  folding 
inward,  which  begins  anteriorly  near  the  angulus  praethalamicus  and  proceeds 
caudally  along  the  upper  (pallio-thalamic)  border  of  the  foramen  of  Monro. 
This  infolding  is  the  chorioid fissure.  In  the  ependymal  mesial  wall  there  are 


Pallium 


Foramen  of  Monro 
Corpus  striatum 


Eye 


III  ventricle 
Chorioid  fissure 


Mesodermal  tissue, 
forming  later  the 
chorioid  plexus. 


Pharynx 
Tongue 


FIG.  441 . — Transverse  section  through  fore-brain  of  a  16  mm.  embryo  (six  to  seven  weeks).     His. 

now  the  following:  limbus  chorioideus  (the  infolded  part)  and  a  small  strip  of  the 
ependyma  wall  below  the  fold,  the  lamina  infrachorioidea  (Fig.  442).  This 
invagination  soon  becomes  very  deep,  resulting  in  the  formation  of  a  double- 
layered  ependymal  fold  (the  chorioid  fold,  plica  chorioidea)  lying  in  the  lateral 
ventricle  over  the  corpus  striatum  (Figs.  441,  426  and  444).  Later,  vascular 
mesodermal  tissue  passes  in  from  the  falx  between  the  lips  of  this  fold  and 
thereby  forms  the  chorioid  plexus  of  the  lateral  ventricles.  The  chorioid  fissure 
is  at  first  quite  short,  but  becomes  elongated  (Fig.  443)  with  the  above-described 
posterior  elongation  of  the  hemisphere  of  which  it  is  a  part,  and  thus  extends 
into  the  inferior  horn  of  the  temporal  lobe.  (Figs.  443  and  444.) 

Toward  the  end  of  the  second  month,  according  to  some  authorities  (His) , 
but  not  until  considerably  later,  according  to  others  (Hochstetter,  Goldstein), 
another  furrow  appears  in  the  limbus  corticalis  above  and  parallel  to  the  chori- 


518 


TEXT-BOOK  OF  EMBRYOLOGY. 


oid  fissure,  and  known  as  the  posterior  arcuate  fissure.  This  fissure  does  not 
extend  at  first  as  far  forward  as  the  chorioid,  but  extends  farther  caudally, 
arching  downward  in  the  temporal  lobe  around  the  caudal  end  of  the  chorioid 
fissure  (Fig.  443) .  The  posterior  arcuate  fissure  is  a  total  fissure,  involving  the 
whole  wall  and  producing  a  fold  on  the  inner  surface  of  the  medial  hemisphere 
wall  (plica  arcuata).  The  temporal  or  caudal  part  of  this  whole  formation 
persists  in  the  adult  without  much  further  change.  The  fissure  here  becomes 
the  hippocampal  fissure  separating  the  fascia  dentata  from  the  gyrus  hippocam- 
pus; the  part  rolled  in  by  the  hippocampal  fissure  produces  the  eminence  in 
the  lateral  ventricle  known  as  the  cornu  ammonis  or  hippocampus  major; 


Frhl-' 


vRh    Vmr  Fstr 


hRh 


FIG.  442. — Diagram  of  a  graphic  reconstruction  of  the  mesial  hemisphere  wall  of  a  16  mm.  human 
embryo  (about  six  weeks).  His,  Ziehen.  Cavities  are  dotted,  cut  surfaces  are  lined. 

Apt,  Angulus  praethalamicus;  Atr,  preterminal  area;  Fpr,  anterior  arcuate  fissure  (fissura  prima); 
Frhl,  mesial  termination  of  lateral  rhinal  fissure;  hRh,  posterior  olfactory  lobe  (tuberculum 
olfactorium  +  substantia  perforata  anterior) ;  Lt,  lamina  terminalis  (lined) ;  Vmr,  depression 
between  the  two  olfactory  lobes;  vRh,  anterior  olfactory  lobe  (bulbus  olfactorius  +  tractus 
olfactorius  +  trigonum  olfactorium). 

the  edge  of  the  limbus  corticalis  forms  the  fascia  dentata;  the  limbus  medullaris 
or  exposed  fibrous  part  is  thefimbria  which  is  continued  by  its  thinning  edge 
or  tania  fimbria  into  the  ependymal  or  epithelial  portion  (lamina  chorioidea) 
of  the  chorioid  plexus  of  the  lateral  ventricle.  The  chorioid  plexus  is  attached 
by  the  taenia  chorioidea  and  lamina  infrachorioidea  (here  the  lamina  affixa)  to 
the  brain  wall,  usually  near  the  junction  of  corpus  striatum  and  thalamus, 
thereby  forming  a  part  of  the  wall  of  the  inferior  horn  of  the  lateral  ventricle. 
At  this  line  of  junction  of  thalamus  and  hemisphere  wall  is  formed  the  stria 
terminalis.  The  fimbria  is  continuous  anteriorly  with  the  posterior  pillar  of 
the  fornix.  (Fig.  444.) 

The  anterior  part  of  the  hippocampal  formation  above  described  undergoes 


THE  NERVOUS  SYSTEM. 

Corpus  callosum  Hippocampal  fissure 

} 


519 


Olfactory  stalk 


Lamina  terminal  is     | 
Anterior  commissure 
Beginning  anterior  column  of  fornix 


Hippocampal  fissure 
Chorioid  fissure 


FIG.  443. — Graphic  reconstruction  of  the  mesial  hemisphere  wall  of  a  human  foetus 

(fourth  month).     His,  from  Quain's  Anatomy. 

c  and  v,  Anterior  and  posterior  parts  of  pre terminal  area;  li,  lamina  infrachorioidea;  km,  limbus  or 
border  of  mesial  hemisphere  wall  (gyrus  dentatus  and  fimbria)  between  hippocampal  and 
chorioid  fissures;  P,  "  stalk  "  of  hemisphere. 


falx 


FIG.  444. — Diagram  of  a  transverse  section  through  the  fore-brain  of  a  human  foetus  (fourth 
month)  to  show  the  relations  of  the  margins  of  the  mesial  walls  of  the  hemispheres.  Hist 
from  Quain's  Anatomy. 

Cs.,  corpus  striatum;  fi.,  limbus  medullaris  (fimbria);  /a.,  limbus  corticalis  (gyrus  dentatus);  h.f.t 
hippocampal  fissure;  Th.,  thalamus 


520 


TEXT-BOOK  OF  EMBRYOLOGY. 


further  modifications,  due  principally  to  the  development  of  commissural  fibers 
in  this  region.  Some  of  these  commissural  fibers  connect  the  representatives 
on  each  side  of  the  hippocampus  (limbus  corticalis)  of  this  region,  forming  the 
fornix  commissure,  but  most  of  them  (corpus  callosum)  connect  the  rest  of  the 
cortical  areas  (neopallial  areas)  of  the  two  hemispheres. 

There  are  two  views  regarding  the  formation  of  these  commissures.  Ac- 
cording to  one  view,  the  first  commissural  fibers  appear  in  the  upper  (dorsal) 
part  of  the  lamina  terminalis.  The  latter  subsequently  expands  pari  passu 

Corpus  callosum      Callosal  (continuation  of  hippocampal)  fissure 
Fornix  (continuation  of  fimbria)     I       I  v 


Olfactory  stalk 
Optic  commissure  (chiasma 


Lamina  terminalis  | 
Anterior  commissure 

Uncus 


ippocampal  fissure 


FIG.  445. — Graphic  reconstruction  of  the  mesial  hemisphere  wall  of  a  120  mm.  foetus  (end  of  four 

months).     His,  from  Quain's  Anatomy. 
6,  Fimbria;  cs  ,  cavity  of  septum  pellucidum   ("fifth"  ventricle,  ventricle  of  Verga);  Icm,  limbus 

corticalis  (gyrus  dentatus);  P,  stalk  of  hemisphere;  v,  outline  of  cavity  of  hemisphere  (lateral 

ventricle). 

with  the  expansion  of  the  corpus  callosum.  The  commissural  fibers  are  thus 
confined  to  the  original  walls  connecting  the  two  hemispheres.  According  to 
the  other  view,  there  is  a  secondary  fusion  of  the  mesial  hemisphere  walls  and 
in  these  fusions  the  fibers  cross.  The  first  fibers  appear  during  the  third  month 
and  form  at  first  a  small  band  in  the  upper  part  of  the  lamina  terminalis  (Fig. 
443) .  These  fibers  come  partly  from  the  limbus  corticalis  (fornix  commissural 
fibers)  and  partly  from  other  parts  of  the  cortex  (callosal  fibers),  in  either  case 
traveling  along  the  intermediate  layer.  According  to  the  fusion  view,  the 
exposed  intermediate  layers  (limbi  medullares)  fuse  where  the  fibers  cross. 
This  fusion  can  easily  be  imagined  by  conceiving  the  opposite  surfaces  in 


THE  NERVOUS  SYSTEM. 


521 


question  to  be  brought  together  in  the  upper  part  of  Fig.  444.  It  is  more  prob- 
able, though,  that  not  only  the  first  fibers  cross  in  the  lamina  terminalis,  but 
that  the  later  ones  also  cross  in  extensions  of  the  latter.  There  are  three  views 
regarding  the  further  development  of  the  corpus  callosum.  The  first  is  that 
all  parts  are  represented  at  this  stage,  future  growth  being  by  intussusception  of 
fibers ;  the  second  is  that  the  part  first  formed  represents  the  genu,  the  rest  being 
added  caudally;  the  third  (His)  is  that  this  first  formed  part  represents  the 
middle  portion  of  the  callosum,  both  anterior  (genu  and  rostrum)  and  posterior 
(splenium)  portions  being  subsequently  added  (Figs.  443  and  445).  This 
latter  view  is  indicated  in  Fig.  445,  the  later  additions  being  shaded  darker. 

As  the  callosal  fibers  connect  the  limbi  medullares,  the  limbus  corticalis 
and  the  arcuate  fissure,  corresponding  to  the  gyrus  dentatus  and  hippocarr  pal 
fissure  of  the  temporal  lobe,  lie  dorsal  to  the  callosum.  The  limbus  corticalis 
is  reduced  to  a  mere  vestige  (indusium  griseum  and  strict  Lancisi)  on  the 
dorsal  surface  of  the  corpus  callosum  the  fissure  becoming  the  callosal  fissure. 
The  part  of  the  limbus  medullaris  ventral  to  the  corpus  callosum,  corre- 
sponding to  the  fimbria  of  the  temporal  lobe,  forms  the  posterior  pillars  and 
body  of  the  fornioc. 

These  relations  are  shown  in  the  following  table  from  His  (slightly  modi- 
fied): 


Upper  callosal  region 

Hippocampal  region 

Upper  lip  of  arcuate 

Gyrus  cinguli 

Gyrus  hippocampi 

fissure 

Arcuate  fissure 

Fissura  corporis   cal- 

Fissura  hippocampi 

Limbus  Corticalis 

losi 

Cortical  layer  of  low- 

Cortical   covering  of 

Gvrus  dentatus 

er  lip    of    arcuate 

callosum  (indusium 

fissure 

griseum  and  striae 

Lancisi) 

Limbus  Medullaris  \ 

Medullary     part     of 
lower  lip 

Callosum  and  fornix 

Fimbria 

Taenia 

Taenia  fornicis 

Taenia  fimbriae 

Lamina  chorioidea 

Plica  chorioidea 

Plica  chorioidea 

Lamina      infrachorio- 

Lamina  affixa 

Taenia  chorioidea 

idea 

Fibers  from  the  hippocampus  enter  the  fimbria  and  pass  forward  in  the  pos- 
terior pillars  and  body  of  the  fornix.  In  or  near  the  lamina  terminalis  these 
fibers  of  the  fornix  descend,  forming  the  anterior  pillars  of  the  fornix,  and  thence 
pass  back  of  the  anterior  commissure  and  caudally  to  the  mammillary  region. 


522  TEXT-BOOK  OF  EMBRYOLOGY. 

They  are  joined  by  fibers  from  the  dorsal  surface  of  the  callosum  (fornioc 
longus),  i.e.,  from  the  vestigial  hippocampal  formation,  many  of  which  also 
descend  in  front  of  the  anterior  commissure  to  the  rhinencephalon.  The  trian- 
gular mesial  area  (septum  pellucidum)  included  between  callosum  and  fornix 
probably  represents  an  extended  part  of  the  lamina  terminalis  or  "commis- 
sure-bed," in  which  a  cavity  is  formed,  the  so-called  fifth  ventricle  and  ventricle 
of  Verga.  A  remnant  of  the  hippocampal  formation  at  the  anterior  end  of 
the  callosum  is  represented  by  the  gyms  subcallosus  (Fig.  445). 

THE  NEOPALLIUM. 

The  hippocampal  or  cornu  ammonis  formation  and  preterminal  area 
represent  the  older  part  of  the  pallium  (archipallium)  comp.  pp.  438  and  439. 
This  part  of  the  pallium  is  olfactory  in  character,  being  mainly  a  higher  center 
for  the  reception  of  secondary  and  tertiary  olfactory  tracts.  In  its  extension 
backward  and  partial  obliteration  by  the  corpus  callosum,  its  embryologic 
presents  a  striking  similarity  to  its  phylogenetic  development  (compare  p.  438). 
The  rest  of  the  pallial  hemispheres  (neopallium)  are  occupied  by  the  non- 
olfactory  higher  centers. 

The  further  growth  of  the  neopallial  hemispheres  leads  to  their  extension 
backward,  overlapping  the  caudal  portions  of  the  brain  tube.  In  the  course 
of  this  extension  the  occipital  lobe  and  its  cavity,  the  posterior  horn  of  the  lateral 
ventricle,  are  formed.  The  growth  of  various  portions  of  the  hemisphere  sur- 
face is  unequal,  producing  folds  (convolutions)  and  fissures.  This  folding 
may  be  partly  due  to  growth  in  a  confined  space,  but  especially  important  is 
the  relation  between  gray  and  white  matter.  The  gray  matter,  containing  not 
only  fibers  but  also  neurone  bodies,  remains  spread  out  in  a  comparatively  thin 
layer,  probably  to  accommodate  associative  connections.  The  white  matter,  on 
the  other  hand,  increases  in  thickness.  This  leads  to  a  folding  of  the  outer 
layer.  The  position  of  these  folds  is  probably  partly  determined  by  the  local 
histological  differentiation  and  growth  of  various  cortical  areas  (p.  527). 
Only  some  of  the  earliest  and  most  important  of  these  folds  will  be  mentioned 
here. 

It  has  been  seen  (p.  509)  that  early  in  the  development  of  the  pallium  a 
shallow  depression  appears  on  the  external  lateral  surface  of  each  hemisphere, 
the  fossa  Sylvii  (Fig.  446).  The  bottom  of  this  is  the  future  insula.  It  is  ex- 
ternal to  the  corpus  striatum  and  does  not  grow  as  rapidly  as  the  parts  bound- 
ing it,  which  consequently  overlap  it,  forming  its  opercula.  These  bounding 
walls  are  formed  by  the  fronto-parietal  lobe  on  its  upper  side,  by  the  temporal 
on  its  lower,  and  by  the  orbital  on  its  anterior.  The  temporal  and  fronto- 
parietal  opercula  begin  about  the  end  of  the  fifth  month,  the  temporal  at  first 


THE  NERVOUS  SYSTEM. 


523 


growing  more  rapidly  but  later  the  fronto-parietal,  thereby  changing  the 
direction  of  the  Sylvian  fissure  from  an  oblique  to  the  more  horizontal  angle 
characteristic  of  man  as  compared  with  the  ape.  In  the  meanwhile  the 
development  of  the  frontal  lobe  leads  to  its  also  overlapping  the  insula.  If  the 


Parietal  lobe 


Occipital  lobe 


Mesencephalon 
Cerebellum 


Bulbus  olfactorius 


Gyrus  olfactor.  lat. 

Gyrus  semilunaris 
Gyrus  ambiens 


FIG.  446. — Lateral  view  of  the  brain  of  a  human  foetus  at  the  beginning  of  the 
4th  month.     Kollmann. 

frontal  lobe  fully  develops,  it  forms  a  U-shaped  operculum  between  the  fronto- 
parietal  and  the  orbital,  if  it  does  not  so  fully  develop  it  forms  a  V-shaped 
operculum,  and  a  still  less  developed  condition  is  shown  by  a  Y-shaped  arrange- 
ment in  which  the  frontal  lobe  does  not  completely  separate  the  fronto-parietal 


Corpus  callosum 
Gyrus  cinguli 
I 


Sulcus  corp.  callosi 
|         Splenium 
I         |  Fissura  parieto-occip. 


Cavum  septi  pellucidi  — 
Lamina  rostralis  — < 
Area  parolfactoria  — 
(praeterminalis) 


Cuneus 


Fissura  calcarina 


N.  olfact.      |      |      Fiss.  rhinica 
N.  optic.     Lob.  temp. 

FIG.  447. — Median  view  of  the  left  half  of  the  brain  of  a  human  foetus  at  the  end 
of  the  7th  month.     Kollmann. 

and  orbital  opercula.  The  opercula  cover  the  fore-part  of  the  Sylvian  fossa 
during  the  first  year.  Conditions  of  arrested  development  are  thus  indicated  by 
the  Y-shaped  anterior  ascending  branch  of  the  Sylvian  fissure  coupled  with  an 
absence  of  the  pars  triangularis  and  also  by  a  partial  exposure  of  the  island 


524 


TEXT-BOOK  OF  EMBRYOLOGY. 


of  Reil.  In  the  ape  the  frontal  operculum  is  absent  and  the  island  of  Reil 
partly  exposed. 

Toward  the  end  of  the  third  month  the  calcarine  fissure  appears,  producing 
on  the  ventricular  surface  the  eminence  known  as  the  calcar  avis.  At  the 
beginning  of  the  fourth  month  the  parieto-occipital  fissure  unites  with  it  forming 
the  cuneus.  The  parieto-occipital  reaches  the  superior  border  of  the  hemi- 
spheres by  the  sixth  or  seventh  month.  At  the  sixth  month  the  fissure  of  Rolando 
(central  fissure)  appears.  The  condition  of  the  surface  of  the  hemisphere  at 
the  end  of  the  seventh  month  is  shown  in  Figs.  447  to  450. 

The  early  histogenetic  development  of  the  pallial  wall,  resulting  in  the  dif- 
ferentiation into  the  usual  ependymal,  mantle  and  marginal  layers,  has  been 
mentioned.  (Fig.  451).  The  next  stage,  already  alluded  to  (p.  519),  marks  a 


Gyms  front,  med. 
Gyrus  front,  inf.  _ 
Gyrus  front,  sup.  — 
Gyrus     praecent. 

Gyrus  cent.  post. 
Lobulus  par.  sup. 
Lobulus  par.  inf. 

Lobus  occipitalis 


Sulcus  front,  sup. 
Sulcus  front,  inf. 
Sulcus  praecentralis 

Sulcus  centralis 


at    Salcus  postcentralis 

m 

g^^ / Sulcus  interparietalis 

Fissura  parieto-occipit. 


FJG.  448. — Dorsal  view  of  the  cerebral  hemispheres  of  a  human  foetus  at  the  end 
of  the  yth  month.     Kollmann. 

difference  in  development  between  the  pallium,  as  well  as  other  supraseg- 
mental  structures,  and  the  rest  of  the  walls  of  the  neural  tube.  This  stage 
consists  apparently  in  a  further  migration  outward  of  the  neuroblasts  and  their 
accumulation  under  the  marginal  layer,  forming,  at  eight  weeks,  a  definite 
layer  of  closely  packed  cells,  the  beginning  of  the  cortex  (Fig.  452).  Later 
neuroblast  migrations  probably  add  to  this  layer.  It  has  already  been  men- 
tioned that  the  fibers  of  the  thalamic  radiation  appear  in  the  pallial  walls  about 
this  time.  They  proceed  internally  to  the  cortical  layer  and  thus  mark  the 
beginning  of  the  fiber  layer  (medullary  layer)  which  by  later  myelination 
becomes  the  white  matter  of  the  hemispheres. 

The  extension  of  the  process  of  differentiation  of  the  cortical  layer  from  the 
region  of  the  corpus  striatum  over  the  rest  of  the  pallium  has  also  been  men- 
tioned (p.  512).  It  is  probable  that  the  afferent  pallial  fibers  (thalamic  radia- 
tion) in  their  growth  keep  pace  with  this  process.  Those  fibers  from  the  lateral 


THE  NERVOUS  SYSTEM. 


525 


geniculate  bodies  proceed  to  the  occipital  region,  those  from  the  medial  genicu- 
late  bodies  to  the  temporal,  and  those  from  the  ventro-lateral  thalamic  nuclei 
(continuation  of  the  medial  fillet)  to  the  future  postcentral  region.  The 
afferent  pallial  fibers  are  often  termed  the  afferent  or  ascending  projection  fibers. 


Sulcus  postcentralis 


Sulcus  centralis 


Lobus  parietal,  sup. 

Region  of  gyrus  sup- 

ramarg.  and  angular 

Ramus  post. 


Sulcus  tempor.  med. 

Post,  pole 
of  cerebrum 


—  Sulcus  front,  inf. 


Ramus  ant.  asc. 
Fissura  Sylvii 


Lobus  temporalis 


Gyrus  temp.  sup.        Gyrus  temp.  med. 


FIG.  449. — Lateral  view  of  the  right  cerebral  hemisphere  of  a  human  foetus  at  the  end 
of  the  yth  month.     Kollmann. 

The  axones  of  the  neuroblasts  of  the  cortical  layer  grow  inward,  entering  the 
medullary  layer.  Their  peripherally  directed  processes  become  the  apical 
dendrites  of  the  pyramid  cells  into  which  most  of  the  cortical  cells  differentiate. 
According  to  Mall  and  Paton,  this  change  of  direction  in  the  growth  of  the  axone 
is  due  to  a  turning  of  the  cell  axis  during  its  outward  migration.  It  would  seem 


Sulcus  orbitalis 

Insula 
Gyrus  olf.  lat. 

Gyrus  semilun. 

Gyrus  ambiens 
Pyramid 
Medulla 


Sulcus  olfactorius 
Lobus  olfactorius 


Post,  pole  of  cerebrum 


FIG.  450. — Ventral  view  of  the  brain  of  a  human  foetus  at  the  beginning 
of  the  sixth  month.     Retzius,  Kollmann. 

more  probable  that  the  cells  retain  an  original  bipolar  character  and  that  the 
inner  processes  differentiate  into  axones  instead  of  the  cells  going  through  a 
monopolar  stage  (pp.  454  and  455  and  Fi§s-  3^6  and  387).  The  axones  of  the 
cortical  cells  form  either  efferent  or  descending  projection  fibers,  proceeding  to 


526 


TEXT-BOOK  OF  EMBRYOLOGY. 


other  parts  of  the  nervous  system,  or  crossed  (callosal)  and  uncrossed  association 
fibers,  connecting  various  cortical  areas  of  the  hemispheres.  The  basilar 
dendritic  processes  of  the  pyramid  cells  and  the  axone  collaterals  develop  last. 
Many  details  of  development  of  the  cells  in  Mammals  are  not  completed  until 
afterbirth  (Fig.  453). 


FIG.  451. 


FIG.  452 


FIG.  451. — Section  through  the  pallial  wall  of  a  two  months'  human  foetus.     His,  Cajal. 
a,  Layer  of  germinal  cells;  b,  nuclear  layer;  c,  mantle  layer;  d,' marginal  layer;  e,  germinal  cell 

FIG.  452. — Section  through  the  pallial  wall  of  a  human  foetus  at  the  beginning  of 

the  third  month.     His,  Cajal. 

a,  Layer  containing  germinal  cells;  b,  fibrous  (medullary)  layer  (rudimentary  white  matter) ;  c,  layer 
of  neuroblasts  forming  rudimentary  cortical  gray  matter;  d,  marginal  layer  (future  molecular 
layer) ;  e,  germinal  cell;  /,  g,  neuroblasts  with  radial  processes.  Spongioblasts  and  myelo- 
spongium  are  shown  on  the  right  side. 

During  the  fourth  and  fifth  fcetal  months  the  cortical  layer  shows  a  differen- 
tiation into  a  denser  outer  and  an  inner  layer.  During  the  sixth  and  seventh 
months  a  differentiation  and  grouping  of  the  nerve  cells  begins  which  results 
in  the  formation  of  six  cortical  layers  (Brodmann).  These  are:  (i)  the  zonal 


>, 


THE  NERVOUS  SYSTEM. 


527 


layer  (marginal  layer,  molecular  layer  of  adult),  (2)  the  external  granular  layer 
(layer  of  small  pyramid  cells  of  adult),  (3)  pyramid  layer  (medium  and  large 
pyramid  cells),  (4)  internal  granular  layer,  (5)  ganglionic  layer  (internal  pyra- 
mid cells),  (6)  multiform  layer  (polymorphous  cells).  By  various  local  modifi- 
cations of  this  six-layered  cortex  the  differentiation  of  the  various  histological 
areas  of  the  adult  cortex  is  brought  about.  In  the  calcarine  region  of  the 
occipital  lobe,  in  the  sixth  month,  the  internal  granular  layer  differentiates  into 


FIG.  453. — Section  through  cortex  of  a  mouse  foetus  before  birth,  showing  later  stages  of 

differentiation  of  pyramid  cells.     Golgi  method.     Cajal. 
a,  large  pyramid  cells;  b,  c.  medium-sized  and  small  pyramid  cells;  d,  beginning  collaterals  of,  ey 
axis-cylinders  or  axones;  /,  horizontal  cell  of  molecular  layer.     Basal  dendrites  of  pyramid 
cells  are  beginning  to  appear. 

two  layers  between  which  is  formed  the  line  of  Gennari  which  contains  termi- 
nations of  the  fibers  from  the  lateral  geniculate  bodies,  representing  the  visual 
pathway.  This  area  is  the  visual  cortex.  In  the  temporal  (future  transverse 
gyri)  and  postcentral  regions,  areas  are  differentiated  which  mark  the  re- 
ception of  the  terminations  of  the  fibers  of  the  acoustic  and  somaesthetic 
(medial  fillet)  pathways.  These  areas  are  thus,  respectively,  the  auditory  cortex 
and  the  somcesthetic  (general  bodily  sensation)  cortex.  (Cf.  Fig.  371.) 

In  the  precentral  region,  the  internal  granular  layer  becomes  merged  with 


528  .  TEXT-BOOK  OF  EMBRYOLOGY. 

the  adjoining  layers  and  practically  disappears,  the  two  inner  layers  become 
more  or  less  fused  and  in  them  certain  cells  develop  to  a  great  size  forming  the 
layer  of  giant  pyramid  cells.  It  is  the  axones  of  these  cells,  in  all  probability, 
which  proceed  as  the  pyramidal  tracts  through  the  middle  part  of  the  internal 
capsule  and  pes  to  the  epichordal  segmental  brain  and  cord.  The  area  in 
which  these  cells  lie  is  the  motor  cortex  (cf.  Fig.  371).  Descending  axones  de- 
velop similarly  from  cells  in  the  calcarine  area,  possibly  here  also  from  large 
pyramidal  cells  of  the  fifth  and  sixth  layers  (solitary  cells  of  Meynert),  which 
probably  pass  to  the  anterior  colliculus  (operating  there  upon  reflex  eye 
mechanisms) . 

In  the  whole  pallium  there  are  thus  four  great  projection  fields,  differen- 
tiated both  by  their  histological  structure  and  their  connections.  These  are  (i) 
the  archipallial  olfactory  area  with  mesial  ascending  and  descending  connections ; 
(2)  the  visual;  (3)  the  acoustic;  (4)  the  somatic.  The  systems  of  projection  fibers 
of  the  three  neopallial  fields  are  lateral.  The  visual  and  acoustic  fields  repre- 
sent certain  specialized  and  concentrated  groups  of  receptors  (rods  and  cones, 
hair  cells  of  organ  of  Corti)  upon  which  stimuli  of  a  certain  definite  nature 
(light  and  sound  waves),  from  distant  objects,  are  focussed  by  means  of  acces- 
sory apparatus  (eye,  ear).  The  somatic  area  represents  receptors  scattered 
over  the  whole  organism.  In  the  visual  and  acoustic  mechanisms,  the  efferent 
element  is  small  or  lacking  in  both  peripheral  apparatus  and  cortical  areas,  in  the 
somatic  the  efferent  element  is  large  and  is  represented  cortically  by  an  area 
(motor,  precentral  area)  distinct  from  that  of  the  receptive  portion  (somaes- 
thetic,  postcentral  area).  Gustatory  and  other  visceral  areas  have  not  been 
well  determined  (vicinity  of  archipallium  ?) . 

These  four  primary  sensori-motor  fields  are  probably  the  first  differentiated 
of  the  various  pallial  cortical  areas.  This  is  evidenced  by  the  myelination 
(comp.  p.  464)  which  first  involves  the  projection  fibers  of  these  areas  (at  or 
soon  after  birth,  Flechsig),  the  afferent  projection  fibers  probably  myelinating 
before  the  efferent  (Figs.  454  and  455). 

The  process  of  myelination  next  spreads  over  areas  adjoining  the  primary 
areas,  the  intermediate  areas  of  Flechsig.  Descending  projection  fibers  from 
these  areas  in  the  frontal,  temporal  and  occipital  lobes  are  probably  represented 
by  the  cortico-pontile  systems  of  fibers,  securing  cerebellar  regulation  of  pallial 
reactions.  The  presence  of  other  fibers  connecting  with  thalamic  nuclei 
is  probable,  but  knowledge  of  their  develoDment  and  connections  is  very 
incomplete. 

The  cells  whose  axones  form  descending  or  efferent  projection  fibers  con- 
stitute only  a  small  fraction  of  the  cortical  cells.  The  great  majority  are  asso- 
ciation cells  whose  axones,  or  collaterals,  pass  across  the  median  line  in  the 
lamina  terminalis  as  the  callosal  fibers  already  mentioned  (p.  520)  or  pass 


THE  NERVOUS  SYSTEM. 


529 


to  distant  or  near  parts  of  the  same  hemisphere.  In  general,  these  develop  later 
than  the  projection  neurones  and  the  completion  of  their  development  is  carried 
to  a  much  later  period.  Variations  which  arise  in  their  differentiation  and  ar- 
rangement probably  contribute  largely  to  the  formation  of  various  histological 
areas  which  develop  at  different  periods.  These  local  inequalities  of  growth 
probably  constitute  a  factor  in  the  production  of  the  convolutions  appearing 
later  than  those  already  mentioned  in  connection  with  the  primary  areas.  The 
last  areas  to  myelinate,  the  terminal  areas  of  Flechsig,  are  poor  in  projection 
fibers  and  are  thus  composed  largely  (entirely  ?,  Flechsig)  of  association  cells. 
It  is  the  extent  of  these  last  developing  areas  which  constitutes  the  principal 
difference  between  the  human  cortex  and  that  of  related  forms.  These  pallial 


B 


FIG.  454.— Diagram  of  cortical  areas  of  mesial  surface  of  pallium  as  determined  by  the  myelogenetic 
method.     Flechsig,  from  Quain's  Anatomy.     For  explanation  see  Fig.  455. 

areas  are  those  which  continue  to  grow  in  human  development.  Myelination 
in  the  cortical  areas  may  continue  for  twenty  years  or  so.  It  is  a  significant 
fact  that  the  last  areas  to  develop  are  comparatively  poor,  even  when  completely 
developed,  in  both  cells  and  fibers  (Campbell).  The  association  neurones 
thus  probably  follow  the  same  order  of  development  as  the  projection  systems. 
As  their  development  spreads  from  the  primary  receptive  areas  (perceptions?), 
the  incoming  stimuli  receive  a  more  and  more  extended  associative  "setting" 
(psychologically,  the  "meaning"  or  "significance"  of  perceptions?),  extensive 
associations  between  the  various  areas  being  provided  by  the  extension  of  their 
development  to  the  terminal  areas  (rendering  possible  the  association  of 
symbols:  mental  processes?). 


530 


TEXT-BOOK  OF  EMBRYOLOGY. 


The  general  biological  significance  of  this  late  development  of  the  pallium 
and  especially  of  its  associative  mechanisms  has  already  been  alluded  to. 
These  "added"  parts  of  the  nervous  system  are  the  most  modifiable  mechan- 
isms of  the  human  organism;  they  are  those  mechanisms  which  perform  its 
newest  and  most  highly  adaptive  adjustments.  The  other  parts  of  the  ner- 
vous system  are  fixed  at  birth,  but  the  cerebral  hemispheres  are  still  plastic 
for  the  reception  and  recording  of  individual  experience.  Such  experience 
symbolized  and  formulated  (spoken,  written,  etc.)  is  transmitted  to  the  next 
generation,  as  already  pointed  out  (p.  440)-  An  example  of  the  far-reaching 
consequences  of  this  capacity  of  the  pallium  is  the  prolonged  period  of  infancy 
and  education  of  man.  ' 


FIG.  455. — Diagram  of  cortical  areas  of  lateral  surface  of  pallium  as  determined  by  the  myelogenetic 

'method.     Flechsig,  from  Quain's  Anatomy. 
The  numerals  indicate,  in  a  general  way.  the  order  of  myelination.     The  primary  areas  (i-io)  are 

indicated  by  dots,  the  intermediate  areas  (11-31)  by  oblique  lines  and  the  terminal  or  final 

areas  (32-36)  by  clear  spaces. 

Anomalies. 

Those  anomalies  of  the  nervous  system  involving  more  general  develop- 
mental anomalies  (cyclopia,  anencephaly,  cranioschisis,  spina  bifida,  etc.)  are 
dealt  with  in  the  chapter  on  Teratogenesis  (XX) .  Owing  to  the  fact  that  the 
nervous  system  consists  of  parts  which  are  more  or  less  separated,  and  yet  con- 
nected and  interdependent,  it  is  in  certain  respects  affected  differently  from  the 
other  organs  when  portions  of  it  are  injured  or  inhibited  in  development.  Thus 
an  injury  or  inhibition  in  development  of  one  part  of  the  nervous  system  may, 
because  of  the  dependence  upon  this  part  of  other  perhaps  distant  parts,  affect 
the  development  of  the  latter.  Even  in  the  adult,  injury  of  an  axone  leads  to  the 


THE  NERVOUS  SYSTEM.  531 

disappearance  of  that  portion  of  the  axone  distal  to  the  point  of  injury;  it  may 
also  lead  to  the  disappearance  of  the  entire  neurone  where  regeneration  is  not 
possible.  Such  an  injury  during  development  will  not  only  cause  a  disappear- 
ance of  the  whole  neurone,  but  it  may  also  lead  to  the  disappearance  of  other 
neurones  forming  links  in  the  same  functional  pathway.  Thus  a  develop- 
mental defect  involving  the  central  area  will  not  only  lead  to  absence  of  the 
pyramidal  tract,  but  also  to  partial  atrophy  of  the  corresponding  fillet  bundles. 
When  one  cerebellar  hemisphere  fails  to  develop,  there  results  a  correlated 
defect  in  its  centripetal  and  centrifugal  pathways.  The  opposite  inferior  olive 
is  practically  absent,  as  is  also  the  central  tegmental  tract  leading  to  that  olive. 
The  pontile  nuclei  of  the  opposite  side,  the  middle  peduncle  leading  from  them 
to  the  affected  cerebellar  hemisphere,  and  the  fibers  in  the  pes  which  pass  to 
the  pontile  nuclei  in  question  are  likewise  suppressed,  and  the  superior 
peduncle  and  red  nucleus  are  absent  or  reduced.  In  this  case  it  is  evident  that 
the  correlated  atrophy  affects  at  least  two  neurones  in  the  pathways  leading  to 
and  from  the  cerebellum.  This  illustrates  the  far-reaching  character  of  cor- 
related developmental  defects  in  the  nervous  system  arising  from  the  nature 
of  the  connections  between  various  portions  of  the  system. 

References  for  Further  Study. 

BARDEEN,  C.  R.:  The  Growth  and  Histogenesis  of  the  Cerebrospinal  Nerves  in  Mam- 
mals. Am.  Jour,  of  Anat.,  Vol.  II,  No.  2,  1903. 

DEJERINE,  J.:    Anatomic  des  centres  nerveux.     Tome  I,  Ch.  2  and  3. 

EDINGER,  L.:    Vorlesungen  iiber  den  Bau  der  nervosen  Zentralorgane.     Seventh  Ed. 

EDINGER,  L.  The  Relations  of  Comparative  Anatomy  to  Comparative  Psychology. 
Jour.  ofComp.  N enrol,  and  Psychol.,  Vol.  XVIII,  No.  5,  Nov.,  1908. 

FLECHSIG,  P. :  Einige  Bemerkungen  iiber  die  Untersuchungsmethoden  der  Grosshirnrinde 
insbesondere  des  Menschen.  Berichten  der  math.-phys.  Klasse  d.  Konigl. -Sachs.  Gesellsch.  d. 
Wissensch.  zu  Leipzig.  1904.  See  also  Johns  Hopkins  Hosp.  Bull,  Vol.  XVI,  1905,  pp 

45-49. 

HARDESTY,  I. :    On  the  Development  and  Nature  of  the  Neuroglia.     Am.  Jour,  of  Anat., 

Vol.  Ill,  No.  3,  July,  1904. 

HARRISON,  R.  G. :  Further  Experiments  on  the  Development  of  Peripheral  Nerves. 
Am.  Jour,  of  Anat.,  Vol.  V,  No.  2,  May,  1906. 

HARRISON,  R.  G.:  Observations  on  the  Living  Developing  Nerve  Fiber.     Anat.  Record. 

Vol.  I,  No.  5,  1907. 

HARRISON,   R.   G.:   Embryonic    Transplantation  and  Development  of    the  Nervous 

System.     Anat.  Record,  Vol.  II,  No.  9,  1908. 

HERRICK,  C.  J.:  The  Morphological  Subdivision  of  the  Brain.    Jour,  of  Comp.  N  enrol. 

and  Psychol.,  Vol.  XVIII,  No.  4,  ipo8- 

His,  W.:  Zur  Geschichte  des  menschlichen  Riickenmarkes  und  der  Nervenwurzeln. 
Abhandl.  der  math.-phys.  Klasse  der  Konig. -Sachs.  Gesellsch.  d.  Wissensch.,  Bd.  XIII,  1887. 

His   W  •  Zur  Geschichte  des  Gehirns,  sowie  der  centralen  und  periphenschen  Nerven 
bahnen'  beim   menschlichen  Embryo.     Abhandl.   d.   math.-phys.   Klasse  d.   Konig.-Sachs. 
Gesellsch.  d.  Wissensch.,  Bd.  XIV,  1888. 


532  TEXT-BOOK  OF  EMBRYOLOGY. 

His,  W.:  Die  Neuroblasten  und  deren  Entstehung  im  embryonalen  Mark.  Abhandl.  d. 
math.-phys.  Klasse  d.  Konig. -Sachs,  d.  Wissensch.,  Bd.  XV,  1890.  Also  Arch.  f.  Anat.  u. 
Physiol.,  Anat.  Abth.,  1889. 

His,  W.:  Ueber.die  Entwickelung  des  Riechlappens  und  des  Riechganglions  und  liber 
diejenige  des  verlangerten  Markes.  Verhandl.  d.  Anat.  Gesellsch.  zu  Berlin,  1889.  Also 
Abhandl.  d.  math.-phys.  Klasse  d.  Konig.-Sdchs.  Gesellsch.  d.  Wissensch.,  Bd.  XV,  1889. 

His,  W.:  Die  Entwickelung  des  menschlichen  Rautenhirns  vom  Ende  des ersten  bis  zum 
Beginndesdritten  Monats.  I.  verlangertesMark.  Abhandl.  d.  math.-phys.  Klasse  d.  Konig.- 
Sachs.  Gesellsch.  d.  Wissensch.,  Bd.  XVII,  1891. 

His,  W.:  Die  Entwickelung  des  menschlichen  Gehirns  wahrend  der  ersten  Monate. 
Leipzig,  1904. 

JOHNSTON,  J.  B.:  The  Nervous  System  of  Vertebrates.     1906. 

KOLLMANN,  J.:  Handatlas  der  Entwickelungsgeschichte  des  Menschen.     Bd.  II,  1907. 

VON  KUPPFER,  K. :  Die  Morphogenie  des  Centralnervensystems.  In  Hertwig 's  Handbuch 
d.  vergleich.  u.  experiment.  Entwickelungslehre  der  Wirbeltiere.  Bd.  II,  Teil  III,  Kap.  8, 
1905. 

MARBURG,  O.:  Mikroskopisch-topographischer  Atlas  des  menschlichen  Zentralnerven- 
systems,  1904* 

MEYER,  A.:  Critical  Review  of  the  Data  and  General  Methods  and  Deductions  of 
Modern  Neurology.  Jour.  ofComp.  Neurol.,  Vol.  VIII,  Nos.  3  and  4,  1898. 

NEUMAYER,  L.:  Histo-  und  Morphogenese  des  peripheren  Nervensystems,  der  Spinal- 
ganglien  und  des  Nervus  sympathicus.  In  Hertwig's  Handbuch  der  vergleich.  und  experi- 
ment. Entwickelungslehre  der  Wirbeltiere,  Bd.  II,  Teil  III,  Kap.  10,  1906. 

RAMON  Y  CAJAL,  S. :  Sur  1'origine  et  les  ramifications  des  fibres  nerveuses  de  la  moelle 
embryonnaire.  Anat.  Anz.,  Bd.  V,  Nos.  3  and  4,  1890. 

RAMON  Y  CAJAL,  S. :  A  quelle  epoque  apparaissent  les  expansions  des  cellules  nerveuses 
de  la  moelle  epiniere  du  poulet?  Anat.  Anz.,  Bd.  V,  Nos.  21  and  22,  1890. 

RAMON  Y  CAJAL,  S.:  Textura  del  sistema  nervioso  del  hombre  y  de  los  vertebrados. 
Madrid,  1899-1904.  Also  translation  into  French  by  Azoulay,  1910-11. 

RAMON  Y  CAJAL,  S.:  Nouvelles  observations  sur  1'evolution  des  neuroblasts,  avec  quel- 
ques  rernarques  sur  1'hypothese  neurogenetique  de  Hensen-Held.  Anat.  Anz.,  Bd.  XXXII, 
Nos.  i,  2,  3  and  4,  1908. 

SCHAPER,  A.:  Die  morphologische  und  histologische  Entwickelung  des  Kleinhirns  der 
Teleostier.  Morph.Jahrbuch,  Bd.  XXI,  1894. 

SCHAPER,  A.:  Die  friihesten  Differenzierungsvorgange  im  Centralnervensystems.  Arch 
f.  Entw.-Mechan.,  Bd.  V,  1897. 

SMITH,  G.  E.:  On  the  Morphology  of  the  Cerebral  Commissures  in  the  Vertebrata,  etc. 
Trans.  Linncean  Soc.  of  London,  2d  Ser.  Zoology,  Vol.  VIII,  Part  12,  1903.  See  also  articles 
by  same  author  in  Jour,  of  Anat.  and  Physiol. 

STREETER,  G.  L.:  The  Development  of  the  Cranial  and  Spinal  Nerves  in  the  Occipital 
Region  of  the  Human  Embryo.  Am.  Jour,  of  Anat.,  Vol.  IV,  No.  i,  1904. 

STREETER,  G.  L.:  The  Peripheral  Nervous  System  in  the  Human  Embryo  at  the  End 
of  the  First  Month.  Am.  Jour,  of  Anat.,  Vol.  VIII,  No.  3. 

ZIEHEN,  TH.:  Die  Morphogenie  des  Centralnervensystems  der  Saugetiere.  In  Hertwig's 
Handbuch  der  vergleich.  u.  experiment.  Entwickelungslehre  der  Wirbeltiere.  Bd.  IL  Teil  III, 
Kap.  8,  1905. 

ZIEHEN,  TH.:  Die  Histogenese  von  Him-  und  Riickenmark.  Entwickelung  der 
Leitungsbahnen  und  der  Nervenkerne  bei  den  Wirbeltierer-.  In  Hertwig's  Handbuch  der 
vergleich.  u.  experiment  Entwickelungslehre  der  Wirbeltiere,  Bd.  II,  Teil  III,  Kap.  IX,  1905, 


CHAPTER  XVIII. 

THE  ORGANS  OF  SPECIAL  SENSE. 
THE  EYE. 

The  receptive  mechanisms  of  all  the  general  and  special  sense  organs 
are  derived  from  the  ectoderm.  With  the  single  exception  of  the  eye,  all 
develop  as  direct  specializations  of  the  ectoderm  in  the  form  of  the  various 
neuro-epithelia.  The  eye  is  peculiar  among  the  sense  organs  in  that  its  recep- 
tive cells  are  not  derived  directly  from  surface  ectoderm,  but  only  indirectly  from 
the  ectoderm  after  it  has  become  folded  in  to  form  the  neural  canal.  The 
neuro-epithelium  of  the  eye  develops  as  a  direct  outgrowth  from  the  central 
nervous  system.  The  retina  is  a  modified  part  of  the  brain;  the  optic  nerves 
correspond  to  central  nervous  system  fiber  tracts.  Of  the  accessory  optic 
structures,  the  lens,  the  epithelium  of  the  lids  and  conjunctiva,  the  eyelashes, 
the  Meibomian  glands  and  the  epithelium  of  the  lacrymal  apparatus  arc  of 
ectodermic  origin;  the  coats  of  the  eye,  the  sclera  and  chorioid,  and  parts  of 


Optic 
depression 


Neural 
plate 


Optic 

depression 


FIG.  456. — Diagram  showing  location  of  optic  areas  before  the  closure  of  the  neural  groove. 

Modified  from  Lange. 

their  modified  anterior  extensions,  the  cornea,  ciliary  body  and  iris,  are  of 
mesodermic  origin.  In  the  sensory  divisions  of  the  other  spinal  and  cranial 
nerves,  with  the  exception  of  the  olfactory,  the  cell  bodies  of  the  neurones  which 
serve  to  connect  the  receptive  mechanisms  with  the  brain  and  cord  are  located 
in  parts  (the  sensory  ganglia  of  the  cranial  and  spinal  nerves)  which  have  be- 
come separated  from  the  crests  of  the  neural  folds  as  the  latter  fuse  to  form  the 
neural  canal.  In  the  eye  the  cell  bodies  of  these  neurones  are  located  in  the 
retina,  but  the  area  of  ectoderm  from  which  the  retina  develops  first  occupies  a 
position  along  the  neural  crest  analogous  to  that  occupied  by  the  anlagen  of  the 
spinal  and  cranial  ganglia.  In  the  case  of  the  retina  this  area,  instead  of  be- 
coming  split  off  in  the  closure  of  the  neural  canal,  becomes  folded  into  the 
canal  and  later  pushed  out  toward  the  surface  in  the  optic  evagination  (Figs.  450, 
457>  4$8). 


534 


TEXT-BOOK  OF  EMBRYOLOGY. 


The  first  indication  of  eye  formation  is  found  in  the  chick  at  the  beginning 
of  the  second  day  of  incubation ;  in  the  human  embryo,  at  what  has  been  estimated 
as  about  the  second  or  third  week.  At  this  stage  the  neural  canal  is  not  yet 
completely  closed  in  and  its  anterior  end  shows  three  primary  brain  vesicles 


Optic  vesicle  area 


Neural  canal 

FIG.  457. — Diagram  showing  location  of  areas  shown  in  Fig.  456  after  the  formation  of  the 
neural  canal.     Modified  from  Lange. 

(p.  440,  Fig.  497).  The  anlagen  of  the  eyes  first  appear  as  bilaterally  sym- 
metrical evaginations  from  the  lateral  walls  of  the  fore-brain  vesicle  (Figs.  459  and 
460),  and  are  at  first  large  in  proportion  to  the  brain  vesicle  itself.  When 
first  formed,  the  optic  evagination  opens  widely  into  the  fore-brain  vesicle  (Fig. 
460,  right  side),  but  as  the  distal  part  of  the  evagination  expands  more  rapidly 


Retina 


H-b 


Optic  stalk 

FIG.  458.  FiG.450. 

FIG.  458. — Diagram  showing,  location  of  the  (dark)  optic  area  (see  Fig.  457)  after  the  beginning  of 
the  formation  of  the  optic  cup  and  optic  stalk.     Lange. 

FIG.  459. — Dorsal  view  of  head  of  chick  of  58  hours'  incubation.     Mihalkovics. 

Lam.  term,  lamina  terminalis;  Fb.,  fore-brain;  Opt.  v.,  optic  vesicle;  M. b.,  mid-brain; 

H.b.,  hind  or  rhombic  brain;  H.,  heart. 

than  the  proximal  part,  there  soon  results  a  spheroidal  optic  vesicle  attached  to 
the  fore-brain  by  the  narrow  optic  stalk  (Fig.  460,  left  side) .  Through  the  latter 
the  cavity  of  the  optic  vesicle  and  the  cavity  of  the  fore-brain  are  in  communi- 
cation. With  the  development  of  the  hemispheres,  that  part  of  the  brain  to 
which  the  optic  stalks  are  attached  becomes  the  inter-brain  (diencephalon). 


THE   ORGANS   OF  SPECIAL  SENSE. 


535 


The  Lens. — As  each  optic  vesicle  grows  out  toward  the  surface,  its  outer 
wall  soon  comes  to  lie  just  beneath  the  surface  ectoderm.  The  cells  of  that 
portion  of  the  ectoderm  which  overlies  the  optic  vesicle  next  proliferate  and 
cause  a  thickening  of  the  ectoderm  (Fig.  460,  left  side) .  This  thickening  of  the 


Fore-brain  vesicle 


Optic  vesicle 


Surface  ectoderm 


Optic  vesicle 


FIG.  460.  —  Section  through  head  of  chick  of  two  days'  incubation.     Duval. 

The  formation  of  the  optic  vesicle  and  stalk  appears  to  be  somewhat  more  advanced 

on  the  left  than  on  the  right. 

ectoderm  over  the  optic  vesicle  is  apparent  in  the  chick  embryo  of  36  hours  in- 
cubation; in  the  human  embryo  it  occurs  about  the  third  or  fourth  week  and 
represents  the  first-step  in  the  development  of  the  crystalline  lens.  The  thick- 

ened  portion  of  ectoderm  is  known  as  the  lens  area  (Fig.  460).     The  latter  next 


Fore-brain 


Lens  imagination  -  -  -  JU: :  @?  ^, '.  ffl   »••":;-  Lens  invagination 

Optic  vesicle  ^^     ^        ^^      ^          ,  ^-^ 

Optic  vesicle 

FIG.  461. — Section  through  head  of  chick  of  three  days'  incubation.     Duval. 

becomes  depressed  against  the  outet  surface  of  the  optic  vesicle  forming  a 
distinct  lens  invaKmation  (Fig.  461).   -This  becomes  cup-shaped  and  then  its 

edges  come  together  and  fuse,  thus  forming  the  lens  vesicle  (Fig.  462).     At  first  the 
lens  vesicle  is  connected  with  the  surface  ectoderm,  but  about  the  eighth  week 


536 


TEXT-BOOK  OF  EMBRYOLOGY. 


a  thin  layer  of  mesoderm  grows  in  between  the  lens  vesicle  and  the  surface 
ectoderm,  completely  separating  them  (Fig.  463).  The  ingrowth  of  the  lens 
vesicle  against  the  outgrowing  optic  vesicle  has  the  effect  as  though  a  small  hard 
ball  (the  lens  vesicle)  had  been  pressed  into  a  larger  soft  ball  (the  optic  vesicle) 


Fore-brain -M'-^  **  —> 


Lens  vesicle  - 


Optic  cup    " 


FIG.  462. — Showing  somewhat  later  stage  in  development  of  optic  cup  and  lens 
than  is  shown  in  Fig.  461.     Duval. 

(Fig.  464) .  The  lens  vesicle  pushes  the  outer  wall  of  the  optic  vesicle  in  against 
the  inner  wall,  the  optic  vesicle  thus  becoming  transformed  into  the  two-layered 
optic  cup  (Figs.  462,  463).  Bonnet  calls  attention  to  the  fact  that  the  two  proc- 
esses, lens  formation  and  the  invagination  of  the  optic  vesicle  to  form  the  optic 


Conjunctival  epithelium 


Vitreous •$?- 


Lens  vesicle 


Retina  (inner  layer 
of  optic  cup) 


Optic  stalk 


Pigmented  layer  of  retina 
(outer  layer  of  optic  cup) 

FIG.  463. — Diagram  of  developing  lens  and  optic  cup.     Duval. 

The  cells  of  the  inner  wall  of  the  lens  vesicle  have  begun  lo  elongate  to  form  lens  fibers.  The  epi- 
thelium over  the  lens  is  the  anlage  of  the  corneal  epithelium.  The  mesodermal  tissue  between 
the  latter  and  the  anterior  wall  of  the  lens  vesicle  is  the  anlage  of  the  substantia  propria 
corneae. 


cup,  are  more  or  less  independent  and  that  it  is  not  correct  to  describe  the  lens  as 
actually  pushing  in  the  outer  wall  of  the  vesicle.  As  evidence  of  this  is  noted 
the  fact  that  typical  optic  cup  formation  may  occur  in  cases  where  no  lens  is 
developed.  The  optic  cup  when  first  formed  is  not  a  complete  cup,  for  the 


THE   ORGANS   OF  SPECIAL  SENSE. 


537 


invagination  of  the  optic  vesicle  is  carried  over  along  the  posterior  surface  of  the 
optic  stalk  forming  the  chorioidalfssure  (Fig.  464,  see  also  p.  545). 

The  lens  area  is  thicker  at  its  center  than  at  its  periphery  and  when  the 
center  of  the  lens  area  becomes  the  bottom  of  the  lens  depression  and  later 
the  posterior  wall  of  the  lens  vesicle  this  greater  thickness  is  maintained.  In 
fact,  the  posterior  wall  of  the  vesicle  becomes  still  thicker  so  that  it  projects  into 
the  cavity  of  the  lens  vesicle  as  an  eminence  (Fig.  465,  g.) .  In  the  chick  the  lens 
vesicle  is  hollow.  In  man  and  in  Mammals  generally  it  is  more  or  less  filled 
with  cells.  These,  however,  degenerate  and  take  no  part  in  the  formation  of  the 


Pigmented  layer  of  retina 
(outer  layer  of  optic  cup) 


Nervous  layer  of  retina 
(inner  layer  of  optic  cup) 


Cavity  of 
optic  vesicle 


Optic  furrow   — 


Rim  of  optic  cup. 


Lens 


Hyaloid  artery  |      Optic  furrow 

Hyaloid  artery  entering 
cavity  of  vitreous 

FIG.  464. — Model  showing  lens  and  formation  of  optic  cup.     A  piece  has  been  removed  from  the 
upper  part  of  cup  to  show  the  cavity  of  the  optic  vesicle  and  the  position  of  the  inner  layer 
'  of  the  cup  (nervous  layer  of  retina) .     Bonnet. 

permanent  lens.  Comparing  the  posterior  with  the  anterior  wall  of  the  lens  at  this 
stage,  the  latter  is  seen  to  be  composed  of  a  single  layer  of  cuboidal  cells,  the  an- 
lage  of  the  anterior  epithelium  of  the  lens  (Figs.  463,  465,  g,  h,  i) .  This  layer  passes 
over  rather  abruptly  into  the  posterior  wah1  which  consists  of  a  single  layer  of 
greatly  elongated  lens  cells,  the  anlagen  of  the  lens  fibers.  The  lens  fibers  con- 
tinue to  elongate  until  by  the  end  of  the  second  month  they  touch  the  anterior 
epithelium,  thus  completely  obliterating  the  cavity  of  the  lens  vesicle  (Fig.  467). 
A  small  cleft  containing  a  few  drops  of  fluid,  the  liquor  Morgagni,  may  remain 
between  the  anterior  epithelium  and  the  lens  fibers. 

