A LABORATORY MANUAL AND TEXT-BOOK

EMBRYOLOGY

By
CHARLES WILLIAM PRENTISS

LATE PROFESSOR OF MICROSCOPIC ANATOMY, NORTHWESTERN UNIVERSITY MEDICAL SCHOOL, CHICAGO

Revised and Rewritten by

LESLIE BRAINERD AREY

PROFESSOR OF MICROSCOPIC ANATOMY AT THE NORTHWESTERN UNIVERSITY MEDICAL SCHOOL

THIRD EDITION, ENLARGED

WITH 388 ILLUSTRATIONS

MANY IN COLOR

PHILADELPHIA AND LONDON

W. B. SAUNDERS COMPANY

1920

5802

Copyright, 1915. by W. B. Saunders Company. Reprinted August, 1915. Revised, entirely reset.

reprinted, and recopyrighted Cctober, 1917. Reprinted July, 1918. Revised,

entirely reset, reprinted, and recopyrighted August, 1920.

Copyright, 1920, by W. B. taunders Company

2954

PREFACE TO THE THIRD EDITION

THE rapid exhaustion of the second edition of this text has hastened
the appearance of the present volume. Its contents have again been sub-
jected to a systematic revision which affects each chapter more or less pro-
foundly. The addition of much new material and the recasting and
modifying of former descriptions will result, it is hoped, in a two-fold gain,
without appreciably increasing the size of the book.

L. B. A.

CHICAGO, ILL.,
August, 1920.

PREFACE TO THE SECOND EDITION

THE untimely death of Professor Prentiss has made necessary the transfer
of his 'Embryology' into other hands. In this second edition, however, the
general plan and scope of the book remain unchanged although the actual descrip-
tions have been extensively recast, rewritten, and rearranged. A new chapter
on the Morphogenesis of the Skeleton and Muscles covers briefly a subject not
included hitherto, ^orty illustrations replace or supplement certain of those
in the former edition.

In preparing the present manuscript a definite attempt has been made to
render the descriptions as clear and consistent as is compatible with brevity and
accuracy. It has likewise been essayed to evaluate properly the embryological
contributions of recent years, and, by incorporating the fundamental advances,
to indicate the trend of modern tendencies. Since no page remains in its entirety
as originally penned by Professor Prentiss, the reviser must assume full respon-
sibility for the subject-matter as it now stands.

It is hoped that those who read this text will co-operate with the writer by
freely offering criticisms and suggestions.

L. B. A.
iii

PREFACE

THIS book represents an attempt to combine brief descriptions of the verte^
brate embryos which are studied in th laboratory with an account of human
embryology adapted especially to the medical student. Professor Charles Sedg-
wick Minot, in his laboratory textbook of ^ir/bryology, has called attention to the
value of dissections in studying mammUi; . embryos and asserts that "dissection
should be more extensively practised tl in is at present usual in embryological

work " The writer has for several years experimented with

methods of dissecting pig embryos, and his results form a part of this book. The
value of pig embryos for laboratory study was first emphasized by Professor Minot,
and the development of my dissecting methods was made possible through the
reconstructions of his former students, Dr. F. T. Lewis and Dr. F. W. Thyng.

The chapters on human organogenesis were partly based on Keibel and
Mall's Human Embryology. We wish to acknowledge the courtesy of the pub-
lishers of Kollmann's Handatlas, Marshall's Embryology, Lewis-Stohr's Histology
and McMurrich's Development of the Human Body, by whom permission was
granted us to use cuts and figures from these texts. We are also indebted to
Professor J. C. Heisler for permission to use cuts from his Embryology, a I to
Dr. J. B. De Lee for several figures taken from his "Principles and Practice of
Obstetrics." The original figures of chick, pig and human embryos -re from
preparations in the collection of the anatomical laboratory of the [Northwestern
University Medical School. My thanks are due to Dr. H. C. Tracy for the loan
of valuable human material, and also to Mr. K. L. Vehe for several reconstruc-
tions and drawings.

C. W. PRENTISS.

NORTHWESTERN UNIVERSITY MEDICAL SCHOOL.

CONTENTS

PAGE

INTRODUCTION i

CHAPTER I. — THE GERM CELLS: MITOSIS, MATURATION AND FERTILIZATION 7

The Ovum , 7

Ovulation and Menstruation 10

The Spermatozoon 1 1

Mitosis and Amitosis 12

Maturation 14

Fertilization 20

CHAPTER II. — CLEAVAGE AND THE ORIGIN OF THE GERM LAYERS 24

Cleavage in Amphioxus, Amphibia, Reptiles and Birds 24

Cleavage in Mammals 27

The formation of Ectoderm and Entoderm (Gastrulation) 28

Origin of the Mesoderm, Notochord and Neural Tube 30

The Notochord 36

CHAPTER III. — THE STUDY OF CHICK EMBRYOS 37

Chick Embryo of Twenty Hours 37

Chick Embryo of Twenty-five Hours (7 Segments) 39

Transverse Sections 41

Chick Embryo of Thirty-eight Hours (17 segments) 45

General Anatomy 45

Transverse Sections 48

Derivatives of the Germ Layers 55

Chick Embryo of Fifty Hours (27 segments) 56

General Anatomy 56

Transverse Sections 61

Extra-embryonic Structures 66

CHAPTER IV. — HUMAN EMBRYOS AND FETAL MEMBRANES 70

Fetal Membranes of the Pig Embryo 70

The Umbilical Cord 72

Early Human Embryos and Their Membranes 73

Anatomy of a 4.2 mm. Human Embryo 81

The Age" of Human Embryos ' 89

CHAPTER V. — THE STUDY OF PIG EMBRYOS 91

The Anatomy of a 6 mm. Pig Embryo 91

External Form and Internal Anatomy 91

Transverse Sections 105

The Anatomy of 10-12 mm. Pig. Embryos. 114

External Form and Internal Anatomy 114

Transverse Sections 127

CHAPTER VI.— THE DISSECTION OF PIG EMBRYOS: DEVELOPMENT OF THE FACE, PALATE,

TONGUE, SALIVARY GLANDS, AND TEETH 139

Directions for Dissecting Pig Embryos 139

Dissections of 18-35 mm. Embryos 142

Development of the Face 146

Development of the Palate 148

Development of the Tongue 151

Development of the Salivary Glands 153

Development of the Teeth 154

CHAPTER VII. — THE ENTODERMAL CANAL AND ITS DERIVATIVES 161

The Pharyngeal Pouches and their Derivatives 162

The Thyreoid Gland 166

The Larynx, Trachea and Lungs 1 66

vii

Vlll CONTENTS

PAGE

The Esophagus, Stomach and Intestine 170

The Liver 176

The Pancreas 179

The Body Cavities, Diaphragm and Mesenteries 180

CHAPTER VIII. — THE UROGENITAL SYSTEM 196

The Pronephros. 196

The Mesonephros 198

The Metanephros 200

The Cloaca, Bladder, Urethra and Urogenital Sinus 206

The Genital Glands and Ducts 209

The External Genitalia 225

The Uterus during Menstruation and Pregnancy 230

The Decidual Membranes 232

The Placenta 237

The Relation of Fetus to Placenta 241

CHAPTER IX. — THE VASCULAR SYSTEM 243

The Primitive Blood Vessels and Blood Cells 243

Haemopoiesis 243

Development of the Heart 247

The Primitive Blood Vascular System 259

Development of the Arteries 262

Development of the Veins 268

The Fetal Circulation and Changes at Birth 276

The Lymphatic System 278

Lymph and Haemolymph Glands 280

The Spleen 280

CHAPTER X. — HISTOGENESIS 282

The Entodermal Derivatives 282

The Mesodermal Tissues 283

The Ectodermal Derivatives 293

The Nervous Tissues 299

CHAPTER XI. — THE MORPHOGENESIS OF THE SKELETON AND MUSCLES 309

The Skeletal System 309

The Axial Skeleton ., 309

The Appendicular System 315

The Muscular System 316

CHAPTER XII. — THE MORPHOGENESIS OF THE CENTRAL NERVOUS SYSTEM 321

The Spinal Cord '. 322

The Brain 326

The Differentiation of the Subdivisions of the Brain . 332

CHAPTER XIII. — THE PERIPHERAL NERVOUS SYSTEM 353

The Spinal Nerves 35-1

The Cerebral Nerves. .......'.'..'."..'..'....... i 357

The Sympathetic Nervous System 366

The Chromaffin Bodies and Suprarenal Gland 368

The Sense Organs 370

INDEX..

• • 393

TEXT-BOOK OF EMBRYOLOGY

INTRODUCTION

THE study of human embryology deals with the development of the
individual from the origin of the germ cells to the adult condition. To
the medical student human embryology is of primary importance because
it affords a comprehensive understanding of gross anatomy. It is on this
account that only recently a prominent surgeon has recommended a
thorough study of embryology as one of the foundation stones of surgical
training. Embryology not only throws light on the normal anatomy of
the adult, but it also explains the occurrence of many anomalies and mon-
sters, and the origin of certain pathological changes in the tissues. Obstet-
rics is essentially applied embryology. From the theoretical side, em-
bryology is the key with which we may unlock the secrets of heredity, the
determination of sex, and, in part, of organic evolution.

There is, unfortunately, a view current among graduates in medicine
that the field of embryology has been fully reaped and gleaned of its
harvest. On the contrary, much productive ground is as yet unworked,
and all well-preserved human embryos are of value to the investigator.
Only through the co-operation of clinicians in collecting and preserving
embryos will our ignorance of early human development be rectified. At
present, practically nothing is known of the maturing ovum, while of
fertilization, cleavage, and the formation of the germ layers we are en-
tirely in the dark. Aborted embryos and those obtained by operation in
case of either normal or ectopic pregnancies should always be saved and pre-
served at once by immersing them intact in 10 per cent formalin or in Zenker's
fluid.

Historical. — The science of modern embryology is comparatively new,
originating with the use of the compound microscope and developing
with the improvement of microscopical technique. Aristotle (384—322
B. c.), however, centuries before had followed the general development of
the chick day by day. The belief that slime and decaying matter was
capable of giving rise to living animals, as asserted by Aristotle, was
disproved by Redi (1668).

A few years after Harvey and Malpighi had published their studies
on the chick embryo, Leeuwenhoek reported the discovery of the sperma-
tozoon by Ham in 1677. At this period it was believed either that fully

i i

2 INTRODUCTION

formed animals existed in miniature in the egg, needing only the stimulus
of the spermatozoon to initiate development, or that similarly preformed
bodies, male and female, constituted the spermatozoa and that these
merely enlarged within the ovum. According to this doctrine of preforma-
tion all future generations were likewise encased, one inside the sex cells
of the other, and serious computations were made as to the probable
number of progeny (200 million) thus present in the ovary of Mother
Eve, at the exhaustion of which the human race would end ! Dalenpatius
(1699) believed thatfhe had observed a minute human form in the
spermatozoon.

The preformation theory was strongly combated by Wolff (1759)
who saw that the early chick embryo was differentiated gradually from
unformed living substance. This theory, known as epigenesis, was proved
correct when, in 1827, von Baer discovered the mammalian ovum and later
demonstrated the germ layers of the chick embryo.

About twenty years after Schleiden and Schwann (1839) had shown
the cell to be the structural unit of the organism, the ovum and spermato-
zoon were recognized as true cells. O. Hertwig, in 1875, was the first to
observe and appreciate the events of fertilization. Henceforth all multi-
cellular organisms were believed to develop each from a single fertilized
ovum, which by continued cell division eventually gives rise to the adult
body, that of man, it is estimated, containing 26 million million cells.
In the case of vertebrates, the segmenting ovum differentiates first three
primary germ layers. The cells of these layers are modified in turn to form
tissues, such as muscle and nerve, of which the various organs are com-
posed, and the .organs together constitute the organism, or adult body.

Primitive Segments — Metamerism. — In studying vertebrate embryos
we shall identify and constantly refer to the primitive segments, or meta-
meres. These segments are homologous to the serial divisions of an adult
earth worm's body, divisions which, in the earth worm, are identical in
structure, each containing a ganglion of the nerve cord, a muscle segment.
or myotome, and pairs of blood vessels and nerves. In vertebrate em-
bryos the primitive segments are known as mesodermal segments, or somites.
Each pair gives rise to a vertebra, to a pair of myotomes, or muscle seg-
ments, and to paired vessels; each pair of mesodermal segments is supplied
by a pair of spinal nerves, consequently the adult vertebrate body is seg-
mented like that of the earth worm. As a worm grows by the formation
of new segments at its tail-end, so the metameres of the vertebrate em-
bryo begin to form in the head and are added tailward. There is this
difference between the segments of the worm and the vertebrate embryo:
The segmentation of the worm is complete, while that of the vertebrate is
incomplete ventrally.

GROWTH AND DIFFERENTIATION OF THE EMBRYO 3

GROWTH AND DIFFERENTIATION OF THE EMBRYO

A multicellular embryo develops by the division of the fertilized ovum
to form daughter cells. These are at first quite similar in structure, and,
if separated, in some animals each may develop into a complete embryo
(sea urchin; certain vertebrates). The further development of the em-
bryo "depends: (i) upon the multiplication of its cells by division; (2)
upon the growth in size of the individual cells; (3) upon changes in their
form and structure.

The first changes in the form and arrangement of the cells give rise
to three definite plates, or germ layers, which are termed from their posi-
tions the ectoderm (outer skin), mesoderm (middle skin) and entoderm
(inner skin). Since the ectoderm covers the body, it is primarily pro-
tective in function, but it also gives rise to the nervous system, through
which sensations are received from the outer world. The entoderm, on
the other hand, lines the digestive canal and is from the first nutritive in
function. The mesoderm, lying between the other two layers, naturally
performs, the functions of circulation, of muscular movement, and of ex-
cretion; it also gives rise to the skeletal structures which support the body.
While all three germ layers form definite sheets of cells known as epi-
thelia, the mesoderm takes also the form of a diffuse network of cells, the
mesenchyma.

The Anlage. — This German word, which lacks an entirely satisfactory
English equivalent, is a term applied to the first discernible cell, or aggre-
gation of cells, which is destined to form any distinct part or organ of the
embryo. In the broad sense the fertilized ovum is the anlage of the entire
adult organism; furthermore, in the early cleavage stages of certain em-
bryos it is possible to recognize single cells or cell groups from which defi-
nite structures will indubitably arise. The term anlage, however, is more
commonly applied to the primordia that differentiate from the various
germ layers. Thus the epithelial thickening over the optic vesicle is the
anlage of the lens.

Differentiation of the Embryo. — The developing embryo exhibits a
progressively complex structure, the various steps in the production of
which occur in orderly sequence. There may be recognized in develop-
ment a number of component mechanical processes which are used
repeatedly by the embryo. The general and fundamental process condi-
tioning differentiation is cell multiplication, and the subsequent growth of
the daughter cells. The more important of the specific developmental
processes are the following: (i) cell migration; (2) localized growth, resulting
in enlargements and constrictions; (3) cell aggregation, forming (a) cords,
(b) sheets, (c) masses; (4) delamination, that is, the splitting of single sheets

INTRODUCTION

into separate layers; (5) folds, including circumscribed folds which produce
(a) evaluations, or out-pocketings, as the intestinal villi, (b) imaginations
or. in^pocketings, as the intestinal glands.

The production of folds, including evaginations and imaginations, due
to unequal rapidity of growth, is the chief factor in moulding the organs and
hence the general form of the embryo.

Differentiation of the Tissues. — The cells of the germ layers that form
organic anlages may be at first alike in structure. Thus the evagination
which forms the anlage of the arm is composed of a single layer of like
ectodermal 'cells, surrounding a central mass of diffuse mesenchyma
(Fig. 136). Gradually the ectodermal cells multiply, change their form
and structure, and give rise to the layers of the epidermis. By more
profound structural changes the mesenchymal cells also are transformed
into the elements of connective tissue, tendon, cartilage, bone, and muscle,
aggregations of modified cells which are known as tissues. The develop-
ment of modified tissue cells from the un differentiated cells of the germ
layers is known as histogenesis. During histogenesis the structure and
form of each tissue cell are adapted to the performance of some special
function or functions. Cells which have once taken on the structure and
functions of a given tissue cannot give rise to cells of any other type. In
tissues like the epidermis, certain cells retain their primitive embryonic
characters throughout life, and, by continued cell division, produce new
layers of cells which are later cornified. In other tissues all of the cells are
differentiated into the adult type, after which no new cells are formed.
This takes place in the case of the nervous elements of the central nervous
system.

Throughout life, tissue cells are undergoing retrogressive changes.
In this way the cells of certain organs like the thymus gland and meso-
nephros degenerate and largely disappear. The cells of the hairs and the
surface layer of the epidermis become cornified and eventually are shed.
Thus, normally, tissue cells may constantly be destroyed and replaced by
new cells.

Cytomorphosis.— This series of changes — an embryonic (undifferen-
tiated) stage ; progressive functional specialization ; gradual degeneration ;
death and removal — which tissue cells experience is known by the term
cytomorphosis.

Postnatal Development. — Development does not cease at birth, but
continues until the adult stage is attained. Birth, itself, initiates ana-
tomical and physiological changes of profound influence on the body.
Throughout the growth period, with its uneven but steadily slowing
growth rate, comes a remoulding of the shape of the body and its parts.
During this time most of the organs lose in relative weight; the skeleton

GROWTH AND DIFFERENTIATION OF THE EMBRYO 5

and especially the muscles gain ; the pancreas, digestive tube, and lungs are
little affected.

Continuity of the Germ Plasm. — According to this important concep-
tion of Weismann, the body-protoplasm, or soma, and the reproductive-
protoplasm differ fundamentally. The germinal material is a legacy
that has existed since the beginning of life, from which representative
portions are passed on intact from one generation to the next. Around
this germ plasm there develops in each successive generation a short-lived
body, or soma, which serves as a vehicle for insuring the transmission and
perpetuation of the former. The reason, therefore, why offspring resem-
bles parent is because each, develops from portions of the same stuff.

The Law of Biogenesis. — -Of great theoretical interest is the fact, con-
stantly observed in studying embryos, that the individual in its develop-
ment repeats hastily and incompletely the evolutionary history of its own
species. This law of recapitulation was first stated clearly by Miiller
in 1863 and was termed by Haeckel the law of biogenesis. In accordance
with it, the fertilized ovum is compared to a unicellular organism like the
Amoeba; the blastula is supposed to represent an adult Volvox type; the
gastrula, a simple sponge; the segmented embryo a worm-like stage, and
the embryo with gill slits may be regarded as a fish-like stage. More-
over, the blood of the human embryo in development passes through
stages in which its corpuscles resemble in structure those of the fish and
reptile; the heart is at first tubular, like that of the fish, and the arrange-
ment of blood vessels is equally primitive; the kidney of the embryo is
like that of the amphibian, as are also the genital ducts. Many other
examples of this law may readily be observed.

Some apparently useless structures appear during development,
perfunctorily reminiscent of ancestral conditions; certain other parts, of
use to the embryo alone, are later replaced by better adapted, permanent
organs. Representatives of either of these types may eventually dis-
appear or they may persist throughout life as rudimentary organs; more
than a hundred of the latter have been listed for man. Still other ancestral
organs abandon their provisional embryonic function, yet are retained in
the adult and utilized for new purposes.

Methods of Study.— Human embryos not being available for indi-
vidual laboratory work, the embryos of the lower animals which best illus-
trate certain points are employed instead. Thus the germ cells of Ascaris,
a parasitic round worm, are used to demonstrate the phenomena of
mitosis and maturation; early stages of echinoderms, or of worms, are
frequently used to demonstrate the cleavage of the ovum and the develop-
ment of the blastula and gastrula; the chick embryo affords convenient
material for the study of the early vertebrate embryo and the formation of

<6 INTRODUCTIONS

tibe gam fayos and embryonic membranes, while the structure of a mam-
malian embrvo, similar to tiiat of the human embryo, is best observed in
the readily-procured embryos of the pig. An idea of the anatomy of
embrvos is obtained first bv examining the exterior of whole embryos and
studying dissections and reconstructions of them. Finally, each embryo
iied in serial sections, the level of each section being determined
by comparing it with figures of the whole embryo.

Along with his study of the embryos in the laboratory, the student
should do a certain amount of supplementary reading. Only the^ist of
human organogenesis is contained in the following chapters. A very
complete bibliography of the subject is given in Keibel and Mall 's ' ' Human
Embryology," to which the student is referred. Below are given the
titles Of some of the more important works on vertebrate and human
embryology, to which the student is referred and in which supplementary
reading is recommended.

TITLES FOR REFERENCE

Broman, I. Normale und abnorme EntwicMting des Menschen. Berg-

maTm. Wiesbaden, 1911.

Duval M. Atlas D'Embryologie. Masson, Paris, 1889.
Hertwig, O. Handbuch der Entwicklungslehre der Wirbeltiere. Fischer,

Jena, 3906.

JRTJR. W. Anatonrie menschlicher Embryonen. Vogel, Leipzig, 1885.
Keibel, F. Normentafel zur Entwicklungsgeschichte der Wirbelthiere.

Bd. I. Fischer, Jena, 1897.
Keibel and Elze. Xormentafel zur Entwicklungsgeschichte des Menschen,

Jena, 1908.

Keibel, F. and Mall, F. P. Human Embryology. Lippincott, 1910-1912.
KeJEcott, W. E. A Textbook of General Embryology. Henry Holt, 1913.
KoDmann, J. Handatlas der Entwicklungsgeschichte des Menschen,

Fischer, Jena, 1907.

Laffie, F. R. The Development of the Chick. Henry Holt, 1908.
Minot. C. S. A Laboratory Text-book of Embryology. Blakiston, 1910.
Wilson, E. B. The Cell in Development and Inheritance. Macmillan,

1*933.

CHAPTER I

THE GERM CELLS: MITOSIS, MATURATION AND FERTILIZATION
THE GERM CELLS

THOSE animals, whose offspring reach maturity with reasonable surety
(as the result of internal fertilization and postnatal care), produce fewer
germ cells, especially ova, than those that leave fertilization to chance and
development to hazard. The codfish produces 10 million eggs in a breeding
period, a sea urchin 29 million; in certain mammals and birds only a single
egg is matured, yet the stock of each remains constant.

The highly differentiated human organism, like all other vertebrates
and mo'st invertebrates, develops from the union of two germ cells, the
ovum and spermatozoon.

The Ovum. — The female germ cell, or ovum, is a typical animal cell
produced in the ovary. It is nearly .spherical in form and possesses a
nucleus with nucleolus, chromatin network, and nuclear membrane (Figs,
i and 2). The nucleus is essential to the life, growth, and reproduction
of the cell. The function of the nucleolus is unknown; the chromatin
probably bears the hereditary qualities of the cell. The cytoplasm, of
the ovum is distinctly granular, containing more or less numerous yolk
granules, mitochondria, and rarely a minute centrosome. The yolk gran-
ules, containing a fatty substance termed lecithin, furnish nutrition for the
early development of the embryo. A relatively small amount of yolk
is found in the ova of the higher mammals, since the embryo develops
within the uterine wall of the mother and is nourished by it. A much
larger amount occurs in the ova of fishes, amphibia, reptiles, birds, a"ncf the
primitive mammalia, the eggs of which are laid and develop outside of the
body. The so-called yolk of the hen's egg (Fig. 3) is the ovum proper and
its yellow color is due to the large amount of lecithin which it contains.

Ova become surrounded by protective membranes, or envelopes.
The vitelline membrane, secreted by the egg itself, is a primary membrane
(Fig. 2) . The follicle cells about the ovum usually furnish other secondary
membranes, such as the zona pellucida. In lower vertebrates tertiary
membranes may be added as the egg passes through the oviduct and uterus
• — the albumen and shell of the hen's egg (Fig. 3) or the jelly of the frog's
egg are of this type.

The human ovum is of relatively small size, measuring from 0.22 to
0.25 mm. in diameter (Fig. i). The cytoplasm is surrounded by a thick,

7

8 THE GERM CELLS: MITOSIS, MATURATION AND FERTILIZATION

radially striated membrane, the zona pellucida. The striated appearance
of the zona pellucida is said to be due to fine canals which penetrate it

FIG. i. — Human ovum, two- thirds the mature size, examined fresh in the liquor folliculi
(Waldeyer). X 415. The zona pellucida is seen as a clear girdle surrounded by the cells of
the corona radiata. Yolk granules occupy a central region of the cytoplasm and enclose the
nucleus and nucleolus. At the right is a spermatozoon correspondingly enlarged.

Cytoplasm
of ovum

FIG. 2. — Ovum of monkey. X 430.

and through which nutriment is transferred from smaller follicle cells
to the ovum during its growth within the ovary. The origin and growth
of the ovum within the ovary (oogenesis) are described on pp. '216-218.

THE GERM CELLS

For the present -it is sufficient to state that each growing ovum is at first
surrounded jjy small nutritive cells known as follicle cells. These increase
in number during the growth of the ovum until several layers are formed
(Fig. 229). A cavity appearing between these cells becomes filled with

iv.y. u'.v. ' b I

FIG. 3. — Diagrammatic longitudinal section of an unincubated hen's egg (Allen Thomson
in Heisler). bl., Blastoderm; w.y., white yolk, which consists of a central flask-shaped mass, and
of concentric layers alternating with the yellow yolk (y.y.); vt., vitelline membrane; w., al-
bumen; chl., chalaza; a.ch., air chamber; i.s.m., inner, s.m., outer layer of the shell membrane;
s, shell.

. FIG. 4. — Section of human ovary (Piersol). a, Germinal epithelium; b, tunica albuginea;
c, cortical stroma containing immature follicles, d; e, shrinkage space between theca and
stratum granulosum of «a well-advanced Graafian follicle;/, liquor folliculi; g, ovum surrounded
by cumulus oophorus.

fluid and thus forms a sac, the vesicular (Graafian) follicle, within which
the ovum is eccentrically located (Figs. 4 and 230). The follicular cells
immediately surrounding the ovum form the corona radiata (Fig. i)
when the ovum is set free.

IO THE GERM CELLS: MITOSIS, MATURATION AND FERTILIZATION

Ovulation and Menstruation. — At birth, or shortly after, ova cease
forming. The number at this time in both ovaries has been placed be-
tween 100,000 and 800,000. Cellular degeneration reduces this supply,

FIG. 5. — Uterine tube and ovary with mature Graafian follicle (Ribemont-Dessaignes).

until, at 1 8 years, the total is from 35,000 to 70,000. Of these, relatively
few reach maturity, only about 200 ripe ova developing in each ovary
during the thirty years of sexual activity. Several years after the meno-

Ovum

Follicle cell

Zona pelluclda
FlG. 6. — Immature follicle containing six ova. From the ovary of a ycung monkey. X 430-

pause no more ova are to be found. When an ovum is ripe, the Graafian
follicle is large and contains fluid, probably under vascular and muscular
pressure. The ripe follicles form bud-like protuberances at the surface of

THE GERM CELLS

II

Perforatorium

Head*

Neck

Connect-
ing piece
of tail

Annuity

Chief piece
of tail

— — Ant. centrosomal body
Post, centrosomal body

-Spiral filament

Sheath of axial

filament
— Mitochondrial sheath

the ovary (Fig. 5) and at these points the ovarian wall has become very
thin. At ovulation, that is, the bursting of the Graafian follicle and the
discharge of the ovum, but one ovum is usually liberated. Several ova,
however, may be produced in a single
follicle in rare cases. Such multiple
follicles have been observed in human
ovaries and are of frequent occurrence
in the monkey (Fig. 6).

The observations of various older
workers (Leopold, Ravano and others)
led Mall (1910) to conclude that they
had ' ' shown conclusively that ovulation
and menstruation are usually syn-
chronous." Since then, Meyer, Ruge,
Shroder, Fraenkel, and Halban, utilizing
better standardized corpora lutea as
criteria, have presented evidence ac-
cepted by Grosser (1914) and Mall
(1918) as proof that ovulation occurs
most often between the fourth and
fourteenth day after the menstrual
onset. A survey of all the clinical data
indicates that any such relation is at
best very loose and that many ova are .
liberated without definite reference to
the menstrual cycle. -. Moreover, in
young girls ovulation may precede the .
inception of menstruation and it may
occur in women during pregnancy or
after the menopause.

The Spermatozoon. — The male cell,
or spermatozoon, of man is a. minute
cell 0.055 mm- long, specialized for.
active movement. Because of their
motility, spermatozoa when first dis-
covered were regarded as parasites
living in the seminal fluid. The sperm
cell is composed of a flattened head, short
neck, and thread-like tail (Figs, i and 7).

The head is about 0.005 mm- m length. It appears oval in surface
view, pear-shaped in profile. When stained, the anterior two-thirds of
the head may be seen to form a cap, and the sharp border of this cap is the

.Axial filament

.Sheath

End piece
of tail '

FIG. 7 . — Diagram of a human
spermatozoon, ' surface view (Meves,
Bonnet).

12 THE GERM CELLS: MITOSIS, MATURATION AND FERTILIZATION

perforatorium by means of which the spermatozoon penetrates the ovum.
The head contains the nuclear elements of the sperm cell. The disc-
shaped neck includes the anterior centrosomal body. The tail begins with
the posterior centrosomal body and is divided into a short connecting piece ,
a chief piece, or flagellum, which forms about four-fifths of the length of the
sperm cell, and a short end piece, or terminal filament. The connecting
piece is marked off from the chief piece by the annulus. The connecting
piece is traversed by the axial filament (filum principale) , and is surrounded :
(i) by the sheath common to it and to the flagellum; (2) by a sheath con-
taining a spiral filament; and (3) by a mitochondrial sheath. The chief
piece is composed of the axial filament surrounded by a cytoplasmic sheath,
while the end piece comprises the naked continuation of the axial filament.
The spermatozoa are motile, being propelled by the movements of the
tail. They swim always against a current at the rate of about 2.5 mm. a
minute. This is important, as the outwardly directed currents induced by
the ciliary action of the uterine tubes and uterus direct the spermatozoa
by the shortest route to the infundibulum. Keibel has found spermatozoa
alive three days after the execution of the criminal from whom they were
obtained. They have been found motile in the uterine tube three and
one-half weeks after coitus and have been kept alive eight days outside
the body by artificial means. It is not known for how long a period
spermatozoa are capable of fertilizing ova. Keibel holds that this would
certainly be more than a week. However, Lillie (1915) has shown with
sea urchins that the ability to fertilize is lost long before vitality or motil-
ity is impaired, and Mall (1918) concludes that the duration of the fertil-
izing power of human spermatozoa is safely less than the corresponding
period in the ovum which is "probably for fully 24 hours after ovulation."
Lode estimates that 200 million spermatozoa are liberated at an average
ejaculation.

MITOSIS AND AMITOSIS

All cells arise from pre-existing cells by division. There are two
methods of cell division — amitosis and mitosis.

Amitosis. — -Cells may divide directly by the simple fission of their
nuclei and cytoplasm. This rather infrequent process is called amitosis.
Amitosis is said by many to occur only in moribund cells. It is the type
of cell division demonstrable in the epithelium of the bladder.

Mitosis. — In the reproduction of typically active somatic cells and in
all germ cells, complicated changes take place in the nucleus. These
changes give rise to thread-like structures, hence the process is termed
mitosis (thread) in distinction to amitosis (no thread) . Mitosis is divided
for convenience into four phases (Fig. 8).

MITOSIS AND AMITOSIS

Prophase. — i. The centrosome divides and the two minute bodies
resulting from the division move apart, ultimately occupying positions at
opposite poles of the nucleus (I-III).

2. Astral rays appear in the cytoplasm about each centriole. They
radiate from it, and the threads of the central or achromatic spindle are
formed between the two

asters, thus constituting
the amphiaster (II).

3. The nuclear mem-
brane and nucleolus dis-
appear, the karyoplasm
and cytoplasm becoming
confluent.

4. During the above
changes the chromatic net-
work of the resting nucleus
resolves itself into a skein,
or spireme, which soon
shortens and breaks up
into distinct, heavily-stain-
ing bodies, the chromosomes
(II, III). A definite num-
ber of chromosomes is
always found in the cells
of a given species. The
chromosomes may be
block-shaped, rod-shaped,
or bent in the form of a
Uor V.

5. The chromosomes
arrange themselves in the
equatorial plane of the
central spindle (IV). If
U- or V-shaped, the angle
of each is directed toward

center. The

/\

A

FIG. 8. — Diagrams of the phases of mitosis (Schafer).

a common

amphiaster and the chromosomes together constitute a mitotic figure, and

at the end of the prophase this is called a monaster.

Metaphase. — The longitudinal splitting of the chromosomes into ex-
actly similar halves constitutes the metaphase (IV, V) . The aim of mitosis
is thus accomplished, an accurate division of the chromatin between the
nuclei of the daughter cells.

14 THE GERM CELLS: MITOSIS, MATURATION AND FERTILIZATION

Anaphase. — At this stage the two groups of daughter chromosomes
separate and move up along the central spindle fibers, each toward one of
the two asters. Hence this is called the diaster stage (V, VI). At this
stage, the centrioles may each divide in preparation for the next division
of the daughter cells.

Telo phase. — i. The daughter chromosomes resolve themselves into a
reticulum and daughter nuclei are formed (VII, VIII).

2. The cytoplasm divides in a plane perpendicular to the axis of the
mitotic spindle (VIII). Two complete daughter cells have thus arisen
from the mother cell.

The number of chromosomes is constant in the cells of a given species. The smallest
number of chromosomes, two, occurs in Ascaris megalocephala univalens, a round worm
parasitic in the intestine of the horse. The largest number known is found in the brine
shrimp, Artemia, where 168 have been counted.

The number for the human cell is in doubt. Guyer (1910) and Montgomery (1912)
counted 22 in the spermatogonia of negroes. For white spermatogonia, Guyer (1913)
reported considerably larger numbers (count not given) than he had formerly found in the
negro. This is suggestive in view of Winiwarter's (1912) apparently careful work on whites
which gave for the oocyte 48, for the spermatogone 47; although this enumeration needs
confirmation, it has been tentatively accepted by many. Wieman (1913) found the most
frequent number in various white somatic cells to be 34, but recently (1917) he asserts
that the number in both negro and white spermatogonia is 24, thereby agreeing with
Duesberg's (1906) count.

MATURATION

We have seen that reproduction in vertebrates follows upon the union
of male and female germ cells. Without special provision this union
would necessarily double the number of chromosomes at each generation.
Such progressive increase is prevented by the processes of maturation
which take place in both the ovum and spermatozoon.

Maturation may be defined as a process of cell division during which
the number of chromosomes in the germ cells is reduced to one-half the
number characteristic for the species. Its significance in the mechanism
of inheritance is discussed on p. 22.

Spermatogenesis. — The spermatozoa take their origin in the germinal
epithelium of the testis. Their general development, or Spermatogenesis,
may be studied in the testis of man or of the rat; the details of their
maturation stages in Ascaris or in insects. Two types of cells are recog-
nized in the germinal epithelium of the seminiferous tubules: the susten-
tacular cells (of Sertoli), and the male germ cells or spermatogonia (Fig.
9). The spermatogonia divide, one daughter cell forming what is known
as a primary spermotocyte. The other daughter cell persists as a spermato-
gone, and, by continued division during the sexual life of the individual,

MATURATION 1 5

gives rise to other primary spermatocytes. The primary spermatocytes
correspond to the ova before maturation. Each contains the number of
chromosomes typical for the male of the species.

The process of maturation consists in two cell divisions of the primary
spermatocytes, each producing, first, two secondary spermatocytes, and
these in turn four cells known as spermatids. During these cell divisions
the number of chromosomes is reduced to half the original number in
the spermatogonia. Each spermatid now becomes transformed into a
mature spermatozoon (Fig. 10). The nucleus forms the larger part of
the head; the centrosome divides, the resulting moieties passing to the
extremities of the neck. The posterior centrosome is prolonged to

Spermatid

Sp'c. II (telo phase)
Sp'c. II (metaphase)

Sp'c. I (pro phase) ...
Sustenlacular cell

Connect ive-t iss lie
wall

'mary spermatocyte
Accessory chromo-
._.- some (?)

Sp'c. I (metaphase)

>
— Spermatogonium

Sp'g. (anaphase)

FIG. 9. — Stages in the spermatogenesis of man arranged in a composite to represent a portion
of a seminiferous tubule sectioned transversely. X 900.

become the axial filament, and the cytoplasm forms the sheaths of the
neck and tail. The spiral filament of the connecting piece is derived from
the cytoplasmic mitochondria.

The way in which the number of chromosomes is reduced may be
seen in the spermatogenesis of Ascaris (Fig. n). Four chromosomes are
typical for Ascaris megalocephala bivalens and each spermatogone contains
this number. In the' early prophase of the primary spermatocyte there
appears a spireme thread consisting of four parallel rows of granules (B).
This thread breaks in twro and forms two quadruple structures known as
tetrads (D-F) ; each is equivalent to two original chromosomes, paired side

i6

THE GERM CELLS: MITOSIS, MATURATION AND FERTILIZATION

by side and split lengthwise to make a bundle of four. At the metaphase
(G) each tetrad divides into its two original chromosomes which already
show evidence of longitudinal fission and are termed dyads. One pair of
dyads goes to each of the daughter cells, or secondary spermatocytes (G-I).
Without the formation of a nuclear membrane, the second maturation
spindle appears at once, the two dyads split into four monads, and each
daughter spermatid receives two single chromosomes (monads) , or one-half
the number characteristic for the species. The tetrad, therefore, repre-

E F

FIG. 10. — Diagrams of the development of spermatozoa (after Meves in Lewis and Stohr).
a.c., Anterior centrosome; a./., axial filament; c.p., connecting piece; ch.p., chief piece; g.c., cap;
n., nucleus; nk., neck; p., protoplasm; p.c., posterior centrosome.

sents a precocious division of the chromosomes in preparation for two
rapidly succeeding cell divisions which occur without the intervention of
the customary resting periods. The easily understood tetrads are not
formed in most animals, although the outcome of maturation is identical in
either case. A diagram of maturation is shown in Fig. 12. The first
maturation division in Ascaris is probably reductional, each daughter
nucleus receiving two complete chromosomes of the original four, whereas
in the second maturation division, as in ordinary mitosis, each daughter
nucleus receives a half of each of the two chromosomes, these being split
lengthwise. In the latter case the division is equational, each daughter
nucleus receiving chromosomes bearing similar hereditary qualities.

In some animals the sequence of events is reversed, reduction occurring
at the second maturation division. In many insects and some vetebrates

MATURATION

it has been shown that the number of chromosomes in the oogonia is even,
the number in the spermatogonia odd. An exact halving of the sperma-
togonial number of chromosomes can not occur in such cases (p. 23).

FIG. II. — Reduction of chromosomes in the spermatogenesis of Ascaris megalocephala
bivalens (Brauer, Wilson). X about noo. A-G, successive stages in the division of the pri-
mary spermatocyte. The original reticulum undergoes a very early division of the chromatin
granules which then form a quadruply split spireme (B, in profile). This becomes shorter (C,
in profile), and then breaks in two to form two tetrads (D, in profile), (E, on end). F, G, H, first
division to form two secondary spermatocytes, each receiving two dyads. 7, secondary sperma-
tocyte. /, K, the same dividing. L, two resulting spermatids, each containing two monads
or chromosomes.

Oogenesis. — -During oogenesis, the ova undergo a similar process of
maturation. Two cell divisions take place, but with this difference: the
cleavage is unequal, and, instead of four cells of equal size resulting, there
are formed one large ripe ovum, or oocyte, and three rudimentary or abor-
tive ova known as polar bodies, or polocytes. The number of chromosomes

1 8

THE GERM CELLS: MITOSIS, MATURATION AND FERTILIZATION

is reduced in the same manner as in the spermatocyte, so that the ripe
ovum and each polar cell contain one-half the number of chromosomes
found in the immature ovum or primary oocyte.

The primitive female germ cells, from which new ova are produced
by cell division, are called oogonia and their daughter cells after a period
of growth within the ovary are the primary oocytes, comparable to the
primary spermatocytes of the male (Fig. 12). During maturation the
ovum and first polocyte are termed secondary oocytes (comparable to
secondary spermatocytes) ; the mature ovum and second polocyte, with

Spermatogonium

Proliferation
period

Spermatocyte i
Spermatocyte 2

Spermatids
Spermatozoa

Oocyte 2 (omtm
and polocyte i)

Ovum and
three polo-
cytcs

Growth
period

Maturation
period

Transforma-
tion period of
spermatozoa

FIG. 12. — Diagrams of maturation in spermatogenesis and oogenesis (Boveri).

the daughter cells of the first polocyte, are comparable to the spermatids.
Each spermatid, however, may form a mature spermatozoon, but only
one of the four daughter cells of the primary oocyte becomes a mature
ovum. The ovum develops at the expense of the three polocytes which
are abortive and degenerate eventually, though it has been shown that in
the ova of some insects the polar cell may be fertilized and segment several
times like a normal ovum. In most animals, the actual division of the
first polocyte into two daughter cells is suppressed. The nucleus of the
ovum after maturation is known as the female pronucleus.

Maturation of the Mouse Ovum. — Typical maturation stages may be
studied in the easily obtained ova of the mouse (Long and Mark, Carnegie
Inst. Publ. No. 142). The first polocyte is formed while the ovum is

MATURATION

still in the Graafian follicle. In the formation of the maturation spindle,
no astral rays and no typical centrosomes have been observed. The
chromosomes are V-shaped. The first polar cell is constricted from the
ovum and lies beneath the zona pellucida as a spherical mass about
25 micra in diameter (Fig. 13). Both ovum and polar cell (secondary

FIG. 13. — Maturation and fertilization of the ovum of the mouse (after Sobotta). A,
C-J, X 500; B X 750. A-D, entrance of the spermatozoon and formation of the polar cells.
D-E, development of the pronuclei. F-J, successive stage in the first division of the fer-
tilized ovum.

oocytes) contain 20 chromosomes, or half the number normal for the
mouse. The first maturation division is the reductional one and the
chromosomes take the form of tetrads.

After ovulation has taken place, the ovum lies in the ampulla of the
uterine tube. If fertilization occurs, a second polocyte is cut off, the
nucleus of the ovum forming no membrane between the production of

20 THE GERM CELLS: MITOSIS, MATURATION AND FERTILIZATION

the first and second polar bodies (Fig. 13 A-D). The second maturation
spindle and second polar cell are smaller than the first. Immediately
after the formation of the second polar cell, the chromosomes resolve them-
selves into a reticulum and the female pronucleus is formed (Fig. 13 D).

Maturation of the Human Ovum. — The only observations are those
of Thompson (1919), who believes to have identified stages in the forma-
tion of all three polar cells prior to ovulation or fertilization. The evi-
dence presented, however, can hardly be accepted as conclusive.

FERTILIZATION

The stimulus initiating development in most multicellular animals
is furnished by a spermatozoon which penetrates the ovum and fuses with
its nucleus. These events constitute fertilization.

Only motile spermatozoa are able to attach to the surface of an egg;
it is probable that forces allied to phagocytosis, rather than vibrational
energy, accomplish the actual 'penetration.' Spermatozoa may enter
the mammalian ovum at any point. If fertilization is delayed too long
after ovulation, the ovum may be weakened and allow the entrance of
several spermatozoa. This is known as polyspermy. In such cases, how-
ever, only one spermatozoon unites with the female pronucleus.

The fundamental results of the process of fertilization are: (i) the
union of the male and female chromosomes to form the cleavage nucleus of the
fertilized ovum; (2) the initiation of cell division, or cleavage of the ovum.

These two factors are separate and independent phenomena. It has been shown by
Boveri and others that fragments of sea urchin's ova containing no part of the nucleus may
be fertilized by spermatozoa, segment, and develop into larvae. The female chromosomes
are thus not essential to the process of segmentation. Loeb, on the other hand, has shown
that the ova of invertebrates may be made to develop by chemical and mechanical means
without the cooperation of the spermatozoon (artificial parthenogenesis). Even adult frogs
have been reared from mechanically stimulated eggs. It is well known that the ova of
certain invertebrates develop normally without fertilization, that is, parthenogenetically.
These facts show that the union of the male and female pronuclei is not the means of initiat-
ing the development of the ova. In all vertebrates it is, nevertheless, the end and aim of
fertilization.

Lillie (1912; 1913) has recently shown that the cortex of sea urchin's ova produces a
substance which he terms fertilizin. This substance he regards as an amboceptor essential
to fertilization, with one side chain which agglutinates and attracts the spermatozoa, and
another side chain which activates the cytoplasm and initiates the cleavage of the ovum.
According to Loeb (1916), agglutination is proved in but few forms and Lillie's interpreta-
tion fails to meet all the facts. Loeb (1913) holds that the spermatozoon actually acti-
vates the ovum to develop by increasing its oxidations and by rendering it immune to the
toxic effects of oxidation.

Fertilization of the Mouse Ovum. — Normally, a single spermatozoon
enters the ovum six to ten hours after coitus. While the second polar cell
is forming, the spermatozoon penetrates the ovum and loses its tail. Its

FERTILIZATION 21

head enlarges and is converted into the male pronucleus (Fig. 13 D). The
pronuclei, male and female, approach each other and resolve themselves
first into a spireme stage, then into two groups of 20 chromosomes. A
centrosome, possibly that of the male cell, appears between them, divides
into two, and soon the first cleavage spindle is formed (F-H). The 20
male and 20 female chromosomes arrange themselves in the equatorial
plane .of the spindle, thus making the original number of 40 (I). Fer-
tilization is now complete and the ovum divides in the ordinary way, the
daughter cells each receiving equal numbers of maternal and paternal
chromosomes.

Fertilization of the Human Ovum. — Spermatozoa, deposited in the
vagina at coitus, ascend through the uterus and uterine tubes, their
course being directed by the downward stroking cilia (p. 12). They
probably reach the ampulla of the uterine tube two or more hours
after coitus. Here the penetration of the ovum is believed usually to
take place about one day after coitus (Mall, 1918, cf. p. 12) although it has
never been observed. This conclusion is supported by direct observation
on other mammals and by the frequency of tubal pregnancies at this site.
Normally, then, the embryo begins its development in the uterine tube,
thence passes to the uterus and becomes embedded in the uterine mucosa.
Rarely ova may be fertilized and start developing before they enter the
tube, but fertilization within the uterus is usually denied.

Twin Development. — Usually but one human ovum is produced and fertilized at
coitus. The development of two or more embryos within the uterus is commonly due to the
ripening, expulsion, and subsequent fertilization of an equal number of ova. In such cases
ordinary, or fraternal twins, triplets, and so on, of the same or opposite sex, result. Iden-
tical, or duplicate twins, that is, those always of the same sex and strikingly similar in form
and feature, are believed to arise from the fission of the embryonic cell mass, each portion
then developing as a separate embryo within the common chorion. The identical quadru-
plets of certain armadillos are known to result from the division of a single blastoderm into
four parts. Separate development of the cleavage cells can also be produced experimen-
tally in many of the lower animals.

Double Monsters. — Occasionally twins are conjoined. All degrees of union, from
almost complete separation to fusion throughout the entire body-length, are known. If
there is considerable disparity in size, the smaller is termed the parasite; in such cases the
extent of attachment and dependency grades down to included twin (fetus in fetu) and
tumor-like fetal inclusions. In some asymmetrical monsters the explication is partial,
as doubling of the head or legs, All of these terata, like identical twins, are regarded as
the products of a single ovum, but with variably incomplete fission, or bifurcation, of the
embryonic mass.

Superfetation. — An ovum, liberated by a pregnant woman and fertilized at a later
coitus, may develop into a second, younger fetus. This rare condition, often denied, is
called superfetation and is not to be confused with striking^ unequal twin development.
Until the fourth month of pregnancy superfetation is theoretically possible (p. 237).

22 THE GERM CELLS: MITOSIS, MATURATION AND FERTILIZATION

The Significance of Mitosis, Maturation and Fertilization. — The complicated proc-
esses of mitosis serve the purpose of accurately dividing the chromatic substance of the
nucleus in such a way that the self-perpetuating chromosomes of each daughter cell may
be the same both quantitatively and qualitatively. This is of importance since it is
believed by most students of heredity that chromatin particles, or genes, in the chromo-
somes bear the hereditary characters, and that these are arranged in definite linear order
in particular chromosomes. At maturation there is a side by side union of like chromo-
somes, one member of each pair having come from the father, the other from the mother
of the preceding generation; each member, however, carries the same general set of heredi-
tary characters as its mate. At this stage of chromosomal conjugation there may be an
interchange,, or 'crossing over,' of corresponding genes, resulting in new hereditary
combinations. The reducing division of maturation separates whole chromosomes of
each pair, but chance alone governs the actual assortment of paternal and maternal mem-
bers to the daughter cells; this mitosis obviously halves the chromosome number char-
acteristic for the species. The significance of the equational maturation mitosis, beyond
accomplishing mere cellular multiplication, is obscure.

Fertilization initiates development and restores the original number of chromosome
pairs (cf. p. 20). The fertilized ovum derives its nuclear substance equally from both
parents, the cytoplasm and yolk almost entirely from the mother, the centrosome probably
from the father.

Mendel's Law of Heredity. — Experiments show that most hereditary characters fall
into two opposing groups, the contrasted pairs of which are termed allelomorphs. As an
example, we may take the hereditary tendencies for black and blue eyes. It is
believed that there are paired chromatic particles, or genes, which are responsible for
these hereditary tendencies, and that paired spermatogonial chromosomes bear one
each of these genes. Each chromosome pair in separate germ cells may possess similar
genes, both bearing black-eyed tendencies or both blue-eyed tendencies, or opposing
genes, bearing the one black, the other blue-eyed tendencies. It is assumed that at
maturation these paired genes are separated along with the chromosomes, and that one
onl of each pair is retained in each germ cell.

In our example, either a blue-eyed or a black-eyed tendency-bearing particle would be
retained. At fertilization the segregated genes of one sex may enter into new combina-
tions with those from the other sex. Three combinations are possible. If the color of the
eyes be taken as the hereditary character: (i) two 'black' germ cells may unite; (2) two
'blue' germ cells may unite; (3) a 'black' germ cell may unite with a 'blue' germ cell. The
offspring in (i) will all have black eyes, and, if interbred, their progeny will likewise inherit
black eyes exclusively. Similarly, the offspring in (2), and if these are interbred their
progeny as well, will include nothing but blue-eyed individuals. The first generation from
the cross in (3) will have black eyes solely, for black in the present example is dominant, as
it is termed. Such black-eyed individuals, nevertheless, possess both black- and blue-
eyed bearing genes their germ in cells; in the progeny resulting from the interbreeding of
this class the original condition is repeated — pure blacks, impure blacks which hold blue
recessive, and pure blues will be formed in the ratio of 1:3:1 respectively. It is thus seen
that blue-eyed children may be born of black-eyed parents, whereas blue-eyed parents
can never have black-eyed offspring. Many such allelomorphic pairs of hereditary
characters are known.

Cytoplasmic Inheritance. — Certain eggs show distinct cytoplasmic zones which
cleavage later segregates into groups of cells destined to form definite organs or parts.
In a sense this represents a refined sort of preformation, but prelocalization is a more exact

FERTILIZATION 23

term. From these facts Conklin and Loeb argue that.the cytoplasm is really the embryo
in the rough, the nucleus, through Mendelian heredity, adding only the finer details.
Morgan, among others, refuses to admit the validity of this interpretation.

The Determination of Sex. — The assumption that the chromosomes are the carriers
of hereditary tendencies is borne out by experimental breeding (Morgan) and by the corre-
lated observations of cytologists on the germ cells of invertebrates, especially insects, and
of some vertebrates. According to Winiwarter (Arch, de Biol., T. 27, 1912) the nuclei
of human spermatogonia contain 47 chromosomes, while those of the oogonia contain 48.
When the reduction of chromosomes takes place in the male cells, one unpaired chromo-
some fails to divide and passes intact to one or the other daughter cells; hence half of the
spermatids contain 24 chromosomes, the other half only 23. All the oocytes and polocytes,
on the contrary, contain 24. There is thus one extra chromosome in each mature ovum
and in each of half the spermatozoa. This chromosome, because of peculiarities of size
or shape, can be identified easily in many animals, and is termed the accessory X,or sex
chromosome. McClung was the first tc assume that the X chromosome is a sex detriminant.
It has since been shown by Wilson and others that the sex chromosome carries the female
sexual characters. When, in the case under consideration, a spermatozoon with 24
chromosomes fertilizes an ovum, the resulting embryo is a female, its somatic nuclei
containing 48 chromosomes. An ovum fertilized by a sperm cell containing only 23
chromosomes (without the sex chromosome) produces a male with somatic nuclei con-
taining but 47 chromosomes. These observations of Winiwarter on man have not yet
been confirmed by other investigators. There is no reason to doubt, however, that sex
is determined in man essentially in the manner described, which agrees with the easily
observed phenomena in insects.

In certain moths and birds the sex chromosome system is the exact reverse of the
common scheme just explained, but the operation of the mechanism is otherwise similar.
The spermatozoa of these forms are all alike in chromosome constitution while the eggs
are of two sorts.

CHAPTER II

CLEAVAGE OF THE FERTILIZED OVUM AND THE ORIGIN OF THE

GERM LAYERS

CLEAVAGE

THE processes of cleavage, or segmentation, not having been ob-
served in human ova, must be studied in other vertebrates. It is probable
that the early development of all vertebrates is, in its essentials, the same.
Cleavage may be modified, however, by the presence in the ovum of large
quantities of nutritive yolk. In many vertebrate ova the yolk collects
at one end, termed the vegetal pole, in contrast to the more purely proto-
plasmic animal pole. Such ova are said to be telolecithal. Examples are
the ova of fishes, amphibians, reptiles, and birds. When very little
yolk is present, the ovum is said to be isolecithal. Examples are the
ova of Amphioxus, the higher mammals, and man. The typical processes
of cleavage may be studied most easily in the fertilized ova of invertebrates
(Echinoderms, Annelids, and Mollusks). Among Chordates, the early
processes in development are primitive in a fish-like form, Amphioxus.
The yolk modifies the development of the amphibian and bird egg, while
the early structure of the mammalian embryo can be explained only by
assuming that the ova of the higher Mammalia at one time contained a
considerable amount of yolk, like the ovum of the bird and of the lowest
mammals, and the influence of this condition persists.

Cleavage in Amphioxus. — The ovum is essentially isolecithal, since
it contains but little yolk (Fig. 14). About one hour after fertilization it
divides vertically into two nearly equal daughter cells, or blastomeres.
The process is known as cell cleavage, or segmentation, and takes place by
mitosis. Within the next hour the daughter cells again cleave in the
vertical plane, at right angles to the first division, thus forming four cells.
Fifteen minutes later a third division takes place in a horizontal plane.
As the yolk is somewhat more abundant at the vegetal pole of the four
cells, the mitotic spindles lie nearer the animal pole. Consequently, in
the eight-celled stage the upper tier of four cells is smaller than the lower
four. By successive cleavages, first in the vertical, then in the horizontal
plane a 16- and 3 2 -celled embryo is formed. The upper two tiers are now
smaller, and a cavity, the blastoccele, is enclosed by the cells. The embryo
at this stage is sometimes called a morula because of its resemblance to a

24

CLEAVAGE

mulberry. In subsequent cleavages, as development proceeds, the size
of the cells is diminished while the cavity enlarges (Fig. 14). The embryo

FIG. 14. — Cleavage of the egg of Amphioxus (after Hatschek). X 200. I. The egg be-
fore the commencement of development; only one polar body, P.B., is present, the other having
been lost during ovulation. 2. The ovum in the act of dividing, by a vertical cleft, into two
equal blastomeres. 3. Stage with four equal blastomeres. 4. Stage with eight blastomeres;
an upper tier of four slightly smaller ones and a lower tier of four slightly larger ones. 5. Stage
with sixteen blastomeres in two tiers, each of eight. 6. Stage with thirty-two blastomeres, in
four tiers, each of eight ; the embryo is represented bisec ted to show the cleavage cavity or blasto-
coele, B. 7. Later stage; the blastomeres have increased in number by further division. 8,
Blastula stage bisected to show the blastoccele, B.

is now a blastula, nearly spherical in form and about four hours old. The
cleavage of the Amphioxus ovum is thus holoblastic, that is, complete, and
nearly equal.

26 CLEAVAGE AND THE GERM LAYERS

Cleavage in Amphibia.- — These ova contain so much yolk that the
nucleus and most of the cytoplasm lie at the upper, or animal pole. The
first cleavage spindle appears eccentrically in this cytoplasm. The first two
cleavage planes are vertical and at right angles, and the four resulting cells
are nearly equal. The spindles for the third cleavage are located near the
animal pole, and the cleavage takes place in a horizontal plane. As a result,
the upper four cells are much smaller than the lower four (Fig. 15 A).
The large, yolk-laden cells divide more slowly than the upper, small cells
(B-D). At the blastula stage, the cavity is small, and the cells of the
vegetal pole are each many times larger than those at the animal pole (E,F).
The cleavage of the frog's ovum is thus complete but unequal.

E F G

FIG. 15.— Cleavage and gastrulation in the frog. Xi2. A-D, cleavage stages ; E, blastula;
F, blastula in median section; G, early gastrula; H, median section of stage G. an., Animal
cells; arch., archenteron; b'c., blastocoele; b'p., blastopore; ect., ectoderm; ent., entoderm;
v'S-> vegetal cells.

Cleavage in Reptiles and Birds. — The ova of these vertebrates contain
a large amount of yolk. There is very little pure cytoplasm except at the
animal pole, and here the nucleus is located (Fig. 3). When segmentation
begins, the first cleavage plane is vertical but the inert yolk does not cleave.
The segmentation is thus meroblastic, or incomplete. In the hen's ovum,
the cytoplasm is divided by successive vertical furrows into a mosaic of
cells, which, as it increases in size, forms a cap-like structure upon the
surface of the yolk (Fig. 16 A). These cells are separated from the yolk
beneath by horizontal cleavage furrows, and successive horizontal cleav-
ages give rise to several layers of cells (Fig. 16 B). The space between
cells and yolk mass may be compared to the blastula cavity of Amphioxus
and the frog (Fig. 18). The cellular cap is termed the germinal disc, or
blastoderm. The yolk mass, which forms the floor of the blastula cavity

FIG. 17. — Diagrams showing the cleavage of the mammalian ( rabbit's) ovum and the formation
of the blastodermic vesicle (Allen Thomson, after van Beneden). X 200.

CLEAVAGE 2 7

and the greater part of the ovum, may be compared to the large, yolk-
laden cells at the vegetal pole of the frog's blastula. The yolk mass never
divides but is gradually used up in supplying nutriment to the embryo
which is developed from the cells of the germinal disc. At the periphery of
the blastoderm new cells constantly form until they enclose the yolk
(Fig. 18 Q.

Vitelline membrane

Blastomere Blastocoele

A B

FIG. 16.— Cleavage of the pigeon's ovum (after Blount). A, blastoderm in surface view;

B, in vertical section.

Cleavage in Mammals. — The ovum of all the higher mammals, like
that of man, is isolecithal and nearly microscopic in size. Its cleavage
has been studied in several mammals but the rabbit's ovum will serve as
an example. The cleavage is complete and nearly equal (Fig. 17), a
cluster of approximately uniform cells being formed within the zona
pellucida. This corresponds to the morula stage of Amphioxus. Next
an inner mass of cells is formed that is equivalent to the germinal disc, or
blastoderm, of the chick embryo (Fig. 17). The inner cell mass is over-
grown by an outer layer which is termed the trophectoderm, because,
in mammals, it later supplies nutriment to the embryo from the uterine
wall. Fluid next appears between the outer layer and the inner cell mass,
thereby separating the two except at the animal pole. As the fluid in-
creases in amount, a hollow vesicle results, its walls composed of the
single-layered trophectoderm except where this is in contact with the
inner cell mass. This stage is known as that of the blastodermic vesicle.
It is usually spherical or ovoid in form, as in the rabbit, and probably
this is the form of the human ovum at this stage. In the rabbit the
vesicle is 4.5 mm. long before it becomes embedded in the wall of the
uterus. Among Ungulates (hoofed animals), the vesicle is greatly elon-
gated and attains a length of several centimeters, as in the pig.

If we compare the mammalian blastodermic vesicle with the blastula
stages of Amphioxus, the frog, and the bird, it will be seen that it is to be
homologized with the bird's blastula, not with that of Amphioxus (Fig. 18).
In each case there is an inner cell mass of the germinal disc. The tro-

2<S

CLEAVAGE AND THE GERM LAYERS

phectoderm of the mammal represents a precocious development of cells,
which, in the bird, later envelop the yolk. The cavity of the vesicle is
to be compared, not with the blastula cavity of Amphioxus and the frog ,
but with the yolk mass plus the cleft-like blastocaele of the bird's ovum. The
mammalian ovum, although almost devoid of yolk, thus develops much

Blastula cavity

Yolk cavity

FIG. 1 8. — Diagrams showing the blastulae: A, of Amphioxus; B, of frog; C, of chick; D, blasto-
dermic vesicle of mammal.

like the yolk-laden ova of reptiles and birds. This similarity has an
evolutionary significance. Its cleavage, however, is complete and the
early stages in its development are abbreviated.

In Primates, but one cleavage stage has been observed. This, a four-celled ovum of
Macacus nemestrinus figured by Selenka, shows the cells nearly equal, and oval in form.
This ovum was found in the uterine tube of the monkey and shows that, in Primates and
probably in man, cleavage as in other mammals take place normally in the oviducts.

THE FORMATION OF ECTODERM AND ENTODERM (GASTRULATION)
The blastula and early blastodermic vesicle show no differentiation
into layers. Such differentiation takes place later in all vertebrate em-
bryos, giving rise first to the ectoderm and entoderm, and finally to the
mesoderm. From these three primary germ layers all tissues and organs
of the body are derived.

The processes of gastrulation, by which ectoderm and entoderm arise,
and of mesoderm formation will be treated separately.

THE FORMATION OF ECTODERM AND ENTODERM (GASTRULATION)

Amphioxus and Amphibia. — In these animals the larger cells at the
vegetal pole of the blastula either fold inward, that is, invaginate (Amphi-
oxus, Fig. 19), or are for the most part asymmetrically overgrown by the
more rapidly dividing cells of .the animal pole (amphibia, Fig. 15 G, H}.
Eventually the invaginating cells obliterate the blastula cavity and come in
contact with the outer layer of cells (Fig. 1 9) . The new cavity thus formed
is the primitive gut, or archenteron, and its narrowed mouth is the blastopore.
The outer layer of cells is the ectoderm, the inner, newly formed layer is
the entoderm. The entodermal cells are henceforth concerned in the
nutrition and metabolism of the body. The embryo is now termed a
Gastrula (little stomach).

A nimal cells

Blastoccele

Entoderm
A rchenteron

Ectoderm

°Aal cells

FIG. 19. — Gastrulation in Amphioxus.

X about 200.
gastrulas.

A, blastula; B, C, early and late

Reptiles and Birds/ — The germinal disc, or blastoderm, in these
animals lies like a cap on the surface of inert yolk (Fig. 3). Since the
enormous amount of yolk makes gastrulation as in Amphioxus and am-
phibians impossible, the process exhibits marked modifications.

There appears caudally on the blastoderm of reptiles a pit-like depres-
sion. From this slight invagination a proliferation of cells forms a layer
which spreads beneath the ectoderm. The inner layer, originating in this
manner, is the entoderm, and the region of the pit, where ectoderm and
entoderm are continuous, is the blastopore. In Fig. 2 1 A these changes are
complete.

In birds, the caudal portion of the blastoderm is rolled or tucked under,
the inner layer formed in this way constituting the entoderm. The
marginal region where ectoderm and entoderm meet bounds the blastopore,
while the space between entoderm and yolk is the archenteron.

Mammals. — As in cleavage, so also in gastrulation the mammalian
ovum exhibits a modified behavior indicative of an ancestral yolk-rich
condition. Cells on the under surface of the inner cell mass become
arranged in a definite sheet, the entoderm, which rapidly spreads and lines

30 CLEAVAGE AND THE GERM LAYERS

the blastodermic vesicle (Figs. 17, 74 A and 75). The entodermal layer
is usually said to arise by splitting, or delamination. Recent careful
work, however, shows that in some mammals, at least, the entoderm cells
originally lie within the inner cell mass and reach the inner surface by
migration (Hartman, 1919).

ORIGIN OF THE MESODERM, NOTOCHORD AND NEURAL TUBE

Amphioxus and Amphibia.— The dorsal portion of the entodermal
sheet, which forms the roof of the archenteron in Amphioxus, gives rise to
paired lateral diverticula, or ccelomic pouches (Fig. 20). These separate
both from the plate of cells in the mid-dorsal line (which forms the noto-

n.g.

•ccel. p.

FIG. 20. — Origin of the mesoderm in Amphioxus (after Hatschek). X about 425. n.g.,
Neural groove; n.c., neural canal; ch., anlage of notochord; ccel. p., ccelomic pouch; ect., ectoderm;
ent., entoderm; a/., cavity of gut; cce., ccelom or body cavity.

chord}, and from the entoderm of the gut, and become the primary meso-
derm. The mesodermal pouches grow ventral and their cavities form the
ccelom, or body cavity. Their outer walls, with the ectoderm, form the
body wall, or somatopleure; their inner walls, with the gut entoderm, form
the intestinal wall, or splanchnopleure. In the meantime, a dorsal plate
of cells, cut off from the ectoderm, has formed the neural tube (anlage of
the nervous system), and the notochordal plate has become a cord, or
cylinder, of cells (axial skeleton) extending the length of the embryo.
In this simple fashion the ground plan of the chordate body is developed.

In Amphibia, instead of mesodermal diverticula solid plates grow out
from the dorsal entoderm between the ectoderm and entoderm. Later,
these plates split into two layers and the cavity so formed give rise to the
ccelom.

Reptiles. — The same pocket-like depression in the caudal portion of
the blastoderm, that gave rise to the cells of the entodermal layer, now
invaginates more extensively and forms a pouch which pushes forward

ORIGIN OF THE MESODERM, NOTOCHORD AND NEURAL TUBE

between ectoderm and entoderm (Fig. 21 A and B). The size of the
invagination cavity varies in different species; in some it is elongated and
narrow, being confined to the middle line of the blastoderm. The floor of

Ectoderm

Blastopore

Entoderm

Notochordal
plate

Remnant of floor

FIG. 21. — Longitudinal sections of the snake's blastoderm at various stages to show the origin
of the notochordal plate (adapted after Hertwig).

this pouch soon fuses with the underlying entoderm and the two thin,
rupture, and disappear, thus putting the cavity of the pouch temporarily
in communication with the space (archenteron) beneath the entoderm

Ectoderm

Mesoderm

Notochordal Entoderm

plate

FIG. 22. — Transverse section of a snake's blastoderm at a level corresponding to the middle of
Fig. 21 C (adapted after Hertwig).

(Fig. 21 C). The cells of the roof persist as the notochordal plate, which
later gives rise to the notochord. The neural folds arise before the mouth
of the pouch (blastopore) closes up, and, fusing to form the neural tube,

CLEAVAGE AND THE GERM LAYERS

incorporate the blastopore into its floor. This temporary communica-
tion between the neural tube and the primitive enteric cavity is the neuren-
teric canal (cf. Fig. 21 Q ; it is found in all the vertebrate groups (cf. Fig. 78).
A transverse section through the invaginated pouch, at the time of
rupture of its floor, and the underlying entoderm will make clear the
relatively slight lateral extent of these changes (Fig. 22).

From about the blastopore, and from the walls of the pouch, mesoder-
mal plates arise and extend like wings between the ectoderm and entoderm
(Fig. 22). As in amphibia, they later separate into outer (somatic) and
inner (splanchnic) layers enclosing the ccelom (cf. Fig. 29 B). The rela-
tion between notochordal plate,
mesoderm, and entoderm shown in
Fig. 22 resembles strikingly the con-
ditions in Amphioxus (Fig. 20 .4).

Birds. — Due to the modified
gastrulation in reptiles, birds, and
mammals through the influence of
yolk, a structure known as the
primitive streak becomes important.
An account of its formation and
significance based on conditions
found in the bird may be introduced
conveniently at this place.

Shortly after the formation of
entoderm there appears in the
median line at the more caudal por-
tion of the blastoderm an elongated opaque band (Fig. 23). Along
this primitive streak, which is at first merely a linear ectodermal thickening,
there forms a shallow primitive groove, bounded laterally by primitive
folds. At its forward end the groove enters a depression, the primitive pit.
In front of this pit the streak ends in a knob, the primitive knot, or node
(of Hensen).

The primitive streak becomes highly significant when interpreted in
the light of the theory of concrescence, a theory of general application in
vertebrate development. It will be remembered that the entoderm of
birds arises by a rolling under of the outer layer along the caudal margin of
the blastoderm. As the blastoderm expands, it is believed that a middle
point on this margin remains fixed while the edges of the margin on each
side are carried caudad and brought together. Thus, a crescentic margin
is transformed into a longitudinal slit, as in Fig. 24. Since this marginal
lip originally bounded the blastopore (p. 29), the longitudinal slit must
also be an elongated blastopore whose direction has merely been changed.

opaca

ij Primitive knot
Primitive pit

__ _j Primitive fold
IB Primitive groove

Area pellucida
Blood island

FIG. 23. — Blastoderm of a chick embryo
at the stage of the primitive streak and
groove (16 hours). X 20.

ORIGIN OF THE MESODERM, NOTOCHORD AND NEURAL TUBE 33

The lips of the slit fuse, forming the primitive streak. The primitive
groove may be interpreted as a further futile attempt at invagination in
the region of the blastopore. The teachings of comparative embryology
support these conclusions, for the neurenteric canal arises at the cranial
end of the primitive streak, the anus at its caudal end, while the primary
germ layers fuse in its substance. All these relations exist at the blasto-
pore of the lower animals.

FIG. 24. — Diagram elucidating the formation of the primitive streak (Duval in Heisler).
The increasing size of the blastoderm during development is indicated by dotted circular
lines. The heavy line represents the crescentic groove from which the primitive streak arises
by the fusion of its edges.

From the thickened ectoderm of the primitive. streak a proliferation
of cells takes place and there grows out laterally and caudally between the
ectoderm and entoderm a solid plate of mesoderm (Fig. 3 1 B, C} . This
soon splits into somatic and splanchnic layers (Fig. 34). An axial
growth, the head process, or notochordal plate, likewise extends forward from
the primitive knot (Figs. 25 and 30). This fuses at once with the ento-
derm and from its sides grow out lateral wings of mesoderm (Fig. 31 A).

Neural plate Primitive knot

Primitive pit Primitive streak Ectoderm

\ Yolk

Head process Entoderm Mesoderm

Yolk

FIG. 25. — Median longitudial section of a chick embryo at the stage of the primitive streak and

head process. X 100.

Since the primitive streak and groove represent a modified blastopore, it
is evident that this cranial extension, the head process, corresponds to the
pouchlike invagination concerned in the formation of notochord and
mesoderm in reptiles. In birds the- fusion of the head process with the
entoderm, the relation of mesodermal sheets to it laterally, the formation
of the notochord from its tissue and the occasional traces in it of a cavity
continuous with the primitive pit (that is, a notochordal, or neurenteric
canal), all recall the conditions described for the less modified invagination
in reptiles.

34

CLEAVAGE AND THE GERM LAYERS

Mammals. — -On the blastoderm of mammals appear a primitive streak
and knot essentially as in birds (Figs. 26 A and 28). Similarly, from the
keel-like ectodermal thickening of the primitive streak mesoderm grows
out laterally and caudally, and from the primitive knot there is continued
forward a head process. All three primary germ layers fuse in the primitive
knot,vthis condition being known in man. The head process of many
mammalian embryos contains a cavity (notochordal canal) , which in some
cases is of considerable size, opening at the primitive pit. As in reptiles,
the floor of this cavity fuses with the entoderm and the two rupture and
disappear. A still persistent portion of the floor is shown in Fig. 27.
Thus a notochordal canal, later enclosed by the neural folds, and then
known as the neur enteric canal, puts the dorsal surface of the blastoderm

FIG. 26.— Early blastoderms of pig embryos (Keibel). X 20. A, Embryo with primi-
tive streak and primitive knot; B, a later 'embryo in which the neural groove is also present,
cephalad in position.

into communication with the enteric cavity beneath the entoderm (Figs.
77 and 78). The roof of the head process, or notochordal canal, is for a
time closely associated with the mesoderm and entoderm (compare these
relations in reptiles, Fig. 22), but it eventually becomes the notochord.

The extent of mesoderm in rabbit embryos is shown in Fig. 28.
Cranial to the primitive knot the notochord is differentiated in the mid-
plane, and the mesoderm extends laterally as two wings. The mesoderm
rapidly grows around the wall of the blastodermic vesicle until it finally
surrounds it and the two wings fuse ventrally (Fig. 29). The single sheet
of mesoderm soon splits into two layers, the cavity between being the
coelom, or body cavity. The outer mesodermal layer (somatic), with the
ectoderm, forms the somatopleure, or body wall; the inner splanchnic

ORIGIN OF THE MESODERM, NOTOCHORD AND NEURAL TUBE

35

layer, with the entoderm, forms the intestinal wall, or splanchnopleure.
The neural tube having in the meantime arisen from the neural folds of
the ectoderm, there is present the ground plan of the vertebrate body,
the same in man as in Amphioxus.

No stages of gastrulation or mesoderm formation have yet been ob-
served in the human embryo, but the primitive streak may be recognized

Post, opening of notochordal
canal
Primitive streak

Ant. persisting portion of
Ant. opening of notochordal canal

notochordal canal

FIG. 27. — Median longitudinal section through the blastoderm of a bat (Vesper'ilio murinus)

(after Van Beneden).

in later stages (Fig. 77), and there is evidence also of a transient opening,
the neurenteric canal, leading from the exterior into the cavity of the primi-
tive gut (archenteron). In Tarsius, an animal classed by Hubrecht with
the primates, the mesoderm has two sources: (i) From the splitting of
ectoderm at the caudal edge of the blastoderm; this forms the extra-

FIG. 28. — Diagrams showing the spread of mesoderm in rabbit embryos (Kolliker). In
A the mesoderm is represented by the pear-shaped area about the primitive streak at the caudal
end of the embryonic disc; in B, by the circular area which surrounds the embryonic disc.

embryonic mesoderm and takes no part in forming the body of the embryo.
(2) The intr a- embryonic mesoderm, which gives rise to body tissues, takes
its origin from the primitive streak as in the chick and lower mammals.
The origin of mesoderm in the human embryo is probably much the same
as in Tarsius.

CLEAVAGE AND THE GERM LAYERS

The Notochord or Chorda Dorsalis. — Unlike in Amphioxus and
amphibia, the head (notochordal) process and mesoderm of higher verte-
brates are not clearly of entodermal origin, but are derived from the
ectoderm, any union with the entoderm being secondary. As the primi-
tive streak recedes caudalward during development the head process is
progressively lengthened at the expense of the former. Ultimately the
primitive streak becomes restricted to the tail region, whereas the entire

Ectoderm

Mesoderm
Entoderm

Mesodermal segment
Ectoderm
Somatic
mesoderm

Archenteron

Entod,

Archenter.

Neural tube

Nephrolome
Notochord

Splanchnic
mesoderm

Ccelom

A B

FIG. 29. — Diagrams showing the origin of the germ layers of mammals as seen in transverse
section (modified from Bryce).

remainder of the body is built up around the head process as an axis. In
later stages, the rod-like notochord extends in the midline beneath the
neural tube from the tail to a dorsal out-pocketing of the oral entoderm,
known as Seessel's pouch (p. 83). It becomes enclosed in the centra of
the vertebrae and in the base of the cranium, and eventually degenerates.
In Amphioxus it forms the only axial skeleton and it is persistent in the
axial skeleton of fishes and amphibians. In man, traces of it are found
as pulpy masses (nuclei pulposi) in the intervertebral discs.

CHAPTER III
THE STUDY OF CHICK EMBRYOS

CHICK embryos may be studied whole and most of the structures identified up to the
end of the second day. The eggs should be opened in normal saline solution at 40° C.
With scissors cut around the germinal disc, float the embryo off the yolk, and remove the
vitelline membrane. Then float the embryo dorsal side up on a glass slide, remove enough
of the saline solution to straighten wrinkles, and carefully place over the embryo a circle
of tissue paper with an opening large enough to leave the germinal disc exposed. Add a
few drops of fixative and float embryo into a covered dish. Following the routine
technical procedure, embryos are stained and sectioned serially or mounted entire.

In the following descriptions we shall use the terms dorsad and ventrad to indicate
toward the back' or 'toward the belly;' cephalad and craniad to denote 'headward;'
candad to denote 'tailward;' later ad to indicate 'toward the side;' and mesad, 'toward the
median plane.'

EMBRYOS OF ABOUT TWENTY HOURS' INCUBATION

The events of cleavage and the formation of the three primary germ
layers in birds have been described in the preceding chapter. The appear-
ance on the disc -like blastoderm (Fig. 3) of the primitive streak and groove
(Fig. 23), and its cranial extension, the head process (Fig. 25), has likewise
received brief treatment (pp. 32-33).

In a chick embryo of twenty hours' incubation (Fig. 30), the primitive
streak is formed as a linear opacity nearer the posterior border of the germinal
disc. Over a somewhat pear-shaped clear area the yolk has been dis-
solved away from the overlying entoderm. This area, from its apear-
ance, is termed the area pellucida. It is surrounded by the darker and
more granular area opaca, which constitutes the remainder of the fairly
sharply limited blastoderm. Whether or not the primitive streak repre-
sents the fused lips of the blastopore, it is certain that it represents the
point of origin for the middle germ layer, the extent of which is indicated
by the shaded area of Fig. 30. It also indicates the future longitudinal
axis of the embryo. The mesoderm extends at first more rapidly caudal
and lateral to the primitive streak. However, there is soon an axial
growth forward from the thickened primitive knot (Figs. 23 and 30). This
is the head process, or notochordal plate. It temporarily fuses with the
entoderm (p. 33) and is continuous laterally with expanding mesodermal
sheets (Figs. 25 and 31).

37

THE STUDY OF CHICK EMBRYOS

I Primitive
*C streak

Blood island

FIG. 30. — Dorsal surface view of a twenty-hour chick embryo, showing primitive streak,
head process and extent of mesoderm (after Duval). X 17. The lines A, B, and C indicate
the levels of the corresponding sections shown in Fig. 31.

Ectoderm

Neural plate

Mesoderm

Ectoderm

Notochordal plate
Primitive knot

Mesoderm Entoderm

FIG. 31. — Transverse sections through the embryonic area of a twenty-hour chick.
X 165. A, through the head process; B, through the primitive knot; C, through the
primitive streak.

EMBRYO OF SEVEN SEGMENTS

39

Head fold

A transverse section through the primitive streak at twenty hours
(see guide line C, Fig. 30) shows the three germ layers distinct laterally
(Fig. 31 C). In the midline, a depression in the ectoderm is the primitive
groove. In this region there is no line of demarcation between ectoderm
and mesoderm. A transverse section through the primitive knot (Fig.
31 B\ guide line B, Fig. 30) shows the three germ layers intimately fused
(cf. Fig. 51). There is a marked proliferation of cells, which are growing
cephalad to form the notochordal plate (head process) (cf. Fig. 25).

A transverse section through the notochordal plate, just beginning
to form at this stage (Fig. 31 A ; guide
line A, Fig. 30) shows the thickening
in the midplane which will separate
from the lateral mesoderm and form
the notochord. It is fused with the
entoderm but not with the ectoderm.

After the notochordal plate be-
comes prominent at twenty hours,
the differentiation of the blastoderm
is rapid. A curved fold, at first in-
volving the ectoderm and entoderm
alone, is formed cephalad of the
notochordal process. This is the
head fold, and is the anlage of the
head of the embryo (Figs. 25 and 32).
The ectoderm has thickened on each
side of the mid-dorsal line, forming
the neural folds. The groove between
these is the neural groove. The
closure of this groove will later form
the neural tube, the anlage of the
central nervous system. The notochord is now differentiated from
the mesoderm and may be seen in the median plane through the
ectoderm. In the mesoderm, lateral to the notochord and cephalad
of the primitive knot, transverse furrows have differentiated two pairs
of block-like mesodermal segments, one incomplete cranially. As develop-
ment proceeds these increase in number, successive pairs being developed
caudally. They will be described in detail later (p. 53).

EMBRYO OF SEVEN SEGMENTS (TWENTY-FIVE HOURS' INCUBATION)

In this embryo (Fig. 33) there is a prominent network of blood vessels
and blood cells in the caudal portion of the area opaca. In its cranial
portion isolated groups of blood and blood vessel-forming cells are seen

FIG. 32. — Surface view of a twenty-one
hour chick embryo, in which the head fold
and first two pairs of primitive mesodermal
segments are present. The head process
is seen through the neural groove (after
Duval). X 13.

THE STUDY OF CHICK EMBRYOS

as blood islands. Together, they constitute the angioblast from which
arises the extra-embryonic blood vascular system. The area pellucida
has the form of a slipper, with broad toe directed forward. The head
fold has become cylindrical and the head of the embryo is free for a short
distance from the germinal disc. The mesoderm extends on each side
beyond the head leaving a median clear space, the proamniotic area.

Anterior neuropore Fore-brain

Pharynx

Free portion of head

Intestinal portal

ght vitelline
vein

M-Neural groove

Left vitettine

Mesodermal
segment j

Area pellucida

Notochord

Area opaca

Primitive streak

FlG- 33- — Dorsal view of a twenty-five-hour chick embryo with seven primitive segments.

X 20.

The entoderm is carried forward in the head fold as the fore- gut, from
which later arise the pharynx, esophagus, stomach, and a portion of the
small intestine. The opening into the fore-gut faces caudad and is the
intestinal portal. The way in which the entoderm is folded up from the
blastoderm and forward into the head is shown well in a longitudinal
section of an older embryo (Fig. 42). The tubular heart lies ventral to
the fore-gut and cranial to the intestinal portal. In later stages it is
bent to the right. Converging forward to the heart, on each side of the

Blood island

EMBRYO OF SEVEN SEGMENTS 41

portal, are the vitelline veins, just making their appearance at this stage.
The lips of the neural folds have met throughout the cranial two-thirds of
the embryo but have not fused. The neural tube, formed thus by the
closing of the ectodermal folds, is open at either end at the neuropores.
Cephalad, trie neural tube has begun to expand to form the brain vesicles.
Of these only the fore-brain is prominent, and from it the optic vesicles
are budding out laterally. The paraxial mesoderm is divided by trans-
verse furrows into seven pairs of block-like primitive segments. Caudally,
between the segments and the primitive streak, there is the undifferen-
tiated mesoderm of the segmental zone, but new pairs of segments will
develop in this region. Looking through the open neural groove (rhom-
boidal sinus), one may see the notochord extending from the primitive
knot cephalad in the midplane until it is lost beneath the neural tube in
the region of the primitive segments. The primitive streak is still prominent
at the posterior end of the area pellucida, forming about one-fourth the
length of the embryo.

TRANSVERSE SECTIONS

Sections through the Primitive Streak and Knot. — Conditions are essentially the
same as in the twenty-hour embryo (Fig. 31).

Section through the Fifth Primitive Segment (Fig. 34). — This general level is charac-
terized by the differentiation of the mesoderm, the approximation of the neural folds and

Neural fold Neural groove

Ectoderm \ I Mesodermal segment

Somatic mesoderm \ jffi& As^. / Ccdom

Splanchnic mesoderm

Descending aorta Entoderm

FIG. 34. — Transverse section through the fifth pair of mesodermal segments of a twenty-five-
hour chick embryo. X 90.

the presence of two vessels, the descending aortce, on each side between the mesodermal
segments and the- entoderm. The neural folds are thick and the ectoderm is thickened
over the embryo. The notochord is a sharply defined oval mass of cells. The mesoder-
mal segments are somewhat triangular in outline and connected by the intermediate cell
mass, or nephrotome, with the lateral mesoderm. The lateral mesoderm is partially
divided by irregular flattened spaces into two layers, the dorsal of which is the somatic
layer, the ventral the splanchnic layer. Later, the spaces unite on either side to form the
coelom, or primitive body cavity. In the area opaca, more laterad than is represented in
the figure, the entoderm is intimately associated with the coarsely granular yolk. Below
the splanchnic mesoderm, blood islands and primitive blood vessels are forming; this portion
of the area opaca is termed the area vasculosa.

42 THE STUDY OF CHICK EMBRYOS

Section Caudal to the Intestinal Portal (Fig. 35). — The section is characterized: (i)
by the closing together of the neural folds to form the neural tube; (2) by the dorsal and
lateral folding of the entoderm, which, a few sections nearer the head end, forms the fore-
gut; (3) by the presence of the vitelline veins laterally between the entoderm and splanchnic
mesothelium; (4) by the wide separation of the somatic and splanchnic mesoderm and the

. -Ectoderm
Descending aorta
Entoderm of fore-gut
Vitelline vein

Entoderm

FIG. 35. — Transverse section caudal to the intestinal portal of a twenty-five-hour chick embryo.

X 90.

consequent increase in the size of the ccelom. In this region the ccelom later surrounds
the heart and forms the pleuro-pericardial cavity.

The neural tube at this level forms the third brain vesicle, or hind-brain. The neural
folds have not yet fused, and at their dorsal angles are the neural crests, the anlages of the
spinal ganglia. Mesodermal segments do not develop in this region; instead a diffuse
network of mesoderm partly fills the space between ectoderm, entoderm, and mesothe-
lium. This is termed mesenchyme and will be described later (p. 53).

Neural tube

Descending aorta
Notochord

Splanchnic mesoderm
Epi-myocardiu m

Ccdom

Splanchnic mesoderm//

Ectoderm
Somatic mesodert,.
Mesenchyma

Fore-gut

Endothelium of heart tube

ntoderm

FIG. 36. — Transverse section through the intestinal portal of a twenty-five-hour chick embryo.

X 90.

Section through the Intestinal Portal (Fig. 36). — This section passes through a vertical
fold of entoderm at the point where the latter is reflexed into the head as the fore-gut (cf .
Fig. 42). The entoderm forms a continuous mass of tissue between the vitelline veins,
thereby closing the fore-gut ventrally. The splanchnic mesoderm is differentiated into
a thick-walled pouch on each side, lateral to the endothelial layer of the veins.

EMBRYO OF SEVEN SEGMENTS

43

Section through the Heart (Fig. 37). — Passing cephalad in the series of sections, the
vitelline veins open into the heart just in front of the intestinal portal. The entoderm in
the head fold now forms the crescentic pharynx of the fore-gut, separated by the heart
and splanchnic mesot helium from the entoderm of the germinal disc. The descending
aortae are larger, forming conspicuous spaces between the neural tube (hind-brain] and the
pharynx. The heart, as will be seen, is formed by the union of two endothelial tubes, con-
tinuous with those constituting the vitelline veins in the preceding sections. The median
walls of these tubes disappear at a slightly later stage to form a single tube, the endocardium.
Thickened layers of splanchnic mesoderm, which, in the preceding section, invested the
vitelline veins laterally, now form the mesothelial wall of the heart. In the median ven-
tral plane, the layers of splanchnic mesoderm of each side have fused and separated from
the splanchnic mesothelium of the germinal disc ; thus the two pleuro-pericardial cavities
are put in communication. The mesothelial wall of the heart forms the myocardium and
cpicardium of the adult. Dorsally, the splanchnic mesoderm, as the dorsal mesocardium,
suspends the heart, while still more dorsally it is continuous with the somatic mesoderm.

Neural tube

Descending aorta

Ectoderm

Somatic mesoderm

Notochord

Eft-myocardium

___ Splanchnic mesoderm

Entoderm-

FIG. 37. — Transverse section through the heart of a twenty-five-hour chick embryo. X 90.

Origin of the Primitive Heart. — From the two sections last described, it is seen that
the heart arises as a pair of endothelial tubes lying in folds of the splanchnic mesoderm.
Later, the endothelial tubes fuse and the mesodermal folds are also brought together. The
heart then consists of a single endothelial tube within a thick-walled investment of meso-
derm. The origin of the endothelial cells of the heart — whether they arise from entoderm
or mesoderm — is not surely known. The vascular system is primitively a paired system,
the heart arising as a double tube with two veins entering and two arteries leaving it
(cf. Figs. 268 and 269).

Origin of the Blood Vessels and Blood.— We have seen that in the area opaca a net-
work of blood vessels and blood islands is differentiated as the angioblast. This tissue
gives rise to primitive blood vessels and blood cells and probably is derived from the splanch-
nic mesoderm. The vessels arise first as reticular masses of cells, the so-called blood
islands. These cellular thickenings undergo differentiation into two cell types, the inner-
most becoming blood cells, the outermost forming a flattened endothelial layer which encloses
the blood cells. All the primitive blood vessels of the embryo are composed of an endothe-
lial layer only. The endothelial cells continue to divide, forming vascular sprouts and in
this way new vessels are in part produced. The first vessels arising in the vascular area
of a chick embryo unite into a close network, some bf the branches of which enlarge to
form vascular trunks. One pair of such trunks, the vitelline veins, is differentiated

44

THE STUDY OF CHICK EMBRYOS

adjacent to the posterior end of the heart and later connects with it. Another pair,
the vitelline arteries, is developed in continuation with the aortae of the embryo. The
vessels of the vascular area thus appear before those of the embryo have developed ; they
probably arise from the splanchnic mesoderm, and, both arteries and veins, are composed
of a simple endothelial wall. As the ccelom develops in the region of the vascular area
of the embryo soon after the differentiation of the angioblast, the anlages of the blood
vessels are formed only in the splanchnic layer. (For the development of the heart and
blood vessels see Chapter IX.)

Ectoderm

Neural tube

Mesenchym

Entoderm of
proamnion

Descending aorta

-^z — Fore-gut

Ectoderm of proamnion

\\

FIG. 38. — Transverse section through the pharyngeal membrane of a twenty-five-hour chick

embryo. X 90.

Section through the Pharyngeal Membrane (Fig. 38). — This section passes through
the head fold and shows the head free from the underlying blastoderm (cf. Fig. 42). Sec-
tions a little caudad in the series prove that this is accomplished by folds of somatopleure.
These bend in from the front and sides, fuse, and the head is progressively 'pinched off'
from the blastoderm (see pp. 80-81). The ectoderm surrounds the head, and near the
mid-ventral line it is bent dorsad, is somewhat thickened, and comes in contact with the
thick entoderm of the pharynx. The area of contact between ectoderm and pharyngeal
entoderm forms the pharyngeal plate, or membrane. Later, this membrane breaks through

Proamnion

FIG. 39. — Transverse section through the fore-brain and optic vesicles of a twenty-five-hour

chick embryo. X 90.

and thus the oral cavity arises. The expanded neural tube is closed in this region and
forms the middle brain vesicle, or mid-brain. The descending aortae appear as small ves-
sels dorsal to the lateral folds of the pharynx. The blastoderm in the region beneath the
'head is composed of ectoderm and entoderm only. This is the proamniotic area. Laterad
may be seen the layers of the mesoderm.

Section through the Fore-brain and Optic Vesicle (Fig. 39). — The neural tube is open
here and constitutes the first brain vesicle, or fore-brain. The opening is the anterior
neuropore. The ectoderm is composed of two or three layers of nuclei and is continuous with

EMBRYO OF SEVENTEEN SEGMENTS

45

the much thicker wall of the fore-brain. The lateral expansions of the forebrain are the
optic vesicles, which eventually give rise to the retina of the eye. The two ectodermal
layers are in contact with each other except in the mid-ventral region, where the mesen-
chyma is beginning to penetrate between and separate them. The proamnion consists
merely of a layer of ectoderm and of entoderm.

CHICK EMBRYO OF SEVENTEEN PRIMITIVE SEGMENTS (THIRTY-EIGHT HOURS)

The long axis of this embryo is nearly straight (Fig. 40), the area

pellucida is dumb-bell shaped and the vascular network is well differenti-

II carl

Proamnion
Optic vesicle
Free portion of head

Vitelline i

• — . Xcural tube

Note

Rhomboidal sinus

Primitive streak

FIG. 40. — View of the dorsal surface of a thirty-eight-hour chick embryo. X 20.

ated throughout the area opaca. The tubular heart is bent to the embryo's
right, and opposite its posterior end the vascular network converges and
becomes continuous with the trunks of the vitelline veins. Connections
have also been formed between the descending aortas and the vascular
area, but as yet the vitelline arteries have not appeared as distinct trunks.

THE STUDY OF CHICK EMBRYOS

The proamniotic area is reduced to a small region in front of the head,
whereas the latter is now larger and. more prominent. In the posterior
third of the vascular area blood islands are still prominent.

Central Nervous System and Sense Organs. — -The neural tube is
closed save at the caudal end where the open neural folds form the rhom-

Optic vesiclt

Paired ventral aorta

Ventral aorta
Bulbus cordis

Ventricle

Splanchnic mesoderm f-^
Intestinal portal— ^^ m «

^* —
Right descending aorta

i* .

Vascular plexus -?V/ '/

Splanchnic mesoderm
Notochord

Mesodermal segment

Segmental zone

'ore-brain

'Pharyngeal pouch 1
Descending aorta

K_ Pharyngeal pouch 2

Somatopleure

d^'j Left vitelline vein
&£i— Entoderm

Section oj mural tube

Somatopleure
Descending aorta

Neural tube
Splanchnic mesoderm

Capillary plexus
Somatopleure

&m — . Neural groove

FIG. 41. — Ventral reconstruction of a thirty-eight-hour chick embryo. The entoderm has been
removed except about the intestinal portal. X 38.

boidal sinus. In the head the neural tube is differentated into the three
brain vesicles, marked off from each other by constrictions. The fore-
brain (prosencephalon) is characterized by the outgrowing optic vesicles.
The mid-brain (mesencephalon) is undifferentiated. The hind-brain
(rhombencephalon) is elongated and gradually merges caudally with the

EMBRYO OF SEVENTEEN SEGMENTS 47

spinal cord. It shows a number of secondary constrictions, the neurom-
eres. The ectoderm is thickened laterally over the optic vesicles to form
the lens placode of the eye (Fig. 43). The optic vesicle is flattened at this
point and will soon invaginate to produce the inner, nervous layer of the
retina. Dorso-laterally, in the hind-brain region, the ectoderm is thick-
ened and invaginated as the auditory placode (Fig. 45). This placode
later forms the otocyst, or otic vesicle, from which is differentiated the
epithelium of the internal ear (membranous labyrinth).

Digestive Tube. — 'The entoderm is still flattened out over the surface
of the yolk caudal to the intestinal portal. In Fig. 41 the greater part of
the entoderm is cut away. The flattened fore-gut, folded inward at the
portal, shows indications of three lateral diverticula, the pharyngeal
pouches. Cephalad, the pharynx is closed ventrally by the pharyngeal
membrane.

Hind-brain Fore-gut Neural tube

Mid-brain.

Fore-brain
Amnionfold.

^.ntestinal portal

~»™^.,, , „ Vitelline vein

Pharyngeal membrane v ',

aorta Dorsal Heart Pericardial cavity
mesocardium

FIG. 42. — A median longitudinal section of the head of a thirty-eight-hour chick embryo.

X about 50.

Heart and Blood Vessels. — After receiving the vitelline veins cepha-
lad of the intestinal portal, the double-walled tube of the heart dilates
and bends ventrad and to the embryo's right (Fig. 41). It then is flexed
dorsad and to the median plane, and narrows to form the ventral aorta.
The aorta lies ventrad to the pharynx and divides at the boundary line
between the mid- and hind-brain into two ventral aortas. These diverge
and course dorsad around the pharynx. Before reaching the optic vesicles
they bend sharply dorsad and caudad, and, as the paired descending aortae,
may be traced to a point opposite the last primitive segments. In the
region of the intestinal portal they lie close together and have fused to
form a single vessel, the dorsal aorta. They soon separate, and, opposite
the last primitive segments, they are connected by numerous capillaries
with the vascular network. In this region, at a later stage, the trunks
of the paired vitelline arteries will be differentiated. The heart beats at
this st?6e; the blood flows from the vascular area by way of the vitelline
veins UD the heart, thence by the aortae and vitelline arteries back again.

48 THE STUDY OF CHICK EMBRYOS

This constitutes the vitelline circulation, and through it the embryo
receives nutriment from the yolk for its future development.

In studying transverse sections of the embryo it is not sufficient
merely to identify the structures seen. The student should determine
also the exact level of each section with respect to Figs: 40, 41 and 42,
and trace the organs from section to section in the series. It is important
to remember that the transverse sections figured and described in this
manual (except those of the fifty-hour chick) are all drawn viewed from
the cephalic surface; hence the right side of the embryo is at the reader's
left.

TRANSVERSE SECTIONS

Section through the Fore-brain and Optic Vesicles (Fig. 43). — The optic stalks con-
nect the optic vesicles laterally with the ventral portion of the fore-brain. Dorsally, the
section passes through the mid-brain, due to the somewhat ventrally flexed head (cf. Fig.

Mid-brain

"Mesenchyme
Optic vesicle

^^ -Lens anlage

Ccelom^

Somatopleure^ __

-Splanchnopleure

FIG. 43. — Transverse section through the fore-brain of a thirty-eight-hour chick embryo. X 75.

42). We have alluded to the thickening of the lens placode. Note that there is now a
considerable amount of mesenchyme between the ectoderm and the neural tube. Layers
of mesoderm are present in the underlying blastoderm.

Section through the Pharyngeal Membrane and Mid-brain (Fig. 44). — In the mid-
ventral line the thickened ectoderm bends up into contact with the entoderm of the rounded
pharynx of the fore-gut. At this point the oral opening will break through. On either
side of the pharynx a pair of large vessels is seen; the ventral pair are the ventral aorta.
Two sections cephalad their cavities open into those of the dorsal pair, the descending
aortae. The section is thus just caudad of the point where the ventral aortae bend dorsad
and caudad to form the descending aortae. The section passes through the caudal end of
the mesencephalon which is here thick walled with an oval cavity. Note the large
amount of undifferentiated mesenchyme in the section. The structure of the blastoderm
is complicated by the presence of collapsed blood vessels.

EMBRYO OF SEVENTEEN SEGMENTS

49

Section through the Hind -brain and Auditory Placodes (Fig. 45). — Besides the audi-
tory placodes already described as the anlages of the internal ear, this section is character-
ized by: (i) the large hind-brain, somewhat flattened dorsad; (2) the broad, dorso-ventrally

Ectoderm

Mesenchyme

Descending aorta —
Ventral aorta

Somali pleure

Mid-brain
Notocnora

Fore-gut

Pharyngeal membrane

Spianchno pleure

FIG. 44. — Transverse section through the pharyngeal membrane of a thirty-eight-hour chick

embryo. X 75.

flattened pharynx, above which on each side lie the descending aortas; (3) the presence of the
bulbar and ventricular portions of the heart. The bulbus is suspended dorsally by the
mesoderm, which here forms the dorsal mesocardium. The ventricle lies on the right side

Ectoderm

Notochord

Descending aorta
Pericardial cavity
Somatic mesoderm

Endotheliu
of ventricle

Hind-brain

Ant. cardinal vein

Entoderm

Endothelium of bidbus
Myocardium

FIG. 45. — Transverse section through the hind-brain and auditory placodes of a thirty-eight-
hour chick embryo. X 75-

of the embryo; a few sections caudad in the series it is continuous with the ventral aorta
(cf. Fig. 41). Between the somatic and splanchnic mesoderm is the large pericardial cavity.
It surrounds the heart in this section. Dorsal to the aortae are the anterior cardinal veins,
which return blood from the head region.

THE STUDY OF CHICK EMBRYOS

Section through the Caudal End of the Heart (Fig. 46). — The section passes through
the hind-brain. The descending aortae are separated only by a thin septum which is
ruptured in this section. The anterior cardinal veins are cut at the level where they bend

Ectoderm

Hind-brain

Mesodermal segment
Anterior cardinal vein
Somatic mesoderm Ccelom

Fore-gut

Entoderm

. . — ^_^ — ^ Splanchnic mesoderm

Vitelline vein/

Heart Myocardium

FIG. 46. — Transverse section through the caudal end of the heart of a thirty-eight-hour chick

embryo. X 75.

ventrad to enter the heart. The mesothelial wall of the heart is continuous with the
splanchnic mesoderm. On the right side of the section there is apparent fusion between
the myocardium of the heart and the somatic mesoderm. A pair of primitive mesodermal

Ectoderm
Mesodermal segment

Neural tube
Notochord

Somatopleure

Extra-embryonic ccelom
Entoderm
Right vitelline vein Spia'nchnic | 'W viteUine vein

mesoderm Entoderm Fore-gut

FIG. 47. — Transverse section through the intestinal portal of a thirty-eight-hour chick embryo.

X 90.

segments may be seen in this section lateral to the hind-brain. It may be noted here that
the primitive segments were not present in the sections of the head previously studied.
Section through the Intestinal Portal (Fig. 47) . — The descending aortce now form a single
vessel, the dorsal aorta, the medium septum having disappeared. The section passes through
the entoderm at the point where it is folded dorsad and cephalad into the head as the fore-

EMBRYO OF SEVENTEEN SEGMENTS 51

gut (cf. Fig. 42). Two sections caudad is found the opening (intestinal portal) where the
fore-gut communicates with the flattened open gut between the entoderm and the yolk.
On each side of the fore-gut are the large mtelline veins, sectioned obliquely. The
splanchnic mesoderm overlying these veins is pressed by them against the somatic
mesoderm and the cavity of the ccelom is thus interrupted on each side.

Neural tube

Mesodermal segment

Neural cavity

Ectoderm
Notochord

Dorsal aorta

matopleure

Coslom
Splanchnic mesoderm

R. vitelline vein

Splanchnopleure Open gut Entoderm

FIG. 48. — Transverse section caudal to the intestinal portal of a thirty-eight-hour chick embryo.

X 90.

Section Caudal to the Intestinal Portal (Fig. 48). — This section resembles the preceding
save that the primitive gut is without a ventral wall. The right mtelline vein is still large.

Section through the Fourteenth Pair of Primitive Segments (Fig. 49) . — The body of
the embryo is now flattened on the surface of the yolk. Here the descending aortae are

Neural tube

Mesodermal segment
Central cells of segment

Somatic mesod<

S-blanchnic mesoderm

Descending aorta

Ectoderm

Pronephric tubule

Entoderm

Notochord

FIG. 49. — Transverse section through the fourteenth pair of mesodermal segments of a thirty-
eight-hour chick embryo. X 90.

still separate and occupy the depressions lateral to the primitive segments. The section
is characterized by the notochord and the differentiated mesoderm which forms the primi-
tive segments, nephrotomes, and somatic and splanchnic mesoderm. Arising from the
nephrotomes are sprout-like pronephric tubules. The tips of these hollow out and unite to
form the primary excretory, or mesonephric duct. All of these structures are described on
PP- 53-54-

52

THE STUDY OF CHICK EMBRYOS

Section through the Rhomboidal Sinus (Fig. 50). — The neural groove is open, the
notochord is oval in form. The ectoderm is characterized by the columnar form of its cells.
At the point where the ectoderm joins the neural fold a ridge of cells projects ventrally
on either side. These projecting cells form the neural crests, and from them the spinal

Neural groove
Ectoderm \ ^Neural crest

_ ____ _ /Segmented zone

Somatic mesoderm

Splanchnic mesoderm Ccelom Notochord Entoderm Blood vessel

FIG. 50. — Transverse section through the rhomboidal sinus of a thirty-eight-hour chick embryo.

X 90.

ganglia are formed. The section is at the level of the segmental zone, where mesodermal
segments have not formed as yet. The mesodermal plates have split laterally into layers,
but the ccelomic cavities are mere slits. Between the splanchnic mesoderm and the ento-
derm blood vessels may be seen.

Somatic mesoderm Ectoderm Primitive knot

Codom Entoderm

Splanchnic mesoderm

FIG. 51. — Transverse section through the primitive (Hensen's) knot of a thirty-eight-hour chick

embryo. X 90.

Section through the Primitive (Hensen's) Knot or Node (Fig. 51). — The section shows
the three germ layers fused inseparably at the 'knot' into a mass of undifferentiated tissue.
The mesoderm is split laterally into the somatic and splanchnic layers.

Somatic mesoderm Primitive groove

Ectoderm

^ Ccelom
Splanchnopleure' / \Primitivestreak Splanchnic mesoderm

Entoderm
FIG. 52. — Transverse section through the primitive streak of a thirty-eight-hour chick embryo.

X 90.

Section through the Primitive Streak (Fig. 52). — In the mid-dorsal line is the primi-
tive groove. The germ layers may be seen taking their origin from the undifferentiated
tissue of the primitive streak, beneath the primitive groove. Laterad, between the splanchnic
mesoderm and entoderm, blood vessels are present as in the preceding sections.

EMBRYO OF SEVENTEEN SEGMENTS

S3

Mesodermal Segments. — -We have seen that these are developed by
the appearance of transverse furrows in the mesoderm (Fig. 53). Later,
a longitudinal furrow partially separates the paired segments from the
lateral unsegmented mesoderm. The segments are block-like with
rounded corners when viewed dorsally, triangular in transverse sections
(Figs. 49 and 53). They are formed cranio-caudally, the most cephalic
being the first to appear. The first four lie in the head region. The
segments contain no definite cavity, but a potential cavity representing
a portion of the coelom is filled with cells, and the other cells of the seg-
ments form a thick mesothelial layer about them (Fig. 49). The ventral
wall and a portion of the median wall of each primitive segment become
transformed into mesenchyma which surrounds the neural tube and
notochord (Fig. 290). The remaining portions of the segments persist as
the dermo-muscular plates. The cells of the mesial wall of the plate, the
myotome, elongate and give rise to the skeletal muscle of the body. These
muscles are thus at first segmented, but later many of the segments fuse.
In the trunk muscles of the adult fish the primitive segmental condition
is retained.

Mesonephric duct

Neural tube

Mesodermal segment

Somatic mesoderm

Splanchnopleure •
Descending aorta-

Notochord Entoderm Ccdom

FIG. 53.— Semi-diagrammatic reconstruction of five mesodermal segments of a forty-eight-hour
chick embryo. The ectoderm is removed from the dorsal surface of the embryo.

The Intermediate Cell Masses or Nephrotomes.— The bridge of cells
connecting the primitive segments with the lateral mesodermal layers
constitutes the nephrotome (Figs. 49 and 53). In the chick, the nephro-
tomes of the fifth to sixteenth segments give rise dorsad to pairs of small
cellular sprouts, the rudimentary kidney tubules of the pronephroi,
segmentally arranged in the furrow lateral to the primitive segments. By
the union of these cell masses distally, solid cords are formed which run

54 THE STUDY OF CHICK EMBRYOS

lengthwise in the furrow. These cords hollow out, grow caudad, and
become the primary excretory (mesonephric) ducts (Fig. 53). More caudally
the intermediate cell masses form the embryonic kidney, or mesonephros,
the tubules of which open into the primary excretory duct. Further
details concerning these provisional kidneys are given on pages 196-200.
Since the genital glands develop in connection with the mesonephros,
and the kidney of the adult (metanephros) is partly developed as an out-
growth of the primary excretory duct, the intermediate cell mass may be
regarded as the anlage of the uro genital glands and their ducts. These
structures are thus of mesodermal origin.

Somatopleure and Splanchnopleure. — In the embryo of seven primi-
tive segments the mesoderm was seen to split laterally into two layers,
the somatic (dorsal) and the splanchnic (ventral) mesoderm (Fig. 34).
These layers persist in the adult, the somatic mesoderm giving rise to the
pericardium of the heart, to the parietal pleura of the thorax, and to the
peritoneum of the abdomen, while the splanchnic layer forms the epicar-
dium and myocardium of the heart, the visceral pleura of the lungs, and
the mesenteries and mesodermal layer of the gut. The somatic mesoderm
and the ectoderm, with the tissue developed between them, constitute
the. body wall, which is termed the somatopleure. In the same way the
splanchnic mesoderm and the entoderm, with the mesenchymal tissue
between them, constitute the wall of the gut, or the Splanchnopleure.

Notochord Neural tube

k '

Splanchnic
mesoderm

Entoderm

Codom
FIG. 54. — Diagrammatic transverse section of a vertebrate embryo (adapted from Minot).

Coelom. — The cavity between the somatopleure and Splanchnopleure
is the ccelom (body cavity) . With the splitting of the mesoderm, isolated
cavities are produced. These unite on each side and eventually form
one cavity — the ccelom. With the extension of the mesoderm, the ccelom
surrounds the heart and gut ventrally (Fig. 54). Later, it is subdivided

EMBRYO OF SEVENTEEN SEGMENTS 55

into the pericardial cavity about the heart, the pleural cavity of the thorax,
and the peritoneal cavity of the abdominal region. In the chick stages
already studied, the embryo was flattened on the surface of the yolk and
and the somatopleure and splanchnopleure did not meet ventrally. If this
union occurred they would conform to the structural relations shown in
Fig. 54, which is essentially the ground plan of the vertebrate body.

Mesenchyme. — In the sections through the head of this embryo, and
through that of the preceding stage, but four primitive segments were found.
The greater part of the mesoderm in the head appears in the form of an
undifferentiated network of cells which fill in the spaces between the defi-
nite layers (epithelia). This tissue is mesenchyme (Fig. 55). The meso-
derm may be largely converted into mesenchyme, as in the head, or any of
the mesodermal layers may contribute to its formation. Thus, it may be

Ectoderm

Alesenchyme

FIG. 55. — Mesenchyme from the head of a thirty-eight-hour chick embryo. X 495.

derived from the primitive segments and from the somatic and splanchnic
mesoderm. The cells of the mesenchyme form a syncytium, or network,
and are at first packed closely together. Later, they may form a more
open network with cytoplasmic processes extending from cell to cell (Fig.
55). The mesenchyme is an important tissue of the embryo; from it are
differentiated the blood and lymphatic systems, together with most of the
smooth muscle, connective tissue, and- skeletal tissue of the body.

The body of the embryo is now composed: (i) of cells arranged in
layers — epithelia, and (2) of diffuse mesenchyme. The term 'epithelium'
is used in a general sense. Those epithelial layers lining the body cavities
are termed mesothelia, while those lining the blood vessels and lymphatics
are called endothelia.

Derivatives of the Germ Layers.— The tissues of the adult are de-
rived from the epithelia and mesenchyme of the three germ layers as
follows :

THE STUDY OF CHICK EMBRYOS

Ectoderm

1. Epidermis and its deriva- A

tives (hair, nails, glands) . i .

2. Conjunctiva and lens of 2.

eye. 3-

3. Sensory epithelia of or- 4.

gans of special sense. 5.

4. Epithelium of mouth,

enamel of teeth, oral 6.
glands. Hypophysis.

5. Epithelium of anus.

6. Male urethra (distad). B.

7. Epithelium of amnion and i.

chorion. 2.

8. Nervous, neuroglia, and 3.

chromaffin cells of nerv-
ous system.
9 Smooth muscle of sweat 4.

glands and of iris.
10. Notochord. =5.

Mesoderm

Mesothelium. i.

Pericardium.

Pleura. 2.

Peritoneum. 3.

Serous layer of intestine. 4.
Epithelium of most of

urogenital organs.
Striated muscle.

1. Skeletal.

2. Cardiac.

Mesenchyme. 5.

Blood cells.

Bone marrow.
Endothelium of blood
vessels and lymphatics.

Entodcrm

Epithelium of digestive
tract.
Liver.
Pancreas.
Epithelium of pharynx.

Eustachian tube.

Tonsils.

Thymus.

Thyreoid.

Parathyreoids.
Epithelium of respiratory
tract.

Larynx.

Trachea.

Lungs.

Lymphoid organs and
suprarenal cortex.
Supporting tissues.
(Connective tissue, car-
tilage and bone.
Smooth muscle.

6. Epithelium of most of
bladder, of female ure-
thra, male prostatic ure-
thra and prostate.

7. Notochord.

CHICK EMBRYO OF TWENTY-SEVEN SEGMENTS (FIFTY HOURS)

This embryo, of nearly- fifty hours' incubation, lies in" the center of
the vascular area and is peculiar in that the head is twisted 90° to the
right. In a dorsal view, therefore, one sees the right side of the head but
the dorsal side of the body. In the region of the mid-brain is a very marked
bend, the cephalic flexure. Below the head, and ventral in position, lies
the tubular heart, now bent in the form of a letter S. Dorsal to the heart,
in the region of the pharynx, three transverse grooves or slits may be seen.
These are the branchial grooves, or gill slits. The head of the embryo is
now covered by a double fold of the somatopleure, the hsad fold of the
amnion. It envelops the head like a veil. Caudally, a fold and opacity
mark the position of the tail bud, from which develops the caudal end of
the body. The curved fold embracing this is the tail fold of the amnion,
which will eventually meet the head fold and completely envelop the
embryo.

Central Nervous System and Sense Organs (Fig. 57). — Cephalad,
the neural tube is divided by constrictions into four vesicles. The fore-
brain of the previous stage is now subdivided into two regions, the telen-
cephalon and diencephalon. The cephalic flexure has been established

EMBRYO OF TWENTY-SEVEN SEGMENTS 57

in the region of the mesencephalon. The hind-brain, as yet undivided,
equals the combined length of the other three vesicles. As the lens of
the eye invaginates, the wall of the optic vesicle folds inward, thus forming
a double-walled structure, the optic cup. The auditory placode has be-
come a sac, the otocyst, which overlies the hind-brain opposite the second

Hind-brain

Otic vesicle

Branchial groove 3

Amnionfold

Atrium

L. vitelline artery
Neural tube

Primitive streak
atid tail bud

Mid-brain

Fore-brain
Optic vesicle
Lens vesicle

rea pellucida

. 56. — Dorsal view of a fifty-hour chick embryo, stained and mounted in balsam. X 14.

branchial groove and is still connected with the outer ectoderm, cut away
in Fig. 57. The rhomboidal sinus is still open at the caudal end of the
neural tube.

Digestive Canal (Fig. 57). — -In a reconstruction from the ventral side,
the digestive canal shows differentiation into three regions. Of these,
the fore-gut has been seen in earlier stages. A greater part of the mid-gut
has been cut away to show the underlying structures ; it is without a ven-
tral wall and overlies the yolk. Caudad, a small portal leads into the
hind-gut which is just beginning to evaginate into the tail fold. The
pharyngeal membrane now lies in a considerable cavity, the stomod&um,

THE STUDY OF CHICK EMBRYOS

formed by the invaginated ectoderm. The median, ectodermal pouch
next the brain wall is known as Rathke's pouch and is the anlage of the
anterior lobe of the hypophysis. The pharynx shows laterally three out-
pocketings, of which the first is wing-like and is the largest. These phar-
yngeal pouches occur opposite the three branchial grooves and here entoderm

Mid-brain

Optic -vesicle
Aperture of lens iiesicl

Fore-brai,

Splanchnopleure
Splanchnic mesoderm

R. vitelline arter

Mesodermal segment

Segmental zone '

Neural plate

Entoderm
Primitive knot

Notochord
Otocyst

Aortic arches i, 2, j
nt. cardinal vein

Atrium

Common cardinal vein

Post.cardinal vein

Descending aorta

'Liver anlage
Intestinal portal
^Entoderm
Somatopleure
'Spinal cord

vitelline artery

Edge of splanchnic mesoderm
Mesodermal segment

Vascular plexus

Hind-gut

FIG. 57. — Semi-diagrammatic reconstruction of a fifty-hour chick embryo, in ventral view.
X 1 8. The entoderm has been removed save in the region of the intestinal"portal and hind-
gut. Owing to the torsion of the embryo, the cranial third of the embryo is seen from the left
side, the caudal two-thirds in ventral view.

and ectoderm are in contact, forming the closing plates. At about this
stage the first closing plate ruptures, thereby forming a free opening, or
branchial cleft, into the pharynx. Between the pouches are developed the
branchial arches, in which course the paired aortic arches. Toward the
intestinal portal the fore-gut is flattened laterally, and before it opens out

EMBRYO OF TWENTY-SEVEN SEGMENTS 59

into the mid-gut there is budded off ventrally a bilobed structure, the anlage
of the liver (Figs. 57 and 63). It lies between the vitelline veins, and in its
later development the veins are broken up into the sinusoids, or blood
spaces of the liver.

Just as the entoderm participates in the head fold to form the fore-
gut, so in the tail fold it forms the hind-gut/ This at once gives rise to a
tubular outgrowth which becomes the allantois, one of the fetal membranes
to be described later (Fig. 70).

Blood Vascular System. — -The tubular heart is flexed in the form of a
letter S, when seen from the ventral side (Fig. 57). Four regions may
be distinguished: (i) the sinus venosu's, into which the veins open; (2) a
dilated dorsal chamber, the atrium; (3) a tubular ventral portion flexed
in the form of a U, of which the left limb is the ventricle, the right limb (4)
the bulbus cordis. From the bulbus is given off the ventral aorta. There
are now developed three pairs of aortic arches which open into the paired
descending aortse. The first aortic arch passes cranial to the first pharyn-
geal pouch and is the primitive arch seen in the thirty-eight-hour embryo.
The second and third arches course on either side of the second pharyngeal
pouch. They are developed by the enlargement of channels in primitive
capillary networks between ventral and descending aortae. Opposite
the sinus venosus, the paired aortic trunks fuse to form the single dorsal
aorta which extends as far back as the fifteenth pair of primitive segments.
At this point the aortae again separate, and, opposite the twentieth
segments, each connects with the trunk of a vitelline artery which was
developed in the vascular area and conveys the blood to it (Fig. 57).
Caudal to the vitelline arteries the dorsal aortae rapidly decrease in size
and soon end.

As in the previous stage, the blood is conveyed from the vascular area to
the heart by the vitelline veins, now two large trunks. In the body of the
embryo there have developed two pairs of veins. In the head have
appeared the anterior cardinal veins, already of large size and lying lateral
to the ventral region of the brain vesicles (Fig. 60). Caudal to the atrium
of the heart, two small posterior cardinal veins are developed. They
lie in the mesenchyma of the somatopleure, laterad in position (Fig. 63).
Opposite the sinus venosus the anterior and posterior cardinal veins of each
side unite and form the common cardinal veins (ducts of Cuvier) which
open into the dorsal wall of the sinus venosus (Fig. 57). The primitive
veins are thus paired like the arteries, and like them develop by the en-
largement of channels in a network of capillaries.

The following series of transverse sections from an embryo of this
stage shows the more important structures. The approximate plane
and level of each section may be ascertained by referring to Figs. 56 and 57.

6o

THE STUDY OF CHICK EMBRYOS

Hind-brain

Nolochord

Ectoder

Lens vesicle

Cavity of fore-brain

Ant. cardinal vein

Aortic arch 1

Optic vesicle
ProsencephaJon

FIG. 58.— Transverse section through the fore-brain and eyes of a fifty-hour chick embryo.

X 50.

Blastoderm
Hind-brai

Notochord
Descending aorta
Ant. cardinal vei
Ventral aorta-

'Amnion
'horion

A nt. cardinal vein

FIG. 59. — Transverse section through the optic stalks and hypophysis of a fifty-hour chick

embryo. X 50.

EMBRYO OF TWENTY-SEVEN SEGMENTS

61

TRANSVERSE SECTIONS

Section through the Fore-brain and Eyes (Fig. 58). — The section passes in front of
the optic stalks, consequently the optic vesicles appear unconnected with the fore-brain.
The thickened ectoderm is invaginated to form the anlages of the lens vesicles. The thicker
wall of the optic vesicles next the lens anlage will give rise to the nervous layer of the re-
tina; the thinner outer wall becomes the pigment layer of the retina. Ventrad in the sec-
tion are the wall and cavity of the fore-brain, dorsad the hind-brain with its thin, dorsal
ependymal layer. Between the brain vesicles on either side are sections of the first aortic
arches, and lateral to the hind-brain are the smaller, paired anterior cardinal veins, which
convey the blood from the head to the heart. The splanchnopleure of the blastoderm is
characterized in this and subsequent sections by the presence of blood vessels in its meso-
dermal layer.

Hind-brain
Ectoderm
Entoderm
Ant. cardinal vein
L. descending aorta

Aortic arch 2
Ventral aorta
Mesoderm

Mesoderm of bulbils-
Endothelium of bidbus

FlG. 60. — Transverse section through the otic vesicles and second aortic arches of a fifty-hour

chick embryo. X 50.

Section through the Optic Stalks and Hypophysis (Fig. 59).— The section passes
just caudal to the lens. The optic vesicles are connected with the wall of the fore-brain
by the optic stalks, which later form the path by which the fibers of the optic nerve pass
from the retina to the brain. Both the ventral and the descending aorta are seen in section
about the cephalic end of the pharynx. Between the ventral wall of the fore-brain
and the pharynx is an invagination of the ectoderm, Rathke's pouch (anterior lobe of the
hypophysis).

Section thiough the Otocysts and Second Aortic Arch (Fig. 60).— The otic vesicles
are sectioned caudal to their apertures and appear as closed sacs, lateral to the wall of the
hind-brain. The cavity of the pharynx is somewhat triangular and its dorsal wall is thin.

62

THE STUDY OF CHICK EMBRYOS

The anterior cardinal veins pass between the otocysts and the wall of the hind-brain.
Ventral to the pharynx, the bulbus cordis is sectioned obliquely where it leaves the heart,
and at this level gives off laterad the second pair of aortic arches which connect dorsad
with the descending aortae. Surrounding the bulbus cordis is the large pericardial cavity.
The student should note that in the sections of this stage so far studied, the mesenchyme
of the head is undifferentiated, the tissues peculiar to the adult not yet having been
formed.

Section through the Second Pharyngeal Pouches and Thyreoid Anlage (Fig. 61).
As this section is taken at a level between the second and third aortic arches, the de-
scending aortas and heart are unconnected. Tangential shavings have been cut from the
walls of the otocysts. Extending laterally from the pharynx are the second pair of pharyn-
geal pouches which have already come in contact with the ectoderm to form closing plates.

Hind-brai;

Ectoderm
Ant. cardinal vein

Descending aorta

Closing plate

Pharynx

Thyreoid anlage

Mesode

Epi-myocardium of bulbns
Endolhelium of bulbus

FIG. 61. — Transverse section through the second pharyngeal j- ouches and thyreoid anlage of a
fifty-hour chick embryo. X 50.

A pocket-like depression in the mid-ventral floor of the pharynx represents the thyreoid
anlage; later it becomes saccular and loses its connection with the pharyngeal entoderm.
The splanchnic mesodermal wall of the heart is destined to give rise later to the epi- and
myocardium.

Section through the Sinus Venosus and Common Cardinal Veins (Fig. 62).— At
this level, the common trunk formed by the anterior and posterior cardinal veins opens into
the thin- walled sinus venosus. The sinus receives all of the blood passing to the heart and
is separated only by a slight constriction from the larger atrium. The muscle plates of the
first mesodermal segments are seen, and the descending aortas have united to form a single
dorsal vessel. On either side of the pharynx are subdivisions of the ccelom which will
form the pleural cavities. These cavities are separated from the pericardial cavity by the

EMBRYO OF TWENTY-SEVEN SEGMENTS

septum transversum (anlage of diaphragm) in which the common cardinal veins cross to the
sinus venosus.

Spinal cord
Mesodermal segment

Dorsal aorta
Mesenchyme

Common cardinal vein

Entoderm
Myocardium

Atrium
Endothelium of heart

FIG. 62. — Transverse section through the sinus venosus and common cardinal veins of a
fifty-hour chick embryo. X 50.

Fore-gut
L. vitelline vein

Splanchnic mesoderm

Posterior cardinal vein

Splanchnic mesoderm
Liver anlage

Vitelline vein

FIG. 63. — Transverse section through the anlage of the liver of a fifty-hour chick embryo.

X 50.

The somatopleuric folds of the amnion envelop the right side of the embryo, and the
ectoderm of these folds now forms the outer layer of the chorion and the inner layer of the
amnion. The mesodermal components of the folds have not yet united.

THE STUDY OF CHICK EMBRYOS

Section through the Anlage of the Liver (Fig. 63). — In this section the cavity of the
fore-gut is narrow, the gut being flattened from side to side. Ventrad there are evaginated
from the entoderm two elongate diverticula which form the anlages of the liver. On either
side of the anlages of the liver are sections of the vitelline veins on their way to the sinus

Splanchnic mesoderm

Ectoderm

Posterior cardinal vet
Notochord-

Somatopleur

Open gut

Entod>

Chorion

Amnion

'entral canal
Spinal cord

Mesodermal segment
R. descending aorta

Ccdom
Somatoplewe

FIG. 64.— Transverse section through the cranial portion of the open intestine of a fifty-hour

chick embryo. X 50.

venosus at a higher level in the series. Note the intimate relation between the entodermal
epithelium of the liver and the endothelium of the vitelline veins. In later stages, as the
liver anlages branch, there is, as Minot aptly expresses it, "an intercrescence of the ento-
dermal cells constituting the liver and of the vascular endothelium" of the vitelline veins.

Mesodermal segment
Descendin,
Somatopleure
Somatic mesoderm

Spinal cord

Ectoderm
Notochord

'omatic mesoaerm

Splanchnopleure' / \ ^Splanchnic mesoderm

Ccdom Entoderm

FIG. 65. — Transverse section through the seventeenth pair of mesodermal segments of a fifty-
hour chick embryo. X 50.

Thus are formed the hepatic sinusoids of the portal system, which surround the cords of
hepatic cells.

The septum transversnm is still present at this level and lateral to the fore-gut are small
body cavities. Lateral to the body cavities appear branches of the posterior cardinal veins.

EMBRYO OF TWENTY-SEVEN SEGMENTS

Section through the Cranial Portion of the Open Intestine (Fig. 64).— The intestine
is now open ventrad, its splanchnopleure passing directly over to that of the vascular area.
The folds of the amnion do not join, leaving the amniotic cavity open. The dorsal aorta
is divided by a septum into its primitive components, the right and left descending aortoe.
Lateral to the aortae are the small posterior cardinal veins. The ccelom is in communica-
tion with the extra-embryonic body cavity.

Section through the Seventeenth Pair of Mesodermal Segments (Fig. 65). — The
body of the embryo is now no longer flexed to the right. On the left side of the figure, the

Mesodermal segment

Nephrotome
Ccelom

Spinal cord

Ectoderm

Somatoplenre

'ephric duct

'omatic mesoderm

Splanchnopleure'

Aorta and vitelline Notochord
artery

FIG. 66. — Transverse section of a fifty-hour chick embryo, at the level of the origin of the vitel-

Hne arteries. X 50.

mesodermal segment shows a dorso-lateral myotome plate. The median and ventral por-
tion of the segment is being converted into mesenchyme. On the right side appears a
section of the primary excretory, or mesonephric duct. The embryonic somalopleure is
arched and will form the future ventro-lateral body wall of the embryo. The lateral in-
foldings of the somatopleure give indication of the later approximation of the ventral
body walls, by which the embryo is separated from the underlying layers of the
blastoderm.

Section through the Origin of the Vitelline Arteries (Fig. 66).— At this level the em-
bryo is more flattened and simpler in structure, the section resembling one through the

Spinal cord
Descending aortc
Somatic mesoderm

Ectoderm

Segmental zone

..Somatic mesoderm

Splanchnic mesoderm

Codom

Notochord Entoderm

FIG. 67. — -Transverse section of a fifty-hour chick embryo through the segmental zone, caudal to

the mesodermal segments. X 50.

mid-gut region of a thirty-eight-hour chick (Fig. 49). The amniotic folds have not ap-
peared. On the left side of the figure the vitelline artery leaves the aorta. On the right
side the connection of the vitelline artery with the aorta does not show, as the section is
cut somewhat obliquely. The posterior cardinal vein is present just laterad of the right
mesonephric duct. The other structures were described in connection with Fig. 49-
Section Caudal to the Mesodermal Segments (Fig. 67).— The mesodermal segments
are replaced by the segmental zone, a somewhat triangular mass of undifferentiated meso-
derm from which later are formed the segments and nephrotomes. The notochord is larger,

66

THE STUDY OF CHICK EMBRYOS

the aorta smaller, and a few sections caudad they disappear. Laterally the somatopleure
and splanchnopleure are straight and separated by the slit-like coelom.

Section through the Notochordal Plate, Cranial to the Hind-gut (Fig. 68).— With the
exception of the ectoderm, the structures near the median plane are merged into an undif-
ferentiated mass of dense tissue, the notochordal plate. The cavity of the neural tube and
its dorsal outline may, however, still be seen. Laterally the segmental zone and the
various layers are differentiated.

Neural tube

Ccelo

Ectoderm

Segmental zone

Splanchnopleure / Notochordal plate

Entoderm

FIG. 68. — Transverse section of a fifty-hour chick embryo through the notochordal plate,
cranial to the hind-gut. X 50.

Section through the Hind-gut and Primitive Streak (Fig. 69). — In this embryo the cau-
dal evagination to form the hind-gut has just begun. The section shows the small cavity
of the hind-gut in the midplane. Its wall is composed of columnar entodermal cells and
it is an outgrowth of the entodermal layer. A few sections cephalad in the series, the hind-
gut opens by its own intestinal portal. Dorsal to the hind-gut may be seen undifferentiated
cells of the primitive streak, continuous dorsad with the ectoderm, ventrad with the entoderm
of the hind -gut, and laterally with the mesoderm.

Somatic mesoderm
Ccelom

Primitive streak

Ectoderm

Somatopleure

Splanchnopleure

Hind-gut

FIG. 69. — Transverse section through the hind-gut of a fifty-hour chick embryo. X 50.

Extra -embryonic Structures. — In the chick embryos which we have
studied, there are large areas developed which are extra-embryonic, that
is, lie outside the embryo. The splanchnopleure of the area vasculosa,
for instance, forms the wall of the yolk sac, incomplete in the early stages.
The amnion, chorion, and allantois are extra-embryonic membranes which
make their appearance at the fifty-hour stage. These structures are
important in mammalian and human embryos and a description of their
further development in the chick, where their structure and mode of devel-
opment is primitive, will lead up to the study of mammalian embryos in
which the amnion and chorion are precociously developed.

EMBRYO OF TWENTY-SEVEN SEGMENTS 67

Amnion and Chorion. — -These two membranes are developed in all
amniote vertebrates (Reptiles, Birds, and Mammals). They are derived
from the extra-embryonic somatopleure. The amnion is purely a protec-
tive structure, but the chorion of mammals has a trophic function, as
through it the embryo derives its nourishment from the uterine wall.
Fig. 70 A shows the amnion and chorion developing. The head fold of
the somatopleure forms first and envelops the head, the tail fold makes its
appearance later. The two folds extend lateral, meet and fuse (Fig. 70
B, C}. The inner leaf of the folds forms the amnion, the remainder of
the extra-embryonic somatopleure becomes the chorion. The actual

X

FIG. 70. — Diagrams showing the development of the ananion, chorion and allantois in
longitudinal section (Gegenbaur in McMurrich). Ectoderm, mesoderm, and entoderm repre-
sented by heavy, light, and dotted lines respectively. Af., Amnion folds; Al., allantois;
Am., amniotic cavity; Ch., chorion; Ys., yolk sac.

appearance of these structures and their relation to the embryo have been
seen in Figs. 63 and 64. The amnion, with its eetodermal layer inside,
completely surrounds the embryo at the end of the third day, enclosing a
cavity filled with amniotic fluid (Fig. 71). In this the embryo floats and
is thus protected from injury. The chorion is of little importance to the
chick. It is at first incomplete, but eventually entirely surrounds the
embryo and its other appendages.

Yolk Sac and Yolk Stalk.— While the amnion and chorion are develop-
ing during the second and third day, the embryo grows rapidly. The head
and tail folds elongate and the trunk expands laterally until only a rela-
tively narrow stalk of the splanchnopleure connects the embryo with the

68

THE STUDY OF CHICK EMBRYOS

yolk. This portion of the splanchnopleure has grown more slowly than
the body of the embryo and is termed the yolk stalk. It is continuous with
the splanchnopleure that envelops the yolk and forms the yolk sac. The
process of unequal growth, by which the embryo becomes separated from
the blastoderm, has been falsely described as a process of constriction
(see p. 80). The splanchnopleure at first forms only an oval plate on the
surface of the yolk, but eventually encloses it. In Fig. 70, C and D,
the relation of the embryo to the yolk sac is seen at the end of the first
week of incubation. The vitelline vessels ramify on the surface of the
yolk sac, and through them all the food material of the yolk is conveyed to
the chick during the incubation period (about twenty-one days).

Yolk sac

Allantois Embryo Amnion Chorion

Shell

Air chamber

Shell membrane

Margin of area vasculosa

FIG. 71.— Diagram of a chick embryo at the end of the fifth day, showing amnion, chorion and
allantois (Marshall). X 1.5.

Allantois. — We have seen that in the fifty-hour chick a ventral
evagination, the hind-gut, develops near its caudal end (Fig. 69). From it
develops the anlage of the allantois, which, as an outgrowth of the splanch-
nopleure, is lined with entoderm and covered with splanchnic mesoderm
(Fig. 70). It develops rapidly into a vesicle connected to the hind-gut
by a narrow stalk, the allantoic stalk. At the fifth day the allantoisjis
nearly as large as the embryo (Fig. 71). Its wall flattens out beneath
the chorion and finally it lies close to the shell but is attached only to the
embryo. The functions of respiration and excretion are ascribed to it.
In its wall ramify the allantoic vessels, which have been compared to the
umbilical arteries and veins of mammalian embryos.

EMBRYO OF TWENTY-SEVEN SEGMENTS 69

The chick embryo is thus protected by the amnion which develops
from the inner leaf of the folded somatopleure and is composed of an inner
ectodermal and an outer mesodermal layer. Nutriment for the growth of
the embryo is supplied by the yolk sac and carried to the embryo by the
vitelline veins. The allantois, which takes its origin from the splanchno-
pleure of the hind-gut and is composed of an inner layer of entoderm and
an outer layer of splanchnic mesoderm, functions as an organ of respiration
and serves as a reservoir for the excreta of the embryonic kidneys. As
we shall see, the allantois becomes more important, the yolk sac less impor-
tant, in some mammals, while in human embryos both yolk sac and allan-
tois are unimportant when compared to the chorion.

CHAPTER IV
HUMAN EMBRYOS AND FETAL MEMBRANES

THE fetal membranes of mammals include the amnion, chorion,
yolk sac, and allantois, structures which we have seen are present in chick
embryos. Most important in mammals is the manner in which the
embryo becomes attached to the uterine wall of the mother, and in this
regard mammalian embryos fall into two groups. Among the Ungulates,
or hoofed mammals (e. g., the pig), the fetal membranes are of a primitive
type, resembling those of the chick. Among Unguiculates (clawed animals
like the bat and rabbit), including Primates (e. g., Man), the fetal mem-
branes of the embryo show marked changes in development and structure.

FETAL MEMBRANES OF THE PIG EMBRYO

The amnion and chorion develop very much as in the chick embryo
(Fig. 70 A, B). Folds of the somatopleure form very early and envelop
the whole embryo. The amnion (Fig. 72) is a closed sac in embryos

•"Spinal cord
Mesodermal segment "

Upper limb bud^^^^^^g^^^j^g^ \^ Amnion

- Somatopleure

Posterior cardinal ^in^^ffjj^^ J Jjjj$Ji^&-~Mesonephric duct
Dorsal aorta*

-Mesentery
~L. umbilical vein
R. umbilical vein" ^p ^f M^L. ntelline vein

-Entoderm of gut

.•.«.-. ---yy, *w "Splanchnic mesoderm

Wall of yolk sac • — -^"^ <***

FIG. 72. — Transverse section through the yolk sac and stalk of a 5 mm. pig embryo, showing

attachment of amnion.

with only a few pairs of segments, but for some time it remains attached
to the chorion by a strand of tissue (Keibel). The yolk sac develops
early, as in all mammals. In the pig it is small and the greater part of it
soon degenerates. It is important only in the early growth of the embryo,
its functions then being transferred to the allantois. Branches of the
vitelline vessels ramify in its wall, as in that of chick embryos, but soon
degenerate. The trunks of the vitelline vessels, however, persist within

70

FETAL MEMBRANES OF THE PIG EMBRYO

the body of the embryo. The allantois, developing as in the chick from
the ventral wall of the hind-gut (Fig. 70 A-D), appears when the embryo is
still flattened out on the germinal disc. In an embryo 3.5 mm. long it is
crescent-shaped and as large as the embryo. It soon becomes larger and
its convex outer surface (splanchnic mesoderm) is applied to the inner
surface (somatic mesoderm) of the chorion.

These surface layers fuse more or less completely. A pair of allantoic
veins and arteries branch in the splanchnic layer of the allantois. These
branches are brought into contact with the mesodermal layer of the cho-

Entoderm of primitive gut

Hind-gut

Amnion

Ectoderm

Fore-gut

Somatic mesoderm
Splanchnic mesoderm

Yolk sac

Entoderm

-Chorionic mesoderm
Ihorionic ectoderm
* 'Uterine epithelium
. Tunica propria of uterus

FIG. 73. — Diagram of the fetal membranes and allantoic placenta of a pig embryo, in median
sagittal section (based on figures of Heisler and Minot).

rion and invade it. The outer ecto dermal layer of the chorion in the mean-
time has closely applied itself to the uterine epithelium, the ends of the
uterine cells fitting into depressions in the chorionic cells (Fig. 73). When
the allantoic circulation is established, waste products given off from the
blood of the embryo must pass through the epithelia of both chorion and
uterus to be taken up by the blood of the mother. In the same way,
nutritive substances and oxygen must pass from the maternal blood
through these layers to enter the allantoic vessels. This exchange does
take place, however, and thus in Ungulates the allantois has become im-

72 HUMAN EMBRYOS AND FETAL MEMBRANES

portant, not only as an organ of respiration and excretion, but as an organ
of nutrition. Through its vessels it has taken on a function belonging to
the yolk sac in birds, and we now see why the yolk sac becomes a rudimen-
tary structure in the higher mammals. Excreta from the embryonic
kidneys are passed into the cavity of the allantois which is relatively large.
The name is derived from a Greek word meaning sausage-like, from its
form in some animals. The chorion is important only as it brings the
allantois into close relation to the uterine wall, but in man we shall see
that it plays a more important role.

THE UMBILICAL CORD

Pig Embryos. — In their early development, the relation of the amnion,
allantois, and yolk sac to each other and to the embryo is much the same
as in the chick of five days (Fig. 71). With the increase in size of the
embryo, however, the somatopleure in the region of the attachment of the
amnion grows ventrad (Fig. 70 D). As a result, it is carried downward
about the yolk sac and 'allantois, forming the umbilical cord (cf. Fig.
241). Thus, in a pig embryo 10 to 12 mm. long, the amnion is attached at
a circular line about these structures some distance from the body of the
embryo (cf. Fig. 119). The ccelom at first extends ventrad into the cord,
but later the mesodermal layers of amnion, yolk stalk, and allantois
fuse and form, a solid cord of tissue. This is the umbilical cord of fetal
life and its point of attachment to the body is the umbilicus, or navel.
The cord is covered by a layer of ectoderm continuous with that of the
amnion and of the embryo, and contains, embedded in a mesenchymal
(mucous) tissue: (i) the yolk stalk and (in early stages) its vitelline
vessels; (2) the allantoic stalk; (3) the allantoic vessels. These latter,
two arteries and a single large vein, are termed, from their position, the
umbilical vessels. At certain stages (Figs. 122 and 123) the gut normally
extends into the ccelom of the cord, forming an umbilical hernia. Later, it
returns to the ccelom of the embryo and the cavity of the cord disappears.
The umbilical cord of the pig is very short.

The Human Umbilical Cord. — This develops like that of the pig and may
attain a length of more than 50 cm. It becomes spirally twisted, just
how is not known. In embryos from 10 to 40 mm. long the gut extends
into the ccelom of the cord (Figs. 179 and 180). At the 42 mm. stage,
the gut returns to the ccelom of the body. The mucous tissue peculiar to
the cord arises from mesenchyme. It contains no capillaries and no nerves,
but embedded in it are the large umbilical vein, the two arteries, the allan-
tois, and the yolk stalk. The umbilical cord may become wound about
the neck of the fetus, causing its death and abortion, or by coiling about
the extremities it may lead to their atrophy or amputation.

EARLY HUMAN EMBRYOS AND THEIR MEMBRANES 73

EARLY HUMAN EMBRYOS AND THEIR MEMBRANES

Descriptions of graded human embryos will introduce the reader to
early mammalian development and indicate the divergencies from the
chick stages already studied. A somewhat detailed account of a 4.2 mm.
human embryo will then link the fifty-hour chick with the pig studies
which follow.

Referring to the blastodermic vesicle of the mamma] (Figs. 1 7 and 18) ,
it is found to consist of an outer layer, which we have called the trophecto-
derm, and the inner cell mass (p. 2 7) . The trophectoderm forms the primi-
tive ectodermal layer of the chorion in the higher mammals and probably
in man. From the inner cell mass are derived the primary ectoderm,
entoderm, and mesoderm. In the earliest known human embryos, de-
scribed by Teacher, Bryce, and Peters, the germ layers and amnion are
present, indicating that they are formed very early. We can only infer
their early origin from what is known of other mammals. The diagrams
(Fig. 74 A and £?) show two stages, the first hypothetical, seen in median
longitudinal section. In the first stage (A) the blastodermic vesicle is
surrounded by the trophectoderm layer. The inner cell mass is differ-
entiated into a dorsal mass of ectoderm and a ventral mass of entoderm.
Mesoderm more or less completely fills the space between entoderm and
trophectoderm. It is assumed that as the embryo grows (5) a split
occurs in the mass of ectoderm cells, giving rise to the amniotic cavity
and dividing these cells into the ectodermal layer of the embryo and into
the extra-embryonic ectoderm of the amnion. At the same time a
cavity may be assumed to form in the entoderm, giving rise to the primi-
tive gut. At about this stage the embryo embeds itself in the uterine
mucosa. In the third stage (C), based on Peters' embryo, the extra-
embryonic mesoderm has extended between the trophectoderm and the
ectoderm of the amnion, and the extra-embryonic ccelom appears. At
first, strands of mesoderm, known as the magma reticulare, bridge across
the ccelom between the somatic and splanchnic layers of mesoderm
(Fig. 76). The amniotic cavity has increased in size, and the embryo
is attached to the trophectoderm by the unsplit layerof mesoderm between
the ectoderm of the amnion and the trophectoderm of the chorion. The
latter shows thickenings which are the anlages of the chorionic villi, sur-
rounded by syncytial trophoderm. In the fourth stage (D), based on
Graf Spec's embryo, the chorionic villi are longer and branched. The
mesoderm now remains unsplit only at the posterior end of the embryo,
where it forms the body stalk peculiar to Unguiculates and Primates. It
connects the mesoderm of the embryo with the mesoderm of the chorion.
Into it there has grown from the gut of the embryo the entodermal diver-
ticulum of the allantois.

74

HUMAN EMBRYOS AND FETAL MEMBRANES

The Chorion. — The human chorion is derived directly from the outer
trophectoderm layer of the blastodermic vesicle and from the extra-
embryonic somatic mesoderm. At first, its structure resembles that of
thej pig's chorion. The trophectodeim of the human embryo, however,
early gives rise to a thickened outer layer, the trophoderm (syncytial and
nutrient layer — Figs. 74 C and 239). When the developing embryo comes

Ectoderm of amnion
Ectoderm of embryo \

Allantoi

D

Body stalk

Ectoderm of
mniotic cavity Cavity Of amnion

Mesoderm of

rophectoderm amnion

Yolk sac Ectoderm of
chorion
Entoderm Cavity of yol

sac

Splanchnic Entoderm
mesoderm yoik Sac

'ra-embry- Mesoderm'
omc ccdom Of yoik sac
Extra-embry-
onic ccelom

Mesoderm
of chorion

~Choriomc meso-
derm
-Trophoderm

Chorionic vitii

FIG. 74. — Four diagrams of early human embryos (based on figures of Robinson and
Minot). A, Hypothetical stage; B, Bryce-Teacher embryo (modified); C, Peters' embryo;
D, Graf Spee's embryo.

into contact with the uterine wall, the trophoderm destroys the maternal
tissues. The destruction of the uterine mucosa serves two purposes:
(i) the embedding and attachment of the embryo, it being grafted, so to
speak, to the uterine wall ; and (2) it supplies the embryo with a new source
of nutrition. To obtain nutriment to better advantage, there grow out
from the chorion into the uterine mucosa branched processes, or villi.
The villi are bathed in maternal blood, and in them blood vessels are
developed, the trunks of which pass to and from the embryo as the um-

EARLY HUMAN EMBRYOS AND THEIR MEMBRANES

75

bilical vessels. The embryo receives its nutriment and oxygen, and gets
rid of waste products through the walls of the villi. The region where
the attachment of the chorionic villi to the uterine wall persists during
fetal life is known as the placenta. It will be described later with the
decidual membranes of the uterus (p. 237 ff.).

Inner cell mass

Entoderm

Trophedodcrm

Cnboidal cells

(of Langhans)

Embryonic ectoderm Entoderm

FIG. 75. — Sections showing the formation of the amnion in bat embryos (after Van Beneden).

X about 1 60.

We saw how the allantois of Ungulates had assumed the nutritive
functions performed by the yolk sac in birds, with a consequent degene-
ration of the ungulate yolk sac. In man and most Unguiculates the func-
tions of the allantois are transferred to the chorion, and the allantois, in
turn, becomes a rudimentary structure.

The Amnion. — This is formed precociously in Unguiculates, and in a
manner quite different from its mode of origin in Ungulates and birds.

76 HUMAN EMBRYOS AND FETAL MEMBRANES

It is assumed that its cavity arises as a split in the primitive ectoderm of
human embryos, as in bat embryos (Fig. 75). Later, a somatic layer of
mesoderm envelops its ectodermal layer, its component parts then being
the same as in birds and Ungulates — an inner layer of ectoderm and an
outer layer of mesoderm (Fig. 74 D). It becomes a thin, pellucid, non-
vascular membrane, and about a month before birth is in contact with the
chorion. It then contains about a liter of amniotic fluid, the origin of
which is unknown. During the early months of 'pregnancy the embryo,
suspended by the umbilical cord, floats in the amniotic fluid which serves
as a water cushion. The embryo is protected from maceration by a white,
fatty secretion, the vernix caseosa.

At birth the membranes rupture. If the chorion bursts alone, the child may be born
enveloped in the amnion, popularly known as a veil, or 'caul.' The amniotic fluid may be
present in excessive amount, the condition being known as hydramnios. If less than the
normal amount of fluid is present, the amnion may adhere to the embryo and produce
malformations. It has been found, too, that fibrous bands or cords of tissue sometimes
extend across the amniotic cavity, and, pressing upon parts of the embryo during its growth,
cause scars and splitting of eyelids or lips. Such amniotic threads may even amputate a
limb or cause the bifurcation of a digit.

Amniotic cavity
Mesoderm of chorionic villus

Ectoderm of chorion

rm of embryo
Mesoderm

Extra-embryonic coelom

Yolk sac
Mesoderm

Entoderm

FIG. 76. — Section of Peters' embryo of 0.2 mm. (about fifteen days). The portion of extra-
embryonic ccelom shown is limited below by a strand of the magma reticulare.

The Allantois. — The allantois appears very early in the human em-
bryo, before the development of the fore-gut -or hind-gut. In Peters'
embryo the amnion, chorion, and yolk sac are present, but not the allan-
tois (Fig. 76). In an embryo 1.54 mm. long, described by von Spec
(Fig. 77), there is no hind-gut, but the allantoic diverticulum of the en-

EARLY HUMAN EMBRYOS AND THEIR MEMBRANES

77

toderm has invaded the mesoderm of the body stalk. This embryo,
seen from the dorsal side with the amnion cut away, shows a marked neural

Neural groove—'^ .. /

Neurenteric canal

Primitive streak

Body stalk

Villi of chorion

Amnion
Embryonic disc

A nlage of heart

Splanchnic mesoderm

'horion
Somatic mesoderm

Body stalk
Primitive streak

Blood vessel

FIG. 77. — Views of a human embryo of 1.54 mm. (von Spee). X 23. A, Dorsal surface; B,
median sagittal section.

groove and primitive streak. In front of the primitive knot a pore is
figured, leading from the neural groove into the primitive intestinal

HUMAN EMBRYOS AND FETAL MEMBRANES

mnion (cut)
.Neural fold

cavity, and hence called the neurenteric canal (p. 34). The fore-gut and
head fold have formed at this stage and there are branched chorionic

villi. Somewhat more advanced
conditions are found in an em-
bryo of 1.8 mm. with five to six
pairs of segments (Fig. 78).

A reconstruction by Dandy
of Mall's embryo, about 2 mm.
long with seven pairs of segments,
shows well the embryonic ap-
pendages i (Fig. 79). The fore-
and hind-gut are well developed,

Neurenteric canal
Primitive streak

FIG. 78. — Kromer human embryo of 1.8
mm., in dorsal view (after Keibel and Elze).

X 20.

the amniotic cavity is large, and
the yolk sac still communicates
with the gut through a wide
opening. The allantois is present

as a curved tube, somewhat dilated near its blind end and embedded in
the mesoderm of the body stalk. As the hind-gut develops, the allantois

Chorion
A mnion

Pharyngeal
membrane
Fore-gut
Heart

___y stalk
Allantoic

stalk
Hind-gut

'Blood island
•Blood vessel

ructions

^^^•^

FIG. 79. — A human embryo of 2 mm. in median sagittal section (adapted from reconst
of Mall's embryo by F. T. Lewis and Dandy). X 23.

comes to open into its ventral wall. A large umbilical artery and vein
are present in the body stalk.

EARLY HUMAN EMBRYOS AND THEIR MEMBRANES

79

In an embryo of 23 somites, 2.5 mm. long, described by Thompson,
the allantois has elongated and shows three irregular dilatations (Fig. 80).
A large cavity never appears distally in the human allantois as in Ungu-
lates, but when it becomes included in the umbilical cord its distal portion
is tubular. The allantois eventually atrophies and is without further
significance (cf. p. 209).

The human allantois is thus small and rudimentary as compared with
that of birds and Ungulates. As we have seen, the cavity is very large

in the pig, and Haller found an
allantoic sac two feet long con-
Phar nx 7 ***^ \ nected w^h a goat embryo of

Pharyngeal
membrane
Thyreoid

Pericardium

Hepatic diverticulum
Septum transversum

Cloacal membrane
Cloaca

Neural folds

Neurenteric canal

FIG. 80. — Median sagittal section of a 2.5 mm. FIG. 81. — Human embryo of 2.11 mm.
human embryo, showing digestive tract (after (Eternod). X 35.

Thompson). X_4O.

two inches. In human embryos it appears very early and is not free,
but embedded in the body stalk. Its functions, so important in birds and
Ungulates, are in man performed by the chorion.

The Yolk Sac and Stalk. — In the youngest human embryos described,
the entoderm forms, a somewhat elongated vesicle (Fig. 76). With the
development of the fore-gut and hind-gut in embryos of 1.54 and 2 mm.
(Figs. 77 and 79), the entodermal vesicle is divided into the dorsal intestine
and ventral yolk sac, the two being connected by a somewhat narrower
region. This condition persists in an embryo 2.5 mm. long (Fig. 80).
In the figure, most of the yolk sac has been cut away. Embryos with

8o

HUMAN EMBRYOS AND FETAL MEMBRANES

9 and 14 pairs of segments, with three brain vesicles and with the amnion
cut away are seen in Figs. 81 and 324. The relation of the fetal appen-

A mnion

Body stalk

FIG. 82. — Human embryo of about 2.5 mm. (His, after Coste). X 15.

dages to the embryo shows well in the embryo of Coste (Fig. 82). The
dorsal concavity is probably abnormal. A robust body stalk attaches the

Amnion

Branchial grooves 1-3

Body stalk

Maxillary process

Mandibular process
Heart

Yolk-sac
FIG. 83. — Human embryo of 2.6 mm., showing amnion, yolk stalk and body stalk (His).

X25.

embryo to the inner wall of the chorion. With the growth of the head-
and tail folds of the embryo, there is an apparent constriction of the yolk

THE ANATOMY OF A 4.2 MM. HUMAN EMBRYO 8l

sac where it joins the embryo. This, however, is a deception. Both
embryo and yolk sac enlarge, whereas the region of union lags and later
becomes the slender yolk stalk (Fig. 84). His' embryo, 2.6 mm. long,
shows the relative size of yolk sac and embryo and the yolk stalk (Fig.
83). The relations of the fetal membranes to the embryo are much the
same as in the chick embryo of five days, save that the allantois of the
human embryo is embedded in the body stalk. The embryo shows a
regular, convex dorsal curvature, there is a marked cephalic bend in the
region of the mid-brain and there are three branchial grooves. The head is
twisted to the left, the tail to the right. At the side of the oral sinus are
two large processes; the dorsal of these is the maxillary, the ventral the
mandibular process. The heart is large and flexed in much the same way
as the heart of the fifty-hour chick embryo.

In later stages, with the development of the umbilical cord, the
yolk stalk becomes a slender thread extending from the dividing line

FIG. 84. — Yolk sac and stalk of a 20 mm. human embryo. X n.

between the fore- and hind-gut to the yolk sac, or umbilical vesicle (Figs.
84 and 119). It loses its attachment to the gut in 7 mm. embryos. A
blind pocket may persist at its point of union with the intestine; this is
known as MeckeVs diverticulum, a structure of clinical importance because
it sometimes telescopes and causes the occlusion of the intestinal lumen.
The yolk stalk may remain embedded in the umbilical cord and extend
some distance to the yolk sac which is found between the amnion and
chorion. The yolk sac may be persistent at birth.

THE ANATOMY OF A 4.2 MM. HUMAN EMBRYO

This embryo, studied and described by His, is regarded by Keibel
as not quite normal. Viewed from the left side (Fig. 85), with the amnion
cut away close to its line of attachment, there may be seen the yolk stalk,
and a portion of the yolk sac and body stalk. There is an indication of
the primitive segments along the dorso-lateral line of the trunk. The
head is bent ventrad almost at right angles, forming in the mid-brain
region the cephalic flexure. There are also marked cervical and caudal
flexures, the trunk ending in a short, blunt tail. The heart is large and

HUMAN EMBRYOS AND FETAL MEMBRANES

flexed as in the earlier stage. Three branchial grooves separate the four
branchial arches. The first arch has developed two ventral processes. Of
these, the maxillary process is small and may be seen dorsal to the stomo-
dceum. The mandibular process is large and has met its fellow of the
right side to form the mandible, or lower jaw. Dorsal to the second
branchial groove may be seen the position of the oval otocyst, now a closed

sac. Opposite the atrial portion
Mid-l

Fore-brain

StomodcRiim

ind-brain
Otocyst

•Amnion (cut)

of the heart, and in the region of
the caudal flexure, bud-like out-
growths indicate the anlages of
the upper and lower extremities.

Central Nervous System and
Sense Organs. The neural tube
is closed throughout its extent
and is differentiated into brain
and spinal cord. The brain tube,
or encephalon, is divided by con-
strictions into four regions, or
vesicles, as in the fifty-hour chick
(Fig. 57). Of these, the most
cephalad is the telencephalon. It
is a paired outgrowth from the
fore-brain, the remaining portion
of which is the diencephalon. The
mid-brain, or mesencephalon,
located at the cephalic flexure, is

not subdivided. The hind-brain, or rhombencephalon, which is long and
continuous with the spinal cord, later is subdivided into the metencephalon
(region of the cerebellum and pons) and myelencephalon (medulla
oblongata). The spinal cord forms a closed tube extending from the
brain to the tail and containing the neural cavity, flattened from side
to side.

The eye is represented by the optic vesicles and the thickened ecto-
dermal anlage of the lens. Its stage of development is between that of
the thirty-eight- and fifty-hour chick embryos.

The otocyst is a closed sac, no longer connected with the outer ecto-
derm as in the fifty-hour chick.

Digestive Canal. — -In a reconstruction of the viscera viewed from the
right side (Fig. 86), the entire extent of the digestive canal may be seen.
The pharyngeal membrane, which we saw developed in the chick between
the stomodaeum and the pharynx, has broken through so that these cavities
are now in communication. The fore-gut, which extends from the oral

Body stalk

FIG. 85. — Human embryo of 4.2 mm., in lateral
view (His). X 15-

THE ANATOMY OF A 4.2 MM. HUMAN EMBRYO

cavity to the yolk stalk, is differentiated into pharynx, thyreoid, trachea
and lungs, esophagus and stomach, small intestine and digestive glands
(pancreas and liver) . The gut is suspended' from the dorsal body wall
by the dorsal mesentery.

The ectodermal limits of the oral cavity are indicated dorsad by the
diverticulum of the hypophysis (Rathke's pouch}. The fore-gut proper

Metencephalon

Aortic arches 2-4,

Notochord.

Descending aort

Trachea,
Lung bud
Esophagus

Hind-gu,

Mesencephalon and cephalic flexure
Rathke's pouch
, Diencephalon

Internal carotid artery

.Optic vesicle

Prosencephalon
Mouth cavity

Pharyngeal pouches 1-4

Ventral aorta

Atrium of heart

Umbilical vein

Liver anlage

Splanchnic mesoderm

Mid-gut

Entoderm of yolk stalk

Tail gut

Umbilical artery
Mesonephric duct

Cloaca
Allantoi's
FiG. 86. — Diagrammatic reconstruction of a 4.2 mm. human embryo, viewed from the right

side (adapted from a model by His).

X 25.

begins with a shallow out-pocketing known as SeesseVs pouch. As the
pharyngeal membrane disappears between these pockets, it would seem
that Seessel's pouch represents the persistence of the blind anterior end
of the fore-gut. No other significance has been assigned to it.

The pharynx is widened laterally, and at this stage shows four
pharyngeal pouches (Fig. 87). Later a fifth pair of pouches is developed
(Fig. 1 68). The four pairs of pharyngeal pouches are important as they

84

HUMAN EMBRYOS AND FETAL MEMBRANES

form respectively the following adult structures: (i) the auditory tubes;
(2) the palatine tonsils; (3) the thymus and parathyreoids ; (4) the.parathy-
reoids. Between the pharyngeal pouches are the five branchial arches in
which are developed five pairs of aortic arches. Between the bases of
the first and second branchial arches, on the floor of the pharynx, is
developed the transient tuberculum impar. Posterior to this unpaired
structure there grows out ventrally the anlage of the thyreoid gland. From

•Month cavity

Pharyngeal pouches 1-4

Esophagus

•Stomach

Hepatic diverticulu
Ventral pancreas

Mesonephric tubule with glomeruliis
Hind-gut

Allantois

Thyreoid anlage

Dorsal pancreas
Yolk stalk
Mesonephros
Mesonephric duct

:ioaca

Tail gut

FIG. 87. — Diagrammatic ventral view of pharynx, digestive tube, and mesonephroi of a
4-5 mm. embryo (based on reconstructions by Grosser and His). X about 30. The liver and
yolk sac are cut away. The tubules of the right mesonephros are shown diagrammatically.

the caudal end of the trachea have appeared ventrally the lung buds.
The trachea is still largely a groove in the ventral wall of the pharynx and
esophagus (Fig. 86). Caudal to the lungs, a slight dilation of the digestive
tube indicates the position of the stomach. The liver diverticulum has
grown out from the fore-gut into the ventral mesentery, cranial to the
wall of the yolk stalk. It is much larger than in the fifty-hour chick,
where its paired anlage was seen cranial to the intestinal portal, and is
separated from the heart by the septum transversum. The small intestine
between the liver and yolk stalk is short and broad. In later stages it

Aortic arches 7-4

Atrium

V Hello-umbilical vein

L. umbilical vein

FIG. 88.— Ventral reconstruction of a 3.2 mm. embryo, showing vessels (His).