When  the  lens  fibers  are  first  formed,  the  longest  fibers  are  in  the  center  and 
the  fibers  gradually  get  shorter  toward  the  periphery  of  the  lens  where  they  pass 
over  into  the  anterior  epithelium  (Fig.  465),  As  the  lens  develops,  the  periph- 


538 


TEXT-BOOK  OF  EMBRYOLOGY. 


eral  fibers  elongate  more  rapidly  than  the  central,  with  the  result  that  in  the  fully 
developed  lens  the  central  fibers  are  the  shortest,  forming  a  sort  of  core  around 
which  the  now  longer  peripheral  fibers  extend  in  much  the  same  manner  as  the 
layers  of  an  onion  (Fig.  467).  The  ends  of  the  fibers  meet  on  the  anterior  and 
posterior  surfaces  of  the  lens,  along  more  or  less  definite  lines  which  can  be  seen 


FIG.  465. — Successive  stages  in  the  development  of  the  lens  in  the  rabbit  embryo.     Rabl. 

a,  b,  c,  d,  and  e,  are  from  embryos  of  from  u  J  to  12  days;  f,  at  end  of  i2th  day;  g,  during  the  i3th 

day;    h,  between  the  i3th  and  i4th  days;  i,  from  an  embryo  of  n  mm. 

on  surface  examination  and  which  are  known  as  sutural  lines.  The  lens  fibers 
are  at  first  all  nucleated  and  as  the  nuclei  are  situated  at  approximately  the  same 
level  in  all  the  fibers,  there  results  a  so-called  nuclear  zone  (Fig.  465,  i).  Later 
the  nuclei  disappear.  The  sutural  lines  become  evident  about  the  fifth  month 
and  mark  the  completion  of  the  lens  formation,  although  lens  fibers  continue 
to  be  formed  throughout  fcetal  and  in  postnatal  life,  probably  by  proliferation 


THE   ORGANS   OF  SPECIAL  SENSE  539 

and  differentiation  of  the  cells  of  the  anterior  epithelium,  in  the  region  where  the 
latter  pass  over  into  the  lens  fibers.  (The  successive  stages  in  the  development 
of  the  lens  are  shown  in  Fig.  465.) 

The  lens  capsule  becomes  differentiated  during  the  third  month.  It  is  con- 
sidered by  some  as  derived  from  the  lens  epithelium  and  of  the  nature  of  a 
cuticular  membrane,  by  others  as  a  product  of  the  surrounding  connective 
tissue. 

By  the  extension  of  mesodermic  tissue  in  between  the  lens  and  the  surface 
ectoderm,  the  lens  becomes  by  the  end  of  the  sixth  week  completely  surrounded 
by  a  layer  of  vascular  connective  tissue.  /This  is  known  as  the  tunica 


lentis,  and  receives  its-  blood  supply  mainly  from  the  hyaloid  artery  (Fig.  467) 

which  is  a  foetal  continuation  of  the  arteria  centralis  retina  (p.  545)  .  Branches 
f  rorn  the  hyaloid  artejjy  break  up  into  a  capillary  network  which  co~versT)otTf 
anterior  and  posterior  surfaces  of  the  lens.  That  part  of  the  tunica  vasculosa 
wjiicli  covers  the  anterior  surface  of  the  lens  is  known  as  the  mcmb^ranapiipillaris. 
After  the  earlier  and  more  rapid  formation  of  lens  fibers  ceases,  the  hyaloid 
artery  begins  (about  the  seventh  month)  to  undergo  regressive  changes,  and  at 
birth  is  normally  absent.  Rarely  more  or  less  of  the  tunica  vasculosa  fails  to 
degenerate,  and  if  the  part  which  persists  is  the  membrana  pupillaris  there 
results  a  malformation  known  as  congenital  atresia  of  the  pupil. 

The  Optic  Cup.  —  The  way  in  which  the  optic  vesicle  becomes  transformed 
into  the  optic  cup  has  been  partially  described  in  considering  the  development  of 
the  lens  (p.  536).  The  growing  lens  vesicle  appears  to  push  in  the  outer  wall  of 
the  optic  vesicle  while  at  the  same  time  the  edges  of  the  latter  are  extending 
around  the  lens  vesicle,  until  what  was  originally  the  outer  wall  of  the  optic 
vesicle  lies  in  apposition  with  the  original  inner  wall,  the  cavity  of  the  primary 
optic  vesicle  thus  becoming  completely  obliterated  (Fig.  466)^.  In  this  way  the 
optic  vesicle  is  transformed  into  a  two-layered  thick-walled  cup,  the  cleft  be- 
tween the  two  layers  corresponding  to  the  cavity  of  the  primary  vesicle.  This 
cup  is  at  first  entirely  filled  with  the  developing  lens  (Fig.  466).  As  the  cup  in- 
creases in  size  faster  than  the  lens,  the  contiguous  walls  of  the  cup  and  lens 
become  separated,  the  cavity  thus  formed  being  the  cavity  of  the  vitreous 
humor  (Fig.  467).  There  seems  to  be  no  question  but  that  in  Mammals  a 
small  amount  of  mesoderm  at  first  separates  the  optic  evagination  from  the  lens 
area  of  the  surface  ectoderm.  This  apparently  disappears,  however,  so  that 
the  two  are  in  direct  contact.  It  is  still  an  open  question  wrhether  a  thin  layer 
of  mesoderm  grows  in  between  the  edges  of  the  cup  and  the  lens  at  or  just  before 
the  beginning  of  the  formation  of  the  vitreous.  The  lens  now  no  longer  fills  the 
optic  cup  but  lies  in  the  mouth  of  the  cup,  while  at  the  same  time  the  margin 
of  the  cup  is  extending  somewhat  over  its  outer  surface,  w^here  with  the  meso- 
derm it  ultimately  gives  rise  to  the  ciliary  body  and  iris,  and  forms  the 


540 


TEXT-BOOK  OF  EMBRYOLOGY. 


boundary  of  the  pupil.     The  remainder  of  the  two-walled  optic  cup  becomes 
the  retina. 

The  Retina. — Of  the  two  layers  which  form  the  wall  of  the  optic  cup  (p.  539) , 
the  outer  (away  from  the  cavity)  forms  the  pigmented  layer,  while  the  inner  forms 
the  remainder  of  the  retina  (Figs.  463,  467).  Soon  after  the  formation  of  the 
optic  cup,  it  is  possible  to  distinguish  a  boundary  zone — the  future  ora  serrata— 
between  the  larger  posterior  part  of  the  retina  or  nervous  retina  and  the  smaller 
anterior  non-nervous  part  which  becomes  the  retinal  portion  of  the  ciliary  body 


Vascular  mesoderm 


.Remains  of  optic 
vesicle  cavity 


Pigmented  layer  of  retina 
(outer  layer  of  optic  cup) 


Vascular  mesoderm 
Wall  of  brain  vesicle 


Ectoderm 


Lens  anlage 
Lens  invagination 


FIG.  466. — Section  through  optic  cup  and  lens  invagination  of  chick  of  fifty-four 

hours'  incubation.     Lange. 

Between  the  lens  anlage  and  the  pigmented  layer  of  the  retina  is  the  broad  inner  layer  of  the  optic 
cup,  the  anlage  of  the  remainder  of  the  retina. 


and  iris.  [  While  the  optic  cup  is  forming,  its  two  layers  are  both  rapidly  in- 
creasing in  thickness  by  mitotic  division  of  their  cells.  Especially  is  this  true  of 
the  inner  layer  over  that  region  which  is  to  become  the  nervous  retina,  and  it  is 
the  rather  abrupt  transition  between  the  thicker  nervous  retina  and  the  com- 
paratively thin  non-nervous  anterior  extension  of  the  retina  that  forms  the  ora 
serrata. 

The  invagination  which  gives  rise  to  the  two-layered  optic  cup  thus  differen- 
tiates what  may  be  called  the  two  primary  layers  of  the  retina,  the  pigmented  layer, 
and  a  broad  layer  from  which  are  to  develop  all  the  other  layers  of  the  retina. 


THE  ORGANS   OF  SPECIAL  SENSE. 


541 


(Figs.  463, 467) .  Further  development  consists  in  a  gradual  differentiation,  within 
the  broad  layer;of  the  various  retinal  elements  and  consequent  demarcation  of  the 
layers  which  constitute  the  adult  retina.  The  next  layer  to  differentiate  is  the 
innermost  layer  of  the  retina,  or  layer  of  nerve  fibers.  This  appears  during  the 
sixth  or  seventh  week  as  a  thin,  clear,  faintly  striated  zone  containing  a  few 
scattered  nuclei.  What  remains  of  the  original  inner  layer  of  the  cup  has  now 
become  a  comparatively  thick  layer  with  numerous  chromatic  and  actively 
dividing  nuclei.  It  may  be  conveniently  designated  the  primitive  nuclear  layer. 


Surface  epithelium 

of  eyelid 

Eyelid  (upper) 

Corneal  epithelium 

Conjunctival 

epithelium 

Substantia 

propria  corneae 

Lens 

Anterior  epithe- 
lium of  lens 

Conjunctival  sac 


Chorioid 
Pigmented  layer 
of  retina 
Split  between 
retinal  layers 
Retina,  except 
pigmented  layer 
Vitreous 

Tunica  vasculosa 
lentis 

Nerve  fiber  layer 
of  retina 


Hyaloid  artery 

Central  artery 
of  retina 

Optic  nerve 


FIG.  467. — Horizontal  section  through  eye  of  human  embryo  of  13-14  weeks.     Modified  from  Lange. 

The  similarity  in  development  between  the  retina  and  wall  of  the  neural  tube 
is  to  be  noted.  Thus  the  layer  of  nerve  fibers  appears  to  correspond  quite 
closely  to  the  marginal  layer  of  the  central  nervous  system,  while  the  primitive 
nuclear  layer  is  probably  homologous  with  the  mantle  layer  (pp.  449,  455). 
There  is  a  similar  correspondence  between  the  retina  and  the  central  nervous 
system  in  regard  to  their  early  cellular  development,  the  retinal  cells  early 
showing  a  differentiation  into  neuroblasts  and  spongiobiasts  (pp.449,  455). 

About  the  end  of  the  eighth  week  the  inner  part  of  the  primitive  nuclear 
layer  differentiates  into  the  layer  of  eanzlion  cetts  (Fig.  468,  h).  These 
are  large  cells  and  with  their  processes  constitute  the  third  or  proximal  optic 
neurone.  They  can  be  first  distinguished  in  the  fundus  of  the  cup  and  gradu- 
ally extend  to  the  ora  serrata.  They  are  the  first  of  the  cellular  dements  of  the 
adult  retina  which  can  be  definitely  recognized  as  such.  From  each  cell,  two 
kinds  of  processes  develop,  dendrites,  which  ramify  in  this  and  in  the  more 
external  layers  of  the  retina,  and  an  axone  which  grows  toward  the  cavity  of 
the  eye  and  becomes  a  fiber  of  the  layer  of  nerve  fibers,  whence  it  continues  into 


542 


TEXT-BOOK  OF  EMBRYOLOGY. 


the  optic  stalk  as  one  of  the  fibers  of  the  optic  nerve.  The  layer  of  ganglion  cells 
is  thickest  in  an  area  situated  somewhat  lateral  to  the  attachment  of  the  optic 
stalk  and  known  as  the  area  centralis.  It  is  distinguishable  about  the  end  of  the 
fourth  month.  In  the  center  of  the  area  centralis  the  retinal  layers  become 
thin  to  form  the  fovea  centralis  which  develops  toward  the  end  of  foetal  life. 
The  macula  lutea  with  its  yellow  pigment  does  not  develop  until  after  birth. 
The  retina  at  this  stage  thus  consists  of  four  layers  which  from  within  out- 
ward are  (i)  the  layer  of  nerve  fibers,  (2)  the  layer  of  ganglion  cells,  (3)  the 
nuclear  layer,  (4)  the  pigmented  layer  (see  Fig.  469) . 

L 


FIG.  468. — Diagram  of  the  development  of  the  retinal  cells.     Kallius,  after  CajaL 
a,  Cone  cells  in  unipolar  stage;  fe,  cone  cells  in  bipolar  stage;  c,  rod  cells  in  unipolar  stage;  d,  rod  cells 
in  bipolar  stage;  e,  bipolar  cells;  /and  i,  amacrme  cells;  g,  horizontal  cell;  h,  ganglion  cells; 
£,  Muller's  cells  or  fibers;  /,  external  limiting  membrane. 

The  further  development  of  the  retina  consists  largely  of  a  differentiation  of 
the  cells  of  the  nuclear  layer.  This  is  extremely  complex  and  our  knowledge 
of  it  meager.  From  the  cells  of  this  layer  develop  (i)  the  rod  and  cone  cells,  (2) 
the  bipolar  cells,  (3)  the  tangential  or  horizontal  cells,  (4)  the  amacrine  cells,  (5) 
Muller's  cells  or  fibers.  The  differentiation  of  these  cells  and  their  processes 
/also  results  in  the  demarcation  of  the  following  layers  of  the  adult  retina;  (i)  the 
^  layer  of  rods  and  cones,  (2)  the  outer  limiting  membrane,  (3)  the  outer  nuclear 
layer,  (4)  the  outer  molecular  layer,  (5)  the  inner  nuclear  layer,  (6)  the  inner 
molecular  layer,  (7)  the  inner  limiting  membrane  (see  Fig.  470). 

Muller's  cells  or  the  sustentacular  cells  (Fig.  468,  k)  develop  from  spongio- 
blasts  which  lie  toward  the  inner  limit  of  the  nuclear  layer.  This  accounts 
for  the  location  of  the  nucleated  portions  of  Muller's  cells.  Processes  of  these 
cells  grow  toward  both  surfaces  of  the  retina  until  they  reach  the  positions  of  the 
future  outer  and  inner  limiting  membranes  where  they  are  believed  to  spread  out 


THE  ORGANS  OF  SPECIAL  SENSE. 


543 


horizontally  and  unite  to  form  these  membranes.  Other  spongioblasts  develop 
into  other  types  of  glia  cells,  mainly  spider  cells,  which  are  most  numerous  in 
the  layer  of  ganglion  cells  and  in  the  layer  of  nerve  libers. 

The  rod  and  tone  cells  are  first  recognizable  as  unipolar  cellsjFig.  468,0,  c}. 
The  single  process  of  each  extends  outward  as  far  as  the  outer  limiting  mem- 
brane. About  as  soon  as  these  cells  are  recognizable,  a  differentiation  between 
the  rod  cells  and  the  cone  cells  can  be  made  by  their  reactions  to  the  Golgi 
silver  stain,  the  cone  cells  impregnating  much  more  completely  than  the  rod 
cells.  Processes  next  grow  out  from  the  inner  ends  of  the  cells  so  that  they 
become  bipolar  (Fig.  468,  b,  d)  .  Both  rod  and  cone  cells  are  at  first  distributed 
throughout  the  entire  nuclear  layer,  but  later  they  become  arranged  in  a  dis- 
tinct layer  just  beneath  the  outer  limiting  membrane.  Each  cell  next  gives 
rise  to  or  acquires  at  its  outer  end  an  expansion  which  extends  through 


Layer  of  nerve  fibers 
Layer  of  nerve  cells 
Inner  molecular  layer 
Inner  nuclear  layer   • 

Outer  undifferentiated  layer 


FiG.  469. — Vertical  section  through  retina  of  a  four  months'  human  embryo.    Modified  from  Lange. 

the  outer  limiting  membrane  into  the  pigmented  layer.  As  the  pigmented 
cells  give  off  pigmented  processes  which  extend  inward  among  the  outer 
ends  of  the  rods  and  cones,  the  layer  of  retina  just  beneath  the  pig- 
mented layer  consists  of  the  outer  ends  of  the  rod  cells,  the  tips  of  the  cone 
cells,  and  the  extensions  of  the  pigmented  cells.  The  nucleated  portions  of 
the  rod  and  cone  cells  form  the  outer  nuclear  layer.  Though  the  layer  of  rods 
and  cones  and  the  outer  nuclear  layer  present  the  appearance  in  haematoxylin- 
eosin  stained  specimens  of  two  distinct  layers,  it  is  evident  from  their  develop- 
ment and  structure  that  they  should  be  regarded  as  a  single  neuro-epithelial 
layer.  The  apparent  separation  into  two  layers  is  due  to  the  interposition  of  the 
outer  limiting  membrane,  through  tiny  holes  in  which  the  rod  and  cone  cells 
extend.  The  inwardly  directed  processes  of  the  rod  and  cone  cells  are  their 
axones.  These  cells  constitute  the  first  or  distal  optic  neurone. 

The  bipolar  cells  (Fig.  468,  e),  which  with  their  processes  constitute  the 
middle  or  second  optic  neurone,  also  develop  from  cells  of  the  nuclear  layer 


544 


TEXT-BOOK  OF  EMBRYOLOGY. 


and  are  probably  bipolar  at  the  time  that  the  rod  and  cone  cells  are  in  the 
unipolar  condition.  Reference  to  the  two  bipolar  cells  shown  in  Fig.  468,  e,  ey 
shows  that  at  this  stage  in  their  development  their  outwardly  directed  processes 
extend  to  the  outer  limiting  membrane.  These  processes  must  either  actually 
shorten  or  else  fail  to  grow  in  length  proportionately  as  the  retina  increases  in 
thickness,  for  in  the  mature  retina  they  end  in  relation  with  the  centrally 
(inwardly)  directed  processes  (axones)  of  the  rod  and  cone  cells.  According  as 
they  are  in  relation  with  rod  cells  or  cone  cells,  they  are  known  as  rod  bipolars 
or  cone  bipolars.  The  retinal  layer  in  which  the  axones  of  the  rod  and  cone 

Inner  limiting  membrane 


Layer  of  nerve  fibe  rs 
Layer  of  nerve  cells 

Inner  molecular  layer 

( horizontal  cells 

Inner  nuclear  iayer^  bipolar  cells 
(amacrine  cells 

Outer  molecular  layer 


Outer  nuclear  layer 

Outer  limiting  membrane 
Layer  of  rods  and  cones 


Layer  of  pigmented  epithelium 

FIG.  470. — Vertical  section  through  retina  of  a  five  and  one-half  months'  human  embryo. 

Modified  from  Lange. 

cells  and  the  dendrites  of  the  rod  and  cone  bipolars  intermingle  is  the  outer, 
molecular  layer  of  the  adult  retina.  It  is  first  distinctly  recognizable  as  a  mo- 
lecular layer  about  the  end  of  the  fifth  month  (Fig.  470). 

The  development  of  the  outer  molecular  layer  separates  the  originally  single 
nuclear  layer  into  two  layers,  an  outer  composed  of  the  nuclei  of  the  rod  and  cone 
cells  and  an  inner  composed  of  the  nucleated  bodies  of  the  rod  and  cone 
bipolars,  of  the  horizontal  cells  (Fig.  468,  g)  and  of  the  amacrine  cells  (Fig.  468, 
/  and  f),  all  of  which  can  be  recognized  in  Golgi  specimens  by  the  end  of  the 
seyegth  month.  The  rod  and  cone  bipolars  and  probably  most  of  the  other 
cells  of  the  inner  nuclear  layer  send  their  axones  centrally  to  lie  in  contact  with 
the  dendrites  and  bodies  of  the  ganglion  cells. 


THE  ORGANS  OF  SPECIAL  SENSE.  545 

With  the  development  Oi  the  cells  of  the  inner  nuclear  layer  and  their  proc- 
esses, there  differentiates  the  inner  molecular  layer  which  separates  the  inner 
nuclear  layer  and  the  layer  of  ganglion  cells.  It  consists  mainly  of  ramifica- 
tions of  the  dendrites  and  axones  of  cells  the  bodies  of  which  lie  in  the  inner 
nuclear  layer  and  in  the  layer  of  ganglion  cells.  (Fig.  470.) 

The  Chorioid  and  Sclera.— These  develop  wholly  from  the  mesoderm. 
The  way  in  which  the  mesoderm  grows  in  between  the  lens  and  the  surface  and 
surrounds  the  optic  cup  has  been  described  (p.  536).  That  part  of  the  meso- 
derm lying  immediately  external  to  the  retina  develops  very  early  a  close- 
meshed  capillary  network.  This  appears  before  there  is  any  definitely  limited 
sclera  and  may  be  considered  the  anlage  of  the  chorioid,  Somewhat  later  the 
mesoderm  which  lies  just  to  the  outside  of  the  chorioid  takes  definite  shape  as  the 
external  fibrous  tunic  of  the  eye  or  sclera. 

The  Vitreous. — The  manner  in  which  the  vitreous  humor  is  formed  has 
been  the  subject  of  much  controversy  and  remains  still  undetermined.  As 
already  noted  in  describing  the  development  of  the  lens  (p.  555),  the  latter  is  at 
first  in  direct  contact  with  the  inner  layer  of  the  retina  (Fig.  466) .  The  lens  and 
the  retina  separate  as  the  vitreous  forms  between  them.  During  the  develop- 
ment of  the  lens  the  arteria  centralis  retinae  does  not  stop7  as  in  the  adult, 
with  its  retinal  branches,  but  continues  across  the  optic  cup  as  the  hyaloid 
artery  to  end  in  the  vessels  of  the  tunica  vasculosa  lentis.  Some  investigators 
consider  the  vitreous  a  transudate  from  these  blood  vessels.  As  the  chorioidal 
fissure  closes,  some  mesodermic  tissue  is  enclosed  with  the  artery,  and  some 
investigators  consider  the  vitreous  a  derivative  of  this  mesoderm.  In  Birds 
the  formation  of  the  vitreous  humor  begins  before  either  mesoderm  or  blood 
vessels  have  penetrated  the  optic  cup,  and  Rabl  suggests  that  the  vitreous  may 
be  a  secretion  of  the  retinal  cells.  Bonnet  describes  a  double  origin  of  the 
vitreous,  differentiating  between  a  retinal  vitreous  and  a  mesoderm  vitreous. 
According  to  Bonnet,  the  primary  vitreous  body  begins  its  formation  before  the 
closure  of  the  chorioidal  fissure.  This  primary  vitreous  appears  at  the 


itime     £  < 

of  formation  of  the  optic  cup,  is  a  fibrillated  secretion  of  the  retinal  cells,  and 
fills  in  the  vitreous  space  with  a  feltwork  of  fine  fibrils.  With  the  formation  of 
the  optic  cup  and  the  closure  of  the  chorioidal  fissure  this  type  of  vitreous  forma- 
tion ceases  and  a  secondary  vitreous  body  formation  takes  place  from  the  cells 
of  the  pars  ciliaris  retinas.  This  is  also  fibrillated  and  there  develops  at  this 
time  the  so-called  hyaloid  membrane  which  closely  invests  the  vitreous.  Among 
the  fibers  of  the  vitreous  body  appears  the  vitreous  humor.  Up  to  this  point  the 
vitreous  is  entirely  non-cellular.  There  next  grow  into  it  mesodermal  cells 
which  have  reached  the  vitreous  through  the  chorioidal  fissure  aloni{  with  the 
hyaloid  artery.  To  what  extent  these  cells  are  used  up  in  the  formation  of  the 
blood  vessels  of  the  vitreous  and  to  what  extent  they  remain  as  connective  tissue 


546  TEXT-BOOK  OF  EMBRYOLOGY. 

cells  of  the  mature  vitreous  after  the  blood  vessels  have  degenerated  is  not 
known. 

As  already  noted,  the  vitreous  is  at  first  crossed  by  the  hyaloid  artery  which 
supplies  the  developing  lens  (p.  539).  As  lens  formation  becomes  less  active 
the  artery  becomes  less  important  and  by  the  end  of  the  third  month  begins  to 
atrophy.  At  birth  nothing  remains  of  it,  but  in  its  former  course  the  vitreous 
is  somewhat  more  fluid  than  elsewhere  and  this  is  known  as  the  hyaloid  canal 
(canal  of  Cloquet). 

The  Optic  Nerve. — Referring  to  the  description  of  the  optic  evagination  it 
will  be  recalled  that  the  optic  vesicle  maintains  its  connection  with  the  brain  by 
means  of  the  optic  stalk  (p.  534) .  The  latter  is  hollow  and  connects  the  cavity 
of  the  optic  vesicle  with  the  cavity  of  the  brain.  When  the  invagination  of  the 
optic  vesicle  to  form  the  optic  cup  occurs  (p.  536,  Fig.  464),  the  invagination  is 
carried  along  the  posterior  surface  of  the  optic  stalk  toward  the  brain,  and  just 
as  the  invagination  of  the  optic  vesicle  results  in  the  obliteration  of  the  cavity 
of  the  vesicle,  so  the  invagination  of  the  optic  stalk  results  in  an  oblitera- 
tion of  its  lumen.  In  Mammals  the  invagination  of  the  optic  stalk  extends  only 
part  way  to  the  brain,  to  the  point  where  the  artery  enters.  The  chorioidal 
fissure  closes  about  the  seventh  week. 

The  optic  stalk  consists  of  supportive  elements  only,  and  serves  as  a  track 
along  which  nerve  fibers  extend  to  connect  the  retina  and  brain.  Nerve  fibers 
appear  in  the  optic  stalk  about  the  fifth  week.  They  appear  first  around  the 
periphery  and  apparently  crowd  the  neuroglia  nuclei  toward  the  center,  so  that 
the  stalk  at  this  stage  may  be  said  to  consist  of  a  mantle  layer  and  a  marginal 
layer,  apparently  analogous  to  these  layers  in  the  retina  and  brain.  The  nerve 
fibers  gradually  invade  the  entire  stalk  so  that  by  the  end  of  the  third  month  the 
stalk  has  become^  transformed  into  the  optic  nerve  among  the  fibers  of  which  the 
original  supportive  elements  of  the  stalk  are  still  represented  by  neuroglia  cells. 

Much  difference  of  opinion  has  existed  in  regard  to  the  origin  of  the  optic 
nerve  fibers,  whether  they  are  processes  of  retinal  cells  which  end  in  the  brain 
or  processes  of  brain  cells  which  end  in  the  retina.  It  is  now  quite  generally 
accepted  that  most  of  the  fibers  of  the  optic  nerve  are  the  axones  of  nenrnneg  the 
cell  bodies  of  which  are  situated  in  the  ganglion  cell  layer  of  the  retina.  These 
axones  pass  centrally  into  the  layer  of  nerve  fibers,  which  they  form,  and  con- 
verge toward  the  optic  nerve.  Through  the  latter  they  pass  to  their  terminations 
in  the  external  geniculate  bodies,  optic  thalami  and  anterior  corpora  quadri- 
gemina.  According  to  Cajal  and  others,  some  centrifugal  fibers  are  present  in 
the  optic  nerve.  These  are  processes  of  cells  situated  in  the  above-mentioned 
nuclei,  and  terminate  in  the  retina.  They  are  fewer  in  number  and  of  later 
development  than  the  centripetal  fibers. 

As  the  mesodermic  anlagen  of  the  chorioid  and  sclera  are  present  before 


THE  ORGANS  OF  SPECIAL  SENSE.  547 

the  nerve  fibers  begin  to  grow  into  the  optic  stalk,  the  fibers  must  pass  through 
these  two  coats  in  their  exit  from  the  eye.  There  results  the  fenestrated  cross- 
ing of  the  optic  nerve  by  these  two  coats,  known  as  the  lamina  cribrosa. 

The  optic  nerve  fibers  are  medullated  but  have  no  neurilemmae.  They  are 
supported  by  neuroglia.  The  connective  tissue  sheaths  which  enclose  the  optic 
nerve  are  direct  extensions  of  the  meninges.  These  structural  peculiarities 
accord  with  the  peculiarities  already  described  in  the  development  of  the 
nerve.  Attention  has  been  called  to  the  fact  (p.  m)  that  just  as  the  retina 
should  be  considered  a  modified  and  displaced  portion  of  the  central  nervous 
system — of  brain  cortex — so  the  optic  nerve  should  be  considered  not  as  a 
peripheral  nerve,  but  as  analogous  to  a  central  nervous  system  fiber  tract. 

The  Ciliary  Body,  Iris,  Cornea,  Anterior  Chamber.— Anteriorly  where 
they  come  into  relation  with  the  lens  and  are  so  arranged  as  to  admit  light  to  the 
retina,  all  three  coats  of  the  eye  are  extensively  modified.  Thus  the  retina  is 
continued  anteriorly  as  the  pars  ciliaris  retinae  and  pars  iridica  retinae,  the 
chorioid  as  the  stroma  of  the  ciliary  body  and  iris,  the  sclera  as  the  cornea. 

THE  CILIARY  BODY  AND  IRIS. — Both  primary  retinal  layers  (the  two  layers 
of  the  optic  cup)  are  continued  anteriorly  as  the  non-nervous  retinal  layer 
of  the  ciliary  body  and  iris.  The  outer  pigmented  layer  consists  at  first  of 
several  layers  of  pigmented  cells,  but  later  becomes  reduced  to  a  single  layer 
of  pigmented  cells  which  do  not,  however,  possess  pigmented  processes  extend- 
ing inward  as  do  the  analogous  cells  of  the  nervous  retina.  The  abrupt  tran- 
sition at  the  ora  serrata  where  the  thick  pars  optica  retinae  passes  over  into  the 
pars  ciliaris  retinae  has  been  mentioned  (p.  540) .  The  inner  laver  of  th<*  primi- 
tive  retina  (optic  cup)  extends  over  the  ciliary  body  and  iris  as  a  single  layer  of 
cells.  These  remain  non-pigmented  over  the  ciliary  body,  but  over  the  iris 
acquire  pigment  so  that  the  two  layers  form  the  pigmented  layer  of  the  iris. 

The  mesodermic  tissue  which  forms  the  stroma  of  the  ciliary  body  and  iris 
is  derived  from  the  mesoderm  lying  between  the  lens  and  the  surface  ectoderm. 
This  separates  into  two  layers  enclosing  between  them  the  anterior  chamber  of 
the  eve,  and  it  is  from  the  posterior  of  these  two  layers  that  mesodermic  tissue 
extends  into  the  ciliary  body  and  iris.  It  is  continuous  with  the  mesoderm  of 
the  tunica  vasculosa  lentis.  During  the  fourth  month  the  ciliary  body  under- 
goes  foldings  to  form  the  ciliary  processes.  These  foldings  at  first  involve 
also  the  iris,  but  the  iris  folds  soon  (end  of  fifth  month)  disappear,  while  the 
ciliary  processes  become  more  prominent. 

Of  the  smooth  muscle  tissue  found  in  the  ciliary  body  and  iris,  the  dilator 
and  contractor  pupillse  are,  according  to  Bonnet,  derived  from  the  cells  of  the 
pigmented  layer  of  the  retina,  i.e.,  from^tpderm.^  The  ciliary  muscle,  on  the 
other  hand,  develops  from  mesoderm.  These  muscles  become  well  developed 
during  the  seventh  month. 


548  TEXT-BOOK  OF  EMBRYOLOGY. 

...  The  suspensory  ligament  of  the  lens,  or  zonula  Zinnii,  first  appears  about  the 
end  of  the  fourth  month.  ,  By  some  the  fibers  of  the  suspensory  ligament 
are  believed  to  differentiate  from  the  vitreous,  by  others  they  are  considered  as 
derived  from  the  pars  ciliaris  retinae.  Spaces  among  the  fibers  of  the  ligament 
enlarge  and  coalesce. to  form  the  canal  of  Petit^ 

THE  CORNEA. — The  way  in  which  the  mesoderm  grows  in  between  the  lens 
vesicle  and  the  surface  ectoderm  has  been  described  (p.  536) .  This  mesoderm 
forms  a  thin  almost  homogeneous  layer  containing  v^rv  few  cells.  Later  that 
part  of  the  layer  which  lies  against  the  lens  becomes  more  cellular  and  vascular, 
so  that  it  is  possible  to  distinguish  between  an  outer  homogeneous  non- vascular 
layer  and  an  inner  cellular  vascular  layer.  The  former  is  the  anlage  of  the 
cornea.  Between  the  two  layers  vacuoles  appear  and  coalesce  to  form  the 
anterior  chamber  of  the  eye  or  cavity  of  the  aqueous  humor.  Subsequent 
growth  of  the  iris  subdivides  this  chamber  into  an  anterior  and  a  ^posterior 
portion.  The  chamber  separates  the  cornea  from  the  pupillary  membrane 
portion  of  the  tunica  vasculosa  lentis.  Bounding  the  chamber  anteriorly  and 
so  forming  the  posterior  layer  of  the  cornea  there  develops  a  single  layer  of 
flat  cells,  the  so-called  " endothelium"  of  Descemet.  Over  the  surface  of  the 
cornea  the  ectoderm  remains  and  gives  rise  to  a  stratified  squamous  epithelium 
four  to  eight  cells  thick,  the  anterior  corneal  epithelium.  Just  beneath  the 
epithelium  a  layer  of  corneal  tissue  retains  its  original  homogeneous  character 
and  forms  the  anterior  elastic  membrane  or  membrane  of  Bowman.  The 
posterior  elastic  membrane  or  membrane  of  Descemet  is  usually  considered  a 
cuticular  derivative  of  the  u  endothelium."  Throughout  the  rest  of  the  cornea 
— substantia  propria  cornea — cells  develop,  either  by  proliferation  of  the 
few  cells  originally  present  or  from  cells  which  grow  in  from  the  surrounding 
cellular  mesoderm,  and  become  arranged  parallel  to  the  surface  as  the  fixed 
connective  cells  of  the  cornea. 

The  Eyelids. — After  the  lens  vesicle  becomes  separated  from  the  surface 
ectoderm,  the  latter  folds  over  above  and  below  to  form  the  first  rudiments 
of  the  upper  and  lower  eyelids.  Each  fold  consists  of  a  core  of  mesoderm  andi 
a  covering  of  ectoderm.  From  the  mesoderm  develop  the  connective  tissue 
elements  of  the  lids  including  the  tarsal  cartilage.  From  the  ectoderm  develop 
the  epithelial  structures  of  the  lids,  the  epidermis,  the  eyelashes  and  the  glands. 
The  edges  of  the  lids  gradually  approach  each  other  and  about  the  beginning 
of  the  third  month  the  epithelium  of  the  upper  licTbecomes  adherent  to  that 
of  the  lower,  thus  completely  shutting  in  the  eyeball.  This  condition  obtains 
until  just  before  birth. 

The  eyelashes  develop  in  the  same  manner  as  other  hairs  (p.  417). 

The  Meibomian  glands,  glands  of  Moll  and  the  lacrymal  glands  develop, 
during  the  period  the  lids  are  adherent,  as  solid  cords  of  ectoderm  which  g.ow 


THE  ORGANS   OF  SPECIAL  SENSE.  549 

into  the  underlying  mesoderm  where  they  ramify  to  form  the  ducts  and  tubules. 
The  anlagen  of  the  ducts  and  tubules  of  these  glands  al'(t  LllUb  at  fust  SUkUfToi ils 
of  cells,  their  lumina  being  formed  later  by  a  breaking  down  of  the  central  cells 
of  the  cords. 

At  the  inner  angle  of  the  conjunctiva  there  develops  beneath  the  eyelid 
folds  a  third  much  smaller  fold.  This  becomes  the  plica  scmilunaris  which 
in  man  is  a  rudimentary  structure,  but  in  many  of  the  lower  Vertebrates, 
especially  Birds,  forms  a  distinct  third  eyelid,  the  so-called  nictitating  mem- 
brane. A  few  hair  follicles  and  sebaceous  glands  develop  in  a  portion  of  this 
fold  forming  the  lacrymal  caruncle.. 

The  Lacrymal  Duct.  At  a  certain  stage  in  development,  a  groove  bounded 
by  the  maxillary  process  and  the  lateral  nasal  process  extends  from  the  eye  to 
the  nose  (Fig.  98).  This  is  known  as  the  naso-optic  furrow.  Tin-  cvlodrrm 
(epithelium)  lying  along  the  bottom  of  this  groove  thickens  about  the  sixth 
week  and  forms  a  solid  cord  of  cells.  As  development  proceeds  and  the  parts 
close  in,  this  cord  of  ectoderm  becomes  enclosed  within  the  mesoderm,  excepting 
at  its  ends  where  it  remains  connected  with  the  surface  ectoderm  of  the  eye  and 
nose,  respectively.  By  a  breaking  down  of  the  central  cells  of  this  cord  a  lumen 
is  formed  and  the  cord  becomes  a  tube,  the  lacrymal  duct.  The  primary  con- 
nection  of  the  laojgnalduct  is  with  the  upper  lid,  but  while  the  lumen  is  being 
formed  an  offshoot  grows  out  to  the  under  eyelid  to  form  the  inferior  branch 
of  the  lacrymal  duct. 

THE  NOSE. 

The  anlage  of  the  organ  of  smell  is  apparent  in  human  embryos  of  about 
three  weeks  as  two  thickenings  of  the  ectoderm,  one  on  each  side  of  the  naso- 
frontal  process.  To  these  thickenings  the  term  olfactory  placodes  has  been 
applied  (Kupffer) .  A  little  later  (in  embryos  of  about  four  weeks) ,  the  placodes 
become  depressed  below  the  surface,  the  depressions  themselves  being  the 
nasal  pits  or  fossa  (see  p  120;  also  Fig.  87).  The  placodes.  which  are 
destined  to  give  rise  to  the  sensory  epithelium,  thus  come  into  closer  relation 
with  the  olfactory  lobes  of  the  brain  (rhinencephalon)  which  represent  out- 
growths of  the  fore-brain  (telencephalon)  (see  p.  471). 

As  described  in  connection  with  the  development  of  the  face,  the  lateral 
nasal  process  arises  on  the  lateral  side,  the  medial  nasal  process  on  the  medial 
side,  of  each  nasal  pit  (p.  120  et  seq.;  also  Fig.  96).  Of  these  processes,  the 
lateral  is  destined  to  give  rise  to  the  lateral  nasal  wall  and  the  wing  of  the  nose, 
the  medial  to  a  part  of  the  nasal  septum  (see  p.  120).  As  development  pro- 
ceeds, the  epithelium  (ectoderm)  of  the  nasal  fossae  grows  still  deeper  into  the 
subjacent  mesoderm,  the  fossae  thus  becoming  converted  into  the  nasal  sacs, 
which  lie  above  the  oral  cavity.  According  to  Hochstetter  and  Peter,  the 


550  TEXT-BOOK  OF  EMBRYOLOGY. 

nasal  sacs  are  not  at  first  in  communication  with  the  oral  cavity,  but  lie  above, 
and  are  separated  from  it  by  a  plate  of  tissue  which  gradually  becomes  thinned 
out  along  the  deeper  part  of  the  sacs  to  form  the  bucco-nasal  membrane  (Hoch- 
stetter).  Later  (in  embryos  of  15  mm.),  the  bucco-nasal  membrane  ruptures 
and  the  deep  ends  of  the  sacs  thus  come  to  open  into  the  mouth  cavity,  the 
openings  being  known  as  the  primitive  choanen.  In  front  of  the  primitive 
choanen,  the  nasal  passages  (formerly  the  nasal  sacs)  are  separated  from 
the  mouth  cavity  by  a  plate  of  tissue,  known  as  the  primitive  palate  (Fig.  471). 
The  latter  is  produced  by  the  fusion  of  the  maxillary  process  with  the  lateral 
and  medial  nasal  processes  (see  p.  121),  the  outer  nares  thus  being  somewhat 
separated  from  the  border  of  the  mouth. 

The  further  separation  of  the  nasal  passages  from  the  o/al  cavity  has  been 
described  in  connection  with  the  development  of  the  mouth  (p.  286)  and  the 


Lateral  nasal  process 

Outer  nasal  opening 

Maxillary  process 

Eye 

Primitive  choanen 

Palatine  process 


FIG.  471. — From  a  model  of  the  anterior  part  of  the  head  of  a  15  mm.  human  embryo.     The  lower 
jaws  (mandibular  processes)  have  been  removed.     Peter, 

development  of  the  palatine  processes  of  the  maxillae.  It  may  be  repeated 
briefly,  however,  that  from  each  maxillary  process  a  horizontal  extension  grows 
across  between  the  oral  and  nasal  cavities  until  it  meets  and  fuses  with  its  fellow 
of  the  opposite  side  and  with  the  nasal  septum  in  the  medial  line,  thus  forming 
the  palate  which  is  continuous  with  the  primitive  palate  mentioned  above. 
(See  Figs.  140  and  47 2.)  In  this  way  the  nasal  cavities  or  chambers  become 
separated  from  the  oral  cavity,  but  remain  in  communication  with  the  pharyn- 
geal  cavity  through  the  posterior  nares. 

The  nasal  cavities  increase  enormously  in  size  and  the  epithelial  surface  in 
extent,  owing  to  (i)  the  formation  of  the  palate  alluded  to  above,  (2)  the  develop- 
ment of  the  nasal  concha  which  has  been  described  on  page  161,  and  (3)  the 
development  of  accessory  cavities — maxillary,  frontal  and  sphenoidal  sinuses, 
which  represent  evaginations,  so  to  speak,  from  the  nasal  cavities. 

Probably  correlated  with  the  above-mentioned  increase  in  extent  of  the 
nasal  chambers  is  the  fact  that  in  lung-breathing  Vertebrates  the  chambers 


THE   ORGANS   OF  SPECIAL  SENSE. 


551 


have  acquired  a  secondary  function.  In  these  forms  the  nose  is  not  only  an 
apparatus  for  receiving  olfactory  stimuli,  but  also  serves  to  convey  air  to  and 
from  the  lungs;  it  is  in  a  sense  a  respiratory  atrium.  The  sensory  epithelium 
which  the  olfactory  nerves  supply  is  limited  to  relatively  small  areas  in  the  supe- 
rior conchae  and  nasal  septum.  Stratified  columnar  ciliated  epithelium  lines  all 
other  parts  of  the  cavities. 

Studies  on  the  development  of  the  olfactory  nerve  have  led  to  diverse 
opinions,  but  the  investigations  of  His  and  Disse  go  to  show  that  the  fibers 
are  processes  of  cells  derived  from  the  thickened  ectoderm  or  olfactory  placodes. 
In  human  embryos  of  about  four  weeks  some  of  the  cells  in  the  upper  part  of 
the  nasal  fossa  become  modified  to  form  the  neuro-epithelium.  From  the 


Jacobson's  organ 
Inferior  concha 

Jacobson's  cartilage 


Palatine  process 


Nasal  septum 


Nasal  cavity 


Oral  cavity 


FIG.  472.— From  a  section  through  the  head  of  a  human  embryo  of  28  mm.,  showing  the  nasal 
septum,  the  nasal  cavities,  the  oral  cavity,  and  the  palatine  processes.     Peter. 

peripheral  pole  of  each  cell  a  short  slender  process  grows  out  to  the  surface  of 
the  epithelium.  From  the  opposite  pole  a  slender  process  (the  axone)  grows 
centrally  until  it  penetrates  the  olfactory  lobe,  where  it  ends  in  contact  with  the 
dendrites  of  the  first  central  neurone  of  the  olfactory  tract.  Most  of  these  cells 
remain  in  the  epithelial  layer,  but  a  few  wander  into  the  subjacent  mesoderm 
and  become  bipolar  cells  which  resemble  the  bipolar  cells  of  the  embryonic 
posterior  root  ganglia  (p.  472).  Other  epithelial  cells  of  the  nasal  fossa  are 
converted  into  the  sustentacular  cells  of  the  olfactory  areas. 

Jacobson's  organ  arises  at  the  beginning  of  the  third  month  as  a  small  out- 
pocketing  of  the  epithelium  on  the  lower  anterior  part  of  the  nasal  septum 
(Fig.  472).  This  evagination  grows  backward  as  a  slender  sac  along  the  nasal 
septum  for  a  distance  of  several  millimeters  and  ends  blindly.  In  the  adult 
the  sac  degenerates  and  often  disappears.  In  some  of  the  lower  Mammals 


552  TEXT-BOOK  OF  EMBRYOLOGY. 

Jacobson's  organ  develops  to  a  greater  degree,  and  some  of  the  epithelial  cells 
send  out  processes  which  pass  to  the  olfactory  lobes. 

THE  EAR. 

The  ear  of  higher  Vertebrates  consists  of  three  parts — the  internal,  middle, 
and  external.  Of  these,  the  internal  is  the  sensory  portion  proper  and,  so  far 
as  the  epithelial  elements  are  concerned,  is  of  ectodermal  origin,  but  secondarily 
becomes  embedded  in  the  subjacent  mesoderm.  It  constitutes  a  complicated 
and  highly  specialized  structure  for  the  reception  of  certain  stimuli  that  are  to  be 
conveyed  to  the  central  nervous  system.  From  a  functional  standpoint  it  may 
be  divided  into  the  portion  composed  of  the  semicircular  canals  and  their  ap- 
pendages, which  is  concerned  in  receiving  and  transmitting  stimuli  destined 

Rh.  br. 

End.  ap. 
Aud.  ves. 


FIG.  473. — Half  of  a  transverse  section  through  the  region  of  the  developing  ear  of  a  sheep 

embryo  of  13  mm.     Bottcher. 

Aud.  ves.,  Auditory  vesicle;  Co.   gang.,   cochlear  ganglion;  End.  ap.,  endolymphatic 
appendage;  Rh.br.,  rhombic  brain. 

for  the  static  and  equilibration  centers  in  the  central  nervous  system,  and  the 
cochlear  portion,  which  is  concerned  in  receiving  and  transmitting  auditory 
stimuli.  The  middle  and  outer  ear  represent  modified  portions  of  the  most 
cranial  of  the  branchial  arches  and  grooves,  and  constitute  an  apparatus  for 
conducting  sound  waves  to  the  cochlear  portion  of  the  inner  ear. 

The  Inner  Ear. — In  embryos  of  2  to  4  mm.,  the  ectoderm  becomes  some- 
what thickened  over  a  small  area  lateral  to  the  still  open  neural  groove  in  the 
region  of  the  future  hind-brain.  This  thickening  is  often  spoken  of  as  the 
auditory  placode  (see  p.  469).  Owing  to  more  rapid  growth  of  the  cells  in  the 
deeper  layers  of  the  placode,  it  soon  becomes  converted  into  a  cup-shaped 
depression  which  is  known  as  the  auditory  pit.  The  edges  of  the  pit  fold 
in  and  fuse  and  the  pit  thus  becomes  the  auditory  vesicle  (otocyst),  which 
finally  becomes  constricted  from  the  parent  ectoderm  and  lies  free  in  the  sub- 
jacent mesoderm  (Fig.  473). 


THE   ORGANS   OF  SPECIAL  SENSE.  553 

At  this  stage  (embryos  of  4  to  5  mm.)  the  auditory  vesicle  is  an  oval  or 
spherical  sac  the  wall  of  which  consists  of  two  or  three  layers  of  undifferen- 
tiated  epithelial  cells.  It  lies  against  the  neural  tube  and  is  connected  with  the 
latter  by  the  acoustic  ganglion  (Fig.  474,  a).  About  the  same  time  an  evagina- 
tion  appears  on  the  dorsal  side  of  the  auditory  vesicle,  forming  the  anlage  of  the 
endolymphatic  appendage  (Fig.  474,  a,  b,  c).  The  evagination  continues  to 
elongate  and  comes  to  form  a  club-shaped  structure,  the  distal  end  of  which 
becomes  flattened  to  form  the  endolymphatic  sac,  the  narrower  proximal  portion 
constituting  the  endolymphatic  duct  (Fig.  474  a-w).  The  epithelium,  which  at 
first  consisted  of  two  or  three  layers  of  cells,  becomes  reduced  to  a  single  layer. 
In  the  chick  the  endolymphatic  appendage  is  formed  out  of  the  original  union 
between  the  ectoderm  and  the  auditory  vesicle  (Keibel,  Krause).  In  Reptiles 
and  Amphibia  (Peter,  Krause)  and  in  man  (Streeter),  on  the  other  hand,  this 
appendage  develops  independently  of  the  union,  appearing  on  the  dorsal  side  of 
the  seam  of  closure  in  the  auditory  vesicle. 

In  embryos  of  about  6  mm.  the  auditory  vesicle  (apart  from  the  endolymph- 
atic appendage)  becomes  differentiated  into  two  portions  or  pouches — a  bulging, 
triangular  one  above,  which  is  connected  with  the  endolymphatic  appendage, 
and  a  more  flattened  one  below.  The  former  is  the  vestibular  pouch,  the  latter 
the  cochlear  pouch  (Fig.  474,  b-f).  Between  the  two  is  a  portion  of  the  vesicle 
which  is  destined  to  give  rise  to  the  saccule  and  utricle,  and  which  may  be  called 
the  atrium  (Streeter).  Properly  speaking,  the  atrium  is  a  division  of  the 
vestibular  pouch.  The  cochlear  pouch  is  phylogenetically  a  secondary  diver- 
ticulum  which  develops  from  the  atrium,  appearing  first  in  the  lowest  land- 
inhabiting  Vertebrates  (Amphibia). 

As  mentioned  above,  the  vestibular  pouch  early  assumes  the  form  of  a 
triangle,  with  the  apex  toward  the  endolymphatic  appendage.  The  three 
borders  of  the  triangle  form  the  anlagen  of  the  semicircular  canals  and  bear  the 
same  interrelation  as  the  latter.  At  the  same  time  a  vertical  groove  (the  lateral 
groove)  appears  between  the  anlage  of  the  posterior  canal  and  the  posterior  end 
of  the  lateral  canal  (Fig.  474,  b,  d). 

The  formation  of  the  semicircular  canals  is  shown  in  Fig.  474,  g-k.  The 
edges  of  the  triangular  vestibular  pouch  expand  and  become  more  or  less 
crescentic  in  shape.  The  two  walls  in  the  concavity  of  each  crescent  come 
together  and  then  break  away  (Fig.  474,  g,  j,  absorp. focus),  thus  leaving  the  rim 
of  the  crescent  as  a  canal  attached  at  its  two  ends  to  the  utricle.  The  breaking 
away  affects  first  the  superior,  then  the  posterior,  and  finally  the  lateral  canal. 
During  these  gross  changes  the  epithelium  becomes  reduced  to  a  single  layer 
of  cells. 

At  one  end  of  each  canal  an  enlargement  appears  to  form  the  ampulla,  as 
shown  in  Fig.  474,  /,  m,  n,  and  Fig.  475.  a.  6.  c. 


554 


TEXT-BOOK  OF  EMBRYOLOGY. 


A^  A 

BBRrW 


THE  ORGANS  OF  SPECIAL  SENSE. 


555 


556  TEXT-BOOK  OF  EMBRYOLOGY. 

The  utricle  and  saccule  represent  divisions  of  the  portion  of  the  vestibular  sac 
which  is  known  as  the  atrium,  and  into  which  the  endolymphatic  appendage 
and  cochlea  open  (see  p.  553).  In  embryos  of  about  20  mm.  a  horizontal  con- 
striction begins  to  divide  the  atrium  into  an  upper  utricular  portion,  into  which 
the  semicircular  canals  open,  and  a  lower  saccular  portion  (Fig.  474,  /,  m). 
The  constriction  begins  on  the  side  opposite  the  endolymphatic  appendage  and 
gradually  extends  across  the  atrium  until  it  finally  divides  the  opening  of  the 
endolymphatic  appendage  into  two  parts  (Fig.  475,  a,  b,  c).  One  of  these 
parts  opens  into  the  utricle,  the  other  into  the  saccule,  the  two  parts  together 
constituting  the  utriculo saccular  duct. 

As  stated  before,  the  two-  or  three-layered  epithelium  of  the  earlier  stages 
becomes  reduced  to  a  single  layer.  The  cells  of  this  layer  are  low  cuboidal, 
with  the  exception  of  those  over  small  areas  in  the  ampullae,  in  the  saccule,  and 
in  the  utricle.  Over  an  elongated  area  in  each  ampulla  (crista  ampullaris),  a 
round  area  in  the  saccule  and  another  in  the  utricle  (macula  acusticd),  the 
epithelium  becomes  high  columnar,  some  of  the  cells  developing  cilia  on  their 
free  borders  ("hair  cells,"  neuro-epithelium) ,  the  others  becoming  the  susten- 
tacular  cells.  These  areas  are  the  end-organs  of  the  vestibular  nerve  (see  p.  469) . 

As  already  mentioned,  the  cochlear  pouch  appears  as  an  outgrowth  from  the 
lower  side  of  the  atrium  (see  also  Fig.  474,  b-f) .  The  pouch  becomes  somewhat 
flattened,  and,  as  it  continues  to  grow  in  length,  becomes  coiled  like  a  snail- 
shell  (Fig.  474,  g-n;  Fig.  475,  a-c).  This  first  formed  coiled  structure  is  the 
cochlear  duct,  or  scala  media.  At  the  same  time,  it  becomes  distinctly  marked 
off  from  the  lower  part  of  the  atrium  (now  the  saccule)  by  a  constriction,  the 
constricted  portion  forming  the  ductusr  reuniens  (Fig.  474,  l-n;  Fig  475,  a-c). 

All  the  structures  thus  far  considered  are  at  first  closely  invested  by  meso- 
derm.  Later,  this  portion  of  the  mesoderm  gives  rise  to  special  tissues,  and,  in 
the  region  of  the  cochlear  duct,  to  the  scala  vestibuli  and  scala  tympani.  The 
cells  immediately  around  the  vesicle  proliferate  and  a  dense  fibrous  layer  is 
formed;  outside  of  this  fibrous  layer  the  tissue  becomes  gelatinous;  outside  of 
this  again  another  fibrous  layer  is  formed,  around  which  cartilage  develops. 
The  inner  fibrous  layer  gives  rise  to  the  connective  tissue  that  supports  the 
epithelial  lining  of  the  vesicle.  The  gelatinous  layer  degenerates  to  form  a 
fluid  known  as  the  perilymph,  the  space  containing  the  fluid  being  the  perilymph- 
atic  space.  The  outer  fibrous  layer  becomes  the  perichondrium — later  the 
periosteum  when  the  cartilage  is  replaced  by  the  petrous  portion  of  the  tem- 
poral bone. 