Umbilical vein

Olfactory pit
Mandibular arch

Common cardinal vein

) ...Allantois

Umbilical artery

Placental attachment

FIG. 89. — Lateral view of human embryo of 4.2 mm., showing aortic arches and venous trunks (His).
mx, Maxillary process; jv., anterior cardinal vein; c.v., posterior cardinal vein; ot, otocyst.

THE ANATOMY OF A 4.2 MM. HUMAN EMBRYO 85

becomes enormously elongated as compared with the rest of the digestive
tube. The yolk stalk is still expansive. The region of its attachment
to the gut corresponds to the open mid-gut of the chick embryo. The
hind-gut and tail fold of this embryo are greatly elongated as compared
with the chick embryo of fifty hours. The hind-gut terminates blindly
in the tail. Near its caudal end it is dilated to form the cloaca. Into
the ventral side of the cloaca opens the stalk of the allantois. Dorso-
laterally the primary excretory (Wolffian) ducts which we saw developed
in the fifty-hour chick have connected with the cloaca and open into it.
Caudal to the cloaca, on the ventral side, is the cloacal membrane, which
later divides and breaks through to form the genital aperture and anus.
That part of the hind-gut between the cloaca and the yolk stalk forms
the rectum, colon, caecum, and appendix, together with a portion of the
small intestine (ileum).

Urogenital Organs. — The opening of the primary excretory (Wolffian)
ducts into the cloaca has been noted. These are the ducts of the mid-
kidney, or mesonephros. At this stage, the nephrotomes, which in the
chick embryos were seen to form the anlages of these ducts, are also form-
ing the kidney tubules of the mesonephros which open into the ducts
(Fig. 87). The mid-kidneys project into the peritoneal cavity as ridges
on each side. A thickening of the mesothelium along the median halves
of the mesonephroi forms the anlages of the genital glands, or gonads
(Fig. 220).

Circulatory System. — -The heart is an S-shaped double tube as in the
fifty -hour chick. The outer myocardium is confined to the heart while the
inner endothelial layer is continuous, at one end with the veins, at the
other end with the arteries. The disposition of the heart tube is well seen
in a ventral view of a younger embryo (Fig. 88). The veins enter the
sinus venosus just cranial to the yolk sac. Next in front is the atrium,
with the convexity of its flexure directed cephalad. The ventricular
portion of the heart is U-shaped and is flexed to the right of the embryo.
The left limb is the ventricle, the right the bulbus.

The arteries begin with the ventral aorta which bends back to the mid-
plane and divides into five branches on each side of the pharynx (Figs. 88 and
89) . These are the aortic arches and they unite dorsally to form two trunks,
the descending aortce. The aortic arches pass around the pharynx between
the pharyngeal pouches in the branchial arches. The arrangement is like
that of the adult fish which has gill slits, branchial arches, and aortic
arches to supply the gills. The descending aortae run caudal, and, opposite
the lung buds, unite to form a single, median dorsal aorta. This, in the
region of the posterior limb buds, divides into the two umbilical arteries,
which, curving cephalad and ventrad, enter the body stalk on each side of

86

HUMAN EMBRYOS AND FETAL MEMBRANES

c /?& d /~*x. /f*s\ e

FIG. 90. — Embryos of four to six weeks (2.1 to II mm.). From His' Normentafel (Keibel

and ElzeJ. X 5.

THE ANATOMY OF A 4.2 MM. HUMAN EMBRYO

FIG. 91. — Embryos of six to eight weeks (12.5 to 23 mm.). From His' Normentafel (Keibel and
Elze). X 2.5. Stage ^(22) marks the transition from embryo to fetus.

88 HUMAN EMBRYOS AND FETAL MEMBRANES

the allantois and eventually ramify in the villi of the chorion. The
vitelline arteries, large and paired in the chick, are represented by a single,
small trunk which branches on the surface of the yolk sac (Fig. 271).
Compared with the arterial circulation of the chick of fifty hours the
important differences are: (i) the development of the fourth and fifth
pairs of aortic arches, and (2) the presence of the chorionic circulation,
by way of the umbilical arteries, in addition to the vitelline circulation
found in the fifty-hour chick.

The veins are all paired and symmetrically arranged (Figs. 88 and 279).
There are three sets of them : (i) The blood from the body of the embryo
is drained, from the head end by the anterior cardinal veins, from the tail
end by the posterior cardinal veins. These veins on each side unite dorsal
to the heart and form a single common cardinal vein which receives the
vitelline and umbilical veins of the same side before joining the heart.
(2) Paired vitelline veins in the early stages of the embryo drain from the
yolk sac the blood carried to it by the vitelline arteries. The trunks of
these veins pass back into the body on each side of the yolk stalk and liver,
and, with the paired umbilical veins, form a trunk that empties into the sinus
venosus of the heart. As the liver develops, it may be seen that the vitel-
line veins break up into blood spaces, called sinusoids (Fig. 279). When
the liver becomes large and the yolk sac rudimentary, the vitelline veins
receive blood chiefly from the liver and intestine. (3) A pair of large
umbilical veins which drain the blood from the villi of the chorion and are
the first veins to appear. These unite in the body stalk, and, again sepa-
rating, enter the somatopleure on each side. They run cephalad to the
septum transversum where they unite with the vitelline veins to form a
common vitello-umbilical trunk which joins the common cardinal and emp-
ties into the sinus venosus.

The veins of this embryo are thus like those of the fifty-hour chick
save that the umbilical vessels are now present and take the place of the
allantoic veins of later chick embryos. The veins, like the heart and arteries,
are primitively paired and symmetrically arranged. As development
proceeds, their symmetry is largely lost and the asymmetrical venous
system of the adult results.

The later stages of the human embryo cannot be described in detail
here. The student is referred to the texts of Minot, and Keibel and Mall.
Figs. 90 and 91 show a series of human embryos described by His, the
ages of which lie between four and eight weeks. The figures show as
well as could any description the changes which lead toward the adult
form when the embryo may be called a fetus (stage a/). The external
metamorphosis is due principally: (i) to changes in the flexures of the

THE AGE OF HUMAN EMBRYOS 89

embryo; (2) to the development of the face; (3) to the development of
the external structure of the sense organs (nose, eye, and ear) ; (4) to the
development of the extremities and disappearance of the tail. The more
important of these changes will be dealt with in later chapters.

THE AGE OF HUMAN EMBRYOS

The ages of the human embryos which have been obtained and de-
scribed cannot be determined with certainty, because too little is known
of the time relations between ovulation, coitus, and fertilization. Further-
more, ovulation need not bear a definite relation to menstruation (p. n).
This lack of a reliable basis makes any computation only approximate.

In 1868, Reichert, from studying the corpus luteum in ovaries ob-
tained during menstruation, concluded that ovulation takes place as
a rule just before menstruation, and that if the ovum is fertilized the
approaching menstruation does not occur. Reichert then decided that a
human embryo of 5 . 5 mm. , which he had obtained from a woman two weeks
after menstruation failed to occur, must be two weeks, not six weeks, old.
His accepted Reichert's views and the ages of embryos were for a long time
estimated on this basis. According to this method, Peters' ovum, ob-
tained thirty days after the last period, is only three or four days old.
This, however, does not agree at all with the known ages of other mam-
malian embryos equally developed.

From numerous clinical observations we must conclude that ovula-
tion does not immediately precede menstruation, but that most pregnan-
cies follow a coitus within a week or ten days after the menses cease. //
is therefore more correct to compute the age of an embryo from the tenth day
after the onset of the last menstruation. To compare an embryo with one
of known age, the crown-rump length (that is, from vertex to breech) is
usually taken. Young embryos vary greatly in size so their structure must
be taken into account as well.

Of practical Interest is the determination of the date of delivery of a
pregnant woman. Most labors occur ten lunar months, or 280 days, from
the first day of the last menstrual period. The month and day of this
date are easily found by counting back three months from the first day of
the last period, and then adding six days. As some women menstruate
once or more after becoming pregnant this computation is not infallible.

HUMAN EMBRYO AND FETAL MEMBRANES

The following are the estimated ages and lengths of human embryos,
according to Mall, and their weights according to Jackson.

Crown-rump length Crown-heel length
(CR) , or sitting (CH) , or standing
height (mm.). height (mm.).

Twenty-one days

Twenty-eight days

Thirty-five days

Forty-two days

Forty-nine days

Second lunar month . . .

Third lunar month

Fourth lunar month . . .

Fifth lunar month

Sixth lunar month

Seventh lunar month . .
Eighth lunar month . . .
Ninth lunar month ....
Tenth lunar month . .

o-5

2-5

5- 5

II. O

17.0
25-0
68.0

121 .0

167 .o

2IO.O

245.0
284.0
3l6.0

345-Q

o-5

2-5

5-5

II. O

19.0

30.0

98.0

180.0

250.0

370.0
425.0
470.0
;oo.o

Weight

.04

3
36

120

330

635

I22O

1700

2240

3200

For comparison and reference the gestation periods of a few representative mammals
innended :

are appended:

Opossum 13 days

Mouse 20 days

Rat 21 days

Rabbit 30 days

Cat.... 8 weeks

Dog, guinea pig 9 weeks

Pig

17 weeks

Sheep ,-:..;.
Cow
Horse

21 weeks
41 weeks
48 weeks

Rhinoceros
Elephant

18 months
20 months

CHAPTER V

THE STUDY OF SIX AND TEN MILLIMETER PIG EMBRYOS
A. THE ANATOMY OF A SIX MM. PIG EMBRYO

VERY young pig embryos of the primitive streak and neural fold
stages have been seen already (Fig. 26). In its early stages the pig
embryo is flattened out on the surface of the yolk sac like a chick embryo
(Fig. 92), but as the head and tail folds elongate, the body becomes flexed
and twisted spirally, making it
difficult to study. In embryos
5 to 7 mm. long, the twist of
the body begins to disappear
and its structure may be seen
to better advantage. The an-
atomy of a 7.8 mm. pig embryo
has been studied by Thyng
(Anal. Record, vol. 5, 1911).

External Form of 6 mm.
Embryo. — When compared with
the form of the 4 mm. human
embryo, the marked difference
in a 6 mm. pig is the convex
dorsal flexure which brings the
head and tail regions close to-
gether (Fig. 93). The cephalic
flexure at the mesencephalon
forms an acute angle and there
is a marked neck, or cervical

FIG. 92. — Pig embryos, (A) of seven and (B)
of eleven primitive segments, in dorsal view with
amnion cut away (Keibel, Normentafel). X 20.

flexure. As a result, the head

is somewhat triangular in form.

The body is bent dorsad in an

even, convex curve and the tail

is flexed sharply dorsad. Lateral to the dorsal line may be

seen the segments, which become larger and more differentiated

from tail to head. At the tip of the head a shallow depression marks

the anlage of the olfactory pit. The lens vesicle of the eye is

open to the exterior. Caudal to the eyes, at the sides of the head, are

four branchial arches separated by three branchial grooves, The fourth

arch is partly concealed in a triangular depression, the cervical sinus.

THE STUDY OF SIX AND TEN MILLIMETER PIG EMBRYOS

formed by the more rapid growth of the first and second arches (cf . Fig. 97) .
The first, or mandibular arch, forks ventrally into two processes, a smaller
maxillary and a larger mandibular process, and the latter with its fellow
forms the mandible or lower jaw. The position of the mouth is indicated
by the cleft between these processes. The groove between the eye and
the mouth is the lacrimal groove.

The second, or hyoid arch is separated from the mandibular arch by
a hyomandibular cleft which persists as the external auditory meatus.
About the dorsal end of the cleft develops the external ear.

Cephalic flexure

Olfactory pit
Yolk sac

Maxillary process Mandibular process

Branchial arch 2

Branchial arch 8
Cervical sinus

Cut edge of amnion
Lower limb bud

FIG. 93. — Pig embryo of 6 mm., viewed from the left side.

X 12.

llrium of heart
Liver

Upper limb bud
Mesodermal segment
Mesonephros

The amnion has been removed.

The heart is large, and through the transparent body wall may be
seen the dorsal atrium and ventral ventricle. Caudal to the heart a
convexity indicates the position of the liver. Dorsal to the liver is the
bud of the upper limb, now larger than in the 4 mm. human embryo.
Extending caudal to the anlage of the upper extremity, a curved convexity
indicates the position of the left mesonephros. At its caudal end is the
bud of the lower limb. The amnion has been dissected away along the
line of its attachment, ventral to the mesonephros. There is as yet no
distinct umbilical cord and a portion of the body stalk is attached to the
embryo.

Due to a shorter term of development, a young pig embryo is some-
what precociously developed in comparison with a human embryo of the
same size (Fig. 94). In a human embryo 7 mm. long the head is larger,

THE ANATOMY OF A SIX MM. PIG EMBRYO

93

the tail shorter. The cervical flexure is more marked, the olfactory pits
larger and deeper. The liver is more prominent than in the 6 mm. pig,
the mesonephros and segments less so.

Spinal cord

Cervical segment 8

Future milk line

Thoracic segment 12

Lumbar segment 5

FIG. 94. — A human embryo 7 mm. long, viewed from the right side (Mall in Kollmann).
X 14. /, //, ///, Branchial arches i, 2, arfd 3; H, Ht, heart; L, liver; L', otic vesicle; R, ol-
factory placode; Tr, semilunar ganglion of trigeminal nerve.

DISSECTIONS OF THE VISCERA

To understand the sectional anatomy of an embryo, a study of dissec-
tions and reconstructions is essential. For methods of dissection see p.
139, Chapter VI. Before studying sections, the student should become
as well acquainted as possible with the anatomy of the embryo and
compare each section with the figures of reconstructions and dissections.

Nervous System. — Fig. 95 shows the central nervous system and
viscera exposed on the right side of a 5.5 mm. embryo. The ventro-lateral
wall of the head has been left intact, together with the lens cavity, ol-
factory pit, and portions of the maxillary and mandibular processes,
second and third branchial arches, and cervical sinus (cf. Fig. 93). The
brain is differentiated into the five regions: telencephalon, diencephalon,

94

THE STUDY OF SIX AND TEN MILLIMETER PIG EMBRYOS

mesencephalon, metencephalon, and myelencephalon. The spinal cord is
cylindrical and gradually tapers off to the tail. The anlages of the
cerebral and spinal ganglia and the main nerve trunks are shown. The
oculomotor nerve begins to appear from the ventral wall of the mesen-
cephalon. Ventro-lateral to the metencephalon and myelencephalon occur

Gang, super ius K. 9 Otocyst

Gang, acousticum n. 8
Gang, geniculi n. 7

Gang, semilunare n. 5

•Metencephalon

Gang, jugulare n. 10
Gang, nodosum n. 10

N. accessories

Gang. Froriep
Gang. ceru. I
N. hypoglossus
Cervical sinus

Small intestine

Mesencephalon
•N. oculomotorius

Diencephalon

ng. petrosum
cj

Lens opening
Olfactory pit
Telencephalon
Yolk sac
Allantois

Ventricle
AUantoic stalk

Hind-gut

FIG. 95. — Dissection of a 5.5 mm. pig embryo, showing the nervous system and viscera from the

right side. X 18.

in order: the semilunar ganglion and three branches of the trigeminal
nerve; the geniculate ganglion and nerve trunk of the n. facialis; the
ganglionic anlage of the n. acusticus and the otocyst. It will be observed
that the nerve trunks are arranged with reference to the branchial arches
and clefts. Caudal to the otocyst a continuous chain of cells extends
lateral to the neural tube into the tail region. Cellular enlargements
along this neural crest represent developing cerebral and spinal ganglia.
They are in order the superior, or root ganglion of the glossopharyngeal
nerve with its distal petrosal ganglion; the ganglion jugulare and distal

THE ANATOMY OF A SEX MM. PIG EMBRYO 95

ganglion nodosum of the vagus nerve; the ganglionic crest and the proximal
portion of the spinal accessory nerve; and the anlage oiFroriep's ganglion, an
enlargement on the neural crest just cranial to the first cervical ganglion.
Between the vagus and Froriep's ganglion may be seen the numerous root
fascicles of the hypoglossal nerve, which take their origin along the ventro-
lateral wall of the myelencephalon and unite to form a single trunk. The
posterior roots of the spinal ganglia are very short; their anterior, or
ventral roots are not shown.

The position of the heart with its ventricle, atrium, and sinus venosus
is shown. The liver is divided into a small dorsal and a large ventral
lobe. The fore-gut emerges from between the liver lobes and curves
ventrad to the yolk stalk and sac. The hind-gut is partly hidden by the
fore-gut; it makes a U-shaped bend from the yolk stalk to the caudal
region. The gut is attached to the dorsal body wall by a double layer
of splanchnic mesoderm which forms the mesentery. The long, slender
mesonephros lies ventral to the spinal cord and curves caudad from a point
opposite the eighth cervical ganglion to the tail region. The cranial
third of the mesonephros is widest and its size diminishes tailwards.
Between the yolk sac and the tail the allantois is seen, its stalk curving
around from the ventral side of the tail region.

Digestive Canal. — The arrangement of the viscera may be seen in
median sagittal and ventral dissections (Figs. 96 and 97), and also in the
reconstruction shown in Fig. 105. The mouth lies between the mandible,
the median frontonasal process of the head, and the maxillary processes
at the sides. The diverticulum of the hypophysis (Rathkes pouch},
flattened cephalo-caudad and expanded laterad, extends along the ventral
wall of the fore-brain (Fig. 105). Near its distal end, the wall of the brain
is thickened and later the posterior lobe of the hypophysis will develop
from the brain wall at this point.

The pharynx is flattened dorso-ventrally and is widest near the mouth.
Its lateral dimension narrows caudad, and opposite the third branchial
arch it makes an abrupt bend, a bend which corresponds to the cervical
flexure of the embryo's body (Figs. 104 and 105). In the roof of the
pharynx, just caudal to Rathke's pouch, is the somewhat cone-shaped
pouch known as SeesseVs pouch, which may be interpreted as the blind,
cephalic end of the fore-gut. The lateral and ventral walls of the pharynx
and oral cavity are shown in Fig. 98. Of the four arches the mandibular
is the largest and a groove partly separates the processes of the two sides.
Posterior to this groove and extending in the median plane to the hyoid
arch is a triangular elevation, the tuberculum impar\ it later vanishes,
apparently contributing nothing to the tongue. At an earlier stage the
median thyreoid anlage grows out from the mid-ventral wall of the pharynx

96

THE STUDY OF SIX AND TEN MILLIMETER PIG EMBRYOS

just caudal to the tuberculum impar. The ventral ends of the second
arches fuse in the mid-ventral plane and form a prominence, the copula.
This connects the tuberculum impar with a rounded tubercle derived
from the third and fourth pairs of arches, the anlage of the epiglottis. Its
cephalic portion forms the root of the tongue (Fig. 156). Caudal to the

Pharynx

Neuromere 4 Rathke's poucl

Anlage of
tongue

R. atrium

Esophagus

Interalrial

foramen

Lung bud

Hepatic
diverliculum

Cranial limb
of the intestine

L. genital fold

Isthmus

M esencephalon
Diencephalon

Bulbus cordis
Telencephalon
Ventricle

Septum trans-
versum

Liver
Yolk sac
Allantois
Tail gut
Cloaca

Metanephros

Spinal cord

Caudal limb of intestine
R. mesonephros Mesonephric duct

FIG. 96. — Median sagittal dissection of a pig embryo of 6 mm., showing viscera and neural

tube. X 1 8.

epiglottis are the arytenoid ridges, and a slit between them, the glottis,
leads into the trachea.

The branchial arches converge caudad and the pharynx narrows
rapidly before it is differentiated into the trachea and esophagus (Figs.
104 and 105). Laterally and ventrally between the arches are the four
paired outpocketings of the pharyngeal pouches. The pouches have each
a dorsal and ventral diverticulum. The dorsal diverticula are large and
wing-like (Fig. 104); they meet the ectoderm of the gill clefts and fuse

THE ANATOMY OF A SIX MM. PIG EMBRYO

97

with it to form the closing plates. Between the ventral diverticula of the
third pair of pouches lies the median thyreoid anlage. The fourth pouch
is smaller than the others. Its dorsal diverticulum just meets the ecto-
derm; its ventral portion is small, tubular in form, and is directed parallel
to the esophagus (Fig. 104).

The groove on the floor of the pharynx caudal to the epiglottis is
continuous with the tracheal groove. More caudally, opposite the atrium

Eye
Maxillary process

Mouth

Branchial arch j
Branchial arch 4

Upper limb bud

Hepatic diverticulum

Umbilical artery
Mesonephric duct

Fronto-nasal process

'Olfactory pit

Mandibular process
Branchial arch 2
Aortic bulb

Trachea
Lung bud

Stomach

Cephalic loop of intestine
Mesonephros
Mesonephric duct
Caudal loop of intestine

Lower limb bud

X 14-

-Rectum

Dorsal aorta and umbilical artery
FIG. 97. — Ventral dissection of a 6 mm. pig embryo. The head has been bent dorsally.

of the heart, the trachea has separated from the esophagus (Fig. 96). The
trachea at once bifurcates to form the primary bronchi and the anlages of
the lungs (Fig. 97). The lungs consist merely of the dilated ends of the
bronchi surrounded by a layer of splanchnic mesoderm. They bud out
laterally on each side of the esophagus near the cardiac end of the stomach,
and project into the pleural ccelom. The esophagus is short and widens
dorso-ventrally to form the stomach. The long axis of the stomach is
nearly straight, but its entodermal walls are flattened together and it has
revolved on its long axis so that its dorsal border lies to the left, its ventral
border to the right, as seen in transverse section (Fig. in).

THE STUDY OF SEX AND TEN MILLIMETER PIG EMBRYOS

Caudal to the pyloric end of the stomach, and to its right, is given off
from the duodenum the hepatic diverticulum. Its opening into the gut is
seen in the ventral dissection (Fig. 97). The hepatic diverticulum is a sac
of elongated oval form from which the liver and part of the pancreas take
origin, and which later gives rise to the gall bladder, cystic duct, and com-
mon bile duct. It is connected by several cords of cells with the trabeculae
of the liver.

The liver is divided incompletely into four lobes, a small dorsal and a
large ventral lobe on each side (Figs. 95 and 112). The lobation does not
show in a median sagittal section. The pancreas is represented by two
outgrowths. The ventral pancreas originates from the hepatic diverticu-
lum near its attachment to the duodenum (Fig. 96). It grows to the

Lateral lingual anlage
Tuberculum impar

Epiglottis
Arytenoid ridge

Branchial arch i
Branchial arch 2

Branchial arch 3
Branchial arch 4
Glottis

FIG. 98. — Dissection of the tongue and branchial arches of a 7 mm. pig embryo, seen in dorsal

view. X 15.

right of the duodenum and ventral to the portal vein. The dorsal pancreas
takes origin from the dorsal side of the duodenum caudal to the hepatic
diverticulum and grows dorsally into the substance of the gastric mes-
entery (Figs. 105 and 113). It is larger than the ventral pancreas, and its
posterior lobules grow to the right and dorsal to the portal vein, and in
later stages anastomose with the lobules of the ventral pancreas.

The intestine of both fore-gut and hind-gut has elongated and curves
ventrally into the short umbilical cord where the yolk stalk has narrowed
at its point of attachment to the gut (Fig. 96). As the intestinal tube
grows ventrad, the layers of splanchnic mesoderm which attach it to the
dorsal body wall grow at an equal rate and persist as the mesentery.

The cloaca, a dorso-ventrally expanded portion of the hind-gut, gives
off cephalad and ventrad the attantoic stalk. This is at first a narrow tube,
but soon expands into a vesicle of large size, a portion of which is seen in
Fig. 96. Dorso-laterad the cloaca receives the primary excretory (mesoneph-
ric) ducts. The hind-gut is continued into the tail as the tail gut, or
postanal gut, which dilates at its extremity as in the 7.8 mm. pig described

THE ANATOMY OF A SIX MM. PIG EMBRYO

99

R. atrium

by Thyng; it soon disappears. The mid-ventral wall of the cloaca is
fused to the adjacent ectoderm to form the cloacal membrane. In this
region later the anus arises.

Urogenital System. — This consists of the mesonephroi, the mesonephric
(Wolffiari) ducts, the anlages of the metanephroi, the cloaca, and the allan-
tois. The form of the mesonephroi is seen in Figs. 95 and 97. Each
consists of large, vascular glomeruli,
associated with coiled tubules lined
with cuboidal epithelium and opening
into the mesonephric duct (Figs. 114
and 208). The Wolffian ducts, begin- R venir-lcie ».
ning at the anterior end of the meso-
nephros, curve at first along its ventral,
then along its lateral surface. At its
caudal end each duct bends ventrad and
to the mid-plane where it opens into a
late'ral expansion of the cloaca (Fig. 96).
Before this junction takes place, an evagination into the mesenchyme
from the dorsal wall of each mesonephric duct gives rise to the anlages of
the metanephroi, or permanent kidneys. A slight thickening of the
mesothelium along the median and ventral surface of each mesonephros
forms a light-colored area, the genital fold (Fig. 96). This area is pointed
at either end and confined to the middle third of the kidney. It is the
anlage of the genital gland, from which either testis or ovary is developed.

-Bulbus cordis
R. atrium

Jj» —L. ventricle

FIG. 99. — Ventral and cranial surface
of ,the heart from a 6 mm. pig embryo.
X 14-

L. common

cardinal vein

L. vitelline vein

R. vitelline vein

Left ventricle

TJ—R. ventricle

FIG. 100. — Dorsal and caudal view of the heart from a 6 mm. pig embryo. X 21.

Blood Vascular System. — The heart lies in the pericardial cavity, as
seen in Fig. 96. The atrial region (Fig. 99), as in the 4.2 mm. human em-
bryo, has given rise to two lateral sacs, the right and left atria. The bulbo-
ventricular loop has become differentiated into right and left ventricles,
much thicker walled than the atria. The right ventricle is the smaller,
and from it the bulbus passes between the atria and is continued as the

THE STUDY OF SIX AND TEN MILLIMETER PIG EMBRYOS

the sinus venosus.

Bidbus cordis

R. venlric,
Intervenlricular
foramen

'or amen ovale
Wall of I. atrium

'Interatrial foramen
Endocardial cushions

Wall of I. ventricle

ventral aorta. Viewed from the caudal and dorsal aspect (Fig. 100),
the sinus venosus is seen dorsal to the atria. It opens into the right atrium
«and receives from the right and left sides the paired common cardinal veins.
These veins drain the blood from the body of the embryo. Caudally,
the sinus venosus receives the two vitelline veins. Of these, the left is
small in the liver and later disappears. The right vitelline vein, now the
common hepatic, carries most of the blood to the heart from the umbilical
veins, and from the liver sinusoids, gut, and yolk sac.

Transverse sections of the embryo through the four chambers of the
heart show the atria in communication with the ventricles through the
atrio-ventricular foramina, and the sinus venosus opening into the right
atrium (Fig. 109). This opening is guarded by the right and left valves of
Septa incompletely separate the two atria and the two •
ventricles. In Fig. 109 the
atrial septum (septum primum)
appears complete due to the
plane of the section. In Fig.
101, from a slightly smaller
embryo, it is seen that the
septum primum grows from the

FIG. ioi.-Dissection of a 5.5 mm. pig's heart dorsal atrial wal1 of the heart
from the left side, showing the septum primum and does not yet meet the en-
and the interatrial and oval foramina. X 14. docardial Cushions between the

atrio-ventricular canals. This

opening between the atria is known as the interatrial foramen. Before it
closes, another opening appears in the septum, dorsal in position. This
is the foramen ovale and persists during fetal life. In Fig. 101 these two
openings may be seen, as may also the dorsal and ventral endocardial
cushions which bound the atrio-ventricular foramina. The outer meso-
thelial layer of the ventricles has become much thicker than that of the
atria. It forms the epicardium and the myocardium, the sponge-like
meshes of which are now being developed.

The Arteries. — These begin with the ventral aorta, which takes origin
from the bulbus cordis. From the ventral aorta are given off pairs of
aortic arches. These run dorsad in the five branchial arches (Figs. 104 and
105) and join the paired descending aortas. The first and second pairs of
aortic arches are very small and take origin from the small common trunks
formed by the bifurcation of the ventral aorta just caudal to the median
thyreoid gland. The fourth aortic arch is the largest. From the appar-
ent fifth arch small pulmonary arteries are developing. There is evidence
that this pulmonary arch is really the sixth in the series, the fifth having
been suppressed in development (cf. Fig. 272 B}. Cranial to the first

THE ANATOMY OF A SIX MM. PIG EMBRYO

pair of aortic arches, the descending aortae are continued forward into
the maxillary processes as the internal carotids. Caudal to the aortic
arches, the descending aortae converge, unite opposite the cardiac end of the
stomach, and form the median dorsal aorta. From this vessel and from the
descending aortae paired, dorsal inter segmental arteries arise. From the
seventh pair of these arteries (the first pair to arise from the medial dorsal
aorta) there are developed a pair of lateral branches to the upper limb buds.

Spinal coid
Ant. cardinal vein

Cervical sinus
Pericardia! cavity

Atri.ilju :. lion of sinus venosus

Sinus venosus

Right vitelline vein

Liver
Large venous sinusoid of liver

Hepatic diverticulum (cut)
Yolk stalk

Portal veir

Cephalic limb

intestinal loop

Right umbilical vein

Vitelline artery

Caudal limb.

intestinal loop

Right umbilical arter

Dorsal aor>

Notochord
Ant. cardinal
•vein

Pharynx

Pericardial

cavity

Left common

cardinal vein

Left horn of sinus venosus

Left vitelline vein
Ductus venosus
Ant. limb bud
Inf. vena cava
Dorsal pancreas
Left vitelline vein
Common vitelline vein

Left umbilical vein

Sup. mesenteric vein
Left umbilical artery
Post, limb bud
Spinal cord

FIG. 102. — Reconstruction in ventral view of a 6 mm. pig embryo, to show the vitelline and
umbilical veins, the latter opened (original drawing by K. L. Vehe>. X 22. In the small
orientation figure (cf. Fig. 105) the various planes are indicated by broken lines — * *.

These vessels are the subclavian arteries. From the dorsal aorta there are
also given off ventro-lateral arteries to the- glomeruli of the mesonephros,
and median ventral arteries. Of the latter, the cceliac artery arises opposite
the origin of the hepatic diverticulum. The mtelline artery takes origin by
two or three trunks caudal to the dorsal pancreas. Of these trunks, the
posterior is the larger and persists as the superior mesenteric artery.
Thyng has figured three trunks of origin in the 7.8 mm. pig. These unite
and the single vitelline artery branches in the wall of the yolk sac.

Opposite the lower limb buds the dorsal aorta is divided for a short

THE STUDY OF SIX AND TEN MILLIMETER PIG EMBRYOS

distance. From each division there arises laterad three short trunks which
unite to form the single umbilical artery on each side. The middle vessel
is the largest and apparently becomes the common iliac artery. A pair of
short caudal arteries, much smaller in size, continue the descending aortae
into the tail region.

The Veins. — The vitelline veins, originally paired throughout, are now
represented distally by a single vessel, which, arising in the wall of the
yolk sac, enters the embryo and courses cephalad of the intestinal loop
(Fig. 102). Crossing to the left side of the intestine and ventral to it, it

Spinal cord

Anterior cardinal vein

Cervical sinus

Pericardial cavity

R. common cardinal vein

Post, cardinal vein

Esophagus

Large venous sinusoid of liver

Anterior limb bud

Inf. vena cave

Post, cardinal vein

Mesonephros (cut surface)

R. subcardinal vein

Venous sinusoid on dorsum oft
mesonephros

Notochord

Pharynx

Trachea

L. common

cardinal vein
Lung

Liver
Stomach (cut edge)

Omental bursa
Mesogastrium

'Mesonephros (cut surface)

Capillary anastomosis between

subcardinal veins
Vitelline artery in dorsal

mesentery
Capillary anastomosis bet-ween

subcardinal veins

Venous sinusoid on dorsum of
mesonephros

'Spinal cord

FIG. 103. — Reconstruction of the cardinal and subcardinal veins of a 6 mm. pig embryo,
showing the early development of the inferior vena cava (K. L. Vehe). X 22. In the small
orientation figure (cf. Fig. 105) the various planes are indicated by broken lines — * *.

is joined by the superior mesenteric vein which has developed in the mes-
entery of the intestinal loop. The trunk formed by the union of these two
vessels becomes the portal vein. It passes along the left side of the gut in
the mesentery. Opposite the origin of the dorsal pancreas it gives off a
small branch, a rudimentary continuation of the left vitelline vein, which
courses cephalad and in earlier stages connects with the sinusoids of the
liver. The portal vein then bends sharply to the right, dorsal to the duo-

THE ANATOMY OF A SIX MM. PIG EMBRYO

denum, and, in the course of the right vitelline vein, passing between the
dorsal and ventral pancreas to the right of the duodenum, it soon enters the
liver and connects with the liver sinusoids. The portal trunk is thus
formed by persisting portions of both vitelline veins, and receives a new
vessel, the superior mesenteric vein. The middle portions of the primitive

Int. car- Ant. car-
Metencephalon otid artery dinal vein
P.I

Thyreoid Ph. P. 2

Mesencephalon

Ventral aorta

Ophthalmic
vein

Myelencephalon
Ph. P. 3

Notochord

Descending aorta

Ph. P. 4

Pulmonary artery
Linguo-facial

Intersegmental
vein

Spinal cord

Mesonephros

Post, cardinal vein Mesonephric arteries

FIG. 104. — Reconstruction of 7.8 mm. pig embryo, showing veins and aortic arches from the left
side (after Thyng). X 15. Ph.P. 1, 2, 3, 4, Pharyngeal pouches.

vitelline veins are connected with the network of liver sinusoids. Their
proximal vitelline trunks drain the blood from the liver and open into the
sinus venosus of the heart. The right member of this pair is much the
larger (Fig. 100) and persists as the proximal portion of the inferior vena
cava. For the development of the portal vein see Chapter IX.

104

THE STUDY OF SIX AND TEN MILLIMETER PIG EMBRYOS

The umbilical veins, taking their origin in the walls of the chorion and
allantoic vesicle, lie caudal and lateral to the allantoic stalk and anasto-
mose (Figs. 102 and 105). Before the allantoic stalk enters the body,
the umbilical veins separate and run lateral to the umbilical arteries.
The left vein is much the larger. Both, after receiving branches from the

Aortic arch i Seessel's pouch
Aortic arch 2 \ ^Jg^>>^ ^- Isthmus
Pharynx
Thyreoid

Aortic arch

106

Notochord

Aortic arch 4
107

Aortic arch 6 and_
pulmonary artery

108
Esophagus

109
Trachea

no

R. lung
in

Caliac artery

114
Ventral pancreas

Dorsal pancreas
Gall bladder

L. umbilical vein

Vitelline artery

Int. carotid artery
106

Rathke's pouch
Optic recess

Telencephalon
Ventral aorta

Bulbus cordis

Interventricular foramen
- L. horn of sinus venosus

L. umbilical vein
Tail gut

Cloaca

Meianephric anlage
114
L. umbilical artery

'Anastomosis between
dorsal aorta

Allantoic stalk
L. dorsal aorta
Mesonephric duct

Cephalic limb of intestinal

Dor sal aorta ^ | Artery to mesonephros

Mesentery Caudal limb of intestinal loop

FIG. 105. — Reconstruction of a 6 mm. pig embryo in the median sagittal plane, viewed
from the right side. The numbered heavy lines indicate the levels of the transverse sections
shown in Figs. 106-1 17. The broken lines indicate the outline of the left mesonephros and the
course' of the left umbilical artery and vein. The latter may be traced from the umbilical cord
to the liver where it is sectioned longitudinally. (Original drawing and reconstruction by
K. L. Vehe). X 16.5.

posterior limb buds and from the body wall, pass cephalad in the somato-
pleure at each side (Fig. 72). Their course is first cephalad, then dorsad,
until they enter the liver. The left vein enters a wide channel, the ductus
venosus, which carries its blood through the liver, thence to the heart by
way of the right vitelline trunk. The right vein joins a large sinusoidal

TRANSVERSE SECTIONS OF A SIX MM. PIG EMBRYO 10$

continuation of the portal vein in the liver. This common trunk drains
into the ductus venosus.

The anterior cardinal veins (Figs. 103 and 104) are formed to drain
the plexus of veins on each side of the head. These vessels extend- caudad
and lie lateral to the ventral portion of the myelencephalon. Each^
anterior cardinal vein receives branches from the sides of the myelen-
cephalon, then curves ventrad, is joined by the linguo-facial vein from
the branchial arches and at once unites with the posterior cardinal of
the same side to form the common cardinal vein. This, as we have seen,
opens into the sinus venosus.

The posterior cardinal veins develop on each side in the mesonephric
ridge, dorso-lateral to the mesonephros (Figs. 103, 104 and 112). Run-
ning cephalad, they join the anterior cardinal veins. When the mesoneph-
roi become prominent, as at this stage, the middle third of each posterior
cardinal is broken up into sinusoids. Sinusoids extend from the posterior
cardinal vein ventrally around both the lateral and medial surfaces of the
mesonephros. The median sinusoids anastomose longitudinally and
form the subcardinal veins, right and left. The subcardinals lie along the
median surfaces 'of the mesonephroi, more ventrad than the posterior
cardinals with which they are connected at either end. There is a trans-
verse capillary anastomosis between them, cranial and caudal to the
permanent trunk of the vitelline artery (Fig. 103). The right subcardinal
is connected with the liver sinusoids through a small vein which develops
in the mesenchyme of the plica venae cavae (caval mesentery) located
to the right of the mesentery (Fig. 112). This vein now carries blood
direct to the heart from the right posterior cardinal and right subcardinal,
by way of the liver sinusoids and the right vitelline trunk (common
hepatic vein). Eventually the unpaired inferior vena cava forms in the
course of these four vessels. (For the development of the inferior vena
cava see Chapter IX.)

TRANSVERSE SECTIONS OF A Six MM. PIG EMBRYO

Having acquainted himself with the anatomy of the embryo from
the study of dissections and reconstructions, the student should examine
serial sections cut in the plane indicated by guide lines on Fig. 105.
Refer back to the external structure of the embryo (Fig. 93), to the lateral
dissection of the organs (Fig. 95), and having determined the exact plane
of each section, interpret the structures seen by comparing with Fig. 105.
The various structures may be recognized by referring to the figures of
sections in the text, and they should be traced section by section through
the series as carefully as time will allow. Remember that the sections
of pig embryos figured here are drawn from the cephalic surface, so that
the right side of the section is the left side of the embryo.

io6

THE STUDY OF SIX AND TEN MILLIMETER PIG EMBRYOS

Section through the Myelencephalon and Otocysts of a 6mm. Embryo (Fig. 106). —
As the head is bent nearly at right angles to the body, this section passes lengthwise
through the myelencephalon. The diencephalon is cut transversely. The cellular walls
of the myelencephalon show a series of six pairs of constrictions, the neuromeres. Lateral
to the fourth pair of neuromeres are the otocysts, which show a median outpocketing at the
point of entrance of the endolymph duct. The ganglia of the nn. trigeminus, facialis, acus-
ticus, and the superior ganglion of the glossopharyngeal nerve occur in order on each side.
Sections of the anterior cardinal vein and its branches show on the left side. Ventral to
the diencephalon are sections of the internal carotid arteries.

Passing along down the series into the pharynx region, observe the first, second, and
third pharyngeal pouches. Their dorsal diverticula come into contact with the ectoderm
of the branchial clefts and form the closing plates.

Fourth ventricle

Neur.

Gang.juglare n. i
Neur. 5
Otocyst
Neur.
Neur.
Neur. 2
Neur. i

Int. carotid artery
Diencephalon

Myelencephalon

ang. superius n. 9

Ant. cardinal vein.

'ang. acusticum n. 8
'Gang, geniculi n. 7

ng. semilunare n. 5
Ant. cardinal vein

'Ant. cardinal vein

FIG. 1 06. — Transverse section through the myelencephalon and otocysts of a 6 mm. pig embryo.
X 26.5. Neur. 1-6, neuromeres 1-6.

Section through the Branchial Arches and the Eyes (Fig. 107). — The section passes
lengthwise through the four branchial arches, the fourth sunken in the cervical sinus.
Dorsad is the spinal cord with the first pair of cervical ganglia. The pharynx is cut across
between the third and fourth branchial pouches. In its floor is a prominence, the anlage
of the epiglottis. Ventral to the pharynx the ventral aorta gives off two pairs of vessels.
The larger pair are the fourth aortic arches which curve dorsad around the pharynx to enter
the descending aorta. The smaller third aortic arches enter the third branchial arches on
each side. A few sections higher up in the series the ventral aorta bifurcates, and the
right and left trunks thus formed give off the first and second pair of aortic arches Cra-
nially, in the angle between their common trunks, lies the median thyreoid anlage. The
anterior cardinal veins are located lateral and dorsal to the descending aortae. The end of

TRANSVERSE SECTIONS OF A SIX MM. PIG EMBRYO

107

the head is cut through the diencephalon and the optic vesicles. On the left side of the figure
the lens vesicle may be seen still connected wi th the ectoderm. The optic vesicle now shows
a thick inner, and a thin outer layer; these form the nervous and pigment layers of the retina
~ respectively.

Section through the Tracheal Groove, Bulbus Cordis and Olfactory Pits (Fig. 108).—
The ventral portion of the figure shows a section through the tip of the head. The lelen-
cephalon is not prominent. The ectoderm is thickened and slightly invaginated ventro-
laterad to form the anlages of the olfactory pits. These deepen in later stages and become
the nasal cavities. In the dorsal portion of the section may be seen the cervical portion
of the spinal cord, the notochord just ventral to it, the descending aorta, and ventro-lateral

Spinal ganglion

Notocho,

Ant. cardinal vein

Pharyn

Pharyngeal pouch
Aortic arch
Pharyngeal pouch 2

Lens of eye
Diencephalor

Neural tube
Myotome

Descending aorta
Branchial arch 4
Branchial arch 3

Branchial arch 2
Mandible

Optic vesicle

FIG. 107. — Transverse section through the branchial arches and eyes of a 6 mm. pig embryo.
X 26.5. X, aortic arch 4.

to them the anterior cardinal veins. The nasopharynx now is small with a vertical groove
in its floor. This is the tracheal groove and more caudad it will become the cavity of the
trachea. The bulbus cardis lies in the large pericardial cavity. On either side the section
cuts through the cephalic portions of the atria. These will become larger as we go caudad
in the series.

Section through the Heart (Fig. 109). — Lateral to the descending aortae are the com-
mon cardinal veins. The right common cardinal opens into the sinus venosus which in
turn empties into the right atrium, its opening being guarded by the two valves of the sinus
venosus. The entrance of the left common cardinal into the sinus venosus is somewhat
more caudad in the series. The trachea has now separated from the esophagus and lies
ventral to it. Both trachea and esophagus are surrounded by a condensation of mesen-

I08 THE STUDY OF SIX AND TEN MILLIMETER PIG EMBRYOS

Myotome

Ant. cardinal vein

R. atrium

Somatopleure

Olfactory pL

Descending aorta
Pharynx

Pericardial cavity

Bulbus cordis

Telencephalon

FIG. 108. — Transverse section through the bulbus cordis and olfactory pits of a 6 mm. pig

embryo. X 26.5.

Spinal cord

Descending aorta
Esophagus

Sinus venosu.
Valve of sinus venos

R. atriu
Atrio-ventricular foramen

I nterventricular sept

R.

Somatopleur

L. common cardinal vein

Trachea
L. atrium
•Septum I
L. ventricle

I nterventricular foramen
Pericardial cavity

FIG. 109. — Transverse section through the four chambers of the heart of a 6 mm. pig embryo.

X 26.5.

TRANSVERSE SECTIONS OF A SIX MM. PIG EMBRYO

IO9

chyme. The myocardium of the ventricles has formed a spongy layer, much thicker than
that of the atrial wall. An incomplete inter-ventricular septum leaves the ventricles in
communication dorsad. The septum primum is complete in this section, but higher up in
the series there is an inter atrial j or amen (cf. Fig. 101). The foramen ovale is hardly
formed.

Section through the Lung Buds and Septum Transversum (Fig. no). — The section
passes through the bases of the upper limb buds. The tips of the ventricles, lying in the
pericardial cavity, still show in this section. Dorsally, the pericardial cavity has given
place to the pleuro-peritoneal cavity. Projecting ventrad into this cavity are the meso-
nephric (Wolffiari) folds in which the posterior cardinal veins partly lie. Into the floor of the
pleuro-peritoneal cavities bulge the dorsal lobes of the liver, embedded in mesenchyma.
This mesenchyma is continuous with that of the somatopleure, and forms a complete trans-
verse septum ventrally between the liver and heart. This is the septum transversum which

Spinal ganglion
Spinal nerv

Descending aor>

Pleuro-peritoneal cavity

R. lung
R. vitelline vein

Septum transversum
Pericardial cavit

R. ventricl

Spinal cord

Upper limb bud
Post, cardinal vein

Esophagus
Dorsal lobe of liver

lesser sac

L. vitelline vein

L. ventricle

FIG. no. — Tranverse section through the right lung bud and septum transversum of a 6 mm.

pig embryo. X 26.5.

takes part in forming the ligaments of the liver and is the anlage of a portion of the dia-
phragm. The two proximal trunks of the vitelline veins pass through the septum. Project-
ing laterally into the pleuro-peritoneal cavities are ridges of mesenchyma covered by
splanchnic mesoderm in which the lungs develop as lateral buds from the caudal end
of the trachea. The right lung bud is shown* in the figure. Between the esophagus and
the lung is a crescent-shaped cavity, the cranial end of the lesser peritoneal sac.

Section through the Stomach (Fig. in).— The section passes through the upper
limb buds and just caudal to the point at which the descending aortae unite to form the
median dorsal aorta. As the liver develops in early stages, it comes into relation with the
plica vena cavce along the dorsal body wall at the right side of the dorsal mesogastrium.
The space between the liver and plica to the right, and the stomach and its omenta to the
left, is a caudal continuation of the lesser peritoneal sac. The dorsal wall of the stomach

no

THE STUDY OF SIX AND TEN MILLIMETER PIG EMBRYOS

Spinal ganglion

Peritoneal cavil
Lesser sac

Common hepatic vein
(R. vitelline)

R. ventral lobe liver

R. ventricl

Post, cardinal vein
Upper limb bud

L. ventral lobe of liver

L. ventricle

FIG. in. — Transverse section through the stomach of a 6 mm. pig embryo. X 26.5.

Spinal cord

Notochord
Post, cardinal vein
Dorsal aorta

Inf. vena cava

Portal vein

R. umbilical vein

Hepatic diverticulum

Peritoneal cavity

M \otome

Post, cardinal vein
Upper limb bud

Dorsal mesogastrium
Dorsal Icbe of liver

L. vitelline vein
L. umbilical vein

FIG. 112. — Transverse section through the hepatic diverticulum of a 6 mm. pig embryo.

X 26.5.

TRANSVERSE SECTIONS OF A SIX MM. PIG EMBRYO III

is rotated to the left, its ventral wall to the right. The liver shows a pair of dorsal lobes and
contains large blood spaces and networks of sinusoids lined with endothelium. Ventral
to the liver, the tips of the ventricles are seen.

Section through the Hepatic Diverticulum (Fig. 112). — The upper limb buds are
prominent in this section. The mesonephric folds show the tubules and glomeruli of the
mesonephroi, and the posterior cardinal veins are connected with the mesonephric sinu-
soids. From the dorsal attachment of the liver there is continued down into this section
a ridge on the dorsal body wall just to the right (left in figure) of the mesentery. In this
ridge lies a small vein which connects cranially with the liver sinusoids, caudally with the
right subcardinal vein. As it later forms a portion of the inferior vena cava, the ridge in
which it lies is termed the plica vena cava, or caval mesentery. The right dorsal lobe of
the liver contains a large blood space into which the portal vein opens. The duodenum is
ventral to the position occupied by the stomach in the previous section. There is given
off from it ventrad and to the right the hepatic diverticulum. In the sections higher up,
small ducts from the liver trabeculae may be traced into connection with it. In the left
ventral lobe of the liver, a large blood space indicates the position of the left umbilical
vein on its way to the ductus venosus.

Myotome— J||{Hl||g|i Spinal cord

, A

L. post, cardinal vein

limb btld

'Dorsal pancreas

' vitelline veln

Duodemim
Distal end of hepatic diverticulum p'' L< umbilical vein

Ventral pancreas
FIG. 113.- — Transverse section through the dorsal pancreas of a 6 mm. pig embryo. X 26.5.

Section through the Dorsal Pancreas (Fig. 113). — At this level the upper limb buds
still show; the mesonephroi are larger and marked by their large glomeruli. The right
posterior cardinal vein is broken up into mesonephric sinusoids. The vein in the plica
venae cavae will, a few sections lower, connect with the right subcardinal vein. The an-
lage of ^ the dorsal pancreas is seen extending from the duodenum dorsad into the mesen-
chyme of the mesentery. It soon bifurcates into a dorsal and right lobe, of which the latter
is slightly lobulated. Ventro-lateral to the duodenum the anlage of the ventral pancreas
is seen cut across. It may be traced cephalad in the series to its origin from the hepatic
diverticulum. To the right of the ventral pancreas lies the portal vein (at this level a por-
tion of the right vitelline). To the left of the dorsal pancreas is seen the remains of the
left vitelline vein. The ventral lobes of the liver are just disappearing at this level. In the
mesenchyme that connects the liver with the ventral body wall lie on each side the umbili-

JPT

112 THE STUDY OF SIX AND TEN MILLIMETER PIG EMBRYOS

cal veins, the left being the larger. Between the veins is the extremity of the hepatic diver-
ticulum. The body wall is continued ventrad to form a short umbilical cord.

Section at the Level of Origin of the Vitelline and Umbilical Arteries (Fig. 114). —
As the posterior half of the embryo is curved in the form of a half circle, sections caudal
to the liver, like this one, pass through the lower end of the body at the level of the pos-
terior limb buds. Two sections of the embryo are thus seen in one, their ventral aspects

Spinal cord

Notochord
R. post, cardinal vein

Dorsal aorta
R. subcardinal vein

Mesentery

Cephalic limb of intestine
R. umbilical vein

Caudal limb of intestine

R. umbilical vein

Tail

Lower limb bud
Mesonephric duel

Dorsal aorta

Spinal co

•Spinal nerve

Post, cardinal vein

Mesonephros

L. subcardinal vein

L. vilelline vein

L. umbilical vein

L. umbilical vein
Rectum

Mesonephric tubule
Mesodermal segment

FIG. 114. — Transverse section of a 6 mm. pig embryo at the level of the origin of the vitelline
artery. The lower end of the section passes through the posterior limb buds. X 26.5.

facing each other and connected by the lateral body wall. In the dorsal part of the sec-
t?on the mesonephroi are prominent, with large posterior cardinal veins lying dorsal to them.
The trunk of the vitelline artery takes origin ventrally from the aorta. It may be traced
into the mesentery, and through it into the wall of the yolk sac. On either side of the
vitelline artery are the subcardinal veins, the right being the larger. In the mesentery may
be seen two sections of the intestinal loop (the small intestine, being cut lengthwise, the large
intestine transversely), and also sections of the vitelline artery and veins. In the lateral

TRANSVERSE SECTIONS OF A SIX MM. PIG EMBRYO

body walls, ventral to the mesonephros, occur the umbilical veins. The left vein is large
and cut lengthwise. The right vein is cut obliquely twice.

In the ventral portion of the section, the lower limb buds are prominent laterally. A
large pair of arteries, the common iliacs, are given off from the aorta and may be traced
into connection with the umbilical arteries. The large intestine, supported by a short
mesentery, lies in the ccelom near the midplane. On each side are the mesonephric folds,
here small and each showing a section of the mesonephric duct and a single vesicular anlage
of the mesonephric tubules. The mesonephric ducts are sectioned as they curve around
from their position in the dorsal portion of the section.

Section through the Primitive Segments and Spinal Cord (Fig. 115). — This section
is near the end of the series, and, as the body is here curved, it is really a frontal section.
At the left side of the spinal cord, the oval cellular masses are the spinal ganglia cut across.
The ectoderm, arching over the segments, indicates their
position. Each segment shows an outer dense layer, the
dermatome, lying just beneath the ectoderm. This plate
curves lateral to the spindle-shaped myotome, which gives
rise to the voluntary muscle. Next comes a diffuse mass
of mesenchyma, the sclerotome, which eventually, with its

Spinal ganglion
Intersegmental.
artery
Myotom

Dermatim

Sderol

Ectoderm
Spinal cord

FIG. 115. — Transverse sec-
tion through the primitive
segments and spinal cord of a
6 mm. pig embryo. X 45.

R. umbilical vein

R. umbilical artery.
Tail—

Mesonephric duct

Spinal cord

L. umbilical vein
Allantois and cloaca

L. umbilical artery
Ccelom

Notochord

FIG. 116. — Transverse section through the umbilical
vessels, allantois and cloaca of a 6 mm. pig embryo.
X 45-

fellow of the opposite side, surrounds the spinal cord and forms the anlage of a vertebra.
A pair of spinal nerves and spinal ganglia are developed opposite each somite, and pairs
of small vessels are seen between the segments. These are dorsal intersegmental arteries.
Section through the Umbilical Vessels, Allantois and Cloaca (Fig. 116). — Having
now studied sections at various levels to near the end of the series, we shall next examine
sections through the caudal region and study the anlages of the urogenital organs. Owing
to the curvature of the embryo, it is necessary to go cephalad in our series. The first
section passes through the bases of the limb buds at the level where the attantoic stalk,
curving inward from the umbilical cord, opens into the cloaca. At either side of the allan-
toic stalk may be seen oblique sections of the umbilical arteries, and lateral to these the
large left and small right umbilical vein. The mesonephric ducts occupy the mesonephric
ridges which project into small caudal prolongations of the ccelom. Midway between the

114

THE STUDY OF SIX AND TEN MILLIMETER PIG EMBRYOS

ducts lies the hind-gut, dorsal to the cloaca. The tip of the tail is seen in section at the
left of the figure.

Section through the Anlages of the Metanephroi, Cloaca and Hind-gut (Fig. 117).—-
The metanephroi are seen as dorsal evaginations from the mesonephric (Wolffian) ducts
just before their entrance into the cloaca. Each consists of an epithelial layer surrounded
by a condensation of mesenchyme. Traced a few sections cephalad the mesonephric ducts
open into the lateral diverticula of the cloaca, which, irregular in outline because it is sec-
tioned obliquely, lies ventral to them and receives dorsad the hind-gut. Caudal to the cloaca
in this embryo the tail bends abruptly cephalad and to the right. The blind prolongation
of the hind-gut may be traced out into this portion of the tail until it ends in a sac-like
dilatation.

R. umbilical vein
R. umbilical artery

Tail

Mesonephric duct
Metanephric anlage

Spinal cord

— — Ventral body wall

r J-i- / -
L. umbilical arterv

' T i.;- , • '

umbilical vein

Cloaca
Hind-gut

Notochord

FIG. 117. — Transverse section through the anlages of the metanephroi of a 6 mm. pig embryo.

X 45-

B. THE ANATOMY OF TEN TO TWELVE MM. PIG EMBRYOS

The study of embryos at this stage is important as they possess the
anlages of most of the organs. The anatomy of a 12 mm. pig embryo
has been ^care fully studied and described by Lewis (Amer. Jour. Anat.,
vol. 2, 1903).

External Form (Fig. 118). — The head is now relatively large on
account of the increased size of the brain. The third branchial arch is
still visible in the embryo, but the fourth arch has sunken in the cervical
sinus; usually both have disappeared at a slightly later stage. The
olfactory pits form elongated grooves on. the under surface of the head,
and the lens of the eye lies beneath the ectoderm, surrounded by the optic
cup. The maxillary and mandibular processes of the first branchial arch
are larger, and the former shows signs of fusing with the median nasal
process to form the upper jaw. Small tubercles, the anlages of the
external ear, have developed about the first branchial cleft which itself
becomes the external auditory meatus.

THE ANATOMY OF TEN TO TWELVE MM. PIG EMBRYOS

At the cervical bend the head is flexed at right angles with the body,
bringing the ventral surface of the head close to that of the trunk, and

Branchial groove 1
Hyoid arch

Cervical flexure
Branchial arch j

Cervical sinus

Upper limb

Milk line

Mesodermal segmen

Myelencephalon

^/Cephalic flexure

^Eye

Maxillary process
Mandibular process
Olfactory pit

Yolk sac

Umbilical cord

Lower limb b
FIG. 118. — Exterior of a 10 mm. pig embryo, viewed from the right side. X 7.

it is probably owing to this flexure that the third and fourth branchial
arches buckle inward to form the cervical sinus. Dorsad, the trunk forms

Cervical flexur

Maxillary process
Attachment of amnion

External ear
Mandibular

Upper limb bud
Mesodermal segment

Lower limb bud

FIG. 119. — Exterior of a human embryo of 12 mm. viewed from the right side, showing attach-
ment of amnion (cut away) and yolk stalk and sac. X 4.

a long curve more marked opposite the posterior extremities. The
reduction in the trunk flexures is due to the increased size of the heart,
liver, and mesonephroi. These organs may be seen through the translu-

n6

THE STUDY OF SIX AND TEN MILLIMETER PIG EMBRYOS

cent body wall, and the position of the septum transversum may be noted
between the heart and the liver, as in Fig. 120. The limb buds are larger
and the umbilical cord is prominent ventrad. Dorsally, the mesodermal
segments may be seen, and, extending in a curve between the bases of the
limb buds, is the milk line, a thickened ridge of ectoderm which forms the

N. ocidomotorius

Metencephalon N. trochlearis
Gang. n. 5 \ I Mesencephalon
Gang. nn. 7 and 8 \

N. facialis
Gang, si perius n. 9
^' Gang, jugular e n. 10
Ga.ig. petrosum n. 9

Gang. Froriep
Gang.nodosum n. 10

N. accessorius

iencephalon

phthalmic r. n. 5

•N. opticus

Maxillary r. n. 5
Telencephalon

Mandibular r. n. 5
Chorda tympani n, 7

Ventricle

Mesonephros

Gang, thorac. 10

Umbilical cord

Genital eminence

FIG. 1 20. — Lateral dissection of a 10 mm. pig embryo, showing the viscera and nervous
system from the right side. ,The eye* has been removed and the otic vesicle is represented by a
broken line. The ventral roots of the spinal nerves are not indicated. X 10.5. n., Xerve;
r., ramus.

anlages of the mammary glands. The tail is long and tapering. Between
its base and the umbilical cord is the genital eminence (Fig. 120).

Human embryos of this stage or slightly older vary considerably in
size (Fig. 119). They differ from pig embryos in the greater size of the
head, the shorter tail, the much smaller mesonephric region, the longer
umbilical cord, and the less prominent segments. The yolk sac is pear-
shaped and the yolk stalk is long and slender.

THE ANATOMY OF TEN TO TWELVE MM. PIG EMBRYOS

Central Nervous System. — Dissections show well the form and rela-
tions of the organs (Figs. 120, 121 and 122). Directions for preparing dis-
sections are given in Chapter VI.

The Brain. — Five distinct regions may be distinguished (Figs. 120
and 122): (i) The telencephalon with its rounded lateral outgrowths, the
cerebral hemispheres. Their cavities, the lateral ventricles, communicate
by the interventricular foramina with the third ventricle. (2) The dien-
cephalon shows a laterally flattened cavity, the third ventricle. Ventro-
laterally from the diencephalon pass off the optic stalks, and an evagina-
tion of the mid-ventral wall is the anlage of the posterior hypophyseal

Accessory gang, i
Accessory gang. 2

Ace. gang. 3

Myelencephalon

Ace. gang 4

Gang, nodosnm

N. 12

FIG. 121. — Dissection of the head of a 15 mm. pig embryo from the right side, to show the
accessory vagus ganglia with peripheral roots passing to the hypoglossal nerve. X 25.

lobe. -(3) The mesencephalon is undivided, but its cavity becomes the
cerebral aqueduct leading caudally into the fourth ventricle. (4) The
metencephalon is separated from the mesencephalon by a constriction, the
isthmus. Dorso-laterally it becomes the cerebellum, ventrally the pons.
(5) The elongated myelencephalon is roofed over by a thin, non-nervous
ependymal layer. Its ventro-lateral wall is thickened and still gives
internal indication of the neuromeres. The cavity of the metencephalon
and myelencephalon is the fourth ventricle.

The Cerebral Nerves. — Of the twelve cerebral nerves, all but the first
(olfactory) and sixth (abducens) are represented in Fig. 120. For a de-
tailed description of these nerves see Chapter XIII. (2) The optic

Il8 THE STUDY OF SIX AND TEN MILLIMETER PIG EMBRYOS

I

nerve is represented by the optic stalk cut through in Fig. 120. (3) The
oculomotor, a motor nerve to four of the eye muscles, takes origin from the
ventro-lateral wall of the mesencephalon. (4) The trochlear nerve fibers,
motor, to the superior oblique muscle of the eye, arise from the ventral
wall of the mesencephalon, turn dorsad and cross at the isthmus, thus
emerging on the opposite side. From the myelencephalon arise in order:
(5) the n. trigeminus, mixed, with its semilunar ganglion and three branches,
the ophthalmic, maxillary, and mandibular; (6) the n. abducens, motor,
from the ventral wall to the external rectus muscle of the eye; (7) the n.
facialis, mixed, with its geniculate ganglion and its chorda tympani, facial,
and superficial petrosal branches in the order named; (8) the n. acusticus,
sensory, arising cranial to the otocyst, with its acoustic ganglion and sensory
fibers to the internal ear; (9) caudal to the otocyst the n. glossopharyngeus,
mixed, with its superior and petrosal ganglia; (10) the n. vagus, sensory,
with its jugular and nodose ganglia; (n) the n. accessorius, whose motor
fibers take origin from the lateral wall of the spinal cord and myelencepha-
lon between the jugular and sixth cervical ganglia; the internal branch of
the n. accessorius accompanies the vagus; the external branch leaves it
between the jugular and nodose ganglia and supplies the sternocleidomas-
toid and trapezius muscles; (12) the n. hypoglossus, motor, arising by five
or six fascicles from the ventral wall of the myelencephalon; its trunk
passes lateral to the nodose ganglion and supplies the muscles of the
tongue.

A nodular chain of ganglion cells extends caudad from the jugular ganglion of the
vagus. These' have been interpreted as accessory vagus ganglia. They may, however,
be continuous with Froriep's ganglion which sends sensory fibers to the n. hypoglossus.
In pig embryos of 15 to 16 mm. this chain is frequently divided into four or five gan-
glionic masses, of which occasionally two or three (including Froriep's ganglion (may
send fibers to the root fascicles of the hypoglossal nerve. Such a condition is shown
in Fig. 121.

The Spinal Nerves. — Each of these has its own spinal ganglion, from
which the dorsal root fibers are developed (Figs. 120 and 136). The
motor fibers take origin from the ventral cells of the neural tube and form
the ventral roots which join the dorsal roots in the nerve trunk.

Besides the nervous system, Fig. 120 also shows the heart, with its
right atrium and ventricle, the dorsal and ventral lobes of the liver, and the
prominent mesonephros. Dorsal and somewhat caudal to the atrium is
the anlage of the right lung. The septum transversum extends between the
heart and the liver.

Pharynx and its Derivatives. — Dorsally, the anterior lobe of the
hypophysis is long and forks at its end (Figs. 122 and 123). In the floor

THE ANATOMY OF TEN TO TWELVE MM. PIG EMBRYOS

119

of the pharynx are the anlages of the tongue and epiglottis (Fig. 156 A).
From each mandibular arch arises an elongated thickening that extends
caudal to the second arch. Between, and fused to these thickenings, is
the triangular tuberculum impar. The opening of the thyreoglossal duct
between the tuberculum impar and the second arch is early obliterated.
A median ridge, or copula, between the second arches connects the tuber-

Metencephalon
Tela chonoidea

Mesencephalon

Neuromeres of myelencephalon

Nolochord
Tongue

Spinal

Esophagus
Trachea
Atrium

Dorsal Pancr

Diencephalon

Post, lobe of hypophysis

Optic recess

Telencephalon
Ant. lobe of hypophysis

Bulbus corals
Ventricle
Yolk sac

Septum transversum
Yolk stalk
Liver

Hepatic diverticulum
Duodenum

L. genital fold

L. mesonephros

Dorsal aorta

Colon

" Caecum

Small intestine
"Attantois
Vrogenital sinus

'Ureter

Mesonephric duct
Umbilical artery (cut away)

Metanephros Rectum

FIG. 122. — Median sagittal dissection of a 10 mm. pig embryo, showing the brain, spinal cord
and viscera from the right side. X 10.5.

culum impar with the epiglottis, which seems to develop from the bases of
the third and fourth branchial arches. On either side of the slit-like
glottis are the arytenoid folds of the larynx. (For the development of the
tongue, see p. 149.) The pharyngeal pouches are now larger than in the
6 mm. pig (Fig. 123). The first pouch persists as the auditory tube and
middle ear cavity, the 'closing plate' between it and the first branchial clef t

THE STUDY OF SIX AND TEN MILLIMETER PIG EMBRYOS

forming the tympanic membrane. The second pouch later largely dis-
appears; about it, develops the palatine tonsil. The third pouch is tubular,
directed at right angles to the pharynx, and meets the ectoderm to form a
closing plate. Median to the plate, the ventral diverticulum of the third
pouch is the anlage of the thymus gland. Its dorsal diverticulum forms
an epithelial body, or parathyreoid. The fourth pouch is smaller and its

Gang. nn. 7 and 8 Gang. n. 5

Otocyst

Pharyngeal pouch 2
Gang, jugular e n. 10

Aortic arch

Pharyngeal pouch 3

Caudal root n.
hypoglossus
Gang. Froriei

Aortic arch 4
Gang. cerv. i

Pharyngeal pouch 4

Aortic arch 6

R. descending aorta

Esophagus

Trachea

Vertebral artery
Subclavian artery
R. lung

R. atrium

Stomach

Post, lobe of hypophysis

Ant. lobe of hypophysis

Eye

Pharyngeal pouch i
Maxillary process
Thyreoid gland
Pulmonary artery

Aorta

Yolk sar

R. ventricle

Septum
transversum

Liver

Hepatic
diverticulum
Cloaca
Allantois
Rectum

Ureter

Dorsal pancreas

Vitelline artery

Ventral pancreas

Descending aorta,

Mesonephric duct
Notochord Cephalic limb intest. loop

Metanephros
Umbilical artery

FIG. 123. — Reconstruction of a 10 mm. pig, to show the position of the various organs from
the right side. The veins are not indicated. Broken lines indicate the outline of the left
mesonephros and the positions of the limb buds. X 10.

dorsal diverticulum gives rise to a second parathyreoid body. Its ventral
diverticulum is a rudimentary thymus anlage. A tubular outgrowth,
caudal to the fourth pouch, is regarded as a fifth pharyngeal pouch in
human embryos and forms the ultimobranchial body on each side (see p.
165). The thyreoid gland, composed of branched cellular cords, is located
in the midplane between the second and third branchial arches (Fig. 123).

THE ANATOMY OF TEN TO TWELVE MM. PIG EMBRYOS

121

Trachea and Lungs.— Caudal to the fourth pharyngeal pouches, the
esophagus and trachea separate and form entodermal tubes (Figs. 122
and 123). Cephalad of the point where the trachea bifurcates to form
the primary bronchi there appears on its right side the tracheal bud of the
upper lobe of the right lung (Fig. 124). This bronchial bud is developed
only on the right side and appears in embryos of 8 to 9 mm. Two second-
ary bronchial buds arise from the primary bronchus of each lung, and
form the'anlages of the symmetrical lobes of each lung.

Lateral nasal process
Lacrimal groove

Maxillary process
Mandibnlar process

Cervical sinus
Trachea

Tracheal lung bud

Upper limb bud

Septum transversum

Hepatic diverticulum
Yolk sac
Y oik stalk ^^

Allantois
R. umbilical artery

Lou'er limb bud

Mesonephric duct

.^ Olfactory pit

Eye

Median nasal process

Branchial arch 2
Branchial arch j
Branchial arch 4

L. lung

Esophagus

Stomach

Mesonephric duct
Ventral pancreas
Mesonephros
Cephalic limb of intestine

'audal limb of intestine
Rectum
Metanephros

Spinal cord
Rectum
FIG. 124. — Ventral dissection of a 9 mm. pig embryo. The head is bent dorsad. X 9-

Esophagus and Stomach. — The esophagus extends as a narrow tube
caudal to the lungs, where it dilates into the stomach. The stomach is
wide from its greater to its lesser curvature and shows a cardiac diver-
ticulum (Lewis). The pyloric end of the stomach has rotated more to the
right, where it opens into the duodenum, from which division of the intes-
tine the liver and pancreas develop.

The liver t with its four lobes, fills in the space between the heart,
stomach, and duodenum (Fig. 122). Extending from the right side of the
duodenum along the dorsal and caudal surface of the liver is the hepatic

122 THE STUDY OF SIX AND TEN MILLIMETER PIG EMBRYOS

diverticulum. It lies to the right of the midplane and its extremity is
saccular. This saccular portion becomes the gall bladder. Several ducts
connect the diverticulum with the liver cords. One of these persists as
the hepatic duct which joins the cystic duct of the gall bladder. The
portion of the diverticulum proximal to this union becomes the common
bile duct, or ductus choledochus. The ventral pancreas arises from the
common bile duct near its point of origin (Fig. 123). It is directed dorsad
and caudad to the right of the duodenum. The dorsal pancreas arises
more caudally from the dorsal wall of the duodenum and its larger, lobu-
lated body grows dorsally and cranially (Figs. 123, 127 and 140). Be-
tween the pancreatic anlages courses the portal vein. In the pig, the
duct of the dorsal pancreas persists as the functional duct.

Intestine. — Caudal to the duodenum, the intestinal loop extends
well into the umbilical cord (Figs. 122 and 123). At the bend of the
intestinal loop is the slender yolk stalk. The cephalic limb of the intestine
lies to the right, owing to the rotation of the loop. The small intestine
extends as far as a slight enlargement of the caudal limb of the loop, the
anlage of the cvcum, or blind gut. This anlage marks the beginning of
the large intestine (colon and rectum). The intestinal loop is supported
by the mesentery which is cut away in Fig. 122. The cloaca is now nearly
separated into the rectum and urogenital sinus. The cavity of the rectum
is almost occluded by epithelial cells (Lewis).

Urogenital System. — The mesonephros is much larger and more
highly differentiated than in the 6 mm, embryo (Figs. 120 and 124).
Along the middle of its ventro-median surface the genital fold is now more
prominent (Fig. 122). In a ventral dissection (Fig. 124) the course of the
mesonephric ducts may be traced. They open into the urogenital sinus,
which also receives the allantoic stalk (Fig. 122).

The metanephros, or permanent kidney anlage, lies just mesial to the
umbilical arteries where they leave the aorta (Fig. 123). Its epithelial
portion, derived from the mesonephric duct, is differentiated into a
proximal, slender duct, the ureter, and into a distal, dilated pelvis. From
this grow out later the calyces and collecting tubules of the kidney. Sur-
rounding the pelvis is a layer of condensed mesenchyma, or nephrogenic
tissue, which is the anlage of '"'he remainder of the kidney.

Blood Vascular System. — The Heart. — In Fig. 125 the cardiac cham-
bers of the right side are opened. The septum primum between the atria
is perforated dorsad and cephalad by the foramen ovale. The inferior
vena cava is seen opening into the sinus venosus, which in turn communicates
with the right atrium through a sagittal slit guarded by the right and left
valves of the sinus venosus. The right valve is the higher and its dorsal
half is cut away. The valves were united cephalad as the septum spurium.

THE ANATOMY OF TEN TO TWELVE MM. PIG EMBRYOS 123

Between the left valve and the septum primum, the sickle-like fold of the
septum secundum is forming; the fusion of these three components gives
rise later to the adult atrial septum. The aortic bulb is divided distally
into the aorta and the pulmonary artery, the latter connecting with the
sixth (apparent fifth) pair of aortic arches. Proximally the bulb is
undivided. The interventricular septum is complete except for the inter-
ventricular foramen which leads from the left ventricle into the aortic
side of the bulb. Of the bulbar swellings which divide the bulb into
aorta and pulmonary trunk, the left joins the interventricular septum,
while the right extends to the endocardial cushion. These folds eventually
fuse and the partition of the ventricular portion of the heart is completed.

Sept. II R. atrium

\ / Sept. I
Left valve of sinus venosus. iffifc ^Foramen male

Right valve of sinus venosus^ )&Sg^j% /^\^ Aorta
Inferior vena cava .,

Simis venosus
Tricuspid valve

ulmonary artery
Interventricular foramen

R. ventricle

FIG. 125. — Heart of 12 mm. embryo, dissected from the right side.

The endocardium at the atrio-ventricular foramina is already undermined
to form the anlages of the tricuspid and bicuspid valves. From the caudal
wall of the left atrium there is given off a single pulmonary vein.

The Arteries. — As seen in Fig. 123, the first two aortic arches have
disappeared. Cranial to the third arch, the ventral aortae become the
external carotids. The third aortic arches and the cephalic portions of the
descending aortas constitute the internal carotid arteries. The ventral
aortae between the third and fourth aortic arches persist as the common
carotid arteries. The descending aortae in the same region are slender
and eventually atrophy. The fourth aortic arch is largest, and on the
left side will form the aortic arch of the adult. From the right fourth arch
caudad, the right descending aorta is smaller than the left. Opposite
the eighth segment, the two aortae unite and continue caudally as the
median dorsal aorta. The sixth aortic arches (cf. p. 100) are connected
with the pulmonary trunk, and from them arise small pulmonary arteries
to the lungs. Dorsal inter segmental arteries arise, six pairs from the de-

124 THE STUDY OF SIX AND TEN MILLIMETER PIG EMBRYOS

scending aortse, others from the dorsal aorta. From the seventh pair,
which arise just where the descending aortas fuse, the subclavian arteries
pass off to the upper limb buds and the vertebral arteries to the head. The
latter are formed by a longitudinal anastomosis between the first seven
pairs of intersegmental arteries on each side, after which the stems of the
first six pairs atrophy.

FIG. 126 A. — Reconstruction of a 12 mm. pig embryo, to show the veins and heart from the
left side. For names of parts see Fig. 126 B on opposite page (F. T. Lewis). X 9.

Ventro-lateral arteries from the dorsal aorta supply the mesonephros
and genital ridge (Fig. 123). Ventral arteries form the coeliac artery to
the stomach region, the vitelline, or superior mesenteric artery, to the
small intestine, and the inferior mesenteric artery to the large intestine.

The umbilical arteries now arise laterally from secondary trunks
which persist as the common iliac arteries.

THE ANATOMY OF TEN TO TWELVE MM. PIG EMBRYOS

125

The Veins. — The cardinal veins have been reconstructed by Lewis in
a 12 mm. pig (Fig. 126). The veins of the head drain into the anterior
cardinal vein, which becomes the internal jugular vein of the adult. After
receiving the external jugular veins and the subdavian veins from the upper

•1.2

•1.3

W.b.

FIG. "1 26 B. — Reconstruction of a 12 mm. pig embryo, to show the veins from the left side
(Lewis). X 9- A. .Umbilical artery; Ao., aorta; Au., right auricle (atrium); card.', card.",
superior and inferior sections of posterior cardinal vein; d, left common cardinal vein; D.C.,
right common cardinal vein; D.V., ductus venosus; Jug.', Jug.", jugular -or ant. cardinal vein;
L., liver; L.s., anlage of lateral sinus; mx., transverse vein; P., pulmonary artery; Sc., subcardinal
vein; Scl., subclavian vein; sis., anlage of sup. longitudinal sinus; Um.d., right umbilical vein;
Ven., right ventricle; V.H.C., common hepatic vein; V.op., ophthalmic vein; V.P., portal vein;
-X", anastomosis between the right and left subcardinal veins.

limb buds the anterior cardinals open into the common cardinal veins
(ducts of Cuvier).

The posterior cardinal veins arise in the caudal region, course dorsal
to the mesonephroi, and drain the mesonephric sinusoids. The sub-

126

THE STUDY OF SIX AND TEN MILLIMETER PIG EMBRYOS

cardinal veins anastomose just caudal to the origin of the superior mesen-
teric artery, and the posterior cardinals are interrupted at this level. The
proximal portions of the posterior cardinals open into the common cardinal
veins as in the 6 mm. embryo. Of the two subcardinal veins, the right
has become very large through its connection with the right posterior
cardinal vein and the common hepatic vein, and now forms the middle
portion of the inferior vena cava. For the 'development of this vein, see
Chapter IX.

Notochord
Pharynx

R. ant. cardinal vein
Pericardial cavity
Sinus venosus

Inf. vena cava

Spinal cord

Ant. cardinal win
Esophagus

Trachea

Portal vein

Ventral pancreas

Cacum

L. vitelline vein
Small intestine

Sup. mesenteric vein
R. umbilical vein
R. umbilical arter

Upper limb

Common car-
dinal vein

Ductus venosus

Liver

Pyloric stomach
Hepatic diverticulum
Dorsal pancreas
Duodenum
L. umbilical vein

Allantois

FIG. 127. — Reconstruction of a 10 mm. pig embryo, to show the umbilical and vitelline
veins from the ventral side, x, indicates sinusoidal connection between left umbilical vein and
portal vein. X 15. In the small orientation figure (cf. Fig. 123) the various planes are indi-
cated by broken lines — * *.

The umbilical veins (Figs. 126 and 127) anastomose in the umbilical
cord, separate on entering the embryo, and course cephalad in the ventro-
lateral body wall of each side to the ventral lobe of the liver. The left
vein is much the larger, and, after entering the liver, its course is to the
right and dorsad. After connecting with the portal vein, it continues
as the ductus venosus and joins the proximal end of the inferior vena cava.
The smaller, right umbilical vein after entering the liver breaks up into
sinusoids. It soon atrophies, while the left vein persists until after birth.

The Vitelline Veins. — Of these, a distal portion of the left and a
proximal portion of the right are persistent. The left vitelline vein,

TRANSVERSE SECTIONS OF A TEN MM. PIG EMBRYO

127

fused' with the right, courses from the yolk sac cephalad of the intestinal
loop. Near a dorsal anastomosis between the right and left vitelline veins,
just caudal to the duct of the dorsal pancreas, the left receives the superior
mesenteric vein, a new vessel arising in the mesentery of the intestinal loop.
Cranial to its junction with the superior mesenteric vein, the left vitelline,
with the dorsal anastomosis and the proximal portion of the right vitelline
vein, forms the portal vein, which gives off branches to the hepatic sinu-
soids and connects with the left umbilical vein. For the development of
the portal vein, see Chapter IX.

TRANSVERSE SECTIONS OF A TEN MM. PIG EMBRYO

Figures are shown of sections passing through the more important
regions; these should be used for the identification of the organs. The
level and plane of each section is indicated by guide lines on Fig. 128.
The student should compare this'with Figs. 118 and 123, and orient each

Myelencephalon
Gang. sup. n. 9
Gang, and n. access.

Pulmonary artery

Metencephalon

•Mesencephalon

Diencephahn

FIG. 128. — Reconstruction of a 10 mm. pig embryo, showing the chief organs of the left
side. The numbered lines indicate the levels of transverse sections shown in the corresponding
figures (129-143). For the names of the various structures not lettered see Fig. 123. X 8.

section with reference to the embryo as a whole. To avoid repetition,
most of the levels illustrated in the transverse sections of the 6 mm. pig
are not represented in the 10 mm. series. For this reason, the former series
will be found very instructive in supplementing the following descriptions.

128

THE STUDY OF SIX AND TEN MILLIMETER PIG EMBRYOS

Transverse Section through the Eyes and Otocysts (Fig. 129).— The brain is sec-
tioned twice, lengthwise through the myelencephalon, transversely through the fore-brain.
The brain wall shows differentiation into three layers: (i) an inner ependymal layer,
densely cellular; (2) a middle mantle layer of nerve cells and fibers; (3) an outer marginal
layer, chiefly fibrous. These same three layers are developed in the spinal cord. A thin,
vascular layer differentiated from the mesenchyma surrounds the brain wall and is the
anlage of the pia mater. The myelencephalon shows three neuromeres in this section.
The telencephalon is represented by the paired cerebral hemispheres, their cavities, the

Fourth ventricle

Gang, jugulare n. 10

Gang, acusticum n.

Mandibular ramus n. 5
Maxillary ramus n. 5

Ant. lobe of hypophysis
Lens vesicle
Third ventricle of diencephalon

Lot. ventricle of telencephal

Wall of myelencephalon

N. accessorius

N. glossopharyngeus

ng. geniculi. n. 7
abducens
Basilar artery

inus cavernosus
Int. carotid artery

ptic vesicle
Foramen interventriculare'

FIG. 129. — Transverse section through the eyes and otocysts of a 10 mm. pig embryo. X 22.5.

lateral ventricles, connecting through the interventricular foramina with the third -ventricle
of the diencephalon. Close to the ventral wall of the diencephalon is a section of the ante-
rior lobe of the hypophysis (Rathke's pouch) near which are the internal carotid and basilar
arteries. Lateral to the diencephalon is the optic cup and lens vesicle of the eye, which are
sectioned caudal to the optic stalk. The outer layer of the optic cup forms the thin pig-
ment layer; the inner, thicker layer is the nervous layer of the retina. The lens is now a
closed vesicle distinct from the overlying corneal ectoderm.

The large vascular spaces are the cavernous sinuses, which drain by way of the vv.
capitis laterales into the internal jugular veins. Transverse sections may be seen of the
maxillary and mandibular branches of the n. trigeminus; the n. abducens is sectioned longi-
tudinally. The small nn. oculomotorius and Irochlcaris should be identified in sections

TRANSVERSE SECTIONS OF A TEN MM. PIG EMBRYO

129

more cephalad in the series. Ventral to the otocyst are seen the geniculate and acoustic
ganglia of the nn. facialis and acusticus. The wall of the otocyst forms a sharply denned
epithelial layer. More cephalad in the series the endolymph duct lies median to the oto-
cyst and connects with it. Dorsal to the otocyst the n. glossopharyngeus and the jugular
ganglion of the vagus are cut transversely while the trunk of the n. accessorius is cut length-
wise.

Section through the First and Second Pharyngeal Pouches (Fig. 130). — The end of
the head, with sections of the telencephalon and of the ends of the olfactory pits, is now

N. accessorius

Gang. Froriep

Myelencephalon

Basilar artery
Notochord

Neural cavity

Gang, petrosum n. g
Pharyngeal pouch 2

Pharyngeal pouch i
Oral cavity

Olfactory pit

Roots of n. hypoglossus

Int. jugular vein

Nn.vagus el accessorius
Descending aorta

N. facialis
Branchial arch 2
Tongue
Mandible

Maxillary process

Telencephalon

FIG. 130. — Transverse section through the first and second pharyngeal pouches of a 10 mm. pig

embryo. X 22.5.

distinct] from the rest of the "section. The pharynx shows portions of the first and
second pharyngeal pouches. Opposite the first pouch externally is the first branchial
groove. A section of the tuberculum impar of the tongue shows near the midplane in the
pharyngeal cavity. The neural tube is sectioned dorsally at the level of Froriep 's ganglion.
Between the neural tube and the pharynx may be seen on each side the several root fascicles
of the n. hypoglossus, the fibers of the nn. vagus and accessorius, and the petrosal ganglion
of the n. glossopharyngeus. Mesial to the ganglia are the descending aorta and lateral to
the vagus is the internal jugular vein.

I30

THE STUDY OF SIX AND TEN MILLIMETER PIG EMBRYOS

Section through the Third Pharyngeal Pouches (Fig. 131). — The tip of the head is
now small and shows on either side the deep olfactory pits lined with thickened olfactory
epithelium. The first, second, and third branchial arches show on either side of the section,
the third being slightly sunken in the cervical sinus. The dorsal diverticula of the third
pharyngeal pouches extend toward the ectoderm of the third branchial groove. The ventral
diverticula, or thymic anlages, may be traced caudad in the series. The floor of the pharynx
is sectioned through the epiglottis. Ventral to the pharynx are sections of the third aortic
arches and the solid cords of the thyreoid gland. Dorsally the section passes through the
spinal cord and first pair of cervical ganglia. Between the cord and pharynx, named in

'Spinal cord

Int. jugular vein
N. hypoglossus
Gang, nodosum n. 10

Pharyngeal pouch j

Aortic arch 3
Thyreoid anlage

Spinal ganglion

Notochord
Ext. branch n. accessorius

Epiglottis
Branchial arch j.

Branchial arch 2
Mandible

Olfactory pit

FIG. 131. — Transverse section through the third pharyngeal pouches of a 10 mm. pig embryo.

X 22.5.

Olfactory epithelium

order, are the internal jugular -veins, the hypoglossal nerve, and the nodose ganglion of the
vagus. Lateral to the ganglion is the external branch of the n. accessorius, and mesial to
the ganglia are the small descending aorta.

Section through the Fourth Pharyngeal Pouches (Fig. 132). — This region is marked
by the disappearance of the head and the appearance of the heart in the pericardial cavity.
The tips of the atria are sectioned as they project on either side of the bulbus cordis. The
bulbus is divided into the aorta and pulmonary artery, the latter connected with the right
ventricle, which* has spongy muscular walls. The pharynx is crescentic and continued
laterally as the small fourth pharyngeal pouches. Into the mid- ventral wall of the pharynx

TRANSVERSE SECTIONS OF A TEN MM. PIG EMBRYO

Spinal cord

Spinal ganglion

R. descending aorta

Pharynx

N. vagus

Tracked groove

R. atrium

Aorta

Pulmonary artery

L. ventricle

R. ventricle

FlG j 32.— Transverse section through the fourth pharyngeal pouches of a 10 mm. pig embryo.

X 22.5.

Spinal ganglion

R, descending aorta
Esophagus

Spinal cord

L. descending aorta •••
Ant. cardinal vein
, vagus

L. atrium
Pulmonary artery

L. ventricle

Cavity of bulbus

R. ventricl

FlG- I33._ Transverse section through the sixth pair of aortic arches and bulbus cordis of
10 mrrt. pig embryo. X 22.5.

132

THE STUDY OF SEX AND TEN MILLIMETER PIG EMBRYOS

opens the vertical slit of the trachea. A section of the -vagus complex is located between
the descending aorta and the internal jugular vein. At this level the jugular vein receives
the linguo-facial vein. The left descending aorta is larger than the right. The ventral
aorta may be traced cranially in the series to the fourth aortic arches. The pulmonary
artery, if followed caudad, connects with the sixth aortic arches as in Fig. 133.

Section through the Sixth Aortic Arches (Fig. 133). — The sixth aortic arch (see p. 100) is
complete on the left side. From these pulmonary arches small pulmonary arteries may be
traced caudad in the series to the lung anlages. The esophagus, now separate from the
trachea, forms a curved horizontal slit. All four chambers of the heart are represented,
but the aorta and pulmonary artery are incompletely separated by the right and left bulbar
swellings, or folds.

Spinal ganglion
Notoc,

Spinal cord

R. descending aorta
Sinus venosus

R. valve of sinus venosus
Pericardial cavil

R. ventricle
Interventricular septum

~- Upper limb bud

Esophagus

L. common cardinal vein

Trachea

L. atrium

Endocardial cushion
Body wall '

FIG. 134. — Transverse section through the sinus venosus of the heart in a 10 mm. pig embryo.

X 22.5.

Section through the Sinus Venosus and the Heart (Fig. 134). — The section is marked
by the symmetrically placed a(riatand ventricles of the heart and by the presence of the
tipper limb buds. Dorsal to the atria are the common cardinal veins, the right vein forming
part of the sinus venosus. The sinus venosus drains into the right atrium through a slit-
like opening in the dorsal and caudal atrial wall. The opening is guarded by the right and
left valves of the sinus venosus, which project into the atrium. The septum primum com-
pletely divides the right and left atria at this level, which is caudal to the foramen ovale
and the atrio-ventricular openings. The septum joins the fused endocardial cushions.
Note that the esophagus and trachea are now tubular and that the left descending aorta
is much larger than the right. Around the epithelium of both trachea and esophagus are
condensations of mesenchyma, from which their outer layers are differentiated.

TRANSVERSE SECTIONS OF A TEN MM. PIG EMBRYO

133

Section through the Foramen Ovale of the Heart (Fig. 135). — The level of this sec-
tion is cranial to that of the previous figure and shows the septum primum interrupted dor-
sally to form the foramen ovale. Each atrium communicates with the ventricle of the same
side through the atria-ventricular foramen. Between these openings is the endocardial cush-
ion, which in part froms the anlages of the tricuspid and bicuspid -valves. The atria are
marked off externally from the ventricles by the coronary sulcus. Between the two ven-
tricles is the interventricular septum. The ventricular walls are thick and spongy, forming
a network of muscular cords, or trabeculce, surrounded by blood spaces, or sinusoids. The
trabeculae are composed of muscle cells, which later become striated and constitute the
myocardium. They are surrounded by an endothelial layer, the endocardium. The mam-
malian heart receives all its nourishment from the blood circulating in the sinusoids until
later, when the coronary vessels of the heart wall are developed. The heart is surrounded
by a layer of mesothelium, the epicardium, which is continuous with the pericardial meso-
thelium lining the body wall.

Foramen male
R. atrium

R. atria-ventricular foramen

R. ventricle

Interventricular septum

L. atrium

•Septum I

Endocardial cushion

L. atrio-ventricular foramen

L. ventricle

FIG. 135. — Transverse section through the foramen ovale of the heart in a 10 mm. pig embryo.

X 22.5.

Section through the Liver and Upper Limb Buds (Fig. 136). — The section is marked
by the presence of the tipper limb buds, the liver, and the bifurcation of the trachea to
form the primary bronchi of the lungs. The limb buds are composed of dense, undiffer-
entiated mesenchyme, surrounded by ectoderm which is thickened at their tips. The
seventh pair of cervical ganglia and nerves are cut lengthwise, showing the spindle-shaped
ganglia with the dorsal root fibers taking origin from their cells. The ventral root fibers
arise from the ventral cells of the mantle layer and join the dorsal root to form the nerve
trunk. On the right side a short dorsal ramus supplies the anlage of the dorsal muscle
mass. The much larger ventral ramus unites with those of other nerves to form the brachial
plexus.

The descending aorta have now fused and the seventh pair of dorsal intersegmental
arteries arise from the dorsal aorta. From these intersegmental arteries the subdavian
arteries are given off two sections caudad in the series. Lateral fo the aorta are the pos-
terior cardinal veins. The esophagus, ventral to the aorta, shows a very small lumen, while
that of the trachea is large and continued into the bronchi on either side. Adjacent to
the esophagus are the cut vagus nerves. The lung anlages project laterally into the cres-
centic pleural cavities,. of which the left is separated from the peritoneal cavity by the sep-

134

THE STUDY OF SIX AND TEN MILLIMETER PIG EMBRYOS

inal cord

Spinal ganglion
Spinal nerve

Post, cardinal vein
Mesonephros

Pleural cavity
Upper limb bud

Liver

Notochord

Dorsal aorta
Esophagus

Bifurcation of trachea
Inferior vena cava

FIG. 136. — Transverse section through the liver and upper limb buds of a 10 mm. pig embryo,
at the level of the bifurcation of the trachea. X 22.5.

/

Spinal ganglL

Descending aorta
Mesonephros

inal cord

Notochord

Sympathetic ganglion
. cardinal vein

Post.

R. lung bud

Esophagus

Lesser peritoneal sac

Inferior vena cava

Mesonephric tubule

'eritoneal cavity
'Dorsal lobe of liver

Sinusoids of liver

Ductus venosus

FIG. 137. — Dorsal half of a transverse section through the lung buds, cranial to the stomach, in
a 10 mm. pig embryo. X 22.5.

TRANSVERSE SECTIONS OF A TEN MM. PIG EMBRYO

135

turn transfer sum. The liver, with its fine network of trabeculae and sinusoids, is large and
nearly fills the peritoneal, or abdominal cavity. The liver cords are composed of liver
cells surrounded by the endothelium of the sinusoids. Red blood cells are developed in
the liver at this stage. The large vein, from the liver to the heart, penetrating the sep-
tum transversum is the proximal portion of the inferior vena cava, originally the right
vitelline vein. Ventral to the bronchi may be seen sections of the pulmonary veins.

Section through Lung Buds, Cranial to Stomach (Fig. 137). — The lungs are sectioned
through their caudal ends and the esophagus is just beginning to dilate into the stomach.
On either side of the circular dorsal aorta are the mesonephroi, while dorso-laterally are
sympathetic ganglia. The pleural cavities now communicate freely on both sides with the
peritoneal cavity. A section of the lesser peritoneal sac appears as a crescent-shaped slit at
the right of the esophagus. In the right dorsal lobe of the liver is located the inferior
vena cava. Near the median plane ventral to the lesser sac is the large ductus venosus.

Spinal cord,

Notochord

Dorsal aorta

Plica vena cava

Inferior vena cava
lesser omentum

Spinal ganglion

Base of upper limb

Glomerulns of
mesonephros

Greater omentum
Stomach

Dorsal lobe of liver
Ductus venosus

Ventral lobe of liver

Ventral attachment of live*

FIG. 1 38. — Transverse section through the stomach and liver of a i o mm. pig embryo. X 22.5 .

Section through the Stomach and Liver (Fig. 138).— Prominent in the body cavity
are the mesonephroi and liver lobes. The mesonephroi show sections of coiled tubules
lined with cuboidal epithelium. Glomeruli of the renal corpuscles are median in position
and develop as knots of small arteries which grow into the ends of the tubules. The thick-
ened epithelium along the median and ventral surface of the mesonephros is the anlage of
the genital gland. The body wall is thin and lined with mesothelium continuous with that
which covers the mesenteries and organs. The mesothelial layer becomes the epithelium
of the adult peritoneum, mesenteries, and serous layer of the viscera. The stomach lies on

136

THE STUDY OF SIX AND TEN MILLIMETER PIG EMBRYOS

the left side and is attached dorsally by the greater amentum, ventrally to the liver by the
lesser amentum. The right dorsal lobe of the liver is attached dorsally to the right of the
great omentum. In the liver, ventral to this attachment, courses the inferior vena cava
and the attachment forms the plica vence cave?. Between the attachments of the stomach
and liver, and to the right of the stomach, is the lesser peritoneal sac. In the liver, to the
left of the midplane is the ductus venosus, sectioned just at the point where it receives the
left umbilical vein and a branch from the portal vein. The ventral attachment of the liver
later becomes the falciform ligament.

Spinal cord

Notochord
Mesonephros

Plica vena cava

Inferior vena cava

Lesser peritoneal sac

Portal vein

Hepatic diverticulum
(Duct and gall bladder)

R. umbilical vein

Sympathetic ramus
Dorsal aorta
Dorsal mesogastrium

Mesonephric duct
Stomach

Ventral lobe of liver
L. umbilical vein

FIG. 139. — Transverse section through the hepatic diverticulum of a 10 mm. pig embryo.

X 22.5.

Section through the Hepatic Diverticulum (Fig. 139).— The section passes through the
pyloric end of the stomach and duodenum, near the attachment of the hepatic diverticu-
lum. The greater omentum of the stomach is larger than in the previous section and to its
right, in the plica venae cavae, lies the inferior vena cava. Ventral to the inferior vena cava
is a section of the portal vein. The ventral and dorsal lobes of the liver are now separate,
and in the right ventral lobe is embedded the saccular end of the hepatic diverticulum which
forms the gall bladder. To the right of the stomach, the diverticulum is sectioned again
just as it enters the duodenum. Ventrally, the left umbilical vein is entering the left ventral
lobe of the liver. It is much larger than the right vein, which still courses in the body wall.
On the left side of the embryo the spinal nerve shows in addition to its dorsal and ventral
rami a sympathetic ramus, the fibers of which pass to a cluster of ganglion cells located
dorso-lateral to the aorta. These cells form one of a pair of sympathetic ganglia and are
derived from a spinal ganglion.

TRANSVERSE SECTIONS OF A TEN MM. PIG EMBRYO

137

Section through the Pancreatic Anlages (Fig. 140).— The lesser peritoneal sac just
above the level of this section has opened into the peritoneal cavity through the epiploic
foramen (of Winslow). The mesonephric ducts are now prominent ventrally in the meso-
nephroi. The duct of the dorsal pancreas is sectioned tangentially at the point where it

Dorsal aorta

Inferior vena cava

R. vitelline or portal vei
Mesonephric duel

Post, cardinal vein

Mesonephros

L. vitelline vein
Dorsal pancreas
Liver

Duodenum

Ventral pancreas-

FIG. 140. — Portion of a transverse section through the pancreatic anlages of a 10 mm. pig

embryo. X 22.5.

takes origin from the duodenum. From the duct the lobulated gland may be traced
dorsad in the mesentery. To the right of the dorsal pancreatic duct is a section of the
ventral pancreas, which may be traced cephalad in the series to its origin from the hepatic
diverticulum. Dorsal to the ventral pancreas is a section of the portal -vein-. The inferior
vena cava appears as a vertical slit in the dorsal mesentery.

Lower limb b

Mesonephric due.

Vein in body wall
L. umbilical artery

Allantois and
urogenital sinus

Rectum

Notochord

Spinal cord

10 mm. pig embryo.

FIG. 141. — Transverse section through the urogenital sinus and recturr of

X 22.5.

Section through the Urogenital Sinus and Lower Limb Buds (Fig. 141).— The figure
shows only the caudal end of a section, in the dorsal portion of which the mesonephroi
were sectioned at the level of the subcardinal anastomosis. A portion of the mesentery
is shown with a section of the colon. In the body wall are veins that drain into the umbili-
cal veins, and on each side are the umbilical arteries, just entering the body from the umbili-

138

THE STUDY OF SEX AND TEN MILLIMETER PIG EMBRYOS

cal cord. Between them, in sections cranial to this, the allantoic stalk is located. Here it
has opened into the crescentic urogenital sinus. Dorsal to the urogenital sinus (dorsal now
being at the bottom of the figure, owing to the curvature of the caudal region) is a section
of the rectum, separated from the sinus by a curved prolongation of the ccelom. From the
ends of the urogenital sinus, as we trace cephalad in the embryo (downward in the series),
are given off the mesonephric ducts.

Lower limb bud
R. umbilical artery

Caudal limb of intestine

Mesonephric duct
Ureter

Notochord

Spinal cord

FIG. 142. — Transverse section of a 10 mm. embryo passing through the lower limb buds at the
level of the openings of the ureters into the mesonephric ducts. X 22.5.

Section through the Mesonephric Ducts at the Opening of the Ureter (Fig. 142).
The section cuts through both lower limb buds near their middle. Mesial to their
bases are the umbilical arteries, which lie lateral to the mesonephric ducts. From the dorsal
wall of the left mesonephric duct is given off the ureter, or duct of the metanephros. Trac-
ing the sections down in the series, both ureters appear as minute tubes in transverse
section. They soon dilate to form the pelvis of the kidney at the level of Fig. 143.
Note the undifferentiated mesenchyme of the lower limb buds and their thickened ectoder-
mal tips.

Mesentery

R. umbilical artery
Vein

Ccelom

Anlage of metanephros
Notochord

Spinal cord

FlG. 143. — Transverse section through the anlages of the metanephroi in a 10 mm. pig embryo.

X 22.5.

Section through the Metanephroi and Umbilical Arteries (Fig. 143). — The section
passes caudal to the mesonephric ducts, which curve along the ventral surfaces of the
mesonephroi (Fig. 124). The umbilical arteries course lateral to the metanephroi; these
consist merely of the thickened epithelium of the pelvis surrounded by a layer of condensed
mesenchyma, the nephrogenic tissue.

CHAPTER VI

THE DISSECTION OF PIG EMBRYOS: DEVELOPMENT OF THE FACE,
PALATE, TONGUE, SALIVARY GLANDS AND TEETH

THE DISSECTION OF PIG EMBRYOS

As the average student will not have time to study series of embryos sectioned in differ-
ent planes, dissections may be used for showing the form and relations of the organs.
Cleared embryos mounted whole are instructive, but show the structures superimposed and
are apt to confuse the student. Pig embryos 10 mm. or more in length may be easily
dissected, mounted as opaque objects, and used for several years. Success in dissecting
such small embryos depends: (i) on the fixation and hardening of the material employed;
(2) on starting the dissection with a clean cut in the right plane; (3) on a knowledge of the
anatomy of the parts to be dissected.

Fixation and Hardening of Material. — Embryos fixed in Zenker's fluid have given
the best results. They should then be so hardened in 95 per cent alcohol that the more
diffuse mesenchyma will readily separate from the surfaces of the various organs, yet the
organs must not be so brittle that they will crumble and break. Embryos well hardened
and then kept for two weeks in 80 per cent alcohol usually dissect well. Old material is
usually too brittle; that just fixed and hardened may prove too soft. As a test, determine
whether the mesenchyma separates readily from the cervical ganglia and their roots.

Dissecting instruments include a binocular dissecting microscope, a sharp safety
razor blade, large, curved, blunt -pointed dissecting needles, pairs of small, sharp-pointed
forceps, and straight dissecting needles, small and large.

Methods of Dissection. — In general, it is best to begin the dissection with a clean,
smooth cut made fay a single stroke with the safety razor blade, which should be flooded
with 80 per cent alcohol. The section is made free hand, holding the embryo, protected
by a fold of absorbent cotton, between the thumb and index finger. Having made pre-
liminary cuts in this way, the embryo may be affixed with thin celloidinto a cover glass and
immersed in a watch glass containing alcohol. We prefer not to affix the embryo, as the
celloidin used for this purpose may interfere with the dissection. Instead, a cut is made
parallel to the plane of the dissection so that the embryo, resting in the watch glass upon
this flat surface, will be in a fairly stable position. It may thus be held in any convenient
position by resting the convex surface of a curved, blunt dissecting needle upon some part
not easily injured. The dissection is then carried on under the binocular microscope,
using the fine pointed forceps, dissecting needles, and a small pipette to wash away
fragments of tissue.

Whole Embryos. — For the study of the exterior, whole embryos may be affixed with
celloidin to the bottoms of watch glasses which may be stacked in wide-mouthed jars of 80
per cent alcohol. The specimens may thus be used several years at a saving of both time
and material. Preliminary treatment consists in immersion in 95 per cent alcohol one
hour, in ether and absolute alcohol at least thirty minutes, in thin celloidin one hour or
more. Pour enough thin celloidin into a Syracuse watch glass to cover its bottom, and
immerse in this a circle of black mat paper, first wet with ether and absolute alcohol. Pour

140

THE DISSECTION OF PIG EMBRYOS

off any surplus celloidin, mount embryo in desired position and immerse watch glass in
80 per cent alcohol, in which the specimen may be kept indefinitely. Embryos may also
be mounted in gelatin-formalin solution in small, sealed glass jars.

Lateral Dissections of the Viscera. — Dissections like those shown in Figs. 144 and
145 may easily be prepared in less than an hour, and make valuable demonstration and

Mesencephalon
Cerebellum \

Gang, geniculi n.7
Gang, acusticum n. 8
Gang, superius n. 9
Gang, accessorii

Gang, jugulare n. 10

Ga'iig. petrosum n.

N. hypoglossus

N. accessorius
Gang. cerv.

Brachial pie.

Lun,

Diaphragm
Dorsal lobe of liver

Mesonephros
Metaneph

Nerve to lower limb

Sciatic nerve

FIG. 144. — Lateral dissection of an 18 mm. pig embryo, showing the nervous system and
viscera from the right side. X 8.

laboratory specimens. Skill is required to demonstrate most of the cerebral nerves, but the
central nervous system, cerebral and spinal ganglia, and viscera may easily be exposed.
Starting dorsally, make a sagittal section of the embryo slightly to one side of the median
line and avoiding the umbilical cord ventrally. With the embryo resting on the flat, sec-
tioned surface, begin at the cervical flexure, and with fine forceps grasp the ectoderm and
dural anlage at its cut edge, separate it from the neural tube and pia mater, and strip it

N. oculomotorius
I N. trochlearis

Gang, semilunare n. 5

Mandibular ramus n. 5
^/Ophthalmic ramus n. 5
N. opticus

Cerebrum

Maxillary ramus n. 5
Chorda tympani n. 7
N. facialis

Gang, nodosum n. iO

R. atrium '
R. ventricle

Ventral lobe of liver

Umbilical cord

LATERAL DISSECTIONS OF THE VISCERA

off ventralwards, exposing the myelencephalon and cervical portion of the cord. As the
mesenchyma is pulled away, the ganglia and roots of the cerebral nerves will be exposed.
The mesenchyma between the ganglia and along the nerves may be removed with the end
of a small blunt needle. Care must be exercised in working over the mesencephalon and

Semilunar ganglion n. 5 Ophthalmic ramus n. 5
Gang, geniculi n. 7 \ I Cerebrum

Mesencephal
Cerebellum

Gang, acusticum n. 8
Gnag. superius n.

Gang, jugulare n. 10

Gang. Freriep

Auricular r. n. 10

Gang. n. cerv. I

Gang, petrosum n.

N. accessorius

N. hypoglossus

Gang. cerv. 5-8

Gang. thor. I

Lung

Diaphragm \

Dorsal lobe of liver
Mesonephros

Hypophysis

N. opticus

Lobus olfactorius

•Maxillary ramus n. 5

Mand. ramus n. 5
Chorda tympani n. 7

N. facialis

Gang, nodosum n. 10

R. atrium
R. ventricle

Ventral lobe of liver
Umbilical cord
Lower limb

Sciatic nerve

Metanephros'

Lumbar gang.

Nerve to lower limb

FIG. 145. — Lateral dissection of a 35 mm. pig embryo, to show the nervous system and viscera
from the right side. X 4.

telencephalon of the brain not to injure the brain wall, which may be brittle. By starting
with a clean dissection dorsally and gradually working ventrad, the more important organs
may be laid bare without injury. The beginner should compare his specimen with the
dissections figured and also previously study the reconstructions of Thyng (1911) and Lewis
(1903).

142 THE DISSECTION OF PIG EMBRYOS

Lateral dissections of embryos 18 mm. and 35 mm. long show infinitely better than
sections the form and relations of the organs, their relative growth, and their change of
position (Figs. 144 and 145). Compare the organs of 6, 10, 18, and 35 mm. embryos and
note the rapid growth of the viscera (see Figs. 95 and 120). Hand-in-hand with the in-
creased size of the viscera goes the diminution of the dorsal and cervical flexures. In the
brain, note the increased size of the cerebral hemispheres of the telencephalon and the pres-
ence of the olfactory lobe of the rhinencephalon. The cerebellum also becomes prominent
and a ventral flexure in the region of the pons, the p online flexure, is more marked. The
brain grows relatively faster than the spinal cord, and, by the elongation of their dorsal
roots, the spinal ganglia are carried ventral to the cord. The body of the embryo also
grows faster than the spinal cord, so that the spinal nerves, at first directed at right angles
to the cord, course obliquely caudad in the lumbo-sacral region.

Median Sagittal Dissections (Figs. 146 and 147). — Preliminary to the dissection, a
cut is made dorsally as near as possible to the median sagittal plane. Beginning caudally at
the mid-dorsal line, an incision is started which extends in depth through the neural tube
and the anlages of the vertebrae. This incision is carried to the cervical flexure, cranial to
which- point the head and brain are halved as accurately as possible. The blade is then
carried ventrally and caudally, cutting through the heart and liver to the right of the mid-
plane and umbilical cord until the starting point is reached. A parasagittal section is next
made well to the left of the median sagittal plane and the sectioned portion is removed,
leaving on the left side of the embryo a plane surface. With the embryo resting upon this
flat surface, the dissection is begun by removing with forceps the right half of the head.
In pulling this away caudalwards, half of the dorsal body wall, the whole of the lateral
body wall, and the parts of the heart and liver lying to the right of the midplane will be
removed, leaving the other structures intact. If the plane of section was accurate, the
brain and spinal cord will be halved in the median sagittal plane. Wash out the cavities of
the brain with a pipette and its internal structure may be seen. Dissect away the mesen-
chyma between the esophagus and trachea and expose the lung. Remove the right meso-
nephros, leaving the proximal part of its duct attached to the urogenital sinus. The right
dorsal lobe of the liver will overlie the stomach and pancreas. Pick it away with forceps
and expose these organs. Dissect away the caudal portion of the liver until the hepatic
diverticulum is laid bare. It is whitish in color and may thus be distinguished from the
brownish liver. Beginning at the base of the umbilical cord, carefully pull away its right
wall with forceps, thus exposing the intestinal loop and its attachment to the yolk stalk.
If the umbilical artery is removed in the caudal portion of the umbilical cord, the allantoic
stalk may be dissected out. To see the anlage of the genital gland, break through and
remove a part of the mesentery, exposing the mesial surface of the left mesonephros and
the genital fold. The dissection of the metanephros and ureter is difficult in small em-
bryos. In 10 to 12 mm. embryos, the umbilical artery, just after it leaves the aorta, passes
lateral to the metanephros and thus locates it. By working carefully with fine needles, the
surface of the metanephros may be laid bare and the delicate ureter may be traced to the
base of the mesonephric duct. The extent of the dorsal aorta may also be seen by removing
the surrounding mesenchyma. With a few trials, such dissections are made in a short time ;
they are invaluable in giving an idea of the form, positions, and relations of the different
organs. By comparing the early (Figs. 96 and 122) with the later stages (Figs. 146 and
i47)~a number of interesting points may be noted.

In the brain, the corpus striatum develops in the floor of the cerebral hemispheres.
The inter-ventricular foramen is narrowed to a slit. In the roof of the diencephalon appears
the anlage of the epiphysis, or pineal gland, and the chorioid plexus of the third ventricle.

MEDIAN SAGITTAL DISSECTIONS

143

This extends into the lateral ventricles as the lateral chorioid plexus. The dorso-lateral
wall of the diencephalon thickens to form the thalamus, and the third ventricle is narrowed
to a vertical slit. The increased size of the cerebellum has been noted. Into the thin dorsal

Isthmus M esencephalon
Metencephalon

Chorioid plexus of fourth ventricle
Hypophysis

Tela chorioidea of fourth ventricle
Myelencephalon

Epiglottis

Intersegmental
arteries

Pancreas

Common bile duel

Duodenum

Third ventricle

Diencephalon

Corpus striatum

Cerebrum

\ Small intestine
•Allantois
•Bladder
'Phallus

—

Urogenital sinus

Rectum

Genital fold

Metanephros

Mesonephric duct Ureter

FIG. 146. — Median sagittal dissection of an 18 mm. pig embryo, showing the brain in section
and the viscera in position. X 8.

wall of the myelencephalon grows the network of vessels that forms the chorioid plexus
of the fourth ventricle, which is now spread out laterally and flattened dorso-ventrally.
About the notochord, mesenchymal anlages which form the centra of the vertebra are
prominent.

144

THE DISSECTION OF PIG EMBRYOS

Turning to the alimentary tract, observe that the primitive mouth cavity is now
divided by the palatine folds into the upper nasal passages and lower oral cavity. In the
lateral walls of the nasal passages develop the anlages of the turUnate bones. On the floor
of the mouth and pharynx, the tongue and epiglottis become more prominent. The trachea
and esophagus elongate and the lungs lie more and more caudad. The dorsal portion ot

Pedunculus cerebri

Cerebellum
Chorioidal plexus, ventricle 4

Tela of vetttricle 4
Myelencephalon

Epiphysis Thalamus
Mesencephalon

Tela chorioidea

Lat. chorioid plexus

Corpus slriatum

Hypophysis
Lobus olfactorius
Turbinate anlage

Palate

Suprarenal gland
Genital gland
Duodenum

Metanephros

Colon
L. mesonephric duct

Ureter

Urogenital sinus with mesonephric duct Rectum

FIG. 147. — Median sagittal dissection of a 35 mm. embryo. X 4.

the septum transversum, the anlage. of a portion of the diaphragm, is thus carried caudad,.
and although originally, when traced from the dorsal body wall, it was directed caudad and
ventrad, now it curves cephalad and ventrad, bulging cephalad into the thorax. The
proximal limb of the intestinal loop elongates rapidly, and, beginning with the duodenum,
becomes flexed and coiled in a characteristic manner. The distal limb of the intestinal

VENTRAL DISSECTIONS

loop is not coiled, but its diverticulum, the cacum, is" more marked. Caudally, the rec-
tum, or straight gut, has completely separated from the urogenital sinus and opens to the
exterior through the anus.

Of the urogenital organs, the genital folds have become the prominent genital glands,
attached to the median surfaces of the mesonephroi. The metanephroi have increased
rapidly in size and have shifted cephalad. Proximal to the allantoic stalk the adjacent
portion of the urogenital sinus has dilated to form the bladder. As the urogenital sinus
grows, it takes up into its wall the proximal ends of the mesonephric ducts, so that these and
the ureters have separate openings into the sinus. Owing to the unequal growth of the
sinus wall, the ureters open near the base of the bladder, the mesonephric ducts more cau-
dally into the urethra. The phallus now forms the penis of the male or the clitoris of the
female. Cranial to the metanephros, a new organ, the suprarenal gland, has developed.
This is a ductless gland and is much larger in human embryos.

The heart, as may be seen by comparing Figs. 96 and 147, athough at first pressed
against the tip of the head, shifts caudally, until in the 35 mm. embryo, it lies in the thorax
opposite the first five thoracic nerves. Later it shifts even further caudad. The same
is true of the other internal organs, the metanephros excepted. As the chief blood vessels
are connected with the heart and viscera, profound changes in the positions of the vessels
are thus "brought about, for the vessels must shift their positions with the organs which
they supply.

Trachea

Septum transfer sum
Stomach

Mesonephric duct
Mesonephros

Umbilical artery
Rectum

Lung
Miillerian duct anlage

Cacum

Small intestine
Large intestine

Allantoit

Ccelom

FIG. 148. — Ventral dissection of a 15 mm. pig embryo, showing lungs, digestive canal and
mesonephroi. The ventral body wall, heart and liver have been removed and the limb buds
cut across. X 6.

Ventral Dissections. — Ventral dissections of the viscera are very easily made. With
the safety razor blade, start a cut in a coronal plane through the caudal end of the embryo
and the lower limb buds (Fig. 148). Extend this cut laterad and cephalad through the
body wall and the upper limb bud. The head may be cut away in the same plane of sec-
tion, and the cut continued through the body wall and upper limb bud of the opposite side
back caudally to the starting point. Section the embryo in a coronal plane, parallel with
the first section and near the back, so that the embryo will rest upon the flattened surface.
With forceps, now remove the ventral body wall. By tearing open the wall of the umbilical
cord along one side, it may be removed, leaving the intestinal loop intact. Pull away the

146

THE DISSECTION OF PIG EMBRYOS

heart, noting its external structure. The liver may also be removed, leaving the stomach
and intestine uninjured. A portion of the septum transversum covering the lungs
may be carefully stripped away and the lungs thus laid bare.

Dissections made in this way show the trachea and lungs, the esophagus, stomach and
dorsal attachment of the septum transversum, the course of the intestinal canal, and also
the mesonephroi and their ducts. Favorable sections through the caudal end of the body
may show the urogenital sinus, rectum, and sections of the umbilical arteries and allantois
(Figs. 97, 124 and 148). In late stages, by removing the digestive organs, the uro-
genital ducts and glands are beautifully demonstrated (Figs. 223 and 224).

DEVELOPMENT OF THE FACE

The heads of pig embryos have long been used for the study of the development of
the face. The heads should be removed by passing the razor blade between the heart and
the adjacent surface of the head, thus severing the neck. Next cut away the dorsal part

Lateral nasal process

Olfactory pit

Medial nasal process

Mandible

Branchial arch 2
Ventral aorta-

Eye

— Lacrimal groove
-Maxillary process

Branchial groove i
Branchial groove 2

Lateral nasal process

Maxillary process
Mandibl,
Branchial groove

External nans

Eye

Medial nasal process

Oral cavity

External ear

FIG. 149. — Two stages showing the development of the face in pig embryos. X 7. A , 12 mm. ;

B, 14 mm.

of the head by a section parallel to the ventral surface, the razor blade passing dorsal to
the branchial clefts and eyes. Mount, ventral side up, three stages from embryos 6, 12,
and 14 mm. long, as shown in Figs. 97 and 149..

In the early stages (Figs. 97 and 124), the four, paired branchial
arches and grooves are seen. Each first arch has already bifurcated into a
maxillary and mandibular process. The third and fourth arches soon sink
into the cervical sinus, while the mandibular processes of the first arch are

DEVELOPMENT OF THE FACE

147

fused early to form the lower jaw. Laterally, the frontal process of the
head is early divided into lateral and median nasal processes by the develop-
ment of the olfactory pits. These processes are distinct and most promi-
nent at 12 mm. (Fig. 149 A). Soon, in 13 to 14 mm. embryos, the median
nasal processes fuse with the maxillary processes of the first arch and con-
stitute the upper jaw (Fig. 149 B). The lateral nasal processes fuse with

FIG. 150. — Development of the face of the human embryo (His). A, Embryo of 8 mm.
(X 7.5); the median frontal process differentiating into median nasal processes, or processes
globulares, toward which the maxillary processes of the first branchial arch are extending. B,
Embryo of 13.7 mm. (X 5); the globular, lateral nasal and maxillary processes are in apposi-
tion; the primitive naris is now better defined. C, Embryo of 17 mm. (X 5); immediate
boundaries of mouth are more definite and the nasal orifices are partly formed, the external
ear appearing. D, Embryo of nearly eight weeks (X 5).

the maxillary processes and form the cheeks, the lateral part of the Up,
and the alee of the nose. Later, the median nasal processes unite and be-
come the median part of the upper lip. Meanwhile, the mesial remainder
of the original frontal process (Fig. 149 A) is compressed and becomes the
septum and dorsum of the nose. The development of the olfactory organ
will be traced on p. 371.

148 THE DISSECTION OF PIG EMBRYOS

The early development of the face is practically the same in human
embryos (Figs. 150 and 370). In embryos of 8 mm. the lateral and median
nasal processes have formed. The maxillary processes next fuse with the
nasal processes, after which the median nasal processes unite. Coincident
with these changes the mandibular processes fuse and from them a median
projection is developed which forms the anlage of the chin.

The external ear is developed around the first branchial groove by the
appearance of small tubercles which form the auricle. The groove itself
becomes the external auditory meatus and the concha of the ear. (For the
development of the external ear see Chapter XIII.)

Epithelial ingrowths begin to separate the lips from the jaws at the fifth week
(Fig. 1 59) . The inner edges of the lips at birth bear numerous villosities. The line of
fusion of the median nasal processes is evident in the adult as the philtrum.

Anomalies. — A common facial defect is hare lip. This is usually unilateral and on
the left side. It may involve both lip and maxilla. Hare lip is attributed to the failure
to fuse of the median nasal and maxillary processes (Kolliker), or the lateral and
median nasal processes (Albrecht).

DEVELOPMENT OF THE PALATE

This may be studied advantageously in pig embryos of two stages: (a) 20 to 25mm.
long; (b) 28 to 35 mm. long. Dissections are made by carrying a shallow incision from
the anlage of the mouth back to the external ear on each side (Fig. 152). The incisions are
then continued through the neck in a plane parallel to the hard palate. Before mounting
the preparation, remove the top of the head by a section cutting through the eyes and nos-
trils, parallel to the first plane of section. Transverse sections through the snout may also
be prepared to show the positions of tongue and palatine folds before and after the fusion
of the latter (Fig. 151).

In pig embryos of 20 to 25 mm. the jaws are close together and the
mandible usually rests against the breast. Shelf -like folds of the maxillae,
the lateral palatine processes, are separated by the tongue and are directed
ventrad (Figs. 151 A and 152 A). The median nasal processes also give
rise to a single, heart-shaped structure, the median palatine process (Fig.
152). In embryos of 26 to 28 mm. the mandible drops, owing to growth
changes, and the tongue is withdrawn from between the palatine processes
(Fig. 151 B). With the withdrawal of the tongue the palatine folds bend
upward to the horizontal plane, approach each other and fuse to form the
palate, thus cutting off the nasal passages from the primitive oral cavity
(Fig. 152 B}. The primitive choanae (cf. Fig. 153), formed by rupture of
the membrane separating the olfactory pits from the oral cavity, now lead
into the nasal passages, which in turn communicate with the pharynx by
secondary, permanent choancs. At the point in the median line where the
lateral and median palatine processes meet, fusion is not complete, leaving

DEVELOPMENT OF THE PALATE

149

Nasal septu

Lateral palatine process

Nasal septum
Lateral palatine process

Mandible

Turbinate anlage

'- — Tongue

FlG. 151. — Sections through the jaws of pig embryos, to show the development of the palate.
X 8. A, 22 mm.; B, 34 mm.

Median palatine
process

Lateral palatine
process
Internal choance

Oral cavity

Median palatine
process

Rapke of lateral
palatine process

Nasal passage
Anlage of uvula

A B

FIG. 152. — Dissections to show the development of the hard palate in pig embryos. X 5-
A, The upper jaw and palatine processes of a 22 mm. embryo in ventral view; B, Fusion of
palatine processes in a 35 mm. embryo.

THE DISSECTION OF PIG EMBRYOS

the incisive fossa, and laterad between the two processes openings persist for
some time, which are known as the incisive canals (of Stenson).

In human embryos these changes are essentially identical (Fig. 153).
The lateral palatine processes begin to fuse cranio-caudally at about the
end^of.the second month. At the same time, palatine bones first appear in

Median palatine process

Processus 'globularis
' (Median nasal process)

Lateral palatine process

Maxillary process

FIG- X53- — The roof of the mouth of a human embryo about ten weeks old, showing the
development of the palate (after His). X 9. In the roof of the mouth are the openings of
the primitive choanae.

the lateral palatine folds and thus form the hard palate. Caudally, the
bones do not develop, and this portion of the folds forms the soft palate and
the uvula (Fig. 152). The unfused backward prolongations of the pala-
tine folds give rise to the pharyngo-palatine arches, which are taken in
adult anatomy as the boundary line between the oral cavity proper and
the pharynx.

Nasal septum

\

Proliferating cells
Lateral palatine process

Mandible

FIG. 154. — Section through the jaws of a 25 mm. pig embryo, to show the change in the position
of the palatine processes with reference to the tongue.

After the withdrawal of the tongue, the lateral palatine processes take up a horizontal
position and their edges are approximated because the cells on the ventral sides of the folds
proliferate more rapidly than those of the dorsal side (Schorr, 1908). That the change in
position of the palatine folds is not mechanical, but due to unequal growth, may be seen
in Fig. 154, a section through the palatine folds of a pig embryo that shows the right

DEVELOPMENT OF THE TONGUE 151

palatine fold in a horizontal position, although the left fold projects ventral to the dorsum
of the tongue. A region of cellular proliferation may be seen on the under side of each
process.

Anomalies. — The lateral palatine processes occasionally fail to unite in the middle
line, producing a defect known as cleft palate. The extent of the defect varies considerably,
in some cases involving only the soft palate, while in other cases both soft and hard palates
are cleft. It may also be associated with hare lip.

DEVELOPMENT OF THE TONGUE

The development of the tongue may be studied from dissections of pig embryos 6, 9,
and 13 mm. long. As the pharynx is bent nearly at right angles, it is necessary to cut away
its roof by two pairs of sections p'assing in different planes. The first plane of section cuts
through the eye and first two branchial arches just above the cervical sinus (Fig. 155, I.),
From the surface, the razor blade should be directed obliquely dorsad in cutting to ward the
median line. Cuts in this plane should be made from either side. In the same way make
sections on each side in a plane forming an obtuse
angle with the first section and passing dorsal to
the cervical sinus (II). Now sever the remaining
portion of the head from the body by a transverse
section in a plane parallel to the first (III). Place
the ventral portion of the head in a watch glass of
alcohol, and, under the dissecting microscope, re-
move that part of the preparation cranial to the
mandibular arches. Looking down upon the floor
of the pharynx, remove any portions of the lateral
pharyngeal wall which may still interfere with a ^ I55._Lateral view of the

clear view of the pharyngeal arches, as seen in head of a ? mm pig embryo The
Figs. 98 and 156. Permanent mounts of the three three lines indicate the planes of sec-
stages mentioned above may be made and used tions to be made in dissecting the
for study by the student. tongue as described in the text.

The tongue develops as two distinct portions, the body and the root,
separated from each other by a V-shaped groove, the sulcus terminalis. In
both human and pig embryos the body of the tongue is represented by three
anlages that appear in front of the second branchial arches. These are
the median, somewhat triangular tuberculum impar, and the paired lateral
swellings of the first, or mandibular arches, all of which are present in
human embryos of 5 mm. (Figs. 98 and 157 A}. At this stage, a median
ventral elevation formed by the union of the second branchial arches (and,
according to some workers, the third as well) constitutes the copula. This,
with the portions of the second arches lateral to it, forms later the base,
or root, of the tongue. Between it and the tuberculum impar is the point
of evagination of the thyreoid gland. The copula also connects the tuber-
culum impar with a rounded prominence that is developed in the mid- ven-
tral line from the bases of the third and fourth branchial arches. This is
the anlage of the epiglottis.

THE DISSECTION OF PIG EMBRYOS

In later stages (Fig. 156 A and B) the lateral mandibular anlages,
bounded laterally by the alveolo-lingual grooves, increase rapidly in size

Branchial
Tubercul

rial arch i IMP JB9J

um impar ^E^H

Branchial arch 2

Branchial arch 3
Branchial arch 4

Arytenoid ridge s£ — \ — xJL-^

•Lateral lingual anlage

Branchial arch i
Lateral lingual anlage

Branchial arch 3

Branchial arch 4

Arytenoid ridge

Tuberculum impar

FIG. 156. — Dissections showing the development of the tongue in pig embryos. X 12. A,
9 mm. embryo; B, 13 mm. embryo.

and fuse with the tuberculum impar, which lags behind in development,
and, according to Hammar atrophies completely. The epiglottis becomes

Lateral tongue swellings Thvreoid diverticulum Lateral tongue swellings

A B

FIG. 157. — The development of the tongue in human embryos. A, 5 mm.; B, 7 mm. (modified

from Peters).

larger and concave on its ventral surface. Caudal to it, and in early
stages continuous with it, are two thick rounded folds, the arytenoid ridges.
Between these is the slit-like glottis leading into the larynx (see p. 167).

DEVELOPMENT OF THE SALIVARY GLANDS 153

The foregoing account applies to the early origin of the mucous membrane alone. The
musculature of the tongue is supplied chiefly by the hypoglossal nerve, and both nerve and
muscles belong historically to the postbranchial region. If not in the development of each
present-day embryo, at leasb in the past the musculature has migrated cephalad and invad-
ed the branchial region beneath the mucous membrane (cf. p. 320). At the same time, the
tongue may be said to extend caudad until its root is covered by the epithelium of the
third and fourth branchial arches. This is shown by the fact that the sensory portions
of the nn. trigeminus andfacialis, the nerves of the first and second arches, supply the body
of the tongue, while the nn. glossopharyngeus and vagus, the nerves of the third and fourth
arches, supply the root and the caudal portion of the body of the tongue.

Anomalies. — Faulty development or incomplete fusion of the several anlages causes
variable degrees of absence or bifurcation of the tongue.

In fetuses of 50 to 60 mm. (CR) the fungiform and filiform papilla;
may be distinguished as elevations of the epithelium. Taste buds appear
in the fungiform papillae of 100 mm. (CR) fetuses and are much more
numerous in the fetus than in the adult. The vallate papilla (Fig. 158 A)
develop on a V-shaped epithelial ridge, the apex of the V corresponding to

A B C

FIG. 158. — Diagrams showing the development of the vallate papillae of the tongue (Graberg
in McMurrich). a, Valley; b, von Ebner's gland.

the site of the thyreoid evagination (foramen caecum). At intervals along
the epithelial ridges, circular epithelial downgrowths occur (85 mm. CR)
which take the form of inverted and hollow truncated cones (Fig. 158).
During the fourth month circular clefts appear in the epithelial down-
growths, thus separating the walls of the vallate papillae from the surround-
ing epithelium and forming the trench from which this type -of papilla
derives its name. At the same time, lateral outgrowths arise from the
bases of the epithelial cones, hollow out and form the ducts and glands of
Ebner. The taste buds of the vallate papillae are also formed early,
appearing in embryos of three months. Foliate papilla probably develop
at about six months.

DEVELOPMENT OF THE SALIVARY GLANDS

The glands of the mouth are all regarded as derivatives of the ecto-
dermal epithelium. They complete their differentiation only after birth.

The parotid is the first to appear. Its anlage has been observed in
8 mm. embryos, near the angle of the mouth, as a keel-like flange in the
floor of the alveolo-buccal (i.e., jaw-cheek) groove (Hammar). The

154 THE DISSECTION OF PIG EMBRYOS

flange elongates, and, in embryos of 17 mm., separates from the parent
epithelium, forming a tubular structure that opens into the mouth cavity
near the front end of the original furrow. The tube grows back into the
region of the external ear, branches, and forms the gland in this region,
while the stem portion of the tube becomes the parotid duct. Acinus
cells are present at five months.

The submaxillary gland arises at 1 1 mm. as an epithelial ridge in the
alveolo-lingual (i.e., jaw-tongue) groove, its cephalic end located caudal to
the frenulum of the tongue. The caudal end of the ridge soon begins to
separate from the epithelium and extends caudad and ventrad into the
submaxillary region, where it enlarges and branches to form the gland
proper; its cephalic unbranched portion, persisting as the duct, soon hol-
lows out.

The sublingual gland develops in 24 mm. embryos as several solid
evaginations of epithelium from the alveolo-lingual groove (Fig. 163):
This group, usually regarded as a sublingual gland, really consists of the
sublingual proper, with its ductus major and of about ten equivalent
alveolo-lingual glands. Mucin cells have appeared by the sixteenth week.

DEVELOPMENT OF THE TEETH

The teeth have a double origin. The enamel is from ectoderm, the
dentine and cement me.sodermal.

Enamel Organ. — There first appears in embryos of about 1 1 mm. an
ectodermal downgrowth, the dental ridge, or lamina, on the future alveolar
portions of the upper and lower jaws (Fig. 159). These laminae are parallel
and mesial to the labial grooves. At intervals, on each curved dental

Lower lip

Mandible

Labial fioij^sgKggffiF-"' Dental papilla
.•.-.;.:....•...,:•-•-- " Dental lamina

A B f

FIG. 159. — Early stages in the development of the teeth (Rose). A, at 17 mm. (>V9o); B,

at 41 mm. (X 45).

lamina, a series of thickenings develop, the anlages of the enamel organs,
which will form enamel and serve as the molds of the future teeth (Fig.
1 60). Soon, the ventral side of each enamel organ becomes concave (40
mm. C H) forming an inverted cup, and the concavity is occupied by dense
mesenchymal tissue, the dental papilla, or anlage of the dentine and pulp

DEVELOPMENT OF THE TEETH

155

(Figs. 159 B and 161). An enamel organ with dental papilla forms the
anlage of each tooth (Fig. 162). Ten such anlages of the decidual, or
milk teeth are present in the upper jaw and ten in the lower jaw of a 40 mm.
fetus (Fig. 165) . Their connection with the dental ridge is eventually lost.
The internal -cells of the enamel organs are at first compact, but later,
by the development of an intercellular matrix, the cells separate, forming

Oral epithelium

Enamel organ

A\

Dental groove

I ^X / y*J^

I x^/ /^fe\ '» ^W ^/^W^^tf

// // _^^ \; /^^-^ I/^T™\ ^^«^

IMM^ >>r \/ vb^5S^ "a

Pa#*tt« Enamel organs ^cks °f enamd or£ans

ABC D
FIG. 1 60. — Diagrams showing the early development of three teeth, one in section (Lewis and

Stohr).
Dental lamina

Epidermis

Outer enamel layer
Enamel pulp
Inner enamel layer
Dental papilla

FIG. 161. — Section through an upper incisor from a 65 mm. human fetus. X 7°-

a reticulum resembling mesenchyme, termed the enamel pulp (Fig. 161).
The outer enamel cells, at first cuboidal, flatten out and later form a fibrous
layer. The inner enamel cells bound the cup-shaped concavity of the
enamel organ. Over the crown of the tooth, these cells, the ameloblasts,
become slender and columnar in form, producing the enamel layer of the

156

THE DISSECTION OF PIG EMBRYOS

tooth along their basal ends (Fig. 163). The enamel is laid down first
as an uncalcified fibrillar layer which later becomes calcified in the form of
enamel prisms, one for each ameloblast. The enamel is formed first at
the apex of the crown of the tooth and extends downward toward the root.
The enamel cells about the future root of the tooth remain cuboidal or

Tip of tongue

F.pidermis of lip

•&jHr.:.;*. ^ .r fl>— *-.jj Enamel organ of tooth

S ubmaxillary duct — *~ ^a? .^'^L/- -. \P&J3$ — -

Sublingital duct — » ^ ^ ^r~—— — JL^___Dental papilla

r&m^*$&- I — -^' J

Meckel's cartilage
Bone of mandible

FIG. 162. — Parasagittal section through the mandible and tongue of a 65 mm. human fetus,
showing the relations of the first incisor anlage. X 14.

^Enamel pulp---

Inner enamel layer
(ameloblasts)

Enamel prisms

Denfine and
dentinal fibers

Odontoblasts

Dental pulp—--

FIG. 163.-

-Section through a portion of the crown of a developing tooth, showing the various
layers (after Tourneux in Heisler).

low columnar in form, come into contact with the outer enamel cells, and
the two layers constitute the epithelial sheath of the root ; it does not pro-
duce enamel prisms (Fig. 164).

The Dental Papilla. — The outermost cells of the dental papilla, at
the end of the four.th month, arrange themselves as a definite layer of
columnar epithelium. Since they produce the dentine, or dental bone,

DEVELOPMENT OF THE TEETH

these cells are known as odontoblasts (Fig. 164). When the dentine
layer is developed, the odontoblast cells remain internal to it, but branched
processes from them (the dentinal fibers of Tomes) extend into the dentine
and occupy the dental canaliculi (Fig. 163). Internal to the odontoblast
layer, the mesenchymal cells differentiate into the dental pulp, popularly

Dental sac

Outer layer Inner layer

Dentine

Odontoblasts

Dental papilla (future pulp)

Blood vessel

Epithelial sheath

Bony trabecula of jaw

FIG. 164. — Longitudinal section of a decidual tooth of a newborn dog. X 42. Above the
enamel, on either side, are artificial shrinkage spaces. (Lewis and Stohr).

known as the 'nerve' of the tooth. This is composed of a framework of
reticular tissue in which are found blood vessels, lymphatics, and nerve
fibers. The odontoblast layer persists throughout life and intermittently
lays down dentine, so that eventually the root canal may be obliterated.
The Dental Sac. — The mesenchymal tissue surrounding the anlage of

158

THE DISSECTION OF PIG EMBRYOS

the tooth gives rise to a dense outer layer and a more open inner layer of
fibrous connective tissue. These layers form the dental sac (Fig. 164).
Over the root of the tooth a layer of osteoblasts, or bone forming cells, de-
velops, and, the epithelial sheath formed by the enamel layers having
disintegrated, these osteoblasts deposit about the dentine a layer of spe-
cialized bone, known as the cement. The cement layer contains typical
bone cells but no Haversian systems. As the tooth grows and fills the
alveolus, the dental sac becomes a thin, vascular layer, the peridental
membrane. This has fibrous attachments to both the alveolar bone and
the cement of the tooth.

When the crown of the tooth is fully developed the enamel organ
disintegrates, and, as the roots of the teeth continue to grow, their crowns

Labial
roove

Dental
lamina

FIG. 165. — Dental lamina and anlages of the upper milk teeth in a

(Rose).

115 mm. human fetus

sixth to eighth month.
eighth to twelfth month.

approach the surface and break through the gums. The periods of
eruption of the various milk, or decidual teeth vary with race, climate,
and nutritive conditions. Usually these teeth are cut in the following
sequence :

Median Incisors

Lateral Incisors

First Molars .................. ......... ... twelfth to sixteenth month.

Canines .................................. seventeenth to twentieth month.

Second Molars ........................... twentieth to thirty-sixth month.

The permanent teeth develop precisely like the temporary set. The
anlages of those permanent teeth which correspond to the decidual, or
milk teeth, are developed in another series along the free edge of the den-
tal lamina (Fig. 160 D) and come to lie mesad of the decidual teeth (Fig.
1 66). In addition, the anlages of three permanent molars are developed
on each side, both above and below, from a backward or aboral extension

DEVELOPMENT OF THE TEETH

159

Of the dental lamina, entirely free from the oral epithelium (Fig. 165.)
The anlages of the first permanent molars appear at seventeen weeks
(180 mm. C H), those of the second molars at six weeks after birth, while
the anlages of the third permanent molars, or wisdom teeth, are not found
until the fifth year. The permanent dentition of thirty-two teeth is then-
complete.

Before the permanent teeth begin to erupt, the roots of the milk
teeth undergo partial resorption, their dental pulp dies, and they are

Permanent second molar "

Deciduous molars
- Mandibular canal

— Permanent first mola'

Permanent premolars

Permanent canine

Mental foramen
Permanent incisors

FIG. 1 66. — Skull of a five-year-old child, showing the positions of the decidual and permanent
teeth (Sobotta-McMurrich).

eventually shed. Toward the sixth year, before the shedding of the
deciduous teeth begins, each jaw may contain twenty-six teeth (Fig. 166).
The permanent teeth are cut as follows :

First Molars

Median Incisors

Lateral Incisors

First Premolars

Second Premolars

Canine \

Second Molars /
Third Molars (Wisdom Teeth) . .

. seventh year.

. eighth year.

. ninth year.

. tenth year.

. eleventh year.

. thirteenth to fourteenth year.

. seventeenth to fortieth year.

160 THE DISSECTION OF PIG EMBRYOS

The teeth of vertebrates are homologues of the placoid scales of elasmobranch fishes
(sharks and skates). The teeth of the shark resemble enlarged scales, and many genera-
tions of teeth are produced in the adult fish. In some mammalian embryos three, or even
four, dentitions are present. The primitive teeth of mammals are of the canine type, and
from this conical tooth the incisors and molars have arisen. Just how the cusped tooth
differentiated — whether by the fusion of originally separate units, or by the development
of cusps on a single primitive tooth — is debated.

Anomalies. — Dental anomalies are frequent and may consist in the congenital absence
of some or all of the teeth, or in the production of more than the normal number. Defect-
ive teeth are frequently associated with hare lip. Cases have been noted in which, owing
to defect of the enamel organ, the enamel was entirely wanting. Third dentitions have been
recorded, and occasionally fourth molars may be developed behind the wisdom teeth.

CHAPTER VII

THE ENTODERMAL CANAL AND ITS DERIVATIVES: THE BODY

CAVITIES

WHEN the head- and tail folds of the embryo develop, there are
formed, both cranial and caudal to the spherical vitelline sac, blind
entodermal tubes, the fore- gut and kind-gut respectively (Figs. 79, 255 and
167,4). The region between these intestinal tubes, open ventrally into

Pharynx

Pharyngeal
membrane

Cloacal
membrane
Allantois

Cloaca

FIG. 167. — Diagrams showing in median sagittal section the human alimentary canal. X 35-
A, 2 mm. embryo (modified after His); B, 2.5 mm. embryo (after Thompson).

the yolk sac, is sometimes termed the mid-gut. As the embryo and the
yolk sac at first grow more rapidly than the connecting region between
them, this region is apparently constricted and becomes the yolk stalk,
or vitelline duct. At either end the entoderm comes into contact ven-
trally with the ectoderm. Thus there are formed the pharyngeal membrane
of the foregut and the cloacal membrance of the hind-gut. In 2 mm.
11 161

1 62 THE ENTODERMAL CANAL AND THE BODY CAVITIES

embryos the pharyngeal membrane separates the ectoderma mouth
cavity, or stomod&um, from the pharyngeal cavity of the fore-gut. In
front of the membrane is the ectodermal diverticulum, Rathkes pouch.
In 2.5 to 3 mm. embryos (Fig. 167 B) the pharyngeal membrane ruptures
and the stomodaeum and pharynx become continuous. The original
blind termination of the fore-gut apparently forms SeesseVs pouch, a
temporary landmark of no special significance.

The fore-gut later forms part of the oral cavity and is futher dif-
ferentiated into the pharynx and its derivatives, and into the esophagus,
respiratory organs, stomach, duodenum, jejunum, and a portion of the
ileum. From the duodenum arise the liver and pancreas. The hind-gut,
beginning at the attachment of the yolk stalk extends caudally to the
cloaca, into which the allantois opens in 2 mm. embryos. The hind-gut
is differentiated into the ileum, caecum, colon, and rectum. The cloaca
is subdivided into the rectum and urogenital sinus (for its development
see Chapter VIII). At the same time the cloacal membrane is separated
into a urogenital membrane and into an anal membrane. The latter
eventually ruptures, forming the anus. The yolk stalk usually loses its
connection with the entodermal tube in embryos of about 7 mm. (Fig. 179).

We have seen how the palatine processes divide the primitive oral
cavity into the nasal passages and mouth cavity of the adult, and have
described the development of the tongue, teeth, and salivary glands —
organs derived wholly of in part from the ectoderm. It remains to
trace the development of the entodermal pharynx and intestinal tract,
and their derivatives.

THE PHARYNGEAL POUCHES

There are developed early from the lateral wall of the pharynx paired
entodermal outgrowths which are formed in succession cephalo-caudad.
In 4 to 5 mm. embryos, five pairs of such pharyngeal pouches are present,
the fifth pair being rudimentary (Figs. 86 and 87). Meantime, the
pharynx has been flattened dorso-ventrally and broadened laterally
and cephalad, so that it is triangular in ventral view (Figs. 87 and 168).

From each pharyngeal pouch develop small dorsal and large ventral
diverticula. All five pouches come into contact with the ectoderm
of corresponding branchial grooves, fuse with it, and form the closing plates.
Although the closing plates become perforate in human embryos only
occasionally, these pouches, neverthless, are homologous to the functional
branchial clefts of fishes and tailed amphibia. The first and second
pharyngeal pouches soon connect with the pharyngeal cavity through wide
common openings. The third and fourth pouches grow laterad and their
diverticula communicate with the pharynx through narrow ducts in 10 to

THE TONSIL

12 mm. embryos (Fig. 168). When the cervical sinus (p. 91) is formed,
the ectoderm of the second, third, and fourth branchial clefts is drawn
out to produce the transient branchial and cervical ducts and the cervical
vesicle. These are fused at the closing plates with the entoderm of the
second, third, and fourth pharyngeal pouches.

The fate of these entodermal pouches is varied and spectacular.
The first differentiates into the tympanic cavity of the middle ear and into

Branchial duct 2 Epithelial body of jd pouch

Branchial groove 1

Cervical sinus

Cervical vesicle

Thymus anlage
Parathyreoid of jth pouch

Pharyngeal pouch i
Pharyngeal pouch 2
Pharyngeal pouch j

Pharyngeal pouch 4
Pharyngeal pouch 5
Esophagus

Epical bud of right lung

Stomach
Dorsal pancreas

FIG. 1 68. — A reconstruction of the pharynx and fore-gut of an 1 1.7 mm. human embryo, seen
in dorsal view (after Hammar). The ectodermal structures are stippled.

the auditory (Eustachian) tube. The second becomes the palatine tonsil
in part. The third, fourth, and fifth pouches give rise to a series of ductless
glands, the thymus, parathyreoids, and the ultimobranchial bodies.

THE TONSIL

By the growth and lateral expansion of the pharynx, the second
pouch is absorbed into the pharyngeal wall, its dorsal angle alone persisting,
to be transformed into the tonsillar and supratonsillar fosses. A mound
of mesodermal lymphoid tissue presses against the epithelium of the
tonsillar fossae in 140 (CR?) fetuses. This association constitutes the
palatine tonsil. Crypts arise by the hollowing of solid epithelial ingrowths.

i64

THE ENTODERMAL CANAL AND THE BODY CAVITIES

A subepithelial infiltration of lymphocytes during the sixth month gives rise to the
median pharyngeal tonsil, which like the lingual tonsil is not of pharyngeal pouch origin.
Immediately caudad is a recess, the pharyngeal bursa, formed by a protracted connection
of the epithelium with the notochord (Huber). It bears no relation to Seesel's pouch.
According to Hammar, the lateral pharyngeal recess of (Rosenmuller) is not a persistent
portion of the second pouch, as His asserted.

Anomalies. — Imperfect closure of the branchial clefts (usually the second) leads to
the formation of cysts, diverticula, or even fistulas.

THE THYMUS

The thymus anlage appears in 10 mm. embryos as a ventral and medial
prolongation of the third pair of pouches (Figs. 168 and 169). The ducts
connecting the diverticula with the pharynx soon disappear so that the
thymus anlages are set free. At first hollow tubes, they soon lose their
cavities and their lower ends enlarge and migrate caudally into the thorax,

Foramen cacum

Palatine tonsil -*&% n
Parathyreoid anlages

Thyreoglossal duct

Thyrcoid anlage
Thymus anlages I *^ Trachea

Ultim abranchial body

FIG. 169. — Diagram of the pharynx and its derivatives. (Modified after Groschuff and Kohn.)
I-V, first to fifth pharyngeal pouches.

usually passing ventral to the left vena anonyma. Their upper ends
become attentuate and atrophy, but may persist as an accessory thymus
lobe (Kohn). The enlarged lower ends of the anlages form the body of
the gland, which is thus a paired structure (Fig. 170). At 50 mm. (CR)
the thymus still contains solid cords and small closed vesicles of entodermal
cells. From this stage on, in development, the gland becomes more and
more lymphoid in character. Its final position is in the thorax, dorsal
to the cranial end of the sternum. It grows under normal conditions
until puberty, after which its involution begins. This process proceeds
slowly in healthy individuals, rapidly in case of disease. True atrophy
of the parenchyma enters at about the fiftieth year.

The ventral diverticulum of the fourth pouch is a rudimentary thymic
anlage. It usually atrophies.

ULTIMOBRANCHIAL OR POSTBRANCHIAL BODIES 165

It is now generally believed that the entodermal epithelium of the thymus is converted
into reticular tissue and thymic corpuscles. The latter are the atrophic and hyalinized
remains of embryonic tubules and cords (Marine, 1915). The lymphoid cells were regarded
by Stohr as entodermal in origin, but most observers derive them from the mesoderm.

Jugular Carotid Carotid

vein artery artery

Jugular vein

Thyraud \-\%\ A Mi Fi Thyreoid

Parathyreoid IV. ~ V\^L i^f^f— Parathyreoid IV.

Parathyroid III. V»«f5^P7/I/ Parathyreoid III.

Thymus -

Superior vena cava

FIG. 1 70. — Reconstruction of the thymus, thyreoid and parathyreoid glands in a 26 mm. human
embryo (after Tourneaux and Verdun). X 15.

THE PARATHYREOID GLANDS

The dorsal diverticula of the third and fourth pharyngeal pouches
each give rise to a small mass of epithelial cells termed a parathyreoid
gland (Fig. 169). Two pairs of these bodies are thus formed, and, with
the atrophy of the ducts of the pharyngeal pouches, they are set free and
migrate caudal ward. They eventually lodge in the dorsal surface of the
thyreoid gland, the pair from the third pouch lying one on each side at
the caudal border of the thyreoid in line with the thymus anlages (Fig. 1 70).
The pair of parathyreoids derived from the fourth pouches are located
on each side near the cranial border of the thyreoid. Their solid bodies
are broken up into masses and cords of polyhedral entodermal cells
intermingled with blood vessels. In postfetal life, lumina may appear in
the cell masses and fill with a colloid-like secretion.

THE ULTIMOBRANCHIAL OR POSTBRANCHIAL BODIES

The ultimobranchial body is the derivative of the fifth pharyngeal
pouch (Fig. 169). By the atrophy of the ducts of the fourth pouches
they are set fra and migrate caudad with the parathyreoids. Each
forms a hollow^esicle which has been erroneously termed the lateral
thyreoid. According to Grosser and Verdun, it takes no part in forming
thyreoid tissue, but atrophies. Kingsbury (1915) denies the origin of
the ultimobranchial body from any specific pouch, and asserts it is "merely
formed by a continued growth activity in the branchial entoderm."

1 66

THE ENTODERMAL CANAL AND THE BODY CAVITIES

THE THYREOID GLAND

In embryos with five to six primitive segments (1.4 mm), there
appears in the mid-ventral wall of the pharynx, between the first and
second branchial arches, a small out-pocketing, the thyreoid anlage. In
2.5 mm. embryos it has become a stalked vesicle (Figs. 167 B an(i 87).
Its stalk, the thyreoglossal duct, opens at the aboral border of the tuber-
culum impar of the tongue (Figs. 157 A); this spot is represented perma-
nently by the foramen caecum (Fig. 180). The duct soon atrophies and the
bilobed gland anlage (Fig. 169) loses its lumen and breaks up into irregular,
solid, anastomosing plates of tissue as it migrates caudad. It takes up a
transverse position with a lobe on each side of the trachea and larynx
(Fig. 170). In embryos of 24 mm., discontinuous lumina begin to appear
in swollen portions of the plates; these represent the primitive thyreoid
follicles (Norris.)

Anomalies — Persistent portion of the thyreoglossal duct may form cysts or even fistulae.

THE LARYNX, TRACHEA AND LUNGS

In embryos of 23 segments, the anlage of the respiratory organs
appears as a groove in the floor of the entodermal tube, just caudal to^the

Trachea

Respiratory anlage

Esophagus

Trachea

Trachea

Apical bu
Primary bronchus

' Ventral bud
Esophagus

FIG. 171. — Diagrams of stages in the early development of the trachea and lungs of human
embryos (based on reconstructions by Bremer, Broman, Grosser, and Narath). X about 50.
A, 2.5 mm.; B, 4 mm.; C, stage B in side view; D, 5 mm.; E, 7 mm.

pharyngeal pouches. This groove produces an external ridge on the
ventral wall of the tube, a ridge which becomes larger and rounded at its
caudal end (Fig. 171). The laryngo-tracheal groove and the ridge are the

LARYNX, TRACHEA AND LUNGS

l67

FIG. 172. — Entrance to
larynx in a 15 to 1 6 mm. human
embryo (from Kallius). X 15.
p, Pharyngo-epiglottic fold; e,
epiglottic fold ; I.e., lateral part
of epiglottis; cun., cuneiform
tubercle; corn., corniculate
tubercule.

b.l.

anlages of the larynx and trachea. The rounded end of the ridge is the

unpaired anlage of the lungs.

Externally, two lateral longitudinal grooves

mark off the dorsal esophagus from the ventral

respiratory anlages. The lung anlage rapidly

increases in size, and becomes bilobed in em-
bryos of 4 to 5 mm. A fusion of the lateral

furrows progressing cephalad, constricts first

the lung anlages and then the trachea from the

esophagus. At the same time the laryngeal

portion of the groove and ridge advances

cranially until it lies between the fourth

branchial arches (Fig. 87). At 5 mm. the

respiratory apparatus consists of the laryngeal

groove and ridge, the tubular trachea, and the

two lung buds (Fig. 711 D).

The Larynx. — In embryos of 5 to 6 mm.

the oral end of the laryngeal groove is bounded on either side by two

rounded prominences, the arytenoid swellings, which, continuous orally

with a transverse ridge, form the
furcula of His (Fig. 157 B). The
transverse ridge becomes the
epiglottis, and, as we saw in con-
nection with the development of
the tongue, it is derived from the
third and fourth branchial arches.
In embryos of 15 mm. the ary-
tenoid swellings are bent near the
middle. Their caudal portions
become parallel, while their ceph-
alic portions diverge nearly at
right angles (Fig. 172). The glottis,
opening into the larynx, thus be-
comes T-shaped and ends blindly,
as the laryngeal epithelium has
fused. In 40 mm. (CR) fetuses
this fusion is dissolved, the ary-
tenoid swellings are withdrawn
from contact with the epiglottis,
and the entrance to the larynx
becomes oval in form (Fig. 173).

At 27 mm. the ventricles of the larynx appear, and, at 37 mm. (CR),

their margins indicate the position of the vocal cords. The elastic and

muscle fibers of the cords are developed by the fifth month.

pl.pt>.* -

f.i.a _.

FIG. 173. — The larynx of 160 to 230 mm.
human fetus (Soulie and Bardier). X 6. b.l..,
Base of tongue; e., epiglottis; f.i.a., interary-
tenoid fissure; o.l., orifice of larynx ; pl.a.e., plica
ary-epiglottica; pl.ph.e., plica pharyngo-
epiglottica: cun., cuneiform tubercle; corn.,
corniculate tubercle.

1 68 THE ENTODERMAL CANAL AND THE BODY CAVITIES

At the end of the sixth week the cartilaginous skeleton of the larynx is indicated by
surrounding condensations of mesenchyme. The cartilage of the epiglottis appears rela-
tively late. The thyreoid cartilage is formed as two lateral plates, each of which has two
centers of chondrification. These plates grow ventrad and fuse in the median plane.

The anlages of the cricoid and arytenoid cartilages are at first continuous. Later, sepa-
rate cartilage centers develop for the arytenoids. The cricoid is at first incomplete dorsad,
but eventually forms a complete ring. The cricoid may therefore be regarded as a modi-
fied tracheal ring. The corniculate cartilages represent separated portions of the aryte-
noids. The cuneiform cartilages are derived from the cartilage of the epiglottis.

The Trachea. — This gradually elongates during development and its
columnar epithelium becomes ciliated. Muscle fibers and the anlages
of the cartilaginous rings appear at 17 mm. The glands develop as
ingrowths of the epithelium during the last five months of fetal life.

FIG. 174. — Ventral and dorsal views of the lungs from a human embryo of about 9 mm.
(after Merkel). Ap., Apical bronchus; Di, D2, etc., dorsal, Vi. Vj, ventral bronchi;
Jc. infracardiac bronchus.

The Lungs. — Soon after the lung anlages, or stem buds, are formed
(in 5 mm. embryos), the right bronchial bud becomes larger and is directed
more caudally (Fig. 171). At 7 mm. the stem bronchi give rise to two
bronchial buds on the right side, to one on the left. The smaller bronchial
bud on the right side is the apical bud. The right and left chief buds,
known as ventral bronchi, soon bifurcate. There are thus formed three
bronchial rami on the right side two on the left, and these correspond to
the primitive lobes of the lungs (Figs. 168 and 174).

On the left side, an apical bud is interpreted as being derived from the first ventral
bronchus (Fig. 174). It develops later and remains small so that a lobe corresponding to
the upper lobe of the right lung is not developed (Narath). The upper lobe of the left
lung thus would correspond to the upper and middle lobes of the right lung.

The bronchial anlages continue to branch in such a way that the stem
bud is retained as the main bronchial stem (Fig. 1 74). That is, the branch-
ing is monopodial, not dichotomous, lateral buds being given off from the
stem bud proximal to its growing tip. Only in the later stages of develop-

LARYNX, TRACHEA AND LUNGS

169

ment has dichotomous branching of the bronchi and the formation of two
equal buds been described. Such buds, formed dichotomously.^do not
remain of equal size (Flint) .

Mediastinum

PI euro-peritoneal membran>

Visceral pleura^
Coronary ligament

Inferior vena cava

Parietal pleura

Plenral cavity
Pleura-peritoneal membrane

Esophagus
Sinusoids of liver

Ductus venosus

Falciform ligamcn

Wall of umbilical cord

FIG. 175. — Transverse section through the lungs and pleural cavities of a 10 mm. human

embryo. X 23.

The entodermal anlages of the lungs and trachea are developed in a
median mass of mesenchyme dorsal and crainial to the peritoneal cavity.
This tissue forms a broad mesentery termed the mediastinum (Fig. 175).
The right and left stem buds of
the. lungs grow out laterad, carry-
ing with them folds of the
mesoderm. The branching of the
bronchial buds takes place within
this tissue which is covered by the
mesothelial lining of the body
cavity. The terminal branches
of the bronchi are lined with ento-
dermal cells ; these flatten out and

Pulmonary artery

, ^^ Pulmonary vein

XV? -':'^N,

FIG. 176. — Ventral view of the lungs of a 10.5
mm. embryo, showing the pulmonary arteries
and veins (His in McMurrich). X 27. Ep.,
Apical bronchus; /, //, primary bronchi.

form the respiratory epithelium of

the adult lungs. The surrounding

mesenchyme differentiates into the

muscle, connective tissue, and

cartilage plates of the lung, tracheal, and bronchial walls. Into it grow

blood vessels and nerve fibers. When the pleural cavities are separated

from the pericardial and peritoneal cavities, the mesothelium covering

170 THE ENTODERMAL CANAL AND THE BODY CAVITIES

the lungs, with the connective tissue underlying it, becomes the visceral
pleura. The corresponding layers lining the thoracic wall form the
parietal pleura. These layers are derived respectively from the visceral
(splanchnic) and parietal (somatic) mesoderm of the embryo.

In 1 1 mm. embryos the two pulmonary arteries, from the sixth pair of
aortic arches, course lateral then dorsal to the stem bronchi (Fig. 176).
The right pulmonary artery passes ventral to the apical bronchus of the
right lung. The single pulmonary vein receives two branches from each
lung, a larger vein from each lower lobe, a smaller vein from each upper
lobe, including the middle lobe of the right side. These four pulmonary
branches course ventrad and drain into the pulmonary trunk. When
this common stem is taken up into the wall of the left atrium, the four
pulmonary veins open directly into the latter.

According to Kolliker, the air cells, or alveoli, of the lungs begin to form in the sixth
month and their development is completed during pregnancy. Elastic tissue appears
during the fourth month in the largest bronchi. The abundant connective tissue found
between the bronchial branches in early fetal life becomes reduced in its relative amount as
the alveoli of the lungs are developed.

Before birth the lungs are small, compact, and possess sharp margins. They lie in
the dorsal portion of the pleural cavities. After birth they normally fill with air, ex-
panding and completely filling the pleural cavities. Their margins become rounded and the
compact fetal lung tissue, which resembles that of a gland in structure, become light and
spongy, owing to the enormous increase in the size of the alveoli and blood vessels. Be-
cause of the greater amount of blood admitted to the lungs after birth, their weight is
suddenly increased.

Anomalies. — Variations occur in the size and number of lobes of the lungs; rarely
there is a third lobe on the left side. In the most common anomaly involving both esopha-
gus and trachea, the esophagus is divided transversely, the trachea opening into the lower
segment, while the upper portion ends as a blind sac.

THE ESOPHAGUS, STOMACH AND INTESTINE

The Esophagus. — -The esophagus in 4 to 5 mm. embryos' is a short
tube, flattened laterally, extending from the pharynx to the stomach.
It grows rapidly in length, and in 7.5 mm. embryos its diameter decreases
both relatively and absolutely (Forssner). At this stage the esophageal
epithelium is composed of two layers of columnar cells, but at birth they
number nine or ten.