In  the  cochlear  region  the  conditions  are  somewhat  modified.  Here  the 
gelatinous  layer  does  not  form  a  complete  covering  for  the  cochlear  duct,  but  is 
interrupted  along  two  lines,  (i)  Laterally  the  fibrous  layer  lying  next  the 
cochlear  duct  is  fused  with  the  perichondrium  (outer  fibrous  layer)  (Fig.  476), 


THE   ORGANS   OF  SPECIAL  SENSE.  557 

(2)  Medially  the  inner  fibrous  layer  is  fused  with  the  perichondrium  of  a  shelf-like 
process  of  cartilage  which  later  ossifies  to  form  the  bony  spiral  lamina  (Fig. 
476).  By  these  two  partitions  the  cochlear  perilymphatic  space  is  separated 
into  two  spiral  compartments  which  communicate  only  at  the  apex  of  the 
cochlea.  The  larger  of  these  compartments,  the  scala  vestibuli,  communicates 
with  the  perilymphatic  space  around  the  utricle  and  saccule.  The  wall  separat- 
ing the  scala  vestibuli  and  cochlear  duct  becomes  thinned  out  to  form  the 


Cochlear  duct 


Cartilage 

Scata  vestibuli 
(gelatinous  tissue) 


Cochlear  duct  /——— ™.j(_- 

Cochlear  (spiral)  ganglion  

Coch.  nerve  to  organ  of  Corti  £____ 

Scala  tympani         111 

Cochlear  nerve  — iL- 

Fibrous  con.  tis.  •    j||i 

Connective  tissue  _/ 

Scala  vestibuli  _JL_________  /  __ 

Perichondrium  _  /V  '.- 

~~f 
Vestibular  membrane  __  K^ 

Lat.  wall  of  coch.  duct     \&# 


Organ  of  Corti  _ 
Scala  tympani 

Cartilage 


V 


FIG.  476. — Section  through  the  developing  cochlea  of  a  90  mm.  cat  embryo.     Bottcher. 

vestibular  membrane  (of  Reissner).  The  smaller  compartment,  the  scala 
tympani,  remains  separated  from  the  cavity  of  the  middle  ear  by  a  thin  mem- 
brane which  closes  the  fenestra  cochlea  (rotunda) .  In  the  wall  between  the 
scala  tympani  and  the  cochlear  duct  the  organ  of  Corti  develops  (see  below). 
A  membrane,  similar  to  that  closing  the  fenestra  cochleae,  occurs  between  the 
cavity  of  the  middle  ear  and  the  utricle,  closing  the  fenestra  vestibuli  (ovalis). 
As  alluded  to  above,  the  organ  of  Corti  develops  from  the  wall  of  the  cochlear 


558  TEXT-BOOK  OF  EMBRYOLOGY. 

duct  between  the  latter  and  the  scala  tympani  (Fig.  476).  The  epithelial  cells 
of  the  cochlear  duct  in  this  region  become  high  columnar  and  arranged  in  two 
ridges  which  extend  throughout  the  entire  length  of  the  duct.  The  cells  of  the 
ridge  nearer  the  axis  of  the  cochlea  give  rise  to  the  membrana  tectoria.  Whether 
this  is  accomplished  by  cuticular  secretion  of  the  cells  or  by  the  fusion  of  long 
hair-like  processes  that  grow  from  their  free  borders  is  not  known.  The  cells  of 
the  outer  ridge  become  differentiated  into  four  groups.  Those  of  the  outer 
group  (next  the  cells  that  give  rise  to  the  membrana  tectoria)  develop  into  the 
inner  hair  cells;  those  of  the  next  group  form  the  pillar  cells;  those  of  the  third 
group  differentiate  into  the  outer  hair  cells;  and  those  of  the  fourth  (outer) 
group  give  rise  to  Hensen's  cells.  The  hair  cells,  as  the  name  indicates,  develop 
delicate  hair-like  processes  on  their  free  borders,  and,  since  the  peripheral 
processes  of  the  spiral  (cochlear)  ganglion  cells  end  around  them,  are  con- 
sidered as  the  sensory  cells  of  the  cochlea,  or  auditory  receptors  (see  p.  469) . 

THE  ACOUSTIC  NERVE. — The  acoustic  ganglionic  mass  is  at  first  closely 
associated  with  the  geniculate  ganglion  (ganglion  of  the  facial  (VII)  nerve),  the 
two  together  often  being  spoken  of  as  the  acustico-facialis  ganglion  (see  also 
p.  508) .  This  lies  in  close  contact  with  the  anterior  wall  of  the  auditory  vesicle 
when  the  latter  is  first  constiicted  from  the  ectoderm.  The  origin  of  the  gang- 
lion has  not  been  traced  in  Ma*M#*als,  but  in  cow  embryos  the  geniculate  has 
been  seen  to  be  connected  with  the  ectoderm  at  the  dorsal  end  of  the  first 
branchial  groove  (Froriep).  The  acoustic  ganglion  probably  belongs  to  the 
lateral  line  system  (Kupffer)  (see  also  p.  430) . 

Although  the  geniculate  and  acoustic  ganglia  are  at  first  closely  associated, 
each  pursues  an  independent  course  of  development.  The  description  here 
will  be  confined  to  the  acoustic.  As  already  mentioned,  this  lies  in  close  apposi- 
tion to  the  side  of  the  neural  tube  and  the  auditory  vesicle  and  just  anterior  to 
the  latter  (Fig.  474,  a).  At  a  very  early  stage  (embryos  of  6-7  mm.),  the  mass 
shows  a  differentiation  into  two  parts — a  dorsal  one,  the  future  vestibular 
ganglion,  and  a  ventral  one,  the  future  cochlear  (spiral)  ganglion  (Fig.  474,  b,  c). 
The  ganglion  cells  become  bipolar  (see  p.  469) ,  and,  as  is  peculiar  to  the  cells  of 
the  acoustic  ganglia,  remain  in  this  condition.  One  process  of  each  cell  grows 
centrally  to  form  a  root  fiber  of  the  acoustic  nerve,  which  terminates  in  contact 
with  dendrites  of  neurones  in  certain  nuclei  in  the  central  nervous  system.  The 
fibers  from  the  cells  of  the  vestibular  ganglion  form  the  vestibular  root,  those 
from  the  cells  of  the  cochlear  ganglion  form  the  cochlear  root.  The  other  proc- 
ess grows  peripherally  and  penetrates  the  wall  of  the  auditory  vesicle  to  enter 
into  relation  with  certain  cells  that  differentiate  from  the  epithelial  lining  of  the 
vesicle. 

The  peripheral  processes  of  the  vestibular  ganglion  cells  come  into  relation 
with  specialized  cells  (hair  cells)  in  the  ampullae  of  the  semicircular  canals 


THE  ORGANS   OF  SPECIAL  SENSE.  559 

(crista  ampullaris)  and  in  the  saccule  and  utricle  (macula  acustica)  (see 
p.  556).  The  nerve  itself  becomes  divided  into  certain  branches,  as  indicated 
in  the  following  table  (Streeter).  The  peripheral  terminations  of  the  various 
branches  are  indicated  in  parentheses.  Compare  with  Fig.  474,  /,  m,  n,  and 
Fig.  475,  a,  b,  c. 

ramus  ampul,  sup.  (crista  ampul.) 


pars  superior 


ramus  ampul,  ext.  (crista  ampul.) 


ramus  recess,  utric.  (macula  acust.) 
N.  vestibularis        j 

J  ramus  saccul.  (macula  acust.) 
[  pars  inferior     j  ramus  ampul,  (crista  ampul.) 

The  vestibular  ganglion  cells,  instead  of  remaining  in  a  compact  mass,  come 
to  form  two  fairly  distinct  masses  in  the  course  of  the  nerve  (Fig.  475,  a,  b,  c). 
One  of  these  apparently  is  connected  with  the  pars  inferior,  the  other  with  the 
pars  superior. 

The  cochlear  ganglion  cells  at  an  early  stage  become  closely  associated  with 
the  developing  cochlear  duct  and,  as  the  latter  forms  a  spiral,  are  carried]  along 
with  it.  They  thus  come  to  form  an  elongated  group  of  cells  extending  through- 
out the  entire  length  of  the  cochlea  (whence  the  name,  spiral  ganglion)  (Fig. 
474,  j-n;  Fig.  475,  a-c).  Consequently,  the  peripheral  processes  of  these  cells, 
which  terminate  in  connection  with  the  hair  cells  of  the  organ  of  Corti,  are  com- 
paratively short.  The  central  processes  are  naturally  longer  and  form  the 
cochlear  nerve  root  which  is  twisted  like  a  rope  in  part  of  its  course  (Fig.  475,  c). 

The  Middle  Ear. — The  cavity  of  the  middle  ear  develops  from  the  upper 
(dorsal)  part  of  the  first  inner  branchial  groove.  The  epithelial  lining  of  the 
cavity  is  thus  of  course  derived  from  entoderm,  and  the  other  structures 
(auditory  ossicles,  etc.)  from  the  adjacent  mesoderm. 

It  has  been  stated  elsewhere  that  the  mesoderm  in  the  first  and  second 
branchial  arches  gives  rise,  among  other  things,  to  certain  skeletal  elements. 
In  the  first  arch  there  develops  a  rod  of  cartilage,  known  as  Meckel's  cartilage, 
which  extends  from  the  symphysis  of  the  lower  jaws  to  the  region  of  the  upper 
part  of  the  first  inner  branchial  groove  (p.  164;  Figs.  136,  139,  142).  The 
proximal  end  of  the  cartilage  becomes  constricted  to  form  two  masses  which 
constitute  the  anlagen  of  the  malleus  and  incus  (Figs.  135  and  136).  In  the 
second  arch  there  develops  a  rod  of  cartilage  which  forms  the  lesser  horn  of  the 
hyoid  bone,  the  stylohyoid  ligament,  and  the  styloid  process  (Figs.  136,  139, 
.42).  In  close  relation  to  the  dorsal  end  of  the  styloid  process,  in  the  mesoderm 
destined  to  give  rise  to  the  periotic  capsule,  a  mass  of  cartilage  appears  which 
is  destined  to  give  rise  to  the  stapes  (except  the  base?).  It  has  not  been  fully 
determined  whether  the  stapes  is  actually  a  derivative  of  the  cartilage  of  the 
second  arch  or  of  the  mesenchyme  near  its  dorsal  end.  It  has  been  suggested 


560  TEXT-BOOK  OF  EMBRYOLOGY. 

that  the  base  of  the  stapes  is  of  intramembranous  origin  and  that  the  rest  of  the 
bone  is  derived  from  the  cartilage  of  the  second  arch.  Its  close  association 
with  the  cartilage  of  the  second  arch  possibly  indicates  its  phylogenetic  origin 
from  the  latter. 

At  first  the  auditory  ossicles  are  embedded  in  the  mesoderm  dorsal  to  the 
first  inner  branchial  groove,  that  is,  dorsal  to  the  cavity  of  the  middle  ear.  As 
development  proceeds,  the  mesoderm  is  converted  into  a  spongy  tissue  which 
finally  degenerates.  At  the  same  time  the  ear  cavity  enlarges  and  wraps  itself, 
as  it  were,  around  the  ossicles.  The  latter  thus  come  to  lie  within  the  cavity 
of  the  tympanum,  but  are  covered  by  a  layer  of  epithelium  (entoderm)  which 
is  continuous  with  that  lining  the  cavity. 

Toward  the  end  of  foetal  life,  outgrowths  from  the  cavity  of  the  tympanum 
begin  to  invade  the  temporal  bone.  This  process  continues  for  some  time 
after  birth  and  results  in  the  formation  of  cavities  within  the  mastoid  part  of 
the  temporal  bone.  These  cavities  are  the  mastoid  cells,  the  epithelial  lining 
of  which  is  continuous  with  that  of  the  tympanic  cavity. 

The  Eustachian  tube  represents  the  lower  (ventral)  portion  of  the  diver- 
ticulum  which  forms  the  cavity  of  the  tympanum.  In  other  words,  as  the 
dorsal  part  of  the  first  inner  branchial  groove  enlarges  to  form  the  cavity  of  the 
middle  ear,  the  narrow  part  of  the  groove,  just  ventral  to  the  cavity,  persists 
as  a  communication  between  the  latter  and  the  pharynx. 

The  Outer  Ear. — The  outer  ear  is  formed  from  the  dorsal  part  of  the  first 
outer  branchial  groove  and  the  adjacent  portions  of  the  first  and  second  arches 
(see  Fig.  87).  The  ventral  part  of  the  groove  flattens  out  and  disappears. 
The  dorsal  part  becomes  deeper  to  form  a  funnel-shaped  depression  (during 
the  second  month ;  Fig.  90) .  From  the  deeper  part  of  the  funnel  a  solid  mass 
of  ectoderm  grows  inward  until  it  comes  into  relation  with  the  mesoderm  im- 
mediately around  the  developing  cavity  of  the  tympanum,  or,  more  specifically, 
the  mesoderm  surrounding  the  handle  of  the  malleus.  Here  it  spreads  out 
into  a  disk-like  mass.  About  the  seventh  month,  the  disk  splits  into  two  layers. 
The  inner  layer,  which  is  separated  from  the  epithelium  of  the  middle  ear  by  a 
thin  sheet  of  mesoderm,  becomes  the  outer  layer  of  the  tympanum.  The 
tympanum  is  thus  composed  of  an  inner  (entodermal)  and  an  outer  (ectoder- 
mal)  layer,  with  a  small  amount  of  mesoderm  between.  From  its  mode  of 
development,  the  tympanum  may  be  considered  in  a  sense  as  the  wall  which 
separates  the  first  inner  from  the  first  outer  branchial  groove. 

The  split  in  the  ectodermal  disk  (see  above)  gradually  extends  outward, 
invading  the  solid  ectodermal  in  vagina  tion  until  it  finally  unites  with  the 
bottom  of  the  funnel-shaped  depression  on  the  surface,  thus  forming  the 
external  auditory  meatus. 

The  external  ear  (or  auricle)  is  derived  from  the  portions  of  the  first  and 


THE  ORGANS  OF  SPECIAL   SENSE. 


561 


second  branchial  arches  surrounding  the  dorsal  part  of  the  first  outer  bran- 
chial groove  (see  Figs.  85,  87,  90,  91).  About  the  end  of  the  fourth  week,  the 
caudal  border  of  the  first  arch  exhibits  three  small  elevations  or  tubercles 
(Fig.  477,  A,  1-3),  the  cranial  border  of  the  second  arch  the  same  number  (Fig. 
477,  A,  4-6).  A  groove,  extending  down  the  middle  of  the  second  arch,  marks 
off  a  ridge  (c)  lying  caudal  to  the  three  tubercles.  The  ventral  tubercle  (i)  of 
the  first  arch  gives  rise  to  the  tragus.  The  middle  tubercle  (5)  of  the  second  arch 


v  * 


FIG.  477. — Stages  in  the  development  of  the  external  ear  (auricle).  A,  Embryo  of  n  mm.;  B,  of 
13.6  mm.;  C,  of  15  mm.;  D,  foetus  at  the  beginning  of  the  30!  month;  E,  foetus  of  8.5  cm.: 
F,  foetus  at  term.  For  explanation  of  numerals,  see  text.  His,  McMurrich. 

develops  into  the  antitragus.  The  middle  and  dorsal  tubercles  (2  and  3)  of 
the  first  arch  unite  with  the  ridge  (c)  on  the  second  arch  to  form  the  helix. 
The  dorsal  tubercle  (4)  of  the  second  arch  gives  rise  to  the  anthelix.  The 
ventral  tubercle  (6)  of  the  second  arch  produces  the  lobule.  It  should  be  noted 
that  in  the  third  month  the  dorsal  and  caudal  portions  of  the  helix  are  bent 
forward  and  conceal  the  anthelix. 

Anomalies. 

Malformations  of  the  nose  have  been  alluded  to  in  connection  with  hare  lip, 
cleft  palate,  etc.,  on  page  212,  and  are  also  discussed  in  the  chapter  on  tera- 
togenesis  (XX).  Malformations  affecting  the  eye  (cyclopia,  microphthalmia, 
etc.)  and  the  ear  (synotia,  etc.)  are  dealt  with  in  the  chapter  on  teratogenesis. 


562  TEXT-BOOK  OF  EMBRYOLOGY. 

References  for  Further  Study. 

THE  EYE. 

GALLENGA:  Entwickelung  des  Auges.  Encyklopadie  der  Augenheilkunde,  Lief.  6  and  7, 
1902. 

HOLDEN:  An  Outline  of  the  Embryology  of  the  Eye,  New  York,  1893. 

VON  KOLLIKER:  Die  Entwicklung  und  Bedeutung  des  Glaskorpers.  Zeitschr.  fur 
wissensch.  Zoolog.,  Bd.  LXVI,  1904. 

LANGE,  O.:  Einblicke  in  die  embryonale  Anatomie  und  Entwicklung  des  Menschen- 
auges.  1908. 

RABL,  C.:  Ueber  den  Bau  und  Entwickelung  der  Linse.  Zeitschr.  fur  wissensch.  Zool., 
Bd.  LXII  and  LXV,  1898;  LXVII,  1899. 

RAYMON  Y  CAJAL.:  Nouvelles  contributions  a  1'etude  histologique  de  la  retine.  Jour,  de 
VAnat.  et  de  la  Physiol,  Vol.  XXXII,  1896. 

ROBINSON.  A.:  On  the  Formation  and  Structure  of  the  Optic  Nerve  and  its  Relation  to 
the  Optic  Stalk.  Jour,  of  Anat.  and  Physiol.,  Vol.  XXX,  1896. 

VON  SPEE:   Recherches  sur  1'origine  du  corps  vitre.     Arch,  de  Biol.,  Vol.  XIX,  1902. 

THE  NOSE. 

BEARD,  J.:  Morphological  Studies.  The  Nose  and  Jacobson's  Organ.  Zool.  Jahrbuch, 
Bd.  Ill,  1889. 

DISSE,  J.:  Die  erste  Entwickelung  der  Riechnerven.     Anat.  Hefte,  Bd.  IX,  1897. 

His,  W.:  Beobachtungen  zur  Geschichte  der  Nasen-  und  Gaumenbildung  beim 
menschlichen  Embryo.  AbhandL  d.  math.-phys.  Klasse  Ko'nig.  Sachs.  Gesellsch.  d. 
Wissensch. ,  1901. 

HOCHSTETTER,  F.°.  Ueber  die  Bildung  der  primitiven  Choanen  beim  Menschen.  Ver- 
handl.  d.  anat.  Gesellsch.,  Bd.  VI,  1892. 

VON  MIHALKOWICZ,  V.:  Nasenhohle  und  Jacobsonsches  Organ.  Eine  morphologische 
Studie.  Anat.  Hefte,  Bd.  XI,  1898. 

PETER,  K.:  Die  Entwickelung  des  Geruchsorgans  und  Jacobson'schen  Organs  in  der 
Reihe  der  Wirbeltiere.  In  Hertwig's  Handbuch  d.  vergleich.  u.  experiment.  Entwickel- 
ungslehre  d.  Wirbeltiere,  Bd.  II,  Teil  II,  1901. 

THE  EAR. 

BAGINSKY,  B.:  Zur  Entwickelung  der  Gehorschnecke.  Arch.f.  mik.  Anat.,  Bd.  XXVIII, 
1886. 

BOETTCHER,  A.:  Ueber  Entwickelung  und  Bau  des  Gehorlabyrinths.  Verhandl.  d. 
Kais.Leop.-Carol.  Akad.,  Bd.  XXXV,  1869. 

BROMAN,  I.:  Die  Entwickelungsgeschichte  der  Gehorknochelchen  beim  Menschen. 
Anat.  Hefte,  Bd.  XI,  1898. 

FUCHS,  H.:  Bemerkungen  iiber  die  Herkunft  und  Entwickelung  der  Gehorknochelchen 
bei  Kaninchen-Embryonen.  Arch.f.  Anat.  u.  Phys.,  Anat.  Abth., Suppl.,  1905. 

HENSEN,  V.:    Zur  Morphologic  der  Schnecke.  Zeitschr.  f.  wissensch.  Zool.,  Bd.  XIII,  1863 

His,  W.:  Zur  Entwickelung  des  Acusticofacialisgebiets  beim  Menschen.  Arch.f.  Anat. 
u.  Phys.,  Anat.  Abth.,  Suppl.,  1899. 

KRATJSE,  R.:  Entwickelungsgeschichte  des  Gehororgans.  In  Hertwig's  Handbuch  d. 
vergleich.  u.  experiment.  Entwickelungslehre  d.  Wirbeltiere,  Bd.  II,  Teil  II,  1902. 

STREETER,  G.  L.:  On  the  Development  of  the  Membranous  Labyrinth  and  the  Acoustic 
and  Facial  Nerves  in  the  Human  Embryo.  Am.  Jour,  of  Anat.,  Vol.  VI,  No.  2,  1907. 


CHAPTER  XIX 
FOETAL  MEMBRANES. 

In  all  Vertebrates,  with  the  exception  of  Fishes  and  Amphibians  which  lay 
their  eggs  in  water,  there  begin  to  develop  gr  a  very  early  stage  certain  accessory 
or  extraembryonic  structures  which  may  be  conveniently  called  jostal  mem- 
branes. The  development  of  these  structures  is  very  closely  i  elated  to  the  de- 
velopment of  the  embryo  itself,  and  their  presence  is  apparently  largely  depend- 
ent upon  the  very  considerable  length  of  embryonic  life  in  these  forms,  during 
which  it  is  necessary  for  the  embryo  to  maintain  a  definite  relation  to  its  food 
supply  and  to  possess  means  of  discharging  waste  products.  The  fcetal  mem- 
branes, therefore,  have  to  do  with  the  protection  and  nutrition  of  the  growing 
embryo  and  also  are  connected  with  the  care  of  the  waste  products  of  fcetal 
metabolism. 

Under  the  head  of  fcetal  membranes  are  to  be  considered  (i)  the  amnion, 
(2)  the  allantois,  (3)  the  chorion;  also  in  connection  with  these,  the  yolk  sac  and 
the  umbilical  cord. 

The  development  of  these  structures  in  Mammals  and  especially  in  man  is 
extremely  complex  and  can  be  best  understood  by  comparison  with  their  simpler 
development  in  Reptiles  and  Birds. 

FOETAL  MEMBRANES  IN  BIRDS  AND  REPTILES. 

Throughout  these  two  classes  there  is  such  uniformity  in  the  formation  of 
the  fcetal  membranes  that  the  chick  may  be  taken  as  typical.  The  chief 
characteristic  of  these  classes,  as  influencing  the  form  and  structure  of  the  fcetal 
membranes,  is  the  very  large  amount  of  yolk  stored  up  within  the  egg  for  the 
nutrition  of  the  embryo.  This  is  made  necessary  by  the  early  separation  of  the 
egg  from  the  mother,  in  contrast  to  the  close  nutritional  relationship  between 
mother  and  foetus  which  obtains  in  Mammals  (excepting  Monotremes),  where 
the  young  are  retained  within  the  body  of  the  mother  up  to  a  comparatively  late 
developmental  stage. 

The  Amnion. — Returning  to  that  point  in  the  development  of  the  blastoderm 
of  the  chick  where  no  trace  of  amnion  has  as  yet  appeared,  we  recall  that  the 
blastoderm  at  this  stage  consists  of  three  layers,  ectoderm,  mesoderm  and 
entoderm;  that  the  medial  line  of  the  embryo  is  marked  by  the  neural  groove, 
flanked  by  the  neural  folds  which  are  continuous  with  each  other  anteriorly;  that 

563 


564 


TEXT-BOOK  OF  EMBRYOLOGY. 


on  each  side  of  the  neural  groove  between  ectoderm  and  entoderm  the  mesoderm 
is  a  solid  mass  of  cells,  while  more  laterally  the  mesoderm  is  split,  its  peripheral 
layer  with  the  adjacent  ectoderm  forming  the  somatopleure,  its  central  layer 
with  the  adjacent  entoderm  forming  the  splanchnopleure;  that  between  soma- 
topleure and  splanchnopleure  is  the  body  cavity.  Ventral  to  the  neural  groove 
is  the  notochord,  while  ventral  to  the  latter  is  the  primitive  gut,  the  roof  of  which 
is  formed  of  entoderm  (Fig.  52), 

The  first  indication  of  amnion  formation  is  the  appearance  of  a  fold — the 
head  amniotic  fold — just  in  front  of  the  anterior  union  of  the  neural  folds  (Figs. 


ar.  op. 


ar.  peL 


FIG.  478 — Dorsal  view  of  embryo  of  bird  (Phaeton  rubricauda)  with  fifteen  pairs  of 

primitive  segments.     Schauinsland. 

ar.  op*y  Area  opaca,  portion  in  which  mesoderm  is  not  yet  present;  ar.  op*,  area  opaca;  ar.  pel.-, 
area  pellucida;  cce.,  bladder-like  dilatation  of  ccelom;  ed.  mes.,  edge  of  mesoderm;  h.  am.  /., 
head  amniotic  fold;  pr.  seg.,  primitive  segments;  x,  portion  of  amniotic  fold  containing  no 
mesoderm. 

478  and  484,  b) .  This  occurs  during  the  second  day  of  incubation.  After  the 
head  fold  has  become  well  developed  and  extends  back  over  the  embryo  like  a 
hood  (Fig.  480),  similar  lateral  and  tail  folds  make  their  appearance  (Figs.  479 
and  484,  a  and  b).  The  folds  continue  to  grow  over  the  dorsum  of  the 
embryo  and  finally  meet  and  fuse  in  the  mid-dorsal  line,  forming  the  amniotic 
suture  (Fig.  481). 

The  amniotic  folds  from  the  beginning  involve  the  somatopleure,  that  is, 
the  ectoderm  and  parietal  mesoderm.  But  since  they  arise  some  distance  from 
the  developing  embryonic  body,  the  extraembryonic  portions  only  are  involved. 
At  the  same  time  a  portion  of  the  extraembryonic  body  cavity  is  also  carried 
dorsally  within  the  folds  (Figs.  479  and  482) .  When  the  folds  unite  over  the 


FCETAL  MEMBRANES. 


565 


embryo  they  break  through  at  the  line  of  contact,  thus  leaving  the  outer  layers 
of  the  folds  continuous  and  the  inner  layers  continuous,  with  the  extraembryonic 
body  cavity  continuous  between  the  outer  and  inner  layers. 


t.  am.  f. 


ect. 


pr.  g. 


ent. 


mes.1 

mes.2 


ent. 


FIG.  479. — Medial  section  of  caudal  end  of  chick  embryo  (at  end  of  second 

day  of  incubation).     Duval. 

al^  Beginning  of  allantoic  evagination;  a.m.,  anal  membrane;  b.c.,  extraembryonic  body  cavity; 
e.g.,  caudal  gut;  ect.,  ectoderm;  ent.,  entoderm;  mes.,  mesoderm;  mes.1,  parietal  mesoderm; 
mes.2,  visceral  mesoderm;  n.  tu.,  neural  tube;  pr.  g.,  primitive  gut;  /.  am.  /.,  tail  amniotic 
fold;  to.,  tail. 

The  result  of  the  development  of  the  amniotic  folds  is: — 
i.  That  the  embryo  is  completely  enclosed  dorsally  and  laterally  by  a  cavity, 
the  amniotic  cavity,  which  is  lined  by  ectoderm  continuous  with  the  ectoderm — 


Area 
opaca 

Edge  of 
mesoderm 


Dorsal  amniotic 
suture 


Primitive 
streak 


FIG.  480.— -Dorsal  view  of  embryo  of  albatross,  showing  amnion  covering  cephalic 

end  of  embryo.     Schauinsland. 
x,  Portion  of  blastoderm  containing  no  mesoderm. 

later  epidermis— of  the  embryo,  the  ectoderm  lining  the  cavity  and  the  overlying 
parietal  mesoderm  together  constituting  the  amnion  (Fig.  483). 

2.  That  the  outer  parts  of  the  amniotic  folds  become  completely  separated 


566 


TEXT-BOOK  OF  EMBRYOLOGY. 


from  the  inner — the  amnion — to  form  a  second  membrane  consisting  externally 
of  ectoderm,  internally  of  mesoderm  and  called  at  first  the  serosa  or  jalse 
amnion,  later  the  primitive  chorion  (Fig.  483). 

3.  That  the  extraembryonic  body  cavity  unites  across  the  medial  line 
dorsally,  thus  separating  the  amnion  from  the  primitive  chorion  (Fig.  484, 
a,  b  and  c). 

During  the  formation  of  the  amnion  the  chick  embryo  is  becoming  more  and 
more  definitely  constricted  off  from  the  underlying  large  yolk  mass  which  is 
liquefying  and  into  which  the  embryo  sinks  somewhat.  At  the  same  time  the 


Ant.  vitelline  vein    Mesoderm 


Omphalomesenteric 
(vitelline)  vein 


Primitive  streak 


Area  opaca 
Sinus  terminalis 

Extraembryonic  body  cavity 

Amnion 
Amniotic  suture 


Area  pellucida 


Amniotic  suture 
>•  Lateral  amniotic  fold 


Tail  amniotic  fold 
Area  opaca 


FIG.  4$ i. — Dorsal  view  of  embryo  of  albatross,  showing  amnion  covering  greater 
part  of  embryo.     Schauinsland. 

amniotic  cavity  continues  to  increase  in  size  and  extends  also  ventrally  beneath 
the  embryo  so  that  the  embryo  is  everywhere  enclosed  within  the  amnion 
except  at  its  narrow  connection  with  the  yolk  (Fig.  484,  c\  d). 

The  amniotic  cavity  is  filled  with  fluid,  the  liquor  amnii,  the  origin  of  which 
is  uncertain.  In  it  the  embryo  floats  freely,  attached  only  by  its  ventral  con- 
nection with  the  yolk.  At  about  the  fifth  day  of  incubation  rhythmical  con- 
tractions of  *he  amnion  begin.  These  are  apparently  due  to  the  development 
of  contractile  fibers  in  its  mesodermic  tissue  and  give  to  the  embryo  a  regular 
oscillating  motion. 


FCETAL  MEMBRANES. 


567 


The  Yolk  Sac. — The  simplest  type  of  yolk  sac  is  found  in  Amphibians  and 
Fishes.     In  Amphibians  the  yolk  is  enclosed  within  the  embryo,  the  cells  form- 


1.  am.  f.    ex.  b.  c.  ser.       ect. 


—  p.  mes. 


pc.  ep.  ht.     pc. 

FIG.  482. — Transverse  section  of  embryo  of  albatross.     Schauinsland. 

Section  taken  through  region  of  heart,  aw.,  amnion;  ao.,  aorta;  a.  v.v.,  anterior  vitelline  veins; 
ect.,  ectoderm;  ent.,  entoderm;  ep.,  epicardium;  ex.  b.  c.,  extraembryonic  body  cavity;  ht.,  heart; 
/.aw./.,  lateral  amniotic  fold;  pc.,  pericardium;  ph.,  pharynx;  p.  mes.,  parietal  mesoderm; 
ser..  serosa  (chorion);  v.mes.,  visceral  mesoderm;  *  point  at  which  extraembryonic  body 
cavity  passes  over  into  the  intraembryonic  (or  ccelom  proper). 

ing  a  part  of  the  intestinal  wall.     The  superficial  cells  are  split  off  to  form  the 
yolk  entoderm.     Investing  the  yolk  entoderm  is  the  visceral  mesoderm  which 

ser.  am.  sut.       am. 


—  p.  mes. 


—  v.  mes. 


P.  PC.        j  j    ! 

ht.      ph.  p.  pc. 

FIG.  483. — Transverse  section  of  embryo  of  albatross.     Schauinsland. 

Section  taken  through  region  of  heart,  am.,  Amnion;  am. sut.,  amniotic  suture;  a. v.v,  anterior 
vitelline  veins;  ect.,  ectoderm;  ent.,  entoderm;  ex.  b.  c.,  extraembryonic  body  cavity;  ht.,  heart; 
i>  pc.,  primitive  pericardial  cavity;  ph.,  pharynx;  p. mes.,  parietal  mesoderm;  ser.,  serosa 
(chorion);  v.mes,  visceral  mesoderm;  *  point  at  which  extraembryonic  body  cavity  passes 
over  into  intraembryonic  (or  coelom). 

is  separated  from  the  parietal  mesoderm  by  the  body  cavity.     Outside  of  the 
parietal  mesoderm  is  the  ectoderm  (Fig.  33).     In  many  of  the  Fishes  the  germ 


568 


TEXT-BOOK  OF  EMBRYOLOGY. 


disk,  as  in  Reptiles  and  Birds,  is  confined  to  one  pole  of  the  egg.  Thus  in  these 
forms  the  embryonic  body  develops  on  the  surface  of  the  large  yolk  mass.  As 
the  embryo  develops  the  germ  layers  simply  grow  around  the  yolk  and  suspend 
it  from  the  ventral  side  of  the  embryo.  At  the  same  time  a  constriction  appears 
between  the  embryo  and  the  yolk  mass,  thus  forming  the  yolk  stalk.  In  this 
case  the  yolk  is  surrounded  from  within  outward,  by  entoderm,  visceral  and 


h.  am.  f. 


FIG.  484. — Diagrams  representing  stages  in  the  development  of  the  foetal  membranes 

in  the  chick.     Hertwig. 

a,  Transverse  section;  b,  c,  d,  longitudinal  sections;  yolk  represented  by  vertical  lines,  al.,  Allantois; 
am.,  amnion;  am.  c.,  amniotic  cavity;  cce.,  ccelom;  dh.,  vitel line  area  between  two  dotted  lines 
which  represent  the  edge  of  the  mesoderm  (at  s.  /.)  and  entoderm  (at  z. g.}\  dg.,  yolk  stalk; 
ds.,  yolk  sac;  d.umb.,  dermal  umbilicus;  ect.,  ectoderm;  ent.>  entoderm;  ex.  b.  c.,  extraem- 
bryonic  body  cavity;  gh.,  area  vasculosa;  h.am.f.,  head  amniotic  fold;  m.,  mouth;  p,mes., 
parietal  mesoderm;  s.  t.,  sinus  terminalis;  ser.,  serosa  (chorion);  t.am./,,  tail  amniotic  fold; 
umb.,  umbilicus;  v  mes.,  visceral  mesoderm;  z.  g.,  dotted  line  represents  edge  of  entoderm. 


parietal  mesoderm,  and  ectoderm  (Fig.  485) .  The  yolk  furnishes  nutriment  for 
the  embryo.  This  is  conveyed  to  the  tissues  by  means  of  blood  vessels. 
Branches  of  the  vitelline  artery  ramify  in  the  wall  of  the  yolk  sac  (in  the  meso- 
dermal.tissue) ;  the  branches  converge  to  form  the  vitelline  veins  which  carry  the 
blood  back  to  the  embryo. 

In  the  chick,  while  the  amnion  is  forming,  the  inner  germ  layer  gradually 
extends  farther  and  farther  around  the  yolk  (Fig.  484,  a,  b,  c  and  d).     At  the 


FCETAL    MEMBRANES.  569 

same  time,  as  already  noted  (p.  566),  the  growth  of  the  amnion  ventrally  results 
in  a  sharp  constriction  which  separates  the  embryo  from  the  underlying  yolk. 
This  constriction  is  emphasized  by  constant  lengthwise  growth  of  the  embryo. 
Following  the  gradual  growth  of  the  entoderm  around  the  yolk,  the  mesoderm 
also  gradually  extends  around,  at  the  same  time  splitting  into  visceral  and 
parietal  layers,  so  that  the  entoderm  is  closely  invested  by  visceral  mesoderm 
(Fig.  484,  a,  &,  c  and  d).  Finally,  both  entoderm  and  mesoderm  enclose  com- 
pletely the  mass  of  yolk.  The  yolk  thus  becomes  enclosed  in  the  yolk  sac  * 
which  consists  of  two  layers,  entoderm  and  visceral  mesoderm.^  The  constricted  v  . 
connection  between  the  yolk  sac  and  the  embryo  is  the  yolk  stalk.  It  is  seen  by 
reference  to  the  diagrams  (Fig.  484)  that  the  entoderm  lining  the  yolk  sac  is 


FIG.  485. — Diagrammatic  longitudinal  section  of  selachian  embryo.     Hertwig. 
a.,  Anus;  d.,  yolk  sac;  dn.,  intestinal  umbilicus;  ds.,  visceral  layer  of  yolk  sac;  hs.,  parietal  layer  of 
yolk  sac;  hn.,  dermal  umbilicus;  lhl,  coelom;  lh2,  exoccelom;  m.,  mouth;  st.,  yolk  stalk. 


directly 'continuous  through  the  yolk  stalk  with  the  entoderm  lining  theprimi-- 
tive  gut>  The  transition  line  between  extra-  and  intraembryonic  entoderm  is 
sometimes  referred  to  as  the  intestinal  umbilicus,  in  contradistinction  to  the  line 
of  union,  on  the  outside  of  the  yolk  stalk,  of  amniotic  and  embryonic  ecto- 
derm (the  latter  becoming  later  the  epidermis)  which  is  known  as  the  dermal 
umbilicus. 

As  in  Fishes  and  Amphibians,  so  also  in  Reptiles  and  Birds,  the  yolk  furnishes 
nourishment  for  the  growing  embryo,  and  is  conveyed  to  the  embryo  by 
the  blood.  At  a  very  early  stage  the  mesoderm  layer  of  the  yolk  sac  (visceral 
mesoderm)  becomes  extremely  vascular.  This  vascular  area  is  indicated  by  an 
irregularly  reticulated  appearance  in  the  periphery  of  the  blastoderm  and  is 
known  as  the  area  vasculosa  (Fig.  51).  The  area  vasculosa  increases  in  size  as 
the  mesoderm  grows  around  the  yolk  and  its  vessels  become  continuous  with 
those  in  the  embryo  (Fig.  159).  Some  of  these  vessels  enlarge  as  branches  of 
two  large  vessels  which  are  given  off  from  the  primitive  aortae,  the  mtelline  or 
omphalomesenteric  arteries.  (When  the  two  aortae  fuse  to  form  a  single 
vessel,  the  proximal  ends  of  the  vitelline  arteries  fuse  likewise.)  The  branches 
of  the  arteries  ramify  in  the  mesoderm  over  the  surface  of  the  yolk  and  then 


570  TEXT-BOOK  OF  EMBRYOLOGY. 

con  verge,  to  form  other  vessels  which  enter  the  embryo  as  thevilellmeoromphalo- 
mesenteric  veins  (Fig.  160).  As  the  mesoderm  extends  farther  and  farther 
around  the  yolk,  the  vessels  extend  likewise  until  the  entire  yolk  is  surrounded 
by  a  dense  plexus  of  blood  vessels  in  the  wall  of  the  yolk  sac. 

The  Allantois. — While  the  embryonic  intestine  is  first  assuming  the  form 
of  a  tube,  there  grows  out  ventrally  from  near  its  caudal  end,  during  the  third 
day  of  incubation,  a  diverticulum  which  is  the  beginning  of  the  allantois  (Fig. 
486).  This  increases  rapidly  in  size  and  pushes  out  into  the  extraembryonic 
body  cavity  behind  the  yolk  stalk.  As  it  is  a  diverticulum  from  the  intestine, 
it  consists  primarily  of  entoderm.  This  pushes  in  front  of  it,  however,  the 
splanchnic  (visceral)  mesoderm  which  becomes  the  outer  layer  of  the  membrane. 
The  connection  between  the  intestine  and  the  allantois  is  known  as  the  urachus. 
In  the  chick  the  allantois  attains  a  comparatively  large  size,  pushing  out  dorsally 


pr.  seg. 


ai.  mes.  ent. 


FIG.  486.  — Longitudinal  section  of  caudal  end  of  chick  embryo  (end  of  third 

day  of  incubation).     Gasser. 

07.,  Allantois;  al. p.,  allantois  prominence;  a.m.,  anal  membrane;  am.,  amnion;  am.  c.,  amniotic 
cavity;  e.g.,  caudal  gut;  cce.,  ccelom;  ect.,  ectoderm;  ent.,  entoderm;  ex.  b.  c.,  extraembryonic 
body  cavity;  mes.,  mesoderm;  pr.  g.,  primitive  gut;  t.,  tail. 

between  the  amnion  and  the  primitive  chorion  and  ventrally  between  the  latter 
and  the  yolk  sac  (Fig.  484,  b,  c  and  d).  The  inner  wall  of  the  allantoic  sac 
blends  with  the  amnion  about  the  seventh  day  of  incubation  and  with  the 
yolk  sac  considerably  later,  while  the  outer  wall  joins  the  primitive  chorion 
to  form  the  true  chorion,  or  as  it  is  sometimes  designated,  the  allanto-chorion 
(see  p.  575) .  As  the  allantois  reaches  the  limit  of  the  yolk,  it  leaves  the  latter, 
and  pushing  the  primitive  chorion  before  it,  continues  around  close  under  the 
shell  (Fig.  484)  until  it  completely  encloses  the  albumen  at  the  small  end  of 
the  egg. 

The  allantois  of  the  chick  performs  three  important  functions : 

1.  It  serves  as  a  receptacle  for  the  excretions  of  the  primitive  kidneys. 

2.  United  with  a  part  of  the  primitive  chorion  to  form  the  albumen  sac,  its 
vessels  take  up  the  albumen  as  nourishment  for  the  embryo.     Because  of  this 
function  and  also  because  of  the  fact  that  little  papillae  sometimes  appear  on  the 


FCETAL  MEMBRANES.  571 

inner  surface  of  the  albumen  sac,  evidently  for  the  purpose  of  increasing  its 
absorptive  surface,  this  albumen  sac  has  been  compared  by  some  to  a  placenta. 

3.  It  blends  with  the  primitive  chorion  to  form  the  true  chorion  and  being 
extremely  vascular  and  lying  just  beneath  the  porous  shell,  it  serves  as  the  most 
important  organ  of  fcetal  respiration. 

The  allantois  in  the  chick  is  an  extremely  vascular  organ,  the  network  of 
small  vessels  in  the  wall  being  composed  of  radicals  of  the  allantoic  or  umbilical 
vessels  of  the  embryo.  Soon  after  the  allantois  begins  to  develop,  two 
branches — the  umbilical  arteries — are  given  off  from  the  aorta  near  its  caudal 
end.  These  pass  ventrally  through  the  body  wall  of  the  embryo  and  thence 
out  via  the  umbilicus  to  break  up  into  extensive  networks  of  capillaries  in  the 
mesodermal  layer  of  the  allantois.  The  capillaries  converge  to  form  the  um- 
bilical veins  which  pass  into  the  embryo  via  the  umbilicus  and  thence  cephalad 
to  the  heart. 

During  the  incubation  period  of  the  chick  there  are  two  extraembryonic  sets 
of  blood  vessels.  One  set,  the  vitelline  (omphalomesenteric)  vessels  (p.  187), 
is  concerned  with  carrying  the  yolk  materials  to  the  growing  embryo.  The 
other  set,  the  umbilical  (allantoic)  vessels,  is  chiefly  concerned  with  respiration 
and  carrying  waste  products  to  the  allantois,  but  is' probably  in  part  concerned 
with  conveying  the  albumen  to  the  embryo.  When  the  chick  is  hatched,  and  the 
fcetal  membranes  are  of  no  further  use  and  disappear,  the  extraembryonic  por- 
tions of  the  blood  vessels  also  disappear.  The  intraembryonic  portions  persist, 
in  part,  as  certain  vessels  in  the  adult  organism. 

The  Chorion  or  Serosa. — This  membrane  is  but  little  developed  in  the 
chick  as  compared  with  Mammals,  especially  the  Placentalia.  Its  mode  of 
origin  as  the  outer  leaves  of  the  amniotic  folds,  cut  off  from  the  amnion  by 
dorso-medial  extension  of  the  mesoderm  and  body  cavity,  has  been  described 
(P-  S^S)  •  It  consists,  as  there  shown,  of  extraembryonic  ectoderm  and  parietal 
mesoderm  (Fig.  483) .  As  first  formed  it  is  confined  to  the  immediate  region 
of  the  embryo  and  of  the  amnion  to  which  it  is  later  loosely  attached.  It  soon 
extends  ventrally  around  the  yolk  where  it  forms  what  is  sometimes  designated 
the  skin  layer  of  the  yolk  sac.  The  relation  of  the  outer  layers  of  the  allantois 
to  the  chorion  has  been  described  on  page  570,  and  is  illustrated  in  Fig.  486. 


FCETAL  MEMBRANES  IN  MAMMALS. 


The  development  of  the  fcetal  membranes  in  Mammals  presents  no  such 
uniformity  as  is  found  in  Birds  and  Reptiles  where  it  was  possible  to  describe 
their  formation  in  the  chick  as  typical  for  the  two  classes.  In  the  different 
Mammals  much  variation  occurs,  not  only  in  the  first  appearance  of  the  mem- 
branes but  also  in  their  further  development  and  ultimate  structure. 

In  some  forms  (rabbit,  for  example)  the  amnion  develops  in  a  manner  very 


572  TEXT-BOOK  OF  EMBRYOLOGY. 

similar  to  that  in  the  chick;  that  is,  by  a  dorsal  folding  of  the  somatopleure. 
There  is,  however,  no  head  fold  unless  a  temporary  structure  known  as  the 
proamnion  be  considered  as  such.  The  entire  rabbit  amnion  is  formed  by  an 
extension  over  the  embryo  of  the  tail  amniotic  fold.  In  other  forms  (bat  and 
probably  man)  the  amnion  and  amniotic  cavity  arise  in  situ  over  the  embryonic 
disk,  without  any  folding  of  the  somatopleure. 

Yolk  is  almost  entirely  lacking  in  most  Mammals,  but  the  yolk  sac  is  always 
present  although  it  soon  becomes  a  rudimentary  structure.  The  fact  that  the 
yolk  sac  is  always  present  points  toward  the  conclusion  that  Mammals  are 
descended  from  animals  which  possessed  large  ova  with  abundant  yolk.  As  a 
matter  of  fact  the  lowest  Mammals,  the  Monotremes,  possess  large  ova  with 
large  quantities  of  yolk.  These  are  deposited  by  the  female,  are  developed  in  a 
parchment-like  shell,  and  are  carried  about  in  the  brood-pouch. 

The  allantoic  sac  in  many  Mammals  is  a  very  rudimentary  structure  which, 
as  in  the  chick,  always  arises  as  an  evagination  from  the  caudal  end  of  the  gut. 
The  allantoic  blood  vessels,  however,  become  vastly  important  since  they  here 
not  only  carry  off  waste  products  from  the  embryo,  as  in  Reptiles  and  in  Birds, 
but  also  assume  the  function  of  conveying  nutriment  from  the  mother  to  the 
embryo.  In  assuming  this  new  function  they  are  no  longer  concerned  with 
the  allantoic  sac  proper  but  enter  into  a  new  relation  with  the  chorion. 

The  chorion  is  the  most  highly  modified  and  specialized  of  all  the  mam- 
malian foetal  membranes.  In  some  cases  (the  rabbit,  for  example)  it  arises  in 
connection  with  the  amnion,  as  in  the  chick,  by  a  dorsal  folding  of  the  somato- 
pleure. In  other  cases  (bat  and  probably  man)  it  arises  at  a  very  early  stage, 
partly  as  a  differentiation  of  the  superficial  layer— of  the  .morula,  partly  as 
extraembryonic  parietal  mesoderm  which  develops  later.  In  all  cases  where 
the  embryo  is  retained  in  the  uterus  (except  Marsupials)  it  forms  a  most  highly 
specialized  and  complex  structure  which,  in  connection  with  the  allantoic 
vessels,  establishes  the  communication  between  the  mother  and  the  embryo. 

For  the  sake  of  clearness  it  seems  best  to  describe  first  the  earlier  stages  of 
the  fcetal  membranes  in  some  case  where  the  development  resembles  that  of  the 
chick;  then  later  to  consider  the  more  specialized  types  of  development,  the 
ultimate  structure  of  the  membranes,  especially  the  chorion,  and  their  relation 
to  the  embryo  and  the  mother. 

Amnion,  Chorion,  Yolk  Sac,  Allantois,  Umbilical  Cord.— Referring 
back  to  the  mammalian  blastoderm  when  it  consists  of  the  three  germ  layers, 
it  will  be  remembered  that  the  embryonic  disk  forms  the  roof,  so  to  speak,  of  a 
large  cavity — the  yolk  cavity  or  cavity  of  the  blastodermic  vesicle  (Fig.  75); 
that  the  ectoderm  of  the  disk  is  continuous  with  a  layer  of  cells  which  extends 
around  the  vesicle — the  extraembryonic  ectoderm;  that  the  entoderm  of  the 
disk  is  continuous  with  the  entoderm  lining  the  cavity  of  the  vesicle;  that  the 


FCETAL  MEMBRANES. 


573 


mesoderm  extends  peripherally  beyond  the  disk  between  the  ectoderm  and 
entoderm  (Fig.  81).  It  will  be  remembered  also  that  the  mesoderm  later  splits 
into  two  layers— the  parietal  and  visceral,  of  which  the  parietal  plus  the  ecto- 
derm forms  the  somatopleure  and  the  visceral  plus  the  entoderm  forms-file 


Prtmltive    Qut 


FIG.  487, — Diagrams  representing  six  stages  in  the  development  of  the  foetal  membranes 

in  a  mammal.     Modified  from  Kulliker. 

The  ectoderm  is  indicated  by  solid  black  lines;  the  entoderm  by  broken  lines;  the  mesoderm 

by  dotted  lines  and  areas. 

splanchnopleure;  and  that  the  cleft  between  the  two  layers  is  the  body  cavity 
or  ccelom. 

In  further  development,  along  with  the  differentiation  of  the  embryonic 
body,  the  somatopleure  begins  to  fold  dorsally  at  a  short  distance  from  the 


574 


TEXT-BOOK  OF  EMBRYOLOGY. 


body  (Fig.  487,  2).  The  folds — amniotic  folds — appear  cranially,  laterally  and 
caudally.  These  folds  continue  to  grow  dorsally  (Fig.  487, 3)  and  finally  meet 
and  fuse  above  the  embryo  (Fig.  487, 4).  They  then  break  through  along  the 
line  of  fusion  so  that  the  extraembryonic  body  cavity  which  has  been  carried  up 
dorsally  over  the  embryo  in  the  amniotic  folds  becomes  continuous  across  the 
mid-dorsal  line.  A  double  membrane  or  rather  two  membranes  are  thus 
formed  which  extend  over  the  embryo.  The  outer  membrane  is  the-  cjiojjon 
and  is  composed  from  without  inward  of  ectoderm  and  parietal  mesoderm. 
The  inner  membrane  is  the  amnion  and  is  composed  from  without  inward  of 
parietal  mesoderm  and  ectoderm  (Fig.  487,  5).  Between  the  amnion  and  the 
chorion  is  a  portion  of  the  extraembryonic  body  cavity,  which,  as  already 
mentioned,  was  carried  dorsally  with  the  amniotic  folds  (Fig.  487,  2,  3,  4  and  5). 


Sclerotome       Myotome 


Upper 
limb  bud 


Entoderm 


Pronephric 
tubule 


FIG,  488. — Transverse  section  of  a  dog  embryo  with  19  primitive  segments. 
Section  taken  through  sixth  segment. 


Bonnet. 


In  the  manner  just  described  the  amnion  becomes  a  sac  which  at  first  en- 
closes the  embryo  laterally,  and  then  laterally  and  dorsally  (Efg-  488) .  ^  Later 
as  the  embryo  becomes  constricted  off  from  the  underlying^  1:avity,  the  amnion 
encloses  it  entirely  except  over  a  small  area  on  the  ventral  side  where  the  embryo 
is  attached  to  the  yolk  sac  (Fig.  487,  3,  4  and  5). 

While  the  amnion  is  being  formed,  the  mesoderm  continues  to  extend 
around  the  vesicle  between  the  ectoderm  and  the  entoderm.  At  the  same  time 
it  splits  into  parietal  and  visceral  layers,  of  which  the  parietal  is  applied  to  the 
ectoderm,  and  the  visceral  to  the  entoderm.  In  this  way  the  extraembryonic 
body  cavity  gradually  extends  farther  and  farther  around  the  vesicle  until 
finally  the  somatopleure  is  completely  separated  from  the  splanchnopleure 
(Fig.  487,  3,  4  and  5).  The  extraembryonic  somatopleure  now  forms  a  com- 
plete wall  for  the  vesicle  and  constitutes  the  chorion.  The  extraembryonic 
splanchnopleure  forms  a  complete  wall  for  the  yolk  cavity  and  constitutes  the 
wall  of  the  yolk  sac.  The  proximal  portion  of  the  yolk  sac  becomes  constricted 


FCETAL  MEMBRANES.  575 

to  form  the  yolk  stalk  which  connects  the  yolk  sac  with  the  ventral  side  of  the 
embryonic  body  (Fig.  487,  5). 

While  the  processes  just  described  have  been  taking  place,  an  evagination  ap- 
pears pushing  out  from  the  ventral  side  of  the  caudal  end  of  the  gut  (Fig.  487,4). 
This  evagination  grows  out  into  the  extraembryonic  body  cavity  (exo- 
coelom),  pushing  before  it  the  visceral  layer  of  mesoderm,  thus  giving  rise  to  a 
thin- walled  sac  which  communicates  with  the  gut — the  allantois  (Fig.  487,  5). 
At  this  stage  the  embryonic  body,  with  its  surrounding  amnion  and  appended 
yolk  sac  and  allantois,  lies  within  the  large  vesicle  formed  by  the  chorion.  Up 
to  this  point  the  development  resembles  that  in  the  chick. 

In  succeeding  stages  a  new  connection  is  established  between  the  embryo  and 
the  chorion  in  the  following  manner :  The  amnion  enlarges  and  fills  relatively 
more  of  the  cavity  within  the  chorion,  while  the  yolk  sac  becomes  smaller  and 
the  yolk  stalk  much  attenuated  (Fig.  487,  6).  At  the  same  time  the  allantois 
also  becomes  attenuated  and  its  distal  end  comes  in  contact  with  the  chorion 
(Fig.  487,  6).  The  growth  of  the  amnion  results  in  the  pushing  together  of  the 
attenuated  yolk  stalk  and  allantofs  so  that  they  lie  parallel  to  each  other  (Fig. 
487,  6),  and  are  together  invested  by  a  portion  of  the  amnion.  As  already 
described,  both  yolk  stalk  and  allantois  are  composed  of  entoderm  and 
mesoderm  while  the  amnion  is  composed  of  mesoderm  and  ectoderm.  Con- 
sequently when  the  three  structures  come  together  and  fuse,  there  is  formed 
a  mass  of  mesoderm  which  contains  the  entoderm  of  the  yolk  stalk  or  vitelline 
duct  and  trie  entoderm  of  the  allantois  or  allantoic  duct,  and  which  is  sur- 
rounded by  the  ectoderm  of  the  amnion.  The  fusion  of  these  three  structures 
in  this  region  thus  produces  a  slender  cord  of  tissue  which  forms  the  union 
between  the  embryo  and  the  chorion  and  which  is  known  as  the  umbilical  cord 
(Fig.  487,  6). 

In  Mammals  the  yolk  sac  contains  little  or  no  yolk  and  consequently  can 
furnish  but  little  nutriment  for  the  embryo;  but  the  union  of  the  allantois  with 
the  chorion,  mentioned  in  the  preceding  paragraph,  allows  the  allantoic  blood 
vessels  to  come  into  connection  with  the  chorion.  And  since  in  Mammals  the 
chorion  is  the  means  of  establishing  the  communication  between  the  embryo 
and  the  mother,  the  allantoic  (umbilical)  vessels  assume  the  function  of  carrying 
nutrient  materials  to  the  embryo  and  also  of  carrying  away  from  the  embryo  its 
waste  products.  (See  p.  192.) 

Further  Development  of  the  Chorion. 

Up  through  the  stages  which  have  been  described  the  correspondence  in  the 
development  of  the  fcetal  membranes  in  Reptiles,  Birds  and  Mammals  is  clear. 
From  now  on,  the  course  of  development  in  Mammals  becomes  more  and 
more  divergent.  The  extensive  development  of  the  yolk  and  yolk  sac  with  its 


576 


TEXT-BOOK  OF  EMBRYOLOGY. 


vascular  system  in  the  egg-laying  Amniotes  has  been  noted.  This  is  dependent 
upon  the  fact  that  the  embryo  very  early  in  its  existence  loses  its  nutritional  con- 
nection with  its  mother  and  is  therefore  dependent  for  its  food  upon  the  yolk 
stored  up  within  the  egg.  This  condition  obtains  up  through  the  lowest  order 
of  Mammals,  the  Monotremes,  which  are  egg-laying  animals.  The  Marsupials 
give  birth  to  young  of  very  immature  development.  In  these  two  orders  of 
Mammals  the  fcetal  membranes  present  essentially  the  same  condition  as  in 
Birds  and  Reptiles.  The  chorion  in  Marsupials,  however,  lies  in  close  ap- 
v  position  to  the  vascular  uterine  mucosa  and  perhaps  provides  for  the  passage  of 


Chorion 


Uterine 
glands 


Blood 
vessels 


Muscularis 


FIG.  489. — Vertical  section  through  wall  of  uterus  and  chorion  of  a  pig.     Photograph. 