In 20 mm. embryos, vacuoles appear in the epithelium and increase the size of the
lumen, which, however, is at no time occluded. Glands begin to develop as epithelial
ingrowths at 78 mm. (CR). The circular muscle layer is indicated at 10 mm. but the
longitudinal muscle fibers do not form a definite layer until 55 mm. (C R). These layers
appear in similar time-sequence throughout the entire digestive tract.

Anomalies. — There may be atresia. This usually involves fistulous relations with
the trachea, as already described (p. -170).

THE ESOPHAGUS, STOMACH AND INTESTINE 171

The Stomach. — The stomach appears in embryos of 4 to 5 mm. as a
laterally flattened, fusiform enlargement of the fore-gut caudal to the lung
anlages (Figs. 177 and 178). Its epithelium is early thicker than that of
esophagus and is surrounded by a heavy layer of splanchnic mesoderm.
It is attached dorsally to the body wall by its mesentery, the greater
amentum, and ventrally to the liver by the lesser amentum (Fig. 190 B).
The dorsal border of the stomach both bulges locally to form the fundus,
and also grows more rapidly than the ventral wall throughout its extent,
thus producing the convex greater curvature. The whole stomach be-
comes curved and its cranial end is displaced to the left by the enlarging

Pharynx
Root of tongue

Thyreoid
Tip of tongue

Rathke's pouch
Trachea
Stomach

Liver
Dorsal pancreas

Hepatic diverti-
culum

Yolk stalk

Allantois

Mesonephric duct

• Cloaca

Hind-gul

FIG. 177. — Median sagittal section of a 5 mm. human embryo, to show the digestive canal
(modified after Ingalls). X 14.

liver (Fig. 168). This forms a ventral concavity, the lesser curvature, and
produces the first flexure of the duodenum.

The rapid growth of the gastric wall along its greater curvature also
causes the stomach to rotate upon its long axis until its greater curvature,
or primitive dorsal wall, lies to the left, its ventral wall, the lesser curvature,
to the right (Fig. 201). The original right side is now dorsal, the left
side ventral in position, and the caudal, or pyloric end of the stomach is
ventral and to the right of its cardiac, or cephalic end. The whole organ
extends obliquely across the peritoneal cavity from left to right (cf . Fig.
138). The change in position progresses rapidly and is already completed
early in the second month (12 to 15 mm.). The rotation of the stomach
explains the asymmetrical position of the vagus nerves of the adult organ,

172

THE ENTODERMAL CANAL AND THE BODY CAVITIES

the left nerve supplying the ventral wall of the stomach, originally the
left wall, while the right vagus supplies the dorsal wall, originally the
right.

In 17 mm. embryos the stomach has reached its permanent position, the cardia
having descended through about ten segments, the pylorus through six or seven.

Tongue

Laryngo-tracheal
groove

Rathke's.
pouch

Metane phros

Mesonephric duct

Allantois

FIG. 178. — Reconstruction of a 5 mm. human embryo, showing the entodermal canal and its
derivatives (His in Kollmann). X 25.

Gastric pits are indicated in 16 mm. embryos, and, at 100 mm. (C R), glands cells of
the gastric glands are differentiated from the gastric epithelium. The gastric pits num-
ber 270,000 at birth but increase by fission to nearly 7 million in the adult. The cardiac
glands are developed early (91 mm. (C R) fetuses).

At 10 mm. the stomach wall is composed of three layers: the entodermal epithelium,
a thick mesenchymal layer, and the peritoneal mesothelium. At 16 mm. the circular
muscle layer is indicated by condensed mesenchyma; a heavier ring forms the pyloric
sphincter. At 91 mm. (C R) the cardiac region shows a few longitudinal muscle fibers,
which become distinct in the pyloric region at 240 mm. (CR).

THE ESOPHAGUS. STOMACH AND INTESTINE

173

The Intestine. — -In 5 mm. embryos (Fig. 177), the intestine, beginning
at the stomach, consists of the duodenum (from which are given off the
hepatic diverticulum and dorsal pancreas), and the cephalic and caudal
limbs of the intestinal loop, which bends ventrad and connects with the
yolk stalk. Caudally, the intestinal tube expands to form the cloaca.
It is supported from the dorsal body wall by the mesentery (Fig. 178).

From 5 to 9 mm. the ventral bend of the intestinal loop becomes more
marked and the attachment of the yolk stalk to it normally disappears

Rathke's pouch

Hypophysis (post, lobe)
Thyreoid

Notochord

Pericardium

Cloacal membrane

Dorsal pancreas
Ventral pancreas

Urogenital sini4s I -4 — i^e^*\

/ 1 \ Peritoneal cavity*

Tail gut \ Mesonephric duct
Rectum

FIG. 179. — Diagram, in median sagittal section, showing the digestive canal of a 9 mm. human
embryo (adapted from Mall). X 9-

(Fig. 179). At this stage the dorsal pancreatic anlage has been developed
from the duodenum, and, in the caudal limb of the intestinal loop, there
is formed an enlargement, due to a ventral bulging of the gut wall, that
marks the anlage of the ccecum and the boundary line between the large
and small intestine.

Succeeding changes in the intestine consist: (i) in its torsion and
coiling, due to its rapid elongation, and (2) in the differentiation of its
several regions. As the gut elongates in 9 to 10 mm. embryos, the intes-

174 THE ENTODERMAL CANAL AND THE BODY CAVITIES

tinal loop rotates. As a result, its caudal limb lies at the left and cranial
to its cephalic limb (Fig. 179).

The small intestine soon lengthens rapidly, and, at 17 mm. (Fig. 180),
forms loops within the umbilical cord. This constitutes a normal umbili-
cal hernia. Six primary loops occur and these may be recognized in the
arrangement of the adult intestine. In embryos of 42 mm. the intestine
has returned from the umbilical cord into the abdominal cavity through a
rather small aperture; the ccelom of the cord is soon after obliterated .

Brain

Hypophysis

Foramen cacum
-Root of tongue

Esophagus

Trachea
-Notochord
•Spinal cord

Urogenital sinus
Anal membrane

FIG." 1 80. — Diagrammatic median sagittal section of a 17 mm. human embryo, showing the
digestive canal (modified after Mall). X 5-

In embryos between 10 and 30 mm., vacuoles appear in the wall of the duodenum and
epithelial septa completely block the lumen. The remainder of the small intestine remains
open, although vacuoles form in its epithelium. Villi appear as rounded elevations of the
epithelium at 23 mm. (Johnson). They begin to form at the cephalic end of the jejunum,
and, at 130 mm. (CR), they are found throughout the small intestine (Berry). Intestinal
glands appear as ingrowths of the epithelium about the bases of the villi. They develop
first in the duodenum at 91 mm. (CR). The duodenum glands (of Brunner) are said to
appear during the fourth month (Brand). In embryos of 10 to 12.5 mm. the circular
muscle layer of the intestine first forms. The longitudinal muscle layer is not distinct
until 75 mm. (CR).

THE ESOPHAGUS, STOMACH AND INTESTINE

J75

The large intestine, as seen in 9 mm. embryos (Fig. 179), forms a tube
extending from the caecum to the cloaca. It does not lengthen so rapidly

A B C

t~_ FIG. 181. — Three stages showing the development of the digestive tube and the mesen-
teries in the human fetus (Tourneux in Heisler).!, Stomach; 2, duodenum; 3, small intestine;
4, colon; 5, yolk stalk; 6, caecum; 7, great omentum; 8, mesoduodenum; 9, mesentery, 10,
mesocolon. The arrow points to the orifice of the omental bursa. The ventral mesentery is
not shown.

as the small intestine, and, when the intestine is withdrawn from the um-
bilical cord (at 42 mm. C R), its cranial, or caeca! end lies on the right side

Ascending
mesocolon

Ascending colon

Cacum

Processus T+jjjj? N^fffo Processus _

vermiformis ^^^ x*^ vermiformis

FIG. 182. — The caecum and vermiform process of a human fetus of 50 mm. (Kollmann): A,
from the ventral side; B, from the dorsal side.

and dorsal to the small intestine (Fig. 181). It extends transversely to
the left side as the transverse colon, then, bending abruptly caudad as the

i76

THE ENTODERMAL CANAL AND THE BODY CAVITIES

descending colon, returns by its iliac flexure to the median plane and forms
the rectum. In stages between 100 and 200 mm. (CR) the lengthening of
the colon causes the caecum and cephalic end of the colon to descend to-
ward the pelvis" (Fig- 181). The ascending colon thus takes the position
which it occupies in the adult.

The distal end of the caeca! anlage early lags in development, and, at
65 mm. (CR), the vermiform process is distinct from the c&cum. These
structures make a sharp U-shaped bend with the colon at 42 mm. (CR),
and this flexure gives rise to the colic valve (Toldt) .

The circular muscle layer of the large intestine appears first at 23 mm., the longitudinal
layer at 75 mm. (C R). In 55 mm. (C R) fetuses villi are present.

Glandular secretions and desquamated entodermal cells, together with swallowed
amniotic fluid, containing lanugo hairs and vernix caseosa, collect in the fetal intestine.
This mass, yellow to brown in color, is known as meconium. At birth the intestine and its
contents are perfectly sterile.

Anomalies. — The intestine may show atresia. This occurs most often in the duo-
denum as a retention of the embryonic
occlusion (p. 174).

In 2 per cent of all adults there is a
persistence of the proximal end of the yolk
stalk to form a pouch, Meckel's diverticu-
lum of the ileum. This varies between 3
and 9, or more, cm. in length and lies
about 80 cm. above the colic valve. It
is clinically important as it may cause
intestinal strangulation in infants.

Congenital umbilical hernia is due
either to the continuance of the normally
transitory embryonic condition or to a
secondary protrusion of the viscera . Other
hernias are explained on pp. 195 and 225.

THE LIVER

In embryos of 2.5 mm. the
liver anlage is present as a median
ventral outgrowth from the ento-
FIG. 183.— Model of the liver anlage of a 4 dermof thefore-gut, just cranial to

mm. human embryo (Bremer). X 160. In., the yolk stalk (Fig 167 B) Its

S iniC°ntaCt *ick walls enclose a cavity which
is continuous with that of the gut.
This hepatic diverticulum becomes embedded at once in a mass of
splanchnic mesoderm, the septum transversum. Cranially, the septum
will contribute later to the formation of the diaphragm ; caudally, in the
region of the liver anlage, it becomes the ventral mesentery (Fig. 189).
Thus, from the first, the liver is in close relation to the septum trans-

THE LIVER

177

versum, and later when the septum becomes a part of the diaphragm the
liver remains attached to it.

In embryos 4 to 5 mm. long, solid cords of cells proliferate from the
ventral and cranial portion of the hepatic diverticulum (Fig. 86). These
cords anastomose and form a crescentic mass with wings extending dorsal
and lateral to the gut (Fig. 177). This mass, a network of solid trabeculae,
is the glandular portion of the liver. The primitive, hollow diverticulum
later differentiates into the gall bladder and the large biliary ducts.

Referring to Fig. 88, it will be seen that the liver anlage lies between
the vitelline veins and is in close proximity to them laterally. The veins
send anastomosing branches into the ventral mesentery. The trabeculae
of the expanding liver grow between and about these venous plexuses, and

FIG. 184.

-The trabeculae and sinusoids of the liver in section (after Minot). X 300. Tr.
Trabeculas of liver cells; Si., sinusoids.

the plexuses in turn make their way between and around the liver cords
(Fig. 183). The vitelline veins on their way to the heart are thus sur-
rounded by the liver and largely subdivided into a network of vessels
termed sinusoids. The endothelium of the sinusoids is closely applied
to the cords of liver cells, which, in the early stages, contain no bile
capillaries (Fig. 184). The transformation of the vitelline veins into the
portal vein and the relations of the umbilical veins to the liver will be
treated in Chapter IX.

The glandular portion of the liver grows rapidly, and, in embryos of 7
to 8 mm., is connected with the primitive hepatic diverticulum by a single
cord of cells only, the hepatic duct (Fig. 185 A). That portion of the
hepatic diverticulum distal to the hepatic duct is now differentiated into
the terminal, solid gall bladder and its cystic duct. Its proximal portion
forms the ductus choledochus. In embryos of 10 mm. (Fig. 185 B], the

i78

THE ENTODERMAL CANAL AND THE BODY CAVITIES

gall bladder and ducts have become longer and more slender. The hepa-
tic duct receives a right and left branch from the corresponding lobes of
the liver. The gall bladder is without a lumen up to the 15 mm. stage.
Later its cavity appears, surrounded by a wall of high, columnar epithelium.

flepatic duct

Ductus choledochus

Ventral pancreas

Gall bladder

Cystic dud

Cystic duct
Ductus choledochus

Ventral pancrea

•Duodenum

Duct of dorsal'

pancreas
Head of dorsal pancreas '

Duodenum

Tail of
dorsal
pancreas

FIG. 185. — Reconstructions showing the development of the hepatic diverticulum and
pancreatic anlages. A, 7.5 mm. human embryo (after Thyng), X 50; B, 10 mm. human
embryo, X 33-

The glandular portion of the liver develops fast and is largest relative
to the size of the body at 31 mm. (Jackson). In certain regions the liver
tissue undergoes degeneration, and especially is this true in the peripheral

FIG. 186. — Diagrams of three stages of the portal and hepatic veins in a growing liver:
a, Hepatic side; d, portal side; b and c, successive stages of the hepatic vein; e and/, successive
stages of the portal vein (Mall).

portion of the left lobe. In general, the external lobes of the liver are
moulded under the influence of the fetal vitelline and umbilical trunks.
The development of the ligaments of the liver is described on p. 193.

THE PANCREAS

I79

During the development of the liver the endothelial cells of the sinusoids become
stellate in outline, and thus form an incomplete layer. From the second month of fetal
life to some time after birth, blood cells are actively developed between the hepatic cells
and the endothelium of the sinusoids. At 22 mm. hollow interlobular ducts develop,
spreading inward from the hepatic duct along the larger branches of the portal vein. In
44 mm. (C R) fetuses, bile capillaries with cuticular borders are present, most numerous
near the interlobular ducts with which some of them connect. At birth, or shortly after,
the number of liver cells surrounding a bile capillary is reduced to two, three, or four.
Secretion of the bile commences at about the end of the third fetal month.

The lobules, or vascular units of the liver, are formed, according to Mall, by the pe-
culiar and regular manner in which the veins of the liver branch. The primary branches
of the portal vein extend along the periphery of each primitive lobule, parallel to similar
branches of the hepatic veins that drain the blood from the center of each lobule (Fig. 186).
As development proceeds, each primary branch becomes a stem, giving off on either side
secondary branches which bear the same relation to each other and to new lobules as did
the primary branches to the first lobule. This process is repeated until thousands of liver
lobules are developed.

Until the 20 mm. stage, the portal vein alone supplies the liver. The hepatic artery,
from the coeliac axis, conies into relation first with the hepatic duct and gall bladder.
Later, it grows into the connective tissue about the larger bile ducts and branches of the
portal vein, and also supplies the capsule of the liver.

Anomalies. — A common anomaly of the liver consists in its subdivision into multiple
lobes. Absence or duplication of the gall bladder and of the ducts may occur. In some
animals (horse, elephant) the gall bladder is normally absent.

THE PANCREAS

Two pancreatic anlages are developed almost simultaneously in
embryos of 3 to 4 mm. The dorsal pancreas arises as a hollow outpocket-
ing of the dorsal duodenal wall, just cranial to the hepatic diverticulum
(Fig. 177). At 7.5 mm. it is separated from the duodenum by a slight
constriction and extends into the dorsal mesentery (Fig. 185 A). The
ventral pancreas develops in the inferior angle between the hepatic diver-
ticulum and the gut (Lewis), and its wall is at first continuous with both.
With the elongation of the ductus choledochus its origin is transferred to
this portion of the diverticulum.

Of the two pancreatic anlages, the dorsal grows more rapidly, and, in
10 mm. embryos, forms an elongated structure with a central duct and
ii regular nodules upon its surface (Fig. 185 B}. The ventral pancreas
is smaller and develops a short, slender duct that opens into the ductus
choledochus. When the stomach and duodenum rotate, the pancreatic
ducts shift their positions as well. At the same time, growth and bending
of the bile duct to the right bring the ventral pancreas into close proximity
with the dorsal pancreas (Figs. 185 and 187).

In embryos of 20 mm., the tubules of the dorsal and ventral pancreatic
anlages interlock (Fig. 187 B}. Eventually, anastomosis takes place be-

l8o THE ENTODERMAL CANAL AND THE BODY CAVITIES

tween the two ducts, and the duct of the ventral pancreas, plus the distal
segment of the dorsal duct, persists as the functional pancreatic duct
(of Wirsung) of the adult. The proximal portion of the dorsal pan-
creatic duct forms the accessory duct (of Santorini), which remains per-
vious, but becomes a tributary of the chief pancreatic duct. The ventral
pancreas forms part of the head and uncinate process of the adult gland.
The dorsal pancreas takes part in forming the head and uncinate process,
and comprises the whole of the body and tail.

Accessory pancreatic duct

Dorsal pancreatic duct ^Stomackj^ / Dorsal pancreas

Dorsal pancreas

, Ventral pancreas -«^^i

Ventral pancreatic duct lT\ Ventrd Pa^

Bile duct Bife duct Pancreatic duct

FIG. 187. — Two stages showing the development of the human pancreas: A, Embryo of 8 mm. ;
B, embryo of about 20 mm. (after Kollmann).

In 10 mm. embryos the portal vein separates the two pancreatic anlages, and later
they partially surround the vein. The alveoli of the gland are developed from the ducts as
darkly staining celluar buds in fetuses of 40 to 55 mm. (C R). The islands characteristic
of the pancreas also bud from the ducts (and alveoli, Mironescu, 1910) and appear first
in the tail at 55 mm. (C R).

Owing to the shift in the position of the stomach and duodenum during development,
the pancreas takes up a transverse position, its tail extending to the left. To its ventral
surface is attached the transverse mesocolon.

Anomalies. — The ventral pancreas may arise directly from the intestinal wall, and
paired ventral anlages also occur. Accessory pancreases are not uncommon. Both the
dorsal and ventral ducts persist in the horse and dog; in the sheep and man the ventral
duct becomes of chief importance; in the pig and ox the dorsal duct.

THE BODY CAVITIES, DIAPHRAGM AND MESENTERIES

The Primitive Ccelom and Mesenteries. — In the Peters embryo the
primary mesoderm has already split to form the extra-embryonic ccelom
(Fig. 74 C). When the intra-embryonic mesoderm differentiates, numer-
ous clefts appear on either side between the somatic and splanchnic layers
of mesoderm. These clefts coalesce in the cardiac region and form two
elongated pericardial cavities, lateral to the paired, tubular heart. Simi-
larly, right and left pleuro- peritoneal cavities are formed between the
mesoderm layers caudal to the heart. The paired pericardial cavities

THE BODY CAVITIES. DIAPHRAGM AND MESENTERIES

181

Pericardial cavity
Surface of fore-gut

extend toward the midplane cranial to the heart and communicate with
each other (Fig. 188). Laterally they are not continuous with thejixtra^
embryonic caelom, for the head of the embryo separates early from the
underlying blastoderm. The pericardial cavities also are prolonged
caudally until they open into the pleuro-peritoneal cavities. These
in turn communicate laterally with the extra-embryonic ccelom. In an
embryo of 2 mm. the coelom thus consists of a U-shaped pericardial cavity,
the right and left limbs of which are continued caudally into the paired
pleuro-peritoneal cavities ; these extend
out into the extra-embryonic coelom.

When the head fold and fore-gut
of the embryo are developed, the layers
of splanchnic mesoderm containing the
heart tubes are folded together ventral
to the fore-gut and form the ventral
mesentery between the gut and the
ventral body wall (Fig. 190), Owing
to the position of the yolk, sac, the
caudal extent of the ventral mesentery
is limited. On each side, at the level
where the vitello-umbilical trunk (Fig.
88) courses to the heart, the splanchnic
mesoderm and the somatic mesoderm
are united (cf. Fig. no). Thus is
formed the septum transversum, which incompletely partitions the ccelom
into a cranial and caudal portion (Fig. 189). Cranial to the septum, the
heart is suspended in the ventral mesentery which forms the dorsal and
ventral mesocardia (Fig. 190 A). Into the ventral mesentery, caudal to
the septum, grows the liver. This portion of the ventral mesentery
gives rise dorsally to the lesser amentum of the stomach, and, where it fails
to separate from the septum transversum, it forms the ligaments of the
liver. Ventrally it persists as the falciform ligament (Fig. 190 B).

Dorsal to the gut, the splanchnic mesoderm of each side is folded
together in the median sagittal plane to constitute the dorsal mesentery
which extends to the caudal end of the digestive canal (Figs. 189 and 190
C}. This suspends the stomach and intestine from the dorsal body wall
and is divided into tfie dorsal mesogastrium, or greater omentum of the
stomach, the mesoduodenum, the mesentery proper of the small intestine,
the mesocolon, and the mesorectum.

The covering layers of the viscera, mesenteries, and body wall are
continuous with each other and consist of a mesothelium overlying con-

• Pleuro-peritoneal canal
Entoderm of gut

Peritoneal cavity
Extra-embryonic coelom
Wall of yolk sac
FIG. 1 88. — Diagrammatic model of
the fore-gut and coelom in an early human
embryo, viewed from above and behind
(modified after Robinson).

182

THE ENTODERMAL CANAL AND THE BODY CAVITIES

nective tissue. The parietal lining is derived from the somatic layer of
mesoderm and the visceral covering from the splanchnic layer.

Esophagus

Pericardial cavity
Ventricle of heart

Ventral mesocardium
Liver _

Ventral mesentery
(falciform ligament)

Dorsal mesocar-
dium

Septum transversum

Stomach

B

Ventral mesentery

(lesser amentum)

Dorsal mesogastrium

Dorsal pancreas

Mesorectum

FIG. 189. — Diagram showing the primitive mesenteries of an early human embryo in
median sagittal section. The broken lines (A , B, and C) indicate the level of sections A , B,
and C, in Fig. 190.

Neural lube

Aorta Notochord

Postcar- 4 .
dinalvein Aori
Dorsal mesentery.

Fore-gut

Lesser

amentum

Liver

Peritoneal

cavity
Falciform
ligament

FIG. 190. — Diagrammatic transverse sections of an early human embryo. A, Through
the heart and pericardial cavities; B, through the fore-gut and liver; C, through the intestine
and peritoneal cavity.

The primitive ccelom lies in the horizontal plane, as in Fig.iSS. Coin-
cident with the caudal regression of the septum transversum, the peri-
cardial cavity is bent ventrad and enlarged (Fig. 191). The ventral

THE BODY CAVITIES. DIAPHRAGM AND MESENTERIES

mesocardium, attaching the heart to the ventral body wall, disappears
and the right and left limbs of the U-shaped cavity become confluent,
ventral to the heart. The result is a single, large pericardial chamber,
the long axis of which now lies in a dorso-ventral plane nearly at right
angles to the plane of the pleuro-peritoneal cavities, and connected with
them dorsally by the right and left pleuro-peritoneal canals.

The division of the primitive ccelom into separate cavities is accom-
plished by the development of three membranes that join in a Y-shaped
fashion (Figs. 194 and 195): (i) the septum transfer sum, which separates

Pericardial cavity

Somj.topl:ure

Septum transversu

Liver trabeculx
Hepatic diverticulnm

Yolk stalk

Bulhus cordis

Dorsal ntesocardium

Sinus venosus

lateral mesocardium
Common cardinal vein

Umbilical vein

Vitelline vein overlying
the stomach

Pleuro-peritoneal canal

Peritoneal cavity

FIG. 191. — Reconstruction cut at tlye left of the median sagittal plane of a 3 mm. human em-
bryo, showing the body cavities and septum trans versum (Kollmann).

incompletely the pericardial and pleural cavities from the peritoneal
cavities; (2) the paired pleuro- pericardial membranes, which complete
the division between pericardial and pleural cavities; (3) the paired
pleuro-peritoneal membranes, which complete the partition between each
pleural cavity, containing the lung, and the peritoneal cavity, which con-
tains the abdominal viscera.

The Septum Transversum. — The vitelline veins, on their way to the
heart, course in the splanchnic mesoderm lateral to the fore-gut. In
embryos of 2 to 3 mm. these large vessels bulge into the ccelom until they
meet and fuse with the somatic mesoderm (Figs. 88 and no). Thus there
is formed caudal to the heart a transverse partition filling the space be-
tween the sinus venosus of the heart, the gut, and the ventral body wall,
and separating the pericardial and peritoneal cavities from each other

1 84

THE ENTODERMAL CANAL AND THE BODY CAVITIES

ventral to the gut. This mesodefmal partition was termed by His the
septum transfer sum. In Fig. 191 it comprises both a cranial portion (desig-
nated "septum transversum"), that is the anlage of a large part of the
diaphragm, and a caudal portion, the ventral mesentery, into which the
liver is growing.

At first the septum transversum does not extend dorsal to the gut, but
leaves on either side a pleuro-peritoneal canal through which the pericardial

and pleuro-peritoneal cavities com-
municate (Fig. 191). In embryos of
4 to 5 mm. the lungs develop in the
median walls of these canals and bulge
laterally into them. Thus the canals
become the pleural cavities and will be
so termed hereafter.

On account of the more rapid
growth of the embryo, there is an
2 apparent constriction at the yolk

4 stalk, and, with the development of

5 T the umbilical cord, the peritoneal cavity

6 is finally separated from the extra-
P embryonic ccelom. Dorsally, the pleural

and peritoneal cavities are permanently
partitioned lengthwise by the dorsal
mesentery.

The septum transversum in 2 mm.
embryos occupies a transverse position
in the middle cervical region (Fig. 192,
2). According to Mall, it migrates
Numerals caudally, its ventral position at first

indicate the length of the embryo at moving more rapidly SO that its posi-

each position of the septum. The letters tjon becomes oblique. In 5 mm. em-

bryos (Fig. 192, 5) it is opposite the
fifth cervical segment, at which level it
receives the phrenic nerve. In stages

later than 7 mm., the septum migrates caudad, until, at 24 mm., it is
opposite the first lumbar segment. During this second period of migration
its dorsal attachment travels faster than its ventral portion. Therefore,
it rotates to a position nearly at right angles to its plane in 7 mm.
embryos, and its original dorsal surface becomes its ventral surface.
The Pleuro-pericardial and Pleuro-peritoneal Membranes. — The
common cardinal veins (ducts of Cuvier), on their way to the heart, curve
around the pleural cavities laterally in the somatic body wall (Figs. 191

543

L

FIG. 192. — Diagram
change in position of the septum trans-
versum (modified after Mall).

showing the

and numbers at the right represent the
segments of the occipital, cervical, thoracic
and lumbar regions.

THE BODY CAVITIES, DIAPHRAGM AND MESENTERIES

and 193). In embryos of 7 mm., each vein, with the overlying mesoderm,
forms a ridge that projects from the body wall mesially into the pleural
canals. This ridge, the pulmonary ridge (of Mall), is the anlage of both
the pleuro-pericardial and pleuro-peritoneal membranes. Later it broadens
and thickens cranio-caudally (Fig. 193), forming a triangular structure
whose apex is continuous with the septum transversum (Fig. 194). Its
cranial side forms the pleuro-pericardial membrane, and, in 9 to 10 mm.

Pericardia! cavity

Common cardinal vein

Pleuro-pericardial membrane

FIG. 193. — Reconstruction of a 7 mm. human embryo, showing from the left side the
pleuro-pericardial membrane, the pleuro-peritoneal membrane and the septum transversum (after
Mall). X 20. The phrenic nerve courses in the pleuro-pericardial membrane. An arrow
passes from pericardial to peritoneal cavity through the pleuro-pericardial canal.

embryos, reduces the opening between the pleural and pericardial cavities
to a mere slit. Its caudal side becomes the pleuro-peritoneal membrane,
which eventually separates dorsally the pleural from the peritoneal cav-
ity (Fig. 195). The two sets of membranes at first lie nearly in the
sagittal plane and a portion of the lung is caudal to the pleuro-peritoneal
membranes (Fig. 193). Between the stages of 7 and n mm. the dorsal
attachment of the septum transversum is carried caudally more rapidly

1 86

THE ENTODERMAL CANAL AND THE BODY CAVITIES

than its ventral portion, and its primary ventral surface becomes its dor-
sal side (Figs. 192 to 194). The pleuro-peritoneal membrane is carried
caudad with the septum transversum until the lung lies in the angle be-
tween the pleuro-peritoneal and pleuro-pericardial membranes and is
included within the spherical triangle which- has been described above
(Fig. 194). During this rotation the dorsal end of the pleuro-pericardial
membrane lags behind and so takes up a position in a coronal plane nearly
at right angles to the septum transversum (Figs. 194 and 195). In 1 1 mm.

Septum transversum

Pleuro-pericardial membrane
Pericardial cavity

Phrenic nerve

Pleural cavity

Mesonephros

Stomach

FIG. 194.-

-Reconstruction of an 1 1 mm. human embryo, to show the same structures as in Fig.
193 at a later stage (after Mall). X 14.

embryos the pleuro-pericardial membranes have fused completely on each
side with the median walls of the pleural canals and thus separate the
pericardium from the paired pleural cavities. By way of the pleuro-
pericardial membranes the phrenic nerves course to the septum transver-
sum (Fig. 194).

The pleuro-peritoneal membranes are continuous dorsally and caudally
with the mesonephric folds; ventrally and caudally they fuse later with
the dorsal pillars of the diaphragm, or coronary appendages of the liver

THE BODY CAVITIES, DIAPHRAGM AND MESENTERIES

l87

Esophagus

Mesoderm of left lung bud,
Pericardial cavity

Pleura-peritoneal

membrane
Phrenic nerve

Septum transversum

Pkural cavity

Right lung bud

Pleuro-pericardial
membrane

Wall of heart

Liver-

Falcifoam ligament

FIG. 195. — Transverse section through a 10 mm. human embryo, showing the pleuro-pericardi al
membranes separating the pericardium from the pleural cavities. X 33.

Esophagus
Right lung.

Coronary appendage of-
liver

Vena cata inferior

Pleural cavity

Pleuro-peritoneai
membrane

Phrenic nerve in septum
transversum

FIG. 196. — Transverse section through a 10 mm. human embryo, showing the' pleuro-peritoneal

membranes. X 16.

1 88

THE ENTODERMAL CANAL AND THE BODY CAVITIES

(Lewis) (Fig. 196). Between the free margins of the membranes and the
mesentery a temporary opening is left on each side, through which the
pleural and peritoneal cavities communicate (Figs. 175, 194 and 200).

A

Esophagus

Common cardinal vein \ Pleuro-pericardial canal
Lung

Pericardia! cavity

Pleural cavity N<^_ "S#3£U^7" 'Lung

'Pleural cavity

Septum transversum Pleura- peritoneal membrane Heart Pericardial membrane

FIG. 197. — Diagrams showing the development of the lungs and the formation of the pericardial
membrane (modified after Robinson). A, Coronal section; B, transverse section.

Owing to the caudal migration of the septum transversum and the
growth of the lungs and liver, the pleuro-peritoneal membrane, at first
lying in a nearly sagittal plane (Fig. 193), is shifted to a horizontal position

(Fig. 194), and gradually its free
margin unites with the dorsal pillars
of the diaphragm and with the
dorsal mesentery. The opening be-
tween the pleural and peritoneal
cavities is thus narrowed and finally
closed in embryos of 19 to 20 mm.
The Diaphragm and Pericardial
Membrane. — The lungs grow and
expand not only cranially and
caudally but also laterally and
ventrally (Fig. 197). Room is made
for them by the obliteration of the
very loose, spongy mesenchyme of
the adjacent body wall (Fig. 196).
As the lungs burrow laterally and
ventrally into the body wall around
the pericardial cavity, the pleuro-
pericardial membranes enlarge at the expense of this tissue and more
and more the heart comes to lie in a mesial position between the lungs
(Fig. 197 B). The pleural cavities thus increase rapidly in size.

FIG. 198. — Diagram showing the origin
of the diaphragm (after Broman). i,
Septum transversum; 2, 3, derivatives of
mesentery; 4, 4, derivatives of pleuro-peri-
toneal membrane; 5, 5, parts derived from
the body wall; A, aorta; Oe, esophagus; VC,
inferior vena cava.

THE BODY CAVITIES. DIAPHRAGM AND MESENTERIES

189

At the same time the liver grows enormously, and on either side a
portion of the body wall is taken up into the septum transversum and
pleuro-peritoneal membranes. The diaphragm, according to Broman,
is thus derived from four sources (Fig. 198): (i) its ventral pericardial
portion from the septum transversum; its lateral portions from (2) the
pleuro-peritoneal membranes, plus (3) derivatives from the body wall;
lastly, a median dorsal portion is formed from (4) the dorsal mesentery.
In addition to these, the striated muscle of the diaphragm, according
to Bardeen (1900), takes its origin from a pair of premuscle masses which
in 9 mm. embryos lie one on each side opposite the fifth cervical segment.

Right umbilical vein
Ventral mesentery

Left umbilical vein

Right lobe of liver

Lesser peritoneal sac

Plica vena cavtz

Ectoderm of body wall

Left lobe of liver
Ventral mesentery
Duodenum

Dorsal mesentery
Left posterior cardinal vein

Dorsal aorta

Neural tube

£- Notochord

FIG. 199. — Diagrammatic model of an embryo of 7 to 9 mm., showing the position of the
lesser peritoneal sac. The embryo is represented as sectioned transversely, caudal to the liver,
so that one looks at the caudal surface of the section and of the liver, and cranially into the
body cavities.

This is the level at which the phrenic nerve enters the septum transversum.
The exact origin of these muscle masses is in doubt, but they probably
represent portions of the cervical myotomes of this region. The muscle
masses migrate caudally with the septum transversum and develop chiefly
in the dorsal portion of the diaphragm (Bardeen, 1900).

The cavities of the mesodermal segments are regarded as portions of the coelom, but
in man they disappear early. The development of the vaginal sacs which grow out from
the inguinal region of the peritoneal cavity into the scrotum will be described in Chapter
VIII.

i go

THE ENTODERMAL CANAL AND THE BODY CAVITIES

The Omental Bursa or Lesser Peritoneal Sac. — According to Broman,
the omental bursa is represented in 3 mm. embryos by a peritoneal pocket
which extends cranially into the dorsal mesentery, to the right of the
esophagus. A similar pocket present on the left side has disappeared in
4 mm. embryos. Lateral to the opening of the primitive lesser peritoneal
sac, a lip-like fold of the mesentery is continued caudally along the dorsal

Body wall

Falciform ligament

Coronary attachment of
liver to diaphragm

Inferior vena cava

Sup. recess of lesser
peritoneal sac

Pleura- peritoneal
membrane

Inferior vena cava
Plica vena caves

Mesonephric fold
Genital fold

Greater amentum

Spleen

Stomach

Lesser peritoneal sac
Aorta

FIG. 200. — A diagrammatic ventral view of the middle third of a human embryo, 12 to 15
mm. long. The figure shows the caudal surface of a section through the stomach and spleen,
a ventral view of the stomach, the liver having been cut away to leave the sectioned edges of the
lesser omentum and. plica venae cavae, and the caudal surface of the septum transversum and
pleuro-peritoneal membrane. Upon the surface of the septum is indicated diagrammatically
the attachment of the liver. (Based on figures of Mall and F. T. Lewis and model by H. C.
Tracy.)

body wall into the mesonephric fold as the plica vena cavae, in which the
inferior vena cava later develops (Fig. 199). The liver, it will be remem-
bered, grows out into the ventral mesentery from the fore-gut, and, ex-
panding laterally and ventrally, takes the form of a cresent. Its right
lobe comes into relation with the plica venae cavae, and, growing rapidly
caudad, forms with the plica a partition between the lesser sac and the

THE BODY CAVITIES, DIAPHRAGM AND MESENTERIES

IQI

peritoneal cavity. Thus the cavity of the lesser peritoneal sac is ex-
tended caudally from a point opposite the bifurcation of the lungs to the
level of the pyloric end of the stomach. In 5 to 10 mm. embryos it is
crescent-shaped in cross section (cf. Fig. m) and is bounded mesially
by the greater omen turn (dorsal mesentery) and the right wall of the
stomach, laterally by the liver and plica venae cavae, and ventrally by the
lesser omentum (ventral mesentery). It communicates to the right

Suprarenal gland

Liver

Lesser peritoneal sac
Duodenum

Vitelline vein
Intestinal loop

Mesonephros
Greater omenti
•Stomach

Left umbilical vein

FIG. 201. — An obliquely transverse section through a 10 mm. human embryo at the level of
the epiploi.c foramen (of Winslow). X 33-

with the peritoneal cavity through an opening between the liver ventrally
and the plica venas cavas dorsally (Figs. 181 and 201). This opening is
the e pi ploic foramen (of Winslow). When the dorsal wall of the stomach
rotates to the left, the greater omentum is carried with it to the left of its
dorsal attachment. Its tissue grows actively to the left and caudally
and gives the omentum an appearance of being folded on itself between
the stomach and the dorsal body wall (Fig. 200). The cavity of the
lesser peritoneal sac is carried out between the folds of the greater omentum
as the inferior recess of the omental bursa.

From the cranial end of the sac there is constricted off a small closed cavity which is
frequently persistent in the adult. This is the bursa infracardiaca and may be regarded
as a third pleural cavity. It lies at the right of the esophagus in the mediastinum.

192

THE ENTODERMAL CANAL AND THE BODY CAVITIES

When the stomach changes its position and form so that its mid-
ventral line becomes the lesser curvature and lies to the right, the position
of the lesser omentum is also shifted. From its primitive location in a
median sagittal plane, with its free edge directed caudally, it is rotated
through 90° until it lies in a coronal plane with its free margin facing
to the right (Fig. 201). The epiploic foramen now forms a slit-like
opening leading from the peritoneal cavity into the vestibule of the
omental bursa. The foramen is bounded ventrally by the edge of the
lesser omentum, dorsally by the inferior vena cava, cranially by the
caudate process of the liver, and caudally by the wall of the duodenum.

During fetal life the greater omentum grows rapidly to the left and
caudad, in the form of a sac, flattened dorso-ventrally. It overlies the

ABC

FIG. 202. — Diagrams showing the development of the mesenteries (Hertwig). A illus-
trates the beginning of the great omentum and its independence of the transverse mesocolon;
in B the two come into contact; in C they have fused. A, stomach; B, transverse colon; C,
small intestine; D, duodenum; E, pancreas; F, greater omentum; G, greater sac; H, omental
bursa.

intestines ventrally and contains the inferior recess of the omental bursa
(Fig. 202). The dorsal wall of the sac during the fourth month usually
fuses with the transverse colon where it overlies the latter (Fig. 202 B).
Caudal to this attachment the walls of the greater omentum may be fused
and its cavity is then obliterated. The inferior recess of the omental
bursa thus may be limited in the adult chiefly to a space between the
stomach and the dorsal fold of the greater omentum, which latter is
largely fused to the peritoneum of the dorsal body wall. The spleen
develops in the cranial portion of the greater omentum and that portion
of the omentum which extends between the stomach and spleen is known
as the gastro-lienic ligament (Fig. 200). The dorsal wall of the omentum
between the spleen and kidney is the lieno-renal ligament.

THE BODY CAVITIES, DIAPHRAGM AND MESENTERIES 193

Further Differentiation of the Mesenteries. — Ligaments of the Liver. —
We have seen (p. 181) that the cranial portion of the ventral mesentery
forms the mesocardium of the heart. In the ventral mesentery, caudal
to the septum transversum, the liver develops. From the first, it is
enveloped in folds of the splanchnic mesoderm ; as the liver increases
in size, these give rise to its capsule and ligaments (Fig. 190 B). Wherever
the liver is unattached, the mesodermal layers of the ventral mesentery
form its capsule (of Glisson), a fibrous layer covered by mesothelium,
continuous with that of the peritoneum (Fig. 1 90 B} . Along its mid-dorsal
and mid-ventral line the liver remains attached to the ventral mesentery.
The dorsal attachment between the liver, stomach, and duodenum is the
lesser omentum. This in the adult is differentiated into the duodeno-
hepatic and gastro-hepatic ligaments. The attachment of the liver to
the ventral body wall extends caudally to the umbilicus and forms the
falciform ligament.

In its early development the liver abuts upon the septum transversum,
and, in 4 to 5 mm. embryos, is attached to it along its cephalic and ventral
surfaces. Soon, dorsal prolongations of the lateral liver lobes, the
coronary appendages, come into relation with the septum dorsally and
laterally. The attachment of the liver to the septum transversum now
has -the form of a cresent, the dorsal horns of which are the coronary
appendages (Fig. 200). This attachment becomes the coronary ligament
of the adult liver. The dorso-ventral extent of the coronary ligament
is reduced during development and its lateral extensions upon the dia-
phragm give rise to the triangular ligaments of each side.

The right lobe of the liver, as we have seen, comes into relation along
its dorsal surface with the plica venae cavce in 9 mm. embryos (Figs. 199
and 200). This attachment extends the coronary ligament caudally
on the right side and makes possible the connection between the veins
of the liver and mesonephros which contributes to the formation of the
inferior vena cava. The portion of the liver included between the plica
venae cavae and the lesser omentum is the caudate lobe (of Spigelius) .

In a fetus of five months the triangular ligaments mark the position
of the former lateral coronary appendages. The umbilical vein courses
in a deep groove along the ventral surface of the liver, and, with the portal
vein and gall bladder, bounds the quadrate lobe.

Changes in the Dorsal Mesentery. — That part of the digestive canal
which lies within the peritoneal cavity is suspended by the dorsal mesentery,
which at first forms a simple attachment extending in the median sagittal
plane between body wall and primitive gut. That portion of it connected
with the stomach forms the greater omentum, the differentiation of which
has been described (p. 192). The mesentery of the intestine is carried

IQ4 THE ENTODERMAL CANAL AND THE BODY CAVITIES

out into the umbilical cord between the limbs of the intestinal loop.
When the intestine elongates and its loop rotates, the caecal end of the
large intestine conies to lie cranially and to the left, the small intestine
caudally and to the right, the future duodeum and colon crossing in
close proximity to each other (Fig. 179). On the return of the intestinal
loop into the abdomen from the umbilical cord, the cascal end of the colon
lies to the right and the transverse colon crosses the duodenum ventrally
and cranially (Fig. 203 A). The primary loops of the small intestine
lie caudal and to the left of the ascending colon (Fig. 203 B}. There
has thus been a torsion of the mesentery about the origin of the superior

Lesser amentum

Dorsal mesogastrin

amentum Transve.
mesoc

CcEcum

Mesentery
Mesorectu

A

FIG. 203. — Diagram showing the development of the mesenteries in ventral view (modified
after Tourneux). *, Cut edge of greater omentum; a, area of ascending mesocolon fused to dor-
sal body wall; b, area of descending mesocolon fused to dorsal body wall. Arrow in omental
bursa.

mesenteric artery as an axis. From this focal point the mesentery of the
small intestine and colon spreads out fan-like. The mesoduodenum is
pressed against the dorsal body wall, fuses with its peritoneal layer, and
is obliterated (Fig. 202). Since the transverse colon lies ventral to the
duodenum it cannot come into apposition with the body wall ; where its
mesentery crosses the duodenum it fuses at its base with the surface of
the latter and of the pancreas. Its fixed position now being transverse
instead of sagittal, the mesentery is known as the transverse mesocolon.
The mesentery of the ascending colon is flattened against the dorsal body
wall on the right and fuses with the peritoneum (Fig. 203). Similarly,
the descending mesocolon is applied to the body wall of the left side.

THE BODY CAVITIES, DIAPHRAGM AND MESENTERIES igz

There are thus left free: (i) the transverse mesocolon; (2) the mesentery
proper of the jejunum and ileum, with numerous folds corresponding to
the loops of the intestine; (3) the iliac mesocolon; (4) the mesorectum,
which retains its primitive relations.

Anomalies : — The persistence of a dorsal opening in the diaphragm, more commonly
on the left side, finds its explanation in the imperfect development of the pleuro-peritoneal
membrane. Such a defect may lead to diaphragmatic hernia, the abdominal viscera pro-
jecting to a greater or less extent into the pleural cavity. Similarly, faulty development
of the left pleuro-pericardial membrane sometimes causes the heart and left lung to occupy
a common cavity.

The mesenteries also may show malformations, due to the persistent of the simpler
embryonic conditions, usually correlated with the defective development of the intestinal
canal. In about 30 per cent of cases the ascending and descending mesocolon are more or
less free, having failed to fuse with the dorsal peritoneum. The primary sheets of the
greater omentum may also fail to unite, so that the inferior recess extends to the caudal
end of the greater omentum.

A striking anomaly is situs viscerum invcrsus, in which the various visceral organs
are transposed right for left and left for right, as in a mirror image. An independent
transposition of the thoracic or abdominal viscera alone may occur. The larger left great
venous trunks are thought to be chiefly responsible for the usual positions of the

CHAPTER VIII
THE DEVELOPMENT OF THE UROGENITAL SYSTEM

THE excretory and reproductive systems are intimately associated
in development. Both arise from the mesoderm of the intermediate
cell mass (nephrotome), which unites the primitive segments with the
lateral somatic and splanchnic mesoderm (p. 53; Fig. 205).

Vertebrates possess excretory organs of three distinct types. The
pronephros is the functional kidney of amphioxus and certain lampreys,
but appears only in immature fishes and amphibians, being replaced by the
mesonephros. The embryos of amniotes (reptiles, birds, and mammals)
possess first a pronephros, and then a mesonephros, whereas the permanent
kidney is a new organ, the metanephros. Whether these glands represent
modifications of an originally continuous organ, or whether they are
three distinct structures, is undecided, but however this may be, the pro-,
meso-, and metanephroi of amniotes develop successively in the order
named, both as regards time and place.

THE PRONEPHROS

The pronephros, when functional, consists of paired, segmentally ar-
ranged tubules, one end of each tubule opening into the ccelom, the other
into a longitudinal pronephric duct which drains into the cloaca (Fig.
204 A}. Near the nephrostome (the opening into the coelom), knots
of arteries project into the ccelom, forming glomeruli. Fluid from the coelom
and glomeruli, and excreta from the cells of the tubules are carried by
ciliary movement into the pronephric ducts.

The human pronephros is vestigial. It consists of about seven pairs
of rudimentary pronephric tubules, formed as dorsal sprouts from the
nephrotomes (Fig. 205) in each segment, from the seventh to the
fourteenth, and perhaps from more cranial segments as well. The nodules
hollow out and open into the ccelom. Dorsally and laterally, the tubules
of each side bend backward and unite to form a longitudinal collecting
duct (Fig. 204 B, A). The tubules first formed in the seventh segment begin
to degenerate before those of the fourteenth segment have developed.
Caudal to the fourteenth segment no pronephric tubules are developed,
but the free end of the collecting duct, by a process of terminal growth,
extends caudad beneath the ectoderm and lateral to the nephrogenic cord,
until it reaches the lateral wall of the cloaca and perforates it.' Thus are

196

THE PRONEPHROS

IQ7

Pronephric duct B

Mesodermal
segments

Neural tube.

Anlages of pronephric
duct

Nephrotome
Somatic mesoderm

Splanchnic mesoderm

Pronephric tubule Ccelom Notochord Entoderm

FIG. 204. — Diagrams showing the development of the pronephric duct and pronephric tubules
(modified from Felix). A represents a later stage than B.

Neural t

Notochord

Cavity of gu

Splanchnic mesodern,

Mesoderm of yolk sac

'Mesodermal segment
'avity of segment

Intermediate cell mass
Anlage of extremity

'Ccelom

JT— Somatic mesoderm
)

Umbilical vein

FIG. 205. — Transverse section of a 2.4 mm. human embryo, showing the intermediate cell mass
or nephrotome (Kollmann).

198 THE UROGENITAL SYSTEM

formed the paired primary excretory (pronephric) ducts. The pronephric
tubules begin to appear in embryos of 1.7 mm., with nine or ten primitive
segments (Felix); in 2.5 mm. embryos (23 segments) all the tubules have
developed and the primary excretory duct is nearly complete. In 4.25
mm. embryos the duct has reached the wall of the cloaca and soon after
fuses with it. The pronephric tubules soon degenerate, but the primary
excretory ducts persist and become the ducts of the mesonephroi, or mid-
kidneys.

THE MESONEPHROS

The mesonephros, like the pronephros, consists essentially of a series of
tubules, each of which at one end is related to a knot of blood vessels and
at the other end opens into the primary excretory duct. Besides possess-
ing an internal glomerulus alone they differ from the pronephric tubules in
that the nephrostomes are transitory, never opening into the mesonephric
chamber. The mesonephric tubules arise just caudal to the pronephros
and from the same general source, that is, the nephrotomes. Only a few
of the more cranial tubules, however, are formed from distinct intermediate
cell masses, for caudal to the tenth pair of segments this mesoderm con-
stitutes unsegmented, paired nephrogenic cords. These may extend
caudally as far as the twenty-eighth segment. The primary excretory
ducts lie lateral to the nephrogenic cords.

When the developing mesonephric tubules begin to expand, there is
not room for them in the dorsal body wall and as a result this bulges
ventrally into the ccelom. Thus, there is produced on either side of the
dorsal mesentery a longitudinal urogenital fold, which may extend from
the sixth cervical to the third lumbar segment (Fig. 220). Later, £his
ridge is divided into a lateral mesonephric fold and into a median genital
fold, the anlage of the genital gland.

Differentiation of the Tubules. — The nephrogenic cord in 2.5 mm.
embryos first divides into spherical masses of cells, the anlages of the
mesonephric tubules. Four of these may be formed in a single segment.
Appearing first in the i3th, i4th and i$th segments, the anlages of the
tubules differentiate both cranially and caudally. In 5.3 mm. embryos
the cephalic limit is reached in the sixth cervical segment, and thereafter
degeneration begins at the cephalic end (Fig. 207). Hence, the more
cranial tubules overlap those of the pronephros. In 7 mm. embryos the
caudal limit is reached in the third lumbar segment.

The spherical anlages of the tubules differentiate in a cranio-caudal
direction (Fig. 206). First, vesicles with lumina are formed (4.25 mm.).
Next, the vesicles elongate laterally, unite with the primary excretory
ducts, and become S-shaped (4.9 mm.). The free, vesicular end of the

THE MESONEPHROS

199

tubule enlarges, becomes thin walled, and into this wall grows a knot of
arteries to form the glomerulus (embryos of 5 to 7 mm.). The tubule, at
first solid, hollows out and is lined with a low columnar epithelium. The
outer wall of the vesicle about the glomerulus is Bowman's capsule, the
two constituting a renal corpuscle of the mesonephros (Fig. 2o6D). In the
human embryo the tubules do not branch or coil as in pig embryos, con-
sequently the mesonephros is relatively smaller. At 10 mm., about 35

Mesonephric duct

Anlageof

mesonephric tubule < -.>•":

Degenerating
mesonephric corpuscle
Degenerating mesonephric
corpuscle and tubule

Tubule

Bowman's capsule

Developing mesonephric

corpuscle
Urogenital sinus

Glomerulus and Bowman's,
capsule

Mesonephric
duct

Metanephros

FIG. 206. — Diagrams showing the FIG. 207. — Diagram showing the anlages

differentiation of the mesonephric tubules of the urinary organs in about 10 mm. human

(modified after Felix). L. lateral; M, embryos, as seen from the left side (based on

median. reconstructions by Keibel and Felix).

'L-

tubules are present in each mesonephros and the glomeruli are conspicuous
Fig. (207). Each tubule shows a distal secretory portion and a proximal
collecting part which connects with the duct (Fig. 208). The glomeruli
form a single median column ; the tubules are dorsal and the duct is lateral
in position. Ventro-lateral branches from the aorta supply the glomeruli,
(Fig. 323), while the posterior cardinal veins (Fig. 72), dorsal in position,
break up into a network of sinusoids about the tubules (see Chapter IX).

200 THE UROGENITAL SYSTEM

The primary excretory (Wolffian) duct, or mesonephric duct, is solid
in 4.25 mm. embryos. A lumen is formed at 7 mm., wider opposite the
openings of the tubules. The duct is important, as the ureteric anlage of
the permanent kidney grows out from its caudal end, while the duct itself
is transformed into the chief genital duct of the male, and its derivatives.

That the human mesonephros is a functional excretory organ is
plausible (Bremer, 1916), but not proved. Degeneration proceeds rapidly
in embryos between 10 and 20 mm. long, beginning cranially. New
tubules are formed at the same time caudally. In all, 83 pairs of tubules
arise, of which only 26 pairs persist at 21 mm., and these are usually
broken at the angle between the collecting and secretory regions. They
are divided into an upper group and a lower group. The collecting portions

Suprarenal gland'
Post, cardinal vein,

Glomerulus
Bowman's capsule

'ollecting tubule
ecretory tubule

Mesonephric duct
Mullerian duct
Anlage of genital gland

FIG. 208. — Reconstruction of the contents of the urogential fold, from transverse sections of a
12 mm. human embryo. X 95.

of the upper group, numbering 5 to 12, unite with the rete tubules of the
testis or ovary. In the male they form the efferent ductules of the epididy-
mis. In the female they constitute the epoophoron. Of the lower group
a few tubules persist in the male, as the paradidymis. In the female they
form the paroophoron.

THE METANEPHROS

The essential parts of the permanent kidney are the renal corpuscles
(glomerulus with Bowman's capsule), secretory tubules, and collecting
tubules. The collecting tubules open into expansions of the duct, the
pelvis and calyces. The duct itself is the ureter, which opens into the
bladder. Like the mesonephros, the metanephros is of double origin.
The ureter, pelvis, calyces, and collecting tubules are outgrowths of the

THE METANEPHROS

mesonephric duct. The secretory tubules and the capsules of the renal
corpuscles are differentiated from the isolated caudal end of the nephro-
genic cord and thus have a similiar origin as the mesonephric tubules.

Mesonephric duct

Outer zone^f nephrogenic cord
Inner zone of nephrogenic cord
Pelvis of kidney

Hind-gut

Bladder

Cloacal membrane — -^

FIG. 209. -^-Reconstruction of the anlages of the metanephros in a human embryo of about 9

mm. (after Schreiner).

Cranial pole tubule

Cranial

/%-'

I jpole tubule

/ y-v \Caudal
^X VJ/ 'pole tubule

Urete

Cranial
pole tubule

Pelvis'

Caudal
pole tubule

Ureter^

Secondary

collecting

tubules

Tertiary collecting
tubule

FIG. 210. — Diagrams showing the development of the primitive pelvis, calyces and collecting
tubules of the metanephros (based on reconstructions by Schreiner and Felix).

In embryos of about 5 mm. the mesonpheric duct makes a sharp bend
just before it joins the cloaca, and it is at the angle of this bend that the
ureteric evagination appears, dorsal and somewhat median in position
(Fig. 216, B, C). The bud grows at first dorsally, then cranially. Its

THE UROGENITAL SYSTEM

distal end expands and forms the primitive pelvis. Its proximal elongated
portion is the ureter. The anlage grows into the lower end of the nephro-
genic cord (Fig. 209), which, in 46 mm. embryos, is separated from the
cranial end of the cord at the twenty-seventh segment. The nephrogenic
tissue forms a cap about the primitive pelvis, and, as the pelvis grows
cranially, is carried along with it. In embryos of 9 to 13 mm. the pelvis,
having advanced cephalad through three segments, attains a position in
the retroperitoneal tissue dorsal to the mesonephros and opposite the
second lumbar segment. Thereafter, the kidney enlarges both cranially
and caudally without shifting its position. The ureter elongates as the
embryo grows in length. The cranial growth of the
kidney takes place dorsal to the suprarenal gland
(Fig. 232).

Primary collecting tubules grow out from the
primitive pelvis in 10 mm. embryos. Of the first
two, one is cranial, the other caudal in position, and
between these there are usually two others (Fig. 2ioB,
C). From an enlargement, the ampulla, at the end
of each primary tubule grow out two, three, or four
secondary tubules. These in turn give rise to tertiary
tubules (Fig. 210 D] and the process is repeated until
the fifth month of fetal life, when it is estimated that
twelve generations of tubules have been developed.

The pelvis and both primary and secondary tubules
FIG. 2ii.— Recon- J J

struction of the ureter, enlarge during development. The first two primary
and tubules become the major calyces, and the secondary

tubules opening into them form

the minor calyces
third and fourth

pelvis, calyces

their branches from

the metanephros of a /T^. \ ™, .11 r •_•>

16 mm. human embryo (Flg' 2I1)' The tubuleS °f the

(Huber). x 50. orders are taken up into the walls of the enlarged

secondary tubules so that the tubules of the fifth
order, 20 to 30 in number, open into the minor calyces as papillary ducts.
The remaining orders of tubules constitute the collecting tubules which
form the greater part of the medulla of the adult kidney.

When the four to six primary tubules develop, the nephrogenic cap
about the primitive pelvis is subdivided and its four to six parts cover the
end of each primary tubule. As new orders of tubules arise, each mass
of nephrogenic tissue increases in amount and is again subdivided until
finally it forms a peripheral layer about the ends of the branches tribu-
tary to a primary tubule. The converging branches of such a tubular
'tree' constitute a primary renal unit, or pyramid, with its base at the
periphery of the kidney and its apex projecting into the pelvis. The
apices of the pyramids are termed renal papilla, and through them the

DIFFERENTIATION OF THE NEPHROGENIC TISSUE

203

larger collecting ducts open. The nephrogenic tissue forms the cortex
of the kidney, and each subdivision of it, covering the tubules of a pyramid
peripherally, is marked off on the surface of the organ by grooves or
depressions. The human fetal kidney is thus distinctly lobated, the loba-
tions persisting until after birth, a condition which is permanent in rep-
tiles, birds, and some mammals (whale, bear, ox). The primary pyramids
are subdivided into several secondary and tertiary pyramids. Between
the pyramids the cortex of nephrogenic tissue dips down to the pelvis,
forming the renal columns (of Bertin). The collecting tubules, on the
other hand, extend out into the cortex as the cortical rays, or pars radiata
of the cortex. In these rays, and in the medulla of the kidney, the col-
lecting tubules run parallel and converge to the papilla?.

4 5

FIG. 212. — Semidiagrammatic figures of the anlage and differentiation of renal vesicles
and early developmental stages of uriniferous tubules of mammals. I and 2, Anlage and suc-
cessive stages in the differentiation of renal vesicles, as seen in sagittal sections; 3, section and
outer form of tubular anlage before union with collecting tubule at the beginning of S-shaped
stage; 4 and 5, successive stages in the development of the tubules, Bowman's capsule, and glo-
merulus beginning with a tubular anlage showing a well-developed S-shape (Huber).

Differentiation of the Nephrogenic Tissue. — In stages from 13 to 19
mm., the nephrogenic tissue about the ends of the collecting tubules
condenses into spherical masses that lie in the angles between the buds of
new collecting tubules and their parent stems (Fig. 212). One such
metanephric sphere is formed for each, new tubule. The spheres are con-

2O4

THE UROGENITAL SYSTEM

verted into vesicles with eccentrically placed lumina. The vesicle elon-
gates, its thicker outer wall forming an S-shaped tubule which unites with
a collecting tubule, its thin inner wall becoming the capsule (Bowman's)
of a renal corpuscle. The uriniferous tubules of the adult kidney have a
definite and peculiar structure and arrangement (Fig. 213 .4). Beginning
with a renal corpuscle, each tubule forms a proximal convoluted portion, a
\J-shaped loop (of Henle) with descending and ascending limbs, a connecting

Arch of collecting tubule
A

Proximal convoluted

tubule
Distal convoluted

tubule
Renal corpuscle

Connecting piec*

Ascending limb of.
Henle's loop

Descending limb of.
Henle's loop

Large collecting

tubule

Arch of collecting tubule

Distal convoluted tubule

Stoerck's loop

Proximal convoluted tubule

Connecting piece
' merulus

Bowman's capsule

Arch of collecting tubule
Proximal convoluted tubule

Distal convoluted tubule
'onnecting piece
'merulus

Bowman's capsule
Stoerck's loop

FIG. 213. — Diagrams showing the differentiation of the various parts of the uriniferous
tubules of the metanephros (based on the reconstructions of Huber and Stoerck): A, From an
adult human kidney; B, C, from human embryos.

piece, which lies close to the renal corpuscle, and a distal convoluted portion
continuous with the collecting tubule. These parts are derived from the
S-shaped anlage, which is composed of a lower, middle and upper limb.
The middle limb, somewhat U-shaped, bulges into the concavity of Bow-
man's capsule (Fig. 213 B). By differentiation the lower portion of the
lower limb becomes Bowman's capsule, ingrowing arteries forming the
glomerulus (Fig. 213 B, C). The upper part of the same limb by enlarge-
ment, elongation, and coiling becomes the proximal convoluted tubule.
The neighboring portion of the middle limb forms the primitive loop (of
Stoerck) ; the base of the middle limb gives rise to the connecting piece,
and the rest of it, with the upper limb of the S, forms the distal convoluted

DIFFERENTIATION OF THE NEPHROGENIC TISSUE

J ....

205

FIG. 214. — Diagram showing the relation of Bowman's capsule and the uriniferous tubules
to the collecting tubules of the metanephros (Huber). c, Collecting tubules; e, end branches of
collecting tubules; r, renal corpuscles; n, neck; pc, proximal convoluted tubule; dl, descending
limb of Henle's loop, /; al, ascending limb of Henle's loop; dc, distal convoluted tubule; j, junc-
tional tubule.

C\ G

FIG. 215. — Several stages in the development of the uriniferous tubules and glomeruli of the
human metanephros of the seventh month (reconstructions by Huber). X 160.

206 THE UROGENITAL SYSTEM

tubule (intermediate piece of Felix). The primitive loop of Stoerck in-
cludes both the ascending and descending limbs of Henle's loop and a por-
tion of the proximal convoluted tubule. Henle's loop is differentiated
during the fourth fetal month (Toldt) and extends from the pars radiata
of the cortex into the medulla (Fig. 214). The concavity of Bowman's
capsule, into which grow the arterial loops of the glomerulus, is at first
shallow. Eventually the walls of the capsule grow about and enclose the
vascular knot, except at the point where the arteries enter and emerge
(Fig. 212, 4 and 5). Renal corpuscles are first fully formed in 28 to 30
mm. embryos. The new corpuscles are formed peripherally from per-
sisting nephrogenic tissue until the tenth day after birth, hence in the
adult the oldest corpuscles are those next to the medulla. Reconstruc-
tions of the various stages in the development of the uriniferous tubules
are shown in Fig. 215.

Renal Arteries. — Bremer (1915) derives the renal arteries not from transformed meso-
nephric vessels, as did Broman (1906), but from a periaortic plexus of multiple aortic
origin. The mechanical selection of permanent channels explains the frequent variations
in the renal vessels.

Anomalies. — The kidneys may fail to ascend from their embryonic position in the
pelvis. Absence of one kidney is not infrequent. The kidneys sometimes fuse, either
completely into a disc-shaped mass, or partially by cortical union ('horse-shoe kidney'};
in such cases the ducts usually are bilateral. Double or cleft ureters and pelves occur.
'Cystic kid ney' results when the uriniferous tubules fail to unite with the collecting tubules.

DIFFERENTIATION OF THE CLOACA, BLADDER, URETHRA AND UROGENITAL

SINUS

In embryos of 1.4 mm., the cloaca, a caudal expansion of the hind-gut,
is in contact ventrally with the ectoderm, and ectoderm and entoderm
together form the cloacal membrane (Fig. 2 1 6 A ) . Ventro-cephalad, the cloaca
gives off the allantoic stalk. At a somewhat later stage, the cloaca receives
laterally the mesonephric ducts and is prolonged caudally as the tail-gut
(Fig. 2i6B).

In embryos of 5 mm., the ureteric anlages of the metanephroi are
present as buds of the mesonephric ducts (Fig. 216 C, D). Next, the
saddle-like partition between the intestine and allantois grows caudally,
dividing the cloaca into a dorsal rectum and ventral, primitive uro genital
sinus. The division is complete in embryos of n to 15 mm., and at the
same time the partition, fusing with the cloacal membrane, divides it into
the anal membrane of the gut and the urogenital membrane. At n mm.,
according to Felix, the primitive urogenital sinus by elongation and con-
striction is differentiated into two regions: (i) a dorsal vesico-urethral
anlage which receives the allantois and mesonephric duct, and is connected
by the constricted portion with (2) the phallic portion of the urogenital

CLOACA, BLADDER, URETHRA AND UROGENITAL SINUS

207

Hind-gut

Hind-gut
Mesonephric
duct

Cloacal membrane

Hind-gut Mesonephric
AUantois

Metanephros

loacal membrane

Cloaca

Tail-gut

* Cloaca] membrane
Tail-gut

FIG. 216. — Four stages showing the differentiation of the cloaca into the rectum, urethra
and bladder (after reconstructions by Pohlman). X about 50. A, from a human embryo of
3.5 mm.; B, at about 4 mm.; C, at 5 mm.; D,&i 7 mm.

Mesonephric duct
Metanephros

Intestine

Allantois

A nlage of bladder

loacal membrane

FIG. 217. — Reconstruction from a 12 mm. human embryo, showing the partial subdivision of
the cloaca into rectum and urogenital sinus (after Pohlman). X 65.

208

THE UROGENITAL SYSTEM

sinus (Figs. 217 and 218). The latter extends into the phallus of both
sexes and forms a greater part of the urethra (Fig. 219); its fate is described
on p. 226 in connection with the external genitalia.

Allantois

Ccdom Rectum

Mesonephric ducts

Metanephros

Ureter

FIG. 218. — Reconstruction of the caudal portion of an 11.5 mm. human embryo, showing the
differentiation of the rectum, bladder and urethra (after Keibel's model). X 25.

Vesko-urelhral anlage
Phallic portion of urogenilal sinus

Genital gland
Mesonephric fold
Anlage of bladder.

Utero-vaginal anlage

Phallic ureth
A nal membrane

Mesonephros
Ureter

Ureter
Miillerian duct

Mesonephric duct
Rectum

Spinal cord

Anal membran

Rectum

FIG. 219. — Reconstruction of the caudal end of a 29 mm. human embryo, showing the
complete separation of the rectum and urogenital sinus and the relations of the urogenital ducts
(after Keibel's model). X 15.

The vesico-urethral anlage enlarges and forms the bladder and a por-
tion of the urethra. In 7 mm. embryos the proximal ends of the meso-
nephric ducts are funnel shaped, and, at 10 mm., with the enlargement of
the bladder, these ends are taken up into its wall until the ureters and meso-

THE GENITAL GLANDS AND DUCTS INDIFFERENT STAGE 2OQ

nephric ducts acquire separate openings. The ureters, having previously
shifted their openings into the mesonephric ducts from a dorsal to lateral
position, now open into the vesico-urethral anlage lateral to the meso-
nephric ducts. The lateral walls of the bladder anlage grow more rapidly
than its dorso-median urethral wall, hence the ureters are carried cranially
and laterally upon the wall of the bladder, while the mesonephric ducts,
now the male ducts, open close together on a hillock, Muller's tubercle, into
the dorsal wall of the urethra (Fig. 219).

Thus a triangular area, roughly bounded by the openings of the ureters and
ejaculatory ducts, is of mesodermal origin. The narrowed apex of the bladder, con-
tinuous with the allantoic stalk at the umbilicus, is known as the urachus. It persists
as the solid, fibrous ligamentum umbilicale medium. Contrary to earlier view^, the
allantois contributes nothing to the bladder or urachus (Felix, 1912).

The transitional epithelium of the bladder appears at 60 mm. (C H). The outer
longitudinal layer of smooth muscle develops in 22 mm. embryos, and, in 26 mm. embryos,
the circular muscle appears. The inner longitudinal musclelayer is found at 55 mm.
(C H) and the sphincter vesicae in fetuses of 90 mm. (C H).

Anomalies. — A conspicuous malformation is that of a persistent cloaca, due to the
failure of the rectum and urogenital sinus to separate. The bladder sometimes opens
widely onto the ventral body wall and is everted through the fissure; a urogenital aper-
ture corresponding to the upper extent of the primitive cloacal membrane (Fig. 216, C, D)
would cause this condition. At times, the urachus remains a patent tube, opening at the
umbilicus. Portions of its epithelium which fail to degenerate may form cysts.

THE GENITAL GLANDS AND DUCTS
A. INDIFFERENT STAGE

In origin and early development, the ovary and testis are identical.
The urogenital fold (p. 198) is the anlage of both the mesonephros and the
genital gland (Figs. 122 and 220). At first two-layered, its epithelium in
embryos of 5 mm. thickens over the ventro-median surface of the fold,
becomes many-layered, and bulges into the ccelom ventrally, producing
the longitudinal genital fold (Fig. 208). The genital fold thus lies mesial
and parallel to the mesonephric fold. Large primordial germ cells are
found in 2.5 mm. embryos in the entoderm of the future intestinal tract
(Fuss). At 3.5 mm. they migrate into the dorsal mesenteric epithelium
and thence into the epithelium of the genital fold. It is probable that the
definitive germ cells of the genital glands are descendants of these ele-
ments. At 10 to 12 mm. the genital anlage shows no sexual differentiation
(Fig. 221). There is a superficial epithelial layer and an inner epithelial
mass of somewhat open structure.

Owing to the great development of the suprarenal glands and meta-
nephroi, the cranial portions of the urogenital folds, at first parallel and
close together, are displaced laterally. This produces a double bend in
each fold, which, in 20 mm. embryos, shows a cranial longitudinal portion, a

210

THE UROGENITAL SYSTEM

Rhombencephalon

Right lung

Mesonephric fold

Lower extremity

Mesencephalon

Prosencephahn

Genital eminence

Tail

FIG. 220. — Ventral view of the urogenital folds in a human embryo of 9 mm. (Kollmann).

Lateral body wall

Post, cardinal vein

Suprarenal gland

Glomerulus

Mesonephric duct

Inner epithelial mass of genital gland
Epithelium of genital gland

Mesenler

FIG. 221. — Transverse section through the mesonephros, genital gland and suprarenal gland
of the right side; from a 12 mm. human embryo. X 165.

THE GENITAL GLANDS AND DUCTS INDIFFERENT STAGE 211

transverse middle portion between the bends', and a longitudinal caudal
portion (Fig. 238 A). In the last named segment, the mesonephric ducts
course to the cloaca, and here the right and left folds fuse, producing the
genital cord (Fig. 232). As the genital glands increase in size they become
constricted from the mesonephric fold by lateral and mesial grooves until
the originally broad base of the genital fold is converted into a stalk (Figs.
225 to 227). This stalk-like attachment extends lengthwise and forms in
the male the mesorchium, in the female the mesovarium. The urogenital
fold is, at the same time, constricted from the dorsal body wall until it is
attached only by a narrow mesentery which eventually forms either the
ligamentum testis or ligamentum ovarii.

A

Lateral body watt

Miillerian groove^ W~ Mesentery

• Mesonephric tubule

• Genital gland

Anl,age of Miillerian duct

FIG. 222. — Transverse sections through the anlage of the right Miillerian duct from a 10
mm. human embryo. X 250. A, showing the groove in the urogenital epithelium; B, three
sections caudad, showing the tubular anlage of the duct.

Indifferent Stage of the Genital Ducts. — -The mesonephric ducts, with
the degeneration of the mesonephroi, become the male genital ducts. In
both sexes there also develop a pair of female ducts (of Miiller). In em-
bryos of 10 mm. these Miillerian ducts develop as ventro-lateral thickenings
of the urogenital epithelium at the level of the third thoracic segment and
near the cranial ends of the mesonephroi. Next, a ventro-lateral groove
appears in the epithelium of the mesonephric fold (Fig. 222 A). Caudally,
the dorsal and ventral lips of the groove close and form a £ube which sepa-
rates from the epithelium and lies beneath it (Fig. 222 B}." Cranially, the
tube remains open as the funnel-shaped ostium abdominale of the Mullerian

THE UROGENITAL SYSTEM

Aorta

Lung

Diaphragm

Ostium abdominale

Miillerian duct

Inferior vena cava

Genital gland
Colon

Attantois

Pulmonary trunk
Pulmonary artery

Esophagus
Mesonephric duct

Umbilical artery

FIG. 223. — Ventral dissection of an 18 mm. pig embryo, to show the anlages of the Mullerian

ducts. X 7.

Trachea

Esophagus

Genital gland

Mesonephric duct

Attantois

Lung

_ Mesonephros
M idler ian duct

-•Colon
Umbilical artery

FIG. 224. — Ventral dissection of a 24 mm. pig embryo, showing the anlages of the Mullerian
ducts at a later stage of development than in Fig. 223. X 6.

INTERNAL SEXUAL TRANSFORMATIONS— TESTIS

213

duct. The solid end of the tube grows caudalward beneath the epithelium,
lateral to the mesonephric, or male ducts (Pigs. 223 to 225). Eventually,
by way of the genital cord, the Miillerian ducts reach the median dorsal
wall of the urogenital sinus and open into it (Figs. 219 and 238 A). Their
further development into uterine tubes, uterus, and vagina is described
on page 220. Embryos not longer than 12 mm. are thus characterized by
the possession of indifferent genital glands and both male and female
genital ducts. There is as yet no sexual differentiation. The develop-
ment and position of the Mullerian ducts is well shown in ventral dissec-
tions of pig embryos (Figs. 223 and 224); the mesonephroi of the pig are
much larger than in man. In the lowest vertebrates the Mullerian duct
arise by a longitudinal splitting of the mesonephric duct.

Ligamentum testi

Mesonephric tubule
Mesorchium
Anlage of rele testis

Mesonephric duct

Miillerian duct
Intermediate cord
Testis cord

Epithelium
Tunica albuginea

FIG. 225. — Transverse section through the left testis and mesonephros of a 20 mm. human

embryo. X 250.

B. INTERNAL SEXUAL TRANSFORMATIONS

Differentiation of the Testis. — In the male embryos of 13 mm. the
genital glands show two characters which mark them as testes: (i) the
occurrence of branched, anastomosing cords of cells, the testis cords; (2)
the occurrence between epithelium and testis cords of a layer of tissue, the
anlage of the tunica albuginea (Fig. 225). According to Felix (1912), the
testis cords of man are developed suddenly from the loose, inner epithelial
mass by a condensation of its cells. The cords converge and grow smaller
.towards the mesorchium, where they form the dense, epithelial anla'ge

214

THE UROGENITAL SYSTEM

of the rete testis. Two or three layers of loosely arranged cells between the
testis cords and the epithelium constitute the anlage of the tunica albugin-
ea. On the contrary, Allen (1904) holds that the testis cords of the rabbit
and pig are formed as invaginations of the surface epithelium.

The testis cords soon become rounded and are marked off by connec-
tive-tissue sheaths from the intermediate cords, columns of undifferentiated
tissue which lie beteen them (Fig. 226). Toward the rete testis the sheaths
of the testis cords unite to form the anlage of the mediastinum testis. The
testis cords are composed chiefly of indifferent cells with a few larger germ
cells. The cells gradually arrange themselves radially about the inside of
the connective-tissue sheath as a many-layered epithelium, in which,
during the seventh month, a lumen appears. The lumina appear in the

Mesorchium
Intermediate cords

Rete

Ductus deferens

Epithelium

Tunica albuginea

Testis cord

Primordial
germ cell

FIG. 226. — Section through the testis of a 100 mm. human fetus. X 44.

peripheral ends of the testis cords, and, extending toward the rete testis,
meet lumina which have formed there. Thus the solid cords of both are
converted into tubules. The distal portions of the testis tubules anasto-
mose and form the tubuli contorti. Their proximal portions remain
straight, as the tubuli recti. The rete testis becomes a network of small
tubules that finally unite with the collecting tubules of the mesonephros
(seep. 219).

The primordial germ cells of the testis cords form the spermatogonia
of the spermatic tubules, and from these at puberty are developed the
later generations of spermatogonia (p. 14). The indifferent cells of the
tubules become the sustentacular cells (of Sertoli) of the adult testis. Cer-
tain cells of the intermediate cords, epithelial in origin, are transformed
into large, pale cells, which, after puberty, are numerous in the interstitial
connective tissue and hence are called interstitial cells. The intermediate
cords, as such, disappear, but the connective-tissue sheaths of the tubules

INTERNAL SEXUAL TRANSFORMATIONS— OVARY

215

unite to form septula which extend from the mediastinum testis to the
tunica albuginea. The latter becomes a relatively thick layer in the adult
testis and is so called because of its whitish appearance.

Differentiation of the Ovary. — -The primitive ovary, like the testis,
consists of an inner epithelial mass bounded by the parent peritoneal
epithelium. The ovarian characters appear much more slowly than those
of the testis. In fetuses of 50 to 80 mm. (C H), the inner epithelial mass,
composed of indifferent cells and primordial germ cells, becomes less dense
centrally and bulges into the mesovarium (Fig. 227). There may be dis-
tinguished a dense, outer cortex beneath the epithelium, a clearer medul-

Tubules of mesonephrc
(Paroophoron)

Ligamenlunt ovarii

Uterine (Mul-
lerian) tube

Primordial
germ cells

Medulla

Cortex .

FIG. 227.— Section of an ovary from a 65 mm. human fetus. X 44.

lary zone containing large germ cells, and a dense, cellular anlage in the
mesovarium, the primitive rete ovarii, which is the homologue of the rete
testis. No epithelial cords and no tunica albuginea are developed at this
stage, as in the testis.

Later, three important changes take place: (i) There is an ingrowth
of connective tissue and blood vessels from the hilus, resulting in the forma-
tion of a mediastinum and septula. (2) Most of the cells derived from the
inner epithelial mass are transformed into young ova, the process extend-
ing from the rete ovarii peripherally (Fig. 227). (3) In fetuses of from 80
to 1 80 mm. (C R) length, the ovary grows rapidly, owing to the formation
of a new peripheral zone of cells, derived perhaps in part from the peri-
toneal epithelium. At the end of this period the septulae line the epithe-
lium with a fibrous sheath, the anlage of the tunica albuginea. Hereafter,
although folds of the epithelium are formed, they do not penetrate beyond
the tunica albuginea, and all cells derived from this source subsequently
degenerate. This new peripheral zone, according to Felix, is always a

216

THE UROGENITAL SYSTEM

single cellular mass in man, cords, or Tfluger's tubes,' never growing in
from the epithelium. Generally it has been believed that the primary
follicles are derived from the subdivision of such cords.

Coincident with the origin of a new zone of cells at the periphery of
the ovary, goes the degeneration of young ova in, the medulla. By the
ingrowth into this region of connective tissue, the ova are separated into
clusters, or cords, the genital cells of which all degenerate, leaving in the

Primordial egg

Germinal epithelium

Primordial ovum

Blocd -vessel

Primordial ova

FIG. 228. — Ovary of five-months' fetus, showing primordial follicles (De Lee).

medulla only a stroma of connective tissue. Late in fetal life, indifferent
cells, by surrounding the young ova of the cortex, produce primordial
follicles (Fig. 229 A}. During the first year after birth the primitive
follicles are transformed into vesicular (Graafian) follicles. By cell divi-
sion, the follicle cells form a zone many layers deep about the young
ovum (Fig. 229 B}. Next, a cavity appears in the sphere of follicle cells;
it enlarges, and produces a vesicle filled with fluid (Figs. 4 and 230). The
ovum is now located eccentrically and the follicle cells directly surrounding
it constitute the cumulus oophorus (egg-bearing hillock). About the
stratum granulosum, formed by the original follicle cells, there is differen-
tiated from the stroma of the ovary the theca jolliculi. This is composed

INTERNAL SEXUAL TRANSFORMATIONS— OVARY

217

" granulosum

s S

vf^^^l^ ( vSS— ^=^-

~ ^ vc: x/ • ' ' ~ ^^^^'^

lordial ova and early stages in the development of the Graafian follicle (De Lee).

^^^--^- ~' .•" •;>••-•. .

SI

A

FIG. 229. — Primo

Cumulus oophorus Ovum
Zona pdlucida\J Nuckus

&i!%&

.

-Stratum granulosum

FIG. 230.— Graafian follicle and ovum from the ovary of a fifteen-year-old girl. X 30.

2l8 THE UROGENITAL SYSTEM

of an inner, vascular tunica internet and an outer, fibrous and muscular
tunica externa.

Fully formed Graafian follicles are found in the ovaries during the
second year and they may be even present before birth. Ovulation may
occur at this time, but usually these precociously formed follicles degen-
erate with their contained ova. Thus, although thousands of ova are
produced in the ovary, comparatively few are set free ready for fertiliza-
tion during the sexually active life of the female, from puberty to the
climacteric period, or menopause. The details of ovulation and its rela-
tion to menstruation has been discussed on p. 10.

The Corpus Luteum. — After ovulation, a blood clot, the corpus hemorrhagicum, forms
within the empty follicle. The follicle cells of the stratum granulosum proliferate, enlarge,
and produce a yellow pigment (R. Meyer, 1911). The whole structure, composed of
lutein cells and connective tissue strands, is termed the corpus luteum, or yellow body.
The blood clot is resorbed and replaced by fibrous scar tissue, white in color, known as
the corpus albicans. If pregnancy does not intervene, the corpus luteum spurium reaches
its greatest development within two weeks and then degenerates. In cases of pregnancy
the corpus luteum verum continues its growth until, at the thirteenth week, it reaches a
maximal diameter of 15 to 30 mm.; at birth it is still a prominent structure in the ovary.
It is believed to produce an important internal secretion, for if the corpus luteum is re-
moved the ovum fails to attach itself to the wall of the uterus, or if already embedded, de-
velopment ceases (Fraenkel). An influence in retarding ovulation and stimulating the
mammary gland function has also been shown experimentally (L. Loeb; O'Donoghue).

Comparison of the Testis and Ovary. — It is clear that the superficial
epithelium, after forming the inner epithelial mass, takes no further part in
the differentiation of the testis and only a small part, if any, in that of the
ovary. The testis cords, rete testis, and tunica albuginea differentiate
early from the inner epithelial mass. The inner epithelial mass of the
ovary develops slowly and passively being divided and moulded by
actively ingrowing connective tissue. The Graafian follicles are not the
homologues of the testis cords, and the tunica albuginea appears late.
The rete ovarii corresponds to the rete testis, but remains a rudimentary
structure.

Anomalies. — Congenital absence or duplication of the testes and ovaries is very rare.
Fused testes and lobed ovaries are also known.

Teratomata. — These peculiar tumor-like growths occur rather frequently in the ovary,
less often in the testis and other regions. The simpler types, caller dermoid cysts, contain
ectodermal derivative such as skin, hair, nails, teeth, and sebaceous glands. They grade
into complexes consisting of organ-like masses, from all three germ layers, intermingled
without order. Misshapen representatives of all tissues and organs may be present.
Among other explanations of the cause, the isolation and subsequent faulty development
of blastomeres has been advanced.

TRANSFORMATION OF THE MESONEPHRIC TUBULES AND DUCTS 2IQ

Transformation of the Mesonephric Tubules and Ducts. — In both
male and female embryos of 21 mm. the mesonephros has degenerated
until only twenty-six tubules at most persist, and these are separated into
a cranial and a caudal group. In the cranial group of 5 to 12 tubules the
collecting portions have separated from the secretory portions. The
free ends of these collecting tubules project against that part of the inner
epithelial mass which gives rise to the rete tubules of either testis or ovary
(Figs. 225 and 227). The cords of the rete develop in contact with the
collecting tubules of the mesonephros and unite with them in fetuses of
60 mm. (C H).

In the male, the lumina of rete and collecting tubules become contin-
uous and the cranial group of the latter are transformed into the ductuli
ejrferentes of the epididymis. During the fifth month of pregnancy the
ductuli efferentes coil at their proximal ends, and when surrounded by
connective tissue they are known as lobuli epididymidis. The lower
group of collecting tubules persist as the vesitigial paradidymis and
ductuli abber antes (Fig. 238 C}.

The efferent ductules convey spermatozoa from the testis tubules
into the mesonephric duct, which thus becomes the male genital duct.
The cranial portion of the mesonephric duct coils and forms the ductus
epididymidis; its blind cranial end persists as the appendix epididymidis.
The caudal portion of the male duct remains straight, and, as the ductus
deferens, extends from the epididymis to the urethra. Near its opening
into the latter it dilates to form the ampulla, from the wall of which is
evaginated the sacculated seminal vesicle in fetuses of 60 mm. (C H).

The epithelium of the genital duct is at first a single layer of columnar cells which
form non-motile cilia at 70 mm. (C H). Quite late in development the surrounding mesen-
chyma gives rise to the muscular layers.

In the female, the rete ovarii is always a rudimentary structure, yet
some time before birth it becomes tubular and unites with the cranial
persisting group of mesonephric collecting tubules which forms a rudi-
mentary structure, the epoophoron (Fig. 238 B}. The epithelial cells of
the latter become ciliated, and smooth muscle tissue is developed corres-
ponding to that of the epididymis. The caudal group of mesonephric
tubules constitute the paroophoron. Usually the greater part of the male
genital ducts atrophy in the female, the process beginning at 30 mm.
Thus the tubules of the epoophoron are left without an outlet. Portions
of the mesonephric ducts persist as (Gartner's) ducts of the epoophoron.

Gartner's ducts may extend as vestigial structures from these epoophoron to the lateral
walls of the vagina, passing through the broad ligament and the wall of the uterus. They
open into the vagina close to the free border of the hymen (R. Meyer). The ducts are
rarely present throughout their entire length and are absent in two-thirds to three-quarters
of the cases examined.

220 THE UROGENITAL SYSTEM

Transformation of the Miillerian Ducts. — The Mullerian, or female
ducts, after taking their origin as described on p. 211, grow caudally,
following the course of the mesonephric ducts (Fig. 224). At first lateral
in position, the Mullerian ducts cross the mesonephric ducts and enter
the genital cord median to them (Fig. 238 A). In embryos of 20 to 30
mm. their caudal ends are dorsal to the urogenital sinus, extending as
far as the Mullerian tubercle, a projection into the median dorsal wall of
the vesico-urethral anlage formed by the earlier entrance of the mesone-
phric ducts (Fig. 219). This tubercle marks also the position of the
future hymen. In fetuses of 70 mm. (C H) the Mullerian ducts break
through the wall of the urethra and open into its cavity. Before this
takes place, the caudal ends of the Mullerian ducts, which are pressed
close together between the mesonephric ducts in the genital cord, fuse,
and in both male and female embryos of 20 to 30 mm. give rise to the
unpaired anlage of the uterus and vagina (Figs. 219 and 231 A). The
paired cranial portions of the Mullerian ducts become the uterine tubes.
During development the ostial ends of the uterine tubes undergo a true
descensus from the third thoracic to the fourth lumbar vertebra.

In the male, these parts are rudimentary. Those portions of the
Mullerian ducts corresponding to the uterine tubes and uterus begin to
degenerate at 30 mm. The vaginal portions remains as a pouch on the
dorsal wall of the urethra, the vagina masculina, or prostatic utricle.
The older term, uterus masculinus, is obviously a misnomer which
should be abandoned. The extreme cranial end of each Mullerian duct
persists as an appendix testis (Fig. 238 C}.

The Uterus and Vagina. — Since the Mullerian ducts develop in the
urogenital folds, they make two bends in their course (Fig. 231 A) corres-
ponding to those of the folds (p. 209). Each consists of a cranial longitu-
dinal portion, a middle transverse portion, and a caudal longitudinal
portion which is fused with its fellow to form the utero-vaginal anlage.
At the angle between the cranial and middle portions is attached the
inguinal J old, the future round ligament of the uterus (Figs. 232 and 233).
The mesenchyma condenses about the utero-vaginal anlage and the middle
transverse portion of the Mullerian ducts, forming a thick, sharply defined
layer, from which is differentiated the muscle and connective tissue of the
uterus and vagina (Fig. 231 B). As development proceeds, the cranial
wall between the transverse portions of the Mullerian ducts bulges out-
ward, so that its original cranial concavity becomes convex (Fig. 231 B}.
The middle, transverse portions of the ducts are thus taken up into the
wall of the uterus forming itsfundus, while the narrow cervix of the uterus
and the vagina arise from the utero-vaginal anlage. Through the dif-
ferentiation of its mesenchymatous wall, the uterus is first brought into
relation with the round ligament.

THE UTERUS AND VAGINA

221

The Hymen. — At the point where the utero-vaginal anlage breaks
through the wall of the urogenital sinus there is present the tubercle of
Miiller that marks the lower limits of the vagina. The tubercle is com-
pressed into a disk, lined internally by the vaginal epithelium, externally
by the epithelium of the urogenital sinus, or future vestibule. These
layers, with the mesenchyma between them, constitute the hymen, which
thus guards the opening into the vagina (Fig. 238 A, B). A circular
aperture in the hymen is for a time closed by a knob of epithelial cells, but
later when the hymen becomes funnel-shaped the opening is compressed
laterally to form a sagittal slit, the ostium vagince. Miiller's tubercle
persists in the male as the colliculus seminalis, from the summit of which
leads off the prostatic utricle.

Uterine tube B Futidus of uterus

Round ligament
^ Transverse portion of

uterine tube

^Mesenthyme

FIG. 231. — Diagrams showing the development of the uterus and vagina (modified after Felix).

Growth of the Uterus. — The uterus shortens one-third soon afters birth and does not
fully recoup this loss until the eleventh year. The virginal size is attained by a short
period of rapid growth, chiefly before puberty.

At 80 mm. (C R) the mucosa and muscularis may be distinguished. The first circular
muscle fibers appear in 180 mm. (C R) fetuses; the other muscle layers develop later. The
epithelium of the uterine tubes and the fundus of the uterus remains simple; that of the
cervix and vagina becomes stratified (38 mm., C R). The tubular fundus glands of the
uterus may not appear until near puberty. The vagina is at first without a lumen;
from the third to the sixth months of fetal life, dorsal and ventral solid outgrowths of epith-
elium form its fornices. The vaginal lumen appears in fetuses of 150 to 200 mm. (C R),
arising by the degeneration of the central epithelial cells.

Anomalies. — Many cases of abnormal uterus and vagina occur. The more common
anomalies are: (i) Complete duplication of the uterus and vagina due to the failure of the
Miillerian ducts to fuse. (2) Uterus bicornis, due to the incomplete fusion of the ducts.
Combined with these defects, the lumen of the uterus and vagina may fail, partly or com-
pletely, to develop and the vaginal canal may not open to the exterior (imperforate
hymen). (3) The body of the uterus may remain flat (uterus planifundus; Fig. 231 A) or
may fail to grow to normal size (uterus fetalis and infantalis). (4) Congenital absence of
one or both uterine tubes, or of the uterus or vagina rarely occurs, but may be associated
with hermaphroditism of the external genitalia. The hymen is of variable shape and may
be imperforate.

THE UROGENITAL S-YSTEM

Ligaments of the Internal Genitalia. — Female. — The loose mesen-
chyma of the genital cord gives rise laterally to the broad ligaments of the
uterus in females. A portion of the primitive genital fold unites the caudal
end of the ovary to the genital cord. This acquires connective tissue and
smooth muscle fibers and forms the proper ligament of the ovary (Fig. 233).
Since the uterus develops in the genital cord, the ligament of the ovary
extends to the posterior surface of the uterine wall. In the male the homo-
logue of the proper ligament of the ovary is the ligament of the testis.

In both sexes the inguinal fold extends from the urogenital fold to the
inguinal crest, located on the inside of the ventral abdominal wall, a
point which marks the future entrance of the inguinal canal. The in-

Diaphragmatic liga
ment of mesonephro.

uprarenal gland

ullerian duct
in mesonephric fold

enital gland

Inguinal fold

Glans of phallus

Genital swelling

FIG. 232. — Ventral dissection of a human embryo of 23 mm., showing the urogenital organs.
The right suprarenal gland has been removed to show the metanephros.

guinal fold thus forms a bridge in 14 mm. embryos between the urogenital
fold, in the middle portion of which the uterus develops in the female, and
the abdominal wall at the entrance of the inguinal canal (Fig. 232). In
the inguinal crest is differentiated the conical anlage of the chorda guber-
naculi, which later becomes a fibrous cord. The abdominal muscles de-
velop around it, forming a tube, the inguinal canal, and the external
oblique muscle leaves a foramen, through which the chorda connects
with a second cord termed in the male the ligamentum scroti, in the female
the ligamentum labiate. The chorda gubernaculi and the ligamentum
labiale together constitute the round ligament of the uterus (Fig. 233),
as they form a continuous cord extending from the urogenital fold to the
base of the genital tubercle. With the development of the uterus in the •
urogenital fold, the round ligament becomes attached to its ventral
surface.

DESCENT OF THE TESTIS AND OVARY

223

Male.— The ligamentum testis, like the ligamentum ovarii, develops
in the genital fold and extends from the caudal end of the testis to the
mesonephric fold, at a point opposite the attachment of the inguinal fold*
The inguinal fold, as we have seen, is continuous with the inguinal crest
and the chorda gubernaculi. A cord develops in the mesonephric fold
and connects the ligamentum testis with the chorda gubernaculi, for in
the male the uterus does not intervene between these two. The chorda
gubernaculi is continued to the integument of the scrotum by way of the
ligamentum scroti. Thus there is formed a continuous cord, the guber-

Suprarenal gland

Diaphragmatic ligamen

Ligamentum ovarii

Round ligament of uterus

Phallus

Metanephros

Pelvis of metanephros

Uterine tube
Rectum

Utero-vaginal anlage
Bladder

nital swelling
Glans clitoridis

FIG. 233. — Ventral dissection of a female human embryo of 34 mm..

are dissected out and the left suprarenal gland has been removed.

naculum testis, extending from the caudal end of the testis through the
inguinal canal to the scrotal integument. The gubernaculum is composed
of the ligamentum testis, a mesonephric cord, .the chorda gubernaculi, and the
ligamentum scroti. It is the homologue of the ovarian ligament plus the
round ligament of the uterus, between which the uterus intervenes (Fig. 233.)
Descent of the Testis and Ovary. — The original position of the testis
and ovary is changed during the later stages of development. At first
they are elongate structures, extending in the abdominal cavity from the
diaphragm caudally towards the pelvis (Fig. 220). Since their caudal
ends continue to grow and enlarge while their cranial portions are atrophy-
ing, there is a wave-like shifting of the glands caudad. An actual internal
descent, however, does not occur. When the process of growth and de-

224 THE UROGEMTAL SYSTEM

generation is completed, the caudal ends of the testis lie at the boundary
line between the abdomen and pelvis, whereas the ovaries are located in
the pelvis itself, a position which they retain. Owing to the rotation of
the ovary about its middle point as an axis, it takes up a transverse position.
It also rotates nearly 180° about the Mullerian duct as an axis, and thus
comes to lie caudal to the uterine tube.

The testis normally leaves the abdominal cavity and descends into
the scrotum. As described above, there is early developed between the
testis and the integument of the scrotum a fibrous cord, the gubernaculum
testis. Owing to changes in the position of the ventral abdominal wall and
umbilical arteries, changes connected with the return of the intestinal coils
into the ccelom, there are formed in each side of the abdominal wall sac-
like pockets, the anlages of^the vaginal sacs. Close to each saccus (processus)
vaginalis lies the caudal end of a testis, while extending into the scrotum out-
side the peritoneum is the gubernaculum testis. The saccus vaginalis later

FIG. 234. — The descent of the testis; a.c.. Abdominal cavity; d-d., ductus deferens; £./.,
gubernaculum testis; s., scrotum; s.v., saccus vaginalis; t.v., tunica vaginalis; x., obliterated
vaginal sac.

invaginates into the scrotum over the pubic bone. Due to the actual and
relative shortening of the gubernaculum testis the descent of the testis
into the vaginal sac begins during the seventh month of fetal life, and.
by the end of the eighth month, or at least before birth, the testis is usually
located in the scrotum (Fig. 234). It must be remembered that the testis
and gubernaculum are covered by the peritoneum before the descent be-
gins, consequently the testis follows the gubernaculum along the inguinal
canal dorsal to the peritoneum, and, when it reaches the scrotum, is invag-
inated into the saccus vaginalis, but does not lie in the coelomic extension.
The gubernaculum of a newborn is but one-fourth its length at the begin-
ning of the descensus. After birth it atrophies almost completely.

Shortly after birth the narrow canal, connecting the saccus vaginalis
with the abdominal cavity, becomes solid and its epithelium is resorbed.
The vaginal sac, now isolated, becomes the tunica vaginalis of the testis.
Its visceral layer is closely applied to the testis and its parietal layer forms
the lining of the scrotal sac. The ductus deferens and the spermatic
vessels and nerves are of course carried down into the scrotum with the
testis and epididymis. They are surrounded by connective tissue, and,

THE EXTERNAL GENITALIA

225

with the spermatic vessels, constitute the spermatic cord. Owing to the
descent of the testis, the ductus deferens is looped over the ureter in the
abdomen (Fig. 238 Q.

In the female, shallow peritoneal pockets, frequently persistent as the
diverticula of Nuck, correspond to the vaginal sacs of the male. Rarely
a more or less complete descent of the ovary into the labium ma jus occurs.

Anomalies. — At times, the testes remain undescended in the abdomen, a condition
known as cryptorchism and associated with sterility in man. In some mammals (whale,
elephant) it is the normal condition. The inguinal canals of man may remain open and
allow the testes to slip back into the abdominal cavity. Such conditions lead to inguinal
hernia of the intestine. Open inguinal canals, with a periodic descent during the breeding
season, occur normally in some animals (rodents, bats).

C. THE EXTERNAL GENITALIA

Indifferent Stage. — The external genitalia of both sexes are similar
until the beginning of the third month of development, when the indifferent
anlages become moulded into sexually distinct organs. There develops
early in the midline of the ventral body wall, between the tail and um-
bilical cord, the cloacal tubercle. Upon this appears a knob-like struc-
ture, the phallus, and the two together constitute the genital eminence (Fig.
220). The cloacal tubercle forms about the base of the phallus genital
swellings, more pronounced laterally. The phallus grows rapidly, carry-
ing with it the phallic portion of the urogenital sinus (Fig. 219). At the
end of the phallus the epithelium of the sinus forms a solid urethral plate.

ABC

FIG. 235. — Three stages in the developement of the external genitalia in human embryos of
24 to 34 mm. (after Tourneux in Heisler). Indifferent stage: i, Phallus; 2, glans; 3, primitive
urogenital opening; 4, genital tubercle or swelling; 5, anus; 6, coccyx.

Along the anal surfaces of the phallus, in the midline, the wall of the uro-
genital sinus breaks through to the exterior and forms the slit -like, prim-
itive urogenital opening (Fig. 235). In embryos of 21 to 26 mm., at the
end of the phallus, the glans is marked off from the base by a circular
groove, the coronary sulcus (Figs. 232 and 23 5.6).

Female. — A deep groove appears about the base of the phallus, separa-
ting it from the genital swellings, which become circular (Fig. 235 C).
From the swelling differentiates : (i) cranially, the mons pubis; (2) laterally,

226

THE UROGENITAL SYSTEM

the right and left labia majora; (3) caudally, the posterior commissure (Fig.
236). The glans of the phallus forms the glans clitoridis of the female.
On the anal surface of the phallus, beginning at the coronary sulcus, the
primitive urogenital opening closes distally, forming the urethral groove.
Proximally it remains open, as the definitive urogenital opening near the
base of the phallus. The lips of this groove and opening enlarge and
become the labia minora. The cranial surface of the phallus forms a fold,

A B C

FIG. 236. — Three stages in the development of the female external genital ia (after Tour-
-•••.. u.^ipr1). i. Clitoris; 2, glans clitoridis; 3, urogenital aperture on each side of which are
the labia minora (7.1; 4., labia majora; 4, anus; 7, labia minora.

•pucium, which, however, is not the exact homologue of the male
m. This in the female is represented by a ring-like rudiment at
the base of the glans clitoridis (Felix, 1912).

Male. --The phallus grows rapidly at its base, so that the glans and
prm 11 u v^ urogenital opening are carried some distance from the anus (Fig.
237). A cylindrical collar of the epithelium, incomplete on the anal side,
grows down into the end of the glans, which becomes the glans penis By
the disappearance of the central cells of the epithelial downgrowth, an
outer cylindrical mantle, the prepucium, or fore-skin, is formed about the
spheroidal glans (cf. Fig. 158). Where the epithelial downgrowth is in-
complete the glans and fore-skin remain connected, the persisting connec-
tion being the frenulum prepucii. The corpora cavernosa penis arise as
paired mesenchymal columns. The corpus cavernosum urethras results
from the linking of similar, unpaired anlages, one in the glans the other
in the shaft.

The urogenital sinus, as we have seen, extends out into the phallus
and in the glans becomes the solid urethral plate. With the great elonga-

THE EXTERNAL GENITALIA

227

tion of the male phallus, the open portion of the urogenital sinus also is
lengthened and forms the greater part of the penile urethra. In fetuses of
70 mm. (C R), the groove-like primitive urogenital opening, located in
the male near the glans and distant from the anus, begins to close and thus
forms a further portion of the urethra. The lips of the urogenital opening,
it will be remembered, correspond to the labia minora, or nymphce, of the
female. Finally, at 100 mm. (C H ?), the solid urethral plate of the glans
splits, forms a groove to the tip of the glans, and this groove in turn is
closed, continuing the urethra to the definitive openrng at the tip of the
glans (Fig. 237 C). Owing to the rapid elongation of the penis, there is
formed between its base and the anus an unpaired area, termed by Felix

ABC

FIG. 237. — Three stages in the development of the male external genitals (after Tourneux
in Heisler). I, Penis; 2, glans; 3, urogenital groove; 4, genital swellings corresponding to labia
majora of female; 5, anus; 7, scrotal area with perineo-scrotal raphe.

(1912) the the scrotal area, as it is the anlage of the scrotum (Fig. 237 A).
At 60 mm. (C H) this forms a median scrotal swelling, continuous laterally
with the paired genital swellings which form the labia majora in the fe-
male. When the scrotal sac develops in the scrotal area, the dense tissue
in the median line is stretched and forms the septum scroti. The attach-
ment of this septum forms an external median depression, the raphe.
The testes descend into the vaginal sacs of the scrotum through the paired
genital swellings, as described on p. 224, but the scrotum itself is an un-
paired structure derived from the scrotal area. After the descent of the
testes the genital swellings disappear (Fig. 237 C}.

Comparing the male and female external genitalia, it is plain that the
glans penis and glans clitoridis are homologous. The labia minora cor-
respond to the phallic folds which close about the primitive urogenital
opening on the anal surface of the penis. The greater part of the shaft
of the male phallus does not develop in the female. On the other hand,
the genital swellings enlarge and become the mons pubis and labia majora

228

THE UROGENITAL SYSTEM

of the female, while in the male they are only temporary structures. The
scrotum does not develop in the female, being represented only by the
posterior commissure of the labia majora.

Accessory Glands. — The prostate gland develops in both sexes as out-
growths of the urethra, both above and below the entrance of the male
ducts. The tubules arise at 55 mm. (C H) in five distinct groups and total
an average number of 63 (Lowsley, 1912). The surrounding mesencyhme
differentiates both white fibrous connective tissue and smooth muscle
fibers into which the anlages of the prostate grow. In the female the
homologue is rudimentary; these isolated paraurethral ducts (of Skene)
number at most three.

The bulbo-urethral glands (of Cowper) arise in male embryos of 30
mm. (C R) as solid, paired epithelial buds from the entoderm of the uro-
genital sinus. The buds penetrate through the mesenchyme of the corpus
cavernosum urethrae, about which they enlarge. The glands branch, and,
at 1 20 mm. (C R), the epithelium becomes glandular. The vestibular glands
(of Bartholin) are the homologues in the female of the bulbo-urethral
glands. They appear. at the same age as the male glands, grow until
after puberty, and degenerate after the climacterium.

HOMOLOGIES OF INTERNAL AND EXTERNAL GENITALIA

Male

Indifferent Stage

Female

Ductuli efferentes.
Paradidymis.

Mesonephric collecting tubules.
Cranial group.
Caudal group.

Epoophoron.
Paroophoron.

Ductus epididymidis.
Ductus deferens.
Seminal vesicle.
Ejaculatory duct.

Mesonephric duct.

Gartner's duct.

(i) Appendix testis.

(2)

(3) Utriculus prostaticus
(Vagina masculina).

Mtillerian duct.

(i) Uterine tube.
(2) Uterus.
(3) Vagina.

Colliculus seminalis.

M tiller's tubercle.

Hymen.

(i) Prostatic and mem-
branous urethra.
(2) Prostate gland.
(3) Bulbo-urethral glands.

Urogenital sinus.

(i) Urethra and vestibule.

(2) Paraurethral ducts.
(3) Vestibular glands.

Glans penis.
Anal surface of penis,
(i)

(2)

(3) Scrotum.

Phallus.
Glans..
Lips of urethral groove.

Genital swellings.

Glans clitoridis.
Labia minora.
(i) Mons pubis.
(2) Labia majora.
(3) Posterior commissure.

THE EXTERNAL GENITALIA

22Q

Miillerian duct

Bladder'

Mesonephros

Urogenital sinus

Intestine

Phallus

Cloaca

INDIFFERENT STAGE

roopnoron
Gartner's duct

Labium majus

Labium minor

Penis

Uterine lube

&- Paradidymis
— Ductulus abberans

Ductus deferens

Seminal vesicle

Scrotum - \ t' \

FIG. 238. — Diagrams to show the development of male and female genital organs from a
common type (after Allen Thompson).

230 THE UROGENITAL SYSTEM

Anomalies. — If the lips of the slit-like urogenital opening on the under surface of the
penis fail to fuse, hypospadias results. Rarely there is a similar defect on the upper sur-
face— epispadias .

True hermaphroditism consists in the presence of both testes and ovaries in the same
individual. It is of rare occurrence in birds and mammals, is not uncommon in the lower
vertebrates, and is the normal condition in many invertebrates (worms, molluscs). Ac-
cording to Pick (1914), there are only four authentic cases in man; these have on one side,
at least, a combined ovotestis. The internal genitalia are faultily bisexual. The external
genitalia show mixed male and female characteristics. The secondary sexual characters
(beard, mammae, voice, etc.) are usually intermediate, tending now one way, now the other.

False hermaphroditism is characterized by the presence of the genital glands of one
sex in an individual whose secondary sexual characters and external or internal genitalia
resembles those of the opposite sex. In masculine hermaphroditism an individual pos-
sesses testes, often undescended, but the external genitals (by retarded development) and
secondary characters are like those of the female. In feminine hermaphroditism ovaries
are present, and sometimes descended, but the other sexual characters, such as enlarged
clitoris or fused labiae, simulate the male. The cause of hermaphroditism is unknown.

THE UTERUS DURING MENSTRUATION AND PREGNANCY: PLACENTA AND
DECIDUAL MEMBRANES

Two sets of important changes take place normally in the wall of the
uterus. One of these is periodic between puberty and the menopause
(about the forty-fifth year) and is the cause of menstruation (monthly
flow). These periodic changes, comparable to the oestrus cycle in lower
animals, may also be regarded as preparatory to the second set of changes
which take place if pregnancy occurs and give rise to the decidual mem-
branes and placenta.

Menstruation. — The periodic changes that accompany the phenome-
non of menstruation form a cycle which occupies twenty-eight days.
This period is divided into: (i) a phase of uterine congestion — six or seven
days; (2) 'a phase of hemorrhage and epithelial desquamation — three to
five days; (3) a phase of regeneration of the uterine mucosa — -four to six
days ; (4) finally, an interval of rest or slight regeneration — -twelve to six-
teen days.

During the first phase, the uterine mucosa is thickened to two or three
times its resting condition, both because of vascular congestion and on
account 'of the actual increase of connective tissue cells. The uterine
glands become longer, and their deeper portions especially are dilated and
more convoluted because they are filled with secretion. Blood escapes
from the enlarged capillaries by diapedesis and forms subepithelial masses.
At the end of this stage, the uterine mucosa shows a deep spongy layer
and a superficial compact layer, these corresponding to similar layers in
the decidual membranes of pregnancy.

During the second phase, that of menstruation proper, the superficial
blood vessels rupture and add to the blood escaping into the uterine cavity ;

THE UTERUS DURING MENSTRUATION AND PREGNANCY 231

there is also an active discharge of secretion from the uterine glands. The
surface epithelium and a portion of the underlying tissue may or may
not be desquamated. In some cases the surface epithelium and most of
the compact layer may be expelled, aided by painful contractions of the
uterus.

In the third stage, the mucosa becomes thin, with straight, narrow
glands, between which are fusiform, closely packed stroma cells. Any
surface epithelium which has been desquamated is regenerated from
the epithelium of the glands, and gradually the mucosa returns to a
resting condition, during which, however, there is a slow process of cell
proliferation.

Implantation of the Ovum. — The earliest known human ova are al-
ready completely embedded in the uterine mucosa. From the careful
study of early human embryos by Bryce and Teacher, Peters, Herzog, and
others, and from more complete observations on other mammals, such as
the guinea pig, the course of events in man is reasonably certain.

Ovulation sets the ripe ovum free within the abdominal cavity; from
whence the beating cilia on the fimbriae of the uterine tube sweep it into
the tubal ampulla. There it may be fertilized and carried to the uterus
by the cilia of the tubal epithelium. During this period of migration,
which is estimated as occupying about eight days, the ovum loses its sur-
rounding follicle cells and pellucid membrane and begins its development.
Thus when it reaches the uterus, and is ready for implantation, it is an
embryo with trophectoderm developed, although the blastodermic vesicle
is not more than 0.2 mm. in diameter (von Spee).

Since ovulation occurs most often in the intermenstruum, Grosser believes that the
embryo reaches the uterus during the premenstrual period. The congestion and loosening
of the uterine tissue at this time would seemingly favor the implantation of the embryo,
and the glandular secretion might afford nutriment for its growth until implantation oc-
curs. The first phase of menstruation, according to this view, prepares the uterine mucosa
for the reception of the embryo. If pregnancy supervenes, it soon inhibits any further
premenstrual changes so that menstruation does not occur. Menstruation proper would
then represent an over-ripe condition of the mucosa and the abortion of an unfertilized
ovum.

If the ovum becomes implanted and develops elsewhere than in the uterus the
condition is known as an extrauterine, or ectopic pregnancy. The commonest site is the
uterine tube, tubal pregnancy. Attachment to the peritoneum, abdominal pregnancy, and
the development of an unexpelled ovum within the ruptured follicle, ovarian pregnancy, are
known also.

The embryo penetrates the uterine mucosa as would a parasite, the
trophectoderm supposedly producing an enzyme which digests away the
maternal tissues until the embryo is entirely embedded (Fig. 239). Dur-
ing implantation, the trophectoderm also absorbs nutriment (chiefly blood)
from the uterine mucosa for the use of the embryo. The process of im-

232

THE UROGENITAL SYSTEM

plantation is supposed to occupy one day. At the point where the embryo
enters the mucosa a fibrin clot soon appears and eventually the opening is
completely closed (Fig. 239).

The Decidual Membranes (Figs. 240 and 241).- — With the increase in
size of the embryo and chorionic vesicle, the superficial covering layer of the
maternal mucosa bulges into the cavity of the uterus and forms the decidua
capsularis (old term, decidua reflexa). The deep layer of the mucosa
next the inner side of the embryo forms the anlage of the future maternal
placenta and is the decidua basalis (decidua serotina). The mucosa lining

Maternal vessel Trophoderm Uterine gland Trophoderm

__

Uterine gland
Uterine epitheli

Maternal vessel

Uterine gland
e epithelium

Blood clot

FIG. 239. — Section through a human embryo of .16 mm. embedded in the uterine mucosa
(semi-diagrammatic after Peters), am., Amniotic cavity; b.s., body stalk; ect., ectoderm of
embryo; ent., entoderm; mes., mesoderm; y.s., yolk sac.

the rest of the uterus is differentiated into the decidua vera (decidua parie-
talis of Bonnet).

Differentiation of the Trophectoderm. — -The chorion is at first com-
posed of an inner, mesodermal layer and an outer, epithelial layer, the
trophectoderm (Fig. 74). From the trophectoderm there is developed an
outer syncytial layer, the trophoderm (Fig. 239). This invades and de-
stroys the maternal tissues. In the latter large vacuoles are formed, either
directly by the syncytial tissue (Bryce and Teacher), or by the blood
escaping from the ruptured vessels under pressure (Peters), and thus
blood lacuna are produced. The trophoderm thickens at intervals and

THE UTERUS DURING MENSTRUATION AND PREGNANCY

233

forms on the surface of the chorion solid cords of cells, the primary villi
(Fig. 239). The chorionic mesoderm grows out into these cords, which
branch profusely and become secondary, or true villi (Fig. 242). During
the development of the villi, the blood lacunae in the trophoderm around
the villi expand, run together, and produce intervillous blood spaces which
surround the villi and bathe the epithelium with blood. The syncytial
trophoderm, from being a spongy network, is now reduced to a continuous

Uterine cavity

Chorionic Cavity

Chorion

frondosum

Decidua

basalis

Decidua capsularis

Muscularis

Decidua vera

Cervical canal

FIG. 240. — Gravid uterus of about one month, longitudinal section.

layer covering the outer surfaces of the villi and chorion. Branches of the
umbilical vessels develop in the mesoderm of the chorion and villi. The
mesodermal core of each villus and its branches is now covered by a two-
layered epithelium, an inner, ectodermal layer with distinctly outl ned
cuboidal cells, and an outer, syncytial trophoderm layer (Fig. 248 A).
The epithelium also forms solid columns of cells which anchor the ends of
certain villi to the maternal tissue. Islands, or nodes, of epithelial cells,
are attached to the villi or lie free in the decidua basalis; they represent

234

THE UROGENITAL SYSTEM

FIG. 241.— Diagrammatic section through a pregnant uterus at the seventh or eighth week
(after Allen Thomson). c,c, Openings of uterine tubes; c', cervix with mucous plug; dv, decidua
vera or parietalis; dr, decidual capsularis; ds, decidua basalis; ch, chorion with villi; the villi
extending into the decidua basalis are from the chorion frondosum; am, amnion; u, umbilical
cord;_c/,_allantois; y,y', yolk sac and stalk.

Mesoderm

Syncytial
Irophoderm

Core of villus

- Canalized fibrin
— Endolhelium

Canalized fibrin Maternal capillary Intermllous space

FIG. 242. — Diagram illustrating the development 'of the chorionic villi and placenta (after

Peters).

THE UTERUS DURING MENSTRUATION AND PREGNANCY 235

portions of the primitive trophectoderm. In the vessels of the chorionic
villi the chorionic circulation of the embryo is established. The blood
vessels of the uterus open into the intervillous blood spaces and here the
maternal blood circulates. The syncytial trophoderm covering the villi
is bathed in the maternal blood. Its functions are three-fold: (i) like
endothelium it prevents the coagulation of the maternal blood; (2) it
allows transudation between the blood of fetus and mother; and (3) it
assimilates substances from the maternal blood and transfers them to that
of the embryo. According to Mall (1915), the trophoderm also forms a
wall which dams or plugs the blood vessels as soon as eroded, and, with
the decidua (p. 240), permits but little blood to pass into the intervillous
spaces (cf. p. 241).

B

FIG. 243. — Human ova: A, of three weeks; B, of six weeks, showing formation of the chorion
laeve by degeneration of the chorionic villi (De Lee).

The Chorion Laeve and Frondosum. — The villi at first cover the
entire surface of the chorion. As the embryo grows more and more
out into the uterine cavity, the decidua capsularis and that portion of the
chorion attached to it are compressed, and the circulation in the inter-
villous spaces of these structures is cut off (Figs. 241 and 243). Thus,
beginning at the pole of the decidua capsularis, the villi in this portion
of the chorion degenerate during the fourth week and form the chorion
l&ve. The villi on that part of the chorion which is attached to the decidua
basalis continue their development, and, persisting, form the chorion
J'rondosum. This, with the decidua basalis of the uterus, constitutes the
placenta (Fig. 240) . The embryo is attached first to the chorion frondosum
by the body stalk (Figs. 77 B and 239), later by the umbilical cord (Fig.

236

THE UROGENITAL SYSTEM

241). Through the umbilical vein and arteries in the cord the placental
circulation of the embryo takes place.

The Decidua Vera. — During the first phase of menstruation the
uterine mucosa begins to differentiate into a broad, superficial compact
layer and into a narrower, deep spongy layer in which are found the dilated
ends of the uterine glands. After pregnancy these two layers are still
further differentiated in the wall of the decidua vera and decidua basalis.
The compact layer is much thicker than the spongy layer and in it are
found numerous stroma cells, enlarged blood vessels, and decidual cells
(Fig. 244). The decidual 'cells, frequently multinucleate, are derived

Amnion

Chorion

Compact layer

•• Vein

-Gland

-Vein

Spongy layer I*

Muscularis -

FIG. 244. — Vertical section through the wall of the uterus about seven months pregnant, with
the membranes in situ (Schaper in Lewis and Stohr). X 30.

from the stroma cells of the mucosa. They are large, being 50 ju in
diameter, with clear cytoplasm and vesicular nuclei. Their function
is in doubt. Glycogen has been found in them, but during the later
months of pregnancy many of them degenerate.

In the spongy layer of the mucosa occur the enlarged and tortuous
uterine glands of pregnancy (Fig. 244). During the first two months of
pregnancy the long axes of the glands are perpendicular to the surface
of the mucosa. Later, as the decidua is stretched and compressed owing
to the growth of the fetus, the glands are broadened and shortened and
the cavities of the glands become elongated clefts parallel to each other
and to the surface of the decidua. The gland cells become stretched

THE UTERUS DURING MENSTRUATION AND PREGNANCY 237

and flattened until they resemble endothelial cells. At birth, or in case
of late abortion, the plane of separation is in the spongy layer. Only
the deep portions of the glands remain attached to the uterine wall, and,
by the division of their cells, regenerate the epithelium of the uterus.

The Decidua Capsularis. — The capsularis, as we have seen, becomes
thin as the embryo grows (Fig. 241). To it is attached the chorion Iceve,
the villi of which degenerate. During the fourth month the increased
size of the fetus brings the capsularis into contact with the decidua vera with
which it fuses, thereby obliterating the uterine cavity. Eventually
it largely degenerates, completely so opposite the internal os uteri, where
the chorionic villi are obliterated also. During pregnancy, the lumen of
the cervix is closed by a plug formed by the secretions of the glands
opening into the cervix uteri (Fig. 241).

FIG. 245. — Mature placenta, a, Entire organ, showing fetal siirfacew ith membranes attached
to the periphery; b, a portion of attached surface showing cotyledons (Heisler).

The Placenta. — The placenta is composed of the decidua basalis,
fetal constituting the maternal portion, and of the chorion frondosum, the
contribution (Fig. 240). The area throughout which the villi of the chorion
frondpsum remain attached to the decidua basalis is somewhat circular
in form, so that at term the placenta is disc-shaped, about seven inches
in diameter and one inch thick (Fig. 245). Near the middle of its fetal
surface is attached the umbilical cord, and this surface is formed by the
amnion, the mesoderm of which is closely applied to, and fused with, that
of the chorion frondosum (Fig. 246).

The Chorion Frondosum. — The villi of this portion of the chorion
form profusely branched, tree-like structures which lie in the intervillous

238

THE UROGENITAL SYSTEM

spaces (Fig. 247). The ends of some of the villi are attached to the wall
of the decidua basalis and are known as the anchoring villi. In the con-
nective-tissue core of each villus are commonly two arteries and two veins

Root of villus

Sectioned villi

Uterine vessel I

Spongy layer

Muscular wall
of uterus

FIG. 246. — Section through a normal placenta of seven months in situ (Minot). X 5.

(branches of the umbilical vessels), cells like lymphocytes, and special
cells of Hofbauer, apparently undergoing degeneration. Lymphatics are
also present. The epithelium of the villi, as we have seen, is at first

THE UTERUS DURING MENSTRUATION AND PREGNANCY

239

composed of a layer of trophectoderm with the outlines of its cuboidal cells
sharply defined (Fig. 248 A). This layer (of Langhans) forms and is
covered by a syncytium, the trophoderm. In the later months of preg-
nancy, as the villi grow, the trophectoderm is used up in forming the
syncytium, so that at term the trophoderm is the only continuous epithelial
layer of the villi (Fig. 248 B). About the margin of the placenta the
trophectoderm persists as the closing ring, which it continuous with^the
epithelium of the chorion laeve.

Muscularis

Uterine
artery Uterine veil,

Uterine.

artery in

septum

Decidua

basalis
'ne artery in
decidual septum

Intervillous
space

Syncytium

cal vein

FIG. 247. — Scheme of placental circulation (Kollmann). Arrows indicate supply and exhaust of
blood in the intervillous spaces.

The Decidua Basalis. — This, the maternal placenta, like the decidua
vera is differentiated into a compact layer, or basal plate, which forms the
floor of the intervillous spaces, and into a deep spongy layer (Figs. 246
and 247). The first is the remains of the compact layer of the uterine
mucosa, formed during the premenstrual phase and partially destroyed
by the implantation of the ovum. The second is the modified spongy
layer of the premenstrual period, and, though thinner, shows the same
differentiation as in the decidua vera. The glandular spaces are less
numerous in the spongy layer of the decidua basalis; between the spaces

240

THE UROGENITAL SYSTEM

occur syncytial giant cells to be derived from the trophoderm of the villi.
It is in the plane of this spongy layer that the separation of the placenta
takes place at birth. The decidua is said to prevent excessive haemor-
rhage during the earlier part of pregnancy by acting as a dam between the
chorionic villi and the eroded uterus (cf. p. 235).

'yncytium

Cuboidal cell~^(of Langhans)

'onnedive tissue

Blood vessel containing
nucleated red corpuscles

Oblique section of the epithelium

Epithelium"—
Epithelial nucleus —

Capillaries *~ - - -

Syncytial knot

Small artery —

Syncytial knot -

— Syncytial knot

Epithelium

--.-W-j~Small -vein

— Capillary

FIG. 248. — Transverse sections of chorionic villi: A, at the fourth week; B, C, at the end of
pregnancy (Schaper in Lewis and Stohr).

The basal plate, or compact layer of the decidua basalis, is composed of
a connective-tissue stroma containing decidual cells, canalized fibrin,
and persisting portions of the epithelium of the villi. The 'canalized
fibrin' (Fig. 242) forms chiefly by a fibrinoid necrosis of the mucosa, but

Uterine muscle
Remains of yolk sac

Maternal blood

sinus
Decidua basal is

Placenta} septum

Marginal sinus

Fused decidua vera and
capsularis

Chorion
Amnion

FIG. 249. — Section of the uterus, showing the relation of an advanced fetus to the placenta and mem-
branes (Ahlfeld).

THE UTERUS DURING MENSTRUATION AND PREGNANCY 241

the fibrin of the maternal blood and the chorionic trophoderm also partici-
pate (Mall, 191 5). From the basal plate, septa extend into the intervillous
spaces but do not unite with the chorion frondosum (Grosser) . Near term,
these constitute the septa placenta which incompletely divided the placenta
into lobules, or cotyledons (Figs. 245 and 247). The maternal arteries and
veins pass through the basal plate, taking a sinuous course and opening
into the intervillous spaces (Fig. 247). Near their entrance they course
obliquely and lose all but their endothelial layers. The original openings
of the vessels into the intervillous spaces were formed during the im-
plantation of the ovum, when their walls were eroded by the invading
trophoderm of the villi. As the placenta increases in size, the vessels
grow larger. The ends of the villi are frequently sucked into the veins
and interfere with the placental circulation. At the periphery of the
placenta is an enlarged intervillous space that varies in extent but never
circumscribes the placenta completely. This space is the marginal sinus
through which blood is carried away from the placenta by the maternal
veins (Fig. 249). The blood of the mother and fetus does not mix,
although the epithelial cells of the villi are instrumental in transferring
nutritive substances to the blood of the fetus and in eliminating wastes
from the fetal circulation into the maternal blood stream of the intervillous
spaces.

Mall (1915) states that there is little evidence of an actual intervillous circulation;
the decidua and trophoderm are active in preventing this (pp. 239 and 240). Some
embryologists hold that the intervillous circulation is peculiar to the second half of
pregnancy. In summary, Mall regards the entire question as still open.

Relation of the Fetus to the Placenta and the Separation of the De-
cidual Membranes at Birth. — The relation of the embryo to the fetal
membranes has been described on p. 73 /./. During the first months of
pregnancy the embryo floats in the cavity of the amnion, attached to the
placenta by the umbilical cord (Fig. 241). Later, as we have seen, the
amnion fuses more or less completely to the chorion frondosum and laeve.
The decidua capsularis fuses with the decidua vera and largely disappears.
Before birth, the placenta is concave on its amniotic surface, its curvature
corresponding to that of the uterus (Fig. 249). At term, the duration of
which is taken as ten lunar months, the muscular contractions of the
uterus, termed 'pains,' bring about a dilation of the cervix uteri, the rup-
ture of the amnion and chorion lasve, and cause the extrusion of the child.
With the rupture of the membranes the amniotic liquor is expelled, the
fetal membranes remaining attached to the decidual membranes. The
pains of labor begin the detachment of the decidual membranes, the plane
of their separation lying in the spongy layer of the decidua basalis and

242 THE UROGENITAL SYSTEM

decidua vera, where there are only thin-walled partitions between the en-
larged glands (Fig. 246). Following the birth of the child, the tension of
the umbilical cord and the 'after pains' which diminish the size of the uterus,
normally complete the separation of the decidual membranes from the wall
of the uterus. The uterine contractions serve also to diminish the size
of the ruptured placental vessels and prevent extensive hemorrhage.
From the persisting portions of the spongy layer and from the epithelium
of the glands, the tunica propria, glands, and epithelium of the uterine
mucosa are regenerated.

The decidual membranes, and the structures attached to them when
expelled, constitute the 'after birth.' The placenta usually is everted
so that its amniotic surface is convex, its maternal surface concave. It
is composed of the amnion, chorion frondosum, chorionic villi with inter-
villous spaces incompletely divided by the septa into cotyledons, and
includes on the maternal side the basal plate and a portion of the spongy
layer of the decidua basalis. Near the center of the placenta is attached
the umbilical cord, and at its margins the placenta is continuous with the
decidua vera and the remains of the chorion Iseve and decidua capsularis.

Placentation. — Except the egg-laying monotremes, all mammals form some kind of
placenta. In the simplest type (Ungulates) the chorionic villi fit into crypts of the uterine
mucosa; as the two surfaces are merely apposed, the endometrium is not cast off at birth.
The highest type, as in Rodentia and Primates, is characterized by a partial destruction of
the uterine mucosa, so that the chorionic villi, dangling in cavernous spaces, are bathed by
the maternal blood which issues from eroded vessels; due to intimate fusions, the mucosa
is largely lost at birth. Intermediate conditions are found in the Carnivora; in this group
there is a chorionic invasion and erosion of the endometrium, yet the maternal blood circu-
lates within intact vessels.

Position of the Placenta in Utero and its Variations. — The position of the placenta is
determined by the point at which the embryo is implanted. In most cases it is situated on
either the dorsal or ventral wall of the uterus. Occasionally it is lateral in position, and,
very rarely (i in 1600 cases), it is located near the cervix and covers the internal os uteri,
constituting a placenta prcevia. A partially or wholly duplicated placenta, or accessory
(succenturiate) placentas may be formed from persistent patches of villi on the chorion
laeve. Cases have been observed in which from three to seven subdivisions of the placenta
occurred.

Gross Changes in the Uterus. — During pregnancy the uterus enlarges enormously,
due chiefly to the hypertrophy of its muscle fibers, and the fundus reaches the level of
the xiphoid process. After birth, it undergoes rapid involution; at the end of one week it
has lost one-half its weight, and in the eighth week the return is complete. The mucosa
is regenerated in two or three weeks from the remains of the spongy layer (Fig. 246).

CHAPTER IX

THE DEVELOPMENT OF THE VASCULAR SYSTEM
THE PRIMITIVE BLOOD VESSELS AND BLOOD CELLS

BOTH the blood cells and the primitive blood vessels arise from a tissue
termed by His the angioblast. Its origin has long been in doubt but recent
investigations by Maximow, Felix, Schulte, and Bremer point to the
mesoderm.

In the body stalk of very young human embryos, Bremer (1914) has shown the
direct origin of angioblast from splanchnic mesothelium. Moreover since this angio-
blast may antedate that of the yolk sac an entodermal origin is excluded. According
to Minot (1912), Riickert, and others, the angioblast arises in the wall of the yolk sac
from the entoderm. A further view, favored by Hertwig (1915), derives the blood
cells from entoderm, the vascular endothelium from mesoderm.

The angioblast consists initially of isolated, solid cords and masses
of cells which appear first in the splanchnic mesoderm of the body stalk and
yolk sac. The solid cords of angioblast soon hollow out, the peripheral
cells forming the endothelium of the primitive vessels, the inner cells, bathed
by a clear fluid, persisting as the primitive blood cells, or mesamceboids of
Minot. By the union of the isolated vascular spaces, the cellular network
is soon converted into a vascular plexus which completely covers the
human yolk sac. In the wall of the yolk sac this network is termed the
area vaculosa, and here aggregations of blood cells form the blood islands
(Figs. 33 and 79).
•

HAEMOPOIESIS

Two sharply contrasted views are held as to the mode of origin
(haemopoiesis) of the various adult blood elements. According to the
monophyletic theory, a common stem-, or mother cell, such as the mes-
amceboid, gives rise to all types of blood elements, both red and white.
The polyphyletic theory, on the contrary, asserts that the erythroplastids
and the several kinds of white cells are derived from two or more distinct
mother cells. The total evidence seems to favor the monophyletic view,
yet there are able dissenters (Stockard, 1915).

The Primitive Blood Cells or Mesamceboids. — These show large,
vesicular nuclei surrounded by a small amount of finely granular cytoplasm
(Fig. 250 a). They are without a distinct cell membrane and are assumed

243

244 THE DEVELOPMENT OF THE VASCULAR SYSTEM

to be amoeboid. During embryonic life, the measmoeboid cells multiply
rapidly by mitosis and develop successively in the wall of the yolk sac, in
the young blood vessels, and in the liver, lymphoid organs, and red bone

Besides the mesamceboids of extra-embryonic origin, totipotent blood-forming cells
appear to rise both from the mesoderm of the embryo and from the mesenchymal cells of
adult connective tissue; such cells are believed by Maximow (1906; 1908) to produce all
types of blood elements,

Origin of the Erythrocytes. — The red blood corpuscles take their
origin as erythroblasts frorn the mesamceboid cells of the embryo, and from
the premyelocytes of adult connective tissue and bone marrow.

v /

FIG. 250. — Blood cells from human embryos of 12 and 20 mm. X 1160. a, Primitive mesa-
moeboid cells; b, erythroblasts; c, d, e, normoblasts ; /, erythrocytes. (a-c, from 12 mm., d-f,
from 20 mm. embryo.)

1. Erythroblasts (ichthyoid blood cells of Minot, so-called because
they resemble the typical red blood cells of fishes,) are characterized by
the presence of haemoglobin in the homogeneous cytoplasm, which is thus
colored red. The nuclei are vesicular, with granular chromatin (Fig.
250 b). There is a definite cell membrane. For the first six weeks of
development (12 mm.) the erythroblast is the only red blood cell found.

2. Normoblasts, also termed sauroid blood cells because they resemble
the red blood cells of adult reptiles, are first formed in the liver from the ery-
throblasts, and are predominant in embryos of two months. They are
distinguished by their small, round nuclei with dense chromatin which
stains so heavily that little or no structure can be seen (Fig. 2 50 c, d) . The
cytoplasm is larger in amount than in erythroblasts.

3. Erythrocytes (red blood corpuscles, erythroplastids) are developed
in mammals from normoblasts which lose their nuclei by extrusion (Fig.

$

FIG. 252. — Human blood-cells (Todd). X 1000. i , Ery throplastid ; 2, normoblasts; 3,ery-
throblast and normoblast; 4, blood-plates, one lying on a red corpuscle; 5, lymphocytes, large
and small; 6, 7, large mononuclear leucocytes, polar and profile views ; 8, neutrophilic leucocytes;
9, eosinophilic leucocytes; 10, basophilic leucocyte; n, neutrophilic myelocyte; 12, eosinophilic
megalocyte; 13, basophilic myelocyte. ,

HAEMOPOIESIS 245

250 /). The nucleus, extruded as several small granules or as a whole
(Fig. 251), is ingested by phagocytes.

Emmel (1914), studying cultures of blood cells from pig embryos, has observed the
formation of bodies resembling erythrocytes by a process of cytoplasmic constriction. He
suggests that his may be their normal method of development in the embryo.

The first red blood corpuscles are spherical and are formed during the
second month, chiefly in the liver. During the third month the enucleated
erythrocytes predominate (Fig. 250 /). Although usually cup-like in
preserved material, their normal shape is that of a biconcave .disc (Arey,
1917). During the later months of fetal life, the red blood corpuscles
are developed in the liver, in the red bone
marrow, and probably in the spleen. Ac-
cording to the view of Minot, the cells from
which they take their origin are mesamce-
boids which have lodged in the blood-
forming organs and undergo cell division
and differentiation there. In the bone „ ™,

FIG. 251.— The development of

marrow these cells are known as premyelocytes. red corpuscles in cat embryos
They differentiate into both erythroblasts (Howell). a, Successive stages in
and myelocytes', from the former normoblasts the development of a normoblast;

. o, the extrusion or the nucleus.

and erythrocytes arise, from the myelocytes

the granular leucocytes are developed. Soon after birth the red bone

marrow is the only source of new red blood corpuscles.

Origin of the Leucocytes. — The white blood cells are divided
into non-granular and granular types (Fig. 252). According to the mono-
phyletic view, it is assumed that both types are derived from the primitive
mesamceboid cells of the embryo.

I. N on- granular Leucocytes:

1. Lymphocytes are ordinarily about the size of a red corpuscle but
some are twice as large. They constitute from 22 to 25 per cent of the
leucocytes in adult blood and are developed in the lymphoid organs of the
embryo and adult. The spherical nucleus, containing numerous small
masses of chromatin, stains darkly and is surrounded by a narrow zone
of clear, faintly basophilic cytoplasm.

2. Large mononuclear leucocytes are two or three times the size of a red
corpuscle. They possess a clear nucleus, usually indented, and considera-
ble faintly basophilic cytoplasm. They comprise i to 3 per cent of all
leucocytes and are developed from the endothelial or reticular cells of
lymph glands (Evans, 1914; Kyes, 1915).

II. Granular or Polymorphonuclear Leucocytes :

The blood-forming cells lodged in the red bone marrow are known as

246

THE DEVELOPMENT OF THE VASCULAR SYSTEM

premyelocytes. They give rise to myelocytes, cells with round or crescentic
nuclei and granular cytoplasm. Similar cells are developed in the lym-
phoid organs. -By undergoing changes : (i) in the form and structure of
their nuclei, and (2) in the size and staining qualities of their cytoplasmic
granules, the myelocytes give rise to three types of granular leucocytes.

i. Neutrophils (70 to 72 per cent of all leucocytes). These have a
finely granular cytoplasm which is neutral in its staining reactions, color-
ing by the interaction of both acid and basic stains. In development, their

FIG. 253. — Giant cell, from the bone marrow of a kitten, showing pseudopodia extending into
a blood vessel (V), and giving rise to blood plates (bp) (Wright).

nuclei take up an eccentric position and become crescentic, horse-shoe
shaped, and, in the older stages, lobate. As it changes in form, the nucleus
undergoes pyknosis and stains intensely.

2. Eosinophils (2 to 4 per cent of all leucocytes). These are charac-
terized by coarse cytoplasmic granules that stain intensely with acid dyes.
In development the nucleus becomes bilobed.

It is commonly held that the eosinophilic granules differentiate endogenously (Dow-
ney, 1914). However, Weidenreich (1913) regards these granules as ingested fragments
of red corpuscles or their hemoglobin derivatives. Badertscher (1913) found numerous
eosinophils and free eosinophilic granules in the vicinity of degenerating muscle fibers in
salamanders. Also, during trichiniasis in man, when there is extensive degeneration of
muscle fibers, the number of eosiniphils in the blood becomes greatly increased.

3. Basophils or Mast Leucocytes (0.5 per cent of all leucocytes).
Their nuclei are very irregular in form and may be broken down into
several pieces which stain intensely. The cytoplasmic granules are varia-
ble in number, size, and form, and often stain so heavily with basic dyes
as to obscure the nucleus. Basophiles have been regarded as degenerating
granular leucocytes, but at present this view is not generally accepted.
They are apparently distinct from the 'mast cells' of the tissues.

DEVELOPMENT OF THE HEART

247

Origin of the Blood Plates. — In the bone marrow and spleen pulp are
giant cells, or megakaryocytes, the cytoplasm of which shows a darkly
staining granular endoplasm and a clear hyaline ectoplasm (Fig. 253).
It has been shown by Wright (1910) and others that the blood plates arise
by being pinched off from cytoplasmic processes of the giant cells. The
central granular mass of the plates represent portions of the endoplasm.
Genuine blood plates and giant cells occur only in mammals.

DEVELOPMENT OF THE HEART

Vasculogenesis. — We have seen that the first blood cells and blood vessels
take their origin in the angioblast, which develops in the wall of the yolk sac
and chorion from the splanchnic
mesoderm. The first vessels
derived from the angioblast
(see p. 243) are small, isolated
blood spaces which unite and
form capillary networks. From
these, endothelial sprouts grow
out, meet, and unite until com-
plete networks are formed. In
human embryos of i mm. or less,
these envelop the lower portion
of the yolk sac, the body stalk,
and chorion.

There are two views as to
the manner in which the heart
and the primitive vascular
trunks of the embryo originate.
According to His and Rabl, and
more recently Minot, Evans,
and Bremer, all the blood vessels
of the embryonic body arise as
endothelial ingrowths from the

FIG. 254. — The caudal end of a chick embryo
of 32 somites, showing the primary capillary plexus
in the posterior limb buds from which the sciatic
artery will differentiate. Aortae have formed
from the mesial margins of the plexuses (Evans).

extra-embryonic yolk-sac angio-
blast. Kolliker, Riicket, and
Mollier (1906), on the contrary,
assert that the intra-embryonic

vessels are formed by the fusion o? discrete anlages in a way similar to
that first occurring on the yolk sac. Corroborative investigations by
Maximow, Huntington, Schulte, and others have shown that the apparent
invasion of angioblast in reality represents a progressive fusion of isolated
mesenchymal tissue spaces. Moreover, direct experimental proof on

248

THE DEVELOPMENT OF THE VASCULAR SYSTEM

Ed.

Ent.

living chick embryos (Miller; Reagan, 1915) leaves little doubt of the
correctness of the Ruckert-Mollier view.

The delicate injection methods of Mall and his students show that
capillary plexuses precede the formation of definite arterial and venous
trunks (Fig. 254). Only by the selection, enlargement, and differentia-
tion of appropriate paths do the
definitive vessels arise. Capillaries,
from which the flow has been di-
verted, atrophy. The primitive,
paired aortae are formed from the
medial margins of such plexuses.
Exceptions to the general rule are
the intersegmental arteries which
arise as single trunks from the
aorta (Evans).

Inheritance, as well as the hy-
drodynamic factors incident to the
blood flow, participates in the
selection of channels . from the
capillary bed.

Origin of the Tubular Heart. —
The heart of the lower fishes
and of amphibians arises in the
ventral mesentery of the fore-gut.
A tubular cavity first appears,
about which the cells differentiate
directly into endo-, myo-, and
epicardium.

In bony fishes, reptiles, birds,
and mammals, the heart is formed,
while the embryo is still flattened
on the surface of the yolk, from
paired anlages which later grow
mesad and fuse. Aggregates of
mesodermal cells, which soon form
thin-walled tubes, first appear be-
tween the entoderm and splanchnic mesoderm; these are flanked by folds
of splanchnic mesoderm that bulge laterally into the ccelomic cavity (Figs.
255 A and 35). Such paired cellular masses (endothelial anlages) are
present in the Spec 1.54 mm. human embryo (Fig. 77). As the embryo
grows away from the yolk and the fore-gut is formed, the entoderm
withdraws from between the endothelial tubes, allowing these as well as
the mesodermal folds to fuse (Figs. 255 B, C; 36 and 37).

. spl.

FIG. 255. — Diagrams to illustrate the origin
of the mammalian heart. Ect., Ectoderm;
End., endothelial tubes; Ent., entoderm; Fg.,
fore-gut; Msc.d., dorsal mesocardium; Ms. spl.,
splanchnic mesoderm (epi- and myocardium).

DEVELOPMENT OF THE HEART

249

The heart is now an unpaired endothelial tube, lying in the folds of
the splanchnic mesoderm (Fig. 190 A). Soon the ventral attachment of
the mesoderm disappears, leaving the heart
suspended by a temporary dorsal meso-
cardium in the single pericardial chamber
(Fig.255 C). The endothelial tube forms
the endocardium, the splanchnic mesoderm
later gives rise to the epicardium and myo-
cardium. This type of heart occurs in
human embryos of 2 mm. (5 or 6 somites,
Fig. .256) and shows three regions: (i) the
atrium, which receives the blood from the
primitive veins; (2) the ventricle', (3) the
bulb, from which is given off the ventral aorta.

As the cardiac tube grows faster than
the pericardial cavity in which it lies, it bends
to the right, the bulbus and ventricle form-
ing a U-shaped loop (Fig. 257). Four
regions may now be distinguished; (i) the
sinus venosus; (2) the atrium, also thin-
walled and lying cranial to the sinus; (3)
the thick-walled ventricular limb, ventrad

and caudad in position; (4) the bulbar limb, cranial to the ventricular
limb and separated from it by the bulbo-ventricular cleft. Next, in

FIG. 256.— The heart of a 2
mm. human embryo in ventral
view (Mall). X 65. The open
tube is the fore-gut.

FIG. 257. — A, Heart of human embryo of 2.15 mm. : a, Bulbus cordis; b, primitive ventricle;
c, atrial portion. B, Heart of human embryo of about 3 mm.: a, Bulbus cordis; b, atrial por-
tion (behind); c, primitive ventricle (in front). Ventral views (His).

embryos of 3 to 4 mm., the bulbo-ventricular loop shifts its position until,
its base is directed caudad and ventrad (Fig. 257 B}. At the same
time the sinus venosus is brought dorsal to the atrium, which in turn is

250

THE DEVELOPMENT OF THE VASCULAR SYSTEM

cranial with relation to the bulbo-ventricular loop, and the bulbar limb is
pressed against the ventral surface of the atrium and constricts • it
(Fig. 258 A).

In embryos of 4 to 5 mm. the right portion of the sinus venosus grows
more rapidly than the left, this being due to the fact that the blood flow of

FIG. 258. — A, Heart of human embryo of about 4.3 mm.: a, Atrium; b, portion of atrium
corresponding to auricular appendage; c, bulbus cordis; d, atrial canal; e, primitive ventricle.
B, Heart of human embryo of about 10 mm.: a, Left atrium; b, right atrium; c, bulbus cordis;
d, interventricular groove; e, right ventricle;/, left ventricle. Ventral views (His).

the'left umbilical vein is shifted to the right side through the liver. As a
result, the enlarged right horn of the sinus opens into the right dorsal wall
of the atrium through a longitudinally oval foramen, guarded on the right
by a vertical fold. This fold which projects into the atrium, is the right

Pulmonary artery Aorta

Aorta—-

Bulbu

R. ventricle „

•Atrium

— Jf...L. ventricle

FIG. 259. — Diagrams to show the reduction of the bulbo-ventricular fold (represented by
diagonal lines) due to its retarded development. (Modified after Keith.)

valve of the sinus venosus. Later, a smaller fold forms the left valve of the
sinus venosus (Fig. 260 B). The atrium is constricted dorsally by the gut,
ventrad by the bulbus. It therefore must enlarge laterally and in so doing
forms the right and left atria (Fig. 258 A, B) with the distal portion of the

DEVELOPMENT OF THE HEART 351

bulb between them. The deep, external groove between the atria and the
bulbo-ventricular part of the heart is the coronary sulcus. As the bulbo-
ventricular region increases in size, the duplication of the wall between the
two limbs lags behind in development and finally disappears (Fig. 259),
leaving the proximal portion of the bulb and the ventricular limb to form
a single chamber, the primitive ventricle. In an embryo of 5 mm. the
heart is thus composed of three undivided chambers : (i) the sinus venosus,
opening dorsad into the right dilatation of the atrium; (2) the bilaterally
dilated atrium, opening by the single transverse atrial canal into (3) the
primitive, undivided ventricle. The three-chambered heart is persistent
in adult fishes, but in bir'ds and mammals a four-chambered heart is
developed, in which venous blood circulates on the right side and arterial
blood on the left. In amphibians and reptiles, transitional types occur.

The important changes next to be considered, leading to the forma-
tion of the four-chambered heart are: (i) the complete division of the
atrium and ventricle, each into right and left chambers^ (2) the division
of the bulb and its distal continuation, the truncus arteriosus, into the
aorta and pulmonary artery; (3) the incorporation of the sinus venosus
into the wall of the right atrium ; (4) the development of the semilunar and
atrio-ventricular valves. The first of these changes is completed only
after birth.

Origin of the Right and Left Atria. — In human embryos of 5 to 7
mm. there develops a thin, sickle-like membrane from the mid-dorsal
wall of the atrium (Figs. 260 and 261). This is called the atrial septum
primum (7). Simultaneously, endothelial thickenings appear in the dorsal
and ventral walls of the atrial canal (Figs. 261 A, B). These are the
endocardial cushions, which later fuse, thus dividing the single atrial canal
into right and left atrio-ventricular canals (Fig. 266). The atrium is now
partly divided into right and left atria, which, however, communicate
ventrad through the interatrial foramen. Next, in embryos of 9 mm., the
septum I thins out dorsad and cephalad and a second opening appears,
the foramen ovale (Figs. 260 and 261 7?). The atria are now connected
by two openings, the interatrial foramen and the foramen ovale. Soon
(embryos of 10 to 12 mm.), the ventral and caudal edge of septum I fuses
with the endocardial cushions, which have in turn united with each other
(Figs. 260 and 261 C}. The interatrial foramen is thus obliterated, but
the foramen ovale persists until after birth. In embryos of 9 mm. the
septum secundum (77) is developed from the dorsal and cephalic wall of
the atrium, just to the right of the septum primum (Fig. 260 C). It is
important, as it later fuses with the left valve of the sinus venosus, whence
the two form a great part of the atrial septum of the late fetal and adult
heart.

252

THE DEVELOPMENT OF THE VASCULAR SYSTEM

Fate of the Sinus Venosus and its Valves. — The opening of the sinus
venosus into the dorsal wall of the right atrium is guarded by two valves
(Fig. 260). Along the dorsal and cephalic wall of the atrium these unite to
form the septum spurium. Caudally the valves flatten out on the floor

Valves of sinus \ enosus
Septum I

io-ventricular canal

Valves of sinus venosus
ieptiim I
Foramen ovate

Sinus venosus

R. valve of sinus venosus

Endocardial cushion
Atrio-ventricular gr<

R. ventricle

R. common cardinal vein

Septum II

L. valve of sinus TCHOSUS

L. atrio-ventricular opening
L. ventricle

FIG. 260. — Horizontal sections through the chambers of the human heart: A, 6 mm.; B, 9 mm.;
C, 12 mm. (A and B are based on figures of Tandler.) X about 50.

of the'atrium, but, as stated previously, the left valve later fuses with the
atrial 'septum II. In embryos of 10 to 20 mm. the atria increase rapidly
in size and the lagging right horn of the sinus venosus is taken up into
the wall of the right atrium. By this absorption the superior vena cava

DEVELOPMENT OF THE HEART

253

Sept. II

Sept. I

Aorta

L. vent.

FIG. 261. — Lateral dissections of the human heart, viewed from the left side: A, 6 mm.;
B, 9 mm.; C, 12 mm. (B is based on a reconstruction by Tandler). X about 38. Cor. sin.,
Coronary sinus; D. end. c., dorsal endo'cardial cushion; For. ov., foramen ovale; Int. /or.,inter-
atrial foramen; I. v. c., inferior vena cava; L. atr., left atrium; L. va. s. v., left valve of sinus
venosus; L. vent., left ventricle; Pul. a., pulmonary artery; Pul. v., pulmonary vein; Sept. /,
Sept. II, septum primum, septum secundum; Sup. v. c., superior vena cava; V. end. c., ventral
endocardial cushion. *

Foramen male

R. valve of sinus venosus
Inf. vena cava-

Aorta

Semilunar valve of
pulmonary artery

R. ventricle

FIG. 262. — Lateral dissection of the hfeart of a 65 mm. human fetus, viewed from the right side.

X 12.

254

THE DEVELOPMENT OF THE VASCULAR SYSTEM

now opens directly into the cephalic wall of the atrium, the inferior vena
cava into its caudal wall (Fig. 261 C). The transverse portion of the
sinus venosus, persisting as the coronary sinus in part, opens into the pos-
terior wall of the atrium.

The right valve of the sinus venosus is very high in 10 to 65 mm. embryos
(first to third month) and nearly divides the atrium into two chambers
(Fig. 262). It becomes relatively lower during the third and fourth

Crista terminalis
Sept. n+L. valve of
sinus venosus
Septum I

Sup. vena cava (opened)

Inf. vena cava
Valve of inf. vena

Valve of coronary sinus

Tricuspid

oranien ovate

Aorta

'emilunar valves
of pulmonary artery

R. ventricle

FIG. 263. — Lateral dissection of the heart of a 105 mm. human fetus, viewed from the right side.

X 7-

months. Its cephalic portion becomes the rudimentary crista terminalis
(Fig. 263); the remainder is divided by a ridge into two parts, of which
the larger cephalic division persists as the valve of the inferior vena cava
(Eustachian valve) located at the right of the opening of the vein, and
the smaller caudal portion becomes the valve of the coronary sinus
(Thebesian valve).

The left valve of the sinus venosus unites with the septum II, and,
in embryos of 20 to 22 mm. or larger, the two bound an oval opening
(Figs. 263 to 265). The bounding wall of the oval aperture is the limbus
ovalis.

Sup. vena cava

Aorta

Pulmonary trunk —

DEVELOPMENT OF THE HEART

Septum II Foramen ovale

255

L. atrium

Septum I

Inferior vena cava

Coronary sinus
Bicuspid valve

L. ventricle

FIG. 264. — Lateral dissection of the heart of a 65 mm. human fetus, viewed from the left side,
showing the septa and the foramen ovale. X 8.

•Sept. I

L. vent

FIG. 265. — Lateral dissections of the human heart, viewed from the left side: A, from a
22 mm. embryo; B, from a 105 mm. fetus. Bic. va., Bicuspid valve; Cor. sin., coronary sinus;
For. oi>., foramen ovale; I.v.c., inferior vena cava; L. atr. vent, c., left a trio- ventricular canal;
L. »«»*.,. left ventricle; Put. a., pulmonary artery; Sept. I, Sept. II, septum primum and septum
secundum.

256

THE DEVELOPMENT OF THE VASCULAR SYSTEM

Aorta

Closure of the Foramen Ovale. — The free edge of the septum I is, in
embryos of 10 to 15 mm., directed dorsad and cephalad (Fig. 261 Cj).
Gradually, in later stages (Figs. 264 and 265), its caudal and dorsal pro-
longation grows cephalad and ventrad until its free edge is so directed.
Coincident with this change, the septum II, with its free edge directed at
first ventrad and cauded, shifts until its free edge is directed dorsad and
cephalad, and overlaps the septum I (Figs. 261 C, 264 and 265). The
opening between these septa persists until after birth as the foramen ovale.
During fetal life the left atrium receives little blood from the lungs,
so that the pressure is much greater in the right atrium. As a result,
the septum I is pushed to the left and the blood flows from the right into
the left atrium through the foramen ovale. After birth, the left atrium
receives from the expanding lungs as much blood as the right atrium, the
septum I is pressed against the limbus of the previously fused septum II
and left sinus valve, and unites with it. The depression formed by the
thinner walled septum I is the. fossa ovalis. .

The Pulmonary Veins. — In embryos of 6 to 7 mm., a single vein
(arising in the cat from a peripulmonary plexus, Brown, 1913) drains into

the caudal wall of the left atrium
at the left of the septum I (Fig.
261 -C). This vein bifurcates
into right and left pulmonary
veins which divide again before
entering the lungs. As the
atrium grows, the proximal por-
tion of the pulmonary vein is
taken up into the atrial wall.
As a result, at first two, then
four pulmonary veins open into
the left atrium.

Origin of the Aorta and
Pulmonary Artery. — In embryos

of 4 to 6 mm. there arise in the aortic bulb (including its distal truncus
arteriosus) longitudinal thickenings, four in the distal half, two in the
proximal half. Of the four distal thickenings (Fig. 266), two, which may
be designated a and c, are larger than the other thickenings, b and d.
Thickenings a and c, which distally occupy left and right positions in
the bulb, meet, fuse, and divide the bulb into a dorsally placed aorta
and ventrally placed pulmonary trunk (Fig. 267). Traced proximally
they pursue a clockwise, spiral course, a shifting from left to ventral, and
c from right to dorsal, both becoming continuous with the proximal
swellings. Thickenings b and d are also prominent at one point

Pulmonary artery

FIG. 266. — Scheme showing division of
bulbus cordis and its thickening into aorta
and pulmonary artery with their valves.
(Explanation in text.)

DEVELOPMENT OF THE HEART

257

proximally; when the bulb in this region is divided by ingrowing con-
nective tissue into the aorta and pulmonary artery, the aorta contains the
whole of the thickenings b and half of a and c, while the pulmonary

'Pulmonary artery
Incomplete bulbar septum

Aorta

Dorsal endocardial cushion

Vtntral endocardial
cushion

Arrow in pulmonary artery

Proximal bulbar septum

Interventricular
foramen

R. airio-ventricular
foramen

R. ventricle

Airio-ventricular
foramen

ventricular
septum

I nterventr icular sukus

Pulmonary artery
Base of aorta

Arrow in aorta

L. atrio-ientricular
foramen

Intervenlricular
septum

FIG. 267. — Stages of the human heart, in ventral view, to show the division of the bulbus and
ventricle: A, 5 mm. embryo; B, 7.5 mm. embryo.

trunk contains the whole of d and half of a and c (Fig. 266). Distally,
the three thickenings now present in each vessel disappear, but prox-
imally they enlarge, hollow out on their distal surfaces, and eventually

258 THE DEVELOPMENT OF THE VASCULAR SYSTEM

form the thin- walled semilunar valves (Fig. 266). The anlages of these
valves are prominent in embryos of 10 to 15 mm. as plump swellings
projecting into the lumina of the aorta and pulmonary artery.

The two proximal bulbar swellings fuse and continue the spiral divi-
sion of the bulb toward the interventricular septum in such a way that the
base of the pulmonary trunk, now ventrad and to the right, opens into the
right ventricle, while the base of the aorta, now lying to the left and dor-
sad, opens into the left ventricle close to the interventricular foramen,
through which the two ventricles still communicate (Fig. 267 B).

Origin of the Right and Left Ventricles. — Coincident with the
division of the aortic bulb there appears at the base of the primitive
ventricular cavity a sagittally placed elevation, the interventricular septum.
(Fig. 260 B). It later grows cephalad and dorsad toward the endocardial
cushions, and forms an incomplete partition between the right and left
ventricles, which still communicate through the persisting interventricular
foramen (Fig. 267 B). Corresponding to the internal attachment of the
septum there is formed externally the interventricular sulcus (Fig. 267 A);
this marks the external line of separation between the large left ventricle
and the smaller right ventricle. The interventricular foramen in embryos
of 15 to 1 6 mm. is bounded: (i) by the interventricular septum; (2) by
the proximal bulbar septum; and (3) by the dorsal portion of the fused
endocardial cushions (Fig. 267). Soon these structures are approximated
and fuse, thereby forming the septum membranaceum, which closes the
interventricular foramen.

The atrio-ventricular valves arise as thickenings of the endocardium
and endocardial cushions about the atrio-ventricular foramina (Figs. 260
and 261). Three such thickenings are formed on the right, two on the
left. The anlages of the valves are at first thick and project into the
ventricles. Later, as the ventricular wall differentiates, the valvular
anlages are undermined, leaving their edges attached to the ventricular
walls by muscular trabeculce, or cords. The muscle tissue of both the
valves and trabeculae soon degenerates and is replaced by connective
tissue, forming the chorda? tendinecs of the adult valves. Thus there are
developed the three cusps of the tricuspid valve between the right
chambers of the heart, and the two flaps of the bicuspid, or mitral valve,
between the left atrium and left ventricle.

Differentiation of the Myocardium. — The myocardium, at first uniformly spongy,
becomes compact at the periphery. The inner bundles remain trestle-like, forming the
trabeculae carnce and the papillary and moderator muscles around all of which the originally
simple endocardial sac is wrapped. The myocardial layers, at first continuous over the
surface of the heart, become divided by connective tissue at the atrio-ventricular canal,
leaving a small bridge alone. This connecting strand, located behind the posterior endo-
cardial cushion, forms the atrio-ventricular bundle.

THE PRIMITIVE BLOOD VASCULAR SYSTEM 259

Descent of the Heart. — At first the heart lies far cephalad in the cervical region, but
it gradually recedes during development until it assumes its permanent position in the
thorax.

Anomalies. — Dextrocardia is associated with a general transposition of the viscera
(p. 195). The aorta and pulmonary artery may also be transposed in the absence of dex-
trocardia. Rarely the paired anlages form a double heart. Of the complete or partial
defects of the septa, most common is a patent foramen ovale. If this fails to close after
birth, the mixed blood produces a purplish hue in the child which is known popularly as a
'blue baby. This condition may be persistent in adult life. Incomplete closure occurs in
about one in four cases, but actual mingling of the blood is rare, due to an approximation
of the overlapping septal folds during atrial systole.

THE PRIMITIVE BLOOD VASCULAR SYSTEM

The first paired vessels of human embryos are formed as longitudinal
anastomoses of capillary networks, that originate first in the angioblast of
the yolk sac and chorion (p. 243). In the Eternod embryo of 1.3 mm., in
which the somites are still undeveloped, such paired vessels are already
formed (cf. Fig. 268). The umbilical veins emerge from the chorion,
fuse in the body stalk, then, separating, course in the somatopleure

Dorsal inter segmental arteries Descending aorta
Umbilical veins

Umbilical arteries

Body stalk
Umbilical vein

Primitive aortic arch
Primitive heart
Vitello-umbilical trunk

. , _, —, - ' Yolk sac

V i tell me arteries

FIG. 268. — Diagram, in lateral view, of the primitive blood vessels in human embryos of 1.5

to 2 mm.

to the paired, tubular heart anlages. From the heart tubes, paired ves-
sels, the ventral aortas, extend cephalad, then bend dorsad as the first aortic
arches and extend caudad as the descending aorta. These, as the umbilical
arteries, bend sharply ventrad into the belly stalk and branch in the wall of
the chorion. The chorionic circulation is thus the first to be established.
In embryos 2 to 2.5 mm. long (5 to 8 somites), the heart has become
a single tube (Fig. 269). From the yolk sac, numerous veins converge
cephalad and form a pair of vitelline veins. These join the umbilical veins,
and, as the vitello-umbilical trunks, traverse the septum transversum and
open into the sinus venosus. The descending aortae give off, dorsally and
cranially, several pairs of dorsal inter segmental arteries, and, ventrad and

260

THE DEVELOPMENT OF THE VASCULAR SYSTEM

caudad, a series of vitelline arteries to the yolk sac. The umbilical arteries
now take their origin from a plexus of ventral vessels in series with the
vitelline arteries. At this stage the vitelline circulation of the yolk sac
is established.