Note  especially  the  close  apposition  of  the  chorionic  and  uterine  epithelium  (and  compare  with 

Fig.  490);  note  also  the  enlarged  blood  vessels  in  the  uterine  mucosa. 


nutrition  from  the  mother  to  the  embryo.  In  all  higher  Mammals,  however,  no 
eggs  are  laid  and  the  embryo  early  acquires  an  intimate  nutritional  relation  to 
its  mother.  This  relation  is  maintained  until  the  embryo  has  reached  a  com- 
paratively advanced  stage  of  development.  As  would  be  expected  therefore, 
there  take  place,  coincidently  with  the  change  in  nutritional  relation  between 
mother  and  embryo,  and  dependent  upon  this  changed  relation,  the  already 
noted  decrease  in,  or  entire  loss  of,  yolk  and  at  the  same  time  the  development  of 
a  special  organ  of  relation  between  embryo  and  uterus.  This  organ  is  devel- 
oped mainly  from  the  chorion  which  becomes  highly  specialized  as  compared 
with  the  very  simple  chorion  described  in  the  chick. 


FCETAL  MEMBRANES. 


577 


In  some  Mammals  (e.g.,  pig,  horse,  hippopotamus,  camel)  there  develops  a 
more  intimate  relation  between  the  chorion  and  the  uterine  mucosa.  In  the 
pig,  for  example,  the  chorionic  vesicle  becomes  somewhat  spindle-shaped,  and, 
except  at  its  tapering  ends,  its  surface  is  closely  applied  to  the  surface  of  the 
uterine  mucosa.  On  that  portion  of  the  chorion  which  is  in  contact  with  the 
uterine  mucosa  small  elevations  or  projections  develop  and  fit  into  correspond- 
ing depressions  in  the  mucosa.  These  projections  involve  the  epithelial 
layer  (ectoderm)  of  the  chorion  and  the  adjacent  connective  tissue  (mesoderm) 
(Fig.  488) .  Furthermore,  the  chorionic  epithelial  cells  and  the  uterine  epithelial 


lu 


Blood  vessel  in 
uterine  mucosa 


FIG.  490.— -From  section  through  wall  of  uterus  and  chorion  of  a  pig.  showing  close  relationship 
between  the  epithelium  of  the  uterus  and  that  of  the  chorion.     Photograph. 

cells  acquire  very  intimate  relations  in  that  the  ends  of  the  former  become 
rounded  and  fit  into  depressions  in  the  ends  of  the  latter  (Fig.  490). 

The  allantois  and  allantoic  vessels  in  the  pig  afford  a  good  example  of  the 
transition  from  the  respiratory  and  excretory  functions  which  they  almost  ex- 
clusively possess  in  Reptiles  and  Birds,  to  the  additional  nutritional  function  of 
these  vessels  in  Mammals.  The  allantoic  sac  becomes  large  and  applies  itself 
to  the  inner  surface  of  the  chorion,  so  that  the  blood  vessels  of  the  allantois  also 
grow  into  and  ramify  in  the  mesodermal  layer  of  the  chorion.  This  brings  the 
allantoic  (umbilical)  blood  vessels  containing  the  fcetal  blood  closer  to  the  uterine 
vessels  containing  the  maternal  blood.  The  two  sets  of  vessels  never  come  in 
contact,  however,  being  always  separated  by  the  chorionic  an.d  uterine  epithe- 


578  TEXT-BOOK  OF  EMBRYOLOGY. 

lium  and  also  by  some  connective  tissue  of  the  chorion  and  of  the  uterine 
mucosa  (Fig.  490).  Food  materials  for  the  embryo  must,  therefore,  pass  through 
the  connective  tissue  and  the  two  epithelial  layers  in  order  to  get  from  the 
maternal  to  the  foetal  blood;  and  waste  products  from  the  embryo  must  also  pass 
through  the  same  tissues  to  get  from  the  fcetal  to  the  maternal  blood.  When  the 
foetal  membranes  of  the  pig  are  expelled  at  birth,  the  rudimentary  chorionic 
villi  simply  withdraw  from  their  sockets  in  the  uterine  mucosa  and  the  chorion 
is  cast  off,  leaving  the  uterine  mucosa  intact. 

In  other  Mammals,  the  attachment  of  the  chorion  to  the  mucous  membrane 
of  the  uterus  is  restricted  to  certain  definite,  highly  specialized  areas.  This 
means  that  the  villi  which  at  first  developed  over  the  entire  chorion,  disappear 
from  the  greater  part  of  it.  Those  villi  which  remain  are  limited  to  a  definite 
area  or  areas  and  develop  extensive  arborizations.  Moreover,  they  do  not 


FIG.  491.— Chorion  of  sheep,  showing  cotyledonary  placenta.     O.  Schultze. 

simply  fit  into  depressions  in  the  uterine  mucosa,  but  become  much  more 
closely  attached  to  it  while  the  mucosa  increases  in  thickness  and  in  vascularity 
over  the  villous  areas.  There  are  thus  formed  two  distinct  though  intimately 
associated  parts  of  a  structure  which  is  known  as  the  placenta — the  uterine  part 
being  designated  the  maternal  placenta  or  placenta  uterina,  the  fcetal  part  the 
placenta  fcetalis.  Such  Mammals  are  grouped  as  Placentalia.  In  the  sheep 
and  cow  a  number  of  placentae — multiple  placenta — are  normally  present  (Fig. 
104).  In  the  dog  and  cat  the  placenta  takes  the  shape  of  a  band  or  a  zone 
of  specialized  tissue  encircling  the  germ  vesicle.  This  is  known  as  a  zonular 
placenta.  In  man  a  single  discoidal  area  develops — discoidal  placenta. 

These  different  forms  of  placentae  vary  also  in  regard  to  the  intimacy  with 
which  maternal  and  fcetal  parts  are  associated.  Thus,  for  example,  in  the 
multiple  placentae  of  the  cow  and  sheep,  the  fcetal  placentae  may  be  easily 


FCETAL  MEMBRANES.  579 

pulled  away  from  the  maternal  placentae;  while  in  the  discoidal  placenta  of 
man,  maternal  and  foetal  parts  are  so  closely  related  that  both  come  away  to- 
gether as  the  after-birth  or  decidua. 

THE  FCETAL  MEMBRANES  IN  MAN. 

The  fcetal  membranes  in  man  are  characterized  by  the  early  development  of 
the  amnion,  the  development  of  an  extremely  complicated  discoidal  placenta  and 
the  rudimentary  condition  of  the  yolk  sac  and  allantois.  The  high  develop- 
ment of  the  placenta — the  organ  of  interchange  between  fcetal  and  maternal 
circulation — is  undoubtedly  dependent  upon  the  very  long  period  of  gestation 
during  which  the  human  foetus  leads  an  entirely  parasitic  existence,  being 
dependent  wholly  upon  the  mother  for  nutrition  and  respiration.  The  exten- 
sive development  of  the  placenta  in  turn  explains  the  rudimentary  condition  of 
the  yolk  sac  and  stalk  and  of  the  allantois,  the  nutritional  and  respiratory  func- 
tions of  these  large  and  important  organs  in  some  of  the  lower  animals,  being  in 
man  taken  up  by  the  placenta. 

The  Amnion. 

In  describing  the  development  of  the  germ  layers  in  the  human  embryo, 
comparisons  were  made  between  one  of  the  youngest  known  human  embryos— 
that  of  Peters — and  the  embryos  of  the  bat  and  mole  (p.  99).  Reference  to  this 
description  and  to  the  figures  shows  that  in  the  bat  and  mole  the  amnion  is 
formed,  not  as  in  the  chick  and  rabbit  by  dorsal  foldings  of  the  somatopleure 
and  fusion  of  these  folds,  but  in  situ  by  a  breaking  down  of  some  of  the  cells  of 
the  inner  cell  mass  and  consequent  cavity  formation.  In  Peters'  embryo  the 
amnion  is  already  present  as  a  closed  cavity.  The  earlier  stages  in  its  forma- 
tion are  not  known.  As  in  the  case  of  the  germ  layers,  however,  the  appear- 
ances in  sections  are  so  closely  similar  as  to  suggest  at  least,  that  the  human 
amnion  is  formed  in  the  same  manner  as  that  of  the  bat  and  mole. 

In  Peters7  ovum  (Fig.  74),  also  in  Bryce-Teacher's  (Fig.  493),  the 
amniotic  cavity  is  seen  already  formed.  It  is  roofed  by  a  single  layer 
of  flat  cells  apparently  analogous  to  the  trophoderm  of  the  bat  (Fig.  59). 
As  in  the  bat  and  chick  this  layer  is  continuous  with  the  higher  ecto- 
derm of  the  embryo  proper  as  represented  here  by  the  embryonic  disk.  The 
extraembryonic  mesoderm  is  already  present  at  this  stage  between  the  ecto- 
derm of  the  amnion  and  the  trophoderm,  the  epithelial  cells  of  the  latter 
being  seen  on  the  surface.  Ventrally  lies  the  yolk  sac  lined  with  entoderm, 
while  laterally  between  the  entoderm  and  ectoderm  is  seen  the  embryonic 
mesoderm.  This  formation  of  the  amnion  in  situ  considerably  shortens  the 
process  of  amnion  formation  as  compared  with  that  in  most  of  the  lower 
animals,  where  it  is  formed  by  dorsal  foldings.  This  results  in  the  very  early 


580  TEXT-BOOK  OF  EMBRYOLOGY. 

formation  of  a  complete  amnion  and  amniotic  cavity  in  such  forms  as  the  bat, 
mole  and  man. 

The  human  amniotic  cavity  is  at  first  small,  the  amnion  covering  only  the 
dorsum  of  the  embryo  to  which  it  is  closely  applied.  The  dorsal  surface  of  the 
disk  is  at  first  concave,  then  flat,  and  later  its  margins  curve  ventrally  as  the  flat 
disk  becomes  transformed  into  the  definite  shape  of  the  embryonic  body.  As 
the  margins  of  the  disk  bend  ventrally  they  carry  with  them  the  attached  amnion. 
As  the  embryo  becomes  constricted  off  from  the  yolk  sac,  the  amnion  is  attached 
only  ventrally  in  the  region  of  the  developing  umbilical  cord.  With  the 
exception  of  this  attachment  the  embryo  thus  comes  to  lie  free,  floating  in 
the  amniotic  fluid  (Fig.  487,  6). 

The  amniotic  cavity,  at  first  small,  increases  rapidly  in  size  and  by  the  third 
month  has  reached  the  limits  of  the  chorionic  vesicle  completely  filling  it.  It 
then  attaches  itself  loosely  to  the  overlying  chorion  thus  completely  obliterating 
the  extraembryonic  body  cavity.  The  amnion  consists  everywhere  of  two 
layers,  an  inner  ectoderm,  the  cells  of  which  are  at  first  flat,  later  cuboidal  or 
even  columnar,  and  an  outer  layer  of  somatic  mesoderm.  At  the  dermal 
navel  (p.  569)  the  amniotic  ectoderm  is  continuous  with  the  surface  ectoderm 
(later  epidermis)  of  the  embryo.  Some  writers  consider  the  fact  that  the 
epithelial  covering  of  the  umbilical  cord  is  stratified  as  indicating  that  it  is 
derived  from  embryonic  ectoderm  rather  than  from  amniotic  ectoderm,  and 
describe  the  transition  between  the  two  as  taking  place  not  at  the  dermal 
umbilicus  but  at  the  attachment  of  the  cord  to  the  placenta.  As  in  lower 
forms  (p.  566)  the  walls  of  the  amniotic  cavity  contain  contractile  elements 
which  determine  rhythmical  contractions  of  the  amnion. 

The  human  amniotic  fluid  is  a  thin,  watery  fluid  of  slightly  alkaline  reaction 
containing  about  one  per  cent,  of  solids,  chiefly  urea,  albumin  and  grape- 
sugar.  The  origin  of  the  fluid  is  not  known.  By  some  it  is  believed  to  be 
mainly  a  secretion  of  the  maternal  tissues,  by  others  as  largely  of  fcetal  origin. 
The  urea  it  contains  is  probably  excreted  by  the  fcetal  kidneys. 

When  the  amount  of  amniotic  fluid  is  excessive  the  condition  is  known  as 
hydramnios.  If,  as  is  sometimes  the  case,  the  amniotic  fluid  is  present  in  very 
small  amount,  adhesions  may  form  between  the  amnion  and  the  embryo. 
These  may  result  in  malformations.  With  or  without  abnormality  in  the 
amount  of  amniotic  fluid,  bands  of  fibrous  tissue  may  stretch  across  the  cavity. 
If  sufficiently  strong  these  may  produce  such  malformations  as  splitting  of 
a  lip  or  of  the  nose,  or  the  partial  or  complete  amputation  of  a  limb. 

In  labor  a  portion  of  the  amnion  filled  with  fluid  usually  precedes  the  head 
through  the  cervical  canal.  It  is  rounded  or  conical,  and  becoming  distended 
and  tense  with  each  uterine  contraction  or  labor  pain,  serves  as  the  natural 
and  most  efficient  dilator  of  the  cervix.  When  the  cervix  is  partially  or  com- 


FCETAL  MEMBRANES.  581 

pletely  dilated,  the  amnion  usually  ruptures — "rupture  of  the  membranes" — 
and  all  or  a  part  of  the  amniotic  fluid  escapes  as  the  "waters."  Usually  a 
varying  amount  of  the  fluid  remains  behind  the  embryo  being  kept  there  by  the 
head  completely  corking  the  cervix.  This  escapes  with  the  birth  of  the  child. 
In  some  cases  the  amnion  ruptures  at  the  beginning  of  labor,  before  there  has 
been  any  dilatation  of  the  cervix.  The  dilating  must  then  be  done  by  the 
child's  head  or  other  presenting  part.  These  are  much  less  adapted  to  the 
purpose  than  the  bag  of  membranes  and  the  result  is  usually  a  difficult  and 
protracted  "dry"  labor.  Rarely  the  amnion  fails  to  rupture  during  labor  and 
the  child  is  born  within  the  intact  bag  of  membranes.  Such  a  child  is  said  to 
be  born  with  a  "caul." 

The  Yolk  Sac. 

In  the  human  embryo  the  yolk  sac  is  but  a  rudiment  of  the  large  and  im- 
portant organ  found  in  some  of  the  lower  animals.  It  develops  early  and  at  the 
end  of  the  second  week  is  an  almost  spherical  sac  with  a  wide  opening  into  the 
intestine  (Fig.  85),  there  being  but  a  slight  constriction  between  the  embryo 
and  the  yolk  sac.  During  the  third  week  the  yolk  sac  becomes  decidedly  con- 
stricted off  from  the  embryo,  remaining  connected,  however,  with  the  intestine 
by  means  of  a  long  pedicle,  the  yolk  stalk  or  vitelline  duct  (Fig.  87).  As  the 
placenta  is  formed,  and  at  the  same  time  the  umbilical  cord,  the  yolk  sac  becomes 
incorporated  with  the  former,  where  it  may  sometimes  be  found  by  careful 
search  after  birth,  while  the  yolk  stalk  becomes  reduced  to  a  strand  of  cells 
which  traverses  the  entire  length  of  the  umbilical  cord  (p.  598). 

Whatever  function  the  rudimentary  human  yolk  sac  has,  must  be  performed 
early,  as  both  sac  and  stalk  soon  undergo  regressive  changes.  Although  no  true 
yolk  is  present,  the  sac  at  first  contains  fluid  and  its  thick  outer  mesodermal  layer 
is  the  place  of  earliest  blood  and  blood  vessel  formation.  This  would  seem  to 
indicate  that  like  the  larger  yolk  sac  of  lower  animals,  the  human  yolk  sac 
serves  temporarily  as  a  blood-forming  organ. 

In  about  three  per  cent,  of  cases  that  portion  of  the  yolk  stalk  which  lies 
between  the  intestine  and  the  umbilicus  fails  to  degenerate,  retaining  its  lumen 
and  its  connection  with  the  intestine.  It  is  then  known  as  MeckeVs  diverticulum 
and  is  of  considerable  surgical  importance,  as  it  may  become  invaginated  into 
the  small  intestine  and  thus  cause  obstruction  of  the  bowel.  The  blind  end  of 
the  diverticulum  may  remain  attached  to  the  umbilicus,  or  it  may  become  free, 
or  in  rare  cases  the  stalk  may  retain  a  lumen  from  the  intestine  to  the  umbilicus, 
through  which  faeces  may  escape— " faecal  fistula."  Occasionally  a  portion  of 
the  gut  from  which  the  yolk  stalk  is  given  off  extends  for  a  short  distance  into 
the  cord.  If,  as  is  sometimes  the  case,  this  extension  fails  to  retract  before 
birth,  a  congenital  umbilical  hernia  is  the  result  (see  Chap.  XX). 


582  TEXT-BOOK  OF  EMBRYOLOGY. 

The  Allantois. 

The  human  allantois,  while  analogous  to  the  allantois  of  Birds  and  Reptiles, 
shows  certain  marked  peculiarities  in  its  development,  in  its  relation  to  sur- 
rounding structures  and  in  its  functions. 

Its  development  is  peculiar  in  that  it  does  not  push  out,  as,  for  example,  in 
the  chick,  as  an  evagination  from  the  primitive  gut  into  the  extraembryonic 
body  cavity,  for  at  the  very  early  stage  at  which  the  human  allantois  first  ap- 
pears, the  primitive  gut  is  not  as  yet  constricted  off  from  the  yolk  sac  and  there 
is  no  extraembryonic  body  cavity  into  which  the  allantois  can  extend.  It  will  be 
remembered  that  in  the  formation  of  the  germ  layers  and  in  the  development  of 
the  amnion  the  human  embryo  shows  a  marked  tendency,  as  compared  with 
lower  forms,  toward  a  shortening  of  the  developmental  process.  This  ab- 
breviation and  consequent  very  early  formation  applies  also  to  the  allantois.  As 
the  embryonic  body  assumes  definite  shape  and  the  amnion  is  formed,  -there  is 
not  the  complete  separation  of  amnion  from  the  chorion  seen,  for  example,  in  the 
chick,  the  embryo  remaining  connected  posteriorly  with  the  chorion  by  means  of 
a  short  thick  cord  of  mesodermic  tissue.  This  is  known  as  the  belly  stalk.  Into 
this  solid  cord  of  mesodermic  tissue  which  connects  the  embryo  with  the 
chorion,  entodermic  cells  extend.  These  are  derived  from  the  embryonic  en- 
toderm  before  the  constriction  which  differentiates  the  primitive  gut  from  the 
yolk  sac  has  made  its  appearance  (Fig.  77).  According  to  some  there  is  a  true 
evagination  from  the  entodermic  sac  quite  analogous  to  the  evagination  in  the 
chick,  resulting  in  a  long  slender  tube  lined  by  entoderm  and  extending  from 
the  embryo  to  the  chorion.  Others  describe  the  entodermic  outgrowth  as  a 
solid  cord  of  cells.  The  mesodermic  layer  of  the  allantois  is  furnished  by  the 
mesoderm  of  the  belly  stalk.  It  is  to  be  noted  in  this  connection  that  the 
mesoderm  of  the  belly  stalk  is  embryonic  mesoderm  and  that  in  Birds,  for 
example,  this  portion  of  the  mesoderm  splits  into  two  layers,  somatic  and 
splanchnic,  with  the  extraembryonic  body  cavity  between  them.  Into  this 
extraembryonic  body  cavity  the  allantois  extends.  In  man  no  such  splitting 
occurs,  so  that  there  is  no  extraembryonic  body  cavity  into  which  the  allantois 
can  extend.  Instead,  it  grows  out  into  the  belly  stalk. 

The  functions  of  the  human  allantois  are  somewhat  different  from  those  of 
the  allantois  of  the  chick.  In  the  latter  it  is  a  direct  respiratory  organ  in  that  it 
brings  the  embryo  into  relation  with  the  outside  air.  In  man  the  allantois, 
accompanied  by  the  allantoic  (umbilical)  blood  vessels,  comes  into  relation 
with  the  placenta.  As  the  placenta  serves  as  the  medium  of  exchange  between 
foetal  and  maternal  circulations,  it  acts  as  a  modified  organ  of  respiration.  In 
the  chick  the  allantoic  cavity  also  serves  for  the  reception  of  the  excretions  from 
the  embryo,  the  allantoic  fluid  containing  nitrogenous  excretives.  In  man  all 


FCETAL  MEMBRANES.  583 

such  elimination  is  carried  on  through  the  placenta  and  there  is  consequently 
no  need  for  the  development  of  a  large  allantoic  sac. 

With  development  of  the  placenta,  that  part  of  the  allantoic  stalk  which  lies 
in  the  umbilical  cord  atrophies.  Of  the  embryonic  portion  of  the  allantois, 
or  the  urachus,  on  the  other  hand,  the  proximal  end  communicates  with  the 
urinary  bladder,  while  the  remainder,  which  extends  from  the  bladder  to  the 
umbilicus  becomes  transformed  into  a  fibrous  cord, — the  middle  umbilical 
ligament  (page  371).  Rarely  that  portion  of  the  allantoic  stalk  between  the 
bladder  and  the  umbilicus  remains  patent  and  opening  upon  the  surface 
forms  a  "urinary  fistula,"  allowing  urine  to  escape. 

In  Reptiles  and  Birds  the  omphalomesenteric  vessels,  passing  along  the  yolk 
stalk  and  ramifying  in  the  mesodermal  layer  of  the  yolk  sac,  convey  the  nutrient 
materials  of  the  yolk  to  the  growing  embryo.  Since  the  allantois  is  an  organ  of 
respiration  and  excretion,  the  allantoic  or  umbilical  vessels  have  nothing  to  do 
with  the  actual  nourishment  of  the  embryo  (p.  191) .  In  Mammals  the  yolk  sac 
is  of  less  functional  value.  Consequently  the  vitelline  vessels,  although  present 
(Fig.  162),  play  a  less  important  role  in  conveying  nutriment.  The  allantoic 
(umbilical)  vessels,  instead  of  ramifying  in  the  wall  of  the  allantois,  as  in  the 
lower  forms,  come  into  connection  with  the  chorion,  passing  primarily  through 
the  belly  stalk.  Since  the  chorion  becomes  the  organ  of  interchange  between 
the  embryo  and  the  mother,  the  allantoic  vessels  assume  a  new  function,  the 
allantoic  (umbilical)  vein  carrying  food  material  from  the  mother  to  the  em- 
bryo, the  arteries  carrying  waste  products  from  the  embryo  to  the  mother. 
Thus  in  Mammals,  as  the  yolk  sac  and  vitelline  vessels  come  to  play  a  less  im- 
portant role  in  the  nutrition  of  the  embryo,  the  allantoic  vessels,  in  connection 
with  the  chorion,  become  practically  the  only  means  by  which  the  embryo 
receives  its  food-supply. 

The  Chorion  and  the  Decidua. 

When  the  fertilized  ovum  reaches  the  uterus  it  becomes  fixed  or  embedded 
In  the  uterine  mucosa.  Fixation  usually  occurs  in  the  upper  half  of  the  uterus 
but  may  occur  near  the  cervix.  Rarely  the  ovum  becomes  fixed  to  the  mucous 
membrane  of  the  tube  instead  of  to  that  of  the  uterus,  and,  developing  there, 
gives  rise  to  a  "tubal"  pregnancy — one  of  the  forms  of  extrauterine  gestation. 

Until  recently,  it  was  believed  that  the  ovum  became  attached  to  the  surface 
of  the  mucous  membrane.  Recent  studies  upon  some  of  the  youngest  human 
ova  and  upon  those  of  some  of  the  lower  Mammals,  however,  seem  to  indicate 
that  the  ovum  in  some  way  pushes  itself  into— buries  itself— in  the  uterine 
mucosa  (Fig.  492).  It  is  argued  that  if  the  ovum  simply  attaches  itself  to  the 
surface  of  the  mucosa,  one  would  expect  to  find,  for  a  time  at  least,  epithelium 
between  the  attached  surface  and  the  stroma.  In  a  very  young  human  ovum 


584 


TEXT-BOOK  OF  EMBRYOLOGY. 


no  such  epithelium  was  found  and  the  ovum  had  the  appearance  of  having 
penetrated  the  stroma  by  which  it  was  surrounded  (Fig.  493).  Thus,  for  the 
first  two  weeks  of  gestation,  the  ovum  lies  embedded  in  the  stroma  of  the  uterine 
mucosa,  giving  so  little  surface  indication  of  its  presence  that  it  is  practically 
impossible  to  locate  it  except  by  serial  sections  of  the  entire  mucosa.  After 
two  weeks  the  position  of  the  ovum  begins  to  be  indicated  by  a  slight  prominence 
of  the  mucous  membrane,  the  summit  of  the  prominence  being  marked  by  an 
entrance  plug  consisting  of  coagulum,  cast  off  cells  and  fibrin  (Fig.  74).  In 


Inner  cell 


Uterine 
epithelium 


Thickening  of 
trophoderm 


Thickening  of  L 

trophoderm 

Degenerating 
uteri--  epithelium 


FIG.  492. — Successive  stages  in  the  implantation  of  the  ovum  of  Spermophilus  citillus.     Rejsek. 

a-  Ovum  (blastodermic  vesicle)  lying  free  in  the  uterine  cavity,      b,  Later  stage  in  which  the 

syncytial  knob  (thickening  of  trophoderm)  has  penetrated  the  uterine  epithelium  as  far  as 

the  basement  membrane,     c,  Still  later  stage  in  which  the  trophoderm  has  penetrated  the 

uterine  stroma;  the  cells  of  the  uterine  epithelium  at  the  point  of  entrance  are  degenerating. 

the  Bryce-Teacher  ovum  no  such  entrance  plug  was  found  (Fig.  493).  At 
this  stage  the  plug  contains  no  glands  or  blood  vessels.  Later  it  becomes 
organized  and  replaced  by  connective  tissue.  Whatever  the  mode  of  fixation 
of  the  ovum  to  the  uterus,  there  immediately  result  important  changes  in  the 
uterine  mucosa  which  lead  to  the  formation  of  the  decidua.  These  changes  are 
both  destructive  and  constructive.  They  are  destructive  in  that  the  epithelial 
covering  of  the  ovum,  the  trophoderm,  has  some  solvent  action  on  the  uterine 
mucosa  and  breaks  down  the  walls  of  the  maternal  blood  vessels  thus  allowing 
the  blood  to  flow  around  the  ovum  (Fig.  493).  They  are  constructive  in  that 
they  result  in  the  formation  of  the  decidua. 


FCETAL  MEMBRANES. 


585 


From  their  relation  to  the  ovum  and  to  the  uterus,  the  deciduse  (by  which  is 
meant  the  uterine  mucosa  of  pregnancy)  have  been  divided  into  the  decidua 
parietalis  or  decidua  verat  the  decidua  basalis  or  serotina,  and  the  decidua  cap  - 
sularis  or  reflexa. 


t3        ,_      •iL-,^-----,— ^- 


-si 


cap.,  Capillary;  cyt.,  cellular  layer  (cyto-trophoderm);  ep.,  uterine  epithelium;  g/.,  uterine  gland ; 
n.  z.,  necrotic  zone  of  decidua  (uterine  mucosa);  P.  e.,  point  of  entrance  of  the  ovum;  tro., 
syncytium  (plasmodium,  plasmodi-trophoderm);  tro.1,  masses  of  vacuolating  syncytium 
invading  capillaries.  The  cavity  of  the  blastodermic  vesicle  is  completely  filled  by  meso- 
derm,  and  embedded  therein  are  the  amniotic.  and  entodermic  (yolk)  vesicles.  The 
natural  proportions  of  the  several  parts  have  been  observed. 


The  decidua  parietalis  is  the  changed  mucosa  of  the  entire  uterus  with  the 
exception  of  that  portion  to  which  the  ovum  is  attached.  The  decidua  basalis 
is  that  portion  of  the  mucosa  to  which  the  ovum  is  attached  and  which  later 
becomes  the  maternal  part  of  the  placenta.  The  decidua  reflexa  is  either  the 


586 


TEXT-BOOK  OF  EMBRYOLOGY. 


extension  of  the  mucosa  over  the  ovum  or  that  part  of  the  mucosa  under  which 
the  ovum  buries  itself  (Fig.  494). 

It  will  be  remembered  that  surrounding  the  entire  young  ovum  is  the  chorion 
and  that  this  membrane  consists  of  two  layers,  an  outer  ectoderm  (trophoderm) 
and  an  inner  mesoderm.  In  the  youngest  known  human  embryo  the  chorion  is 


a 

Decidua  parietalis 
Decidua  capsularis 


Decidua  basalis       1 

I  Placenta 
Chorion  froriclosum  J 


FIG.  494. — Semidiagramatic  sagittal  section  of  human  uterus  containing  an 

embryo  of  about  five  weeks.     Allen  Thompson. 

a,  Ventral  (anterior)  surface;  c,  cervix  uteri;  ch,  chorian;  g,  outer  limit  of  decidua; 
m,  muscularis;  p,  dorsal  (posterior)  surface. 


a  shaggy  membrane,  its  entire  surface  being  covered  with  small  projections  or 
villi.  Later  these  villi  disappear  from  all  of  the  chorion  except  that  part  of  it 
which  becomes  attached  to  the  uterine  mucosa  and  forms  the  fcetal  part  of  the 
placenta.  The  latter  is  known  as  the  chorion  frondosum,  while  the  smooth 
remainder  of  the  chorion  is  known  as  the  chor ion  .Iceve. 
There  are  thus  to  be  considered: 


1.  The  decidua  parietalis. 

2.  The  decidua  capsularis. 

3.  The  decidua  basalis 

4.  The  chorion  frondosum 


forming  the  placenta. 


FCETAL  MEMBRANES.  587 

The  Decidua  Parietalis. — The  changes  in  the  uterine  mucosa  which 
result  in  the  formation  of  the  decidua  parietalis  are  similar  to,  though  more 
extensive  than,  the  changes  which  take  place  during  the  earlier  stages  of  men- 
struation. There  is  congestion  of  the  stroma  with  proliferation  of  the  con- 
nective tissue  elements  and  increase  in  the  length,  breadth  and  tortuosity  of  the 
glands.  These  changes  result  as  in  menstruation  in  thickening  of  the  mucosa 
so  that  at  the  height  of  its  development  the  decidua  parietalis  has  a  thickness  of 
.  about  i  cm.  It  extends  to  the  internal  os  where  it  ends  abruptly,  there  being  no 
decidua  formed  in  the  cervix. 

In  the  superficial  part  of  the  mucosa  the  glands  wholly  or  almost  wholly 
disappear  and  their  place  is  taken  by  the  proliferating  connective  tissue  of  the 
stroma.  The  result  is  a  layer  of  comparatively  dense  connective  tissue — the 
compact  layer.  Beneath  this  layer  are  found  remains  of  the  uterine  glands  in 
the  shape  of  widely  open,  somewhat  tortuous  spaces  which  extend  for  the  most 
part  parallel  to  the  muscularis.  Some  of  these  glandular  remains  retain  part 
of  their  epithelium.  Lying  in  the  proliferating  stroma,  these  spaces  give  to  this 
layer  the  structure  which  has  led  to  its  being  designated  the  spongy  layer. 

During  the  latter  half  of  pregnancy  the  decidua  parietalis  becomes  greatly 
thinned,  due  apparently  to  pressure  from  the  growing  embryo  with  its  mem- 
branes. With  this  thinning,  the  few  remaining  glands  of  the  compact  layer 
disappear.  The  character  of  the  spongy  layer  changes,  the  glands  collapsing  or 
being  reduced  to  elongated,  narrow  spaces  parallel  to  the  muscularis.  The 
entire  tissue  also  becomes  much  less  vascular  than  in  early  pregnancy. 

If  the  foetal  membranes  are  in  situ  the  compact  layer  is  in  contact  with  the 
ectodermic  (epithelial)  layer  of  the  chorion.  Next  to  this  lies  the  mesodermic 
(connective  tissue)  layer  of  the  chorion.  Delicate  adhesions  connect  the 
mesodermic  tissue  of  the  chorion  with  the  mesodermic  layer  of  the  amnion. 
Covering  the  latter  is  the  amniotic  ectoderm  (epithelium). 

The  Decidua  Capsularis. — Early  in  its  development  this  has  essentially 
the  same  structure  as  the  decidua  parietalis.  Its  older  or  more  common  name, 
decidua  reflexa,  indicates  the  earlier  idea  that  this  portion  of  the  decidua  repre- 
sents a  growing  around  or  reflection  of  the  uterine  mucosa  upon  the  attached 
ovum.  Peters,  after  examining  the  very  early  ovum  which  bears  his  name, 
came  to  the  apparently  warranted  conclusion  that  instead  of  the  uterine  mucosa 
growing  out  around  the  ovum,  the  ovum  buries  itself  in  the  mucosa,  and  that  by 
the  time  the  ovum  had  reached  the  size  of  the  one  he  examined  (i  mm.),  it  was 
almost  entirely  covered  over  by  the  mucosa  (Fig.  74).  See  also  Fig.  493.  In 
Peters'  ovum  a  coagulum  consisting  of  blood  cells,  other  cast  off  cells  and 
fibrin  marked  the  point  at  which  the  ovum  probably  entered  the  stroma. 
Later  this  is  replaced  by  connective  tissue  and  for  a  considerable  time  the  point 
is  marked  by  an  area  of  scar  tissue. 


588  TEXT-BOOK  OF  EMBRYOLOGY. 

By  about  the  fifth  month  the  rapidly  growing  embryo  with  its  membranes 
has  filled  the  uterine  cavity,  and  the  decidua  capsularis,  now  a  very  thin  trans- 
parent membrane,  is  everywhere  pressed  against  the  decidua  parietalis.  It 
ultimately  either  disappears  (Minot)  or  blends  with  the  decidua  parietalis 
(Leopold,  Bonnet). 

The  Decidua  Basalis. — As  the  decidua  basalis  is  that  part  of  the  mucosa 
to  which  the  chorion  frondosum  is  attached,  it  is  convenient  to  consider  the 
two  structures  together. 

Decidua 


"Fastening"  vilii 


Terminal  villi 


FlG.  495. — Isolated  villi  from  chorion  frondosum  of  a  human  embryo  of 
eight  weeks.     Kollmann's  Atlas. 

At  a  very  early  stage,  villi  develop  over  the  entire  surface  of  the  chorion 
(Fig.  493).  Very  soon,  however,  the  villi  begin  to  increase  in  number  and  in 
size  over  the  region  of  the  attachment  of  the  ovum  and  to  disappear  from  the 
remainder  of  the  chorion,  thus  leading  to  the  already  mentioned  distinction 
between  the  chorion  frondosum  and  the  chorion  laeve  (p.  586) . 

THE  CHORION  FRONDOSUM  or  fcetal  portion  of  the  placenta  consists  of  two 
layers  which  are  not,  however,  sharply  separated. 

1.  The  compact  layer.     This  lies  next  to  the  amnion  and  consists  of  con- 
nective tissue. "  At  first  the  latter  is  of  the  more  cellular  embryonal  type.     Later 
it  resembles  adult  fibrous  tissue. 

2.  The  villous  layer.     The  chorionic  villi,  when  they  first  appear,  are  short 


FCETAL  MEMBRANES. 


589 


simple  projections  from  the  epithelial  layer  of  the  chorion  and  consist  wholly  of 
epithelium.  Very  soon,  however,  two  changes  take  place  in  these  projec- 
tions. They  branch  dichotomously  giving  rise  to  secondary  and  tertiary  villi, 
forming  tree-like  structures  (Fig.  495).  At  the  same  time  mesoderm  grows 
into  each  villus  so  that  the  central  part  of  the  originally  solid  epithelial  villus  is 
replaced  by  connective  tissue,  which  thus  forms  a  core  or  axis.  This  connective 
tissue  core  is  at  first  free  from  blood  vessels,  but  toward  the  end  of  the  third  week 
terminals  of  the  umbilical  (allantoic)  vessels  grow  out  into  the  connective  tissue 
and  the  villus  becomes  vascular.  Each  villus  now  consists  of  a  core  of  vascular 
mesodermic  tissue  (embryonal  connective  tissue)  covered  over  by  trophoderm 


Syncytium 


Cellular  layer 
(of  Langhans) 


Blood  vessels 


Mesoderm 
(core  of  villus) 


Intervillous 
space 


FIG.  496. — Section  of  proximal  end  of  villus  from  chorion  frondosum  of  human  embryo 

of  two  months.     Photograph. 

In  the  space  above  the  villus  is  a  mass  of  cells  such  as  are  invariably  found  among  or  attached  to 

the  villi  (see  text,  page  594). 


(epithelium).  At  first  the  epithelium  of  the  villus  consists  of  distinctly  outlined 
cells.  Very  soon,  however,  the  epithelium  shows  a  differentiation  into  two 
layers.  The  inner  layer  lying  next  to  the  mesoderm  is  called  the  layer  of 
Langhans  or  cyto-trophoderm.  Its  cell  boundaries  are  distinct  and  its  nuclei 
frequently  show  mitosis.  The  outer  covering  layer  consists  of  cells  the  bodies 
of  which  have  fused  to  form  a  syncytium — the  syncytial  layer  or  plasmodi- 
trophoderm.  This  is  a  layer  of  densely  stained  protoplasm  of  uneven  thickness 
(Figs.  496  and  497).  It  contains  small  nuclei  which  take  a  dark  stain.  As 
this  layer  is  constantly  growing,  and  as  these  nuclei  do  not  show  mitosis,  it  has 
been  suggested  that  they  probably  multiply  by  direct  division. 


590  TEXT-BOOK  OF  EMBRYOLOGY. 

At  an  early  stage  large  masses  of  cells  appear  among  the  villi,  sometimes  being 
attached  to  the  villi  (Figs.  496  and  498) .  The  origin  of  these  masses  is  not  known 
with  certainty.  They  may  represent  thickenings  of  the  syncytium  in  which  the 
cell  boundaries  have  reappeared,  or  they  may  represent  outgrowths  from 
Langhans'  layer.  In  some  cases  the  cells  are  small  with  darkly  staining  nuclei, 
in  other  cases  large  and  homogeneous  with  large  vesicular  nuclei.  Large 
multinuclear  cells,  or  giant  cells,  with  homogeneous  cytoplasm,  also  appear. 
In  some  cases  they  apparently  lie  free  in  the  intervillous  spaces  although 


Hofbauer's  celJ 


Capillary 


FIG.  497. — Transverse  section  of  chorion  villus  from  human  embryo  of  two  months,  showing  meso- 
dermal  core  of  villus  and  surrounding  cellular  layer  (cyto-trophoderm)  and  syncytium  (plas- 
modi-trophoderm).  Hofbauer's  cell  is  an  example  of  large  cells  found  in  the  villi,  but  the 
significance  of  which  is  not  known.  From  retouched  photograph.  Grosser. 


it  is  claimed  by  some  investigators  that  they  merely  represent  sections  of 
tips  of  the  syncytial  masses.  A  structure  known  as  canalized  fibrin  (which 
takes  a  brilliant  eosin  stain)  begins  to  develop  in  the  earlier  months  of  preg- 
nancy and  gradually  increases  in  amount  during  the  later  stages.  It  is  found 
in  relation  with  the  large  cell  masses  among  the  villi  and  is  probably  a  degen- 
eration product  of  these  masses. 

In  the  later  months  of  pregnancy  the  covering  layer  of  the  villi  loses  its 
distinctly  epithelial  character,  the  cyto-trophoderm  or  cellular  layer  disappearing 
and  the  plasmodi-trophoderm  or  syncytial  layer  becoming  reduced  to  a  thin 


FCETAL  MEMBRANES. 


591 


homogeneous  membrane.  At  points  in  this  membrane  are  knob-like  projections 
composed  of  darkly  staining  nuclei.  These  are  known  as  nuclear  groups,  or 
proliferation  islands,  and  probably  represent  the  proximal  portions  of  the  large 
cell  masses  already  described  (compare  Figs.  497  and  499). 

Certain  of  the  uterine  stroma  cells  increase  greatly  in  size  and  become  the 
decidual  cells.  These  are  large  cells — 30  to  100  microns — and  vary  in  shape. 
Late  in  pregnancy  they  acquire  a  brownish  color  and  give  this  color  to  the 
superficial  layer  of  the  decidua  parietalis.  Each  cell  usually  contains  a  single 


Syncytium 


Trophoderm 
mass 


FIG.  498. — Section  c/  cuorion  of  human  embryo  of  one  month  (9  mm.).     Grosser. 


large  nucleus.  Some  contain  two  or  three  nuclei.  A  few  are  frequently 
multinuclear. 

Some  of  the  chorionic  villi  float  freely  in  the  blood  spaces  of  the  maternal 
placenta — floating  villi;  others  are  attached  to  the  maternal  tissue — fastening 
villi.  The  villi  are  separated  into  larger  and  smaller  groups  or  lobules  by  the 
growth  of  connective  tissue  septa  from  the  maternal  placenta  down  into  the 
decidua  basalis.  These  are  known  as  placental  septa,  while  the  groups  of 
chorionic  villi  are  known  as  cotyledons  (Figs.  500  and  502). 

Both  decidual  cells  and  chorionic  villi  are  important  from  a  diagnostic 


592 


TEXT-BOOK  OF  EMBRYOLOGY. 


standpoint,  as  the  finding  of  them  in  curettings  or  in  a  uterine  discharge  may 
be  accepted  as  proof  of  pregnancy. 

During  the  early  months  of  pregnancy — first  four  months — the  decidua 
basalis  has  essentially  the  same  structure  as  the  decidua  parietalis.  Its  surface 
epithelium  disappears  very  early,  perhaps  even  before  the  attachment  of  the 
ovum.  The  glandular  elements  and  the  connective  tissue  undergo  the  same 
changes  as  in  the  decidua  parietalis  and  here  also  result  in  the  differentiation 
of  a  compact  layer  and  a  spongy  layer.  Both  layers  are  much  thinner  than 
in  the  decidua  parietalis. 

As  already  noted,  connective  tissue  septa  pass  from  the  superficial  layer  of  the 
decidua  basalis  down  into  the  fcetal  placenta  subdividing  the  latter  into  cotyle- 
dons. .  At  the  margin  of  the  placenta  the  decidua  basalis  passes  over  into  the 


Remnant  of  syncytium 

Capillaries  <vj  ~ 


Remnant 
of  syncytium 


Nuclear  group -, 


Artery  — 


Capillary 

Nuclear  group 
FIG.  499. — Transverse  sections  of  chorionic  villi  at  the  end  of  pregnancy.     Schaper. 

thicker  decidua  parietalis  and  here  the  chorion  is  firmly  attached  to  the  decidua 
basalis. 

There  still  remains  to  be  considered  what  may  be  called  the  border  zone 
between  the  decidua  basalis  and  the  chorion  frondosum.  The  whole  purpose 
of  the  placenta  is  the  interchange  of  materials  between  the  maternal  and  fcetal 
circulation.  It  is  in  the  border  zone  that  this  interchange  takes  place.  The 
entire  structure  of  this  zone  is  for  this  function,  while  all  the  rest  of  the  placenta 
serves  to  transport  the  blood  to  and  from  this  area.  We  have  considered  on  the 
maternal  side  the  structure  of  the  superficial  (compact)  layer  of  the  decidua 
basalis  (p.  587) ,  on  the  fcetal  side  the  structures  of  the  villous  layer  of  the  chorion 
frondosum  (p.  588) .  Unfortunately,  this  border  zone  has  an  extremely  com- 
plicated structure  which  is  difficult  of  interpretation  in  the  usual  microscopic 
section.  This  has  led  to  much  confusion  in  description  and  many  differences 
of  opinion  as  to  actual  structure.  We  can  here  consider  only  the  more  generally 


FCETAL  MEMBRANES. 


593 


accepted  facts,  referring  the  student  to  special  articles  on  the  subject  for  further 
details. 

In  the  fully  developed  placenta,  the  chorionic  villi  lie  either  free  (floating 


villi)  or  attached  to  the  decidua  (fastening  villi)  in  what  are  known  as  inter- 
villous  spaces  (Fig.  500).     In  sections  the  villi  are,  on  account  of  their  structure, 


594 


TEXT-BOOK  OF  EMBRYOLOGY. 


?•  Base  of  villus 


Villi  in  section 


Blood  vessel 


Uterine  glands 
J  Base  of  decidua 


FlG.  501. — Vertical  section  through  wall  of  uterus  and  placenta  in  situ;  about  seven  months' 

development.     Minot. 


FCETAL  MEMBRANES. 


595 


cut  in  all  directions,  many  sections  of  villi  being  entirely  free  from  their  basal 
connections.  The  villi  thus  present  the  appearance  of  projections,  peninsulas, 
or  islands  lying  in  spaces  filled  with  blood  (Fig.  501). 

Branches  from  the  arteries  of  the  uterine  muscularis  enter  the  decidua  basa- 
lis.  They  take  very  tortuous  courses  through  the  latter  and  in  it  lose  their  con- 
nective tissue  and  muscular  coats,  and,  while  of  considerably  larger  diameter 
than  most  capillaries,  become  reduced  to  endothelial  tubes.  These  follow  the 
intervillous  (placental)  septa  in  which  they  branch  and  from  which  they  finally 
open  directly  into  the  intervillous  spaces  along  the  edges  of  the  cotyledons. 
The  maternal  blood  is  thus  poured  into  the  intervillous  spaces  at  their  peri- 
phery. After  flowing  through  them  it  passes  into  veins  which  leave  the 
intervillous  spaces  near  the  center  of  the  cotyledons  (Fig.  500). 


Chorion  laeve  + 
Decidua  parietalis 


Decidua  basalis 


Cotyledon 
(lobe) 


Cotyledon 
(lobe) 


FIG.  502 . — Placenta  at  birth,  seen  from  the  uterine  side.     Bonnet. 

The  relation  of  these  spaces  to  the  maternal  blood  vessels  is  not  easy  to  make 
out  in  ordinary  sections,  but  many  observations  have  established  the  fact  that 
both  arteries  and  veins  open  directly  into  the  spaces.  The  entire  system  of 
intervillous  spaces  may  thus  be  considered  as  a  part  of,  or  an  appendage  to,  the 
maternal  vascular  system,  the  maternal  blood  flowing  from  the  arteries  into 
these  spaces  and  returning  from  these  spaces  to  the  mother  through  the  veins. 
The  foetal  blood,  on  the  other  hand,  circulates  in  the  capillaries  of  the  connective 
tissue  of  the  villi  separated  from  the  maternal  blood  of  the  intervillous  spaces  by 
the  epithelial  villous  covering  already  described  (p.  589) .  It  is  between  the 
maternal  blood  of  the  intervillous  spaces  and  the  foetal  blood  in  the  villous 
capillaries  that  the  interchange  of  material  takes  place.  Both  the  maternal 
and  foetal  vascular  systems  are  closed  systems  so  that  no  blood  can  pass  directly 


596  TEXT-BOOK  OF  EMBRYOLOGY. 

from  mother  to  foetus  or  from  foetus  to  mother.  This  can  be  absolutely  proved  in 
early  pregnancy  by  the  fact  that  nucleated  red  cells  are  at  this  stage  constantly 
present  in  the  blood  of  the  fcetiis  but  never  normally  present  in  the  maternal 
circulation.  The  normal  circulation  of  blood  through  spaces  unlined  by  endo- 
thelium  is  such  a  remarkable  exception  in  histology  that  repeated  attempts 
have  been  made  to  demonstrate  an  endothelial  lining  to  the  intervillous  spaces 
but,  up  to  the  present  time,  no  such  lining  has  been  found. 

The  manner  in  which  the  intervillous  spaces  are  formed  still  remains  the 
subject  of  much  controversy.  The  similarity  of  development  in  the  human 
ovum  and  in  the  ovum  of  the  bat  has  already  been  noted.  In  the  bat  the 
chorion  when  first  formed  consists  of  two  thin  layers,  an  inner  mesodermal 
layer  and  an  outer  ectodermal  layer  (trophoderm).  From  analogy  there  is 
every  reason  to  believe  that  the  early  human  chorion  has  the  same  struc- 
ture. Proof  of  this  is,  however,  as  yet  wanting,  as  in  the  earliest  human  ova 
the  trophoderm  is  already  a  thick  layer.  There  are  also  present  over  the 
entire  surface  of  the  chorion  and  thus  in  contact  not  only  with  the  future 
decidua  basalis  but  also  in  contact  with  the  entire  future  decidua  capsularis, 
well  developed  villi,  each  consisting  of  a  core  of  mesoderm  and  of  a  thick  covering 
of  trophoderm  (Fig.  74).  Between  the  villi,  bounded  by  the  villi  and  by  the 
decidua,  are;  pools  of  maternal  blood.  Peters  suggested  that  rapid  prolifera- 
tion of  the  cells  of  the  trophoderm  might  result  in  an  opening  up  of  the  maternal 
vessels  with  which  they  came  in  contact  and  give  rise  to  repeated  effusions  of 
maternal  blood.  This  blood  would  be  poured  out  mainly  within  the  tropho- 
derm but  bounded  externally  by  the  decidua.  The  blood  pools  thus  formed 
would  represent  the  first  stage  in  the  formation  of  the  intervillous  spaces.  Ac- 
cording to  Bonnet  and  others  the  chorionic  villi  of  the  developing  placenta  are 
constantly  opening  up  new  decidual  vessels,  the  trophoderm  eroding  or  dis- 
solving more  and  more  decidual  tissue,  so  that  the  intervillous  spaces  are  con- 
stantly increasing  in  size  with  growth  of  the  placenta. 

The  placenta  at  birth  is  a  discoid  mass  of  tissue  between  15  and  20  cm.  in 
diameter,  about  3  to  4  cm.  thick  and  weighs  from  500  to  1200  grms.  As  its 
area  of  attachment  marks  the  point  where  the  ovum  becomes  fixed  to  the 
uterine  mucosa  and  as  the  point  of  fixation  of  the  ovum  varies,  the  placenta  may 
be  attached  to  any  portion  of  the  uterine  wall.  It  is  most  frequently  attached 
in  the  region  of  the  fundus  and  more  frequently  to  the  posterior  wall  than  to 
the  anterior.  If  the  fixation  of  the  ovum  is  sufficiently  low,  the  placenta  may 
partly  or  completely  close  the  internal  os,  thus  giving  rise  to  what  is  known  as 
placenta  pr&via. 

The  Umbilical  Cord. — As  the  amnion  grows  and  extends  ventrally  with 
the  ventral  bending  of  the  embryonic  disk,  the  yolk  stalk  and  sac,  now  very 
much  attenuated,  become  pressed  against  the  cord  of  mesodermal  tissue  which 


FCETAL  MEMBRANES. 


597 


connects  the  embryo  with  the  chorion,  and  incorporated  with  it  to  form  the 
umbilical  cord  (Figs.  81  and  82). 

The  umbilical  cord  thus  consists  of :  (Fig.  503) : 

1.  Amnion.     This  is  attached  to  the  embryo  at  the  navel.     It  is  at  first 
loosely  connected  with  the  underlying  tissue  of  the  cord  so  that  it  is  easily 
peeled  off;  later  it  becomes  firmly  adherent.     The  epithelium  of  the  amniotic 
covering  of  the  cord  is  stratified  and  is  described  by  some  (Minot,  McMurrich) 
as  of  embryonic  ectodermic  origin  instead  of  as  part  of  the  amnion. 

2.  What  may  be  called  the  ground  substance  or  substantia  propria  of  the 
cord.     This  is  an  embryonic  connective  tissue  often  described  as  "mucous 

Umbilical  vein 


Amnion 


Umbilical      Allantoic 
arteries  stalk 

FlG.  503.— Transverse  section  of  umbilical  cord  of  a  pig  embryo  six  inches  in  length.    Photograph. 

tissue."  It  consists  of  a  soft  gelatinous  intercellular  substance  and  irregular, 
branching  stellate  cells.  On  account  of  its  consistency  it  has  been  called 
"Wharton's  jelly." 

3.  Three  umbilical  vessels— two  arteries  and  one  vein.  All  these  vessels 
are  thick  walled  and  the  developing  smooth  muscle  is  in  bundles  separated  by 
considerable  connective  tissue.  The  two  umbilical  arteries  carry  venous  blood 
from  the  foetus  to  the  placenta  where  their  branches  ultimately  give  rise  to  the 
capillaries  of  the  chorionic  villi.  From  the  villi  the  blood  enters  the  terminals 
of  the  umbilical  vein  and  returns  as  arterial  blood  to  the  foetus  (Fig.  504). 

As  they  traverse  the  cord  the  arteries  make  a  number  of  spiral  turns  around 
the  vein  and  give  to  the  cord  the  appearance  of  being  spirally  twisted.  The 


598  TEXT-BOOK  OF  EMBRYOLOGY. 

cause  of  this  twisting  is  not  known.  In  places  where  the  turns  are  quite  abrupt 
and  there  are  considerable  accumulations  of  connective  tissue,  the  cord  has  a 
knotted  appearance.  These  points  are  known  as  false  knots.  Rarely  the  cord 
is  actually  tied  into  a  more  or  less  complex  knot — true  knot — probably  due  to 
movements  of  the  fcetus. 

4.  Remnants  of  the  allantoic  stalk  and  of  the  yolk  stalk.  These,  if  present, 
are  continuous  or  broken  cords  of  epithelial  cells.  Rarely  one  or  the  other  may 
retain  its  lumen  or  some  of  the  yolk  stalk  vessels  may  remain. 

As  the  yolk  stalk  is  carried  around  to  be  incorporated  as  part  of  the  umbilical 
cord  there  is  enclosed  with  it  a  small  part  of  the  extraembryonic  body  cavity. 

The  human  umbilical  cord  averages  50  cm.  in  length  and  has  a  diameter  of 
about  1.5  cm. 

The  Expulsion  of  the  Placenta  and  Membranes. — After  the  birth  of  the 
child,  the  uterine  contractions  usually  cease  temporarily  and  the  uterine  walls 
remain  contracted  around  the  placenta.  In  the  course  of  a  few  moments  the 
uterine  contractions  are  resumed  and  the  placenta  and  membranes  are  ex- 
pelled as  the  after -birth. 

The  line  of  separation  of  the  placenta  and  of  the  decidua  parietalis  from  the 
uterine  mucosa  is  through  the  deeper  part  of  the  spongy  layer  (Fig.  500).  By 
this  separation  many  blood  vessels  are  opened,  the  hemorrhage  being  con- 
trolled by  the  firm  contractions  of  the  uterine  muscle.  The  condition  of  the 
uterine  mucosa,  after  child-birth,  has  been  described  as  an  exaggeration  of  its 
condition  at  the  end  of  menstruation.  Reconstruction  of  the  mucosa  takes 
place  by  proliferation  of  the  still  remaining  connective  tissue  and  of  the  gland- 
ular elements, 

Anomalies. 

The  manner  in  which  the  placenta  is  formed — by  excessive  development  of 
the  decidua  and  chorion  over  a  limited  area  and  atrophy  of  the  chorion  through- 
out the  remainder  of  its  extent — suggests  the  most  frequent  variations  from  the 
normal. 

The  villi  instead  of  developing  over  the  usual  discoid al  area  may  develop  along 
a  band-like  area  which  more  or  less  completely  encircles  the  chorion.  This  gives 
rise  to  an  annular  placenta  similar  to  that  seen  in  the  Garnivora.  Continued 
development  of  the  villi  over  the  entire  chorion  may  occur.  This  results  in  a 
thin  "placenta  membranacea."  Such  a  placenta  is  apt  to  be  adherent  and  may 
thus  cause  a  serioiu  postpartum  condition.  Failure  of  the  villi  to  atrophy  and 
their  continued  development  over  more  than  a  single  area  give  rise  to  variations 
in  form  and  number  of  placenta.  When  there  are  two  not  very  distinctly 
separated  areas  the  condition  is  known  as  placenta  bipartita.  Two  completely 
separated  placentae  with  distinct  branchings  of  the  umbilical  vessels  to  supply 


FCETAL  MEMBRANES.  599 

them  are  known  as  placenta  duplex.  Placenta  triplex  and  up  to  placenta  septu- 
plex  have  been  described.  When  one  or  more  placental  lobules  develop  at  a 
little  distance  from  the  main  placental  mass  but  connected  with  the  latter  by 
blood  vessels,  the  result  is  the  not  uncommon  placenta  succenturiata.  Placenta 
spuria  is  applied  to  such  an  accessory  lobule  when  it  has  no  vascular  connection 
with  the  main  placenta  and  consequently  no  function. 

Anomalies  of  the  placenta  associated  with  multiple  pregnancies  and  with 
anomalies  of  the  foetus  will  be  found  under  their  respective  heads. 

Anomalies  of  the  cord  are  for  the  most  part  dependent  upon  anomalies  of 
the  foetus  and  of  the  placenta. 

References  for  Further  Study. 

BENEKE:  Sehr  junges  menschliches  Ei.  Monatsschr.  f.  Geburtshilfe  u.  Gyndkologie,  Bd. 
XXII,  1904. 

BONNET,  R.t  Lehrbuch  der  Entwickelungsgeschichte  des  Menschen.     Berlin,  1907. 

BRYCE,  T.  H.:  Embryology.     In  Quain's  Anatomy,  nth  ed.,  Vol.  I,  1908. 

BRYCE,  T.  H.,  and  TEACHER,  J.  H.:  An  Early  Ovum  Imbedded  in  the  Decidua. 
Glasgow,  1908. 

CRAGIN,  E.  B.:  Text-book  of  Obstetrics.     1915. 

FRASSI,  L.:  Uber  ein  junges  menschliches  Ei  in  situ.     Arch.f.  mik.  Anat.,  Bd.  LXX,  1907. 

GROSSER,  O.:  Die  Eihaute  und  der  Placenta.     1908. 

HERTWIG,  O.:  Lehrbuch  der  Entwickelungsgeschichte  des  Menschen  und  der  Wirbel- 
tiere.  Berlin,  1906. 

HOFBAUER,  J.:  Biologic  der  menschlichen  Placenta.     Wien  and  Leipzig,  1905. 

HUBRECHT,  A.  A.  W.:  Placentation  of  Erinaceus  Europaeus.  Quart,  Jour,  of  Mic.Sci., 
Vol.  XXX,  1889. 

VON  HUEKELOM,  S. :  Ueber  die  menschliche  Placentation.  Archiv.  fur  Anat.  und Physiol., 
Anat,  Abth.,  1898. 

KEIBEL,  F.,  and  MALL,  F.  P»:  Manual  of  Human  Embryology.     Vol.  I,  1910. 

KOLLMANN,  J.:  Lehrbuch  der  Entwickelungsgeschichte  des  Menschen.     Jena,  1898. 

KOLLMANN,  J.:  Handatlas  der  Entwickelungsgeschichte  des  Menschen.     Bd.  I,  1907. 

LEOPOLD,  G.:  Ueber  ein  sehr  junges  menschliches  Ei  in  situ.     Leipzig,  1906. 

MARCHAND,  F.:  Beobachtungen  an  jungen  menschlichen  Eiern.  Anat.  Hefte,  Bd.  XXL 
1903. 

McMuRRiCH,  J.  P.:  The  Development  of  the  Human  Body.     Philadelphia,  1907. 

MINOT,  C.  S.:  Uterus  and  Embryo.    Jour,  of  Morphol.,  Vol.  II,  1889. 

MINOT,  C.  S.:  Laboratory  Text -book  of  Embryology.     Philadelphia,  1903. 

PETERS,  H.:  Ueber  die  Einbettung  des  menschlichen  Eies  und  das  frUheste  bishei 
bekannte  menschliche  Placentationsstadium.  Leipzig,  1899. 

MERTTENS,  J.:  Beitrage  zur  normalen  und  pathologischen  Anatomic  der  menschlichen 
Placenta.  Zeitschr.  f.  Geburtshilfe  u.  Gynakologie,  Bd.  XXX,  XXXI,  1894. 

REJSEK,  J.:  Anheftung  (Implantation)  des  Saugetiereies  an  die  Uteruswand,  insbesondere 
des  Eies  von  Spermophilus  citillus.  Arch.  f.  mik.  Anat.,  Bd.  LXIII,  1904. 

Rossi  DORIA,  T.:  Ueber  die  Einbettung  des  menschlichen  Eies,  studirt  an  einem  kleinen 
Eie  der  zweiten  Woche.  Arch.  f.  Gynak.,  Bd.  LXXVI,  1905. 

SELENKA,  E.:  Studien  iiber  die  Entwickelungsgeschichte  der  Tiere;  (Menschenaffen) . 
Wiesbaden,  1901-1906.  Parts  8- 10. 


600  TEXT-BOOK  OF  EMBRYOLOGY. 

STRAHL,  H. :  Die  Embryonalhiillen  der  Sauger  und  die  Placenta.     In  Hertwig's  Handbuch 
der  vergleich.  u.  experiment,  Entwickelungslehre  der  Wirbeltiere.     Bd.  I,  Tei)  II,  1902. 
WEBSTER,  J.  C..  Human  Placentation.     Chicago,  1901, 


CHAPTER  XX. 

TERATOGENESIS. 

MALFORMATIONS  INVOLVING  MORE  THAN  ONE  INDIVIDUAL. 
Classification,  Description,  Origin. 

To  give  a  complete  list  of  the  numerous  malformations  in  man,  even  of 
those  which  affect  the  external  form  of  the  body,  is  obviously  beyond  the  scope 
of  this  book.  In  this  chapter  it  is  the  purpose  of  the  writers  merely  to  describe 
in  a  general  way  the  most  striking  malformations  and  discuss  briefly  the  causes 
underlying  the  origin  of  malformations.  For  further  details  concerning  the 
subject  the  student's  attention  is  directed  to  "  References  for  Further  Study " 
(p.  624). 

The  classification  of  malformations  is  attended  by  great  difficulties.  This 
is  due  mainly  to  the  fact  that  their  complexities  are  not  wholly  understood.  It 
is  due  also  in  a  measure  to  the  fact  that,  apart  from  certain  malformations 
which  always  occur  in  like  manner  in  different  individuals,  there  are  so  many 
irregularities  and  deviations  from  any  type  that  might  arbitrarily  be  chosen. 
The  classification  made  by  St.  Hilaire  three-quarters  of  a  century  ago, 
although  apparently  complete,  showed  many  incongruities  as  teratology 
became  more  firmly  established  upon  an  embryological  basis.  Later 
Bischoff  formulated  a  division  based  upon  the  embryological  significance 
of  malformations.  This  in  turn  was  elaborated  by  Forster,  and  Forster's 
scheme  has  been  adopted  by  Marchand  and  others.  As  knowledge  concern- 
ing teratogenesis  is  added  to,  it  may  be  that  further  changes  in  classification  will 
be  necessary,  especially  in  view  of  the  fact  that  much  light  is  being  thrown  by 
experimental  methods  upon  the  origin  of  malformations. 

Marchand's  scheme  of  duplicate  monsters  is  given  here  as  a  convenient  one 
for  a  comprehensive  view  of  anomalous  conditions  affecting  two  individuals. 
I.  Both  bodies  derived  from  anlagen  which  developed  from  one  ovum 
and    which    were    originally  similar   and    symmetrical:    Symmetrical 
duplicity. 
A.  Both  bodies  originally  complete :     Complete  duplicity. 

i.  The  two  bodies  remain  separate;  union  confined  to  chorion* 
Twins;  free  duplicities. 

a.  Both  bodies  formed  alike,  each  capable  of  living:    Equal 
monochorionic  twins. 
601 


602  TEXT-BOOK  OF  EMBRYOLOGY. 

b.  One  body  normal,  the  other  abnormal  or  much  mal- 
formed:    Unequal  monochorionic  twins. 

2.  The  two  bodies  united;  formed  alike  (equal),  or  one  remains 
more  or  less  rudimentary  (unequal) :  Twins  joined  together; 
duplicate  monsters. 

a.  Union  confined  to  lower  end  of  body :     Double  monsters 
with  posterior  union;  anterior  duplicity. 

b.  Union  confined  to  middle  of  body,  or  extending  from 
middle  forward:     Double  monsters  with  middle  union. 

c.  Union  limited  to  upper  end  of  body,  or  extending  from 
upper  end  downward:     Double  monsters  with  anterior 
union;  posterior  duplicity. 

B.  Duplicity  does  not  affect  entire  anlage,  but  only  a  part :   Incomplete 
duplicity. 

1.  Two  incomplete  anlagen  (or  primitive  streaks)  pass  over  into 
a  single  anlage:    Posterior  incomplete  duplicity. 

2.  An  originally  single  anlage  forms  by  dichotomous  growth  two 
separate  upper  (anterior)  ends:  Anterior  incomplete  duplicity. 

In  addition:     Triplicity,  quadruplicity,  etc.,  (multiplicity). 
II.  Both   bodies   derived   from   two   originally  dissimilar,  asymmetrical 
anlagen,  of  which  one,  always  rudimentary,  becomes  more  or  less  en- 
closed and  nourished  by  the  other:  True  parasitic  duplicity;  asym- 
metrical duplicity. 

In  addition:     Teratoid  tumors. 

SYMMETRICAL  DUPLICITY. 

As  seen  from  the  foregoing  scheme,  there  are  included  under  this  head 
double  forms  in  which  both  embryos  develop  within  a  single  chorion  (mono- 
chorionic twins),  and  in  which  the  bodies  may  be  distinct  and  separate 
(complete  duplicity)  or  may  be  united  (incomplete  duplicity).  In  complete 
duplicity  each  embryo  usually  possesses  its  own  amnion  and  umbilical  cord, 
but  both  are  attached  to  the  same  placenta.  In  such  cases  the  two  in- 
dividuals probably  developed  from  one  fertilized  ovum  and  thus  received 
equivalent  chromatin  which,  with  similar  nutritional  conditions,  guided 
the  formation  of  equal  monochorionic  twins.  They  may  grow  to  maturity, 
and  they  always  bear  a  remarkable  resemblance  to  each  other  in  physical 
features  and  in  mental  characteristics  and  are  always  of  the  same  sex.  More 
commonly,  however,  the  development  of  separate  monochorionic  twins  is 
unequal,  caused  probably  by  dissimilar  chromatin  and  nutrition.  In  some 
instances  the  less  favored  individual  is  but  slightly  affected,  so  that  it  may 
be  born  and  be  able  to  maintain  an  independent  existence.  On  the  other 


TERATOGENESIS.  603 

hand,  the  nutrition  of  one  embryo  may  be  so  seriously  impaired  that  it  dies. 
When  death  occurs  during  the  earlier  months  of  pregnancy  the  dead  embryo 
is  subjected  to  pressure  by  the  living  one  and  is  sometimes  distorted  and 
flattened  into  a  thin  mass  known  as  a  fcetus  papyraceus. 

Equal  growth  of  monochorionic  twins  implies  an  almost  perfect  nutritive 
balance,  since  both  embryos  derive  their  nourishment  from  the  same  placenta. 
Any  condition  that  disturbs  the  nutritive  balance  tends  to  affect  adversely  the 
less  favored  embryo,  so  that  development  does  not  proceed  equally  (unequal 
monochorionic  twins).  One  of  the  first  consequences  of  such  a  disturbance 
may  be  an  impaired  or  arrested  development  of  the  heart,  in  which  case  the 
weaker  embryo  may  become  an  acardiac  monster. 

This  condition  does  not  necessarily  imply  the  absence  of  the  heart  in  the 
affected  twin;  for  it  may  possess  a  functionating  heart,  or  it  may  become  an 
amorphous  mass  of  tissue  which  derives  its  total  blood  supply  through  the 
action  of  the  heart  of  the  stronger  twin,  or  there  may  be  any  form  between  the 
two  extremes.  In  any  case  the  acardiac  monster — acardiacus — receives  its 
blood  wholly  or  in  part  through  the  agency  of  the  stronger  heart. 

Acardia  is  always  accompanied  by  a  so-called  "reversal  of  the  circulation;" 
and  there  are  three  periods  at  which  it  may  originate,  (i)  It  may  originate 
before  the  heart  develops.  As  is  well  known,  the  heart  appears  independently 
of  the  area  vasculosa  and  joins  the  vessels  secondarily  (p.  191).  If,  for  any 
reason,  the  heart  of  one  of  the  embryos  fails  to  develop,  anastomoses  may 
occur  between  the  vascular  anlagen  of  the  two  vascular  areas  and  consequently 
the  normal  embryo  assumes  the  duty  of  nourishing  the  other.  The  latter  be- 
comes an  acardiac  monster.  (2)  It  may  originate  after  the  heart  has  begun  to 
develop,  but  before  the  placental  circulation  is  established.  If,  for  any  reason, 
the  heart  of  one  embryo  should  cease  to  develop  further,  there  would  probably 
be  sufficient  anastomoses  between  the  vitelline  vessels  of  the  two  embryos  to 
enable  the  affected  embryo  to  live  and  become  an  acardiac  parasite.  In  this 
case  no  placental  circulation  would  develop  in  the  parasite.  (3)  Acardia  may 
originate  after  the  establishment  of  the  placental  circulation.  Since  there  is 
but  one  chorion  or  placenta  for  both  embryos  there  is  naturally  a  communica- 
tion between  the  two  circulations  in  the  chorionic  villi.  There  are  also  likely 
to  be  anastomoses  between  the  umbilical  arteries  and  veins.  If,  for  any  reason, 
the  heart  action  of  one  of  the  embryos  should  become  impaired,  there  would  be 
an  influx  of  blood  into  the  vessels  of  that  embryo  owing  to  diminished  pressure. 
Thus  the  blood  from  the  stronger  heart  would  be  pumped  into  the  affected 
embryo  as  well  as  into  the  placenta.  This  blood,  being  impure,  fails  to  nourish 
the  weaker  embryo  properly  and  the  result  is  atrophy  or  degeneration. 

Upon  the  basis  of  other  malformations  that  naturally  accompany  impaired 
development  of  the  heart,  acardiac  monsters  are  divided  into  four  classes. 


604  TEXT-BOOK  OF  EMBRYOLOGY. 

i.  Acardiacicompleti. — The  general  development  of  the  acardiacus  depends  upon 
the  sufficiency  of  the  blood  supply  which  it  receives.  If  there  is  a  well  developed 
anastomosis  between  the  two  placental  circulations  the  weaker  embryo  may 
receive  a  moderately  good  blood  supply  and  develop  into  a  fairly  normal  foetus. 
A  well  formed  trunk  and  head  may  be  present  and  the  extremities  may  be 
represented  in  part  or  in  full.  2.  Acardiaci  acormi. — These  may  possess  only  a 
head,  or  they  may  possess  a  head  and  traces  of  a  trunk  and  extremities. 
Their  evolution  depends  upon  unusual  combinations  of  anastomoses  in  their 
venous  channels.  3.  Acardiaci  acephali. — No  head  is  present.  The  lower 
part  of  the  trunk  is  present,  and  sometimes  other  parts  of  the  trunk.  The  ex- 
tremities may  be  complete,  incomplete  or  absent.  These  forms  are  also  due 
to  peculiar  combinations  of  vascular  anastomoses.  4.  Acardiaci  amor  phi. — As 
the  name  indicates,  there  is  no  typical  form  for  the  affected  embryo.  It  bears  no 
resemblance  to  a  normal  embryo,  but  is  merely  an  irregular  mass  of  tissue. 

In  symmetrical  duplicity,  instead  of  the  two  embryos  in  one  chorion  being 
distinct  and  separate  individuals,  they  may  be  joined  together  to  a  greater  or 
lesser  extent.  The  two  individuals  may  develop  to  practically  the  same 
degree  (equal  united  twins,)  or  one  may  remain  more  or  less  rudimentary 
(unequal  united  twins.)  As  may  be  seen  by  reference  to  the  scheme  on  page  605, 
there  are  three  modes  of  union — posterior,  middle  and  anterior. 

Posterior  Union. — This  may  be  either  dorsal  or  ventral.  In  dorsal  posterior 
union  the  two  bodies  are  joined  together  in  the  pelvic  region,  with  the  dorsal 
surfaces  of  the  twins  directed  toward  each  other.  The  umbilicus  is  double  and 
the  two  umbilical  cords  converge  toward  a  common  placenta — pygopagus. 
The  general  anatomical  features  are  as  follows.  There  is  a  single  coccyx 
and  a  single  sacrum;  pelvic  bones  and  symphyses  are  present  in  normal 
number;  near  the  ends  of  the  large  intestines  the  two  digestive  tubes  unite  to 
form  a  common  lumen,  and  the  two  recta  open  through  a  common  anus  between 
the  more  dorsally  situated  pair  of  extremities;  the  two  spinal  cords  unite  near 
their  lower  ends  to  form  a  single  conus  and  filum  terminate;  the  urogenital 
tracts  are  united  only  to  a  slight  degree.  This  form  of  monster  is  of  interest 
because  it  is  able  to  live  for  years;  indeed  a  number  of  them  have  lived  to 
maturity. 

In  case  of  ventral  posterior  union  the  attachment  may  be  confined  to  the 
pelvic  region  or  may  involve  the  entire  trunk.  In  the  former  instance — 
ischiopagus — the  right  pubic  bone  of  one  pelvis  fuses  with  the  left  pubic  bone 
of  the  other  pelvis,  the  ventral  surfaces  of  the  two  sacra  facing  each  other. 
The  axes  of  the  bodies  may  be  in  line,  or  they  may  form  an  angle.  The  con- 
tinuous ventral  surfaces  of  the  two  bodies  contain  a.  single  umbilicus.  The 
organs  in  the  pelvic  region  may  be  single  or  double.  The  lower  extremities 
may  be  fully  developed,  or  there  may  be  only  three,  or  rarely  two.  Sometimes 


TERATOGENESIS.  605 

one  of  the  twins  is  rudimentary,  the  thorax  and  head  being  absent,  but  the 
extremities  present  in  part  (ischiopagus  parasiticus).  Ischiopagi  seldom 
survive  owing  to  atresia  of  the  anus. 

In  case  the  attachment  extends  along  the  entire  trunk  of  each  twin — 
ischiothoracopagus — the  two  sacra  are  usually  fused  to  form  a  single  sacrum. 
The  thoraces  of  the  twins  are  joined  by  means  of  a  common  sternum.  The 
upper  extremities  may  all  be  present  (tetrabrachius),  or  there  may  be  three 
(tribrachius),  or  only  two  (dibrachius)  and  a  very  rudimentary  third.  The 
lower  extremities  are  subject  to  the  same  variations  as  the  upper.  The  ex- 
ternal genitalia  and  anus  are  single.  The  alimentary  tube  is  double  as  far  as 
the  lower  end.  The  thoracic  viscera  are  partly  double.  Monsters  of  this 
type  may  live  for  years. 

Middle  Union. — In  the  case  of  middle  union  a  ventral  or  ventro-lateral 
attachment  extends  from  the  umbilicus  for  a  variable  distance  toward  the  head. 
In  most  cases  the  umbilicus  itself  is  single.  The  union  may  occur  in  the 
region  of  the  xiphoid  process — xiphopagus — or  it  may  involve  the  entire  region 
of  the  sternum — sternopagus  or  thoracopagus.  In  the  case  of  xiphopagus, 
a  bridge  joining  the  twins  extends  from  the  common  umbilicus  to  the 
xiphoid  processes.  The  latter  are  usually  united  across  the  bridge.  The 
thoracic  cavities  are  separate.  The  two  livers  may  be  connected  by  a  bridge  of 
hepatic  tissue,  in  which  case  the  two  peritoneal  cavities  are  in  communication, 
or  the  livers  may  remain  separate,  in  which  case  the  peritoneal  cavities  do  not 
communicate.  The  two  alimentary  tubes  may  or  may  not  communicate  in  the 
region  of  the  stomach.  Xiphopagi  may  live  for  many  years,  as  instanced  by 
the  "Siamese  Twins." 

In  the  case  of  sternopagus  the  union  extends  upward  from  the  common  um- 
bilicus, so  that  the  two  sterna  are  fused  into  a  single  bone.  There  is  a  com- 
mon thoracic  cavity,  separated  from  the  abdominal  cavity  by  a  single  diaphragm. 
One  or  two  hearts  may  be  present.  The  middle  portions  of  the  two  alimentary 
tubes  form  a  single  tract.  The  two  livers  are  fused  into  a  common  mass.  The 
genitalia  are  distinct  and  separate.  The  extremities  may  be  normal,  or  in  case 
of  a  ventro-lateral  union,  the  approximated  upper  extremities  may  be  fused. 
Such  monsters  are  usually  born  dead;  if  born  alive,  they  survive  but  a  short 
time  owing  to  defective  development  of  the  heart. 

As  other  varieties  of  thoracopagus  the  following  may  be  mentioned :  Thora- 
copagus parasiticus,  in  which  one  twin  is  much  arrested  in  development,  a  head 
and  heart  being  present,  and  attached  to  the  thoracic  region  of  the  stronger 
twin.  Gastrothoracopagus  dipygus  (dipygus  parasiticus),  in  which  extremities 
and  trunk  are  present  at  least  in  part  and  are  attached  to  the  lower  part  of  the 
thorax  or  to  the  epigastrium  of  the  other  twin.  The  head  is  not  present.  Such 
twins  may  live  for  years,  as  instanced  by  Laloo.  Cephalothoracopagus  diproso- 


606  TEXT-BOOK  OF  EMBRYOLOGY. 

pus,  in  which  the  attachment  may  extend  into  the  neck  and  head  region,  so 
that  there  is  a  union  from  the  head  to  the  umbilicus.  This  type  is  distinguished 
from  the  anterior  union  in  that  the  head  portions  of  the  twins  are  united 
laterally,  so  that  both  more  or  less  completely  developed  faces  are  turned 
toward  the  common  ventral  side,  while  the  bodies  have  their  ventral  sides 
directed  toward  each  other. 

Anterior  Union. — In  this  type  of  union  the  attachment  may  be  dorsal  and 
confined  to  the  head  (dorsal  anterior  union),  or  ventral  and  reaching  as  far  as 
the  umbilicus  (ventral  anterior  union). 

In  dorsal  union  the  heads  of  the  twins  are  joined  at  the  crowns,  so  that 
the  two  bodies  lie  in  a  straight  line,  or  form  an  angle  with  each  other.  Such 
a  monstrosity  is  known  as  craniopagus  (cephalopagus) .  The  attachment 
usually  involves  the  cranial  vault,  the  two  brains  remaining  separated  by 
their  membranes  within  a  common  cranial  cavity.  Such  monsters  are  rare 
and  survive  but  a  short  time.  A  very  rare  variety  of  craniopagus  is  the 
form  known  as  craniopagus  parasiticus,  in  which  one  twin  is  reduced  to  a 
rudimentary  structure  and  is  parasitic  upon  the  other.  In  all  the  above  cases 
the  term  autosite  is  applied  to  the  better  developed  twin. 

In  ventral  and  ventro-lateral  union  the  attachment  involves  the  head, 
neck  and  thorax — syncephalus,  cephalothoracopagus  janiceps.  The  twins  pass 
through  their  development  in  common,  each  individual  contributing  its 
quota  of  structure  to  the  composite  monster.  The  sternum  is  single,  the  oeso- 
phagus single,  the  larynx  and  trachea  double  or  single,  the  stomach  single,  the 
intestine  double.  The  two  hearts  may  be  united,  but  more  commonly  are 
separated,  one  being  situated  ventrally,  the  other  dorsally.  Two  faces  are 
formed,  one  belonging  to  each  embryo.  The  faces  may  be  alike  or  nearly  so 
(Janus  symmetros),  or  one  may  be  misplaced  or  unequally  developed  (Janus 
asymmetros),  which  often  results  in  cyclopia,  synotia,  or  obliteration  of  the 
"opening  of  the  mouth. 

In  some  cases  the  greater  part  of  the  body  is  single  and  only  a  part  is  double 
(incomplete  duplicity).  The  malformation  may  affect  only  the  upper  end  or 
head  (superior  incomplete  duplicity) ,  or  only  the  lower  end  (inferior  incomplete 
duplicity).  In  the  former  case  the  skull  is  single,  with  possible  traces  of  a 
double  formation — diprosopus.  There  are  two  faces  with  varying  degrees  of 
fusion  between  them;  all  four  eyes  may  be  present,  or  the  two  approximated 
eyes  may  be  fused  or  they  may  be  wanting  (diprosopus  tetroph-,  trioph-, 
diophthalmus).  The  two  mouths  may  be  fused  (diprosopus  monostomus), 
and  with  a  greater  degree  of  fusion  between  the  faces  the  two  approximated 
ears  may  .also  be  fused  or  be  entirely  lacking.  In  dicephalus  the  head  is 
double,  and  sometimes  the  upper  end  of  the  vertebral  column. 

Inferior  incomplete  duplicity  is  rare.     To  this  category  of  duplicate  monsters 


TERATOGENESIS.  607 

probably  belong  certain  cases  of  partial  duplicity  in  the  pelvic  region,  with 
sometimes  an  extra  set  of  genitalia.  Possibly  also  a  few  cases  of  a  third  lower 
extremity  would  come  under  this  head. 

Multiplicity. — Monochorionic  triplets  are  rare,  only  a  few  cases  being 
recorded.  Two  cases  of  monochorionic  quadruplets  are  on  record,  and 
one  case  of  quintuplets.  Incomplete  multiplicities  are  extremely  rare.  One 
case  of  incomplete  triplicity  has  been  described — tricephalus.  Two  verte- 
bral columns  were  present  in  this  monster,  bearing  one  and  two  heads  re- 
spectively. Two  thoracic  cavities,  each  enclosing  a  heart,  were  separated  by 
a  thin  septum.  The  abdominal  viscera  were  single.  The  lower  half  of  the 
body  and  the  lower  extremities  were  normal,  as  were  also  the  genital  organs, 
which  were  male. 

ORIGIN  OF  SYMMETRICAL  DUPLICITY. 

The  origin  of  duplicities  has  always  been  most  difficult  to  explain,  and 
the  many  solutions  suggested  have  been  replete  with  conjecture.  The  diffi- 
culty has  been  caused  by  the  lack  of  direct  observation  upon  formative  stages 
either  in  the  lower  or  higher  animals.  Within  recent  years,  however,  experi- 
mental work  upon  the  lower  forms  has  begun  to  throw  some  light  upon  this 
obscure  problem.  Among  the  theories  which  have  been  formulated  are  two 
that  stand  out  most  clearly — the  fusion  theory  (Marchand,  Ziegler)  and  the 
fission  theory  (Ahlfeld  and  others). 

According  to  the  fusion  theory,  there  are  present  two  originally  distinct 
anlagen  within  a  single  ovum.  These  two  anlagen  may  develop  separately  and 
independently  and  produce  twins.  They  may  come  in  contact  during  develop- 
ment and  fuse  to  a  greater  or  lesser  degree,  thus  producing  some  kind  of  dupli- 
cate monster.  If  fusion  does  occur  it  occurs  between  similar  parts  of  the  two 
anlagen;  in  other  words,  like  tissues  and  organs  fuse — liver  with  liver,  muscle 
with  muscle,  bone  with  bone,  and  so  on.  Such  unions,  however,  probably 
occur  only  in  very  early  stages  of  development,  for  when  tissues  are  once  formed, 
union  is  effected  with  much  greater  difficulty.  Consequently  fusions  between 
two  anlagen,  leading  to  double  monsters,  probably  take  place  at  a  very  early 
period  of-  intrauterine  life. 

According  to  the  fission  theory,  duplicity  is  the  result  of  the  division  of  a 
single  anlage  in  the  earliest  stages  of  development,  before  the  formation  of  the 
primitive  streak.  The  cleavage  is  produced  by  mechanical  resistance  of  the 
zona  pellucida.  Since  the  greatest  mass  of  growing  material  is  in  the  head 
region,  the  resistance  is  greatest  there,  and  hence  it  is  argued  that  duplicities 
would  be  most  common  in  the  head  region,  which  accords  with  the  facts.  A 
modification  of  the  fission  theory  to  explain  duplicities  which  affect  a  relatively 
email  area  has  been  suggested.  Incomplete  anterior  duplicity,  for  example,  is 


608  TEXT-BOOK  OF  EMBRYOLOGY. 

not  the  result  of  fission  but  of  bifurcation  which  accompanies  the  development 
of  the  head  end  of  the  embryo  along  divergent  axes.  The  difference  between 
fission  and  bifurcation  is  that  the  former  is  the  passive  result  of  active 
mechanical  forces,  while  the  latter  is  a  part  of  active  formative  processes. 

Experiments  on  eggs  of  lower  animals  point  to  the  conclusion  that  each  of 
the  two  blastomeres  resulting  from  the  first  cleavage  contains  the  material 
necessary  to  produce  an  entire  body.  In  order  to  cause  a  blastomere  to  pro- 
duce a  whole  body,  however,  it  is  necessary  to  subject  it  to  unnatural  conditions. 
For  example,  if  one  of  the  two  primary  blastomeres  of  the  frog  is  killed  and  the 
other  left  to  grow  in  its  natural  position  it  will  produce  a  half-embryo;  but  if  the 
remaining  blastomere  is  inverted  it  will  produce  a  whole  embryo  (Morgan). 
On  the  other  hand,  in  view  of  certain  experiments  on  the  eggs  of  Amphioxus, 
it  has  been  asserted  that  duplicity  is  associated  with  double  gastrulation; 
when  these  eggs  were  shaken  during  the  first  cleavage,  some  developed  into 
double  gastrulae  (Wilson,  Hertwig).  For  a  further  discussion  of  these  causes, 
see  page  612. 

ASYMMETRICAL  DUPLICITY. 

In  this  type  of  malformation  the  two  anlagen  from  which  the  monster  is 
derived  are  primarily  dissimilar  and  unequal.  One  anlage  usually  remains  in 
a  rudimentary  condition,  bears  little  or  no  resemblance  to  a  foetus,  and 
becomes  a  parasite  upon  or  within  the  body  derived  from  the  other  anlage 
(parasite,  foetal  inclusion,  foetus  in  fcetu).  Sometimes,  however,  the  dependent 
embryo  may  develop  quite  complete  parts,  such  as  extremities,  but  always 
remains  attached  to  the  stronger  embryo,  from  which  it  derives  its  nourishment 
(implantation).  Parasitic  inclusions  and  implantations  may  be  attached  to 
the  autosite  in  the  region  of  the  head,  neck,  thorax,  abdomen,  etc. 

Parasitic  duplicities  in  the  head  region  may  take  the  form  of  masses  pro- 
truding from  the  orbital  region — prosopopagus  parasiticus  or  much  more  com- 
monly from  the  mouth — epignathus,  sphenopagus.  In  the  latter  case  the  tumor 
is  enveloped  by  skin  containing  hair  follicles  and  sweat  glands,  and  usually 
consists  of  cysts  and  intervening  embryonic  tissue.  It  sometimes  contains  teeth, 
cartilage,  bone,  fat  and  nerve  tissue,  even  traces  of  an  intestinal  canal  and 
of  liver  tissue.  One  epignathus  has  been  described  as  having  an  imperfect 
set  of  female  genitalia  which  lay  between  two  rudimentary  lower  extremities. 

Occasionally  irregular  tumors  are  found  in  the  region  of  the  pituitary  body 
(encranius),  which  contain  rudiments  of  various  tissues  and  organs.  In  such 
cases  the  parasitic  anlage  has  possibly  been  included  during  the  imagination 
which  forms  the  oral  part  of  the  pituitary  body.  Tumors  consisting  of  various 
tissues,  such  as  lymphatic,  adipose,  muscle,  etc.,  are  also  found  in  the. brain 


TERATOGENESIS.  609 

ventricles.     They  possibly  represent  parasitic  anlagen  which  have  become  en- 
closed within  the  brain  vesicles  as  the  neural  groove  closed  in  dorsally. 

Certain  foetal  inclusions  attached  to  the  region  formed  by  the  branchial 
arches  are  spoken  of  as  cervical  parasites.  These  are  usually  cystic  tu- 
mors, covered  with  skin  and  containing  teeth,  bone  and  parts  of  a  head  and 
extremities. 

Closely  associated  with  the  cervical  parasites  is  a  group  of  tumors  found 
within  the  anterior  mediastinum  in  the  region  of  the  thymus  gland,  and  known 
as  thoracic  parasites.  It  must  be  borne  in  mind,  however,  that  some  of  the 
tumors  found  in  the  cervical  and  thoracic  regions  are  not  true  parasitic  in- 
clusions, but  are  dermoid  cysts  (resembling  the  parasites)  derived  from  the 
ectoderm.  True  parasitism  implies  origin  from  all  three  germ  layers.  From 
a  structural  standpoint  it  is  sometimes  very  difficult,  even  impossible,  to  distin- 
guish between  true  parasitic  inclusions  and  dermoid  cysts  that  are  derived  from 
ectoderm. 

Very  rarely  in  the  human  subject  some  parasitic  structure  is  attached  to  the 
back.  One  case  of  a  supernumerary  penis  in  the  lumbar  region  has  been  de- 
scribed; another  case  is  on  record  of  an  almost  complete  set  of  female  genitalia 
on  the  back  of  a  male.  Such  malformations  can  be  explained  only  by  assum- 
ing the  partial  development  of  another  embryonic  anlage. 

"Sacral  parasites  are  the  most  frequent  of  the  true  parastic  growths.  These 
are  cystic  tumors  which  are  attached  to  and  hang  from  the  sacrum  or  the 
coccyx.  The  tumors  are  covered  with  skin  which  blends  with  the  skin  of  the 
autosite.  In  the  existence  of  such  elements  as  fat,  bone,  muscle,  and  nerves, 
and  the  rudiments  of  intestines  and  extremities  is  found  the  evidence  of  their 
fcetal  origin. 

Foetal  inclusions  in  the  abdominal  region  are  not  frequent.  One  very  rare 
intraparietal  (or  subcutaneous)  inclusion,  in  a  child  two  and  one-half  years 
old,  proved  to  be  a  cystic  tumor  which  contained  a  fairly  well  formed  foetus 
with  defective  head  and  extremities.  Engastric  (intraabdominal)  parasites 
are  usually  found  in  the  region  of  the  lesser  peritoneal  sac,  at  the  root  of  the 
transverse  mesocolon.  These  tumors  are  usually  enclosed  within  a  sac  of 
mesenteric  or  peritoneal  tissue.  There  may  be  well  marked  fcetal  structures, 
such  as  head,  trunk,  extremities,  etc.,  or  only  traces  of  rudimentary  organs- 
The  presence  of  an  intraabdominal  parasite  does  not  necessarily  cause  the 
death  of  the  autosite  immediately  after  birth;  for  one  case  in  particular  is  on 
record  in  which  the  autosite  (a  boy)  lived  to  be  fifteen  years  old  with  a  parasite 
that  was  capable  of  independent  movement. 

Parasitic  Structures  in  the  Sexual  Glands. — The  type  of  tumor  referred  to 
here  forms  a  group  that  is  of  especial  interest  owing  to  their  relative  frequency 
of  occurrence  and  to  their  peculiar  mode  of  production.  In  connection  with 


610  TEXT-BOOK  OF  EMBRYOLOGY. 

the  ovary  dermoid  cysts  and  other  solid  masses  occur.  The  cysts  consist  of  a 
sac  enclosing  hair  and  adipose  tissue;  not  infrequently  teeth  are  also  present,  as 
well  as  sebaceous  and  sweat  glands.  Sometimes  there  are  also  bone,  cartilage, 
muscle,  and  nerve  tissue  and  traces  of  the  digestive  and  respiratory  systems  and 
of  thyreoid  gland;  more  rarely  traces  of  mammary  glands,  finger  nails  and 
retinal  pigment  are  present.  In  the  rarer  solid  tumors  that  develop  in  rela- 
tion to  the  ovary  all  three  germ  layers  are  represented,  but  their  derivatives 
are  more  rudimentary  and  not  so  regularly  arranged  as  in  the  cysts. 

Parasitic  growths  in  the  testis  are  much  less  frequent  than  in  the  ovary. 
The  cysts  are  rarer  than  the  solid  masses.  These  are  probably  homologous 
with  the  parasites  of  the  ovary. 

ORIGIN  or  ASYMMETRICAL  (PARASITIC)  DUPLICITY. 

Parasitic  duplicity  implies  primary  inequality  of  the  embryonic  anlagen;  in 
other  words,  the  anlage  of  the  parasite  is  inferior,  so  to  speak,  to  the  anlage  of 
the  host.  During  development  the  inequality  or  asymmetry  persists  or  be- 
comes more  conspicuous  until  the  parasite  is  more  or  less  enclosed  within  the 
autosite.  As  the  autosite  develops  in  a  manner  at  least  simulating  the  normal, 
the  parasite  remains  in  a  more  or  less  rudimentary  condition,  with  perhaps  only 
a  few  tissues  which  show  any  differentiation.  In  some  cases  the  parasite 
becomes  enclosed  partially  or  completely  within  the  autosite  (epignathus),  in 
other  cases  the  parasitic  growth  apparently  occurs  primarily  within  the  autosite 
(ovarian  cysts). 

The  manner  in  which  the  rudimentary  anlage  becomes  surrounded  by  the 
more  nearly  perfect  anlage  is,  of  course,  not  known  through  direct  observation. 
But  it  seems  reasonable  to  assume  that  such  enveloping  occurs  in  connection 
with  or  as  a  part  of  the  normal  processes  of  folding  by  which  the  external  form 
of  the  body  is  established.  This  folding  occurs  at  the  cephalic  and  caudal  poles 
of  the  embryonic  disk  and  also  along  its  entire  length.  In  addition  there  is 
also  the  folding  in  of  the  neural  groove  along  the  dorsum  of  the  embryo,  and 
the  invagination  of  the  branchial  grooves.  One  can  readily  imagine  the  para- 
sitic anlage  as  attached  to  some  one  of  the  areas  that  are  folded  in,  so  that 
it  is  carried  wholly  or  partially  into  the  interior  of  the  stronger  embryonic 
anlage  and  becomes  surrounded  by  the  tissues  of  the  autosite  to  produce  a 
true  foetal  inclusion. 

There  seems  to  be  little  doubt  as  to  the  existence  of  a  second,  more  or  less 
rudimentary  anlage  which  becomes  the  parasite;  in  other  words,  there  is  almost 
certainly  a  duplicity  to  begin  with,  although  it  may  be  an  asymmetrical  one. 
It  is  also  plausible  to  assume  that  for  a  time  the  weaker  anlage  develops  in- 
dependently of  the  stronger,  but  that  later  it  is  dependent  upon  the  stronger 


TERATOGENESIS.  61 1 

for  its  nutrition.  The  problem,  however,  is  to  explain  the  origin  of  the  rudi- 
mentary anlage  which  produces  the  parasite.  In  view  of  the  facts  concerning  the 
early  stages  of  development— the  facts  concerning  maturation,  fertilization  and 
segmentation  of  the  ovum,  and  the  formation  of  the  germ  layers — there  are  two 
possible  and  plausible  modes  of  origin  of  the  rudimentary  anlage.  (i)  The 
anlage  of  the  parasite  may  be  the  result  of  the  imperfect  development  of  a 
fertilized  polar  body.  (2)  The  anlage  of  the  parasite  may  be  a  special  or  an 
isolated  group  of  segmentation  cells. 

1.  It  is  generally  agreed  that  the  polar  bodies  are  abortive  or  rudimentary 
ova  extruded  during  the  processes  of  maturation  of  the  female  sex  cell;  and  that 
these  rudimentary  ova  probably  contain  the  same  morphological  constituents 
as  the  mature  ovum  itself.     It  is  also  known  that  in  a  few  of  the  lower  forms 
the  polar  bodies  are  capable  of  being  fertilized  and  undergoing  a  considerable 
degree  of  development,  and  that  in  some  of  the  higher  forms  (rabbit,  dog)  the 
spermatozoa  may  exist  for  some  time  inside  the  zona  pellucida  in  the  vicinity 
of  the  polar  bodies.     In  view  of  these  facts  it  does  not  seem  impossible  that  in 
a  few  exceptional  cases  in  Mammals  the  polar  bodies  may  become  fertilized 
and  produce  rudimentary  anlagen  capable  of  giving  rise  to  parasites.     Such 
an  anlage  would  naturally  lie  in  close  proximity  to  the  larger  normal  anlage 
and   might   readily  become  attached  to  or  finally  enclosed  within  it.     As  a 
more  remote  possibility,  the  polar  body  might  become  enclosed  between  the 
blastomeres  and   thus  finally  produce  the  parasitic  anlage  within  the  meso- 
dermal  tissue  where  it  might  become  an  inclusion  in  some  internal  organ, 
such  as  the  genital  gland.     A  polar  body  has  been  found  between  the  blasto- 
meres (rabbit).     (Bischoff,  Assheton,  Bonnet.) 

2.  The  view  that  the  parasite  may  arise  as  the  result  of  the  development  of  a 
special  or  an  isolated  group  of  segmentation  cells  has  more  advocates  than  the 
view  given  in  the  preceding  paragraph.     One  of  the  most  interesting  phases  of 
this  theory  is  the  view  that  tumors  of  the  sexual  glands,  as  well  as  those  of  other 
regions,  are  the  products  of  development  of  the  germ  cells  as  distinguished  from 
the  somatic  cells.     In  the  skate  it  has  been  demonstrated  that  certain  cells  are 
set  apart  at  a  very  early  period  of  development  (during  segmentation),  which 
are  destined  to  give  rise  to  the  sex  cells  of  the  embryo,  and  which  take  no 
part  in  its  general  development.     Normally  these  special  cells  pursue  a  course 
of  development  and  differentiation  which  leads  to  the  formation  of  the  mature 
sexual  elements  (ova  or  spermatozoa)  of  the  individual,  but  do  not  participate 
in  its  general  development.     From  this  one  may  conclude  that  the  primitive 
germ  cell,  the  one  set  apart  for  the  production  of  the  mature  sex  cells,  is,  so 
to  speak,  a  sister  to  the  embryo  and  is  not  a  derivative  of  the  embryo.     It 
seems  not  impossible  that  some  aberrant  members  of  this  group  of  germ  cells, 
without  undergoing  the  changes  incident  to  maturation,  might  pursue  a  course 


612  TEXT-BOOK  OF  EMBRYOLOGY. 

of  development  of  their  own  accord  and  give  rise  to  a  rudimentary  twin — the 
foetal  inclusion  or  parasite.  In  this  case  one  must  regard  the  germ  cells  as  pos- 
sessing an  inherent  potentiality  which  may  institute  formative  processes;  but  the 
actual  cause  of  the  spontaneous  development  is  unexplained.  (Born,  Wilson, 
Morgan,  Driesch,  Schultze). 

Another  possible  source  of  parasitic  growths  is  suggested  by  experiments  in 
which  some  of  the  cells  during  segmentation  have  been  separated  from  the 
general  mass.  The  artificially  segregated  cells  may  develop  into  perfect  em- 
bryos smaller  than  the  normal,  or  into  partial  embryos.  Further  experiments 
along  the  same  line  on  the  frog  justify  the  assumption  that  the  segregated  cells 
or  masses  may  become  enclosed  within  the  developing  larger  embryo  and  there 
undergo  further  growth  and  differentiation  and  give  rise  to  inclusions  or 
parasites.  (Roux.) 

As  a  matter  of  fact  there  seems  to  be  no  good  reason  for  considering  any  one 
of  the  above  views  as  expressing  the  only  possibility  as  to  the  source  of  unequal 
duplicities  or  parasitic  growths.  There  is  nothing  to  show  that  all  three 
methods  may  not  contribute  to  the  various  kinds  of  duplicities  including 
certain  teratomata  of  the  sexual  glands. 

MALFORMATIONS  INVOLVING  ONE  INDIVIDUAL. 

Description,  Origin. 

While  the  more  limited  malformations  and  anomalies  affecting  individual 
organs  are  discussed  in  the  chapters  dealing  with  those  organs,  it  seems  best 
to  consider  here  some  of  the  gross  malformations  in  a  single  individual, 
especially  those  which  affect  the  external  form  of  the  body. 

DEFECTS  IN  THE  REGION  OF  THE  NEURAL  TUBE. 

The  term  cranioschisis  has  been  given  to  a  group  of  malformations,  01 
defects,  in  the  roof  of  the  skull  and  in  the  brain.  Depending  upon  the  degree 
of  defect,  the  group  is  divided  into  two  classes — acrania  and  hemicrania— 
which  include  conditions  from  a  complete  absence  of  the  roof  of  the  skull  to 
partial  arrest  of  development.  Associated  with  these  conditions  are  varied 
defects  and  malpositions  of  parts  or  of  the  whole  of  the  brain. 

In  extensive  acrania  the  entire  roof  of  the  skull  is  lacking,  and  the  brain 
and  its  membranes  are  reduced  to  small  masses  of  tissue  lying  upon  the  floor 
of  the  skull.  The  defect  may  also  extend  to  the  cervical  vertebrae — cranio- 
rachischisis.  These  vertebras  remain  open  dorsally  and  are  bent  inward 
(lordosis).  The  ears  are  set  upon  the  shoulders  and  the  neck  seems  to  be 
lacking. 


TERATOGENESIS.  613 

Sometimes  the  rudimentary  brain  shows  traces  of  structures  which  the 
normal  brain  possesses,  and  is  raised  above  the  level  of  the  defective  skull  like 
a  turban — acrania  with  exencephaly.  With  acrania  are  usually  associated 
facial  clefts,  defects  in  the  eyes,  etc. 

The  malformation  known  as  hemicrania  is  limited  to  a  part  of  the  skull, 
usually  the  posterior  part.  The  brain  mass  often  protrudes  through  an  opening 
in  the  cranial  vault  and  forms  a  mass  on  the  back  of  the  head  or  hanging  down 
upon  the  neck — hemicrania  with  exencephaly. 

In  the  various  forms  of  cephalocele  or  cerebral  hernia  the  roof  of  the  skull  is 
more  nearly  complete  and  the  protrusion  of  the  cranial  contents  is  limited 
to  circumscribed  areas.  The  protruding  mass  may  consist  of  brain  substance 
only — encephalocele,  or  of  the  membranes  only — meningocele,  or  of  both— 
meningoencephalocele.  Sometimes  the  brain  ventricles  are  distended  by  the 
accumulation  of  fluid — hydrencephalocele,  or  a  sac  formed  by  the  membranes 
may  be  distended  by  fluid — hydromeningocele. 

A  condition  known  as  hydrencephaly  is  sometimes  met  with.  Fluid  ac- 
cumulates in  the  brain  cavities  after  the  skull  is  formed,  causing  a  general 
enlargement  of  both  brain  and  skull,  without  hernia  (congenital  hydrocephaly) . 

A  combination  of  hydrencephaly  and  cephalocele  may  also  occur.  The 
cervical  vertebrae  adjoining  the  skull  are  cleft  dorsally  and  the  protruding  mass 
lies  in  the  cleft — iniencephaly. 

Hydromicrencephaly  means  an  accumulation  of  fluid  with  a  rudimentary 
brain  and  a  correspondingly  small  skull. 

Porencephaly  is  a  lower  grade  of  hydromicrencephaly,  in  which  fluid  ac- 
cumulates in  the  third  and  lateral  ventricles  and  affects  the  adjacent  frontal 
and  parietal  lobes.  If  the  individual  lives  with  this  malformation,  the  intellect 
is  impaired  and  the  extremities  contract  and  atrophy.  . 

Microcephaly  and  micrencephaly  go  together  as  abnormal  smallness  of  the 
skull  and  brain.  The  brain,  aside  from  the  diminutive  size,  may  not  be  de- 
formed. These  conditions,  in  which  the  body  is  of  the  usual  size,  should  not 
be  confused  with  those  found  in  dwarfs  in  whom  the  body  also  is  small 
(nanocephaly) . 

In  the  region  of  the  spinal  cord  there  is  a  group  of  malformations  consisting 
of  varying  degrees  of  clefts  in  the  vertebral  canal.  The  clefts  may  remain  open 
— rachischisis — or  they  may  be  covered  by  a  sac-like  prominence — spina  bifida 
(spina  bifida  cystica,  rachischisis  cystica).  Both  forms  of  cleft  may  occur  in 
any  region  of  the  vertebral  column  and  may  be  limited,  or  involve  the  entire 
column. 

The  malformation  known  as  rachischisis  appears  as  a  widely  open  groove 
bounded  laterally  by  rudimentary  laminae  of  the  vertebrae.  The  deformity  may 
include  the  entire  vertebral  column — holorachischisis,  or  it  may  be  confined  to 


614  TEXT-BOOK  OF  EMBRYOLOGY. 

a  small  part — merorachischisis,  and  is  usually  accompanied  by  curvature  of  the 
spine.  Sometimes  the  deformity  of  the  vertebral  column  is  continuous  with 
cranioschisis — craniorachischisis.  The  more  or  less  rudimentary  spinal  cord 
lies  along  the  bottom  of  the  cleft.  When  the  rachischisis  is  total  the  spinal 
cord  is  practically  wanting — amyelus. 

Spina  bifida  is  marked  by  the  presence  of  a  cyst  which  protrudes  through  a 
cleft  in  the  vertebral  column;  externally  it  presents  the  appearance  of  a  sac- 
like  structure  of  variable  size.  Three  different  types  of  spina  bifida  may  be 
recognized,  depending  upon  the  structures  involved.  If  the  cord  and  its  mem- 
branes are  included  in  the  cyst  it  is  known  as  myelomeningocele;  if  only 
the  membranes,  as  spinal  meningocele;  if  the  cord  itself  is  dilated,  as  myelo- 
cystocele. 

Myelomeningocele  is  the  most  common  form  of  spina  bifida  and  usually 
occurs  in  the  lumbo-sacral  region,  rarely  in  the  cervical  or  thoracic  region. 
Its  appearance  is  that  of  a  rounded  tumor  in  the  medial  line,  and,  if  the  child 
lives,  the  tumor  increases  in  size  and  may  become  as  large  as  a  child's  head. 
The  spinal  cord  is  bent  dorsally  and  attached  to  the  sac.  The  pia  mater  and 
arachnoid  surround  the  cord,  while  the  dura  is  incomplete.  The  spinous 
processes  and  the  adjacent  parts  of  the  arches  of  the  vertebrae  are  absent. 
From  one  to  several  vertebrae  may  be  affected. 

In  spinal  meningocele  the  spinal  membranes  bulge  out  to  form  a  sac  filled 
with  fluid.  The  vertebrae  are  not  necessarily  defective,  for  the  sac  may  pro- 
trude between  the  arches  or  through  the  intervertebral  foramina;  it  more 
often  protrudes  laterally  than  dorsally.  The  presence  of  meningocele  is 
not  at  all  incompatible  with  life,  but  the  sac  usually  enlarges  to  a  good-sized 
tumor. 

In  myelocystecele  (syringomyelocele)  the  central  canal  of  the  spinal  cord  is 
dilated  locally,  with  the  result  that  a  portion  of  the  cord  with  the  pia  and 
arachnoid  becomes  a  cystic  tumor.  It  may  occur  in  any  region,  and  is  fre- 
quently associated  with  asymmetrical  defects  of  the  vertebral  column. 

Spina  bifida  occulta,  a  condition  in  which  neither  cleft  nor  tumor  is  visible 
externally,  is  usually  found  in  the  lumbo-sacral  region.  The  position  of  the 
defect  is  indicated  by  a  small  depressed  cicatrix  or  by  a  small  tuft  of  hair. 
The  spinal  cord  is  elongated  and  extends  into  the  sacral  canal.  The  spinal 
canal  is  sometimes  dilated  and  the  cauda  equina  affected,  in  consequence  of 
which  there  are  sensory  and  motor  disturbances  in  the  lower  extremities. 
Paralytic  club-foot  and  derangement  of  the  bladder  functions  may  result 
from  such  a  deformity  of  the  cord. 

Diastematomyelia,  or  doubling  of  the  spinal  cord,  sometimes  accompanies 
rachischisis.  The  cord  in  such  cases  is  represented  by  two  atrophic  bands. 


TERATOGENESIS. 

ORIGIN  OF  MALFORMATIONS  IN  THE  REGION  OF  THE  NEURAL  TUBE. 

Normally  the  neural  tube  is  formed  from  a  band  of  ectoderm  extending 
along  the  dorsum  of  the  embryonic  disk.  The  ectodermal  band  becomes 
thickened,  a  groove  appears  along  the  middle  line  and  the  margins  are  raised 
above  the  surface  of  the  embryo,  forming  the  neural  groove.  The  margins  of 
the  band  continue  to  push  upward  and  finally  meet  and  fuse  with  each  other 
throughout  their  entire  length  in  the  middorsal  line.  The  surface  ectoderm 
then  breaks  away  from  the  line  of  fusion  and  forms  a  continuous  layer  upon  the 
dorsum  of  the  embryo,  thus  leaving  the  neural  groove,  now  the  neural  tube, 
extending  the  entire  length  of  the  embryo  immediately  beneath  the  ectoderm. 

The  formation  of  the  neural  tube  is  a  fundamental  process,  occurring 
at  an  early  period.  It  is  obvious  that  any  interference  with  its  development 
will  be  followed  by  serious  defects  in  the  nervous  system  and  the  structures 
that  immediately  surround  it.  A  most  natural  result  of  such  interference  would 
be  the  failure  of  the  two  margins  of  the  neural  groove  to  unite,  and  it  is  not 
improbable  that  the  various  forms  of  cranioschisis  are  the  results  of  imperfect 
or  complete  lack  of  closure  of  the  cephalic  end  of  the  neural  groove.  Such 
failure  of  the  neural  groove  to  close  would  leave  the  dorsum  of  the  head  region 
open,  so  that  not  only  the  brain  but  also  the  cranial  vault  would  be  affected. 
If  the  failure  to  close  is  complete,  a  high  degree  of  acrania  would  result.  In 
case  of  partial  closure  some  form  of  hemicrania  might  follow. 

Rachischisis,  with  partial  or  total  absence  of  the  spinal  cord,  may  also  be 
attributed  to  defective  closure  of  the  neural  tube,  total  rachischisis  being  due  to 
complete  lack  of  closure,  partial  rachischisis  to  partial  lack  of  closure. 

The  origin  of  spina  bifida  has  been  a  much  discussed  question.  The  earlier 
view  that  the  deformity  was  due  to  accumulation  of  fluid  within  the  spinal  canal 
and  rupture  of  the  distended  sac  is  now  usually  considered  untenable.  At  the 
present  time  it  is  generally  agreed  that  spina  bifida  is  closely  related  to  defective 
closure  of  the  neural  tube,  although  the  exact  nature  of  this  relation  is  not 
known. 

According  to  one  investigator  the  defective  fusion  of  the  margins  of  the 
neural  groove  is  due  to  deficient  growth  of  the  blastoderm  (von  Reckling- 
hausen).  Another  view  is  that  the  separation  between  the  neural  tube  and 
the  adjacent  ectoderm  is  incomplete  (Torneux).  Still  another  investigator 
considers  the  defective  development  due  to  some  primary  defect  in  the  germ 
(Ziegler).  Experimental  studies  on  the  frog's  egg  suggest  to  another  observer 
that  spina  bifida  is  caused  by  defective  closure  of  the  blastopore  (Hertwig). 
Recently  it  has  become  possible  to  produce  spina  bifida  at  will  in  some  of  the 
lower  Vertebrates  (frog,  Axolotl)  by  treating  the  developing  eggs  with  a  solution 
of  sodium  chlorid  (Hertwig).  At  the  same  time  other  defects  in  the  nervous 


616  TEXT-BOOK  OF  EMBRYOLOGY. 

system  (anencephaly)  are  produced.     In  these  experiments  the  malformations 
follow  retarded  closure  or  lack  of  closure  of  the  neural  tube. 