Dorsal inter segmental arteries A nt. cardinal veins

\ I Descending aortas
Umbilical arteries

Body stalk

Umbilical vein

Vitelline arteries

Aortic arch i
Heart

Vitello-umbilical trunk
Vitelline veins

Yolk sac

FIG. 269. — Diagram, in lateral view, of the primitive blood vessels in human embryos of 2 to

2.5 mm

In embryos of 15 to 23 somites (Fig. 270) the veins of the embryo
proper develop as longitudinal anastomoses of branches from the segmental
arteries. The paired anterior cardinal veins of the head are developed first,

Posterior cardinal veins
Vitelline artery,

A nt. cardinal veins
i

Descending aortcB

Umbilical arteri

M ortic arches i and 2
Heart

•iinus venosus
Vitelline veins
FIG. 270. — Diagram of the blood vessels of a human embryo of 2.6 mm.

Body stalk

Umbilical veins

and, coursing back on either side of the brain, they join the vitello-um-
bilical trunk. In embryos of 23 somites, the posterior cardinals are present.
They lie dorsal tp the nephrotomes, and, running cephalad, join the
anterior cardinal veins to form the common cardinal veins. Owing to the
later enlargement of the sinus venosus, the proximal portions of the com-

THE PRIMITIVE BLOOD VASCULAR SYSTEM

26l

mon venous trunks are taken up into its wall, and thus three veins open
into each horn of the sinus venosus: (i) the umbilical veins from the
chorion; (2) the vitelline veins from the yolk sac; (3) the common cardinal
veins from the body of the embryo.

The descending aorta have now fused caudal to the seventh interseg-
mental arteries and form the single dorsal aorta as far caudad as the origin
of the umbilical arteries.

First cervical artery.
Pulmonary artery
Ant. cardinal vein
Post, cardinal vein

Bulbus cordis
Ophthalmic artery
Ant. cerebral artery

Common cardinal vein

Vitelline artery
(Superior mesenteric)

Caudal artery
Umbilical artery

Subclavian artery
Casliac artery"

Dorsal aorta

Inf. mesenteric artery

FIG. 271. — Arteries and cardinal veins of the right side in a 4.9 mm. human embryo (modified
after Ingalls). X 20. H, Heart; I-VI, aortic arches.

Of the numerous vitelline arteries one pair is prominent; it fuses into
a single vessel which courses in the mesentery and later becomes the
superior mesenteric artery. By the enlargement of capillaries connecting
the ventral and dorsal aortae, a second pair of aortic arches is formed at
this stage (Fig. 270).

In embryos 4 to 5 mm. in length, five pairs of aortic arches are
successively developed: the first, second, third, fourth, and sixth (Fig.
271). An additional pair of transitory vessels, which extend from the
ventral aorta to the sixth arch, appear later in embryos of 7 mm.,
but soon degenerate (Fig. 272 B}. They are interpreted as being the

THE DEVELOPMENT OF THE VASCULAR SYSTEM

fifth pair in the series. From each dorsal, or descending aorta there
develop cranially the internal carotid arteries. These extend toward
the optic stalks where they bend dorsad and caudad, connecting
finally with the first intersegmental arteries of each side (Fig. 271). The
descending aortae are now fused to their extreme caudal ends and the
umbilical arteries take their origin ventrally. Twenty-seven pairs of
dorsal intersegmental arteries are present. From the seventh cervical pair
of these the subdavian arteries of the upper limbs arise. Of the ventral
vitelline vessels three are now prominent : the ccsliac artery in the stomach-
pancreas region, the vitelline, or superior mesenteric', in the small intestine
region, and the inferior mesenteric of the large intestine region.

A

Aortic arch 3
Aortic arch 2,

Aortic arch i

Dorsal aorta

Aortic arch 4
A ortic arch 6

Int. carotid artery
Aortic arch 2

External carotid
Aortic arch 6
Pulmonary artery

Bulbus cordis

Aortic arch 4

Aortic arch 5

Dorsal aorta

FlG. 272. — Aortic arches of human embryos: A, of 5 mm.; B, of 7 mm. (after Tandler). I-IV,

pharyngeal pouches.

DEVELOPMENT OF THE ARTERIES

Transformation of the Aortic Arches. — The ancestral aortic arches
are early transformed into more appropriate vessels. The third pair is
largest at 5 mm. (Fig. 272, .4); at 7 mm. the first and second aortic
arches (are obliterated (Figs. 272 B and 273), but the descending and

DEVELOPMENT OF THE ARTERIES

263

ventral aortae cranial to the third arch persist as parts of the internal
and external carotid arteries respectively. The third arches f orm ^the
stems of the internal carotids, while the ventral aortse between the
third and fourth arches become the common carotids. In embryos
of is mm. the bulbus cordis has been divided into the aortic and pul-
monary trunks, so that the aorta opens into the left ventricle and
the pulmonary trunk into the right ventricle. The descending aortae
between the third and fourth arches disappear, but the fourth arch on the
left side persists as the aortic arch of the adult. On the right side, the
fourth aortic arch persists with the descending aorta as far as the seventh

External carotid

Internal carotid
Common carotid

Aortic arch

Ductus arteriosus
Vertebral artery
Subdavian artery

Left pulmonary artery
Ventral aorta

Right sub-
daman artery

Right pul-
monary artery

Trunk of pul-
monary artery

FIG. 273. — Diagram showing the aortic arches and their derivatives in human embryos.

intersegmental artery and forms part of the right subclavian artery, which
is thus a more complex vessel than the left. The segment of the fourth
arch proximal to the right common carotid becomes the innominate
artery. The fifth arches of amniotes are rudimentary (p. 100). On
the right side, the sixth arch between the origin of the right pulmonary
artery and descending aorta is early lost ; on the left side, it persists as the
ductus arteriosus and its lumen is only obliterated after birth. The
proximal portion of the right sixth arch forms the stem of the right pul-
monary artery, but the proximal portion of the left arch is incorporated in
the pulmonary trunk. Most of the pulmonary artery arises from a post-
branchial plexus; union with the sixth arch is acquired secondarily
(Huntington, 1919).

The aortic arches of the embryo are of especial importance comparatively. Five
arches are formed in connection with the gills of adult fishes. In adult tailed amphibia,

264 THE DEVELOPMENT OF THE VASCULAR SYSTEM

three or four arches, and in some reptiles two arches, are represented on either side. In
birds the right, in mammals the left fourth arch persists as the arch of the aorta.

The different courses of the recurrent laryngeal nerves are easily explained. The vagus
early gives off paired branches which reach the larynx by passing caudal to the primit ive
fourth aortic arches. When the latter, through growth changes, descend into the chest,
loops of both nerves are carried with them. Hence, after the transformation of the fourth
arches, the left recurrent nerve remains looped around the arch of the aorta, the right
around the right subclavian artery (cf. Fig. 273).

Branches of the Dorsal Aorta. —From the primitive aortae arise: (i)
dorsal, (2) lateral, and (3) ventral branches (Fig. 274). .

i. The dorsal branches are intersegmental and develop small dorsal
and large ventral rami. From the dorsal rami are given off neural branches
which bifurcate and form dorsal and ventral spinal arteries.

Postcostal anastomosis

^ ^ _ .„ _ . ^ . ^Precostal anastomosis

Dorsal ramus.

Ventral \

-Lateral (visceral) artery
•Ventral (splanchnic) artery

Ventral anastomosis

FIG. 274. — Diagram of the trunk, in transverse section, showing the arrangement of the aortic

branches.

As we have seen (Fig. 271), the internal carotids are recurved cranially
in the 5 mm. embryo and anastomose with the first two pairs of dorsal
intersegmental arteries. By longitudinal postcostal anastomoses (Fig.
274) of the dorsal rami of the first seven pairs of dorsal intersegmental
arteries, the vertebral arteries arise (Fig. 27.5). The original trunks of the
first six pairs. are lost, so that the vertebrals take their origin with the
subclavians from the seventh pair of intersegmental arteries (Fig. 276).
In embryos of 9 mm. the vertebrals in the region of the metencephalon
fuse to form a single, median ventral vessel, the basilar artery, which thus
is connected cranially (by way of the circulus arteriosus) with the internal
carotids, caudad with the vertebral arteries.

The internal carotids (Fig. 271), after giving off the ophthalmic arteries, give rise
cranially to the anterior cerebral artery, from which arise later the middle cerebral artery

DEVELOPMENT OF THE ARTERIES

26 =

Spinal ganglion

~ Costo-cervical
trunk

Subclavian artery

FIG. 275. — The development of the vertebral and subclavian arteries and the costo-cervical
trunk in a young rabbit embryo (modified after Hochstetter). Ill AB.-IV AB., Aortic arches;
A .v.c.b. cephalic portion of vertebral artery; C. d. and C.v., internal and external carotid arteries.

FIG. 276. — Arterial system of a human embryo of 10 mm. (His). X 18. Ic, Internal carotid
artery: P, pulmonary artery; Ve, vertebral artery; III-VI, persistent aortic arches.

266

THE DEVELOPMENT OF THE VASCULAR SYSTEM

and the anterior choriodal artery; all of these supply the brain. Caudalward many small
branches to the brain wall are given off, and, quite late in development (48 mm. C R),
they form a true posterior cerebral artery (Mall).

The ventral rami of the dorsal intersegmental arteries become promi-
nent in the thoracic and lumbar regions and persist as the intercostal and
lumbar arteries, segmentally arranged in the adult. Longitudinal precos-
tal anastomoses (Fig. 274) constitute the costo-cervical and thyreo-cervical
trunks (Fig. 275). The subclavian and a portion of the internal mammary
artery are derived from the ventral ramus of the seventh cervical seg-

mental artery. The remainder of the
internal mammary and the superior and
inferior epigastric arteries are formed by
longitudinal ventral anastomoses (Fig.
274) between the extremities of the ven-
tral rami from the thoracic and lumbar
intersegmental arteries, beginning with the
second or third thoracic (Fig. 277). \

2. The lateral (visceral) branches of
the descending aortae are not segmentally
arranged. They supply structures arising
from the nephrotome region (mesonephros,
sexual glands, metanephros.and suprarenal
glands). From them later arise the renal,
suprarenal, inferior phrenic, and internal
spermatic or ovarian arteries.

3. The ventral (splanchnic} branches
are at first rather definitely interseg-
mental. Primitively they form the paired
vitelline arteries to the yolk sac (Figs.
268 to 270). Coincident with the de-
generation of the yolk sac the prolongations of the ventral vessels to its
walls disappear, and the paired persisting arteries, passing in the mesentery
to the gut, fuse to form unpaired vessels from which three large arteries
are derived: the coeliac artery, the superior mesenteric, and the inferior
mesenteric (Fig. 271).

The primitive coeliac axis arises opposite the seventh intersegmental artery. To-
gether with the mesenteric arteries, it migrates caudalward until eventually its origin is
opposite the twelfth thoracic segment (Mall). This migration, according to Evans, is
due to the unequal growth of the dorsal and ventral walls of the aorta. Similarly, the
superior mesenteric artery is displaced caudad ten segments, the inferior mesenteric artery
three segments.

FIG. 277. — The development of the
internal mammary and deep epigastric
arteries in a human embryo of 13 mm.
(Mall in McMurrich).

DEVELOPMENT OF THE ARTERIES

267

The Umbilical and Iliac Arteries. — As previously described, the
umbilical arteries arise in young embryos of 2 to 2.5 mm. from the primi-
tive aortae opposite the fourth cervical segment. They take origin from a
plexus of ventral vessels of the vitelline series (Fig. 270), and are gradually
shifted caudad until they arise from the dorsal aorta opposite the twenty-
third segment (fourth lumbar). In 5 mm. embryos, the umbilical arteries
develop secondary lateral connections with the aorta (Fig. 278 A). The
new vessels pass lateral to the mesonephric ducts, and, in 7 mm. embryos,
the primitive ventral stem-artery has disappeared. The segment of this

Seventh inter segmental
artery

Ccdiac artery
V. pancreas

Tenth dorsal inter segmental artery
Dorsal aorta

'celiac axis

, Vitflline artery
• ', (Superior
mesenteric)

Mesonephric arteries
Dorsal aorta

R. umbilical artery
Cloaca

Common iliac artery
A B

FIG. 278. — Reconstructions, showing the development of the umbilical and iliac arteries (after
Tandler): A, 5 mm. human embryo; B, 9 mm. human embryo.

new trunk, proximal to the origin of the external iliac artery which soon
arises from it, become.s the common iliac. The remainder of the umbilical
trunk constitutes the hypogastric artery. When the placental circulation
ceases at birth, the distal portions of the hypogastric arteries, from pelvis
to umbilicus, atrophy, forming the solid obliterated hypogastric arteries
of adult anatomy.

The middle sacral artery is the direct caudal continuation of the aorta.
Its dorsal position is the result of secondary growth changes.

Arteries of the Extremities. — It is assumed that in man, as in observed birds and mam-
mals, the first vessels of the limb buds form a capillary plexus.

Upper Extremity. — The capillary plexus takes origin by several lateral branches from
the aorta. In human embryos of 5 mm. but one connecting vessel remains, and this takes
its origin secondarily from the seventh dorsal intersegmental artery, forming the ventral
ramus of this artery and its lateral offset (Fig. 274) . The portion of this vessel in what will

268 THE DEVELOPMENT OF THE VASCULAR SYSTEM

become the free arm is plexiform at first, but later becomes a single stem which forms
successively the subclavian, axillary, brachial, and interosseous arteries. Subsequently
the median, radial, and ulnar arteries of the arm are formed.

Lower Extremity. — In embryos of 7 mm. there is given off from the secondary lateral
trunk of the umbilical artery (i. e., from the future common iliac) a small branch which
forms the chief arterial stem of the lower extremity, the future popliteal and peroneal arter-
ies. This, the arteria ischiadica, is superseded in embryos of 15.5 mm. by the external
iliac and femoral arteries, of which the latter annexes the branches of the ischiadic distal to
the middle 'of the thigh. The arteria ischiadica persists proximally as the inferior gluteal
artery.

DEVELOPMENT OF THE VEINS

We have seen that in embryos of 23 somites three systems of paired
veins are present: the umbilical veins from the chorion, the vitelline veins
from the yolk sac, and the anterior and posterior cardinal veins, which
unite in the common cardinal veins, from the body of the embryo. Thus,
three veins open into the right horn of the sinus venosus, and three into
the left (Fig. 270).

Changes in the Vitelline and Umbilical Veins. — Vena portoe. — With
the increase in size of the liver anlages there is an intercrescence of the
hepatic cords and the endothelium of the vitelline veins. As a result, these
veins form in the liver a network of sinusoids (Fig. 279), and each vein is
divided into a distal portion which passes from the yolk sac to the liver,
and into a proximal portion which carries blood from the liver sinusoids to
the sinus venosus. Soon the proximal portion of the left vitelline vein is
largely absorbed into the sinusoids of the liver and shifts its blood flow into
the right horn of the sinus venosus. In the meantime the liver tissue
grows laterally, comes into contact with the umbilical veins, and taps
them so that their blood flows more directly to the heart through the
sinusoids of the liver (Fig. 280). As the channel of the right proximal
vitelline is larger, the blood from the left umbilical vein flows diagonally
to the right horn of the sinus venosus. When all the umbilical blood
enters the liver, as in embryos of 5 to 6 mm., the proximal portions of the
umbilical veins atrophy and disappear (Fig. 281). In 5 mm. embryos the
vitelline veins have formed three cross anastomoses with each other (Figs.
280 and 281) : (i) a cranial transverse connection in the liver, ventral to
the duodenum; (2) a middle one, dorsal to the duodenum; and (3) a
caudal one, ventral to it. There are thus formed about the gut a cranial
and a caudal venous ring. In embryos of 7 mm. the left umbilical vein
has enlarged, while the corresponding right vein has degenerated. Of the
two venous loops, only the right limb of the cranial ring and the left limb of
the caudal ring, together with the median dorsal anastomosis, persist. * A
new vein the superior mesenteric, develops in the mesentery of the intes-
tinal loop and joins the left vitelline vein just caudal to its dorsal middle

DEVELOPMENT OF THE VEINS

269

Right vitelline vci

Ventricle

f^eft umbilical vein
Left vitelline vein

FIG. 279. — Reconstruction of the blood vessels of a 4.2 mm. human embryo in ventral view

Ductus venosus

Right horn of sinus venosus

Caudal anastomosis of vitelline veins

Right vitelline vein

Left horn of sinus venosus^ ;
Left vitelline vein

Cranial anastomosis of vitelline
veins

Middle anastomosis of vitelline
veins

Right umbilical vein -W *m I " e umbilical vcin

<ns •B^

Left vitelline vein

FIG. 280. — Reconstruction of the veins of the liver in a 4.9 mm. human embryo (after Ingalls).

270

THE DEVELOPMENT OF THE VASCULAR SYSTEM

anastomosis with the right vitelline vein. Subsequently, with the atrophy
of the yolk sac, the left vitelline vein degenerates caudal to its junction
with the superior mesenteric vein. The persisting trunk between the
superior mesenteric vein and the liver is the vena portce, and thus represents :

(1) a portion of the left vitelline vein in the left limb of the caudal ring;

(2) the middle transverse anastomosis between the vitelline veins; (3)
the portion of the right vitelline vein which forms the right limb of the
cranial ring.

In the liver, the portal vein, through its cranial anastomosis between
the primitive vitelline veins, is connected with the left umbilical vein

Efferent Common Ductus
hepatic vein hepatic vein venosus

Efferent
Pancreas hepatic vein

Afferent ht patic ve

, t

^Afferent hepatic vein

"Obliterated L. vitelline vein

Vitelline L umbilical vein
_ vein

FIG. 281. — A diagram showing the development of the portal vein as illustrated in a human
embryo of about 7 mm. (modified after His).

(Fig. 281). As the right lobe of the liver grows, the course of the umbilical
and portal blood through the intrahepatic portion of the right vitelline
vein becomes circuitous, and hence a new, direct channel to the sinus
venosus is formed through the hepatic sinusoids. This is the ductus
venosus (Fig. 281), which is obliterated after birth and forms the ligamen-
tum venosum of the postnatal liver.

According to Mall, the intrahepatic portion of the right vitelline vein persists proxi-
mally as the right ramits of the -hepatic vein, and distally as the ramus arcuatus of the portal
vein. The intrahepatic portion of the left vitelline vein drains secondarily into the right
horn of the sinus venosus, and proximally forms later the left hepatic ramus, Distally,
where it is connected with the left umbilical vein, it becomes the ramus angular is of the
vena porta?. In this way two primitive portal, or supplying trunks, and two hepatic, or
draining trunks, originate. Later there are differentiated first four, then six, such opposed
trunks within the liver, and the six primary lobules supplied and drained by these trunks
may be recognized in the adult liver.

DEVELOPMENT OF THE VEINS 271

Of the umbilical veins, the right disappears early; the left persists
during fetal life, shifts to the median plane, and courses in the free edge
of the falciform ligament. After birth its lumen is closed, and from the
umbilicus to the liver it forms the ligamentum tere's. In early stages,
veins from the body wall drain into the umbilical veins.

The Anterior Cardinal Veins and the Origin of the Superior Vena
Cava. — The anterior cardinal veins consist each of two parts (Fig. 271):

(1) the true anterior cardinals, located laterad in the segmented portion
of the head and neck and draining into the common cardinal veins;

(2) the vena capitis medialis, extending into the unsegmented head proper
and running ventro-lateral to the brain wall. In embryos of 20 mm. there
has formed by anastomosis a large connection between the right and left
anterior cardinals, which carries the blood from the left side of the head
into the right vein (Fig. 282 C). Soon, the left anterior cardinal loses
its connection with the common cardinal on the left side; the remaining
portions become the accessory hemiazygos and the inconstant oblique
vein of the left atrium (Fig. 282 D). The proximal portion of the left
common cardinal, with the tranverse portion of the sinus venosus, persists
as the coronary sinus. The right common cardinal and the right anterior
cardinal vein, as far as its anastomosis with the left anterior cardinal
become the superior vena cava. The anastomosis itself forms the left
vena anonyma, while that portion of the right anterior cardinal between
the anastomosis and the right subclavian vein is known as the right
vena anonyma. The distal portions of the anterior cardinals become the
internal jugular veins of the adult, while the external jugular and sub-
clavian veins are new vessels which develop somewhat later.

The vena capitis medialis (Fig. 271) is the continuation of the anterior cardinal vein
into the head of the embryo, where at first it lies mesial to the cerebral nerves. Later, it .is
partly shifted by anastomoses lateral to the cerebral nerves and forms the vena capitis
lateralis (Figs. 283 and 284). In n mm. embryos this emerges with the n. facialis, and,
caudal to the n. hypoglossus, becomes the internal jugular. Cranially, in the region of the
fifth nerve, the median vein of the head persists as the sinus caver nosus and receives the
ophthalmic vein from the eye and the anterior cerebral vein from the fore- and mid-brain
regions (Fig. 284 C). Between the n. trigeminus and the facialis, the middle cerebral vein
from the metencephalon (cerebellum) joins the v. capitis lateralis before it leaves the
cranium. More caudally, the posterior cerebral vein from the myelencephalon emerges
through the jugular foramen and is drained with the others by the v. caprtis lateralis into
the internal jugular (Fig. 284 B). Soon, the cerebral veins reach the dorsal median line
(Fig. 284 C), and longitudinal anastomoses are formed: (i) between the anterior and mid-
dle cerebral veins, giving rise to the superior sagittal sinus; and (2) between the middle
and posterior cerebral veins forming the greater part of the transverse sinsuses. In embryos
of 33 mm. the v. capitis lateralis disappears and the blood from the brain passes through the
superior sagittal and lateral sinuses and is drained by way of the jugular foramen into the
internal jugular vein (Fig. 284 C, D). The middle cerebral vein becomes the superior

THE DEVELOPMENT OF THE VASCULAR SYSTEM

R. ant. cardinal vein

R. post, cardinal vein
R. com. cardinal vein

Subclavian vein
R. vitelline vein
R. umbilical vein
R. post, cardinal vein

Mesons
R. subcardinal vein

R.

R. ant. cardinal vein

R. siibclavian vei
R. com. cardinal vei

Inf. vena cava

R. post, cardinal vei

Mesonephros
R. subcardinal vein

Metanephros

R. ischiadic ve,
R. caudal veil

Int. jugular vein L. vena anonyma

Ext. jugular
Subclavian

vein Int. jugular vein

.Com. cardinal vein

Supracardinai

vein

Metanephros

Ext. jugular vein
Subclavian vein
Azygos vein

Coronary sinus
Inf. vena cava

Hepatic vein

Hemi-azygos vein

R. suprarenal vein

R. renal vein

L. renal vein

Spermatic veins

Ext. iliac vein
Com. iliac vein

Ace. hemi-

Ischiadic vein
Caudal vein

Hypogastric vein
C Median sacral vein D

FIG. 282. — Four diagrams showing the development of the superior and inferior venas
cavae and the fate of the cardinal veins (modified after Kollmann). X, in A, vein of the plica
venae cavae:*, anastomosis between subcardinal veins; X, in C, anastomosis between anterior
cardinal veins which forms the left vena anonyma; *, in C, cranial anastomosis between the
azygos veins; z, caudal anastomosis between supracardinal veins; K, kidney; S, suprarenal
gland; T, testis.

DEVELOPMENT OF THE VEINS

273

petrosal sinus, but the inferior petrosal sinus is formed as a new channel median to the
internal ear. The anterior cerebral vein becomes the superficial middle cerebral of adult
anatomy. A more detailed account of these changes may be found in the original work
of Mall (Amer. Jour. Anat., vol. 4, 1905).

The Posterior Cardinal Veins and the Origin of the Inferior Vena
Cava. — The posterior cardinal veins course cephalad along the dorsal
sides of the mesonephroi and open into the common cardinal veins (Fig.
282 A}. Each receives an ischiadic vein from the posterior extremities,
mesonephric branches from the rnid-kidney and dorsal inter segmental
veins from the body wall (Fig. 282 B}. Median and ventral to the meso-
nephros are developed the subcardinal veins, which are connected at
intervals with the posterior cardinal veins by mesonephric sinusoids,
and with each other by anastomoses ventral to the aorta. Thus all the
blood from the mesonephroi, posterior extremities, and dorsal body wall
is in early stages drained by the posterior cardinal veins alone.

The development of the unpaired vena cava inferior begins when com-
munication is established between the right hepatic vein of the liver and the
right subcardinal vein of the mesonephros, primarily a tributary of the
posterior cardinal vein (Lewis, 1902).

The liver on the right side becomes attached to the dorsal body wall,
and from its point of union a ridge, the plica venae caves (Fig. 199), extends
caudalward. According to Davis (1910), capillaries from the subcardinal
vein invade the plica venae cavae, and, growing cranially, meet and fuse
with capillaries extending caudad from the liver sinusoids. Thus is
formed the vein of the plica ven&cavce (x, Fig. 282 A), which is already present
in human embryos of 2.6 mm. (Kollmann). This vein rapidly enlarges,
as also do the sinusoidal connections between the subcardinals and pos-
terior cardinals at one point. Thus the blood from both lower posterior
cardinals is now carried to the heart, chiefly by way of the right subcardinal
and right hepatic veins (Fig. 282 B).

Soon, the posterior cardinals, just cranial to their enlarged anasto-
moses with the subcardinals, become small and are interrupted (Fig.
282 Q . Cranial to their interruption, these veins atrophy and are replaced
by the thoracic portions of new vessels, the supracardinal veins, which
lie dorso-mesial to the posterior cardinals and extend on each side from
the common cardinals veins to the union of the primitive iliac vessels.
The new veins communicate in the thoracic region by a cross anastomosis
and become the azygos and hemiazygos of the adult. The more caudal
portions of the posterior cardinal veins likewise atrophy and are also re-
placed by the supracardinal vessels of the lumbar region (Fig. 282 C).

The blood from the lower trunk and leg region is now drained by the
unpaired inferior vena cava, which is composed of the following veins: (i)

274

THE EDVELOPMENT OF THE VASCULAR SYSTEM

Middle cerebral vein Posterior cerebral vein

Sinus cavernosus
Anterior cerebral vein

N. hypoglossus
V. capitis lateralis

FIG. 283. — Vein? of the head of a 9 mm. human embryo (after Mall). X 9.

Auditory vesicle
Vena capitis medialis
Trigeminal nerve t
Ophthalmic vein

Superior sagit-
tal sinus

Confluence of the sinuses

„..,.. , Superior

Primitive jugular sagittal

vein ™

Middle cerebral vein

Posterior cerebral

vein

Anterior cerebral vein \
Ophthalmic vein
Trigeminal nerve

Vena capitis
1 lateralis

Auditory vesicle

Confluence of the

sinuses \
Superior
sagittal
sinus

Trigeminal nerve
Ophthalmic vein

Anterior cerebral vein
'Middle cerebral vein
| Auditory vesicle

Straight sinus

Confluence
of the sinuses

B

Inferior sagittal siww

Great cerebral vein
Superior sagittal

Superior
pelrosal
sinus
Trans-
verse
sinus

Auditory vesicle

Ophthalmic vein \ Inf. pelrosal sinus
Trigeminal nerve

FIG. 284. — Four diagrams showing the development of the veins of the head (after Mall)
A, At four weeks; B, at five weeks; C, at the beginning of the third month; D, from an older fetus.

Posterior
cerebral
vein
Jugular

vein

Vena capitis
lateralis

Anterior cere-
bral vein
Sphenopari-

' ' inus

DEVELOPMENT OF THE VEINS

275

the common hepatic and right hepatic veins (primitive right vitelline) ;
(2) the vein of the plica venae cavae; (3) an inter-renal portion of the right
subcardinal vein with its great mesial anastomosis; (4) the right supra-
cardinal vein, below the level of the kidneys.

The permanent kidneys take up their positions opposite the great anas-
tomosis between the subcardinals, and at this point the renal veins are
developed (Fig. 282 B) ; the longer left renal vein differs from the right
in that proximally it represents a left portion of the anastomosis itself
(Fig. 282 D). A cephalic portion of the left subcardinal vein persists
as the left suprarenal vein, which thus opens into the left renal instead of
joining the inferior vena cava as does the right suprarenal vein of similar
origin. The left spermatic or ovarian vein early drains into the left caudal
border of the great subcardinal anastomosis, which, as we have seen,
contributes to the left renal- vein. The right spermatic or ovarian vein
opens into the right border of that portion of the subcardinal anastomosis
which is incorporated into the inferior vena cava. Thus the subcardinal
veins aid in the formation of the inferior vena cava and the spermatic
or ovarian vessels, whereas they constitute all of the suprarenal veins; the
rest of the subcardinal system atrophies.

The lumbar veins develop from the same right supracardinal plexus
that gives rise to the caudal segment of the inferior vena cava. Caudal
to its lowest transverse connection with its mate (z, Fig. 282(7), the right
subcardinal vessel becomes the right common iliac vein. The correspond-
ing portion of the similar left vein, plus the transverse anastomosis,
becomes the left common iliac vein. The external and internal (hypo-
gastric) iliacs persist after the posterior cardinal veins disappear and now
join the new common iliacs.

Veins of the Extremities. — The primitive capillary plexus of the upper and lower limb
buds gives rise to a border vein (Figs. 285 and 322), which courses about the periphery of
the flattened limb buds (Hochstetter). In the upper extremity, the ulnar portion of the
border vein persists, forming at different points the subclavian, axillary, brachial, and basil-
ic veins. The border vein at first opens into the dorsal wall of the posterior cardinal vein
(embryos of 10 mm.), but, as the heart shifts its position caudalward, it finally drains by a
ventral connection into the anterior cardinal , or internal jugular vein (Lewis) . The cephalic
vein develops secondarily in connection with the ulnar border vein; later, in embryos of
23 mm., it anastomoses with the external jugular and finally drains into the axillary vein,
as in the adult. With the development of the digits, the w. cephalica and basilica become
distinct, as in embryose of 35 mm., but later are again connected by a plexus on the dorsum
mani, as in the adult (Evans).

In the lower extremity, the fibular portion of the primitive border vein persists. Later,
the v. saphena magna arises separately from the posterior cardinal, gives off the w.
femoralis and tibialis posterior, and annexes the fibular border vein at the level of the knee.
Distal to this junction the border vein persists as the v. tibialis anterior, and, probably, the
v. saphena parva; proximally, it becomes greatly reduced, forming the v. glutea inferior.

276

THE DEVELOPMENT OF THE VASCULAR SYSTEM

Anomalies. — Anomalous blood vessels are of common occurrence. They may be
due: (i) to the choice of unusual paths in the primitive vascular plexuses; (2) to the per-
sistence of vessels usually obliterated, e. g., double superior or inferior venae cavas; right
aortic arch; permanent ductus arteriosus; (3) to incomplete development, e. g., double
aortae.

Dorsal subdavian vei

V. lingua-facial is

V. linguo-facialis
Ant. cardinal win

'om. cardinal win

Dorsal subdavian
vein

V . ulnaris prima

V. thoraco-epigastrica Post, cardinal vein

V, cephalica

V. linguo-facialis V. jugularis
externa

V. cephalica

V. card. ant.

V. card. com.
V. card post.

V.brachialis'

FIG. 285. — Four reconstructions of the veins of the human right arm (after F. T. Lewis).
X about 15. A, 10 mm. embryo; B, 11.5 mm. embryo; C, 16 mm. embryo; D, 22.8 mm.
embryo.

THE FETAL CIRCULATION AND CHANGES AT BIRTH

During fetal life oxygenated placental blood enters the embryo
by way of the large umbilical vein and is conveyed to the liver (Fig. 286).
There it mingles with the small amount of venous blood brought in by the
portal vein. Thence it is carried to the inferior vena cava either directly,
through the ductus venosus, or indirectly through the liver sinusoids and
hepatic vein. The impure blood of the inferior vena cava and portal vein

FETAL CIRCULATION

277

affects but slightly the greater volume of pure placental blood. Entering
the right atrium, it mingles somewhat with the venous blood returned
through the superior vena cava. It is said that the blood from the
inferior vena cava is directed by the valve of this vein through the foramen
ovale into the left atrium (following the path of the sounds in Figs. 262

Internal jugular vein

Subclavian vein
Superior vena cava

Right atrium
Valve of inf. vena cava

Inferior vena cava

Common carotid artery

Subclavian artery
Arrow in ductus arteriosus

Small intestine

V

Iliac art rev and vein

Umbilical vein

Umbilcal cord
Umbilical artery

FIG. 286. — Diagrammatic outline of the organs of circulation in the fetus of six months
(Allen Thomson). The arteries are conventionally colored red and the veins blue, irrespec-
tive of the nature of the blood conveyed by them. Arrows show the course of blood through
the heart, a, Aortic arch; dv, ductus venosus, hv, hepatic vein, vp, portal vein.

to 264), which, before birth, receives little venous blood from the lungs.
This purer blood of the left atrium enters the left ventricle, and is driven
out through the aorta, to be distributed chiefly to the head and upper
extremities.

The venous blood of the superior vena cava, slightly mixed, is sup-
posed to pass from the right atrium into the right ventricle, whence it

278 THE DEVELOPMENT OF THE VASCULAR SYSTEM

passes out by the pulmonary artery. A small amount of this blood is
conveyed to the lungs by the pulmonary arteries, but, as the fetal lungs
do not function, most of it enters the dorsal aorta by way of the ductus
arteriosus. Since the ductus is caudal to the origin of the subclavian and
carotid arteries, its less pure blood is distributed to the trunk, viscera, and
lower extremities. The placental circuit is completed by the hypogastric,
or umbilical arteries by way of the umbilical cord.

Pohlman (Anat. Rec., vol. 2, 1908) interprets his experiments to indicate that, con-
trary to the generally accepted view, there is a mingling of the blood which enters the right
atrium through the two caval veins. If this occurs, there would be no difference in the
quality of blood distributed to the various parts of the body.

Changes at Birth. — At birth the placental circulation ceases and the
lungs become functional. The umbilical arteries and veins, no longer used,
contract and their lumina are obliterated by the thickening of the inner
coat (tunica intima). The lumen of the umbilical artery is said to be
occluded after four days, that of the umbilical vein within a week. The
cord-like vein is persistent as the ligamentum teres of the liver ; the arteries
become the obliterated hypogastrics.

• The ductus venosus atrophies because after birth only the blood from
the portal vein enters the liver, and this is all drained into the liver sinu-
soids, forming the portal circulation. The ductus venosus is obliterated
within two months and becomes the fibrous ligamentum venosum, em-
bedded in the wall of the liver.

The ductus arteriosus ceases to function after birth, as all the blood
from the pulmonary arterial trunk is conveyed to the expanded lungs.
In most cases the ductus becomes impervious within four months after
birth and persists as a solid, fibrous cord, the ligamentum arteriosum.

After birth, the large amount of blood now returned to the left
atrium from the functional lungs equalizes the pressure in the two atria
(p. 256). As a result, both during diastole and systole, the septum
primum, or valve of the foramen ovale, is pressed against the septum
secundum, closing the foramen ovale. Eventually, the two septa fuse —
in one-third of all cases within three months, in two-thirds by the tenth
year (p. 259).

THE LYMPHATIC SYSTEM

The lymphatic system originates in a plexus of lymphatic capillaries
distributed along the primitive main venous trunks. By the dilation
and coalescence of this network at definite regions five lymph sacs appear
(Fig. 287). Paired jugular sacs arise in 10 to n mm. embryos, lateral to
the internal jugular veins. In embryos of 23 mm. the unpaired retro-
peritoneal sac develops at the root of the mesentery, adjacent to the supra-

THE LYMPHATIC SYSTEM

279

renal bodies, and the cisterna chyli also appears, Paired posterior sacs
arise in relation to the sciatic veins in embryos 24 mm. long. These sacs
at first contain blood which they soon discharge into neighboring veins,
thereupon losing their venous connections. With relation to the lymph
sacs as centers, the thoracic duct (at 30 mm.) and the peripheral lymphatics

FIG. 287. — Flat reconstruction of the primitive lymphatic system in a human embryo 30
mm. long (Sabin). X about 3.5. C.c., Cisterna chyli; Lg., lymph gland; S.l.jug., jugular
lymph sac; S.l.mes., retroperitoneal lymph sac; S.l.p., posterior lymph sac; S.l.s., subclavian
lymph sac; V.c., cephalic vein; V.c.i., inferior vena cava; V.f., femoral vein; V.j.t., internal
jugular vein; V.I. p., deep lymphatics; V.l.s., superficial lymphatics; V.r., renal vein; V.s.t
sciatic vein; V.u.(p.) primitive ulnar vein.

develop. The jugular- sacs alone acquire with, the internal jugular veins
secondary connections that are late^r utilized by the thoracic and right
lymphatic ducts. The various sacs themselves are eventually transformed
into chains of lymph nodes.

Two discordant views exist as to the exact mode of origin and growth
of the lymphatics. According to Sabin (1909; 1916) and Lewis (1906),

280 THE DEVELOPMENT OF THE VASCULAR SYSTEM

sprouts, arising from the endothelium of veins, form the single and paired
sacs already described. From these five sacs the thoracic duct and
peripheral lymphatics develop chiefly as endothelial outgrowths. Thus,
lymphatic vessels grow to the head, neck, and arm from the jugular sacs;
to the hip, back, and leg from the posterior sacs; and to the mesentery
from the retroperitoneal sac.

Other investigators (Huntington, 1911; 1914; McClure 1915) hold
that the lymph sacs are formed in situ by the fusion of discrete mesen-
chymal spaces which become lined with an endothelium of transformed,
bordering mesenchymal cells. Venous connections are purely secondary.
The thoracic duct and the peripheral vessels develop similarly by the
progressive fusion of separate clefts; hence, endothelium can differentiate
continually from young mesenchyma. The further growth of endothelium
already formed, is not denied. This general doctrine of the local origin of
endothelium is unquestionably correct (cf. p. 247).

Lymph Glands. — Paired lymph glands appear during the third
month, first in the axillary, iliac, and maxillary regions. Those from the
lymph sacs develop later. Plexuses of lymphatics first form, either as
ordinary networks of peripheral vessels, or as secondary networks pro-
duced by a connective-tissue invasion of the primitive lymph sacs. In
either case, a capillary plexus, with simple connective-tissue septa, marks
the first stage of development. Next (Fig. 288 A), lymphocytes collect
in the connective tissue, forming cortical nodules which become associated
with blood capillaries and later acquire germinal centers. Finally, the
lymphoid tissue is channeled by sinuses formed from lymphatic capillaries.
The peripheral sinus develops afferent and efferent vessels. The central
sinuses cut the lymphoid tissue into medullary cords. In the larger
lymph glands (Fig. 288 B) the connective tissue forms a definite capsule
from which trabeculce dip into the gland.

Haemal (Haemolymph) Glands. — Their origin is traced by Meyer
(1917) to condensations of mesenchyme which develop in relation to
blood vessels, not lymphatics. The peripheral sinus arises independently ;
its vascular connections are secondary.

The Spleen. — This appears in embryos of about 10 mm. as a swelling
on the left side of the dorsal mesogastrium near the dorsal pancreas (Fig.
289 A). The thickening is due to a temporary proliferation and invasion
of mesothelial cells into the underlying mesenchyme, which, meanwhile,
has also undergone local enlargement and vascularization. It is said that
these cells from the peritoneal epithelium give rise to a large part, at least,
of the future spleen. The splenic anlage becomes pinched off from the
mesogastrium (Fig. 289 B) with which it is ultimately joined by a narrow
band only.

Afferent lymphatic vessels

Netwom oj lymphatic,
vessels

Young connective tiss

Lymphoid tissu

Peripheral lymph sinus
Capsule

Trabecula
Reticidar tissue cells

Np;

Lymphatic vessel Blood vessels Lymphatic vessel

mpft sinus

Afferent lymphatic vessels

Peripheral sinus

Lymph sinus

Capsuli

\ r ^-vs^sae:

\ f ',

Secondary nodule

Medullary cord

Trabecula •

Efferent lymphatic vessels

FIG. 288.— Diagrams representing four stages in the development of lymph glands. The earlier stages
are shown on the left side of each figure (Lewis and Stohr).

THE LYMPHATIC SYSTEM

28l

At first the blood vessels constitute a closed system. The peculiar
adult circulation is acquired relatively late. Lifschitz has shown that,
in human fetuses between 150 and 300 mm. long, red blood cells are
actively formed in the splenic pulp as clusters around the giant cells.

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Mesogastrium

Pancreas £££-:V

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Mesogastrium

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A B

FIG. 289. — Two stages in the early development of the human spleen (dorsal is below). A,
from an embryo of 10.5 mm. (Kollmann); B, from a 20 mm. embryo (Tonkoff).

The lymphoid tissue of the spleen first appears as ellipsoids about the
smallest arteries in fetuses of four months. At seven months, the ovoid
splenic corpuscles form as lymphoid nodules about the larger arteries.
The capsule, trabeculcs and reticulum differentiate from the cells of the
common anlage.

The Glomus Coccygeum. — The coccygeal gland is present in 150 mm.
(CH) fetuses as an encapsulated cluster of polyhedral cells at the apex
of the coccyx. Later it becomes lobulated by the ingrowth of connective-
tissue trabeculae and receives a rich vascular supply. According to
Stoerck (1906), its tissue at no time resembles the chromafrm bodies,
as is often stated.

CHAPTER X
HISTOGENESIS

THE primitive cells of the embryo are alike in structure. The pro-
toplasm of each exhibits the fundamental properties of irritability, con-
tractility, reproduction, and metabolism (the absorption, digestion, and
assimilation of nutritive substances and the excretion of waste products,
processes through which growth and reproduction are made possible).
As development proceeds, there is a gradual differentiation of the cells
into tissues, each tissue being composed of like cells, the structure of which
has been adapted to the performance of a certain special function. In
other words, there is division of labor and adaptation of cell structure to
the function which each cell performs. The differentiation of tissue
cells from the primitive cells of the embryo is known as histogenesis.
On page 56 the derivatives of the germ layers were given. We shall now
take up briefly the histogenesis of the tissues derived from the entoderm,
mesoderm, and ectoderm.

HISTOGENESIS OF THE ENTODERMAL EPITHELIUM

The cells of the entoderm are little modified from their primitive
structure. From the first they are concerned with the processes of absorp-
tion, digestion, assimilation, and excretion. They form always epithelial
layers, lining the digestive and respiratory canals, and the glandular
derivatives of these. In the pharynx, esophagus, and trachea the cells
are early of columnar form and ciliated. The epithelium of the pharynx
and esophagus becomes stratified and the surface layers flatten to form
squamous cells. The stratified epithelium is developed from a basal
germinal layer like the epidermis of the integument (see p. 294). Through-
out the rest of the digestive canal the simple columnar epithelium of the
embryo persists. At the free ends of the majority of the cells a cuticular
membrane develops. Other cells are converted into unicellular mucous
glands, or goblet cells. As outgrowths of the intestinal epithelium, are
developed the simple tubular glands of the stomach and intestine, and the
liver and pancreas.

In the respiratory tract, the entoderm forms at first a simple columnar
epithelium. Later, in the trachea and bronchi this is differentiated into a
pseudostratified, ciliated epithelium. The columnar epithelium of the

282

HISTOGENESIS OF THE MESODERMAL TISSUES

283

alveoli and alveolar ducts of the lungs is converted into the flattened
respiratory epithelium.

The development of the thymus and thyreoid glands, liver and pan-
creas may be found in Chapter VII.

HISTOGENESIS OF THE MESODERMAL TISSUES

The differentiation of the mesoderm has been described on p. =13 ff.
It gives rise to the mesodermal segments, intermediate cell masses, somatic
and splanchnic layers, all of which are epithelia, and to the diffuse mesen-
chyme. The somatic and splanchnic layers of the mesoderm form on their
coelomic surfaces a single layer of squamous cells, termed the mesothelium.

Somatic mesoderm
Splanchnic

Mesodermal segment
Central cells of segment
Ederolome
Ectoderm

Intermediate
cell mass

Urogenital ridge.

Splanch
mesoder

FIG. 290. — Transverse section of a 4.5 mm. human embryo, showing the development of the
sclerotomes (Kollmann). X about 300.

This is the covering layer of the pericardium, pleurae, peritoneum, mesen-
teries, serous layer of the viscera, and lining the of vaginal sac in the scro-
tum. From this mesothelium is derived the spleen and also the epithelia
of the genital glands and the Mullerian ducts.

The intermediate cell masses, or nephrotomes, are the anlages of the
pronephros, mesonephros, metanephros, and their ducts (p. 196).

The Sclerotomes and Mesenchyme. — The cavities of the mesodermal
segments become rilled with diffuse, spindle-shaped cells, derived from
the adjacent walls; their median walls are next converted into similar
tissue and the whole migrates mesially towards the neural tube and
notochord, and eventually surrounds these structures (Figs. 290 and 323).
This diffuse tissue is mesenchyme (see p. 55), and that derived from a single

284 HISTOGENESIS

mesodermal' segment constitutes a sclerotome. The sclerotomes ulti-
mately are converted into connective tissue, ^vertebrae, and the basal
portion of the cranium. The persisting lateral plate of the mesodermal
segment becomes a dermo-myotome, from which the voluntary muscle
is differentiated, and, probably, the corium of the integument.

In the head region, cranial to the otocysts, ho mesodermal segments
are formed, but the 'primitive mesoderm is converted directly into mesen-
chyme. Mesenchyme is derived also from the somatic and splanchnic
mesoderm and from the primitive-streak tissue. From the mesenchyme
a number of tissues are developed (see p. 56). The origin of the blood
and primitive blood vessels and lymphatics has been described (Chapter
IX); it remains to trace the development of the supporting tissues and
muscle fibers.

THE SUPPORTING TISSUES

The supporting tissues are peculiar in that a fibrous, hyaline, or
calcified matrix is formed during their development from the mesenchyme,
and this becomes greater in amount than the persisting cellular elements
of the tissue.

CONNECTIVE TISSUE

Different views are held as to the differentiation of connective-tissue
fibers. According to Laguess and Merkel, the fibers arise in an inter-
cellular matrix, derived from the cytoplasm of mesenchymal cells. Szily
holds that fibers are first formed as processes of epithelial cells and that
into this fibrous network mesenchymal cells later migrate. The view
generally accepted, that of Fleming, Mall, Spalteholz, and Meves, is
that the primitive connective-tissue fibers are developed as parts of the
cell, that is, are intracellular in origin.

The mesenchyme is at first compact, the cell nuclei predominating.
Soon a syncytium is developed, the cytoplasm increasing in amount
and forming an open network. Next, the cytoplasm is differentiated into
a perinuclear, granular endoplasm and an outer, distinct, hyaline layer
of ectoplasm (Fig. 291 A) (Mall, 1902). In the ectoplasm fibrils appear,
apparently not mitochondrial in origin (M. R. Lewis, 1918).

Reticular Tissue. — Fine fibers arise in the ectoplasm of the mesenchy-
mal syncytium. The nuclei and endoplasm persist as clasping reticular
cells. According to Mall, reticular fibers differ chemically from white
connective-tissue fibers.

White Fibrous Connective Tissue. — The differentiation of this tissue
may be divided into two stages: (i) a prefibrous stage, during which
the ectoplasm is formed rapidly by the endoplasm of the cells, and fibrils

CONNECTIVE TISSUE

resembling those of reticular tissue appear in the ectoplasm (Fig. 291 A);
(2) the anastomosing fibers take the form of parallel bundles and are
converted, through a chemical change, into typical white fibers. The
spindle-shaped cells are transformed into the connective-tissue -cells
characteristic of the adult. In areolar tissue, the bundles of white fibers
are interwoven to form a mesh work ; in tendon they are arranged in compact,
parallel fascicles. The cells of the tendons are compressed between the
bundles of fibers and this accounts for their peculiar form and arrangement.

Mesenchymal cell

FibrillcE in ectoplasmic
matrix

I Mesenchymal cell

I Cartilage matrix

Cell of syncytmm
Elastic fiber

Cartilage cell

FIG. 291. — The differentiation of the supporting tissues (after Mall). X 270. A, White
fibers in the corium of a 5 cm. pig embryo; B, elastic fibers in the umbilical cord of a 7 cm. pig
embryo; C, cartilage from the occipital bone of a 20 mm. pig embryo.

In the cornea of the eye, the cells retain their processes. The corneal
tissue is thus embryonic in character and is without elastic fibers or blood
vessels.

Elastic Tissue. — With the exception of the cornea and tendon,
yellow elastic fibers develop in connection with all white fibrous .connective
tissue. Like the white fibers, they are produced in the ectoplasm of the
mesenchymal syncytium (Fig. 291 B}. They are developed as single
fibers, but may coalesce to form the fenestrated membranes of the arteries.
According to Ranvier, elastic fibers are produced by the union of ecto-
plasmic granules, but this view is not supported by either Mall or Spalte-
holz.

286

HISTOGENESIS

Adipose Tissue. — Certain of the mesenchymal cells give rise, not
to fibroblasts, but to fat cells. They secrete within their cytoplasm
droplets of fat which increase in size and become confluent (Fig. 292).
Finally, a single fat globule fills the cell, and the nucleus and cytoplasm
are pressed to the periphery. The fat cells are most numerous along the
course of the blood vessels in areolar connective tissue and appear first
during the fourth month.

Nucleus
Fat globules
b

Mes. Precartilage Cartilage

FIG. 292. — Developing fat cells,
the fat blackened with ' osmic acid
(after Ranvier).

FIG. 293. — Diagrams of the development of
cartilage from mesencyhma (Lewis and Stohr). A,
Based upon Studnicka's studies of fish; B, upon
Mall's study of 'mammals. Mes., mesenchyma.

CARTILAGE

Cartilage has been described as developing in two ways: (i) The
mesenchymal cells increase in size and form a compact, cellular precarti-
lage. Later, the hyaline matrix is developed between the cells from their
cytoplasm (Fig. 293 A}. The matrix may in this case be regarded as
the ectoplasm of the cartilage cells. (2) According to Mall, mesenchymal
cells give rise first to an ectoplasm in which fibrillae develop. Next,
the cells increase in size and are gradually extruded until they lie in the
spaces of the ectoplasmic matrix (Figs. 291 C and 2 93 B}. Simultaneously,
the ectoplasm undergoes both a chemical and structural change and is
converted into the hyaline matrix peculiar to cartilage. About the car-
tilage cells the endoplasm produces capsules of hyaline substance.

The interstitial growth of cartilage is due: (i) to the proliferation of adult cartilage
cells; (2) to the production of new matrix. Appositional growth also takes place, through
the mitotic activity of the connective-tissue sheath, the perichondrium. Its inner cells
are transformed into young cartilage cells.

BONE

287

In hyaline cartilage, the matrix remains hyaline. Infibro-cartilage, the fibrillations of
the primitive ectoplasm are converted into white fibers. In elastic cartilage, yellow elastic
fibers are formed in the hyaline matrix, according to Mall; before the hyaline matrix is
differentiated, according to Spalteholz. Most of the bones of the skeleton are preformed
in cartilage.

BONE

Bone is a tissue appearing relatively late in the embryo. There are
developed two types : the membrane bones of the face and cranium, and
the cartilage bones which replace the cartilaginous skeleton. The mode
of histogenesis, however, is identical in both.

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FIG. 294. — Two stages in the development of bone. A, Section through the frontal bone
of a 20 mm. pig embryo (after Mall). X 270. B, Section through the periosteum and bone
lamellae of the mandible of a 65 mm. human fetus. X 325.

Membrane Bone. — The flat bones of the face and skull are not pre-
formed as cartilage. The form of a membrane bone is determined by the
development of a periosteal membrane from the mesenchyma. The bone
matrix is differentiated within the periosteum from enlarged columnar
cells, the osteoblasts (bone formers). Osteoblasts appear in clusters and
from their cytoplasm is differentiated a fibrillated ectoplasmic matrix
like that which precedes the formation of connective tissue and cartilage
(Fig. 294 A). This fibrillated matrix, apparently by a chemical change,

288 HISTOGENESIS

is converted into a homogeneous bone matrix, which first takes the form of
spicules. Others view the fibrillated matrix as an intercellular product
and the bone matrix as an interfibrillar deposit. However this may be,
the spicules coalesce, form a network of bony plates, and constitute the
bone matrix upon the surface of which osteoblasts are arranged in a
single layer like the cells of an epithelium (Fig. 294 B). As the matrix
of the bone is laid down, osteoblasts become engulfed and form bone cells.
The bone cells are lodged in spaces termed lacunas. These are connected
by microscopic canals, the canaliculi, in which delicate cell processes
course.

Ossification begins at the middle of the bone and proceeds in all
directions from this primary center. The plates of the spongy membrane
bone are formed about blood vessels as centers. As the bone grows at
the periphery, the bone matrix is resorbed centrally. At this time, large,
multinculeate cells appear upon the surfaces of the bone matrix. These
cells are known as osteoclasts (bone destroyers). There is, however, no
positive evidence that the osteoclasts are active in dissolving the bone.
They may be interpreted also as degenerating, fused osteoblasts (Arey,
1920). The cavities in which they arevfrequently lodged are known as
Howship's lacuna. The bone lamellas of the central portion of the mem-
brane bone are gradually resorbed, and this portion of the bone is of a
spongy texture. Some time after birth, compact bone lamellas are laid
down by the osteoblast cells of the inner layer of the periosteum. In the
case of flat bones, compact inner and outer plates, or tables, are thus devel-
oped with spongy bone between them. The spaces in the spongy bone
are filled by derivatives of the mesenchyme : reticular tissue, blood vessels,
fat cells, and developing blood cells. These together constitute the red
bone marrow.

Cartilage Bone. — The form of the cartilage bone is determined by the
preformed cartilage and its surrounding membrane, the perichondrium
(Fig. 296). Bone tissue is developed as in membrane bones, save that
the cartilage is first gradually destroyed and the new bone tissue develops :
(i) in, and (2) about it. In the first case, the process is known as endo-
chondral bone formation. In the second case, it is known as perichondral,
or per io steal bone formation.

Endochondral Bone Formation. — The cartilage cells enlarge, become
arranged in characteristic rows, and lime is provisionally deposited in
the matrix (Fig. 295). The perichondrium becomes the periosteum.
From its inner or osteogenic layer, which is densely cellular, ingrowths
invade and resorb the cartilage and fill the primary marrow cavities.
The invading osteogenic tissue gives rise to osteoblasts and bone marrow.
The osteoblasts deposit bone directly upon persisting portions of the carti-

FIG. 295.— A longitudinal section of the two distal phalanges from the finger of a five-
months' human fetus (Sobotta). X 15. Kn, Cartilage showing calcification and resorption;
eK, endochondral bone; M, marrow cavity; p K, periosteal bone.

BONE

289

lage. As new bone is developed peripherally, it is resorbed centrally to
form large marrow spaces. Eventually, all of the cartilage matrix, and
probably the cartilage cells as well, are destroyed.

Perichondral Ossification. — Compact bone is developed by the
osteogenic layer of the periosteum, and thus are produced the periosteal
lamellae. In the ribs this is said to be the only method of ossification.
Those bone lamellae deposited about a blood vessel are concentrically
arranged and form the concentric lamella of an Haversian system. The
Haversian canal of adult bone is merely the space occupied by bloodvessels.
Between the Haversian systems are interstitial lamella.

-Cartilage

•Bony diaphysis

-Bone marrow

Epiphysis

Diaphysis

Epiphysis

FIG. 296. — Diagrams to show the method of growth of : A, vertebra; B, sacrum; C-F, a long

bone (tibia).

Growth of Cartilage Bones. — In cartilage bones there is no inter-
stitial growth as in cartilage. Most of the cartilage bones have more than
one' center of ossification and growth is due to the expansion of the inter-
vening cartilage. Flat bones grow at the periphery; ring like bones, such
as the vertebrae, have three primary centers of ossification, between which
the cartilage continues to grow (Fig. 296 A). In the case of the numerous
long bones of the skeleton, the primitive ossification center forms the shaft,
or diaphysis (Fig. 296 C-F). The cartilage at either end of the diaphysis^
grows rapidly and thus the bone increases in length. Eventually, osteo-
genic tissue invades these cartilages and new ossification centers, the
epiphyses, are formed, one at either end. When the growth of the bone

2QO HISTOGENESIS

in length is completed, the epiphyses, by the ossification of the intervening
cartilage, are united to the diaphysis.

The shaft of the long bones grows in diameter by the peripheral
deposition of bone lamellae and the central resorption of the bone. In
the larger long bones, spongy, or cancellated bone tissue persists at the
ends, but in the middle portion a large medullary, or marrow cavity is
developed. This is filled chiefly with fat cells and constitutes the yellow
bone marrow.

Regeneration of Bone. — If bone is injured or fractured, new bone is developed by osteo-
blasts derived either from the periosteum or from the bone marrow. The repair of a
fracture is usually preceded by the formation of cartilage which unites the ends of the bones
and is later replaced by bone. In adults, the periosteum is regarded as especially important
in the regeneration of bone tissue.

Joints. — In joints of the synarthrosis type, in which little movement
is allowed, the mesenchyma between the ends of the bones differentiates
into connective tissue or cartilage. This persists in the adult.

In joints of the diarthrosis type, the bones are freely movable. The
mesenchyma between the bones develops into an open connective tissue
in which a cleft appears, the joint cavity. The cells lining this cavity
flatten out and form a more or less continuous layer of epithelium, the
synomal membrane. From the connective tissue surrounding the joint
cavity are developed the various fibrous ligaments typical of the different
joints. Ligaments or tendons which apparently course through the adult
joint cavities represent secondary invasions, covered with reflexed synovial
membrane and hence really external to the cavity.

THE HISTOGENESIS OF MUSCLE

The muscular system is composed of muscle fibers ; these form a tissue
in which contractility has become the predominating function. The
fibers are of three types: (i) smooth muscle cells, found principally in the
walls of the viscera and blood vessels; (2) striated skeletal muscle, chiefly
attached to the elements of the skeleton and producing voluntary move-
ments; (3) striated cardiac muscle, forming the myocardium of the heart.
All three types are derived from the mesoderm. The only exceptions are
the smooth muscle of the iris, and the smooth muscle of the sweat glands,
which are derived from the ectoderm.

Smooth Muscle. — Certain stellate cells of the mesencyhma enlarge,
jslongate, and their cytoplasm becomes more abundant. The resulting
spindle-shaped cells remain attached to each other by cytoplasmic bridges
and develop in the superficial layer of their cytoplasm coarse, non-con-
tractile myoglia fibrils (Fig. 297), similar to the primitive fibrillae of con-

THE HISTOGENESIS OF MUSCLE

29I

nective tissue (McGill, 1907). The myoglia fibrils may extend from cell
to cell, thus connecting them. These fibrils are the products of coalesced
granules found within the cytoplasm of the myoblasts. In embryos of
30 mm. fine myofibrillae are differentiated in the cytoplasm of the myoblasts
and give it a longitudinally striated appearance. The cytoplasmic pro-
cesses of the muscle cells, the cytoplasmic bridges, later give rise to white

FIG. 297. — Two stages in the development of smooth muscle fibers (after McGill). A,
from the esophagus of a 13 mm. pig (X55o); coalescing granules give rise to coarse myoglia
fibrils. B, from the esophagus of a 27 mm. pig (X 850); both coarse myoglia fibrils and fine
myofibrils are present.

connective-tissue fibers which envelop the muscle fibers and bind them
together. Smooth muscle also increases in amount by mitotic division
and the transformation of interstitial connective -tissue cells.

Striated Skeletal Muscle. — All striated voluntary muscle is derived
from the mesoderm, either from the myotomes of the segments (muscles of

FIG. 298. — Stages in the histogenesis of skeletal muscle (after Godlewski). A, myoblast
a 13 mm. sheep embryo; B, myogeneous myofibrils in a myoblast of a 10 mm. guinea pig em-
bryo; C, myoblast with longitudinally splitting striated myofibrils from an 8.5 mm. rabbit
embryo.

the trunk) of from the mesenchyma (muscles of the head). According
to Bardeen (1910), after the formation of the sclerotome (Fig. 290),
which gives rise to skeletal tissue, the remaining portion of the primitive
segment constitutes the myotome; all of its cells become myoblasts. On
the contrary Williams (1910), finds that in the chick only the cells of the
dorsal and mesial walls of a mesodermal segment are myoblasts. By

2Q2 HISTOGENESIS

multiplication they form a mesial myotome, while the lateral cells of the
original mesodermal segment persist as a dermatome and give rise only to
the connective tissue of the corium (Fig. 223). The dermatome lies
lateral to the myotome (Fig. 47) and the two together constitute the
der mo -myotome.

As to the manner of origin of the individual muscle fibers, there is also
a difference of opinion. It is generally believed that the myoblasts
elongate, and, by the repeated mitotic division of their nuclei, become
multinucleated. Godlewski, (1902), however, holds that several myo-
blasts unite to form a single muscle fiber. The nuclei lie at first centrally,
surrounded by the granular sarcoplasm (Fig. 298 A). The sarcoplasmic
granules become arranged in rows and constitute the myofibrillce, which
increase in number by longitudinal splitting (Fig. 298 B, C). The myo-
fibrillae soon differentiate alternating dark and light bands, due to dif-
ferences in density, and the individual fibrillas, become so grouped that
their dark and light bands coincide (Fig. 298 C}. During development,
the muscle fibers increase enormously in size, the nuclei migrate to the
surface, and the myofibrillae are arranged in bundles, or muscle columns
(sarcostyles). The fibrils of each column are said to arise by the longitu-
dinal splitting of single, primitive myofibrils.

While smooth muscle forms a syncytium and the enveloping connec-
tive-tissue fibers are developed directly from the muscle cells, in the case
of striated skeletal muscle each fiber is a multinucleated entity which is
bound to others by connective tissue of independent origin.

According to Baldwin (1912), the nucleus and perinuclear sarcoplasm is separated
from the rest of the muscle fiber by the sarcolemma. With Apathy (1888), he would
therefore regard the myofibrillag as a differentiated product of the muscle cells, to be homo-
logized with connective-tissue fibers. There is little to support this view.

During the later stages in the development of striated voluntary muscle there is,
according to many observers, an active degeneration of the muscle fibers.

Striated Cardiac Muscle. — This is developed from the splanchnic
mesoderm that forms both the epicardium and the myocardium (Fig.
255). The cells of he myocardium at first form a syncytium in which myo-
fibrillae develop from the linear union of cytoplasmic granules. The myo-
fibrillae are developed at the periphery of the syncytial strands of cytoplasm
and extend long distances in the syncytium. They multiply rapidly
and form dark and light bands, as in skeletal muscle. The syncytial
character of cardiac muscle persists in the adult and the nuclei remain
central in position. The intercalated discs, typical of adult cardiac muscle,
probably appear in the early months of fetal life.

THE EPIDERMIS

293

HISTOGENESIS OF THE ECTODERMAL DERIVATIVES

Besides forming the enamel of the teeth and the salivary glands
(p. 1531!), the ectoderm gives rise : (i) to the epidermis and its derivatives
(subcutaneous glands, nails, hair, and the lens and conjunctiva of the
eye); (2) to the nervous system and sensory epithelia; (3) to parts of
certain glands producing internal secretions, such as the pituitary body,
suprarenal glands, and chromaffin bodies.

We shall describe here the histogenesis of the epidermis, the develop-
ment of its derivatives, and the histogenesis of the nervous tissues, re-
serving for final chapters the development of the nervous organs and the
glands formed in part from them.

THE EPIDERMIS

The single-layered ectoderm of the early embryo, by the multiplica-
tion of its cells, becomes differentiated into a two-layered epidermis,

Epitrichium

Intermediate layer
Stratum germinativum

FIG. 299. — Sections of the integument from a 65 mm. human fetus. X 440. A, From
the neck, showing a two-layered epidermis and the beginning of a third intermediate layer;
B, from the chin, with three well developed epidermal layers.

composed of an inner layer of cuboidal or columnar cells, the stratum
germinativum, and an outer layer of flattened cells, the epitrichium, or
periderm (Fig. 299 A}.

The stratum germinativum is the reproducing layer of the epidermis.
As development proceeds, its cells divide and gradually give rise to new
layers above, until the epidermis becomes a many-layered, or stratified
epithelium. The periderm is always the outermost layer of the epidermis.
During the third and fourth months the epidermis is typically three-
layered, the outer, flattened layer forming the periderm, a middle layer of
polygonal cells, the intermediate layer, and the inner, columnar layer, the

294 HISTOGENESIS

stratum germinativum (Fig. 299 B}. After the fourth month the epider-
mis becomes many layered. The inner layers of cells now form the stra-
tum germinativum and are actively dividing cells, united with each other
by cytoplasmic bridges. The outer layers of cells become cornified, the
cornification of the cells proceeding from the stratum germinativum
toward the surface. Thus, next the germinal layer, are cells containing
keratohyalin which constitute the double-layered stratum granulosum. A
thicker layer, above the stratum granulosum, shows cells in which drops
of a substance called eleidin are formed. These droplets, supposed to
represent softened keratohyalin, give these cells a clear appearance when
examined unstained. Hence the layer is termed the stratum lucidum.
In the outer layers of the epidermis the thickened walls of the cells become
cornified and in the cells themselves a fatty substance collects. These
layers of cells constitute the stratum corneum. Its cells are also greatly
flattened, especially at the surface.

When the hairs develop they do not penetrate the outer periderm layer
of the epidermis, but, as they grow out, lift it off (sixth month). Hence
this layer is known also as the epitrichium (layer upon the hair). Des-
quamated epitrichial and epidermal cells mix with the secretion of the
sebaceous glands to form the pasty vernix caseosa that smears the fetal
skin. Pigment granules appear soon after birth in the cells of the stratum
germinativum. These granules are probaly formed in situ. Negr€> chil-
dren are quite light in color at birth, but within six weeks their integument
has reached the definitive degree of pigmentation.

The derma, or corium, of the integument is developed from mesen-
chyme, perhaps from definite dermatomes (Fig. 323) of the mesodermal
segments (p. 292). At about the end of the third month a differentiation
into the compact corium proper and the areolar subcutaneous tissue occurs.
From the corium, papilla project into the stratum germinativum.

Anomalies. — The deposition of pigment in the epidermis and elsewhere may fail
(albinism), or be over abundant (melanism). The defects of pigmentation sometimes
affect local areas only. Naevi are either pigmented spots ('moles'), or purple discolora-
tions (birthmarks') caused by cavernous vascular plexuses in the corium. Ichthyosis
results from an excessive thickening of the stratum corneum. In severe cases, horny
plates 5 mm. thick are formed; these are separated by deep cracks. Dermoid cysts (p.
218) resulting from epidermal inclusions, are not infrequent along the lines of fusion of
embryonic structures, e. g., branchial grooves, mid-dorsal and mid-ventral body wall.

THE HAIR

Hairs are derived from thickenings of the epidermis and begin to
develop at the end of the second month on the eyebrows, upper lip, and
chin. The hair of the general body integument appears at the beginning
of the fourth month.

THE HAIR

295

The first evidence of a hair anlage is the elongation of a cluster of
epidermal cells in the inner germinal layer (Fig. 300 ,4). The bases of
these cells project into the corium, and, above them, cells of the epidermis
are arranged parallel to the surface. The elongated cells continue to grow
downward until a cylindrical hair anlage is produced (Fig. 300 B, C).
This consists of an outer wall, formed of a single layer of columnar cells,
continuous with the basal layer of the epidermis. This wall bounds a
central mass of irregularly polyhedral epidermal cells. About the hair an-
lage the mesenchyma forms a sheath, and at its base a condensation of
mesenchyme produced the anlage of the hair papilla, which projects into

Epidermal anlage of ^^'^>^^^^^^^^^^^ff>s^^^^f^^f^^^1^

'^^SmililjS^^^f'^!!? ^^V.^^-BJ^-T'^^^' ^-Piaerma^ anlage of

Anlage of hair papilla

^

Epidermal anlage of hair C A

Mesenchymal sheath

Hair bulb

Hair papilla

FIG. 300. — Section through the integument of the face of a 65 mm. human fetus, showing three
stages in the early development of the hair. X 330.

the enlarged base of the hair anlage. As development proceeds, the
hair anlage grows deeper into the corium and its base enlarges to form the
hair bulb (Fig. 300 Q. The hair differentiates from the based epidermal
cells surrounding the hair papilla. These cells give rise to a central core
which grows toward the surface, distinct from the peripheral cells which
form the outer sheath of the hair (Fig. 301). The central core of cells be-
comes the inner hair sheath and the shaft of the hair. Two swellings of the
outer hair sheath appear on the lower side of the obliquely directed hair
anlage. The more superficial of these is the anlage of the sebaceous gland
(Fig. 301). The deeper swelling is the epithelial bed, a region where the
cells by rapid division contribute to the growth of the hair follicle.

Superficial to the bulb, the cells of the hair shaft become cornified
and differentiated into an outer cuticle, middle cortex, and central incon-
stant medulla. The hair grows at the base and is pushed out through the

296

HISTOGENESIS

central cavity of the anlage, the cells of which degenerate. When the
hair projects above the surface or the epidermis it breaks and carries with
it the epitrichial layer. The mesenchymal tissue which surrounds the hair
follicle in the neighborhood of the epithelial bed gives rise to the smooth
fibers of the arrector pili muscle. Pigment granules develop in the basal
cells of the hair and give it its characteristic color.

Inner hair sheath

Outer hair sheath — -
Mesenchymal sheath

Epidermis

Arrector pili muscle fibers
Sebaceous gland

Epithelial bed
Root of hair

•Hair bulb
• Hair papilla

FIG. 301. — Longitudinal section through a developing hair from a five and one-half months'
human fetus (after Stohr). X 220.

The first generation of 'lanugo' hairs are short-lived, all except those
covering the face being cast off soon after birth. The coarser, replacing
hairs develop, at least in part, from new follicles. Thereafter, hair is shed
periodically throughout life.

Anomalies. — Hypertrichosis refers to excessive hairiness which may be general or
local, as in the exhibited 'hairy monsters.' In the rare hypotrichosis, the congenital ab-
sence of hair is usually associated with defective teeth and nails.

SWEAT GLANDS

The sudoriparous, or sweat glands begin to develop in the fourth
month from the epidermis of the finger tips, the palms of the hands, and
the soles of the feet. They are formed as solid downgrowths from the
epidermis, but differ from hair anlages in having no mesenchymal papillae
at their bases. During the sixth month the tubular anlages of the gland
begin to coil, and, in the seventh month, their lumina appear. The inner
layer of cells forms the gland cells, while the outer cells become trans-
formed into smooth muscle fibers which here arise from the ectoderm. In
the axillary region, sweat glands occur which are large and branched.

MAMMARY GLANDS

297

MAMMARY GLANDS

The tubular mammary glands are peculiar to mammals. In embryos
• of 9 mm. (Figs. 94 and 1 18) an ectodermal thickening extends ventro-later-
ally between the bases of the limb buds on either side. This linear
epidermal thickening is the milk line. In the future pectoral region of this
line, by the thickening and downgrowth of the epidermis, there is formed
the papilla-like anlage of the mammary gland (Fig. 302 A). From this
epithelial anlage buds appear (B) which elongate and form solid cords,
15 to 20 in number, the anlages of the milk ducts (C). These branch in
the mesenchymal tissue of the corium and eventually produce the alveolar

Epidermis Gland anlage

'Duct

Smooth muscle
of areola

3JIIJI&SJ& Panniculus
~^~ adiposus

--.'•':••'..•' • .V •••••; [ l[> 'vg-? •'• ^; •• ~, -V-

FIG. 302. — Sections representing three stages in the development of the human mammary
gland (Tourneux). A, fetus of 32 mm.; B, of 102 mm.; C, of 244 mm. *, Groove limiting
glandular area.

end pieces of the mammary glands. In the region where the milk ducts
open on the surface the epidermis is evaginated to form the nipple. The
glands yield a little secretion ('witch milk') at birth; they enlarge rap-
idly at puberty and are further augmented during pregnancy, while two
or three days after parturition they become functionally active.

The mammary glands are regarded as modified sweat glands. This homology is made
because their development is similar, and because in the lower mammals their structure is
the same. Rudimentary mammary glands (of Montgomery), which also resemble sweat
glands, occur in the areola about the nipple. In many mammals, numerous pairs of mam-
mary glands are developed along the milk line (pig, dog, etc.) ; in some a pair of glands is
developed in the pectoral region (primates, elephants) ; in others, glands are confined to the
inguinal region (sheep, cow, horse).

Anomalies. — Supernumerary mammary glands (hypermastla) or nipples (hy perihelia)
are not infrequent between the axilla and groin. These represent independent differen-
tiations along the primitive milk line.

298

HISTOGENESIS

THE NAILS

The anlages of the nails proper are derived from the epidermis and
may be recognized in fetuses of 45 mm. (CR). A nail anlage forms on
the dorsum of each digit and extends from the tip of the digit almost to
the articulation of the terminal phalanx. At the base of the anlage, that
is, proximally, the epidermis is folded inward to form the proximal nail
fold (posterior nail fold of the adult) (Fig. 303 C). The nail fold also ex-
tends laterally on either side of the nail anlage and forms the lateral nail
fold of the adult (A, B}.

The material of the nail is developed in the lower layer of the proxi-
mal nail fold (C). In certain of 'the epidermal cells, which, according to

Sole plate

Eponychium

FIG. 303. — Figures showing the development of the nail. A, From a 40 mm. human fetus
(X 20); B, from a 100 mm. fetus (X 13); C, longitudinal section from a 100 mm. fetus (X 24).
(Kollmann.)

Bowen, represent a modified stratum lucidum, there are developed kera-
tin, or horn fibrils during the fifth month of fetal life. These appear
without the previous formation of keratohyalin granules, as is the case in
the cornification of the stratum corneum. The cells flatten and form the
plate-like structure of which the solid substance of the nail is composed.
Thus the nail substance is formed in the proximal nail fold as far distad as
the outer edge of the lunula (the whitish crescent at the base of the adult
nail). The underlying epidermis, distal to the lunula, takes no part in the
development of the nail substance. The corium throws its surface of
contact with the nail into parallel longitudinal folds that produce the
longitudinal ridges of the nail. The nail is pushed toward the tip of the

HISTOGENESIS OF THE NERVOUS TISSUES

299

digit by the development of new nail substance in the region of the nail
fold. The stratum corneum and the epitrichium of the epidermis for a
time completely cover the nail matrix and are termed the eponychium
(Fig. 303 C}. Later, this is thrown off, but a portion of the stratum
corneum persists during life as the curved fold of epidermis which adheres
to the base of the adult nail. During life the nail constantly grows at its
base (proximally) , is shifted distally over the nail bed, and projects at the
tip of the digit.

The nails of man are the homologues of the claws and hoofs of other mammals. Dur-
ing the third month thickenings of the integument over the distal ends of the metacarpals
and metatarsals become prominent. These correspond to the touch-pads on the feet of
clawed mammals. Similar pads are developed on the under sides of the distal phalanges.

HISTOGENESIS OF THE NERVOUS TISSUES

The primitive anlage of the nervous system consists of the thickened
layer of ectoderm along the mid-dorsal line of the embryo. This is the
neural plate (Fig. 304 A, B) which is folded to form the neural groove

Neural groove Neural plate

Neural groove Neural plate

Ectoderm

Neural groove

Neural tube

Neural tube

Neural cavity

FIG. 304. — Four sections showing the development of the neural tube in human embryos.
A, An early embryo (Keibel); 5, at 2 mm. (Graf Spee); C, at 2 mm. (Mall); D, at 2.7 mm.
(Kollmann).

(Figs. 77 A and 78). The edges of the neural plate come together and form
the neural tube (Fig. 304 C, D). The cranial portion of this tube enlarges
and is constricted into the three primary vesicles of the brain (Fig. 324).
Its caudal portion remains tubular and constitutes the spinal cord. From
the cells of this tube, and the ganglion crest connected with it, are differ-

3oo

HISTOGENESIS

entiated the nervous tissues, with the single exception of the nerve cells
and fibers of the olfactory epithelium.

Differentiation of the Neural Tube. — The cells of the neural tube
differentiate into two products. There are formed: (i) nerve cells and
fibers, in which irritability and conductivity have become the predominant

Ependymal layer

Marginal layer Ependymal layer
Mesoderm Marginal layer

Internal limiting membrane

Ependymal layer

External limiting membrane
External limiting membrane

Internal limiting membrane

Germinal cell
1

Internal limiting membrane

Mesoderm Marginal layer * Mantle layer Ependymal layer

FIG. 305. — Three stages in the differentiation of the neural tube (after Hardesty). X 690.
A, From a rabbit embryo before the closure of the neural tube; B, from a 5 mm. pig embryo
after closure; C, from a 7 mm. pig embryo; D, from a 10 mm. pig embryo. *, Boundary be-
tween mantle and marginal layers.

functions; (2) neuroglia cells and fibers, which constitute the supporting,
or skeletal tissue, peculiar to the nervous system. The differentiation
of these tissues has been studied by Hardesty (1904) in pig embryos.
The wall of the neural tube, consisting at first of a single layer of columnar
cells, becomes many-layered, and, finally, three zones are differentiated
(Fig. 305 A-D). As the wall becomes many-layered the cells lose their

HISTOGENESIS OF THE NERVOUS TISSUES

301

sharp outlines and form a compact, cellular syncytium which is bounded,
on its outer and inner surfaces, by an external and internal limiting mem-
brane (B}. In a 10 mm. embryo the cellular strands of the syncytium are
arranged radially and nearly parallel (D) . The nuclei are now so grouped
that there may be distinguished three layers: (i) an inner ependymal zone,
with cells abutting on the internal limiting membrane, their processes
extending peripherally; (2) a middle mantle, or nuclear zone, and (3) an
outer, or marginal zone, non-cellular, into which nerve fibers grow. The
ependymal zone contributes cells for the development of the mantle layer
(D). The cellular mantle layer forms the gray substance of the central
nervous system, while the fibrous marginal layer constitutes the white
substance of the spinal cord.

The primitive germinal cells of the neural tube divide by mitosis and
give rise to the ependymal cells of the ependymal zone and to indifferent

Ependymal cells

Neuroblasls

Neuroglia cells

FIG. 306. — Diagrams showing the differentiation of the cells of the neural tube (after Schaper).

cells of the mantle layer. From these latter arise spongioblasts and
neuroblasts (Fig. 306). The spongioblasts are transformed into neuroglia
cells and fibers, which form the supporting tissue of the central nervous
system; the neuroblasts are primitive nerve cells, which, by developing
cell processes, are converted into neurons. The neurons are the structural
units of the nervous tissue.

The Differentiation of Neuroblasts into Neurons. — The nerve fibers
are developed as outgrowths from the neuroblasts, and a nerve cell with
all its processes constitutes a neuron or cellular unit of the nervous system.
The origin of the nerve fibers as processes of the neuroblasts is best seen
in the development of the root fibers of the spinal nerves.

This neuron concept of the development of the nerve fibers is the one generally accepted
at the present time. It assumes that all axons and dendrites are formed as outgrowths
from nerve cells, an hypothesis first promulgated by His. The embryological evidence is

332 HISTOGENESIS

supported by experiment. It has long been known from the work of Waller that if nerves,
are severed, the fibers distal to the point of section, and thus isolated from their nerve cells
will degenerate; also, that regeneration will take place from the central stumps of cut nerves,
the fibers of which are still connected with their cells. More recently Harrison (1906),
experimenting on amphibian larvae, has shown: (i) that no peripheral nerves develop if
the neural tube and crest are removed; (2) that isolated ganglion cells growing in clotted
lymph will give rise to long axon processes in the course of four or five hours.