DEFECTS  IN  THE  REGION  OF  THE  FACE  AND  NECK,  AND  THEIR  ORIGIN. 

Associated  with  malformations  of  the  brain  there  is  a  group  of  defects  which 
involye  the  eyes  and  nose,  and  to  which  the  term  cyclocephaly  has  been  applied. 
The  cerebral  hemispheres  are  derivatives  of  the  fore-brain.  Sometimes  they 
fail  to  develop  properly  and  are  represented  by  a  single  mass  occupying  a 
considerable  portion  of  the  cranial  cavity.  The  eyes  primarily  represent 
lateral,  symmetrical  outgrowths  from  the  fore-brain  vesicle.  If  the  cerebral 
hemispheres  fail  to  develop,  the  development  of  the  eyes  is  profoundly  influ- 
enced. Instead  of  being  widely  separated  there  may  be  any  degree  of  mal- 
formation from  a  mere  narrowing  of  the  distance  between  them  to  a  complete 
fusion  into  a  single  organ  within  a  single  medial  orbit — synophthalmia  or  cyclo- 
pia.  Within  this  orbit  the  eye  may  possess  double  or  partially  blended  cor- 
neae,  pupils,  lenses,  and  optic  nerves,  or  it  may  have  single  structures. 

Since  the  fronto-nasal  process,  which  plays  an  important  part  in  the  forma- 
tion of  the  nose,  depends  for  its  normal  shape  upon  the  development  of  the  fore- 
brain  region,  various  degrees  of  malformation  of  the  nose  almost  invariably 
accompany  cyclopia.  In  a  typical  cyclops  the  nose  is  reduced  to  a  fleshy  mass 
protruding  from  the  frontal  region. 

It  is  not  unusual  to  find  clefts  of  the  upper  lip  (hare  lip)  and  of  the  palate 
(cleft  palate)  associated  with  cyclopia;  for  the  normal  union  of  the  fronto- 
nasal  and  maxillary  processes  depends  upon  the  development  of  the  fore-brain 
region.  The  branchial  arches  likewise  may  be  affected  with  resulting  mal- 
formations of  the  mouth  and  external  ear.  The  two  ears  may  be  united  across 
the  ventro-medial  line — synotus  or  cyclotus,  and  the  mouth  slit  may  be  absent — 
cydostomus. 

The  eye  may  also  be  the  seat  of  local  defects.  It  may  remain  abnormally 
small — micf 'ophthalmia,  or  incompletely  developed,  or  may  be  entirely  lacking 
— anophthalmia.  The  eyelids  .  may  enclose  an  abnormally  narrow  fissure — 
ankyloblepharon,  or  the  fissure  may  be  wanting — cryptophthalmia,  or  the  lids 
may  be  adherent  to  the  eyeball — symblepharon.  Sometimes  there  is  a  cutaneous 
fold  which  partly  fills  the  inner  canthus  like  the  nictitating  membrane  in  lower 
forms — epicanthus. 

Malformations  of  the  face  are  not  uncommon,  all  such  congenital  defects 
being  due  to  incomplete  fusion  of  the  processes  which  form  the  jaws  and 
greater  part  of  the  face  (see  page  1 20) .  In  extreme  cases  there  is  an  early 
and  complete  arrest  of  development  of  all  the  parts  which  normally  form  the 
face — aprosopus.  Arrested  development  of  the  first  pair  of  branchial  arches 


TEKATOGENESIS.  617 

results  in  abnormally  small  lower  jaws — micrognathy,  or  in  almost  complete 
absence  of  the  lower  jaws — agnathus;  in  the  latter  case  the  ears  are  brought 
together  in  the  ventro-medial  line — synotus.  Rarely  the  mandible  is  partly 
duplicated,  due  to  the  development  of  a  secondary  mandibmar  process — 
dignathus. 

Clefts  in  the  upper  lip,  maxilla  and  palate  follow  the  lines  of  primary  union 
of  the  processes  which  form  these  structures  (consult  Figs.  98  and  99) .  The 
cleft  may  affect  the  lip  alone,  may  be  single  or  double,  but  is  always  lateral — 
hare  lip  (cheiloschisis).  It  may  affect  the  *.p  and  maxilla  (cheilognathoschisis), 
or  the  lip,  maxilla  and  palate  (hare  lip  and  cleft  palate,  cheilognathouranos- 
chisis).  (For  a  further  discussion  of  hare  lip  and  cleft  palate,  see  p.  180). 

Occasionally  there  is  an  entire  lack  of  union  between  the  naso-frontal  process 
an$  the  maxillary  process.  The  result  is  an  oblique  cleft  which  extends  up- 
ward from  the  mouth — oblique  facial  cleft  (cheilognathoprosoposchisis) .  The 
processes  which  form  the  boundaries  of  the  mouth  slit  (maxillary  and  mandib- 
ular  processes)  sometimes  fail  to  fuse  to  the  normal  extent,  thus  giving  rise  to 
macrostomus;  or  the  fusion  may  proceed  beyond  the  normal  limit,  giving  rise  to 
microstomus;  rarely  complete  fusion  of  the  processes  on  one  side  with  each  other 
and  with  their  fellows  of  the  opposite  side  results  in  closure  of  the  mouth  slit — 
astomus  or  atresia  oris.  Clefts  in  the  lower  lip,  due  to  imperfect  union  of  the 
two  mandibular  processes  in  the  medial  line,  are  rare. 

The  branchial  arches  (apart  from  the  first  which  has  already  been  con- 
sidered) and  the  branchial  grooves  are  also  subject  to  defective  developmental 
processes.  Malformations  of  the  ear,  with  closure  of  the  external  auditory 
meatus,  due  to  abnormal  development  of  the  first  groove  and  surrounding  parts, 
are  sometimes  met  with  either  alone  or  in  connection  with  other  facial  defects. 
Cervical  fistula  are  the  results  of  imperfect  closure  of  some  of  the  grooves  along 
with  rupture  of  the  membranes  that  separate  the  bottoms  of  the  external 
grooves  from  the  bottoms  of  the  internal  grooves  or  pharyngeal  pouches.  The 
fistula  may  be  complete,  that  is,  there  may  be  a  communication  between  the 
pharyngeal  cavity  and  the  exterior;  or  it  may  be  incomplete,  opening  either 
into  the  pharynx,  or  on  the  surface  of  the  body.  The  internal  opening  of  a 
cervical  -fistula  is  usually  in  the  lower  part  of  the  pharynx  or  in  the  posterior 
palatine  arch  near  the  tonsil.  The  external  opening  varies  in  position.  It  is 
usually  situated  near  the  sterno-clavicular  articulation,  or  at  the  inner  or 
outer  edge  of  the  sterno-mastoid  muscle.  The  majority  of  cervical  fistulae  are 
probably  derived  from  the  second  branchial  groove.  They  all  have  the  form  of 
narrow  canals  lined  with  mucous  membrane.  Medial  cervical  fistulae,  the  ex- 
ternal openings  of  which  are  situated  in  the  medial  line,  are  rare. 

It  sometimes  happens  that  during  the  closure  of  the  branchial  grooves  por- 
tions of  the  walls  of  the  grooves  becomes  enclosed  within  the  walls  of  the 


618  TEXT-BOOK  OF  EMBRYOLOGY. 

pharynx,  that  is,  within  the  sides  of  the  neck.  This  abnormal  process  results  in 
various  forms  of  cysts  and  tumors.  The  most  common  are  simple  retention 
cysts,  known  as  branchial  or  branchio genetic  cysts,  which  vary  from  small 
insignificant  structures  to  large  tumors.  If  derived  from  the  external  branchial 
furrows,  they  are  dermoid  in  character,  lined  with  ectodermal  derivatives,  and 
contain  sebaceous  material.  If  derived  from  the  internal  furrows,  they  con- 
tain mucous  fluid,  the  lining  epithelium  is  likely  to  be  columnar  and  is  claimed 
by  some  to  be  ciliated. 

DEFECTS  IN  THE  THORACIC  AND  ABDOMINAL  REGIONS,  AND  THEIR  ORIGIN. 

As  described  elsewhere  (see  page  285),  the  digestive  tube  (primitive  gut)  and 
ventral  body  wall  are  formed  primarily  by  a  bending  ventrally  and  fusing  of  the 
originally  flat  germ  layers.  The  splanchnopleure  on  each  side  first  bends 
ventrally  and  fuses  with  its  fellow  of  the  opposite  side  in  the  medial  line  to  form 
the  gut,  and  soon  afterward  the  somatopleure  likewise  fuses  in  the  ventro- 
medial  line  to  form  the  body  wall.  Naturally  a  defective  fusion  of  the  two 
sides  of  the  somatopleure  would  result  in  a  more  or  less  extensive  medial  cleft. 
The  cleft  may  be  limited  to  a  small  portion  of  the  abdomen  or  thorax,  or  may 
extend  from  the  neck  to  the  pelvis. 

When  the  cleft  is  very  extensive  and  involves  the  thoracic  and  abdominal 
walls,  the  condition  is  known  as  thoracogastroschisis.  In  this  case  most  of  the 
viscera  protrude  through  the  cleft  (ectopia  viscerum)  and  are  covered  merely 
by  peritoneum.  Spinal  curvature  of  a  low  or  high  degree  is  usually  associated 
with  the  eventration. 

The  cleft  may  involve  the  entire  abdominal  wall — gastroschisis  completa— 
and  the  abdominal  viscera  may  protrude  through  it.  In  a  somewhat  lesser 
degree  of  fission,  parts  of  the  abdominal  viscera,  covered  with  peritoneum, 
may  protrude  and  form  what  is  known  as  omphalocele.  Not  uncommonly 
portions  of  the  intestine  and  omentum  protrude  through  an  abnormally  large 
umbilical  ring — umbilical  hernia.  The  region  below  the  umbilicus  is  not  in- 
frequently the  seat  of  fissures  in  the  abdominal  wall,  through  which  the  bladder 
may  protrude  (ectopia  vesicae) .  Fissures  in  the  thoracic  wall  vary  in  extent. 
When  the  defect  is  extensive  the  heart  and  pericardium  protrude  through  the 
opening  (ectopia  cordis). 

MALFORMATIONS  OF  THE  EXTREMITIES. 

Any  degree  of  deficiency  may  exist,  from  total  absence  of  extremities  to 
the  lack  of  a  single  finger.  The  malformations,  however,  are  not  confined  to 
total  or  partial  lack  of  members,  for  supernumerary  fingers  and  toes  are  some- 
times present.  The  following  is  the  classification  given  by  Piersol: 


TERATOGENESIS.  619 

1.  One  or  More  Extremities  Wanting. — (a)  Amelus.     Both  upper  and  lower 
extremities  are  practically  absent,     (b)  Abrachius,  A  pus.     Either  the  upper  or 
lower  extremities  are  wanting,  the  other  pair  often  being  well  formed,     (c) 
Monobrachius,  Monopus.     One  upper  or  one  lower  extremity  is  absent,  the 
others  being  fully  developed. 

2.  One  or  More  Extremities  Defective. — (a)  Peromelus.     All  the  extremities 
are  imperfect.     A  striking  variety  of  this  is  the  suppression  of  the  proximal 
segments  of  the  extremities,  the  hands  and  feet  being  fairly  well  formed  (phoco- 
melus).     (b)  Perobrachius,  Peropus.     The  former  signifies  defective  develop- 
ment- of  the  upper,  the  latter  of  the  lower  extremities. 

3.  One  or  More  Extremities  Abnormally  Small  but  well  Formed. — (a)  Micro- 
melus.    All  the  extremities  are  diminutive,  but  without  any  other  malformation, 
(b)   Microbrachius,  Micropus.     One  or  both  upper  extremities  may  be  small,  or 
one  or  both  lower. 

4.  Bones  Defective  or  Absent. — Such  malformations  are  rare. 

5.  Lower  Extremities  Fused. — (a)  Sympus  (symelus  siren).     The  lower  ex- 
tremities are  fused  more  or  less  completely,  and  the  lower  end  of  the  trunk  is 
abnormal.     The  feet  may  be  imperfect  and  double  (sympus  dipus),  or  a  single 
foot  may  be  present  (sympus  monopus),  or  the  feet  may  be  wanting  (sympus 
apus) . 

6.  Hands  or  Feet  Defective. — There  is  a  great  variety  of  malformations  of  the 
hands  and  feet  due  to  arrested  development  of  some  of  the  digits.     The  varia- 
tions include  all  degrees  of  suppression  from  the  shortening  of  a  finger  or  toe  to 
almost  total  absence  of  digits.     Fusions  of  two  or  more  digits  are  not  uncom- 
mon.    Occasionally   a   structure,    suggesting  the  webs  on  the  feet  of  some 
aquatic  animals,  is  present. 

The  condition  known  as  polydactyly  (an  increase  over  the  normal  number 
of  digits)  is  occasionally  met  with.  The  increase  may  range  from  a  partial 
doubling  of  the  distal  segment  of  a  finger  or  toe  to  a  two-fold  quota  of  digits. 
Cases  of  ten  digits  are  extremely  rare,  as  are  even  cases  of  seven  or  eight.  One 
supernumerary  finger  or  toe,  rudimentary  or  complete,  is  not  uncommon.  The 
extra  digits  may  appear  on  a  single  hand  or  foot,  or  on  both  hands  or  feet,  or  on 
all  four  extremities,  not  necessarily  showing  any  symmetry.  A  statement  of  the 
possible  modes  of  origin  of  polydactyly  will  be  found  on  page  181. 

AMNIOTIC  ADHESIONS.— Many  malformations  affecting  the  embryo  or  foetus 
have  been  included  under  this  head.  It  has  been  generally  thought  that  the 
amnion  might  become  attached  to  some  part  of  the  embryo  in  such  a  way  as 
to  cause  malformations  by  interfering  with  the  normal  processes  of  ^growth. 
The  amnion  might  become  attached  to  the  head  and  by  interfering  with 
normal  growth  produce  hare  lip,  facial  clefts  and  generally  serious  disturb- 
ances. Undue  pressure  on  an  extremity  would  cause  it  to  be  stunted,  or 


620  TEXT-BOOK  OF  EMBRYOLOGY. 

an  encircling  band  of  amniotic  tissue  might  cause  constriction  or  even  ampu^ 
tation  of  some  of  the  extremities,  or  of  some  of  the  digits.  Under  the  same 
-head  there  might  also  be  included  certain  disturbances  possibly  caused  by  the 
umbilical  cord.  The  cord  by  becoming  wound  around  the  neck  or  extremities 
and  interfering  with  development  may  even  cause  the  death  of  the  foetus. 

Causes  Underlying  the  Origin  of  Monsters. 

Within  the  past  century  the  old  grotesque  notions  that  monsters  were  the 
results  of  supernatural  influences  or  of  sexual  congress  with  lower  animals  have 
been  overthrown  as  teratology  has  been  placed  upon  an  embryological  basis. 
The  very  old  belief  that  impressions  on  the  maternal  senses  may  influence  the 
development  of  the  embryo  is  still  held  by  those  who  possess  little  or  no  scien- 
tific knowledge,  and  is  not  uncommon  even  among  gynecologists  and  obstetri- 
cians. While  remarkable  cases  of  coincidence  have  been  recorded,  there  seems 
to  be  no  proof  whatever  that  maternal  impressions  are  reflected  upon  the  child 
in  the  uterus.  On  the  other  hand,  there  has  gradually  accumulated  a  large 
amount  of  negative  evidence  obtained  from  experimental  work.  The  results  of 
this  work  have  been  such  as  to  indicate  that  external  influences — mechanical  or 
physico-chemical — cause  the  production  of  monsters. 

Opposed  to  the  theory  that  monsters  are  due  to  external  influences  is  the 
view  that  their  cause  lies  within  the  germ,  that  is,  that  some  inherent  defect  in 
the  constitution  of  one  or  both  of  the  parental  germ  cells  is  brought  out  in  the 
new  organism  that  develops  after  their  union.  According  to  this  theory, 
therefore,  heredity  is  the  important  factor  in  teratogensis.  While  the  oc- 
currence of  defective  conditions  in  the  germ  cells  cannot  be  demonstrated,  the 
apparent  influence  of  heredity  in  the  production  of  malformations  has  long  been 
recognized.  Certain  malformations,  even  so  great  as  to  put  the  embryo  or 
fcetus  in  the  class  of  monsters,  have  been  known  to  occur  in  families  through 
successive  generations.  Such  cases  may  be  mere  coincidences,  yet  more  prob- 
ably they  are  indicative  of  hereditary  influence. 

All  the  theories,  therefore,  are  concerned  with  the  question  "whether  the 
conditions  that  produce  a  monster  are  germinal  and  hereditary  or  are  external  influ- 
ences acting  upon  a  normal  germ"  (Mall).  Some  defend  the  germinal  or 
hereditary  factor  as  the  most  potent  cause  in  the  production  of  malformations, 
while  others  just  as  strongly  advocate  the  view  that  normal  or  abnormal 
development  depends  largely  upon  external  factors.  It  does  not  seem  possible 
to  deny  the  importance  of  heredity  in  the  development  of  the  normal  organism; 
nor,  on  the  other  hand,  can  the  importance  of  external  influence,  of  environ- 
ment, upon  normal  development  be  denied.  The  same  factors  may  be  con- 
sidered as  active  in  abnormal  development,  and  it  does  not  seem  that  either 


TERATOGENESIS.  621 

factor  can  reasonably  be  considered  as  the  only  cause  in  the  production  of 
malformations.  Granting,  however,  that  both  hereditary  and  external  influ- 
ences are  at  work  in  the  production  of  monsters,  it  is  still  difficult  to  determine 
the  separate  role  of  each  factor;  on  the  one  hand,  either  influence  may  appear 
capable  of  having  produced  some  given  anomaly;  on  the  other,  both  of  them 
may  have  been  responsible  for  its  appearance. 

The  first  phase  of  the  theory  of  external  influence  was  presented  three- 
quarters  of  a  century  ago  when  attempts  were  made  to  produce  monsters.  The 
experiments  led  to  the  formulation  of  the  mechanical  theory,  which,  when  applied 
to  human  monsters,  considers  them  as  the  results  of  mechanical  influences  upon 
the  embryo,  such  as  the  pressure  caused  by  tight  lacing  or  by  contractions  of  the 
uterus.  This  theory  was  gradually  transformed  into  the  view  that  amniotic 
bands  compress  or  constrict  the  embryo,  thus  bringing  about  malformations. 
In  its  turn  the  latter  supposition  has  recently  been  criticized  and  the  view  sub- 
stituted that  the  amniotic  adhesions  are  the  results  of  malformations  and  not 
the  cause  of  them  (Mall). 

The  theory  of  external  influence  seems  recently  to  be  losing  ground  in  favor 
of  the  physico-chemical  theory.  The  latter  has  gradually  been  evolved  during 
the  course  of  a  great  number  of  experiments  on  the  production  of  malformations 
and  monsters  among  the  lower  forms  of  animals.  It  has  gained  ground  because 
certain  definite  malformations  have  been  obtained  by  subjecting  the  living  egg 
or  young  embryo  to  unusual  conditions.  The  experiments  consist  of  interfering 
in  some  way  with  the  normal  course  of  development.  The  interference  may  be 
mechanical  or  chemical,  or  both,  but  is  always  of  such  a  nature  as  to  cause  the 
egg  or  embryo  to  develop  under  unnatural  conditions — either  in  an  unnatural 
environment  or  after  having  had  some  of  its  own  substance  wholly  or  partly 
removed.  The  results  obtained,  the  strange  creatures  which  develop  after 
such  interference,  are  not  infrequently  comparable  with  malformations  and 
monsters  found  among  the  higher  animals,  and  they  strongly  suggest  that  mal- 
formations among  the  higher  forms  of  animal  life  are  the  results  of  similar  in- 
terference with  the  normal  course  of  development  of  the  egg. 

THE  PRODUCTION  OF  DUPLICATE  (OR  POLYSOMATOUS)  MONSTERS. — By 
shaking  sea-urchin  ova  when  in  the  two-cell  stage  so  that  the  blastomeres  are 
separated,  each  blastomere  can  be  made  to  grow  into  a  whole  embryo.  De- 
pending upon  the  degree  of  separation,  the  two  embryos  will  be  separate  or  more 
or  less  united  forming  a  double  monster.  If  sea-urchin  ova  are  placed  in  a 
mixture  of  equal  parts  sea-water  and  distilled  water  shortly  after  fertilization, 
the  cell  membranes  rupture  and  part  of  the  protoplasm  bulges  out.  When  the 
ova  are  replaced  in  normal  sea-water  cleavage  begins  and  one  of  the  two  primary 
nuclei  wanders  into  the  extruded  protoplasm.  Each  nucleus  with  its  proto- 
plasm becomes  an  embryo,  and  the  result  is  a  double  monster.  If  the  outflow  of 


622  TEXT-BOOK  OF  EMBRYOLOGY. 

protoplasm  originally  occured  in  several  places,  each  droplet  produces  an 
embryo  and  the  result  is  a  triple  or  quadruple  monster  (Loeb). 

Similar  experiments  have  also  been  performed  on  Vertebrates.  For  example, 
the  two  primary  blastomeres  of  Amphioxus  have  been  partly  separated  and 
double  monsters  developed.  The  blastomeres  in  the  four-cell  stage  have  been 
incompletely  separated,  resulting  in  double  embryos  of  equal  size,  or  triple 
embryos,  or  quadruple  monsters.  Frog's  eggs  have  been  made  to  produce 
double  monsters  by  keeping  them  turned  upside  down  after  the  morula  stage; 
the  same  result  has  also  been  produced  by  loosely  tying  a  ligature  in  the  furrow 
between  the  two  primary  blastomeres.  A  most  curious  result  has  been  obtained 
by  splitting  the  limb  bud  of  a  growing  tadpole  one  or  more  times.  Two  or  even 
a  cluster  of  limbs  may  develop  where  only  one  does  normally  (Tornier). 

These  few  examples  from  the  great  number  of  experiments  which  have  been 
performed  serve  to  show  that  great  light  can  be  thrown  upon  the  problems  of 
teratogenesis  by  experimental  embryology.  While  they  do  not  prove  that  there 
are  no  other  possible  modes  of  origin  for  malformations,  they  indicate  the  im- 
portance of  external  influences  upon  development,  and  afford  tangible  evidence 
in  the  study  of  monsters. 

THE  PRODUCTION  OF  MONSTERS  IN  SINGLE  EMBRYOS. — In  single  embryos 
of  the  lower  forms  it  is  possible  to  produce  by  various  means  a  great  variety  of 
malformations,  many  of  which  are  likewise  comparable  with  malformations 
found  in  human  embryos.  By  placing  recently  fertilized  eggs  of  Fundulus 
in  a  1.5  per  cent,  aqueous  solution  of  potassium  chlorid,  embryos  may  be 
produced  in  which  the  heart  is  developed  but  does  not  beat,  and  in  which  the 
blood  vessels  appear  in  their  normal  positions  but  with  irregular lumina  (Loeb). 
After  extirpating  the  heart  anlage  from  very  young  frog  embryos,  the  latter  grow 
irregularly  and  become  edematous;  the  larger  vascular  trunks  are  distended, 
but  the  capillary  system  is  imperfect  or  absent,  and  the  development  of  ninny 
other  organs  is  inhibited  (Knower.)  Similar  results  may  be  obtained  by 
placing  the  young  embryos  in  aceton-chloroform  which  inhibits  the  heart 
action. 

It  is  possible  to  produce  typical  spina  bifida  in  frog  embryos  by  putting 
them,  during  the  early  stages  of  development,  into  a  0.6  per  cent,  solution  of 
sodium  chlorid  (Morgan  and  Tsuda).  If  the  eggs  of  Axolotl  are  treated  with 
a  0.7  per  cent,  solution  of  sodium  chlorid  all  the  embryos  have  spina  bifida 
(Hertwig).  If  the  eggs  of  Fundulus  are  placed  in  a  solution  of  magnesium 
chlorid,  50  per  cent,  of  them  produce  embryos  with  cyclopia  (Stockard). 

Even  these  few  examples  from  the  enormous  number  of  experiments  that 
have  been  tried  in  the  study  of  single  monsters  again  lead  to  the  conclusion  that 
at  least  some  malformations  in  single  individuals  are  due  to  external  influences 
and  not  to  germinal  defects. 


TERATOGENESIS.  623 

THE  SIGNIFICANCE  OF  THE  FOREGOING  IN  EXPLAINING  THE  PRODUCTION 
OF  HUMAN  MONSTERS. — There  is,  of  course,  no  way  to  obtain  experimental 
evidence  for  or  against  any  theory  so  far  as  the  human  subject  is  concerned. 
But  it  is  possible  to  compare  the  results  of  experiments  on  the  lower  animals 
with  condions  found  in  human  embryos.  So  many  malformed  human  embryos 
resemble  in  a  general  way  and  often  in  detail  the  monsters  in  the  lower  forms 
produced  by  experimental  means  that  a  probable  similarity  in  the  causation 
of  them  at  once  suggests  itself.  The  monsters  in  the  lower  forms  are  artifici- 
ally produced  by  interfering  with  the  normal  course  of  development  of  the 
egg,  and  by  disturbing  the  normal  conditions  of  nutrition  and  growth.  The 
disturbing  factors  are  mechanical  or  chemical,  or  both. 

According  to  the  recent  opinion  of  Mall,  the  primary  disturbing  factors  in 
man  are  not  poisons  in  the  maternal  blood,  corresponding  with  chemical  agents 
used  in  experiments,  but  the  faulty  implantation  of  the  ovum  in  the  uterine 
mucosa.  This  means  that,  after  the  fertilized  and  segmenting  ovum  has 
passed  down  the  oviduct  and  entered  the  uterus,  it  fails  to  become  properly 
embedded  in  the  mucous  membrane.  The  immediate  result  is  an  imperfect 
formation  of  the  foetal  coverings,  especially  of  the  chorion. 

The  reasons  for  the  faulty  implantation  are  not  clear,  but  they  are  possibly, 
even  probably,  to  be  found  in  the  condition  of  the  uterus.  The  most  plausible 
explanation  is  that  some  form  of  endometritis  makes  the  uterine  mucosa  in- 
capable of  properly  adapting  itself  for  the  reception  of  the  ovum. 

In  the  case  of  the  human  embryo,  such  an  imperfection  in  the  agency  through 
which  it  receives  its  nourishment  might  be  considered  in  a  sense  analogous  to 
the  external  influences  that  produce  monsters  in  the  lower  forms. 

Recognizing  the  fact  that  a  given  animal  passes  through  its  embryonic 
stages  at  a  specific  rate  of  development,  which  is  probably  dependent  upon 
the  rate  of  oxidation  in  the  protoplasm,  Stockard  has  conducted  an  extensive 
series  of  experiments  on  animals  (Fundulus,  or  sea-minnow)  and  analyzed  the 
results  with  the  view  of  throwing  light  upon  the  probable  causes  of  malforma- 
tions and  monsters.  His  experiments  comprised  the  interruption  or  slowing 
of  the  rate  of  embryonic  development  either  by  temporarily  lowering 
the  surrounding  temperature  and  thereby  reducing  the  rate  of  oxidation  in 
the  protoplasm  or  by  cutting  off  the  supply  of  oxygen.  When  the  tempera- 
ture of  the  eggs  during  the  cleavage  stages  was  reduced  for  a  time  to  5°  or  6° 
Centigrade  and  then  raised  to  normal  it  was  found  that  in  later  development 
a  significant  percentage  of  twins  and  a  number  of  malformations  appeared. 
Similar  results  were  obtained  by  directly  reducing  the  supply  of  oxygen. 
When  exposed  to  such  experimental  conditions  in  later  stages  of  development, 
the  eggs  did  not  produce  duplicate  monsters.  There  seemed  to  be  a  critical 
stage  at  which  it  was  necessary  to  apply  the  experimental  conditions  in  order 


624  TEXT-BOOK  OF  EMBRYOLOGY. 

to  produce  certain  types  of  malformations.  From  this  it  was  inferred 
that  the  results  of  inhibiting  the  rate  of  development  depend  upon  the 
developmental  moment  at  which  the  interruption  occurred.  These  and  other 
results  obtained  by  Stockard  led  him  to  the  conclusion  that  changes  in  the 
conditions  of  temperature  and  oxygen  supply  are  the  most  frequent  causes  of 
abnormal  and  monstrous  development  and  embryonic  death.  In  the 
mammals,  with  their  relatively  constant  temperature,  the  developmental 
environment  is  under  natural  control,  but  it  is  not  always  perfectly  regulated. 
This  lack  of  perfect  regulation  causes  disturbances  in  the  oxygen  supply 
which  are  regarded  as  potent  factors  in  the  production  of  malformations  and 
monsters. 

A  significant  fact  relative  to  inhibition  of  development  is  found  in  the 
normal  production  of  quadruple  offspring  of  the  nine-banded  armadillo. 
In  this  animal  the  egg  undergoes  the  early  developmental  stages  up  to 
blastocyst  formation  while  it  is  traversing  the  oviduct.  When  it  reaches 
the  uterus  the  blastocyst  lies  in  the  lumen  for  about  three  weeks  before 
it  becomes  embedded  in  the  uterine  mucosa.  During  this  period  develop- 
ment practically  ceases,  and  the  logical  cause  of  the  stoppage  is  the  lack  of 
oxygen.  Then  when  implantation  occurs  development  sets  in  again  and  the 
blastoderm  divides  into  four  embryonic  rudiments  which  give  rise  to  the  four 
offspring. 

As  stated  above,  Mall  attributed  the  production  of  monsters  and  malfor- 
mations to  faulty  implantation  of  the  ovum  in  the  uterine  mucosa  with  the 
resulting  disturbances  in  the  nutritional  relations  of  the  developing  embryo. 
Stockard  has  added  in  this  connection  the  specific  factor  of  disturbance  in  the 
oxygen  supply. 

References  for  Further  Study. 

AHLFELD,  F.:  Die  Missbildungen  des  Menschen.    Leipzig,  1880-1882. 

AHLFELD,  F.:  Lehrbuch  der  Geburtshilfe.    Leipzig,  1903. 

BALLANTYNE,  J.  W.:  Antenatal  Pathology.     2  Vols.     Edinburgh,  1904. 

BARDEEN,  C.  R.:  Abnormal  Development  of  Toad  Ova  Fertilized  by  Spermatozoa 
exposed  to  the  Roentgen  Rays.  Jour,  of  Exp.  ZooL,  Vol.  IV,  1907. 

BEARD,  J.:  The  Morphological  Continuity  of  the  Germ  Cells  in  Raja  batis.  Anat. 
Am.,  Bd.  XVIII,  1900. 

CONKLIN,  E.  G.:  The  Cause  of  Inverse  Symmetry.     Anat.  Aw.,  Bd.  XXIII,  1903. 

DARESTE,  C.:  Recherches  sur  la  production  des  monstrosites.     Paris,  1891. 

DRIESCH,  H.:  Entwickelungsmechanische  Studien.  Zeitschr.  f.  wissensch.  ZooL,  Bd. 
LIII,  Bd.  LV. 

FORSTER:  Die  Missbildungen  des  Menschen.     Jena,  1865. 

GUDERNATSCH,  J.  F. :  Hermaphroditismus  vera  in  Man.  Am,  Jour,  of  Anat.,  Vol.  XI, 
1911. 

HERTWIG,  O.:  Urmund  und  Spina  bifida.     Arch.  f.  mik.  Anat.,  Bd.  XXXIX,  1892. 


TERATOGENESIS.  625 

HERTWIG,  O. :  Die  Entwickelung  des  Froscheies  unter  dem  Einfluss  schwacherer  und 
starkerer  Kochsalzlosungen.  Arch.  f.  Mik.  Anal.,  Ed.  XLIV,  1895. 

HERTWIG,  O.:  Missbildungen  und  Mehrfachbildungen.  In  Hertwig's  Handbuch  der 
vergleich.  u.  experiment.  Entwickelungslehre  der  Wirbeltiere,  Bd.  I,  Teil  I,  1903. 

HIRST  and  PIERSOL:  Human  Monsters.     Philadelphia,  1891. 

KNOWER,  H.  McE.:  Effects  of  Early  Removal  of  the  Heart  and  Arrest  of  the  Cir- 
culation on  the  Development  of  Frog  Embryos.  Anat.  Record,  Vol.  VII,  1907. 

LOEB,  J.:  Beitrage  zur  Entwickelungsmechanik  der  aus  einem  Ei  entstehenden 
Doppelbildungen.  Roux's  Arch.  f.  Entwickelungsmechanik  der  Organismen,  Bd.  I,  1895. 

LOEB,  J.:  Studies  in  General  Physiology.     Chicago,  1905. 

MALL,  F.  P.:  A  Study  of  the  Causes  Underlying  the  Origin  of  Human  Monsters. 
Jour,  of  Morphol.,  Vol.  XIX,  1908. 

MALL,  F.  P.:  On  the  Frequency  of  Localized  Anomalies  in  Human  Embryos  and 
Infants  at  Birth.  Am.  Jour,  of  Anat.,  Vol.  XXII,  1917. 

MARCHAND,  L.:  Missbildungen.  In  Eulenburg's  Real-Encyclopadie  der  gesammten 
Heilkunde,  Bd.  XV,  1897. 

MORGAN,  T.  H.:  Half-embryos  and  whole  Embryos  from  one  of  the  first  two  Blasto- 
meres  of  the  Frog's  Egg.  Anat.  Am.,  Bd.  X,  1895. 

MORGAN,  T.  H.:  Ten  Studies  in  Roux's  Arch.  f.  Entwickelungsmechanik  der  Organ- 
ismen, Bd.  XV-XIX,  1902-1905. 

NEWMAN,  H.  H. :  The  Biology  of  Twins.  1917. 

PANUM:  Entstehung  der  Missbildungen.     Berlin,  1880. 

PIERSOL,  G.  A.:  Teratology.  In  Wood's  Reference  Handbook  of  the  Medical 
Sciences,  Vol.  VII,  1904. 

•SCHULTZE,  O.:  Die  kunstliche  Erzeugung  von  Doppelbildungen  bei  Froschlarven  mit 
Hilfe  abnormer  Gravitationswirkung.  Roux's  Arch.  f.  Entwickelungsmechanik  der 
Organismen,  Bd.  I,  1895. 

SCHWALBE,  E.:  Die  Morphologic  der  Missbildungen  des  Menschen  und  der  Thiere. 
Jena,  1906-1907. 

STOCKARD,  C.  R.:  The  Artificial  Reproduction  of  a  Single  Median  Cyclopean  Eye  in 
the  Fish  Embryo  by  Means  of  Sea- water  Solutions  of  Magnesium  Chlorid.  Roux's  Arch. 
f.  Entwickelungsmechanik  der  Organismen,  Bd.  XXIII,  1907! 

STOCKARD,  C.  R.:  Developmental  Rate  and  Structural  Expression:  An  Experimental 
Study  of  Twins,  "  Double  Monsters  "  and  Single  Deformities,  and  the  Interaction  among 
Embryonic  Organs  during  their  Origin  and  Development.  Am.  Jour,  of  Anat.,  Vol. 
XXVIII,  No.  2,  1921. 

TORNIER,  G.:  An  Knoblauchskroten  experimentell  entstandene  uberzahhge  Hmter 
gliedmassen.  Roux's  Archf.  Entwickelungsmechanik  der  Organismen,  Bd.  XX,  1905. 

WILDER,  H.  H.:  Duplicate  Twins  and  Double  Monsters.     American  Jour,  of  Anat., 

Vol.  Ill,  1904. 

WILLIAMS,  J.  W.:  Obstetrics.     New  York,  1903. 

WILSON,  E.  B.:  On  Multiple  and  Partial  Development  in  Amphioxus.  Anat.  Aw., 
Bd.  VII,  1893. 


INDEX 


Abdominal  cavity,  308,  347 

regions,  defects  of,  618 
Abducens,  VI,  nerve,  432,  434 
Aberrant  ductule,  387 
Abrachius,  619 
Acardia,  254,  603 
Acardiaci,  acephali,  604 

acormi,  604 

amorphi,  604 

completi,  604 
Acardiacus,  603 
Accessory  chromosomes,  22,  23 
Acini,  the,    413 
Acoustic  area   (see  also  Auditory  area),    528 

ganglion,  558 

VIII,    nerve,    432,    435,    469,    470,    473, 
488,  558 

nerve,  ganglion  cells  of,  559 

radiation,  440,  441 
Acrania,  612,  613,  615 

with  exencephaly,  613 
Acrocephaly,  180 
Acromion  process,  167 
Acrosome,  6 

Acustico-facialis  ganglion,  558 
Acustico-lateral  system, 

influence  on  nervous  system,  416,  429,  436 
Adami,  concerning  hermaphroditism,  405 
Adenoid  tissue,  300 
Adipose  tissue,  135 
Aditus  laryngis,  330,  331 

Afferent  peripheral  neurones,  417,  427,  459  to 
472 

peripheral  nerve  fibers,  42 1 

root  fibers,  421 
After-birth,  598 

After-brain  (myelencephalon),  425 
Age,  copulation,  123 

fertilization,  123 

menstrual,  123 

Age,  length  and  weight  of  body,  122 
Agnathus,  325,  617 

Ahlfeld's   fission   theory  of  symmetrical   du- 
plicity, 607 
Air  sacs,  335 


Ala  cinerea,  497 

magria,  159 

parva,  159 
Alar  plate,  447,  460,  482,  485,  489,  493,  497, 

498 

Albinism,  415 
Albrecht,    concerning    formation    of    incisive 

bone,  164 
Alimentary  tube,  285 

intestinal  region  of,  286 

cesophageal  region  of,  286 

origin  of,  285,  286 

pharyngeal  region  of,  286 

stomach  region  of,  286 

yolk  stalk  of,  286 
Alimentary  tube  and  appended  organs,   285 

anomalies  of,  323 

histogenesis  of  gastrointestinal  tract,  310 
of  liver,  318 
of  pancreas,  322 

intestine,  306 

liver,  314 

mouth,  286 

cesophagus,304 

pancreas,  319 

pharynx,  298 

salivary  glands,  296 

stomach,  304 

teeth,  291 

tongue,  289 
Alisphenoid  bone,  159 
Allanto-chorion,  570 
Allantoic  blood-vessels,  in  Mammals,  572 

duct,  306,  582 

sac,  572 
Allan tois,  the,  570 

blood-vessels  of,  in  chick,  571 
in  Mammals,  577 
in  man,  583 

functions  of,  in  chick,  570 
in  man,  582 

in  Mammals,  575 

in  man,  582 

relation  of,  to  chorion,  570 
Allen,  concerning  sex  cells,  374 


627 


628 


INDEX 


Alopecia,  415 

Alternation  of  vertebrae  and  myo tomes,  148, 

264 

Amelus,  610 
Amnion,    100,    101,    102,    105,    108,    no,     in 

formation  from  amniotic  fold,  565 

in  Birds,  563 

in  Mammals,  572,  574 

in  man,  579 

in  Reptiles,  563 

rhythmical  contractions  of,  566,  582 
Amniotic  adhesions,  619 

cavity,  89,  90,  92,  96,  100,   101,  104,  105, 
108,  565,  579 

fluid,  580 

folds,  564 

in  Mammals,  574 

suture,  564 
Amphicytes,  462 
Amphimixis,  33 
Amphioxus,  cleavage  in,  35 

early  development  of,  35 

gastrulation  in,  38,  39 

mesoderm  formation  in,  42 

ovum  of,  35 

Ampullae  of  semicircular  canal,  553,  558 
Amyelus,  614 
Anal  membrane,  310 

opening,  310 

pit,  58,  63,  310 
Anencephaly,  282,  616 
Angioblast,  238 
Angiomata,  415 
Angle  of  the  mouth,  119,  287 
Angulus  praethalamicus,  507,  510,  517 
Ankyloblepharon,  616 
Animalculists,  XIII 
Annular  placenta,  598 
Anomalies,  see  also  Teratogenesis 

of  the  alimentary  tract,  323 

of  the  diaphragm,  351 

of  the  large  vascular  trunks,  256 

of  the  heart,  254 

of  the  integumentary  system,  414 

of  the  mesenteries,  352 

of  the  muscular  system,  282 

of  the  nervous  system,  530 

of  the  omenta,  352 

of  the  pericardium,  352 

of  the  placenta,  598 

of  the  respiratory  system,  334 

of  the  skeletal  system,  177 

of  the  umbilical  cord,  599 


Anomalies  of  the  urogenital  system,  399 

of  the  vascular  system,  254 
Anomalous  position  of  the  heart,  254 
Anophthalmia,  616 
Anterior  colliculi,  see  Anterior  corpora    quad- 

rigemina 
Anterior  (cerebral)  commissure,  424 

commissure  of  the  cord,  473,  474 

corpora  quadrigemina,  437,  487,  500,  503, 
546 

horn  (ventral  gray  column),  477 

neuropore,  421 

perforated  space,  511 
Anthelix,  561 
Antitragus,  561 
Aorta,  dorsal,  187,  209 
Aortae,  primitive,  187 
Aortic  arches,  188,  210 
Apdthy,  concerning  peripheral  nerves,  464 
Apolar  cells,  454 

Appendage  of  the  epididymis,  386 
Appendicular  skeleton,  166 

anomalies  of,  180 

derivation  of,  167 
Appendix  testis,  391 

vermiform,  310 
Aprosopus,  616     . 
Apus,  619 

Aquaeductus  Sylvii,  426 
Arch  of  the  aorta,  211 
Archencephalon,  423 
Archenteron, 

in  Amphioxus,  38,  40 

in  the  chick,  70,  71,  75 

in  the  frog,  56,  57 

Archipallial    commissure,     see    Fornix    com- 
missure 
Archipallium,  438,  475,  507,  511,  516  to   522 

connections  of,  475,  507,  528 
Arcuate  fibers  (external),  485 

(internal),  478,  485 
Arcus  aortae,  211 
Area  opaca,  68,  72,  73,  74,  79 

pellucida,  68,  72,  73,  74,  79 

vasculosa,  79,  186,  569 
Areola,  the,  413 
Areolar  tissue,  135 
Arm,  115,  121 
Arrectores  pilorum,  408 
Arteria  centralis  retinae,  539 
Arteries,  209 

allantoic,  191,  210 

anomalies  of,  256 


INDEX 


629 


Arteries,  basilar,  212 

brachial,  217 
carotid,  211 
cerebral,  214 

coeliac,  215 

epigastric,  214 

femoral,  218 

gastric,  215 

gluteal,  219 

hepatic,  215 

hj'aloid,  539 

hypogastric,  217 

iliac,  216,  217 

innominate,  212 

intercostal,  214 

internal  spermatic,  216 

lumbar,  214 

mammary,  214 

median,  217 

mesenteric,  215 

omphalomesenteric,  189,  215,  569,  571 

ovarian,  216 

peroneal,  219 

popliteal,  218 

pulmonary,  204,  212 

radial,  218 

renal,  216 

saphenous,  218 

sciatic,  218 

splenic,  215 

subclavian,  211,  213,  217 

testicular,  216 

tibial,  219 

ulnar,  217 

umbilical,  191,  210,  571 

vertebral,  213 

vesical,  217 

vitelline,  187,  210,  569,  571 

volar  interosseous,  217 
Articular  cavity,  174 
Aryepiglottic  ridges,  331 
Arytenoid  ridge,  331 

Ascaris   megalocephala,   for   study   of    matu- 
ration, ii 

Assheton,  concerning  origin  of  parasitic  duplic- 
ity, 611 
Astomus,  617 
Astragalus,  the,  172 
Asymmetrical  duplicity,  618 

origin  of,  610 

parasitic  structures  in  the  sexual  glands, 

609 
Atlas,  the,  152 


Atresia  of  the  anus,  326 

oris,  617 
Atria  of  heart,  200 

of  lungs,  335 
Atrial  septum,  202 
Atrio-ventricular  canal,  202 
Atrium  of  inner  ear,  553 
Auditory  area  of  pallium,  440,  527,  528 
meatus,  external,  origin  of,  114,  561 
nerve,  see  Acoustic  VIII 
ossicles,  derivation  of,  165,  559 
Pit,  552 
placode,  552 
vesicle,  552 

Auerbach,  plexus  of,  461 
Aula,  512 
Auricle,  560 

Autonomic  system  (sympathetic),  428 
Autosite,  608 
Axial  filament,  6,  14 
skeleton,  146 
anomalies  of,  177 
head,  154 
notochord,  146 
primitive,  146 
ribs,  152 
sternum,  153 
vertebrae,  147 
thread,  6,  14 
Axis  (epistropheus),  152 
Axone,  the,  448,  455 

Balfour,  concerning  peripheral  nerves,  463 

Bardeen,  concerning  peripheral  nerves,  463 

Bartholin's  glands,  373 

Basal  plate,  447,  472,  477,  482,  484,  494 

Basilar  artery,  212 

Basioccipital  bone,  158 

Basisphenoid  bone,  159 

Basket  cells,  499 

Baskets,  499 

Beard,  concerning  sex  cells,  374 

Bechterew,  v.,  central  tegmental  tract  of, 
489 

Belly  stalk,  96,  101,  102,  108,  no,  in,  582 

Bertini,  columns  of,  367 

Bicornuate  uterus,  403 

Bielschowsky,  method  of  staining,  533 

Bilateral  hermaphroditism,  404 

Bile  capillary,  318 

Bipartite  uterus,  403 

Bischoff,  concerning  origin  of  parasitic  duplic- 
ity, 6n 


630 


INDEX 


Bladder  (see  also  Urinary  Bladder],  370 

anomalies  of,  401 
Blastema,  metanephric,  362 
Blastemal  stage,  148 
Blastoccel,  38.  39,  54,  55,  68,  107 
Blastocyst,  87,  90,  91,  108 
Blastoderm,  68,  69,  70,  71,  72,  75 
Blastodermic  vesicle,  87,  108 
Blastomeres, 

of  Amphioxus,  36,  37 

in  the  chick,  67,  68 

of  the  frog,  52,  53 

in  Mammals,  85 
Blastopore, 

in  Amphioxus,  39 

in  the  chick,  70,  71,  72,  73,  76 

in  the  frog,  56,  57,  59 
Blastula,  37,  38,  54,  55 
Blood,  cells  of,  236 

'    relation  of  maternal  and  fcetal   blood  in 

Mammals,  577 
in  man,  583,  595 
Blood  cells,  development  of,  236 

erythroblasts,  239 

erythrocytes,  239 

haemoblasts,  237 

histogenesis  of,  236 

leucocytes,  239 

lymphoblasts,  237 

lymphocytes,  239 

megaloblasts,  239 

mesamoeboid,  238 

mononuclear  leucocytes,  239 

normoblasts,  239 

primitive,  186,  237 
lymphocytes,  237,  238 

table  showing  development  of,  242 
Blood  islands,  78,  186,  237 
Blood  plates,  242 
Blood  vascular  system,  185 
Blood  vessels,  allantoic,  function  of,  572 

arteries,  209 

factors  in  development  of,  195 

heart,  196 

origin  of,  193 

placental,  595 

sinusoids,  229 

veins,  219 
Blue  babies,  256 

Body,  age,  length  and  weight  of,  122 
Body  cavity,  see  Coelont 
Bone,  compact,  140 

diaphysis  of,  144 


Bone,  epiphysis,  144 

growth  of,  144 

intracartilaginous,  140 

shaft  of,  144 

spongy,  139 

subperiosteal,  140 
Bone  cells,  139 

destroyers,  139 

formers,  139 

marrow,  145 
Bones,  defective  or  absent,  619 

derived  from  the  branchial  arches,  162 

membrane,  of  the  skull,  160 
Bonnet,   concerning  derivation  of    pigmented 
layer  of  retina,  547 

concerning  double  origin  of  vitreous,  545 

concerning  origin  of  parasitic   duplicity, 

611 

Born,  concerning  potentiality  of  germ  cells,  612 
Bowman,  membrane  of,  548 
Bowman's  capsule,  347,  365 
Brachia,  anterior.  500,  503 
Brain,  the,  112,  423,  443 

after-brain  (myelencephalon),  425 

aquaeductus  Sylvii,  426 

archencephalon,  423 

cephalic  flexure  of,  424 

cerebellum,  425,  447,  482,  495 

corpora  striata,  425,  437,  444,  448,  509,  511 

defects  in,  612,  613 

deuterencephalon,  423 

diencephalon,  425,  437,  444,  448,  501 

distinguishing    features    of    human    and 
their  biological  significance,  438,  440 

end-brain  (telencephalon),  425 

epichordal  part  of,  423,  427 
segmental,  482 

fore-brain  (prosencephalon) ,  424 

hind-brain  (metencephalon) ,  425 

inter-brair,  (diencephalon),  425 

isthmus,  425,  483 

medulla  oblongata,  447,  482 

mid-brain  (mesencephalon),  424 

plica  encephali  ventralis,  423 

plicarhombo-mesencephaiica,  445 

prechordal  part,  423,  427 

rhinencephalon,  425,  437,  475,  507,  510 
to  511 

rhombic  (rhombencephalon) ,  424 

rhombo-mesencephalic  fold  of,  424 

segmental,  427 

character  of,  426,  427 

telencephalon,  425,  437,  508  to  531 


INDEX 


631 


Brain,  ventral  cephalic  fold,  423 

ventricles  of,  426,  448,  512 
Branchial  arches,  malformations  of,  616 
arches,  origin  of,  112,  118 
cysts,  618 

epithelial  bodies,  300 
glomus  caroticum,  304, 
parathyreoids,  301 
thymus,  302 
thyreoid  gland,  300 
grooves,  origin  of,  112,  118 
Branchiogenetic  cysts,  618 
Branchiomeric  muscles,  271 
segmentation,  430,  459 
Brachium,   conjunctivum,   see* Superior    cere- 

bellar  peduncle 

ponds,     see     Middle    cerebellar    peduncle 
quadrigeminum  inferius,  441 
Brandt,  concerning  anomalies  of  hair,  415 
Bremer,  concerning  spinal  accessory  nerve,  466 
Brodmann,  concerning  cortical  layers,  526 
Bronchial  rami,  334 
B  runner,  glands  of,  312 
Bryce-Teacher's  ovum,  99,  108,  579,  585 
Bucco-nasal  membrane,  550 
Burdach,  columns  of,  429,  441,  488 

nuclei  of  the  columns  of,  429,  436,   437, 

490 
Bursa  pharyngea,  300 

Caecum,  the,  306,  309 

Cajal,   concerning   development   of  cerebellar 
cells,  518 

concerning  neurofibrils  and  early  develop- 
ment of  nerve  cells,  454,  455 

concerning  optic  nerve,  546 

concerning  peripheral  nerves,  464 
Calcaneus  (os  calcis),  172 
Calcar  avis,  523 
Calcarine  area,  440 
Calcification  centers,  137,  141 

zone,  140,  142 
Calyces,  363 

Campbell,  concerning  cortical  areas,  529 
Canal  of  Cloquet,  546 

of  Petit,  548 
Canalized  fibrin,  590 
Canals  of  Gartner,  386 
Capillaries,  villous,  595 
Capitulum  of  rib,  153 
Capsule  of  Glisson,  315,  343 
Carotid  arteries,  211 

gland,  399 


Carotid  skein,  399 

Carpal  bones,  168 

Carpenter,  concerning  ciliary  ganglia,  471 

Cartilage,  136 

cuboid,  172 

cuneiform,  172 

episternal,  153 

ethmoidal,  160 

laryngeal,  332 

Meckel's,  157,  162 

of  hip  bone,  171 

thyreoid,  332 

triticeous,  332 

Wrisberg's,  333 
Cartilaginous  primordial  cranium.  156 

stage,  148 
Cauda  equina,  482 
Caudal  gut,  311 

lymph  sac,  244,  248 
"Caul,"  581 
Cavity,  abdominal,  347 

amniotic,  89,  90,  92,  96,  TOO,  101,  104,  105, 
108,  565,  579 

body,  340 

extraembryonic  body  (see  Exoccelom) 

parietal,  196,  342 

pericardial,  340,  341 

peritoneal,  340,  343 

pleural,  340,  343 

primitive  pericardial,  196,  199,  341 

segmentation,  38,  54,  68 
Cell  migration,  of  nervous  system,  448,   449, 

454,  455,  456,  489,  497 
Cell  organization,  significance  of  germ,  9 
Cell  proliferation,  449,  484,  489,  497 

in  neural  tube,  449 
Cells,  air,  335 

apolar  of  neural  tube,  454 

association,  427,  438,  498,  500,  528 

basket,  499 

bipolar  of  neural  tube,  454 
of  retina,  543 

blood,  236 

bone,  139,  142 

chromaffin,  396 

cochlear  ganglion,  559 

cone,  471,  475,  542,  543 

decidual,  591 

dermal,  412 

ependyma,  451,  453 

epithelial,  449 

fat,  136 

follicular,  378 


632 


INDEX 


Cells,  germ,  differences  between,  9 
in  heredity,  9 
organization  of,  9 
polarity  of,  9 

germinal  of  neural  tube,  449,  453 

giant,  145 

granule,  518 

hair,  556,  558,  559 

heart-muscle,  262,  281 

Hensen's,  558 

indifferent,  374 
of  neural  tube,  454 

interstitial,  382 

liver,  318 

lutein,  380 

lymphoid,  304 

mastoid,  560 

mesodermal,  340,  408 

mitral,  475 

monopolar,  455 

Miiller's,  542 

myelocytes,  145,  241 

myoblasts,  276 

neuroglia,  451,  453 

odontoblasts,  294 

of  Sertoli,  n,  15,  16,  382 

osteoblasts,  139 

osteoclasts,  139,  145 

phaeochrome,  396 

pillar,  558 

polymorphous,  527 

Purkinje,  497 

pyramid,  525,  526,  528 

rod,  443,  471,  475,  542 

sex,  374 

solitary,  of  Meynert,  528 

somatic,  i 

spermatids,  n 

spermatocytes,  n 

spermatogenic,  n 

spermatogonia,  n 

supporting,  n,  15,  16 

sustentacular,  542 

vestibular  ganglion,  559 

wandering,  323 

Cement  substance,  origin  of,  133 
Central  canal,  479 
Centralis,  496 
Centrolecithal  ova,  6 
Centrosome,  the,  6,  13,  14,  27,  28 

in  fertilization,  28 
Cephalic  flexure,  no,  115,  424,  443 
Cephalization,  420 


Cephalocele,  613 
Cephalopagus,  606 
Cephalothoracopagus  diprosopus,  605 

janiceps,  606 

Cerebellar  hemispheres,  442,  496 
Cerebellum,  425,  427,  436,  482,  495 

afferent  connections  of,  436 

basket  cells  of,  499 

cells  of  Purkinje,  497,  499 

centripetal  fibers  of,  499 

climbing  fibers  of,  500 

cortex,  497 

efferent  connections  of,  436 

flocculi,  496 

granular  layer  of,  497 

granule  cells  of,  498 

hemispheres  of,  442,  496 

lobes  of,  496 

middle  peduncle  of,  436,  442 

molecular  (plexiform)  layer,  497 

mossy  fibers,  500 

nodule,  496 

parallel  fibers  of,  498 

peduncles  of,  436,  441,  443,  493,  500 

postnatal  development,  498,  499 

superior  peduncle  of,  436 

taenia  of,  483 

velum  of,  483 

vermis  of,  496 

Cerebral  hemispheres  (see  also  Pallium},  427, 
440,  444,  508,  511  to  530 

hernia,  613 

Cerebrospinal  ganglia,  421 
Cervical  depression,  113,  115 

enlargement,  429 

fistula,  complete,  617 
incomplete,  617 

flexure,  448 
Cervix,  the,  385 

plicae  palmatae  of,  385 
Chalaza,  5 

Cheilognathoprosoposchisis,  617 
Cheilognathoschisis,  617 
Cheilognathouranoschisis,  617 
Cheiloschisis,  617 
Cheeks,  119 

Chiari,  concerning  sebaceous  cysts,  415 
Chiasma  eminence,  424 
Chick,  cleavage  in,  67 

early  development  of,  66 

gastrulation  in,  70,  71,  72,  73,  76 

origin  of  mesoderm  in,  77,  78 
Chin,  origin  of,  119,  121 


INDEX 


633 


Choanen,  primitive,  550 

Chondrification  first  occurrence  in  head  skele- 
ton, 156 
Chondrocranium,  157 

ossification  of,  158 
Chorda  (see  also  Notochord] 

dorsalis,  146 

tympani,  432,  468 
Chordae  tendinae,  206 
Chordal  sheath,  146 
Chorio  epitheliomata,  402 
Chorioid,  defective  pigmentation  of,  415 

fissure,  of  pallium,  517 

fold,  517 

of  rhombencephalon,  513 

of  eye,  545 

plexus  of  fourth  ventricle,  423,  483,  495 
of  lateral  ventricle,  423,  513,  513,  517 
of  third  ventricle,  423,  513 
Chorioidal  fissure  of  eye,  537,  545 
Chorion,  100,  101,  102,  108 

function  of,  571 

in  chick,  571 

in  Mammals,  572,  574 

in  man,  583 

relation  of,  to  allantois,  583 
Chorion  frondosum,  586,  588 

Iseve,  586,  588 

Chorionic  villi,  101,  578,  586 
Chromaflin  cells,  396 

granules,  396 

Chromatin  as  inheritance  material,  9 
Chromophilic  bodies,  448,  459 
Chromosomes,  9,  12,  16,  17,  18.  19,  20,  21,  22, 
23,  27 

accessory,  22,  23 

diploid  number  of,  n,  16 

haploid  number  of,  12,  16 

identity  of,  21 

qualitative  differences  in,  21 

segregation  of,  21 

synapsis  of,  12,  16,  21 
Chryptorehism,  402 
Cilia,  of  the  cells  of  gastrula,  40 
Ciliary  body  of  eye,  547 

ganglion,  471 
Circulation,  changes  in,  at  birth,  234 

allantoic,  292,  209 

foetal,  course  of,  234 

reversal  of,  565 

vitelline,  189 
Circulus  arteriosus,  212 
Cisterna  chyli,  244 


Clark,   W.   C.,   concerning  the  joint    capsule 

and  cavity,  177 
Clarke's  columns,  436,  481 
Clava,  494 
Clavicle,  168 
Cleavage  (segmentation),  in  Amphioxus,  35,  37 

in  the  chick,  67,  68,  69 
.    in  the  frog,  51,  53 

in  Mammals,  85 

of  ova  of  opossum,  85,  87 
of  mouse,  85,  86 
of  rat,  85,  87 

regular,  36 

total,  36 

Cleft  palate,  180,  616,  617 
Climbing  fibers,  500 
Clitoris,  the,  394 
Cloaca,  the,  310,  370 

persistence  of,  326 
Cloacal  membrane,  370 
Closing  plate,  593 
Coccygeal  gland,  254 
Cochlea,  430,  437 
Cochlear  ganglion  cells,  559 
of  VIII  nerve,  469 

part  of  acoustic  (auditory)  nerve,  432 

pouch,  553 

terminal  nuclei,  436 
Ccelom,  46,  60,  65,  80,  81,  96,  98,  104,  340 

embryonic,  340 
Coelomic  space,  45 
Collaterals,  474,  499,  526 
Colloid  secretion  of  thyreoid  gland,  300 
Colon,  the,  307 

ascending,  309 

descending,  309 

sigmoid,  309 

transverse,  309 
Colostrum  corpuscles,  414 
Column  cells,  473 

heteromeric,  473 

tautomeric,  473 
Columns,  anterior  white,  477 

dorsal  gray  (posterior  horn),  428,  477 

posterior  white,  460,  473,  477 
Columns  of  Bertini,  367 

of  Burdach,  429,  441,  388 
nuclei  of,  429,  441,  490 

of  Goll,  429,  441,  480,  488 
nuclei  of,  429,  441,  490 
Commissura  habenularis,  425,  508 

mollis  (see  Massa  intermedia),  505 
Commissural  column  cells,  473 


634 


INDEX 


Commissure,  anterior  (cerebral).  424 
neopallial,  438 
posterior,  424,  503,  508 
Concha,  115 
Conchse,  inferior,  160 
middle,  160 
superior,  160 
Concrescence,  58 
Cones,  471,  475;  542,  543 
Confluens  sinuum,  221 
Conjugation,  33 
Connective  tissue  follicle,  410 
tissues,  the,  129 
adipose,  135 
areolar,  135 
cartilage,  136 
development  of  the,  129 
embryonic,  135 
fibers  of,  134 
fibrillar  forms,  134 
ground  substance  of,  134 
histogenesis  of,  131 
intermuscular,  279 
osseous,  137 
osteogenetic,  139 
periosteum,  139 
Contractile  fibrils,  263 
Contractions,  rhythmical,  of  the  amnion,  in 

man,  580 

Convolutions  of  cerebral  hemispheres,  5 1 2 
Coordinating    centers,    higher,    see    Supraseg- 

mental  structures 
Coordination,  417 
Copulation,  24 
Coracoid  process,  167 
Cords,  medullary,  376 
Pfliiger's  egg,  378 
rete,  374 
sex,  375,  376 
Cornea,  548 

elastic  membranes  of,  548 
endothelium  of  Descemet,  548 
membrane  of  Bowman,  548 
substantia  propria  corneae,  548 
Cornu  ammonis,  518,  522 
Corona  radiata,  2 

of  cerebral  hemispheres,  507 
Coronoid  process,  164 
Corpora  quadrigemina.  437,  487,  500 
anteria  brachia  of,  500 
layers  of,  500 

Corpus  callosum,  438,  513,  520,  528 
genu  of,  521 


Corpus  callosum,  splenium  of,  521 

haemorrhagicum,  380 

luteum,  123,  380 
changes  in,  380 

Luysii,  507,  508 

sterni,  154 

striatum,  425,  437,  447,  448,  509,  511 
crura  of,  509,  511,  513 
tail  (caudaj,  513 

Correns,  concerning  determination  of  sex,  405 
Cortex,  cerebral,  524 
Cortical  layer  of  telencephalcn,  512 
Cortico-pontile  fibers  (of  the  pes),  436,  441, 

442,  494,  528 

Corti's  organ,  430,  437,  528,  557 
Costal  process,  148 
Cotyledon  (lobe),  595 
Cotyledons,  591 
Covering  layer  (see  also  Enveloping  layer],  85, 

103,  107 

Cowper's  glands,  373 
Cranial  cavity,  development  of,  139 
Craniopagus,  606 

parasiticus,  606 
Craniorachischisis,  614 
Cranior-rachischisis,  612 
Cranioschisis,  612,  615 
Crescents  of  Gianuzzi,  298 
Cribriform  plate,  1.60 
Cricroid  cartilage,  165 
Crista  ampullaris,  556,  559 

galli,  1 60 

Crusta,  see  Pes  pedunculi 
Cryptophthalmia,  616 
Cuboid  cartilages,  172 
Culmen,  496 
Cumulus  ovigerus,  380 
Cuneiform  cartilage,  172 

ridge,  331 
Cuneus  of  cerebral  hemispheres,  524 

of  medulla,  494 
Cutis  plate,  131,  132,  262 
Cuvier,  ducts  of,  191,  220,  222 
Cyclocephaly,  616 
Cyclopia,  530,  559,  606,  616 
Cyclostomus,  616 
Cyclotus,  616 

Cylinder  furrow  of  His,  479 
Cylindrical  form  of  body,  107 
Cystadenomata,  403 
Cystic  tumors,  609 
Cysts,  402 

dermoid,  415 


INDEX 


635 


Cysts,  sebaceous,  415 
Cytoplasm,  egg,  2 
Cyto-trophoderm,  99,  585,  589,  590 

Darkschewitsch,  nucleus  of,  487 
Decidua,  584 

basalis,  100,  588 

capsularis,  100,  587 

parietalis,  587 
Decidual  cells,  591 
Decussation  of  Forel,  487 

of  Meynert,  500 
DeFormatione  Foetus,  XIII 
De  Formato  Fcetu,  XIII 
de  Graaf,  Regnier,  XIII 
de    Graaf,    Regnier,  concerning  the  Graafian 

follicle,  XIII 

Deiter's  nucleus,   tracts  from,   436,   481,  487 
Dendrites,  455 

apical,  525 

of  pyramidal  cells,  526 
Dens,  the  (odontoid  process),  152 
Dental  groove,  292 

papilla,  292 

sac,  295 

shelf,  292 
Dentinal  canals,  295 

fibers,  295 

pulp,  292,  294 
Dentine,  292,  294 

formation,  295 
Dermal  navel,  569,  580 

umbilicus,  569 
Dermis,  the,  408 

arrectores  pilorum,  408 

pigment  of,  408 

tactile  corpuscles  of  Meissner  of,  408 

tunica  dartos,  408 
Dermoid  cysts,  415,  609 
Descemet,  membrane  of,  548 
Descent  of  ovary,  392,  407 

of  testicle,  389,  407 
Determination  of  sex,  21 
Deuterencephalon,  423 
Deutoplasm,  2,  5 
Dextrocardia,  255,  324 
Diaphragm,  the,  340,  345 

anomalies  of,  352 

caudal  migration  of,  346 

changes  in  position  of,  346 

ligaments  of,  346 

muscular  elements  of,  269 

primary,  344 


Diaphragmatic  hernia,  352 
Diaphysis,  144 
Diaplexus,  503 
Diarthrosis,  175 
Diastematomyelia,  614 
Diatela,  503 
Dibrachius,  605 
Dicephalus,  606 
Didelphys,  uterus,  403 

Diencephalon     (inter-brain),    425,   437,    444, 
448,  501,  508 

epithalamus,  437,  438,  475,  506 

hypophysis,  437,'  503 

hypothalamus,  437,  438,  448,  50 1,  503 

nuclei  of,  437 

Rathke's  pouch.  501 

sulcus  hypothalamicus,  501 
Monroi,  501 

thalamus,  437,  448,  475,  506 
Digits,  beginnings  of,  115,  121 

defects  or  absence  of,  619 
Diploid  number  of  chromosomes,  n,  16 
Diprosopus,  606 

diophthalmus,  606 

monostomus,  606 

tetrophthalmus,  606 

triophthalmus,  606 
Dipygus  parasiticus,  605 
Discoidal  placenta,  578 
Disse,  concerning  olfactory  nerve,  551 
Diverticulum  of  Nuck,  392 
Dollinger,  XIII 
Dorsal  flexure,  112,  115 

mesogastrium,  348 

septum  of  spinal  cord,  480 
Dorso-,  lateral  plate,  see  Alar  plate 
Double  heart,  255 
Driesch,  concerning  potentiality  of  germ  cells, 

612 

"Dry"  labor,  581 
Ducts,  allantoic,  306,  582 

alveolar,  335 

cochlear,  556 

Cuvier's,  191,  220,  222,  343 

cystic,  315 

deferent,  386 

ejaculatory,  386 

endolymphatic,  553 

hepatic,  315 

lacrymal,  549 

mesonephric,  356,  370 

Mullerian,  369,  383,  387 

of  the  epididymis,  386 


636 


INDEX 


Ducts,  oviduct,  384 

pronephric,  354,  355 

reuniens.  556 

Santorini's,  320 

seminiferous,  372 

Steno's  296 

thoracic,  244,  248 

thyreoglossal,  300 

utriculosaccular,  556 

Wharton's,  297 

Wirsung's,  320 

Wolffian,  356 
Ductule,  aberrant,  387 

efferent,  387 
Ductus  arteriosus,  207,  212,  236 

choledochus,  315 

pleuro-pericardiacus,  352 

venosus,  225,  229 
Duodenum,  the,  306,  307 

change  of  position  of,  350 
Duplicate  monsters,  601 

asymmetrical  duplicity,  608 

Marchand's  scheme  of,  601 

symmetrical  duplicity,  602 

teratoid  tumors,  604 

true  parasitic  duplicity,  608 
Duplicity  incomplete,  606 

Ear,  420,  427,  437,  476,  552 
anomalies  of,  561,  617 
cochlea,  430 

Corti's  organ,  430,  437,  528,  557 
external,  552,  560 
internal,  552 
labyrinth.  430 
middle,  552,  559 
Ear,  inner, 

acoustic  nerve,  558 
atrium,  553 
auditory  pit,  552 

placode,  552 

vesicle  (otocyst),  552,  553 
cells  of,  558 
cochlear  pouch,  553 
ducts  of,  556 

endolymphatic  appendage  of,  553 
fenestra  cochleae  (rotunda),  557 

vestibuli  (ovalis),  557 
membrana  tectoria,  558 
organ  of  Corti,  557 
perilymph,  556 
perilymphatic  space,  556 
saccule,  556 


Ear,  scala  media,  556,  557 
tympani,  556,  557 
vestibuli,  556,  557 

semicircular  canals  of,  553 

spiral  lamina,  557 

utricle,  556 

vestibular  membrane  (of  Reissner),  557 

pouch,  553 
Ear,  middle,  559 

Eustachian  tube,  560 

incus,  559 

malleus,  559 

mastoid  cells,  560 

stapes,  559 
Ear,  outer,  560 

anthelix,  561 

antitragus,  561 

auricle,  561 

external  auditory  meatus,  114,  560 

helix,  561 

lobule,  561 

tragus,  561 

tubercles  of,  561 

tympanum,  561 
Ectoderm, 

in  Amphioxus,  38,  40,  46 

in  the  chick,  70,  71,  72,  74,  75,  76 

in  frog,  57,  58,  60 

in  Mammals;,  88,  90,  92,  108 

in  man,  101,  102,  104,  105 
Ectopia  cordis,  179,  255,  352,  618 

vesicae,  618 

viscerum,  618 

of  the  kidneys,  399 
Ectopic  gestation,  32 
Ectoplasm,  138 

Edinger,  concerning  the  oral  sense,  438 
Effectors,  418,  421,  427 
Efferent  ductules,  386 

peripheral  nerve  fibers,  422 

peripheral  neurones,  417,  427,  456  to  459 

root  fibers,  456 
Egg  (see  ovum) 

nests,  378 

cords,  Pfliiger's,  378 
Egg-cylinder,  91,  92 
Eggs,  centrolecithal, 

meiolecithal,  5 

mesolecithal,  5 

poly leci thai,  6 

Eigenmann,  concerning  sex  cells,  374 
Ejaculatory  duct,  386 
Embryo,  118 


INDEX 


637 


Embryo,  age  of,  1 23 

length  of,  1 23 

weight  of,  124 
Embryonic  ccelom,  340 

connective  tissue,  135 

disk  (see  also  Germ  disk),  89,  93,  94,  95,  96, 

97,  1 08 
Enamel  organ,  292 

prisms,  293 

pulp,  293 

Encephalocele,  613 
Encranius,  608 

End-brain  (telencephalon) ,  425,  437,  508,  531 
Endocardium,  origin  of,  196 
Endolymphatic  duct,  553 

sac,  553 

Endomysium,  280 
Endothelium,  186,  237 
Engastric  (intraabdominal)  parasites,  609 
Enteroccel,  43 
Entoderm, 

of  Amphioxus,  38,  40,  46 

of  the  chick,  70,  71,  72,  74,  75,  76 

of  the  frog,  57,  78,  60,  61 

of  Mammals,  88,   89,  90,  91,  92,  95,  96, 
97,  108 

of  man,  101,  102,  103,  104,  105 
Entodermal  tube,  285 
Entrance  plug,  584 
Entypy  of  germ  layers,  89,  90 
Enveloping  layer,  see  Covering  layer  (tropho- 

derm),  85,  103,  107 
Eparterial  bronchial  ramus,  335,  338 
Ependyma  cells,  451 
Epiboly,  39,  57,  58,  73,  89 
Epicanthus,  616 
Epichordal  brain,  lateral  series  of  nuclei  of, 

457,  458 

medial  series  of  nuclei  of,  457,  458 
Epichordal  segmental  brain  and  nerves,  427, 

429 

Epicondyles,  168 
Epidermis,  the,  407 

epitrichium  of,  407 
periderm  of,  407 
stratum  corneum,  408 

germinativum  of,  407 
granulosum,  407 
lucidum,  408 

Epididymis,  anomalies  of,  402 
appendage  of  the,  386 
duct  of,  386 
Epigamous  determination  of  sex,  382 


Epigenesis,  doctrine  of,  XIII 
Epiglottis,  331 
Epignathus,  608,  610 
Epimysium,  280 
Epiphyses  of  vertebrae,  151 
Epiphysis  of  bone,  144 

(pineal  body),  424,  437,  503 
Epiploic  foramen,  348 
Epispadias,  402 
Episternal  cartilages,  153 
Epistropheus,  (the  axis),  152 
Epithalamic  region,  see  Epithalamus 
Epithalamus,  437,  438,  475,  506 
Epitrichium,  407 
Eponychium,  the,  410 
Epoophoron,  the,  385 
Erythroblasts,  239 
Erythrocytes,  239 
Eternod's  embryo,  109,  no,  443 
Ethmoidal  labyrinth,  160 
Eustachian  tube,  560 
Exencephaly,  613 
Exoccipital  bone,  158 
Exocoelom,  101,  104,  105,  108 
External  auditory  meatus,  origin  of,  114,  560 

ear,  first  appearance  of,  114 

form   of   the    body,    age    and    length    of 

embryos,  107,  123 
development  of,  107 
extremities,  121 
branchial  arches,  face,  neck,  112,  118 

geniculate  bodies,  see  Geniculate  bodies 

genital  organs   (see   also  Genital  organs, 
external),  393 

genitalia,    first    appearance  of,    117,  393 

influences  as  affecting  monsters,  620,  621 
Extraembryonic  body  cavity  (see  exocoelom) 
Extra  ventricular  cell-divisions,  455 
Extrauterine  gestation,  583 
Extremities,  development  of,  121 

lower,  fused,  619 

malformations  of,  6 18,  619 

muscles  of  the,  272 

nerve  supply  of,  273 

one  or  more  abnormally  small  but  well 
formed,  619 

one  or  more  defective,  619 

one  or  more  wanting,  619 

rotation  of,  122 
Eye,  113,  420,  427,  429>  43°,  437.  476,  533 

anomalies  of,  561,  616 

anterior  chamber,  548 

ciliary  body,  547 


638 


INDEX 


Eye,  chorioid,  545 

cornea,  548 

first  indication  of  formation  of,  534 

formation  of  muscles  of,  271 

general  development  of,  533 

influence  on  nervous  system,  429 

innervation  of  muscles  of,  432 

iris,  547 

lens,  535 

muscles  of,  430 

optic  cup,  536,  539 
depression,  533 
nerve,  546 

retina,  540 

sclera,  545 

vitreous,  545 
Eyelashes,  548 
Eyelids,  548 

Fabricus  ab  Aquapendente,  XIII 
Face,  development  of,  118,  549 

malformation  of,  616 
Facial  cleft,  oblique,  629 
Facialis,  VII,  nerve,  432,  434 
Factors  (genes,  in  heredity),  9 
"Faecal  fistula,"  581 
Fallopian  tube,  24 
Falx  cerebri,  512 
Fascia,  135 

dentata,  439,  518 
Fasciculi,  see  Tracts 
Fasciculus  cortico-spinal,  441 

cuneatus,  see  Columns  of  Burdach 

dorsal  spino-cerebellar,  441 

frontal  cortico-pontile,  441 

gracilis,  see  Columns  of  Gott 
Fasciculus  mammillo-tegmental,  507 

medial  longitudinal,   436,  474,  481,  486 

occipital  cortico-pontile,  4/11 

retroflexus  of  Meynert,  508 

solitarius,  see  Tractus  solitarius 

temporal  cortico-pontile,  441 

thalamomammillary,  507 

ventral  spino-cerebellar,  441 
Fat,  developing,  136 
Feet,  malformations  of,  619 
Female  pronucleus,  28 
Femur,  172 
Fenestra  cochleae,  557 

vestibuli  (ovalis),  557 
Fertilization,  27 

in  the  frog,  50 

of  human  ovum,  32 


Fertilization  in  mammals,  30,  32,  84 

membrane,  31 

in  the  sea-urchin,  28,  29 

significance  of,  33 

in  the  star-fish,  29 

time  and  place  of,  31 
Fertilized  ovum,  27 
Fibers,  afferent  peripheral  nerve,  421 

afferent  root,  421,  460 

arcuate  (external),  485 
(internal),  478,  485 

association    (see   also    Cells,    association), 
526 

connective  tissue,  134 

cortico  pontile,  see  Cortico  pontile  fibers 

cortico-spinal,  see  Tracts,  pyramidal 

efferent  peripheral  nerve,  422,  456 
ventral  root  fibers,  456 

muscle,  263 

nerve,  various  views  concerning  develop- 
ment of,  463,  464 

neuroglia,  453 

olivo-cerebellar,  436,  491,  499 

projection    (ascending    and    descending), 
440,  516,  525,  529 

visceral  (splanchnic),  457,  461 
Fibrillar  connective  tissue,  134 
Fibrillogenous  zone,  454 
Fibrils,  connective  tissue,  134 
Fibroblasts,  135 
Fibula,  172 
Filia  olfactoria,  472 
Fillet,  lateral,  436,  441,  493,  500 

medial,  436,  441,  490,  491.  500,  507,  527 
Filum  terminale,  482 
Fimbria,  518 
Fimbriae,  384 

Fingers,  development  of,  115,  121         . -: '•-. 
Fissure,  anterior  arcuate,  510 

calcarine,  524 

callosal,  521 

central,  524 

great  longitudinal,  512 

of  Rolando,  524 

of  Sylvius,  523 

parieto-occipital,  524 

posterior  arcuate,  518 

prima,  of  His,  510 

primary,  of  cerebellum, 

secondary,  of  cerebellum,  496 

rhinal,  medial  and  external,  510 

ventral  longitudinal,  480 
Fissures  of  cerebral  hemispheres,  512 


INDEX 


639 


Flechsig,    concerning    myelogenetic    areas    of 

pallium,  528,  529 
Flechsig's  tract,  441,  482 
Flexure,  cephalic,  no,  115 
dorsal,  112,  115, 
sacral,  112,  115 
Flocculi,  496 

Floor  plate  (ventral  median  plate),  423 
Fcetal  inclusion,  608 
membranes,  363 
allantois,  570 
amnion,  563 
chorion,  571 
earlier  stages  in  Mammals,  compared 

with  chick,  572 
function  of,  563 
in  Birds,  563 
in  Mammals,  571 
in  man,  579 
in  Reptiles,  563 

references  for  further  study  of,  599 
serosa,  571 
Fostus,  the,  118 
in  fcetu,  608 

papyraceus,  603 

Follicle,  Graafian,  rupture  of,  24,  380 
Fontanelles,  162 
Foot,  development  of,  115,  121 
Foramen  caecum  linguae,  290,  300 
of  Magendie,  483 
of  Monro,  501,  509,  512,  516 
of  Winslow,  348 
ovale,  203,  236 
transversarium,  153 
Foramina  of  Luschka,  484 
Fore-arm,  115,  121 

Fore-brain  (prosencephalon) ,  424,  427,  437 
anterior  (cerebral)  commissure,  424 
chiasma  eminence,  424 
commissura  habenularis,  425 
corpora  striata,  425 
diencephalon,  437 
epiphysis  of,  424 
ganglia  habenulae,  425 
infundibulum,  424 
lamina  terminalis  of,  424 
pallium,  425 
paraphysis  of,  424 
pineal  body,  424 
processus  neuroporicus,  424 
recessus  postopticus,  424 

praeopticus,  424 
rhinencephalon,  425,  437 


Fore-brain,  velum  transversum,  424 
Forel's  decussation,  487 

Form  of  the  body,  development  of  the  external, 
107 

general,  107 
Formatio  reticularis,  435,  481,  485,  488 

alba,  486 

grisea,  486 
Fornix,  anterior  pillars  (columns),  446,  507,  521 

body  of,  521 

commissure,  520 

longus,  522 

posterior  pillar  (columns),  518,  521 

psalterium,  520 

Forster,  concerning  malformations,  601 
Fossa,  nasal,  114 

oral,  no,  in,  118,  119 
Fossa  Sylvii,  509,  510,  522 
Frenulum  linguae,  297 
Fretum  Halleri,  200,  206 
Frog,  cleavage  in,  51,  53 

early  development  of,  49 

gastrulation  in,  55,  56,  57 

mesoderm  formation  in,  59,  60,  61 

ovum  of,  3,  49 
Frontal  bone,  162 

lobe,  512 
Froriep,  concerning  acustico-facialis  ganglion, 

56i 
Funiculus,  dorsal  (posterior)  or  posterior  white 

column,  460,  473,  477 
lateral,  481 
teres,  494 
ventral  (anterior)  or  ventral  white  column, 

477 

ventro-lateral,  477 
Furcula,  the,  331 

Galea  capitis,  6,  15 
Gall  bladder,  315 
Ganglia,  cerebrospinal,  421 
sympathetic,  ciliary,  471 
otic,  471 
peripheral,  461 
prevertebral,  461 
sphenopalatine,  471 
submaxillary,  471 
vertebral,  461 
visceral,  429,  457 
Ganglion,  acoustic,  558 
acustico-facialis,  561 
cochlear,  469,  561 
Gasserian,  430,  470 


640 


INDEX 


Ganglion,  geniculate,  468,  561 

habenulae,  425,  503 

interpeduncular,  508 

nodosum,  465 

petrosum,  465 

Scarpa's,  469,   (see  also  Nerves,  cranial 
VIII} 

semilunar,  430,  470 

spinal,  460 

spirale,  469,  562 

vestibular,  469,  561 
Gartner,  canals  of,  386 

Gasserian  ganglion,  peripheral  branches  of,  430 
Gastrointestinal  tract,  development  of  glands 
in,  312 

histogenesis  of  the,  311 

lymph  follicles  of,  312 

mucous  membrane  of,  311 
Gastroschisis,  282 

completa,  618 

Gastrothoracopagus  dipygus,  605 
Gastrula,  38,  39,  40,  57,  58 

rotation  of,  61,  62 
Gastrulation, 

in  Amphioxus,  38,  39 

in  the  chick,  70,  71,  72,  73,  76 

in  the  frog,  55,  56,  57,  61,  62 

in  Mammals,  88 
Geniculate  bodies,  lateral  (external),  440,  441, 

475,  503,  525,  527,  546 
medial  (internal),  440,  441,  507,  525 
Geniculate  ganglion,  468 
Genital  cord,  389  - 
folds,  394 
glands,  the, 

changes  in  the  position  of,  387 
development  of  the  ligaments  of,  387 
Genital  glands,  differentiation  of,  375 
ducts  of,  383 
migration  of,  389 
stroma  of,  374 
organs,  external,  393 

first  appearance  of,  117,  393 
(female),  clitoris,  394 
glans  clitoridis,  394 
labia  rnajora,  394 

minora,  394 
prepuce,  394 
vestibulum  vaginae,  394 
(male),  penis,  394 
prepuce,  394 
raphe,  396 
scrotum,  396 


Genital  organs,  (male),  urethra,  394 
ridge,  359,  464,  393 

swellings,  394 

tubercle,  the,  394 
Gennari,  line  of,  527 
Genu  facialis,  487 

Germ  cell  organization,  significance  of,  9 
Germ  cells,  i 

female,  i 
male,  i,  6 

hill,  24,  380 

layers,  in  Amphioxus,  38,  42 

in  the  chick,  70,  77 

in  the  frog,  55,  59 

in  mammals,  88,  93 

in  man,  99 

ring,  38,  54,  55 

wall,  69,  70,  71,  72,  75 
Germinal  epithelium,  374 

cells  of,  374 

rete  cords  of,  374 

sex  cords  of,  375 
Giant  glomeruli,  369 
Gianuzzi,  crescents  of,  298 
Gill  arches,  musculature  of,  280,  429 
Gill-cleft  organs,  422 
Gills,  influence  on  nervous  system,  429 
Giraldes,  organ  of,  387 
Glands,  accessory  thyreoid,  301 

anterior  ligual,  297 

Bartholin's,  373 

Brunner's,  311 

bulbo-urethral,  373 

carotid,  399 

coccygeal,  254 

Cowper's,  373 

duodenal,  311 

Ebner's,  291 

formation  of,  311 

hsemolymph,  251 

indifferent  (genital),  377 

lacrymal,  548 

lingual,  291 

liver,  314 

lymph,  249 

mammary,  412 

Meibomian,  548 

of  Mall,  548 

parotid,  297 

prehyoid,  301 

salivary,  296 

sebaceous,  412 

sublingual,  297 


INDEX 


till 


Glands,  submaxillary,  296 

sudoriferous,  412 

suprahyoid,  301 

suprarenal,  396 

sweat,  412 

thymus,  302 

thyreoid,  300 

uterine,  385 

vestibular,  373 
Glans  clitoridis,  394 

penis,  394 
Glia,  see  Neuroglia 
Glisson,  capsule  of,  315,  344 
Glomeruli  of  kidney,  363,  364 
Glomus  caroticum,  304,  399 

coccygeum,  254 
Glossopalatine  arch,  299 
Glossopharyngeus,  IX,  nerve,  432 
Goll,  column  of,  429,  441,  482,  488 

nuclei  of  columns  of,  429,  436,  437,  490 
Graafian  follicle,  23,  24,  378,  379 

de  Graaf's  description  of,  XIII 

primary,  377,  378 
Graf  v.  Spec's  ovum,  101,  102,  109 
Granules,  keratin,  409 
Gray  column  (dorsal  or  posterior),  428 
(ventral  or  anterior),  428,  477 

matter  of  cord  and  segmental  brain,  474 
Gray  ramus  communicans,  462 
Ground  bundles  of  the  cord,  435,  474,  477,  479, 

486,  488 
Growth  of  bones,  144 

intracartilaginous,  144 

long,  144 

Gubernaculum  tfcstis,  388,  389 
Gurwitsch,  concerning  peripheral  nerves,  463 

concerning  the  myelin  sheath,  464 
Gustatory  area,  528 

system,  422,  430 

Gyri,  transverse  of  temporal  lobe,  527 
Gyrus  ambiens,  511 

dentatus,  439,  518,  521 

olfactorius  lateralis,  511 

semilunaris,  511 

subcallosus,  522 

Habenula,  503 
Hsemangiomata,  415 
Haemoblasts,  237 
Haemoglobin,  238,  239 
Hsemolymph  glands,  251 
Haemopoiesis,  236 

views  concerning,  236 
41 


Haemopoiesis,  views  concerning,  monophyletic, 

236 

polyphyletic,  236 
Hair,  the,  410 

anomalies  of,  415 
cells,  556,  558,  559 
connective  tissue  follicle  of,  410 
germs,  410 
Henley's  layer,  410 
Huxley's  layer,  410 
lanugo,  the,  410 
papilla,  410 
shaft,  410 
Hamatate,  169 
Hammar,  concerning  the  tuberculum  impar, 

290 
Hands,  development  of,  114,  121 

malformations  of,  619 
Haploid  number  of  chromosomes,  12,  16 
Hardesty,  concerning  development  of  neurog- 

lia,  449 

Hare-lip,  166, 180,  616,  617 
Harrison,  concerning  neurilemma  cells,  463 
Hartman,  concerning  cleavage,  87 
Harvey,  XIII 
Hassan's  corpuscles,  303 
Haversian  canals,  143 
lamellae,  143 
spaces,  143 

Head,  beginning  of,  no 
amniotic  fold,  564 
fold,  82 

process  (primitive  axis),  74,  76,  77,  82,  97 
skeleton,  154 

anlagen  of,  155,  157 

anomalies  of,  179 

bones  derived  from  the  branchial  arches, 

162 

cartilage  of,  155 

cartilaginous  primordial  carnium,  156 
chondrification  of,  155 
chondrocranium,  157 
diagram  of  skull  of  new-born  child,  161 
membrane  bones  of  the  skull,  160 
ossification  of  the  chondrocranium,  158 
periotic  capsule,  157 
table  showing  types  of  development  of 

bones  of,  166 
somatic  musculature  of  (eye,  tongue),  in- 

nervation  of,  432 
volume  of,  125 
Heart,  the,  no,  in,  196 
anomalies  of,  254 


642 


INDEX 


Heart  beat,  209 

changes  after  birth,  206 

development  of,  196 

double,  254 

interventricular  furrow,  200 

migration  of,  342,  345 

muscle,  histogenesis  of,  280 

origin  of,  196 

papillary  muscles  of,  206 

septa  of,  202 

sinus  venosus,  191,  201 

valves,  205 
Held,  concerning  early  development  of  neuro- 

fibrils,  454 
Helix,  561 

Hemicrania,  612,  613 
Hemispheres,    cerebral,    427,    440,    444,    508, 

5ii,  530 

of  cerebellum,  496 
Henle's  layers,  410 

loop,  364 

Hensen,    concerning    peripheral    nerves,    464 
Hensen's  cells,  558 

node,  74,  75,  77,  93,  97 
Hepatic  cords,  318 
Hepatoduodenal  ligament,  350 
Hepatogastric  ligament,  350 
Heredity,  9,  20,  33,  34 
Heredity,  important  factor  in  teratogenesis,  620 

in    relation    to    anomalies    of    muscular 
system,  283,  284 

influence  of,  in  albinism,  415 
Hermaphroditism,  404 

bilateral,  404 

false,  404 

feminine  false,  404 

lateral,  404 

masculine  false,  404 

true.  404 

unilateral,  404 
Hernia,  diaphragmatic,  352 

umbilical,  581 
Herrick,  concerning  the  gustatory  tracts,  438 

concerning  gustatory  pathway,  489 
Hertwig,    concerning    duplicity    from    double 
gastrulae,  608 

concerning  the  mammary  gland.  413 

concerning  spina  bifida,  615 

on  production  of  monsters,  622 
Heteromeric  column  cells,  473 
Hind-brain  (metencephalon),  425 
Hippocampal  fissure,  518 

formation,  439,  513,  518,  522 


Hippocampus  major,  518,  522 

His,  concerning  angulus  praethalamicus,  510 

concerning  germinal  cells.  449 

concerning  limbus  corticalis  and  medul- 
laris,  512 

concerning  neuro blasts,  455 

concerning  olfactory  nerve,  551 

concerning  peripheral  nerves,  464 

cylinder  furrow  of,  479 

marginal  furrow  of,  479 

trapezoid  area  of,  511 

Hochstetter,  concerning  the  bucco-nasal  mem- 
brane .  549,  550 
Holorachischisis,  613 

Horns,  anterior  (ventral  gray  column),  428,  477 
Horseshoe  kidney,  399 
Howslip;s  lacunae,  140 
Huber,  concerning  cleavage,  85 
Humerus,  168 

Hunteri,  gubernaculum,  389 
Huxley's  layer,  410 
Hyaloid  canal,  546 

membrane  of  vitreous,  546 
Hydatid  of  Morgagni,  384 

non-stalked,  384 
Hydramnios,  580 
Hydrencephalocele,  613 
Hydrencephaly,  613 
Hydrocephaly,  congenital,  613 
Hydromeningocele,  613 
Hydromicrencephaly,  613 
Hymen,  the,  385 

anomalies  of,  404 
Hyoid,  165 

arch,  434 

Hyperkeratosis,  414 
Hypermastia,  415 
Hyperthelia,  415 
Hypertrichosis,  415 
Hypochordal  bar,  152 
Hypoglossus,  XII,  nerve,  432,  485 
Hypophyseal  pouch,  501 
Hypophysis,  437,  503 
Hypospadias,  402 

Hypothalamic  region,  see  Hypothalamus 
Hypothalamus,  437,  438,  448,  501,  506 
Hypotrichosis,  415 

Ichthyosis,  414 
Identity  of  chromosomes,  21 
Idiochromosomes,  16 
Ilium,  the,  171 
Imperforate  hymen,  404 


INDEX 


643 


Incisive  bone,  163 
Incisura  prima,  510 
Incus,  165,  559 
Indifferent  glands,  377 

anomalies  derived  from,  404 

stage,  diagram  showing,  393 

table  showing  structures  derived  from, 

393 

structures,  374 
Indusium  griseum,  521 
Infracardiac  ramus,  336 
Infundibular  process,  502 
Infundibulum,  424,  448,  501 
Inguinal  ligament,  388 

ring,  the,  390 
Iniencephaly,  613 
Inner  cell  mass,  85,  87,  89,  103,  107 

layer  of   neural   tube,  455,  472,  484,  497, 

500,  512,  524 
Innominate  artery,  212 

bone,  171 

veins,  223 

Insula  (island  of  Reil),  522 
Integumentary  system,  the,  407 

anomalies  of,  414 

glands  of  the  skin,  412 

hair.  410 

nails,  409 

skin,  407 

Inter-brain    (diencephalon),   see   Diencephalon 
Intercarotid  ganglion  399 
Intercellular  substance,  origin  of,  133 
Intermediary  plexus  of  lymph  glands,  250 
Intermediate  areas  of  Flechsig,  528 

cell  mass,  80,  98,  131,  354 

(medullary)  layer  of  telencephalon,  512 

plate,  4 79 ,  481 

Intermuscular  connective  tissue,  279 
Internal  capsule  of  fore-brain,  442,  507.  515,  516 
528 

geniculate  bodies,  see  Geniculate  bodies 
Interrenal  organs,  398 
Interventricular  furrow,  200 
Intervertebral  fibrocartilage.  148,  152 
Intervillous  spaces,  595 
Intestinal  crypts  of  Lieberkuhn,  312 

region,  286 

tract,  colon,  307,  309 
duodenum,  307 

mesenterial  small  intestine,  307 
vermiform  appendix,  310 

umbilicus,  569 
Intestine,  the,  306 


Intestine,  anomalies  of,  326 

crypts  of  Lieberkuhn.  312 

loops  of,  307,  308 

villi  of,  312 

Imagination,  38,  39,  56,  57,  71,  72,  73,  89 
Inversion  of  germ  layers,  89,  90,  91,  93 
Involution,  38,  39,  40,  57,  58,  70,  73,  89 
Iris,  547 

defective  pigmentation  of,  415 
Ischiopagus,  604 

parasiticus,  605 
Ischiothoracopagus,  605 
Ischium,  the,  171 
Island  of  Reil,  522 
Islands  of  Langerhans,  323 
Isthmus,  425,  483 
Iter,  see  Aquaductus  Sylvii 

Jacobson's  organ,  551 
Janus  asymmetros,  606 

symmetros,  606 
Jaws,  malformations  of,  606,  607 

splanchnic    musculature,    innervation   of, 

432,  434 
Johnston   concerning  mesencephalic  root  of  V, 

493 

concerning  the  optic  recess,  501 
Joint  capsule,  175 

cavity,  175 
Joints,  173 

diarthrosis,  175 

synarthrosis,  174 

synchondrosis,  174 

syndesmosis,  174 
Jugular  lymph  sac,  244,  247 

Kallius,  concerning  the  mammary  gland,  412 

Karyolysis,  239 

Karyorrhexis,  239 

Keibel,    concerning   origin   of   endolymphatic 

appendage  in  the  chick,  553 
Keratin  granules,  409 
Kidney,  the,  361 

anomalies  of,  396 

Bowman's  capsule,  365 

capsule  of,  368 

changes  in  position  of,  369 

columns  of  Bertini,  367 

congenital  cysts  of,  400 

convoluted  tubule   Henle's  loop  of,  364 

cortex  of,  368 

derivation  of.  361 

floating,  40x3 


644 


INDEX 


Kidney,  glomeruli  of,  363 

and  blood  vessels  of,  364 
hilus  of,  367 

Malpighian  pyramids  of,  367 
medulla  of,  368 
metanephric  blastema  of,  362 
migration  of,  369 
movable,  400 
nephrogenic  tissue  of,  362 
relation  to  suprarenal  gland,  398 
renal  columns  of,  367 
corpuscle  of,  367 
papillae  of,  363,  368 
pelvis,  361 
pyramids  of,  367 
tubules  of,  convoluted,  363 

straight,  362 
ureter,  361 
Kidney,  urinary  function  of,  369 

Knomer,    H.    McE  ,    on    production    of 

monsters  in  single  embryos,  622 
Kclliker,  XIV 

concerning  formation  of  incisive  bone.  164 

Krause,   concerning   origin  of  endolymphatic 

appendage  in  chick  and    Amphibia, 

553 

Kupffer,  v.,  concerning  the  acoustic  ganglion, 

558 

concerning  the  differentiation  of  the  neu- 
ral tube,  423 

concerning  olfactory  placodes,  549 

• 
Labia  majora,  394 

minora,  394 
Lacrymal  bone,  162 

duct,  549 

glands,  548 
Lacunae,  139 
Laloo,  605 
Lamellae,  Haversian,  143 

interstitial,  143 
Lamina  affixa,  520 

cribrosa  (of  eye),  547 
(of  nose),  1 60 

infrachorioidea,  517,  518 

lateral  pterygoid,  162 

medial  pterygoid,  161 

perpeiidicularis,  160 

terminalis,  414,  509,  517 
Langerhans,  islands  of,  323 
Langhan's  layer,  589 

outgrowths  from  590 
Lanugo,  the,  410 


Laryngeal  pouch,  331,  338 
Larynx,  the,  331 

anomalies  of,  338 

cartilages  of,  332 

development  of,  165,  331 
Lateral  geniculate  bodies,  see  Genicidate  bodies 

lemniscus,  436 

line  cranial  nerves,  432 
organs,  421,  422,  430,  432 

nasal  process,  1 20 

plates  (of  neural  tube),  423 

recesses  of  fourth  ventricle,  483 
Lecithin,  3 

Leg,  development  of,  117,  121 
Lemmocytes,  462 
Lemniscus,  lateral,  see  Fillet,  lateral 

medial,  see  Fillet,  medial 
Length  of  embryos,  122 
Lens,  535 
anterior  epithelium  of,  537 

area,  535 

capsule,  539 

fibers  of,  537 

hyaloid  artery  of,  539 

invagination,  535 

membrana  pupillaris  of,  539 

tunica  vasculosa  of,  539 

vesicle,  535 
Leucocytes,  239 
Lewis,  concerning  anomalies  of  pancreas, 

327 

Lieberkiihn,  crypts  of,  312 
Life  cycle,  complete,  in  the  female,  380 

complete,  in  the  male,  382 
Ligaments,  broad,  of  the  uterus,  392 

costo- vertebral,  152 

diaphragmatic  of  the  mesonephros,  388 

hepatoduodenal,  350 

hepatogastric,  350 

inguinal,  388 

middle  umbilical,  371,  583 

origin  of  fibers  of,  135 

ovarian,  392 

round,  of  liver,  230 
of  uterus,  392 

sphenomandibulor,  164 

stylohyoid,  165 

suspensory  of  the  lens,  548 

umbilical,  217 
Ligamentum  arteriosum,  209,  212,  236 

coronarium  hepatis,  346 

suspensorium  (falciforme)  hepatis,  346 

teres  hepatis,  346 


INDEX 


Limb  buds,  differentiation  of.   113,  114,  117, 

121,  273,  275 
Limbus  corticalis  of  His,  512 

fossae  ovalis,  205 

medullaris,  512 
Lingual  glands,  291 

papillae,  290 

tonsils.  299 
Lingula  (of  cerebellum),  496 

(of  sphenoid),  159 
Lip,  clefts  of,  164,  180,  616,  617 

lower,  origin  of,  119,  121 

upper,  origin  of,  119.  121 
Liquor  amnii,  566 

folliculi,  379 
Liver,  the,  314 

anomalies  of,  326 

bile  capillary  of,  318 

capsule  of  Glisson,  315 

cells  of,  318 

circulation  of,  315 

ducts  of,  315 

gall  bladder  of,  315 

growth  of,  318 

hepatic  cylinders  of,  316 

histogenesis  of,  318 

lobe  of  Spigelius,  318 

lobes  of,  317 

pars  hepatica  of,  314 
cystica  of,  314 

round  ligament  of,  230,  318 

vasa  aberrantia  of,  319 

veins  of,  229,  317 
Lobus  pyriformis,  439,  511 
Loeb,     concerning    production    of    monsters, 

622 

Longitudinal  fasciculus,  medial,  436 
Lordosis,  612 
Lower  extremities,  171 
Lumbar  enlargement,  429 
Lunate  bone,  167 
Lung  groove,  330 
Lungs,  the,  334 

anomalies  of,  338 

atria  of,  335 

changes.in,  at  birth,  337 

ducts  of,  335 

eparterial  bronchial  ramus  of,  335,  338 

influence  on  nervous  system,  429 

lobes  of,  335 

weight  of,  337 
Lunula,  the,  410 
Luschka,  foramina  of,  484 


Lymph,  origin  of,  252 
follicles,  253 

of  gastrointestinal  tract,  3*13 
of  tonsils,  299 
glands,  the,  249,  314 
hearts,  243,  244,  246 
sacs,  243,  244,  246 
Lymphangiomata,  415 
Lymphatic  system,  the,  242 
glands  of,  249 
glomus  coccygeum,  254 
hgemophoric  function  of,  248 
spleen,  252 
thymus  gland,  254 

views  concerning,  242 
Lymphocytes,  229 

primitive,  237,  238 

MacBride,  concerning  gastrulation,  40 

Macromeres,  38,  54,  68 

Macrostomus,  617 

Macula  acustica,  559 
lutea,  542 

Magendie,  foramen  of,  483 

Male  pronucleus,  28 

Malformation   involving   one    individual    (see 
Monsters},  612 

Malformations  of  more  than  one  individual  (see 
Duplicate  monsters),  601 

Mall,  concerning  development  of  the  maxilla, 

163 

concerning  development  of  pyramids,  525 
concerning  ossification  of  incisive  bone, 

163 

formulae  for  estimating  age  of  embryos,  1 23 
on  faulty  implantation  of  the  ovum,  621 
Malleus,  165,  559 
Malpighian  corpuscle,  357 

pyramids,  367 

Mammalian  development,  early,  84 
ovum,  84 

cleavage  of,  85 
Mammary  gland,  the,  412 
anomalies  of,  415 
areolar  glands  of,  413 
colostrum  corpuscles,  414 
growth  of,  in  female,  413 
growth  of,  in  male,  413 
nipple,  413 
of  pregnancy,  413 
Mammillary  bodies,  503 

region,  448,  503 
Mandible,  164 


646 


INDEX 


Mandibular  process,  112,  118,  119,  287 

layer  of  neural  tube,  455,  472.  484,  497, 

500,  512,  524 
Manubrium  sterni,  154 

Marchand's    fusion    theory    of    symmetrical 
duplicity,  607 

scheme  of  duplicate  monsters,  60 1 
Marginal  furrow  of  His,  479 

layer  of  neural  tube,  449, 484, 497,  500,  512 
Mark  and  Long,  concerning  maturation,  18 
Marrow,  145 

cavity,  primary,  141 

formation  of  blood  cells  in,  240 

red,  146 

spaces,  primary,  139 

yellow,  146 

Marsupials,  early  nutritional  conditions  in,  576 
Masculine  false  hermaphroditism,  404 
Massa  intermedia,  505 
Mastoid  process,  159 
Maternal  impressions,  620 
Maturation,  n 

comparison  of  in  male  and  female,  19,  20 

in  mammals,  84 

of  the  ovum,  16 
in  Ascaris,  17 
in  the  mouse,  18 

significance  of,  20 

of  the  sperm,  1 1 
Maxilla  bone,  162 
Maxillary  process,  112.  118,  287 
McMurrich,    concerning    derivation    of    the 
dermis,  408 

concerning  umbilical  cord,  597 
Mechanical  theory  of  monsters,  621 
Meckel's  cartilage,  157,  162.  164 

diverticulum,  308,  581 
Medial  fillet,  see  Fillet,  medial 

geniculate  bodies,  see  Geniculate  bodies 

lemniscus,  see  Fillet,  medial 

longitudinal  fasciculus,  436,  474,  481,  486, 
487 

nasal  process,  120 
Mediastinum  testis,  383 
Medulla  oblongata,  447,  482 

taenia  of,  483 
Medullary  cords,  376,  377 

layer  of  telencephalon,  512,  524 

sheath,  see  Myelin  sheath 
Megakaryocytes,  242 
Megaloblasts.  241 
Meibomian  glands,  548 
Meiolecithal  ova,  5 


Meissner,  plexus  of,  461 

tactile  corpuscles  of,  408 
Membrana  preformativa,  294 

tectoria,  558 

Membrane  bones  of  the  skull,  160 
Mendelian  inheritance,  9 
Mendel's  law  of  segregation,  21 
Meningocele,  613 
Meningoencephalocele,  613 
Menstruation,  25 

relation  to  ovulation,  25 
Merorachischisis,  614 
Mesencephalon  (mid-brain),  424,  445 
Mesenchyme,  133 
Mesenterial  small  intestine,  307 
Mesenteries,  340,  347,  350 

anomalies  of,  352 
Mesentery  of  the  jejunum,  350 
Mesoappendix,  351 
Mesocardium,  dorsal,  196,  342 

ventral,  196,  342 
Mesocolon,  ascending,  351 

descending,  351 

sigmoid,  351 

transverse,  350 
Mesoderm,  derivatives,  from,  1 29 

development  of,  41,  59,  77,  93,  95 
in  Amphioxus,  41,  42,  44,  46 
in  the  chick,  77,  78,  79,  80,  81 
in  the  frog,  59,  60,  61,  64 
in  Mammals,  93,  108 
in  primates,  95,  96 

gastral,  43,  6 1 

parietal,  45,  60,  80,  81,  96,  98.  108 

peristomal,  43,  6 1 

visceral,  45,  60,  80,  81,  96,  98,  108 
Mesodermal  somites,  43,  45,  47,  60,  65,  79    80, 

81,  82,  96,  98,  104,  no 
Mesoduodenum,  350 
Mesogastrium,  dorsal,  304,  347 

ventral,  305,  347 
Mesolecithal  ova,  5 
Mesonephric  duct,  356 

mesentery,  388 

ridge,  355,  358 
Mesonephroi,  atrophy  of,  in  the  female.  385 

in  the  male,  386 
Mesonephros,  356 

Bowman's  capsule,  357 

degeneration  of,  360 

diaphragmatic  ligament  of,  359,  388 

disappearance  of,  360 

function  of,  359 


INDEX 


647 


Mesonephros,  glomerulus  of,  357 

Malpighian  corpuscle  of,  357 

renal  portal  system  of,  360 

significance  of,  360 

tubules  of,  356 
Mesorchium,  376,  389 
Mesorectum,  351 
Mesosalpinx,  386,  392 
Mesothelium,  340,  393 
Mesovarium,  376,  389,  392 
Metacarpals,  169 
Metamerism,  47 
Metanephric  blastema,  362 
Metanephros,  see  Kidney 
Metaplexus,  483 
Metapore,  483 
Metatarsals,  173 

Metathalamic  portion  of  thalamus,  506,  516 
Metathalamus,    see    Metathalamic    portion    of 

thalamus 

Metencephalon  (hind-brain),  425 
Metopic  suture,  180 
Metopism,  180, 
Meyer,  concerning  mesencephalic  root  of,  V, 

493 
Adolf,  concerning  segments  of  segmental 

brain  and  cord,  475,  476 
concerning   suprasegmental  and  segmen- 
tal structures,  420,  427 
Meynert,  solitary  cells  of,  528 
Meynert's  decussation,  500 
Micrencephaly,  613 
Microbrachius,  619 
Microcephaly,  613 
Micrognathus,  325,  617  , 
Micrognathy,  325,  617 
Micromelus,  619 
Micromeres,  38,  54,  68 
Micropthalmia,  561,  616 
Micropus,  619 
Microstomus,  617 

Mid-brain  (mesencephalon),  424,  445 
optic  lobes,  425 
roof,  427,  437 

descending  tracts  to  after-brain  and  cord 

segments,  437 
Middle  peduncle  of  cerebellum,  436,  441,  443, 

493,  5oo 

Milk  ridge,  the,  412 
teeth,  292,  295 

Mimetic  musculature  and  its  innervation,  434 
Minot,  concerning  fcetal  membranes  of  um- 
bilical cord,  597 


Mitoses  (see  also  Cell  proliferation  and  Gemi- 
na!  cells),  449,  484,  489,  500 

extraventricular,  455 

of  neural  tube  cells,  449,  500 
Mitosis,  significance  of,  20 
Mitotic  division  of  sex  cells,  374 
Mitral  cells,  475 
Monobrachius,  619 
Monochorionic  quadruplets,  607 

triplets,  607 

twins  (equal),  602,  603 

(unequal),  603 

Mononuclear  leucocytes,  239 
Monopolar  cells,  455 
Monopus,  619 
Monotremes,  early  nutritional  conditions  in, 

576 

Monro,  foramen  of,  501,  509,  512,  516 
Monsters,  amniotic  adhesions,  619 

causes  underlying  origin  of,  620 

defects  in  region  of  face  and  neck,  and 
their  origin,  617 

defects  in  region  of  neural  tube,  612 
origin  of,  615 

defects   in    the   thoracic   and   abdominal 
regions,  and  their  origin,  618 

in  single  embryos,  622 

malformations  of  extremities,  618 
polysomatous,  621 

production  of  duplicate,  621 
Montgomery,  concerning  areolar  glands,  413 
Morgagni,  hydatid  of,  387 

concerning   development   of   blastomeres, 
618 

concerning    production    of   spina    bifida, 
622 

liquor,  537 

non-stalked  hydatid  of,  384 
Morula,  85,  86,  103,  107 
Mossy  fibers,  500 
Motor  cortex  (see  also  Pallium  precentral  area 

of),  528 
Mouth,  the,  286 

angle  of  the,  119,  287 

anomalies  of,  325 

development  of,  288 

influence    on    nervous    system,    429 

origin  of,  286 
Mucous  tissue,  597 
Mullerian  ducts,  369,  383 

atrophy  of,  387 
Multiple  placentae,  578 
Multiplicity,  605 


648 


INDEX 


Muscle  fibers,  change  of  direction  of,  264 

theories  concerning  internal  structure  of, 

278 

heart,  histogenesis  of,  280 
plates,  132,  263 

tissue,    histogenesis    of    striated    volun- 
tary, 276 

smooth,  280 

Muscles,  branchlomeric,  271 
differentiation  of,  274 
extrinsic,  of  the  upper  extremity, 
anomalies  of,  283 
lattissimus  dorsi,  274 
levator  scapulae,  2  74 
pectoralis,  274 
serratus,  274 
trapezius,  274 
innervation  of,  263 
of  the  extremities,  272 

derivation  of,  272 

derivation   from   premuscle    sheath   of 
muscles  of  lower  extremity,  275 

differentiation   from   mesenchymal   tis- 
sue, 273 

extrinsic  muscles,  274 

migration  of,  275 
of  the  head,  269 

chondroglossus,  272 

constrictor  muscles  of  the  pharynx,  272 

development   and  innervation   of,    271 

digastricus,  271,  272 

epicranius,  272 

glossopalatinus,  272 

laryngeal,  272 

masseter,  271 

mentalis,  272 

muscles  of  the  soft  palate,  272 

mylohyoideus,  271 

obliquus  inferior,  271 
superior,  271 

platysma,  272 

quadratus  labii  superioris,  272 

recti  inferior,  271 
medialis,  271 

recti  superior,  271 

rectus  lateralis,  271 

pterygoidei,  271 

risorius,  272 

stapedius,  272 

sternomastoideus,  272 

stylohyoideus,  272 

stylo-pharyngeus,  272 

tempo ralis,  271 


Muscles  of  tensor  tympani,  271 

veli  palatini,  271 
trapezius,  272 
triangularis,  272 
of  the  trunk,  264 
coccygeus,  269 
geniohyoideus,  268 
intercostales,  267 
levator  ani,  269 
longus  capitis,  267 
longus  colli,  267 
olbiqui  abdominis,  267 
omohyoideus,  268 
perineal,  269 
psoas,  267 
pyramidalis,  268 
quadratus  lumborum,  267 
rectus  abdominis,  268 
capitis  anterior,  267 
sacrospinal,  269 
scaleni,  267 

sphincter  ani  externus,  269 
sternohyoideus,  268 
sternothyreoideus,  268 
transversus  abdominis,  267 

thoracis,  267 

Muscular  system,  the,  262 
anomalies  of,  282 
skeletal  musculature,  262 
visceral  musculature,  262,  280 
Musculature,  hyoid,  271 
skeletal,  262 

diaphragm,  the,  269 
early  character  of,  261 
loss  of  segmental  character,  263,  264 
muscles  of  the  extremities,  272 
of  the  head,  269 
of  the  trunk,  264 
myotomic  origin,  262,  269,  272 
visceral,  280 

mesodermic  origin  of,  280 
Myelencephalon  (after-brain),  425,  482 
Myelin  sheath,  448,  464 
Myeloblasts,  145,  241 
Myelocystocele,  614 
Myelocytes,  145,  241 

Myelogenetic  fields  (areas)  of  Flechsig,  528 
Myelomeningocele,  614 
Myeloplaxes,  145,  241 
Myelospongium,  449,  453 
Myoblasts,  272,  276 
Myocardium,  197,  280 
Myoccel  (ccelom),  46,  80,  340 


INDEX 


C.19 


Myo tomes,  46,  131,  263 

alternation  of,  with  vertebrae,  148,  264 
change  of  direction  in  fibers  of,  264 
degeneration  of,  264 
differentiation  of,  264 
fusion  of,  264,  283 
longitudinal  splitting  of,  264,  283 
migration  of,  264,  283 
tangential  splitting  of,  264,  283 

Naevi  pigmentosi,  415 
Nail  groove,  409 

wall,  409 
Nails,  the,  409 

epitrichium  of,  410 
eponychium  of,  410 
lunula  of,  410 
migration  of,  409 
replacement  of,  410 
Nanocephaly,  613 
Nares,  outer,  550 
posterior,  550 
Nasal  bone,  162 

cavity  (nostril),  120 
conchae,  550 
fossae,  559 
pit,  120,  288,  559 
process,  lateral,  120 

medial,  120 
sacs,  559 
septum,  1 60,  288 
Naso-frontal  process,  119,  286 
Naso-optic  furrow,  119,  549 
Navicular  bone,  168 
Neck,  development  of,  no,  117 
Neopallial  commissure   (see  also  Corpus  cal- 

losum),  438 
Neopallium,  437,  438,  442,  522  to  530 

centrifugal  connection  (see  also  Tracts, 
pyramidal,  Cortico-pontilc  fibers  and 
Fibers,  projection  descending),  441,  442, 
516,  525,  528 

centripetal  connections  (see  also  Fillets, 
Thalamic  radiations  and  Fibers,  projec- 
tion ascending),  440,  441,  507,  516, 
525,  528 

Nephrogenic  tissue,  362 
Nephrostomes,  356 
Nephro tomes,  80,  99,  358 
Nerve  fibers,  afferent  peripheral,  421,  456 

efferent  peripheral,  422 
Nerves,  cranial,  abducens,  VI,  432,  485 

nucleus  and  roots  of,  458,  485,  487,  494 


Nerves,  acoustic  (auditory)  VIII,  432,  435,  469, 
470,  473,  488,  558 

cochlear  ganglion,  469,  558 
part,  432,435 

cochlear  root,  470,  558 

vestibular  ganglion,  469,  558 
part,  432,  435 

vestibular  root,  470,  473,  488,  558 
facialis,  VII,  432,  434 

afferent  roots,  solitary  tract,  469,  488 

chorda  tympani,  468 

efferent  nucleus  and  roots  of,  458,  487 

geniculate  ganglion  of,  468,  558 
glossopharyngeus,  IX,  432,  434 

afferent  part  of,  432 
roots,  469 

efferent  nucleus  and  efferent  root  of,  458 

ganglion  of  the  trunk  (petrosum),  465 
of  the  root,  465 

lingual  and  tympanic  branches  of,  468 
great  superficial  petrosal  branch  468 
hypoglossus,  XII,  432,  485 

nucleus  and  roots  of,  438,  494 
lateral  line,  432 
olfactory,  I,  437,  471,  475 

terminal  nuclei,  or  mitral  cells  of  the 

olfactory  bulb,  475 
optic,  II,  424,  437,  475,  500,  546 

ganglion  cells  of,  575 
oculomotor,  III,  432 

nucleus  and  roots  of,  458 
somatic,  432  to  436 
spinal  accessory,  XI,  434,  435 

efferent  fibers  of,  466, 

nuclei  and  roots  of,  458 
splanchnic,  430  to  435 
trigeminus,  V,  430,  432,  434 

afferent  root  (portion  major),  and  spinal, 
V,  430,  471,  473,  488 

efferent  nuclei  and  roots  of,  458 

Gasserian  or  semilunar  ganglion,  430, 470 

mandibular  branch,  470 

maxillary  branch,  470 

mesencephalic  root  of,  473 

opthalmic  branch,  470 
trochlear,  IV,  432 

nucleus  and  roots  of,  458 
vagus,  X,  432,  434 

afferent  roots,  469 

efferent  fibers  of,  466 

nuclei  and  roots  of,  458,  488 

ganglia  of  root,  465 

ganglion  of  trunk  (nodosum),  465 


«50 


INDEX 


Nerves,  spinal,  peripheral,  dorsal  branch  of, 

457,  460 

ventral  branch,  457,  460 
Nervous  system,  the  417 
anomalies  of,  530 
anterior  neuropore,  421 
brain,  423 
central  distinguished  from  peripheral, 

419 

cerebrospinal  ganglia,  421 
components  of,  afferent  and  efferent,  417 
derivation  of,  421 
epichordal  segmental  brain  and  nerves, 

429 

general    considerations    of,    417,    418 
human,  459 
nerve  fibers,  421 
neural  crest,  421 

folds,  421 

groove,  421 

plate,  421 

tube,  421 

primitive  nervous  mechanism,  418 
root  fibers  of,  421 
spinal  cord  and  nerves,  423,  427 
three-neurone  reflex  arc,  420 
two-neurone  reflex  arc,  418 
vertebrate,  420 
central,  419 

suprasegmental  structures  of,  420,  427 
human,     afferent    peripheral    and    sym- 
pathetic neurones,  459 
anomalies  of,  539 
cell  proliferation  of,  449 
cerebellum,  425,  427,  436,  482,  495 
corpora  quadrigemina,  437  487,  500 
development    of    the    lower    (interseg- 

mental)  intermediate  neurones,  472 
differentiation  of  peripheral  neurones  of 

cord  and  epichordal  segmental  brain, 

456 
early  differentiation 

of  nerve  elements,  453 
epicordal  segmental  brain,  482 
epithelial  stage  of,  449 
further  differentiation  of  neural  tube, 

476 
general    development    of,    during    first 

month,  442 
histogenesis  of,  448 
spinal  cord,  476 
peripheral,  417 
effectors  of,  418 


Nervous  system,  peripheral,  receptors  of;  418 
sympathetic,  428 

efferent  peripheral  visceral  neurones  of, 

421 

vertebrate,    bilateral    character    of,    420 
cephalization,  420 
general  features  compared  with  human, 

427 

general  plan  of,  420 
segmentation  of,  420 
typical,  420 
Neural  crest,  60,  421,  460 

relation  to  cerebrospinal  ganglia,  421 
segmentation  of,  421 
separation  of,  421 
folds,  63,  64,  81,  97,  no,  421,  442 

fusion  of,  421,  442 

groove,  64,  81,  98,  101,  103,  no,  421,  442 
plate,   41,   42,   61,   63,    75,   81,   421,   442 

differentiation  of,  423 
tube,  41,  43,  64,  81,  99,  104,  no,  421,  442 
alar  plate,  447,  482,  485,  489 
basal  plate,  447,  482,  484 
blood  vessels  of,  478 
cells  of,  449,  451,  453,  454 
cervical  flexure,  448 
defects  in  the  region  of,  615 
floor  plate  of,  423,  443 
further  differentiation  of,  476 
lateral  plates  of,  423,  443 
layers  of,  449,  455,  484 
limiting  membranes  of,  449 
neuromeres,  426,  447 
order  of  development  of,  448,  476,  485, 

489,  512 

origin  of  malformations  of,  615 
roof  plate  of,  423,  443,  483 
sulcus  limitans,  447,  482 
Neurenteric  canal,  43,  64,  101,  286 
Neurilemma,  448,  462 
Neurilemma,  cells  of,  462 
Neuroblasts  of  His,  455 
Neuro-epithelium,  551,  556 
Neurofibrils,  448,  454,  459 
Neuroglia  cells,  451,  455 

fibers,  453 

Neuromeres,  426,  447 
Neurone  layer,  see  Mantle  layer 
Neurones,  afferent  peripheral,  417,  427,  459  to 

472 

afferent  versus  efferent,  427 
association,  427,  438,  498,  500,  528 
central,  419 


INDEX 


651 


Neurones,  differentiation,  448 
distal  (first;  optic,  546 
efferent  peripheral,  417,  427,  456  to  459 
intermediate,  419,  429,  472 

intersegmental    (see   also  Ground   bun- 
dles and  Formatio  reticularis) ,  429, 

435,  448,  472  to  476,  485 
of  epichordal  segmental  brain,  435 
to  suprasegmental  structures,  429 
intersegmental,  of  epichordal  brain,  485 

to  488 

middle  (second)  optic,  546 
somatic  efferent,  429 
splanchnic  efferent,  429 
suprasegmental,  448 
Neuropore,  42 

anterior,  421,  443 
Nipple,  the,  413 
Nodule  of  cerebellum,  496 
Normoblasts,  239 
Nose,  119,  121,  420,  427,  475,  552 
anomalies  of,  180,  616 
bucco-nasal  membrane,  550 
Jacobson's  organ,  551 
nasal  conchae,  550 
origin  of,  549 
primitive  choanen,  550 

palate,  550 
sinuses  of,  550 

Notochord,  42,  60,  64,  65,  78,  79,  80,  i  05,  146 
Nuck,  diverticulum  of,  392 
Nuclear,  layer  of  neural  tube,  449 
Nuclei,  lateral,  436 

of  columns  of  Burdach,  429,  436,  441,  490 

of  columns  of  Goll,  429,  436,  441,  490 

of  thalamus,  507 

pontile,  436,  489,  500 

receptive,  437 

red  (ruber),  436,  487 

terminal  of  afferent  nerves  of  epichordal 

brain,  488  to  495 
of  tractus  solitarius,  432,  489,  494 
of  V,  430,  490,  493,  494 
of  VIII,  432,  492 
tracts  from  Deiter's,  436,  481 
Nucleus  ambiguous,  X,  458,  487 

caudatus  of  corpus  striatum,  516 

commissuralis,  489 

dentatus,  441,  442,  500 

dorsal  efferent,  X,  458 

habenulse,  425,  503 

incertus,  494 

inferior  olivary,  436,  489,  490,  494 


Nucleus,  intercalates,  494 

lateral,  490 

lenticularis,  516 

lentiformis,  516 

of  Darkschewitsch,  487 
Nutrition  of  earliest  stages  of  embryo,  572 

Obex,  483 

Obturator  foramen,  171 
Occipital  bone,  158,  160 
Occulomotor,  III,  nerve,  432 
Odontoblasts,  294 
Odontoid  process  (dens},  152 
(Esophageal  region,  286 
(Esophagus,  the,  304 

anomalies  of,  325 
(Estrus,  24,  25 
Olfactory  apparatus,  see  Nose 

area  (see  also  Arc  hi  pallium),  528 

bulbs,  422,  511 

lobes,  439,  448,  510,  511 

anterior,  439,  509,  510,  511,  549 
posterior,  439,  509,  510,  511,  549 

I,  nerve,  437,  438,  471,  475 
peduncle,  511 

placodes,  549 

stalk,  511 

tracts,  437,  438,  475,  507 
Olives,  accessory,  490 

inferior,  436,  489,  490,  494 

superior,  493 

Olivo-cerebellar  fibers,  491,  499 
Omenta,  anomalies  of,  352 
Omental  bursa,  348 

epiploic  foramen  of,  348 
Omentum,  347 

greater,  348 

lesser,  349 
Omosternum,  179 
Omphalocele,  618 
Omphalomesenteric   arteries,    187,    215 

veins,  187 
Oocyte,  primary,  2,  16,  18,  20 

secondary,  19,  20 
Oogonia,  16 

Opercula  of  insula,  522,  523 
Optic  apparatus,  see  Eye 

chiasma,  475,  501 

cup,  536,  539,  547 

depression,  533 

evagination,  534,  546 

lobes,  425,  437,  438 

II,  nerve,  424,  437,  475,  500,  546 


652 


INDEX 


Optic  neurone,  first  or  distal,  543 
second  or  middle,  543 

radiation,  440,  441 

stalk,  534,  546 

thalami,  546 

tract,  438,  475,  500,  546 

vesicle  area,  534 

vesicles,  424,  444,  534 
Ora  serrata,  540 
Oral  fossa,  no,  in,  118,  119 

pit,  287 

Orbitosphenoid  bone,  159 
Organ  of  Corti,  430,  437,  528,  557 

of  Giraldes,  387 

of  Rosenmiiller,  385 
Organogenesis,  127 
Os  calcis  (calcaneus),  172 

centrale,  181 

coxae,  171 

Ossa  suprasternalia,  153 
Osseous  tissue,  137 
Ossification  center,  139,  142 

endochondral,  140 

intracartilaginous,  140 

intramembranous,  137 

subperiosteal,  140,  142 

stage,  150 

Osteoblasts,  139,  242 
Osteoclasts,  139,  145,  242 
Osteogenetic  tissue,  139,  141 
Ostium  abdominale  tubas,  384 
Otic  ganglion,  471 
Otocyst,  552 
Ova,  centrolecithal,  6 

classification  of,  5 

meiolecithal,  5 

mesoleGithal,  5 

number  of,  25 

polylecithal,  6 

primitive,  378 

number  of,  380 
Ovarian  cysts,  610 

(Graafian)  follicle,  379 
liquor  folliculi,  379 
rupture  of,  379 
stratum  granulosum  of,  379 

zona  pellucida,  379 

radiata,  379 

Ovarian  ligament,  the,  392 
Ovary,  the,  23 

anomalies  of,  403 

corpus  haemorrhagicum,  381 
luteum,  380 


Ovary,  descent  of,  390,  407 
diverticulum  of  Nuck,  392 
egg  nests,  378 
ligaments  of,  392 
medullary  cords  of,  376,  377 
migration  of,  387,  392 
Mullerian  duct  of,  383 
parasitic  growths  of,  609 
Pfluger's  egg  cords  of,  378 
primary  Graafian  follicle  of,  378 
rete  of,  377 

stratum  germinativum,  377 
theca  folliculi,  379 
Oviduct,  24,  384 

anomalies  of,  403 
fimbriae,  384. 

non-stalked  hydatid  of  Morgagni,  384 
ostium  abdominale  tubae  of,  384 
Ovists,  XIII 
Ovium,  i 

Ovulation,  23,  24,  25 
Ovum,  the,  379 

of  Amphioxus,  35 
of  the  frog,  3 

cytoplasm  of,  4,  49 

membranes  of,  4 

nucleus  of,  4,  49 

pigment  of,  4,  49 

symmetry  of,  49,  50,  51 

yolk  of,  4,  49 
of  the  bird,  4 

cytoplasm  of,  4,  66 

membranes  of,  5,  66 

nucleus  of,  5,  66 

yolk  of,  5,  66 

faulty  implantation  of,  623 
human,  2,  23,  24,  84,  95,  99,  118 

maturation  of,  84 

nucleus  of,  3 
chromatin,  3 
nuclear  membrane,  3 
nucleolus,  3 
mammalian,  84 

fertilization  of,  84 

maturation  of,  84 

Palate,  the,  288 

bone,  162 

cleft,  1 80,  616,  617 

primitive,  550 
Palatine  processes,  288 
Pallium,  425,  437,  444,  508,  509,  511  to  530 

archipallium,  438,  475>  5°7,  511,  516  to  52.2 


INDEX 


653 


Pallium,  association  neurones  of,  438,  498,  500, 
528 

calcarine  area  or  region  (see  also  Visual 
area),  527,  528 

corpora  striata,  425,  437,  511 

cortex  of,  524 

development  of,  438 

hemispheres  of,  427,  440,  444,  508,  511  to 
530 

layer  of  giant  pyramid  cells,  5  28 

layers  of,  527 

neopallium,  420,  522  to  530 

postcentral  area  of,  441,  525,  527,  528 

precentral  area  of,  442,  527,  528 

rhinencephalon,  422,  437,  510 
Pancreas,  the,  319 

anomalies  of,  327 

cells  of,  323 

connective  tissue  of,  321 

duct  of  Santorini  of,  320,  327 
of  Wirsung  of,  320,  327 

histogenesis  of,  322 

islands  of  Langerhans,  323 
Pander,  XIII 
Papillae,  filiform,  290 

fungiform,  290 

hair,  410 

lingual,  290 

nerve,  408 

renal,  366,  368 

vascular,  408 
Papillares  muscle,  206 
Paradidymis,  the,  384 
Paraphysis,  424,  504 
Parasitic  duplicity,  608 

origin  of,  610 

Parasitic  structures  in  the  sexual  glands,  609 
Parathyreoids,  301 
Parietal  bones,  162 

cavity,  196 
of  His,  342 

mesoderm,  45,  60,  80,  81,  96,  98,  108,  340 

recess,  dorsal,  of  His,  342 
Parolfactory  area  of  G.  Elliot  Smith  (see  also 

Prcterminal  area),  436,  511 
Paroophoron,  the,  386 
Parovarium,  the,  385 
Pars  basilaris,  158 

ciliaris  retinae,  547 

cystica,  314 

hepatica,  314 

mastoidea,  159 

optica  retinae,  547 


Pars  petrosa,  159 
squamosa,  158 

subthalamica,  see  Hypothalamns 
Partes  laterales,  158 
Parthenogenesis,  33 
Patella,  the,  172 
Paton,  concerning  development  of  pyramids, 

525 

concerning  peripheral  nerves,  464 
Peduncles  of  cerebellum,  middle,  436,  441,  443, 

493.  500 

inferior  cerebellar,  see  Rcstiform  body 
superior,  436,  441,  443,  500 
Pellicle  of  cytoplasm,  136 
Pelvic  girdle,  171 
Penis,  the,  394 

supernumerary,  609 
Perforated  space,  posterior,  503 
Periblast,  69 

Pericardial  cavity,  primitive,  186 
Pericardium,  the,  340,  347 

anomalies  of,  352 
Perichondrium,  141 
Periderm,  the,  407 
Perilymph,  556 
Perilymphatic  space,  556 
Perimysium,  280 
Perineal  body,  the,  394 
Perobrachius,  619 
Perichordal  sheath,  154 
Periosteal  buds,  141 
Periosteum,  139 
Periotic  capsule,  157 
Peripheral     nervous     system,     see     Nervous 

system,  peripheral 
Peristomal  mesoderm,  43,  61 
Peritoneum,  352 
Peritonsillar  fissure,  496 
Permanent  teeth,  296 
Peromelus,  619 
Peropus,  619 

Persistence  of  the  cloaca,  326 
Pes  pedunculi,  436,  441,  493,  494,  528 
Peter,  concerning  nasal  sac,  549,  550 

concerning  origin  of  endolymphatic  appen- 
dage in  Amphibia,  553 
Peters'  ovum,  100,  101,  108,  579 
Peyer's  patches,  313 
Pfliiger's  egg  cords,  378 
Phaeochrome  cells,  396 

granules,  396 
Phaeochromoblasts,  397 
Phalanges,  169 


654 


INDEX 


Pharyngeal  membrane,  287,  299 

region,  386 

tonsils,  299 

Pharyngopalatine  arch,  299 
Pharynx,  the,  298 

anomalies  of,  325 

development  of,  298 

glossopalatine  arch,  299 

pharyngopalatine  arch,  299 

pillars  of  the  fauces,  299 
Physico-chemical  theory  of  monsters,  621 
Piersol,  classification  of  malformations  of  the 

extremities,  618 
Pigment,  408 

of  neurones,  448,  459 
Pillars  of  the  fauces,  299 
Pineal  body,  424,  437,  503 

stalk,  503 
Pisiform,  169 

Pituitary  body,  irregular  tumors  of,  608 
Placenta,  578 

anomalies  of,  598 

annular,  598 

attachment  of,  to  ovum   and   to  uterine 
wall,  596 

bipartita,  598 

blood  vessels  of,  595 

chorion  frondosum,  586,  588 

decidua  basalis,  586,  588 

discoidal,  578 

duplex,  599 

expulsion  of,  598 

fcetalis,  578 

functions  of,  592 

maternal,  578 

rnembranacea,  598 

praevia,  596 

relations  of,  to  uterine  mucosa,  578,  588 

size  of,  596 

spuria,  599 

succenturiata,  599 

uterina,  578 

zonular,  578 
Placentae,  multiple,  578 
Placental  septa,  591 
Placentalia,  578 
Placodes,  422,  465,  475 

auditory,  552 

epibranchial,  422 

olfactory,  549 

suprabranchial,  422 
Plagiocephaly,  180 
Plasmodi-trophoderm,  99,  585,  589,  590 


Pleura,  the,  336,  347 
Pleural  cavities,  343 
Pleuroperitoneal  membranes,  345 
Pleuroperitoneum,  340 
Plexus,  Auerbach's,  461 

chorioideus.  see  Chlorioid  plexus 

Meissner's,  461 

vitelline,  186 
Plica  arcuata,  518 

chorioidea  (fold),  517 

encephali  ventralis,  423 

rhombo-mesencephalica,  445 

semilunaris,  549 
Plicae  palmatae,  385 
Polar  bodies,  18,  19,  20 

relation  to  production  of  monsters,  611 
Polydactyly,  181,  611 
Polykaryocytes,  145,  243 
Polylecithal  ova,  6 
Polysomatous  monsters,  621 
Polyspermy,  31 
Pons  varolii,  445,  493 
Pontile  nuclei,  436,  489,  493,  500 
Pontine  flexure,  447 
Porencephaly,  613 
Portio  major,  471 

Postbranchial  branches  of  nerves,  434 
Posterior  arcuate  fissure,  518 

colliculi,  see  Posterior  corpora  qnadrigemina 

corpora  quadrigemina,  437,  487,  500 

horn  (dorsal  gray  column),  478 

longitudinal     fasciculus,     see    Fasciculus, 
medial  longitudinal 

nares,  289 

Prebranchial  branches  of  nerves,  434 
Precervical  sinus,  115 
Preformation  theory,  XIII 
Preformationists,  XIII 
Pregnancy,  abdominal,  32 

duration  of,  123 

mammary  gland,  during,  413 

tubal,  32 

Premolar  teeth,  296 
Premuscle  sheath,  274 

tissue,  265 
Preoptic  recess,  501 
Prepuce,  in  the  female,  394 

in  the  male,  394 
Presphenoid  bone,  159 

Preterminal  area  of  G.  Elliot  Smith,  439,  511 
Primary  areas  or  fields  of  Flechsig,  528 

oocyte,  2,  1 6,  18,  20 

spermatocytes,  n,  12,  13,  16 


IXDKX 


Primitive  body  cavity  (coelom),  46,  60,  65,  80, 
81,  96,  98,  104 

axis  (head  process),  74,  76,  77,  82,  95 

coordinating  mechanism,  474 

folds,  74,  75,  77,  102 

groove,  74,  75,  77,  79,  94,  102,  103,  no 

gut  (see  also  Archenteron) ,  285,  340 

knot  (Hensen's),  74,  75,  77,  93,  97 

pericardial  cavity,  196,  280,  341 

Pit,  74,  75,  77 

plate,  75,  77 

segments,  46,  79,  80,  262,  268 

streak,  74,  75,  76,77,78,82,91,92,93,94, 

102,  103 

Primordial  cranium,  157 
Proamnion,  77,  79,  572 
Processus  neuroporicus,  424 

reticularis,  481,  486 

vaginalis  peritonei,  390 
Proctodaeum,  58 

Production  of  duplicate  (polysomatous)  mon- 
sters, 621 

of  monsters  in  single  embryos,  622 
Progamous  determination  of  sex,  382 
Projection  fields,  528 
Pronephric  duct,  354,  355 
Pronephros,  the,  354 

pronephric  duct  of,  354 
tubules  of,  355 

significance  of,  355 
Pro-oestrus,  25 
Prosencephalon  (fore-brain),  424,  427,  437 

diencephalon,  425,  437 

peripheral  neurones  of,  471 

telencephalon,  425,  437 
Prosopopagus  parasiticus,  608 
Prostate  gland,  372 
Psalterium,  see  Fornix  commissure 
Pterygoid  hamulus,  159 

process,  159,  161 
Pubis,  the,  171 
Pulmonary  artery,  204,  212 
Pulp  of  teeth,  294,  295 
Pulpy  nuclei,  147 
Pulvinar  thalami,  503 
Purkinje  cells,  497,  499 
Pygopagus,  604 

Pyramids  (see  also  Tracts,  pyramidal],  442,  491, 
493,  494 

Quadrigemina,   anterior,  see  Anterior  corpora 

quadrigemina 
posterior,  see  Posterior  corpora  quadrigemina 


Rabbit,  formation  of  amnion  of,  572 
Rabl,  concerning  origin  of  vitreous,  545 

concerning  sex  cells,  374 
Rachischisis,  282,  613,  615 

cystica,  613 
Radius,  168 
Ramus,  164 

communicans,  gray,  462 

white,  457,  462 
Raphc  (of  epichordal  segmental  brain),  485 

(of  scrotum),  396 
Rathke's  pocket,  288 

pouch,  501 
Receptors,    418,    421,    427,    430,    432 

visual,    471,    475 
Recessus    postopticus,    424,    501 

praeopticus,    424,    501 
Recklinghausen,     von,     concerning     deficient 

growth  of  blastoderm,  615 
Rectum,  the,  310,  370 
Red  blood  cells,  239 

Reduction  of  chromosomes  (see  also  Matura- 
tion), 11,  380 
Reflex  arc,  476 

three-neurone,  419 

two-neurone,  418 
Regnier  de  Graaf,  XIII 
Reichert,  XIV 
Rejuvenescence  theory,  33 
Renal  corpuscle,  367 

papillae,  367 

pelvis,  primitive,  361 

pyramids,  367 

tubules,  convoluted,  363 

straight,  361 
Respiratory  system,  the,  330 

anomalies  of,  338 

larynx,  331 

lungs,  334 

trachea,  333 

Restiform  body,  436,  491 
Rete  cords,  374 

ovarii,  377 

testis,  381,  382 
Retention  cysts,  618 

Reticular  formation,  435,  441,  485  to  488 
gray,  486 
white,  486 

tissue,  origin  of  fibers  of,  134 
Retina,  424,  471,  475,  540 

amacrine  cells  of,  542 

area  centralis,  542 

bipolar  cells  of,  475,  543 


656 


INDEX 


Retina,  cone  bipolars,  544 

defective  pigmentation  of,  415 

differentiation  of  cells  of  nuclear  layer,  542 

distal  (first)  optic  neurone,  543 

fovea  centralis,  542 

layer  of  ganglion  cells  of,  541 
of  nerve  fib'ers  of,  541 

macula  lutea,  542 

middle  (second)  optic  neurone,  543 

Mtiller's  or  sustentacular  cells,  542 

nervous  part,  540 

non-nervous  part,  540 

ora  serrata,  540 

pigmented  layer,  540 

primitive  nuclear  layer  of,  541 

rod  and  cone  cells  of,  542,  543 

bipolars,  544 

Retterer,  concerning  lymphatic  tissue  of  ton- 
sils, 299 
Rhinencephalon,   425,   437,   475,   507,   510  to 

5ii 
Rhombencephalon  (rhombic  brain),  424,  445, 

465 

Rhombic  brain  (rhombencephalon),  431,  445 
cerebellum,  425 
tela  chorioidea,  425 

grooves,  459 

lip,  483,  489,  495 

Rhombo-mesencephalic  fold,  424,  445 
Rhythmical  contractions,  566,  580 
Ribs,  the,  152 

capitulum  of,  153 

costo-vertebral  ligaments  of,  152 

foramen  transversarium,  153 

ossification  of,  153 

tuberculum  of,  153 
Rods,  471,  475,  542,  543 
Rolando,  fissure  of,  524 

substantia  gelatinosa  of,  490 

tuberculum  of,  594 

Roof  plate  (dorsal  median  plate),  423,  443,  483 
Root  fibers,  afferent,  421 

sheath,  the,  410 

Rosenberg's  theory  concerning  vertebrae,   178 
Rosenmiiller,  organ  of,  385 
Rotation  of  extremities,  122 
Roux,  concerning  source  of  parasitic  growths, 

612 

Rubro-spinal  tract,  436,  481 
Rupture  of  the  membranes,  581 

Saccule,  556 

Sacral  flexure,  112,  115 


Salivary  glands,  the,  296 

crescents  of  Gianuzzi,  298 

histogenesis  of,  297 

sublingual,  296 

submaxillary,  296 
Santorini,  duct  of.  320 
Sarcoolasm,  278 
Scala  media,  556 

tympani,  556,  557 

vestibuli,  556,  557 

Schaper,  concerning  development  of  cerebel- 
lum, 497 

Scaphocephaly,  180 
Scapula,  167 
Schleiden,  XIV 

Schmidt,  concerning  mammary  gland,  412 
Schultz,  concerning  potentiality  of  germ  cells, 

612 

Schwann,  XIV 
Sclera,  545 

Sclerotome,  131,  147,  262,  276 
Scrotum,  the,  390,  396 
Sebaceous  glands,  the,  412 
Secondary  egg  membranes,  4 

oocyte,  19,  20 
Secretory  function,  298 

Segmental  part  of  epichordal  brain,  427,  429 
Segmentation  (see  also  Cleavage), 

cavity,  38,  54,  68 

cells,  development  of  isolated  group  of, 

to  form  monsters,  6 1 1 
Segments,  primitive,  46,  79,  80,  262,  269 

of  segmental  brain  and  cord,  475,  476 
Semilunar  ganglion,  430 
Seminal  filament  or  spermatozoon,  i,  6 

vesicles,  386 

Seminiferous  tubules,  381 
Sense  organs,  special,  533 

anomalies  of,  561 

ear,  552 

eye,  533 

nose,  549 
Septa,  the,  202 

anomalies  of,  254 
Septal  marginal  layer,  484 
Septum  aorticum,  204 

atriorum,  202 

medullse,  484 

pellucidum,  439,  522 

spurium,  205 

superius,  202 

transversum    (see    also    Diaphragm),  342, 
344,  347 


INDEX 


657 


Septum  ventriculorum,  204 
Serosa,  571 

Sertoli,  cells  of,  u,  15,  16 
Sex  cells,  374 
cords,  375 

determination  of,  21 
Sexual  elements,  374 
Sheaths,  myelin  (medullary),  448,  464 

neurilemma,  448 

Sherrington,   concerning  effectors   and   recep- 
tors, 418 

Shoulder  girdle,  167 
Siamese  twins,  605 
Sigmoid  colon,  209 
mesocolon,  351 
Sinus,  cavernous,  220 
confluence  of,  221 
coronarius,  223 
frontal,  550 
maxillary,  550 
petrosal,  222 
precervical,  115 
sagittal,  222 
sphenoidal,  550 
terminalis,  187 
transverse,  221 
venosus,  191,  201 
Sinusoidal  circulation,  316 
Sinusoids,  229,  315,  316 
Situs  viscerum  in  versus,  323 
Skeletal  musculature,  see  Musculature,  skeletal 
system,  anomalies  of,  177 
appendicular  skeleton,  166 
axial  skeleton,  146 
development  of  the,  129 

of  joints,  1 73 
head  skeleton,  154 
notochord,  146 
ribs,  152 
sternum,  153 
vertebrae,  147 

Skeleton,  axial  (see  also  Axial  skeleton),   146 
appendicular,     (see     also      Appendicular 

skeleton),  166 
Skin,  the,  407 

anomalies  of,  414 
dermis,  408 
epidermis,  407 
glands  of,  412 
pigment  of,  408 
Skull,  defects  of,  612 

development  of,  154 
Smegma  embryonum,  412 
42 


Smith,  G.  Elliott,  concerning  archipallium,  439 
Smooth  muscle,  280 

histogenesis  of,  281 
Sole  plate,  409 

Somaesthetic  area  of  pallium,  440,  527,  528 
Somatic  area  (see  also  Pallium,  precentral  area), 

528 

segmentation,  420,  430 
structures,  428 
Somatochrome  cells,  459 
Somatopleure,  340,  573 
Somites,  mesodermic,  43,  45,  47,  60,  65,  79,  80, 

81,  82,  96,  98,  104,  no 
Spermatids,.u,  12,  13,  16,  20 
Spermatocytes,  n 

primary,  n,  12,  13,  16,  20 
secondary,  12,  13,  16,  20 
Spermatogenic  cells,  1 1 
Spermatogenesis,  n,  15,  16,  22 
Spermatogonia,  u,  20 
Spermatozoa,  n,  16,  30,  31,  32 
forms  of,  7,  8 
number  of,  7,  9 

Spermatozoon,  the,  6,  13,  28,  29,  30,  31 
diagram  of,  7 
discovery  of,  XIII 
human,  6,  14 
acrosome,  6 
axial  filament,  6,  14 
body,  6 

centrosome,  6,  14 
end  knob,  6,  14 
galea  capitis,  6,  15 
head,  6,  14 
middle  piece,  14 
neck,  6 
nucleus,  6,  13 
spiral  filament,  6,  14 
tail,  6 

Spermium,  i 
Sphenoid  bone,  159,  161 
Sphenomandibular  ligament,  163 
Sphenopagus,  608 
Sphenopalatine  ganglion,  471 
Spigelius,  lobe  of,  318 
Spina  bifida,  613,  614,  615 
cystica,  613 
occulta,  614 

Spinal  accessory,  XI,  nerve,  434,  465 
cord,  the,  423,  424,  443,  476 
Clarke's  column,  436,  481 
dorsal  funiculi,  460,  473,  477 
gray  column,  428,  478 


658 


INDEX 


Spinal  cord,  dorsal  funiculi,  septum  of,  480 
growth  of,  482 
lack  of,  614 
malformations  of,  613 
ventral  funiculi,  477 
gray  column,  428 
ventro-lateral  funiculus,  477 

ganglion,  460,  461 

cells,  unipolarization  of,  461 

meningocele,  614 

V,  430,  471,  488 

Spino-cerebellar  tracts,  436,  441,  482 
Spiral  fibers  of  spermatozoon,  6,  14 

lamina,  557 

Splanchnic  mesoderm,  45,  60,  80,  81,  96,  98, 
108,  310 

or  visceral  structures,  428 
Splanchnocrel,  46 
Splanchnopleure,  340,  573 
Spleen,  the,  252 

cavernous  veins  of,  253 

cells,  254 

haematopoietic  function  of,  253 

pulp  cords  of,  253 

splenic  corpuscles  of,  253 
Splenic  corpuscles,  253 
Spongioblasts,  449,  453 
Spongy  bone,  139 
Stapes,  165,  559 
Sternopagus,  605 
Sternum,  the,  153 

corpus  sterni,  154 

cleft,  179 

malformations  of,  605 

manubrium  sterni,  154 

ossification  of,  154 

xyphoid  process  of,  154 
St.  Hilaire,  concerning  malformations,  593 
Stockard,  on  production  of  monsters,  622 
Stomach,  the,  304 

anomalies  of,  436 

practical  suggestions  for  study  of,  327 

region,  286 

rotation  of,  305 

Strahl,  concerning  the  mammary  gland,  412 
Stratum  granulosum,  379 

cells  of,  380 
Streeter,     concerning     the     acoustic     nerve, 

559 

concerning  atrium  of  inner  ear,  553 
concerning  development  of  IX,  X,  XI, 

cranial  nerves,  465,  466 
concerning  floor  of  fourth  ventricle,  494 


Streeter,  concerning  origin  of  endolymphatic 

appendage  in  man,  553 
concerning  origin  of  genu  facialis,  487 
concerning  rhombic  grooves,  459 
Stria  medullaris,  503,  508 
semicircularis,  513 
terminalis,  513,  518 
Striae  Lancisi,  521 

Striated  involuntary  muscle  tissue,  280 
voluntary  muscle  tissue,  cells  of,  276 
endomysium  of,  280 
epimysium  of,  280 
fibers  of,  271 
histogenesis  of,  276 
intermuscular  tissue  of,  280 
perimysium  of,  280 
sarcoplasm,  278 
Stylohyoid  ligament,  165 
Styloid  process,  160,  165 
Subclavian  artery,  211,  213,  217 
Sublingual  'gland,  297 
Submaxillary  ganglion,  471 

gland,  296 

Subperiosteal  ossification,  140,  142 
Substantia  gelatinosa  of  Rolando,  490 

propria  corneae,  548 
Sudoriferous  glands,  the,  412 
Sulcus  hypothalamicus,  501 
limitans,  447,  482,  494 
Sulcus,  longitudinalis,  204 

Monroi,  501 
Superior  peduncle  of  cerebellum,  436,  441,  443, 

500 

Supracondyloid  process,  180 
Supraglenoidal  tuberosity,  167 
Supraoccipital  bone,  158 
Suprarenal  glands,  396 
chromaffin  cells,  396 
cortical  substance  of,  397 
lipoid  granules  of,  396 
medullary  substance  of,  397 
organs,  398 

phaeochrome  cells  of,  396 
relation  to  kidney,  398 

Suprasegmental  structures  of  Adolf  Meyer  (see 
also  Cerebellum,  Mid-brain  roof,  Cor- 
pora quadrigemina  and  Pallium),  420, 
427,  436,  437,  475,  476 
characteristics  of,  427 
connections  of,  see  Cerebellum,  Mid-brain 
roof,    Corpora    quadrigemina,    Archi- 
pallium  and  Neopallium 


INDEX 


059 


Suprasegmental  structures,  tracts  to  (see  also 
Cerebellum,  Mid-brain  roof,    Corpora 
qnadrigemina,  Arc  hi  pallium  and  Neo- 
pallium),  436,  441,  481 
Suprasternal  bones,  153,  179 
Sylvii,  fossa  of,  509,  510,  522 
Symblepharon,  616 
Symmetrical  duplicity,  602 

anterior  union,  606 

complete  duplicity,  601,  602 

middle  union,  605 

multiplicity,  607 

origin  of,  607 

posterior  union,  604 
Sympathetic  (autonomic)  system,  428 

nervous     system,     see     Nervous     system, 

sympathetic 
Sympathoblasts,  397 
Symphysis  of  lower  jaws,  287 
Sympus  apus,  619 

dipus,  619 

monopus,  619 

symelus  siren,  619 
Synapsis,  12,  1 6 
Synarthrosis,  174 
Syncephalus,  606 
Synchondrosis,  174 
Syncytial  layer,  99,  589 
Syncytium  of  heart  muscle,  281 
Syndesmosis,  174 
Synophthalmia,  616 
Synosteosis,  179 
Synotia,  561,  606 
Synotus,  616,  617 
Synovial  fluid,  175 
Syringomyelocele,  614 

Tactile  corpuscles  of  Meissner,  408 
Taenia  fimbriae,  518 

of  cerebellum,  475 

of  cerebral  hemispheres,  512 

of  medulla,  483 
Tail,  117 

bud,  63 

fold,  82 
Talus,  172 

Tarsus,  bones  of  the,  172 
Taste  buds  (see  also  Gustatory  system),  420,  430 
Tautomeric  column  cells,  473 
Teeth,  the,  291 

dental  groove,  292 
papilla,  292 
shelf,  292 


Teeth,  dentinal  canals,  295 
fibers  of,  295 
pulp  of,  294 

dentine,  292,  294,  295 

enamel,  293 
organ,  292 

membrana  preformativa,  294 

milk,  292 

odontoblasts,  294 

permanent,  295 

true  molars,  295 
Tegmental  swelling,  487,  505 
Tegmentum,  494,  508 
Tela  chorioidea,  425,  503 
Telencephalon  (end-brain),  425,  437,  508,  531 
i        corpus  striatum,  425,  437,  444,  448,  509 

pallium,  425,  437,  444,  508,  509 

rhinencephalon,  425,  437,  475,  507,  510, 

5" 
Temporal  bone,  159,  161 

lobe,  512 
Tendons,  135 
Teratogenesis,  601 

causes  underlying  origin  of  monsters,  620 

malformations  involving  more  than  one 
individual,  601 

malformations  involving  one   individual, 

612 

Teratoid  tumors,  399,  400 
Teratomata,  612 
Terminal  arborizations,  457,  474 

areas  of  Flechsig,  529 
Testicle,  the,  381 

anomalies  of,  402 

cells  of,  382 

descent  of,  389,  407 

mediastinum  testis,  382 

migration  of,  388,  392 

processus  vaginalis  peritonei,  390 

rete  testis,  381,  382 

seminiferous  tubules,  convoluted,  381 
straight,  381 

stroma  of,  382 

tunica  albuginea  of,  375,  381 

vaginalis  propria,  392 
Testis,  mediastinum,  382 

parasitic  growths  of,  610 

rete,  381,  382 
Tetrabrachius,  605 
Thalamic  radiations,  440,  441,  507,  515,  516, 

524 

Thalamus,  437,  448,  475,  S°6,  516 
Theca  folliculi,  379 


660 


INDEX 


Theoria  generationis,  XIII 
Thigh,  development  of,  117,  121 
Thoracic  duct,  244,  248 

.region,  defects  of,  618 
Thoracogastroschisis,  618 
Thoracopagus,  605 

parasiticus,  605 
Thoracoschisis,  352 
Thymus  gland,  254,  302 

anomalies  of,  426 

atrophy  of,  303 

histogenesis  of,  303 

malformations  of,  605 

tumors  of,  609 

Thyng,  concerning  anomalies  of  pancreas,  327 
Thyreoglossal  duct,  301 
Thyreoid  gland,  300 

anomalies  of,  325 

colloid  secretion  of,  300 

epithelial  bodies,  301 

its  relation  to  formation  of  blood  cells,  304 

parathyreoids,  301 

thyreoglossal  duct  of,  301 
Thyreoids,  lateral,  301 

theories  concerning,  301 
Tibia,  172 
Tissues,  adenoid,  300    - 

adipose,  135 

chromaffin,  399 

connective,  129 

lymphatic,  of  the  tongue,  299 

mesenchymal,  133 

muscle,  276,  280 

nephrogenic,  362 

osseous,  137 

premuscle,  265 

retroperitoneal,  399 

subcutaneous,  408 
Toes,  development  of,  121 
Tongue,  the,  289 

filiform  papillae  of,  290 

foramen  caecum  liguae,  290 

fungiform  papillae  of,  290 

innervation  of,  432 

lingual  papillae  of,  290 

lingualis  muscle  of,  290 

tuberculum  impar,  289 

valla te  papillae  of,  291 
Tonsilla,  496 
Tonsils,  the,  299 

crypts  of,  299 

lingual,  299 

lymph  follicles  of,  299 


Tonsils,  pharyngeal,  299 

Tooth  tumors,  developmental,  296 

Torneux,  concerning  malformations  of  neural 

tube,  615 
Tornier,  concerning  production  of  vertebrate 

monsters,  621 
Trabeculae  carneae,  206 
Trachea,  the,  333 
Tracts,  see  also  Fasciculi, 
central  tegmental,  489 
cortico-spinal,  see  Tracts,  pyramidal 
Flechsig's,  436,  441,  482,  491 
from  Deiter's  nucleus,  436,  481 
from  suprasegmental  structures,  441,  482 
Gower's,  436,  441,  482,  491 
gustatory  (see  also  Tractus  solitaries),  432, 

437,  438 

olfactory.  437,  438,  475,  507 
optic,  437,  438,  475,  547 
predorsal,  437,  500 
pyramidal,  441,  442,  482,  491,  494.  496, 

528 
reticular     formation      +     ventro-lateral 

ground  bundle  system,  474 
reticulo-spinal,  486 
rubro-spinal,  436,  481,  487 
Tracts,  secondary  and  tertiary  olfactory,  475 

optic  (see  also  Optic  nerve),  475 
spino-cerebellar  (dorsal) ,  436,  441,  482,  491 

(ventral),  436,  442,  482,  491 
spino-tectal  and  thalamic,  441,  482 
to  Deiter's  nucleus,  436 
to    suprasegmental    structures,    436,  441, 

481,  488,  495 

Tractus  solitarius  (communis)  of  VII,  IX  and 
X  nerves,  432,  469,  473,  474,  488, 
491 

Tragus,  561 

Transposition  of  the  viscera,  323 
Transverse  mesocolon,  350 
Trapezium  (bone),  169 

(of  medulla)  493 
Trapezoid,  the,  169 

area  of  His  (see  also  Preterminal    area}, 

439,  5n 

Tribrachius,  605 
Tricephalus,  607 
Trigeminus,  V,  nerve,  430,  432,  434 

Gasserian  ganglion,  430 

spinal  V  root,  430 
Trigonum  (bone),  181 

(brain),  511 
Triquetral  bone,  168 


INDEX 


661 


Trochanters,  172 

Trochlea,  168 

Trochlear,  IV,  nerve,  432 

Trophoblast,  88,  99 

Trophoderm,  88,  99,  100,  108,  584,  586 

Truncus  arteriosus,  188 

Tsuda,  concerning  production  of  spina  bifida, 

622 

Tubal  pregnancy,  32 
Tuber  cinereum,  503 
Tubercles,  greater,  168 

lesser,  168 
Tuberculum  of  rib,  153 

impar,  289 

of  Rolando,  494 

Tumors  of  sexual  glands,  origin  of,  611 
Tunica  albuginea,  375 

vasculosa  lentis,  539 

dartos,  408 

vaginalis  propria,  392 
Turbinated  bones,  160 
Twins,  equal  monochorionic,  601,  602,  603 

free  duplicities,  601 

unequal  monochorionic,  602 
Tympanum,  560 

Ulna,  1 68 

Umbilical  arteries,  191,  210,  571 

ccelom,  307 

cord,  596 

anomalies  of,  $99 
in  Mammals,  575 
in  man,  596 
length  of,  human,  598 

hernia,  581,  618 

ligament,  middle,  371,  583 

veins,  191,  219,  571 
Umbilicus,  dermal,  569 

double,  604 

intestinal,  569 
Unicornuate  uterus,  403 
Unilateral  hermaphroditism,  404 
Unipolarization  of  spinal  ganglion  cells,  461 
Unna,  concerning  anomalies  of  hair,  415 
Uracho-vesical  fistula,  402 
Urachus,  371,  5 70,  583 

anomalies  of,  401 
Ureters,  the,  361 

anomalies  of,  400 

relations  of,  to  cardinal  veins,  229 
Urethra,  the,  371,  394 

anomalies  of,  402 
Urinary  bladder,  the,  370,  371 


"Urinary  fistula,"  583 
Urogenital  sinus,  the,  370 
system,  the,  354 
anomalies  of,  399 

development  of  suprarenal  glands,  396 
genital  glands,  373 
kidney,  361 
mesonephros,  356 
metanephros,  361 
pronephros,  354 
urethra,  370 
urinary  bladder,  370 
urogenital  sinus,  370 
Urorectal  fold,  the,  370 
Uterus,  the,  385 

anomalies  of,  403 
bicornuate,  403 
bipartite,  403 
didelphys,  403 
fixation  of  ovum  to,  584 
infantile,  403 
masculinus,  387 
relation  of  placenta  to,  579 
unicornuate,  403 
Utricle,  556 

Utriculosaccular  duct,  556 
Utriculus  prostaticus,  387 
Uvula,  496 

Vagina,  the,  385 

anomalies  of,  403 
Vagus,  X,  nerve,  432,  434 
Valves,  the,  205 

anomalies  of,  254 
Valvula  bicuspidalis,  206 

mitralis,  206 

sinus  coronarii,  205 

tricuspidalis,  206 

venae  cavae  inferioris,  205 
Valvulae  semilunares  aortas,  206 

semilunares  arteriae  pulmonalis,  206 

venosae,  205 
Vas  deferens,  386 

epididymis,  393 
Vasa  aberrantia,  319,  393 

efferentia,  386 
Vascular  arteries,  209 

blood  vessels,  185 

blood  and  blood  cells,  236 

changes  in  the  circulation  at  birth,  234 

development  of  the,  185 

heart,  196 

histogenesis  of  blood  cells,  236 


662 


INDEX 


Vascular  lymphatic  system,  242 

system,  anomalies  of,  254,  603 

veins,  219 

Vasculogenesis,  principles  of,  193 
Veins,  accessory  hemiarzygos,  229 

anomalies  of,  257,  615 

ascending  lumbar,  229 

axillary,  232 

azygos,  228 

basilic,  232 

brachial,  232 

cardinal,  220,  222,  224 

cavernous,  251 

cephalic,  231 

cerebral,  220 

common  iliac,  228 

femoral,  234 

fibular,  233 

hemiazygos,  229 

hepatic,  231 

inferior  sagittal,  222 

internal  spermatic,  227 

jugular,  223 

jugulocephalic,  233 

lateralis  capitis,  220 

of  Galen,  222 

omphalomesenteric,  187,  219,  570 

ovarian,  227 

portal,  230 

primary  ulnar,  231 

radial,  232 

renal,  226 

revehent,  225 

saphenous,  234 

sciatic,  234 

subcardinal,  225 

subclavian,  223,  235 

subintestinal,  46 

supracardinal,  228 

suprarenal,  228 

testicular,  227 

tibial,  233,  234 

umbilical,  191,  219,  571 

vitelline,  187,  570 
Velum,  anterior  medullary,  496 

posterior  medullary,  483,  496 

transversum,  424,  504 
Vena  cava,  inferior,  224,  226 

superior,  223 
Veno-lymphatics,  249 
Ventral  cephalic  fold  of  brain,  423 

mesentery,  347 

mesogastrium,  347 


Ventral  root  fibers,  see  Efferent  root  fibers 
Ventricle,  331 

of  Verga,  522 
Ventricles  of  the  brain,  426 

fourth,  426,  448 

lateral,  426,  512 

anterior  horn  of ,  5 1 2 
descending  horn  of,  512 
posterior  horn  of,  512 

third,  426,  448 
Ventricular  septum,  202 
Ventro-lateral  plate,  see  Basal  plate 
Vermiform  appendix,  310 
Vermis,  496 

Vernix  caseosa,  407,  412 
Vertebrae,  the,  147 

alternation  of  vertebra;  and  myotomes,  148 

anomalies  of,  177 

blastemal  stage  of,  148 

bodies  of,  148 

cartilaginous  stage  of,  148 

costal  process,  148 

intervertebral  fibrocartilage,  148 
Vertebrae,  ligaments  of,  152 

ossification  stage,  150 

sclero tomes  of,  146 
Vertebrae  cervical,  defects  of,  612 
Vertebral  arch,  148 

articular  process  of,  1 50 

spinous  process  of,  150 

transverse  process  of,  150 
Vertebrate,  the  definition  of,  420 

differentiation  of  the  anterior  end  of,  420 

nervous  system,  see  Nervous  system,  •ver- 
tebrate 

Vesical  fissure,  402 
Vesicle,  auditory,  552 

blastodermic,  87,  108 

optic,  534 
Vesicles,  brain,  424,  443 

seminal,  386 
Vestibular  ganglion  cells,  559 

membrane  (of  Reissner),  557 

nerve,  559 

part  of  acoustic  (auditory)  nerve,  432 
descending  r<5ot  of,  432 

pouch,  553 
Vestibule,  430 
Vestibulum  vaginae,  394 
Vicq  d'Azyr's  bundle,  507 
Vignal,  concerning  the  myelin  sheath,  464 
Villi,  chorionic,  578,  586 

fastening,  591 


INDEX 


Villi,  floating,  591 

Visceral  mesoderm,  45,  60,  80,  81,  96,  98,  108 

musculature,  see  Musculature,  -visceral 

neurones,  sympathetic,  421 

or  splanchnic  structures,  428 
Visual  area  of  pallium,  440,  527,  528 

cortex,  527 
Vitelline  arteries,  210,  569 

circulation,  189 

duct,  581 

membrane,  2 

plexus,  1 86 

veins,  187,  570 
Vitellus,  2 
Vitreous,  545 

humor,  545 
Vocal  cords,  superior,  or  false,  331 

true,  331 

Volar  arch,  superficial,  217 
Voluntary  muscle,  striated,  histogenesis  of,  276 

origin  of,  262,  263 
Vomer,  160,  162 
Von  Baer,  XIII 
Von  Baer's  law,  354 
Von  Loewenhoek,  concerning  the  discovery  of 

the  spermatozoon,  XIII 
Von  Spec's  embryo,  101,  102,  109 

"Waters,"  the,  581 

Webs  between  digits,  121 

Weight  of  embryos,  122 

Wharton's  jelly,  597 

White  columns  (see  also  Dorsal  funiculus),  473 

matter  of  cerebral  hemispheres,  524 
of  cord  and  segmental  brain,  474 

ramus  communicans,  457,  462 
Wiedersheim,  concerning  the  mammary  gland, 

4i3 
concerning  duplicity  with  double  gastru- 

lation,  608 

Wieman,  concerning  spermatogenesis,  16 
Wilson,  E.  B.,  concerning  fertilization,  28 


Wilson,  J.  F.,  concerning  intermediate  region 
in  the  cord,  494 

concerning  intermediate  plate,  494 
Winslow,  foramen  of,  348 
Wirsung,  duct  of,  320 

Wlassak,  concerning  the  myelin  sheath,  464 
Wolffian  duct,  346 

ridge,  358 
"Wolf's  snout,"  180 

theory  of  epigenesis,  XIII 
Woods,  concerning  sex  cells,  374 

X-chromosome,  15,  1 6 
Xiphoid  process,  154 

malformations  of,  605 
Xiphopagus,  605 

Y-chromosome,  15,  16 
Yolk,  3 

lack  of,  in  Mammals,  572 

plug,  56 

sac,  82,  95,  96,  100,  101,  103,  104,  105,  no, 

in,  567 

formation  of  in  chick,  567 
function  of,  568 
in  Mammals,  572,  574 
in  man,  581 
stalk,  109,  112,  286,  568,  575 

Zander,  concerning  the  nails,  409 

Ziegler,    concerning   malformations   of   neural 
tube,  615 

Ziegler's  fusion  theory  of  symmetrical  duplic- 
ity, 607 

Zona  pellucida,  2,  379 
radiata,  379 

Zonula  Zinnii,  548 

Zonular  placenta,  578 

Zygomatic  bone,  162 

Zymogen  granules,  323 

Zygote,  27 


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