A second theory, supported by Schwann, Balfour, Dohrn, and Bethe, assumes that the
nerve fibers are in part differentiated from a chain of cells, so that the neuron would repre-
sent a multicellular, not a unicellular structure. Apathy and O. Schulze modified this
cell-chain theory by assuming that the nerve fibers differentiate in a syncytium which inter-
venes between the neural tube and the peripheral end organs. Held further modified this
theory by assuming that the proximal portions of the nerve fibers are derived from the
neuroblasts and ganglion cells and that these grow into, a syncytium' which by differentia-
tion gives rise to the peripheral portion of the fiber.

Efferent Fibers of the Spinal Nerves. — At the end of the first month,
clusters of neuroblasts separate themselves from the syncytium in the
mantle layer of the neural tube. The neuroblasts become pear-shaped,
and from the small end of the cell a slender primary process grows out
(Figs. 307 and 308). This process becomes the axon or axis cylinder.
The primary processes may course in the marginal layer of the neural tube,
or, converging, may penetrate the marginal layer ventro-laterally and form
the ventral roots of the spinal nerves. Similarly, the efferent fibers of
the cerebral nerves grow out from neuroblasts of the brain wall. Within
the cytoplasm of the nerve cells and their primary processes, strands of
fine fibrils are early differentiated (Fig. 307 B). These, the neurofibrillcz,
are usually assumed to be the conducting elements of the neurons. The
cell bodies of the efferent neurons soon become multipolar by the develop-
ment of branched secondary processes, the dendrons or dendrites.

Development of the Spinal Ganglia and Afferent Neurons. — After the
formation of the neural plate and groove, a longitudinal ridge of cells
appears on each side where the ectoderm and neural plate are continuous
(Fig. 309 A). This ridge of ectodermal cells is the neural, or ganglion
crest. When the neural tube is formed and the ectoderm separates from
it, the cells of the ganglion crest overlie the neural tube dorso-laterally
(Fig. 309 C). As development continues they separate into right and
left linear crests, distinct from the neural tube, and migrate ventro-
laterally to a position between the neural tube and myotomes. In this
position the ganglion crest forms a band of ce?& extending the whole
length of the spinal cord and as far cephalad as the otic vesicles. At
regular intervals in its course along the spinal cord the proliferating cells
of the crest give rise to enlargements, the spinal ganglia (Fig. 358). The
spinal ganglia are arranged segmentally and are connected at first by

HISTOGENESIS OF THE NERVOUS TISSUES
A

303

FIG. 307. — The differentiation of neuroblasts in chick embryos of the third day. A,
Transverse section through the spinal cord, showing neuraxons (F) growing from neuroblasts
and from bipolar ganglion cells (d). B, Single neuroblasts, showing neurofibrils and incre-
mental cone (c). Cajal.

Dorsal root

~~Spongioblasts

Neuroblasts

Ventral root

FIG. 308. — Transverse section of the spinal cord from a human fetus of five weeks, showing
the origin of ventral root fibers from neuroblasts (His in Marshall) 150. X.

304

HISTOGENESIS

Neural crest

FIG. 309. — Three stages in the development of the ganglion crest in human embryos (after von
Lenhossek in Cajal).

FIG. 310. — Stages in the formation of unipolar ganglion cells (Cajal). From a 44 mm. human

fetus.

HISTOGENESIS OF THE NERVOUS TISSUES 305

bridges of cells that later disappear. In the hind-brain region, certain
ganglia of the cerebral nerves develop from the crest but are not segment -
ally arranged.

The cells of the spinal ganglia differentiate into: (i) ganglion cells,
and (2) supporting cells, groups which are comparable to the neuroblasts
and spongioblasts of the neural tube. The neuroblasts of the ganglia
become fusiform and develop a primary process at either pole; thus these
neurons are of the bipolar type (Fig. 307, d). The centrally directed
processes of the ganglion cells converge, and, by elongation, form the
dorsal roots. They penetrate the dorso-lateral wall of the neural tube,
bifurcate, and course cranially and caudally in the marginal layer of the
spinal cord. By means of branched processes they come in contact with
the neurons of the mantle layer. The peripheral processes of the gang-
lion cells, as the dorsal spinal roots, join the ventral roots, and together
with them, constitute the trunks of the spinal nerves (Fig. 325).

At first bipolar, (Fig. 310, A), the majority of the ganglion cells be-
come unipolar, either by the fusion of the two primary processes or by the
bifurcation of a single process. The process of the unipolar ganglion is
now T-shaped. Many of the bipolar ganglion cells persist in the adult,
while others develop several secondary processes and thus become multi-
polar in form. In addition to forming the spinal ganglion cells, neuro-
blasts of the ganglion crest are believed to migrate ventf ally and form the
sympathetic ganglia (Fig. 325).

Differentiation of the Supporting Cells of the Ganglia. *— The support-
ing cells of the spinal ganglia at first form a syncytium in the meshes of
which are found the neuroblasts. They differentiate: (i) into flattened
capsule cells, which form capsules about the ganglion cells; and (2) into
sheath cells, which ensheath the axon processes of both dorsal and ventral
root fibers and are continuous with the capsules of the ganglion. It is
probable that many of the sheath cells migrate peripherally along with
the developing nerve fibers (Harrison). They are at first spindle-shaped,
and, as primary sheaths, enclose bundles of nerve fibers. Later, by the
proliferation of the sheath cells, the bundles are separated into single fibers,
each with its sheath (of Schwann), or neurilemma. Each sheath cell forms
a segment of the neurilemma, the limits of contiguous sheath cells being
indicated by constrictions, the nodes of Ranvier.

The Myelin Sheath. — During the fourth month an inner myelin, or
medullary sheath appears about many nerve fibers. This consists of
a spongy framework of neurokeratin in the interstices of which a fatty sub-
stance, myelin, is deposited. The origin of the myelin sheath is in doubt.
By some (Ranvier) it is believed to be a differentiation of the neurilemma,
the myelin being deposited in the substance of the nucleated sheath cell.

306

HISTOGENESIS

By others (Kolliker, Bardeen) the myelin is regarded as a direct or indirect
product of the axis cylinder. Its integrity is dependent at least upon the
nerve cell and axis cylinder, for, when a nerve is cut, the myelin very soon
shows degenerative changes.

In the central nervous system there is no distinct neurilemma sheath
investing the fibers. Sheath cells are said to be present and most numer-
ous during the period when myelin is developed. Hardesty derives the
sheath cells in the central nervous system of the pig from a portion of the
supporting cells, or spongioblasts, of the neural tube, and finds that these
cells give rise to the myelin of the fibers.

V

FIG. 311. — Ependymal cells from the embryonic neural tube. A, Chick embryo of first day;
B, of third day. (Cajal).

Those fibers which are first functional receive their myelin sheaths
first. The myelination of nerve fibers is only completed between the second
and third year (Westphal). Many of the peripheral fibers, especially
those of the sympathetic system, remain unmyelinated and supplied only
with a neurilemma sheath. The myelinated fibers, those with a myelin
sheath, have a glistening white appearance and give the characteristic
color to the white substance of the central nervous system and to the periph-
eral nerves. Ranson (1911) has shown that large numbers of unmyelin-
ated fibers also occur in the peripheral nerves and spinal cord of adult

HISTOGENESIS OF THE NERVOUS TISSUES

307

mammals and man. Those found in the spinal nerves arise from the small
cells of the spinal ganglia.

Development of the Supporting Cells of the Neural Tube. — The

spongioblasts of the neural tube (p. 301) differentiate into the supporting
tissue of the central nervous system. This includes the ependymal cells
which line the neural cavity, and form one of the primary layers of the
neural tube, and neuroglia cells and their fibers.

FIG. 312. — Ependymal cells of the lumbar cord from a human fetus of 44 mm. (Cajal).
A, Floor plate; B, central canal; C, line of future fusion of neural walls; E, ependymal cells;
*, neuroglia cells and fibers.

We have described how the strands of the syncytium formed by the
spongioblasts become arranged radially in the neural tube of early embryos
(Fig. 305 D). As the wall of the neural tube thickens, the strands elon-
gate pari passu and form a radiating branched framework (Fig. 311).
The group of spongioblasts which line the neural cavity constitute the
ependymal layer. Processes from these cells radiate and extend through
the whole thickness of the neural tube to its periphery. The cell bodies
are columnar and persist as the lining of the central canal and ventricles
of the spinal cord and brain (Fig. 312).

308 HISTOGENESIS

Near the median line of the spinal cord, both dorsally and ventrally,
the supporting tissue retains its primitive ependymal structure in the
adult. Elsewhere, the supporting framework is differentiated into neuro-
lia cells and fibers. The neuroglia cells form part of the spongioblastic
syncytium and are scattered through the mantle and marginal layers of the
neural tube. By proliferation they increase in number and their form
depends upon the pressure of the nerve cells and fibers which develop
around them.

Neuroglia fibers are differentiated (in a manner comparable to the
formation of connective-tissue fibers, Fig. 291) from the cytoplasm and
cytoplasmic processes of the neuroglia cells, and, as the latter primarily
form a synctium, the neuroglia fibers may extend from cell to cell. The
neuroglia fibers develop late in fetal life and undergo a chemical transfor-
mation into neurokeratin, the same substance that is found in the sheaths
of myelinated fibers.

CHAPTER XI
THE MORPHOGENESIS OF THE SKELETON AND MUSCLES

I. THE SKELETAL SYSTEM

THE skeleton comprises: (i) the axial skeleton (skull, vertebras, ribs,
and sternum) and (2) the appendicular skeleton (pectoral and pelvic gir-
dles and the limb bones) . Except for the flat bones of the face and skull,
which develop directly in membrane, the bones of the skeleton exhibit first
a blastemal, or membranous stage, next a cartilaginous stage, and finally
a permanent, osseous stage.

For a detailed account of the development of the various bones of the
skeleton the student is referred to Bardeen, Keibel and Mall, vol. i.

THE AXIAL SKELETON

The primitive axial skeleton of all vertebrates is the notochord, or
chorda dor sails, the origin of which has been traced on pp. 34 and 36. The
notochord constitutes the only skeleton of Amphioxus, whereas in fishes
and amphibians it is replaced in part, and in higher animals almost en-
tirely, by the permanent axial skeleton. In the development of mammals,
this transient elastic rod disappears early, except in the intervertebral
discs where it persists as the nuclei pulposi.

The Vertebrae and Ribs. — The mesenchyme derived from the sclero-
tomes grows mesad (Figs. 290 and 323) and comes to lie in paired segmen-
tal masses on either side of the notochord, separated from similar masses
before and behind by the inter segmental arteries. In embryos of about 4
mm., each sclerotome soon differentiates into a caudal, compact portion
and a cranial, less dense half (Fig. 313 A). From the caudal portions,
horizontal tissue masses now grow toward the median line and enclose the
notochord, thus establishing the body of each vertebra. Similarly, dorsal
extensions form the vertebral arch, and ventro-latera' outgrowths, the
costal processes. The looser issue of the cranial halves also grows mesad
and fills in 'the intervals between successive denser regions.

The denser caudal half of each sclerotomic mass presently unites with
the less dense cranial half of the sclerotome next caudad to form the an-

30Q

3io

THE MORPHOGENESIS OF THE SKELETON AND MUSCLES

lages of the definitive lerlebra (Fig. 313 B}. Mesenchymal tissue, filling
the new intervertebral fissure thus formed, gives rise to the interv,rtebral
discs. Since a vertebra is formed from parts of two adjacent sclerotomes,
it is evident that the intersegmental artery must now pass over the body
of a vertebra, and the myotomes and vertebrae alternate in position.

Following this blastemal stage, centers of chondrification appear, two
centers in the vertebral body, one in each half of the vertebral arch, and
one in each costal process. These centers enlarge and fuse to form a
cartilaginous vertebra; the union of the costal processes, which will give
rise to ribs, with the body is, however, temporary, an articulation forming

Myotome.

Ectoderm—

>Sderotome

^Intersegmental

artery
...Notochord

Myotome—

Ectoderm

Notochord

A nlage of vertebra
—Intervertebral fissure
-Intersegmental artery

A B

FIG. 313. — Frontal sections through the mesodermal segments of the left side of human
embryos. A, at about 4 mm., showing the differentiation of the sclerotomes into less dense
and denser regions; B, at about 5 mm., illustrating the union of the halves of successive sclero-
tomes to form the anlages of the vertebrae.

later. Transverse and articular processes grow out from the vertebral
arch, and the rib' cartilages, having in the meantime formed tubercles,
articulate with the transverse processes somewhat later. The various
ligaments of the vertebral column arise from mesenchyme surrounding the
vertebras.

Finally, at the end of the eighth week, the stage of ossification sets in.
A single center appears in the body, one in each half of the arch, and one
near the angle of each rib (Fig. 296^). The replacement of cartilage to
form a solid mass is not completed until several years after birth. At
about the seventeenth year, secondary centers appear in the cartilage still
covering the cranial and caudal ends of the vertebral body and form che
disc-like, bony epiphyses. These unite with the vertebra proper to con-
stitute a single mass at about the twentieth year.

While the foregoing account holds for vertebras in general, a few devia-
tions occur. When the atlas is formed, a body differentiates as well, but
it is appropriated by the body of the epistropheus (axis), thereby forming
the tooth-like dens of the latter. The sacral and coccygeal vertebrae
represent reduced types. At ,about the twenty-fifth year the sacral ver-
tebrae unite to form a single bony mass, and a similar fusion occurs between
the rudimentary coccygeal vertebrae.

THE AXIAL SKELETON 3! I

The ribs, originating as ventro-lateral outgrowths from the vertebral
bodies, reach their highest development in the thoracic region. In the
cervical region they are short; their tubercles fuse with the transverse
processes and their heads with the vertebral bodies, thus leaving intervals,
the transverse foramina, through which the vertebral vessels course. In
the lumbar region the ribs are again diminutive and are fused to the
transverse processes. The rudimentary ribs of the sacral vertebra are
represented by flat plates which unite on each side to form a pars ateralis
of the sacrum. With the exception of the first coccygeal vertebra, ribs
are absent in the most caudal vertebrae.

The Sternum. — The sternal anlages arise as paired mesenchymal
bands, with which the first eight or nine thoracic ribs fuse secondarily
(Whitehead and Waddell, 1911). After the heart descends into the
thorax, these cartilaginous sternal bars, as they may now be termed, unite
in a cranio-caudal direction to form the sternum, at the same time incor-
porating a smaller mesial sternal anlage (Fig. 314). . Ultimately, one or
two pairs of the most caudal ribs lose their sternal connections, the cor-

FIG. 314. — Formation of the sternum in a FIG. 315. — Sternum of a child, showing centers
human fetus during the third month (modified of ossification,

after Ruge).

responding portion of the sternum constituting the xiphoid process in part .
At the cranial end of the sternum there are two imperfectly separated epi-
ternal cartilages with which the clavicles articulate. These usually unite
with the longitudinal bars and contribute to the formation of the manu-
brium. Variations in the ossification centers are not uncommon, although
a primitive, bilateral, segmental arrangement is evident (Fig. 315). In
the two cranial segments, however, unpaired centers occur.

The Skull. — The earliest anlage of the skull consists in a mass of dense
mesenchyme which envelops the cranial end of the notochord and extends
cephalad into the nasal region. Laterally, it forms wings which enclose

312.

THE MORPHOGENESIS OF THE SKELETON AND MUSCLES

the neural tube. Except in the occipital region, where there are indica-
tions of the incorporation into the skull of three or four vertebrae, the skull
is from the first devoid of segmentation.

Chondrification begins in the future occipital and sphenoidal regions,
in the median plane and extends cephalad and to a slight extent dorsad.
At the same time the internal ear becomes invested with a cartilagin-
ous periotic capsule which eventually unites with the occipital and sphen-
oidal cartilages (Fig. 316). The chondro cranium as it is termed is thus
confined chiefly to the base of the skull, the bones of the sides, roof, and
the face being of membranous origin. Chondrification also occurs more
or less extensively in the branchial arches, and, as will appear presently,
the first two pairs contribute substantially to the formation of the skull.

Inter parietal

-l - -Supra-occipital
---/-- -Exoccipital

-Condyle
— Basi-occipital

FIG. 317. — Occipital bone of a human fetus
of four months (after Sappey). The portions
still cartilaginous are shown as a homogeneous
background.

as

FIG. 316. — Reconstruction of the chon-
drocranium of a human embryo of 14 mm. (Levi
in McMurrich). as, Alisphenoid; bo, basi-
occipital; bs, basisphenoid; eo, exoccipital; m,
Meckel's cartilage; os, orbitosphenoid ; p, perio-
tic; ps, presphenoid; so, sella turcica; s, supra-
occipital.

In the period of ossification, which now ensues it becomes evident that
some bones which are separate in adult lower animals fuse to form com-
pound bones in the human skull. The sphenoid and temporal bones, for
example, represent five primitive pairs each. As such components may
arise either in membrane or cartilage, the compound nature of certain
adult bones is explained.

Ossification of the Chondrocranium. — The Occipital Bone. — Oss'fica-
tion begins in the occipital region during the third month. Four centers
appear at right angles about the foramen magnum (Fig. 317). From the
ventral center arises the basilar (basi-occipital) part of the future bone;
from the lateral centers the lateral (exocipital) parts which bear the
condyles; and from the dorsal, originally paired center, the squamous
(supra-occipital] part below the superior nuchal line The squamous

THE AXIAL SKELETON

313

(inter parietal} part above that line is an addition of intramembranous
origin. These several components do not fuse completely until about the
seventh year.

The Sphenoid Bone. — Ten principal centers arise in the cartilage that
corresponds to this bone (Fig. 318): (i and 2) in each ala magna (ali-
sphenoid); (3 and 4) in each ala parva (orbito sphenoid); (5 and 6) in the
corpus between the alae magnae (basis phenoid) ; (7 and 8) in each lingula;
(9 and 10) in the corpus between the alas parvae (pre sphenoid). Intra-
membranous bone also enters into its composition forming the orbital,
and temporal portion of each ala magna and the mesial laminae of each
p'terygoid process (except the hamulus). Fusion of the various parts is
completed during the first year.

A la magna Ala parva

(Alisphenoid) Presphenoid (Orbitos phenoid)

Lingula >' ' (/ \ %-- Pterygold

Basisphenoid process

FIG. 318. — Sphenoid bone of a human fetus
of nearly four months (after Sappey). Parts
still cartilaginous are represented in stipple.

Nasal septum
— Perpendicular plate
~Crista galli
•Cribriform plate
- Labyrinth

FIG. 319. — Ethmoid bone of a human fetus of
four months (modified after Kollmann).

The Ethmoid Bone. — The ethmoid cartilage consists of a mesial
mass, which extends from the sphenoid to the tip of the nasal process, and
of paired masses lateral to the olfactory fossae. The lower part of the
mesial mass persists as the cartilaginous nasal sep'um but oss fication of
the upper portion produces the lamina perpendicularis and the crista
galli (Fig-. 319). The lateral masses ossify at first into the spongy bone of
the ethemoidal labyrinths. From this, the definitive honeycomb struc-
ture (ethmoidal cells) and the concha are formed through evaginations of
the nasal mucous membrane and the coincident resorption of bone.
(Similar invasions of the mucous membrane and dissolution of bone pro-
duce the frontal, sphenoidal, and maxillary sinuses; p. 376). Fibers of
the olfactory nerve at first course between the unjoined mesial and lateral
masses. Later, cartilaginous, and finally, bony trabeculas surround these
bundles of nerve fibers, and, as the cribriform plates, interconnect the
three masses.

The Temporal Bone. — Several centers of ossification in the periotic
capsule unite to form a single center from which the whole cartilage is

THE MORPHOGENESIS OF THE SKELETON AND MUSCLES

Squamosum

transformed into the petrous and mastoid portions of the temporal bone
(Fig. 320). The mastoid process is formed after birth by a bulging of the
petrous bone, and its internal cavities, the mastoid cells, are formed and

lined by the evaginated epithelial lining of
the middle ear. The squamosal and tympanic
portions of the temporal bone are of intra-
membranous origin, while the styloid process
originates from the proximal end of the
second, or hyoid branchial arch.

Membrane Bones of the Skull. — From
the preceding account it is evident that,
although the bones forming the base of the
skull arise chiefly in cartilage, they receive
substantial contributions from membrane
bones. The remainder of the sides and roof
of the skull is wholly of intramembranous

origin, each of the parietals forming from a single center, the frontal
from paired centers. At the incomplete angles between the parietals and
their adjacent bones, union is delayed for some time after birth. These
membrane-covered spaces constitute the fontanelles.

Tympanicum

' Petrosum

FIG. 320. — The left temporal
bone at birth. The portion of
intracartilaginous origin is repre-
sented in stipple.

Malleus

Incus

Stapes
Styloid process-

Tympanic ring
Stylo-hyoid lig.

Temporal squama

•Zygoma

Mandible

Cricoid cartilage

Meckel's cartilage

Hyoid cartilage (lesser horn)
Hyoid cartilage (greater horn)
rhyreoid cartilage

FIG. 321. — Lateral dissection of the head of a human fetus, showing the derivatives of. the
branchial arches (after Kollmann).

The vomer forms from two centers in the connective tissue flanking the
lower border of the lamina perpendicularis of the ethmoid. The cartilage
of the ethmoid thus invested undergoes resorption.

Single centers of ossification in the mesenchyme of the facial region
give rise to the nasal, lacrimal, and zygomatic, all pure membrane bones.

THE APPENDICULAR SKELETON

315

The Branchial Arch Skeleton. — The first branchial arch forks into an
upper maxillary and a lower mandibular process (Fig. 119). Cartilage
fails to appear in the maxillary processes, due to accelerated development,
hence the palate bones and the maxilla arise directly in membrane. Each
palate bone develops from a single center of ossification. According to
one view five centers contribute to the formation of each maxilla; Mall,
however, maintains that there are but two centers, one .giving rise to the
portion bearing the incisor teeth, the other to the remainder of the maxilla.

The entire core of the mandibular process becomes a cartilaginous bar,
Meckel' s cartilage, which extends proximally into the tympanic cavity of
the ear (Fig. 321). Membrane bone, developing distally in the future
body, encloses Meckel's cartilage and the inferior alveolar nerve, whereas
proximally in the ramus the membrane bone merely lies lateral to these
structures — hence the position of the adult mandibular foramen. The por-
tion of Meckel's cartilage enclosed in bone disappears, while the cartilage
proximal to the mandibular foramen becomes in order, the spheno-mandi-
bular ligament, the malleus, and the incus (p. 389 and Fig. 387).

Each second branchial arch comes into relation proximally with the
periotic capsule. This upper segment of the cartilage becomes the stapes
and the styloid process of the temporal bone (Figs. 321 and 387). The
succeeding distal portion is transformed into the stylo-hyoid ligament and
connects the styloid process with the distal end of the arch, which also
undergoes intracartilaginous ossification to form the lesser horn of the hyoid
bone.

The cartilage of the third branchial arches ossifies and gives origin to
the greater horns of the hyoid bone, while a plate connecting the two arches
becomes its body.

The fourth and fifth branchial arches co-operate in the formation of the
thyreoid cartilage of the larynx.

THE APPENDICULAR SKELETON

Whereas the axial skeleton originates chiefly from the sclerotomes of
the mesodermal segments, the appendicular skeleton is apparently derived
from the unsegmented somatic mesenchyme. In embryos of 9 mm.,
mesenchymal condensations have formed definite blastemal cores in the
primitive limb buds (Fig. 323). Following this blastemal stage, the vari-
ous bones next pass through a cartilaginous stage and finally an osseous
one.

The Upper Extremity. —The clavicle is the first bone of the skeleton
to ossify, centers appearing at each end. Prior to ossification it is com-
posed of a peculiar tissue which makes it difficult to decide whether the
bone is intramembranous or intracartilaginous in origin.

316 THE MORPHOGENESIS OF THE SKELETON AND MUSCLES

The scapula arises as a single plate in which there are two chief centers
of ossification. One center early forms the body and spine. The other,
after birth, gives rise to the rudimentary coracoid process, which in lower
vertebrates extends from the scapula to the sternum. Union between the
coracoid process and the body does not occur until about the fifteenth
year.

The humerus, radius, and ulna ossify from single primary centers ar d
two or more epiphyseal centers (Fig. 296 C-F).

In the cartilaginous carpus there is a proximal row of three, and a dis-
tal row of four elements. Other inconstant cartilages may appear, and
subsequently disappear or become incorporated in other carpal bones.
The pisiform is regarded as a sesamoid bone which develops in the tendon
of the flexor carpi ulnaris ; in the same category is the patella which forms in
the tendon of the quadriceps extensor cruris.

The Lower Extremity. — The cartilaginous plate of the os coxa is at
first so placed that its long axis is perpendicular to the vertebral column
(Fig. 322). Later, it rotates to a position parallel with the vertebral
column, and shifts slightly caudal to come into relation with the first
three sacral vertebrae. A retention of the membranous condition in the
lower half of each primitive cartilaginous plate accounts for the obturator
membrane which closes the foramen of the same name. Three centers of
ossification appear, forming the ilium, ischium, and pubis. The three
bones do not fuse completely until about puberty.

The general development of the femur, tibia, fibula, tarsus, metatarsus,
and phalanges is quite similar to that of the corresponding bones of the
upper extremity.

Anomalies. — Variations in the size, shape, and number of skeletal parts are common.
Developmental arrest and over-development are the prime causative factors. Variations
in the number of vertebrae (except cervical) are not infrequent. The last cervical and first
lumbar vertebrae occasionally bear ribs, due to the continued development of the primitive
costal processes. Cleft sternum or cleft xiphoid process represents an incomplete fusion
of the sternal bars. Additional fingers or toes (polydactyly) may occur; the cause is obscure.
Hare lip and cleft palate have already been mentioned (pp. 148, 151).

IL THE MUSCULAR SYSTEM

The skeletal muscles, with the exception of those attached to the
branchial arches, originate from the myotomes of the mesodermal seg-
ments (pp. 53, 291 and Fig. 323). Although the primitive segmental
arrangement of the myotomes is, for the most part, soon lost, their original
innervation by the segmental spinal nerves is retained throughout life.
For this reason, the history of adult muscles formed by fusion, splitting,
or other modifications may be traced with considerable certainty.

THE MUSCULAR SYSTEM

317

The development of the human musculature is fully described by
W. H. Lewis in Keibel and Mall, vol. i.

Fundamental Processes. — The changes occurring in the myotomes
during the formation of adult muscles are referable the operation of the
following fundamental processes :

(1) A change in direction of muscle fibers from the original cranio-
caudal orientation in the myotome. The fibers of but few muscles retain
their initial orientation.

(2) A migration of myotomes, wholly or in part, to more or less remote
regions. Thus the latissimus dorsi originates from cervical myotomes, but
finally attaches to the lower thoracic and lumbar vertebrae and to the crest
of the ilium. Other examples are the serratus anterior and the trapezius.

(3) A fusion of portions of successive myotomes. The rectus abdomi-
nis illustrates this process. .

(4) A longitudinal splitting of myotomes into several portions. Ex-
amples are found in the sterno- and omo-hyoid and in the trapezius and
sterno-mastoid.

(5) A tangential splitting into two or more layers. The oblique and
the transverse muscles of the abdomen are formed by the common process.

(6) A degeneration of myotomes, wholly or in part. In this way
fascias, ligaments, and aponeuroses may be produced.

Muscles of the Trunk. — Ventral extensions grow out from the cervical
and thoracic myotomes, and a fusion that is well advanced superficially
occurs between all the myotomes in embryos of 10 mm. A dorsal, longitu-
dinal column of fused myotomes, however, can still be distinguished from
the sheet formed from the combined ventral prolongations (Fig. 322).

From the superficial portions of the dorsal column there arise by
longitudinal and tangenital splitting the various long muscles of the back and
neck, which are innervated by the dorsal rami of the spinal nerves. The
deep portions of the myotomes to not fuse, but give rise to the several
intervertebral muscles, which thus retain their primitive segmental arrange-
ment.

The muscles of the neck, other than those innervated by the dorsal
rami and those arising from the branchial arches (p. 319) differentiate
from ventral extensions of the cervical myotomes. In the same way the
thoraco-abdominal muscles arise from the more pronounced ventral pro-
longations of the thoracic myotomes that grow into the body wall along
with the ribs (Fig. 322). Reference has already been made to the prob-
able contribution from cervical myotomes to the formation of the dia-
phragm (p. 189).

The ventral extensions of the lumbar myotomes (except the first)
and of the first two sacral myotomes do not participate in the formation

318 THE MORPHOGENESIS OF THE SKELETON AND MUSCLES

of the body wall. If -they persist at all, it is possible that they contribute
to the formation of the lower limb. The ventral portions of the third and
fourth sacral myotomes give rise to the muscles of the perineal region.

Muscles of the Limbs. — It has generally been believed that the muscles
of the extremities are developed from buds of the myotomes which grow

FIG. 322. — Reconstruction of a 9 mm. embryo, to show the partially fused myotomes and
the premuscle masses of the limbs (Bardeen and Lewis). X 13. Distally, in the upper ex-
tremity, the radius, ulna and hand plate are disclosed; in the lower extremity the os coxae and
the border vein show.

into the limb anlages. In sharks this is clearly the case, and in man the
segmental nerve supply is suggestive, but not proof, of a myotomic origin.
According to Lewis, "there are no observations of distinct myotome buds
extending into the limbs" in man. Nevertheless, a diffuse migration of
cells from the ventral portion of the myotomes has been recorded by va-

THE MUSCULAR SYSTEM

319

rious observers, recently by Ingalls. These cells soon lose their epithelial
character and blend with the undifferentiated mesenchyma of the limb
buds (Figs. 322 and 323). From this diffuse tissue, which at about 9 mm.
forms premuscle masses, the limb muscles are differentiated, the proxi-
mal muscles being the first to appear. The progressive differentiation into
distinct muscles reaches the level of the hand and foot in embryos of
20 mm.

Spinal ganglion

Dermatome

f" ••<< 4v^% T>;i '. ; v • -,,

!'»% %.^y"l:^ I'' •••••- J

Myotome
Spinal nerve

Arm bud Vta

Proliferating cells of
myotome

Mesonephric duct

Mesonephric tubule and
glomerulus

Ccelom
Somatic mesoderm

FIG. 323. — Transverse section of a 10.3 monkey embryo, showing the myotome and the mesen-
chyma of the arm bud (Kollmann). A, aorta; *, sclerotome.

Muscles of the Head. — Distinct mesodermal segments do not occur
in the head region. It is possible, however, that a premuscle mass, from
which the eye muscles of man are developed, is comparable to three myo-
tomic segments having a similar fate in the shark (cf. p. 366).

The remaining muscles of the head differ from all other skeletal mus-
cles in that they arise from the splanchinc mesoderm of the branchial
arches and are innervated by nerves (visceral) of a different category than
those (somatic) which supply myotomic muscles (p. 356). The meso-
derm of the first branchial arch gives rise to the muscles of mastication and
to all other muscles innervated by the trigeminal nerve. Similarly, the

320 THE MORPHOGENESIS OF THE SKELETON AND MUSCLES

muscles of expression, and other muscles supplied by the facial nerve,
originate from the second, or hyoid arch. The third arch probably gives
origin to the pharyngeal muscles, and the third and fourth arches to the
intrinsic muscles of the larynx.

The muscles of the tongue are supplied by the n.hypoglossus, and there-
fore it has been assumed that they are derived from myotomes of the
occipital region (p. 153). According to Lewis, "there is, however, no direct
evidence whatever for this statement, and we are inclined to believe from
our studies that the tongue musculature is derived from the mesoderm of
the floor of the mouth."

Anomalies. — Variations in the form, position, and attachments of the muscles are
common. Most of these anomalies are referable to the variable action of the several
developmental factors listed on p. 317).

CHAPTER XII
THE MORPHOGENESIS OF THE CENTRAL NERVOUS SYSTEM

In discussing the histogenesis of the nervous tissue the early develop-
ment of the neural tube has been described as an infolding of the neural
plate (Fig. 78) and a closure of the neural groove (Fig. 304). The groove
begins to close in embryos of 2 mm. along the mid-dorsal line, near the
middle of the body, and the closure extends both cranially and caudally
(Fig. 324). Until the end of the third week there still persists an opening

Mesencephalon

Rhombcntephalon
Myelencephalon

Amnion (cut)

Mesodermal segment 14
Open neural groove

Prosencephalon

Stomodaum

Amnion (cut)

Yolk sac

Body stalk

FIG. 324. — Human embryo of 2.4 mm., with a partially closed neural tube (after Kollmann)'

X 36.

at either end of the neural tube, somewhat dorsad. These openings are
the neurc pores (Fig. 330). Before the closure o the neuropores, in em-
bryos of 2 to 2.5 mm., the cranial end of the neural tube has enlarged
and is constricted at two points to form the three primary brain vesicles.
The caudal two-thirds of the neural tube, which remains smaller in diam-
eter, constitutes the anlage of the spinal cord.
21 321

322

THE MORPHOGENESIS OF THE CENTRAL NERVOUS SYSTEM
THE SPINAL CORD

The spinal portion of the neural tube is at first nearly straight, but is
bent with the flexure of the embryo into a curve which is convex dor sally.
Its wall gradually thickens during the first month and the diameter of its
cavity is diminished from side to side. By the end of the first month,

Neural cavity

Marginal layer

Dorsal

Ependymal layer
Spinal ganglion— +±

Nerve trunk Sympathetic ganglion

FIG. 325. — Transverse section through a 10 mm. human embryo at the level of the arm buds,
showing the spinal cord and a spinal nerve of the right side. X 44.

three layers have been developed in its wall, as described on p. 301 (Fig.
325). These layers are the inner ependymal layer, which forms a narrow
zone about the neural cavity, the middle mantle layer, cellular, and the
outer marginal layer, fibrous.

The Ependymal Layer is differentiated into a dorsal roof plate and a
ventral floor plate (Fig. 326). Laterally, its proliferating cells contribute
ncuroblasts and neuroglia cells to the mantle layer. The proliferation of
cells ceases first in the ventral portion of the layer, which is thus narrower
than the dorsal portion in 10 to 20 mm. embryos (Figs. 325 and 326).
Consequently, the ventral portion of the mantle layer is differentiated first.
The neural cavity is at first somewhat rhomboidal in transverse section ,

THE SPINAL CORD

323

wider dorsally than ventrally. Its lateral angle forms the sulcus limitans
(Fig 334), which marks the subdivision of the lateral walls of the neural

Roof plate

Dvrsal column

Dorsal funiculus

Neural cavity

Marginal layer

Ependymal layer

Floor plate Ventral median fissure

FIG. 326. — Transverse section of the spinal cord from a 20 mm. human embryo. X 44.

tube into the dorsal alar plate (sensory) and ventral basal plate (motor).
When the ependymal layer ceases to contribute new cells to the mantle

Dorsal funiculus

Lat. funiculus
Central canal

Dura mater

Spinal
ganglion

Ventral funiculus

FIG. 327. — Transverse section of the spinal cord from a 34 mm. human embryo, showing also
the spinal ganglion and dura mater on the left side. X 44.

layer, its walls are approximated dorsally. As a result, in 20 mm. embryos
the neural cavity is wider ventrally (Fig. 326). In the next stage, 34 mm.,
these walls fuse and the dorsal portion of the neural cavity is obliterated

324

THE MORPHOGENESIS OF THE CENTRAL NERVOUS SYSTEM

(Fig. 327). In a 65 mm. (CR) fetus the persisting cavity is becoming
rounded (Fig. 328). It forms the central canal of the adult spinal cord.
The cells lining the central canal are ependymal cells proper. Those in the
floor of the canal form the persistent floor plate. Their fibers extend ven-
trad, reaching the surface of the cord in the depression of the ventral median
fissure.

• When the right and left walls of the ependymal layer fuse, the epen-
dymal cells of the roof plate no longer radiate, but form a median septum
(Fig. 327). Later, as the marginal layers of either side thicken and are

Dorsal median septum Fasciculus gracilis

Dorsal root^^_. ^ XL^-r- ^_ .Fasciculus cuneatus

Dorsal column

-Subslantia gelatinosa

Lat. funiculu

Lat. column

Ventral column

Ventral funiculus Ventral median jissure

FIG. 328. — Transverse section of the spinal cord from a 65 mm. human fetus. X 44.

approximated, the median septum is extended dorsally. Thus the roof
plate is converted into part of the dorsal median septum of the adult spinal
cord (Fig. 328).

The Mantle Layer, as we have seen, receives contributions from the
proliferating cells of the ependymal layer. A ventro-lateral thickening
first becomes prominent in embryos of 10 to 15 mm. (Fig. 325). This is
the ventral (anterior) gray column, or horn, which in later stages is sub-
divided, forming also a lateral gray column (Fig. 328). It is a derivative of
the basal plate. In embryos of 20 mm. a dorso-lateral thickening of the
mantle layer is seen, the cells of which constitute the dorsal (posterior)
gray column, or horn (Figs. 327 and 328) ; about these cells the collaterals
of the dorsal root fibers end. The cells of the dorsal gray column, deriva-
tives of the alar plate of the cord, thus form terminal nuclei for the afferent
spinal nerve fibers. Dorsal and ventral to the central canal, the mantle
layer forms the dorsal and ventral gray commissures. In the ventral floor

THE SPINAL CORD

325

plate, nerve fibers cross from both sides of the cord and form the ventral
(anterior) white commissure.

The Marginal Layer is composed primarily of a framework of neuro-
glia and ependymal-cell, processes. Into this framework grow the axons
of nerve cells, so that the thickening of this layer is due to the increasing
number of nerve fibers contributed to it by extrinsic ganglion cells and
neuroblasts. When their myelin develops, these fibers form the white
substance of the spinal cord. The fibers have three sources (Fig. 360):
(i) they may arise from the spinal ganglion cells, entering as dorsal root
fibers and coursing cranially and caudally in the marginal layer; (2) they
may arise from neuroblasts in the mantle layer of the spinal cord, (a) as
fibers which connect adjacent nuclei of the cord (fasiculi proprii or ground
bundles), or (6) as fibers which extend upward to the brain; (3) they may
arise from neuroblasts of the brain, (a) as descending tracts from the
brain stem, or (6) as long, descending cerebrospinal tracts from the cortex
of the cerebrum.

Of these fiber tracts, (i) and (20} appear during the first month;
(2 6) and (3 a) during the third month; (3 6) at the end of the fifth month.

The dorsal root fibers from the spinal ganglion cells, entering the cord
dorso-laterally, subdivide the white substance of the marginal layer into a
dorsal funiculus and lateral funicnlus. The lateral f uniculus is marked off
by the ventral root fibers from the ventral funiculus (Fig. 327). The
ventral root fibers, as we have seen, take their origin from the neuroblasts
of the ventral gray column in the mantle layer. They are thus derivatives
of the basal plate.

The dorsal funiculus is formed chiefly by the dorsal root fibers of the
ganglion cells, and is subdivided into two distinct bundles, the fasiculus
gracilis, median in position, and the fasciculus cuneatus, lateral. The
dorsal funiculi are separated only by the dorsal median septum (Fig. 328).

The lateral and ventral funiculi are composed : (i) of fasciculi proprii,
or ground bundles, originating in the spinal cord; (2) of ascending tracts
from the cord to the brain; (3) of the descending fiber tracts from the
brain. The fibers of these fasciculi intermingle and the fasciculi are thus
without sharp boundaries. The floor plate of ependymal cells lags behind
in its development, and, as it is interposed between the thickening right
and left walls of the ventral funiculi, these do not meet and the ventral
median fissure is produced (cf. Figs. 325 and 328).

The development of myelin in the nerve fibers of the cord begins late in the fourth
month of fetal life and is completed between the fifteenth and twentieth years (Flechsig,
Bechterew) . Myelin appears first in the root fibers of the spinal nerves and in those of the
ventral commissure, next in the ground bundles and dorsal funiculi. The cerebrospinal
(pyramidal) fasciculi are the last in which myelin is developed; they are myelinated during

326

THE MORPHOGENESIS OF THE CENTRAL NERVOUS SYSTEM

Cerebrum
Mesencephalon..
Cerebellum

Cervical
enlargement

Lumbar
enlargement

the first and second years. As myelin appears in the various fiber tracts at different periods,
this condition has been utilized in tracing the extent and origin of the various fasciculi in
the central nervous system.

The Cervical and Lumbar Enlargements. — At the levels of the two
nerve plexuses supplying the upper and lower extremities, the spinal cord
enlarges. As the fibers to the muscles of the extremities arise from nerve
cells in the ventral gray column, the number of these cells and the mass of
the gray substance is increased ; since larger numbers of fibers from the
integument of the limbs also enter the cord at this level, there are like-
wise present more cells about which sensory
fibers terminate. There is formed consequently
at the level of the origin of the nerves of the
brachial plexus the cervical enlargement, opposite
the origins of the nerves of the lumbo-sacral
plexus the lumbar enlargement (Fig. 329).

At the caudal end of the neural tube of a
four months' fetus, an epithelial sac is formed
which is adherent to the integument. Cranial to
the sac, the central canal is obliterated, this part
of the neural tube forming the filum terminate.
The caudal end of the central canal is irregularly
expanded and is known as the terminal ventricle.
After the third month the vertebral column
grows faster than the spinal cord. As the cord
is fixed to the brain, the vertebras and the asso-
ciated roots and ganglia of the spinal nerves shift
caudally along the cord. The origin of the
coccygeal nerves in the adult is opposite the first
lumbar vertebra and the nerves course obliquely
downward, nearly parallel to the spinal cord. As

the tip of the neural tube is attached to the coccyx, its caudal portion
becomes stretched into the slender, solid cord known as the filum terminale.
The obliquely coursing spinal nerves, with the filum terminale, constitute
the cauda equina.

THE BRAIN

We have seen that in embryos of 2 to 2.5 mm. the neural tube is
nearly straight, but that its cranial end is enlarged to form the anlage
of the brain (Fig. 324). The appearance of two constrictions in the wall
of the anlage subdivides it into the three primary brain vesicles — the fore-
brain, or prosencephalon, mid-brain, or mesencephalon, and hind-brain,
or rhombencephalon.

FIG. 329— Dissection of
the brain and cord of a three
months' fetus, showing the
cervical and lumbar enlarge-
ments (after Kolliker in
Marshall). Natural size.

THE BRAIN

327

In embryos of 3.2 mm., estimated age four weeks, three important
changes have taken place (Fig. 330): (i) the neural tube is bent sharply
in the mid-brain region (the cephalic flexure) , so that the axis of the fore-
brain now forms a right angle with the axis of the hind-brain; (2) the
fore-brain shows indication dor sally of a fold, the mar go thalamicus
which subdivides it into the telencephalon and the diencephalon; (3) the
lateral walls of the fore-brain show distinct evaginations, the optic vesicles,
which project laterad and caudad. A ventral bulging of the wall of the
hind-brain indicates -the position of the future pontine flexure.

A nterior

ncuropore Pallium of telencephalon

,Diencephalon

Pallium

Corpus slrialum

A nterior
neuropore

Future pontine _$ E^
flexure

Mesencephalon Optic

v recess

Isthmus Future pontine
flexure

Rhombcncephalon

Mesencephalon

Cephalic flexure

: - Rliombenceplialot:

A B

FIG. 330. — Reconstructions of the brain of a 3.2 mm. human embryo (after His). X about 35.

A, Lateral surface; B, in median sagittal section.

In embryos of 7 mm. (five weeks) the neuropores have closed (Fig.
331). The cephalic flexure, now more marked, forms an acute angle,
and the pontine flexure, just indicated in the previous stage, is now a
prominent ventral band in the ventro-lateral walls of the hind-brain.
This flexure forms the boundary line which subdivides the rhomben-
cephalon into a cranial portion, the metencephalon, and into a caudal portion ,
the myelencephalon. At a third bend, the whole brain is flexed ventrally
at an angle with the axis of the spinal cord. This bend, the cervical
flexure, is the line of demarcation between the brain and spinal cord
(cf. Fig. 333 A). The telencephalon and diencephalon are more dis-
tinctly subdivided, and the evaginated optic vesicle forms the optic cup,
attached to the brain wall by a hollow stalk, in which later grows the

328

THE MORPHOGENESIS OF THE CENTRAL NERVOUS SYSTEM

optic nerve. The walls of the brain show a distinct differentiation in
certain regions. This is especially marked in the myelencephalon, which
has a thicker ventro-lateral wall and thinner dorsal wall.

Embryos of 10.2 mm. show the structure of the brain at the begin-
ning of the second month (Figs. 341 and 344). The five brain regions
are now sharply differentiated externally, but the boundary line between
the telencephalon and diencephalon is still indistinct. The telencephalon
consists of paired, lateral outgrowths, the anlages of the cerebral hemispheres
and rhinencephalon (olfactory brain). In Fig. 359 the external form of
the brain is seen with the origins of the cerebral nerves. It will be noted

Diencephalon

Pallium

Mesencephalon

Cephalic
flexure

Pallium

Mesencephalo)

Opti
cup
Pontine flexure — £

Myelencephalon —

Meten-
cephalon
Corpus striatum

Optic recess

By,

FIG. 331. — Reconstructions of the brain of a 7 mm. human embryo (His). A, Lateral view;
B, in median sagittal section.

that, with the exception of the first four (the olfactory, optic, oculomotor,
and trochlear), the cerebral nerves take their superficial origin from the
myelencephalon.

The cephalic flexure forms a very acute angle, and, as a result, the
long axis of the fore-brain is nearly parallel to that of the hind-brain
(Fig. 359). The oculomotor nerve takes its origin from the ventral wall
of the mesencephalon. Dorsally, there is a constriction, the isthmus,
between the mesencephalon and metencephalon, and here the fibers of
the trochlear nerve take their superficial "origin. The dorsal wall of the
myelencephalon is an exceedingly thin ependymal layer which becomes
the tela chorioidea. The ventro-lateral walls of this same region, on the
other hand, are very thick.

A median sagittal section of a brain at a somewhat later stage shows
the cervical, pontine, and cephalic flexures well marked (Fig. 332; the

,

THE BRAIN

thin, dorso -lateral roof of the myelencephalon has been removed). The
telencephalon is a paired structure. In the figure, its right half projects
cranial to the primitive median wall of the fore-brain, which persists as
the lamina terminates (cf. Fig. 342). The floor of the telencephalon is
greatly thickened caudally as the anlage of the corpus striatum. A slight
evagination of the ventral wall of the telencephalon, just cranial to the
corpus striatum, marks the anlage of the rhinencephalon. The remaining
portion of the telencephalon forms the pallium, or cortex, of the cerebral
hemispheres. The paired cavities of the telencephalon are the lateral
(first and second) ventricles, and these communicate through the interven-

Cerebra! peduncle,
Hypothalamus £
EpUhalamus
Thalamuy.
Diencephalon- •

Cerebral aqueduct
^Mesencephalon

Pallium.
Telencephalon-.

^.Rhombcnccpkalic isthmus

Cerebellum
\- Metencephalon
Rhomboid fossa

\ Myelencephalon

Ehinencephalon \ Corpus striatum Pons
Lamina tcrminalis

Spinal cord

FIG. 332. — Brain of a 13.6 mm. human embryo in median sagittal section (after His in Sobotta).
I, Optic recess; 2, ridge formed by 3, the optic chiasma; 4, infundibular recess.

tricular foramina (of Monro) with the cavity of the diencephalon, the third
ventricle. The cavities of the olfactory lobes communicate during fetal
life with the lateral ventricles and were formerly called the first ventricles.
The crossing of a portion of the optic nerve fibers in the floor of the
brain forms the optic chiasma, and this, with the transverse ridge produced
by it internally, is taken as the ventral boundary line between the telen-
cephalon and diencephalon (Fig. 332). A dorsal depression separates
the latter from the mesencephalon. The lateral wall of the diencephalon
is thickened to form the thalamus, the caudal and lateral portion of which
constitutes the metathalamus . From the metathalamus are derived the
geniculate bodies. In the median dorsal wall, near the caudal boundary
line of the diencephalon, an outpocketing begins to appear in embryos of

330 THE MORPHOGENESIS OF THE CENTRAL NERVOUS SYSTEM

five weeks (Fig. 332). This is the epithalamus, which later gives rise to
the pineal body, or epiphysis.

The thalamus is marked off from the more ventral portion of the
diencephalic wall, termed the hypothalamus, by the obliquely directed
sulcus limitans (Fig. 341). Cranial to the optic chiasma is the optic
recess, regarded as belonging to the telencephalon (Fig. 332). Caudal
to it, is the pouch-like infundibulnm, an extension from which, during
the fourth week, forms the posterior lobe of the hypophysis. Caudal to
the infundibulum, the floor of the diencephalon forms the tuber cinereum
and the mammillary recess; the walls of the latter thicken later and give
rise to the mammillary bodies.: An oblique transverse section through the
telencephalon and hypothalamic portion of the diencephalon (Fig. 343)
shows the relation of the optic recess to the optic stalk, the infundibulum,
and Rathke's pouch, and the extension of the third ventricle, the proper
cavity of the diencephalon-, into the telencephalon between the corpora
striata.

The mesencephalon in 13.6 mm. embryos (Fig. 332) is distinctly
marked off from the metencephalon by the constriction which is termed
the isthmus. Dorso-lateral thickenings form the corpora quadrigemina.
Ventrally, the mesencephalic wall is thickened to form the tegmentum
and crura cerebri. In the tegmentum are located the nuclei of origin for
the oculomotor and trochlear nerves. The former, as we have seen, takes
its superficial origin ventrally, while the trochlear nerve fibers bend dorsad,
cross at the isthmus, and emerge on the opposite side. As the walls of
the mesencephalon thicken, its cavity later is narrowed to a canal, the
cerebral aqueduct (of Sylvius) .

The walls of the metencephalon are thickened dorsally and laterally
to form the anlage of the cerebellum. Its thickened ventral wall becomes
the pons (Varolii). Its cavity constitutes the cranial portion of the
fourth ventricle.

The caudal border of the pons is taken as the ventral boundary line
between the metencephalon and myelencephalon. The myelencephalon
forms the medulla oblongata. Its dorsal wall is a thin, non-nervous,
ependymal layer, which later becomes the posterior medullary velum. From
its thickened ventro-lateral walls the last eight cerebral nerves take their
origin. Its cavity forms the greater part of the fourth ventricle, which
opens caudally into the central canal of the spinal cord, cranially into the
cerebral aqueduct. The increase in the flexures of the brain and the relative
growth of its different regions may be seen by comparing the brains of
embryos of four, five, and seven weeks (Fig. 333).

THE BRAIN

331

Telencephalon

Cervical flexure

-Myelencephalon

Melencephalon
Myelencephalon

FIG. 333. — Brains of human embryos, from reconstructions by His: A, 4.2 mm. embryo
(X2o); B, 6.9 mm. embryo (X 16); C, 18.5 mm. embryo (X 4). o, Optic vesicle; in, infun-
dibulum; m, mammillary body; pf, pontine flexure; ol, olfactory^Jobe; b, basilar artery;
p, Rathke's pouch (American Text-Book of Obstetrics).

In the table on page 332 are given the primitive subdivisions of the
neural tube and the parts derived from them:

332

THE MORPHOGENESIS OF THE CENTRAL NERVOUS SYSTEM
DERIVATIVES OF THE NEURAL TUBE

PRIMARY VESICLES.

[SUBDIVISIONS.

DERIVATIVES.

CAVITIES.

Prosencephalon

Telencephalon

Rhinencephalon
Cerebral cortex
Corpora striata
Pars optica hypothalami

Lateral ventricles
Cranial portion of third
ventricle

Diencephalon

Epithalamus
Thalamus
Metathalamus
Hypothalamus
Hypophysis
Tuber cinercum
Mammillary bodies

Remainder of third ven-
tricle

Mesencephalon

Mesencephalon

Corpora quadrigemina
Tegmentum
Crura cerebri

Aquaeductus cerebri

Rhombencephalon

Metencephalon

Cerebellum
Pons

Fourth ventricle

Myelencephalon

Medulla oblongata

Spinal cord

Spinal cord

Central canal.

DIFFERENTIATION OF THE SUBDIVISIONS OF THE BRAIN
The Myelencephalon. — We have seen (p. 322 ff.) that the wall of
the spinal cord differentiates dorsally and ventrally into roof plate and

A

Roof plate

Mantle layer-

Sulcus limitans

Ependymal
layer

Marginal
layer

Spinal
ganglion

Alar plah
S. limitans

Basal plate

Ventral spinal root

FIG. 334. — Transverse sections from a 10 mm. human embryo. X 44 A, Through the upper
cervical region of the spinal cord; B, through the caudal end of the myelencephalon.

floor plate, laterally into the alar plate and basal plate. The boundary
line between the alar and basal plates is the sulcus limitans (Fig. 334 A).

THE BRAIN

333

The same subdivisions may be recognized in the myelencephalon. It
differs from the spinal cord, however, in that the roof plate is broad, thin,
and flattened to form the ependymal layer (Figs. 334 B and 335). In the

Alar plate

\ N. hypoglossus
N. accessorius

N. vagus

FIG. 335. — Transverse sections through the myelencephalon of a 10.2 mm. embryo (His).
X 37. A, Through the nuclei of origin of the spinal accessory and hypoglossal nerves; B,
through the vagus and hypoglossal nerves.

Inner layer

Roof plate

Tractus solitarius

Rhombic lip
Restiform body

Formatio reticularis grise

Formatio reticularis alba

Spinal tract of
N . trigcminus

Neuroblasts from
^ alar plate

Marginal layer

N . hypoglossus Septum medulla: Neuroblasts from alar plate
(Rudiment of accessory olive)

FIG. 336. — Transverse section through the myelencephalon of a 22 mm. embryo (His).

alar and basal plates of the myelencephalon, the marginal, mantle, and
ependymal zones are differentiated as in the spinal cord (Fig. 335).
Owing to the formation of the pontine flexure at the beginning of the
second month, the roof plate is broadened, especially in the cranial portion
of the myelencephalon, and the alar plates bulge laterally (Figs. 336 and

334

THE MORPHOGENESIS OF THE CENTRAL NERVOUS SYSTEM

337 A). The cavity of the myelencephalon is thus widened from side
to side, and flattened dorso-ventrally. This is most marked cranially,
where, between the alar plates of the myelencephalon and metencephalon ,
are formed the lateral recesses of the fourth ventricle (Figs. 337 and 353) .
Into the ependymal roof of the myelencephalon blood vessels grow, and,
invading the lateral recesses, form there the chorioid plexus of the fourth
ventricle. The plexus consists of small, finger-like folds of the ependymal
layer and its covering mesenchymal layer. The line of attachment of the
ependymal layer to the alar plate is known as the rhombic lip and later
becomes the tccnia and obex of the fourth ventricle (Fig. 337 B).

Mid-brain

Cerebellum

Lateral recess

Rlwmbic lip

Lateral lobe of cerebellum Lobules of vermis

Flocculus

B Lateral lobe of Pyramis

Corporaquadrigemina. — -^ cerebellum

Cerebrum

Anlage of
vermis

Lateral lobe of
cerebellum

Rhombic lip 'W^m^mi.ObeX Flocculu/ ^ \ ^Umla

Nodulus

FIG. 337. — Dorsal views of four stages in the development of the cerebellum. A, 13.6 mm.
(His); B, 24 mm.; C, no mm.; D, 150 mm.

In early stages the floor of the myelencephalon is constricted trans-
versely by the so-called rhombic grooves, six in number; the intervals be-
tween successive grooves are neuromeres (cf. Figs. 96 and 122). Some have
have viewed these as evidential of a former segmentation of the head
similar to that of the trunk. It is more probable, however, that they
merely stand in relation to certain cerebral nerves and hence their seg-
mental arrangement is secondary.

The further growth of the myelencephalon is due: (i) to the rapid
formation of neuroblasts, derived from the ependymal and mantle layers ;
(2) to the development of nerve fibers from these neuroblasts; (3) to the

THE BRAIN

335

development and growth into it of fibers from neuroblasts in other parts
of the brain and spinal cord.

The neuroblasts of the basal plates early give rise chiefly to the efferent
fibers of the cerebral nerves (Fig. 335). They thus constitute motor
nuclei of origin of the trigeminal, abducens, facial, glossopharyngeal, vagus
complex, and hypoglossal nerves, nuclei corresponding to the ventral and
lateral gray columns of the spinal cord. The basal plate likewise produces
the reticular formation, which is derived in part also from the neuroblasts
of the alar plate (Fig. 336). The axons partly cross as external and internal
arcuate fibers and form a portion of the median longitudinal bundle, a fasci-
culus corresponding to the ventral ground bundles of the spinal cord.
Other axons grow into the marginal zone of the same side and form inter -
segmental fiber tracts. The reticular formation is thus differentiated into
a gray portion, situated in the mantle zone, and into a white portion lo-
cated in the marginal zone (Fig. 336) . The marginal zone is further added
to by the ascending fiber tracts from the spinal cord and the descending
pyramidal tracts from the brain. As in the cord, the marginal layers of
each side remain distinct, being separated by the cells of the floor plate.

The alar plates differentiate later than the basal plates. The afferent
fibers of the cerebral nerves first enter the mantle layer of the alar plates,
and, coursing upward and downward, form definite tracts (tractus soli-
tarius, descending tract of fifth nerve). To these are added tracts from the
spinal cord, so that an inner gray and an outer white substance is formed.
Soon, however, the cells of the mantle layer proliferate, migrate into the
marginal zone, and surround the tracts. These neuroblasts of the alar
plate form groups of cells along the terminal tracts of the afferent cerebral
nerves (which correspond to the dorsal root fibers of the spinal nerves)
and constitute the receptive, or terminal nuclei of the fifth, seventh, eight,
ninth, and tenth cerebral nerves. Caudally, the nucleus gracilis and nuc-
leus cuneatus are developed from the alar plates as the terminal nuclei for
the afferent fibers which ascend from the dorsal funculi of the spinal cord.
The axons of the neuroblast forming these receptive nuclei decussate
through the reticular formation, chiefly as internal arcuate fibers, and as-
cend to the thalamus as the median lemniscus.

There are developed from neuroblasts of the alar plate other nuclei,
the axons of which connect the brain stem, cerebellum, and fore-brain.
Of these the most conspicuous is the inferior olivary nucleus.

The characteristic form of the adult myelencephalon is determined by
the further growth of the above-mentioned structures. The nuclei of
origin of the cerebral nerves, derived from the basal plate, produce swell-
ings in the floor of the fourth ventricle that are bounded laterally by the
sulcus limitans. The terminal nuclei of the mixed and sensory cerebral

336 THE MORPHOGENESIS OF THE CENTRAL NERVOUS SYSTEM

nerves lie lateral to this sulcus. The enlarged cuneate and gracile nuclei
bound the ventricle caudally and laterally as the cuneus and clava. The
inferior olivary nuclei produce lateral, rounded prominences, and ventral
to these are the large cerebro -spinal tracts, or pyramids.

The Metencephalon. — Cranial to the lateral recesses of the fourth
ventricle, the cells of the alar plate proliferate ventrally and form the
numerous and relatively large nuclei of the pons. The axons from the cells of
these nuclei mostly cross to the opposite side and form the brachium pontis
of the cerebellum. Cerebral fibers from the cerebral peduncles end about
the cells of the pontine nuclei. Others pass through the pons as fascicles
of the pyramidal tracts.

A

Mesencephalon

i

Cerebellum

ft :'^6U^^^-

Ependymal layer

Posterior medullary velum Anterior medullary velum

FIG. 338.— Median sagittal sections of the metencephalon and adjoining parts. A, from a 24
mm. embryo; B, from a 150 mm. fetus.

The Cerebellum. — When the alar plates of the cranial end of the myel-
encephalon are bent out laterally, the caudal portions of their continua-
tions into the metencephalic region are carried laterally also. As a result,
the alar plate of the metencephalon takes up a transverse position and
forms the anlages of the cerebellum (Fig. 337 A). During the second
month the paired cerebellar plates thicken and bulge into the ventricle
(Fig. 338 A). Near the mid-line, paired thickenings indicate the anlages
of the vermis, while the remainder of the alar plates form the anlages of the
lateral lobes, or cerebellar hemispheres (Figs. 337-6 and 353).

The cerebellar anlages grow rapidly both laterally and in length, so
that their surfaces are folded transversely. During the third month their
walls bulge outward and form on either side a convex lateral lobe, connected
with the pons by the brachium pontis (Fig. 337 C). In the meantime the
anlages of the vermis have fused in the mid-line, producing a single struc-
ture marked by transverse fissures. The rhombic lip gives rise to the
flocculus and nodulus. Between the third and fifth months the cortex

THE BRAIN

337

cerebelli grows more rapidly than the deeper layers of the cerebellum, and
its principal lobes, folds, and fissures are formed (Fig. 337 C, D). The
hemispheres derived from the lateral lobes are the last to be differentiated.
Their fissures do not appear until the fifth month.

Cranial to the cerebellum the wall of the neural tube remains thin
dorsally, and constitutes the anterior medullary velum of the adult (Fig. 338
B}. Caudally, the ependymal roof of the fourth ventricle becomes the
posterior medullary velum. The points of attachment of the vela remain
approximately fixed, while the cerebellar cortex grows enormously. As
a result, the vela are folded in under the expanding cerebellum (Fig. 338).

The anlages of the cerebellum show at first differentiation into the same three layers
which are typical for the neural tube. During the second and third months, cells from the
ependymal, and perhaps from the mantle layer of the rhombic lip migrate to the surface
of the cerebellar cortex and give rise to the molecular and granular layers which are charac-
teristic of the adult cerebellar cortex (Schafer) . The later differentiation of the cortex is
only completed at birth, or later. The cells of the granular layer become unipolar by a
process of unilateral growth. The Purkinje cells differentiate later. Their axons, and
those of entering afferent fibers, form the deep medullary layer of the cerebellum.

The cells of the mantle layer may take little part in the development of the cerebellar
cortex, but give rise to neuroglia cells and fibers and to the internal nuclei. Of these, the
dentate nucleus is seen at the end of the third month; later, its cellular layer becomes folded,
producing its characteristic convolutions. The fibers arising from its cells form the greater
part of the brachium conjunctivum.

D. IV.

— Alar plate

•Marginal layer

Nucleus
' N. III.

r....- R0ot fibers N.I II.

A B

FIG. 339. — Transverse sections through the mesencephalon of a- 10.2 mm. embryo (His).
A, Through the isthmus and origin of the trochlear nerve; B, through the nucleus of origin of the
oculomotor nerve. D. IV., Decussation of oculomotor nerve; M.I., mantle layer.

The Mesencephalon. — The basal and alar plates can be recognized in
this subdivision of the brain, and each differentiates into the three primi-
tive layers (Fig. 339). In the basal plate the neuroblasts give rise to the
axons of motor nerves — the oculomotor cranial in position, the trochlear

338 THE MORPHOGENESIS OF THE CENTRAL NERVOUS SYSTEM

caudal (Fig. 339 B). In addition to these nuclei of origin, the nucleus
ruber (red nucleus) is developed in the basal plates, ventral and somewhat
cranial to the nucleus of the oculomotor nerve. The origin of the cells
forming the red nucleus is not definitely known. The alar plates form the
paired superior and inferior colliculi, which together constitute the corpora
quadrigemina (Figs. 337 -B and 349). The plates thicken and neuroblasts
migrate to their surfaces, forming stratified ganglionic layers comparable
to the cortical layers of the cerebellum and the cerebellar nuclei. With the
development of the superior and inferior colliculi the cavity of the mesen-
cephalic region decreases in size and becomes the cerebral aqueduct.

The mantle layer of the basal plate region is enclosed ventrally and
laterally by the fiber tracts which develop in the marginal zone. Ven-
tro-laterally, appear the median and lateral lemnisci; ventrally, the de-
scending tracts from the cerebral cortex, which together constitute the
peduncles of the cerebrum, develop later.

Roof plate (with chorioid plexus) .

Alar plate or Thalamus

'ulcus limitans
Basal plate or Hypothalamus

•Mammillary recess
FIG. 340. — Transverse section through the diencephalon of a 13.8 embryo (His). X 29.

The Diencephalon. — In the wall of the diencephalon we may recog-
nize laterally the alar and basal plates, dorsally the roof plate, and ven-
trally the floor plate (Fig. 340). The roof plate expands, folds as seen in
the figure, and into the folds extend blood capillaries. The roof plate
thus forms the ependymal lining of the tela chorioidea of the third ventricle.
The vessels and ingrowing mesenchymal tissue form the chorioid plexus.
Cranially, the tela chorioidea roofs over the median portion of the telen-
cephalon and is folded laterally into the hemispheres as the chorioid plexus
of the lateral ventricles. Laterally, the roof plate is attached to the alar
plates, and at their point of union are developed the ganglia habenula.

The epiphysis, or pineal body, is developed caudally as an evagination
of the roof plate. It appears at the fifth week (Fig. 335) and is well
developed by the third month (Fig. 342). Into the thickened wall of the

THE BRAIN

339

anlage is incorporated a certain amount of mesenchymal tissue, and thus
the pineal body proper is formed.

The alar plate is greatly thickened and becomes the anlage of the
thalamus and metathalamus. The latter, really a part of the thalamus,
gives rise to the lateral and median geniculate bodies.

The sulcus limitans (Fig. 341) forms the boundary line between the
thalamus (alar plate) and the hypothalamus (basal plate plus the floor
plate). The basal plate is comparatively unimportant in the diencephalic

Sulcus limitans

Hypothalamus

Pallium

Mammillary recess

Corpus striatum \ Infundibulum

Optic ridge

FIG. 341. — Median sagittal section of the fore- and mid-brain from a 10.2 mm. embryo (after

region, as no nuclei of origin for motor nerves are developed here. In
the floor plate the ridge formed by the optic chiasma constitutes the
pars optica hypothalamica.

The Hypophysis. — The hypophysis, or pituitary body, has a double
origin. Its glandular portions develop from the ectodermal Rathke's
pouch, which appears at about 3 mm. just in front of the pharyngeal
membrane (Fig. 86). This pouch early comes in contact with a sac-like
extension of the infundibulum, the anlage of the neural hypophyseal
lobe (Figs. 122, 341 and 343). Rathke's pouch, at first flat, grows laterally
and caudally about the neural lobe, and loses its stalked connection with
the oral epithelium at the end of the second month (Fig. 146). The
original cavity of the pouch becomes the residual lumen of the adult
gland. In embryos of about 20 mm., its walls differentiate into the

340

THE MORPHOGENESIS O7 THE CENTRAL NERVOUS SYSTEM

glandular cords of the anterior lobe. That portion of the wall between
the lumen and the neural lobe remains thin and constitutes the pars
intermedia. Recently, a further glandular portion, the pars tuberalis,

Diencephalon ^
Chorioid plexus

Corpus striatum sfl
Telencephalon /

Thalamus

..----^^ I Pineal body (epithalamus)
Cerebral peduncle
' Cerebral aqueduct
* Mesencephalon

• Pans

Optic Hypo-
ichiasma physis MeJulla.

Lamina terminalis / Hypothalamus oblonzata
Rhinencephalon

i - Isthmus
- Cerebellum
" Metencephalon
Rhomboid fossa
- Myelencephalon

""*• Spinal cord
• Central canal

FIG. 342. — Median sagittal section of the brain from a fetus of the third month (His in Sobotta).

Pallium

Foramen Monroi

Third ventricle

Optic vesicle
Lens ves

Infundibulum'

Rathke's pouch'

FIG. 343. — Oblique transverse section through the diencephalon and telencephalon of a 10 mm.

embryo. X 61.

has been recognized, lying along the tuber cinereum; it develops from the
fusion of paired lateral lobes, at the base and in front of Rathke's pouch.
The anlage of the neural lobe is transformed into a solid mass of neuroglia

THE BRAIN

341

tissue and remains connected to the diencephalbn by a permanent in-
fundibular stalk (Fig. 147). The anterior lobe and the pars intermedia
elaborate important internal secretions.

Caudal to the infundibulum, in the floor plate, are developed in
order the tuber cinereum and the mammillary recess (Figs. 341, 344 and
346). The lateral walls of the latter thicken and give rise to the paired
mammillary bodies.

The third ventricle lies largely in the diencephalon and is at first
relatively broad. Owing to the thickening of its lateral walls, it is com-
pressed until it forms a narrow, vertical cleft. In a majority of adults
the thalami are approximated, fuse, and form the massa intermedia, or
commissura mollis, which is encircled by the cavity of the ventricle.

Mesencephaton Diencephalon Pallium

Mammillary body

Hypophysis

Optic stalk Lobus olfactorius

FIG. 344. — Lateral view of the fore- and mid-brains of a 10.2 mm. embryo (His).

The Telencephalon. — This is the most highly differentiated division
of the brain (Fig. 344). The primitive structures of the neural tube
can no longer be recognized, but the telencephalon is regarded as repre-
senting greatly expanded alar plates and is, therefore, essentially a paired
structure. Each of the paired outgrowths expands cranially, dorsally,
and caudally, and eventually overlies the rest of the brain (Figs. 344, 345
and 346). The telencephalon is differentiated into the corpus striatum,
rhinencephalon, and pallium (primitive cortex of cerebral hemisphere)
The median lamina between the hemispheres lags behind in its develop-
ment and thus there is formed the great longitudinal fissure between the
hemispheres. The lamina is continuous caudally with the roof plate of

342

THE MORPHOGENESIS OF THE CENTRAL NERVOUS SYSTEM

the diencephalon ; cranially it becomes the lamina terminalis, the cranial
boundary of the third ventricle (Figs. 332 and 342).

The Chorioid Plexus of the Lateral Ventricles.— It will be remembered
(p. 338) that the chorioid plexus of the third ventricle develops in the folds
of the roof plate of the diencephalon. Similarly, the thin, median wall
of the pallium at its junction with the wall of the diencephalon is folded
into the lateral ventricle. A vascular plexus, continuous with that^of
the third ventricle, grows into this fold, and projects into the lateral

Fissura prima
Chorioid plexus of lat. ventricle

Pallium — r

Pineal body
Superi-or colliculus

Corpus striatum
Hippocampus

Roof plate

Mesencephalon

FIG. 345. — The fore-brain and mid-brain of an embryo of 13.6 mm., seenfrom the dorsal surface.
The pallium of the telencephalon is cut away, exposing the lateral ventricle (His).

ventricle of either side (Figs. 345 and 347). The fold of the pallial wall
forms the chorioidal fissure and the vascular plexus is the chorioid plexus
of the lateral ventricle. This is a paired structure, and, with the plexus
of the third ventricle forms a T-shaped figure, the stem of the T overlying
the third ventricle, its curved arms projecting into the lateral ventricles just
caudal to the interventricular foramen. Later, as the pallium extends,
the chorioid plexus of the lateral ventricles and the chorioidal fissures
are extensively elongated into the temporal lobe and inferior horn of the
lateral ventricle (Fig. 348).

The interventricular foramen (of Monro) is at first a wide opening (Fig.
343), but is later narrowed to a slit, not by constriction but because its
boundaries grow more slowly than the rest of the telencephalon (Fig. 347) .

THE BRAIN

343

The third ventricle extends some distance into the caudal end of the
telencephalon, and laterally in this region the optic vesicles develop. Into
each optic stalk extends the optic recess (Fig. 343).

Diencephalon

l.Iesencephalon

Pallium

Corpus mammillare

Tuber cinereum

Pars ant. olf. lobe
Pars post. olf. lobe

Infundibulum Ototic stalk
FIG. 346. — Lateral view of the fore-brain and mid-brain of a 13.6 mm. embryo (His).

Lateral ventricle

Cliorioid plexus of lateral
•ventricle

Thalamus
Corpus striatum

Third ventricle \

FIG. 347. — Transverse section through the fore-brain of a 15 mm. embryo, showing the early
development of the chorioid plexus and fissure (His).

The corpus striatum is developed as a thickening in the floor of each
cerebral hemisphere (Fig. 331). It is already prominent in embryos of
six weeks (13.6 mm.), bulging into the lateral ventricle (Figs. 345 and 347).
It is in line caudally with the thalamus of the diencephalon and in develop-

344

THE MORPHOGENESIS OF THE CENTRAL NERVOUS SYSTEM
Falx

FIG. 348. — A transverse section through the telencephalon of an 83 mm. fetus (after His).
Th, Thalamus; Cs, corpus striatum; h.f., hippocampal fissure ; fa, marginal gray seam;./*, edge
of white substance.

Chorioid fissure

Sup. colliciilus

Olfactory lobe

FIG. 349. — Lateral view of the brain of a 53 mm. fetus. The greater part of the pallium
of the right cerebral hemisphere has been removed, leaving only that covering the lenticular
nucleus, and exposing the internal capsule, caudate nucleus and hippocampus (His).

THE BRAIN

345

ment is closely connected with it, although the. thalamus always forms a
separate structure. The corpus striatum elongates as the cerebral hemi-
sphere lengthens, its caudal portion curving around to the tip of the in-
ferior horn of the lateral ventricle and forming the slender tail of the caudate
nucleus (Fig. 349). The thickening of the corpus striatum is due to the
active proliferation of cells in the ependymal layer which form a promi-
nent mass of mantle layer cells. Nerve fibers to and from the thalamus to
the cerebral cortex course through the corpus striatum as laminae^ which

Anterior horn

Nucleus candatus

I nterventricular
foramen

Third ventricle

Chorioid plexus of
•lat. ventricle

Posterior horn

Lenticular nucleus
Ant. columns of
fornix
internal capsule

Thalamus
Hippocam}

FIG. 350. — Horizontal (coronal) section through the fore-brain of a 160 mm. fetus (His).

are arranged in the form of a wide V, open laterally, when seen in hori-
zontal sections. This V-shaped tract of white fibers is the internal cap-
sule, the cranial limb of which partly separates the corpus striatum into
the caudate and lenticular nuclei (Fig. 350). The caudal limb of the
capsule extends between the lenticular nucleus and the thalamus.

The thalamus and corpus striatum are separated by a deep groove
until the end of the third month (Fig. 347). As the structures enlarge,
the groove between them disappears and they form one continuous mass
(Fig. 350). According to some investigators there is direct fusion between
the two.

346 THE MORPHOGENESIS OF THE CENTRAL NERVOUS SYSTEM

The Rhinencephalon. — The olfactory apparatus is divided into a
basal portion and a pallial portion. The basal portion consists: (i) of a
ventral and cranial evagination (pars anterior) , formed mesial to the cor-
pus striatum, which is the anlage of the olfactory lobe and stalk (Fig. 346).
This receives the olfactory fibers and its cells give rise to olfactory tracts.
The tubular stalk connecting the olfactory lobe with the cerebrum loses
its lumen. (2) Caudal to the anlage of the olfactory lobe a thickening of
the brain wall develops (pars posterior) which extends mesially along the
lamina terminalis and laterally becomes continuous with the tip of the
temporal lobe (Fig. 346). This thickening constitutes the anterior per-
forated space and the parolfactory area of the adult brain (Fig. 356).

The pallial portion of the rhinencephalon is termed the archipallium
because it forms the entire' primitive wall of the cerebrum, a condition
which is permanent in fishes and amphibia. Later, when the neopallium,
or adult cortex, arises, the archipallium forms a median strip of the pallial
wall curving along the dorsal edge of the chorioidal fissure from the an-
terior perforated space around to the tip of the temporal lobe, where it is
again connected with the basal portion of the rhinencephalon. The
archipallium differentiates into the hippocampus (Figs. 345 and 349), a
portion of the gyrus hippocampi, and into the gyrus dentatus. It resembles
the rest of the cerebral cortex in the arrangement of its cells. The infold-
ing of the hippocampus produces the hippocampal fissure.

Commissures of the Telencephalon. — The important commissures
are the corpus callosum, fornix, and anterior commissure. The first is the
great transverse commissure of the neopallium, or cerebral cortex, while
the fornix and anterior commissure, smaller in size, are connected with the
archipallium of the rhinencephalon. The commissures develop in rela-
tion to the lamina terminalis, crossing partly in its wall and partly in
fused adjacent portions of the median pallial walls. Owing to the fusion
of the pallial walls dorsal and cranial to it, the lamina terminalis thickens
rapidly during the fourth and fifth month (Streeter) . "It [the lamina
terminalis] is distended dorsalward and antero-lateralward through the
growth of the corpus callosum, the shape of which is determined by the
expanding pallium." Between the curve of the corpus callosum and
the fornix, the median pallial walls remain thin and membranous, and
constitute the septum pellucidum of the adult. The walls of this sep-
tum enclose a cavity, the so-called fifth ventricle, or space of the septum
pellucidum (Fig. 351).

The fornix takes its origin early, chiefly from cells in the hippocampus.
The fibers course along the chorioidal side of the hippocampus cranially,
passing dorsal to the foramen of Monro (Fig. 351 A). In the cranial
portion of the lamina terminalis, fibers are both given off to the basal

THE BRAIN

347

portion of the rhinencephalon and received from it. In this region,
fibers crossing the midline form the hippocampal commissure. Other
fibers, as the diverging anterior pillars x>f the fornix, curve ventrally and
end in the mammillary body of the hypothalamus. The commissure
of the hippocampus, originally cranial in position, is carried caudalward
with the caudal extension of the corpus callosum (Fig. 351 B}.

Corpus callosum

Body of fornix

Hippocampal commissure

Anterior commissure

Chorioid fissure
Ant. pillar of fornix Thalamus

B
Body of fornix Hippocampal commissure

Septum pellucidu

Corpus callosum

Ant. commissure __ _ . . _ „_.„ „...

' Thalamus
Ant. pillar of fornix

FIG. 351. — Two stages in the development of the cerebral commissure. (Based on recon-
structions by His and Streeter). A, Median view of the right hemisphere of an 83 mm.Jetus;
B, of a 120 mm. fetus.

The fibers of the anterior commissure cross in the lamina terminalis
ventral to the hippocampal commissure. They arise in a cranial and a
caudal division. The fibers of the former take their origin from the olfac-
tory stalk and the adjacent cortex. The fibers of the caudal division pass
ventrally about the corpus striatum, between it and the cortex, and may
be derived from one or both of these regions.

348

THE MORPHOGENESIS OF THE CENTRAL NERVOUS SYSTEM

The corpus callosum appears cranial and dorsal to the hippocampal
commissure in the roof of the thickened lamina terminalis (Fig. 351 A).
Through its fibers, which arise from neuroblasts in the wall of the neo-
pallium (cerebral cortex), nearly all regions of one hemisphere are asso-
ciated with corresponding regions of the other. With the expansion of
the pallium, the corpus callosum is extended cranially and caudally by
the development of interstitial fibers. The fibers first found in the corpus

Lobus parietalis

Lateral
fissure

Lobus
fronialis

Lobus
temporalis

Pans

Lobus
occipitalis

Cerebellum

Myelenceph-
alon

Spinal cord

FIG. 352. — Lateral view of the brain of a 90 mm. fetus (His).

callosum arise in the median wall of the hemispheres. In fetuses of five
months this great commissure is a conspicuous structure and shows the
form which is characteristic of the adult (Fig. 351 B).

Form of the Cerebral Hemispheres. —When the telencephalon ex-
pands cranially, caudally, and at the same time ventrally, four lobes may
be distinguished (Fig. 352): (i) a cranial frontal lobe; (2) a dorsal parietal
lobe; (3) a caudal occipital lobe; and (4) a ventro-lateral temporal lobe.
The ventricle extends into each of these regions and forms respectively

THE BRAIN

349

the anterior horn, the body, the posterior horn, and the inferior horn of the
lateral ventricle. The surface extent of the cerebral wall, the thin gray
cortex, increases more rapidly than the underlying, white medullary layer.
As a result, the cortex is folded, producing convolutions between which
are depressions, the fissures and sulci. The chorioidal fissure is formed,
as we have seen (p. 342), by the ingrowth of the chorioid plexus. During
the third month the hippocampal fissure develops as a curved infolding
along the median wall of the temporal lobe. Internally, the infolded

Occipital lobe of
cerebrum

Corpora,
quadrigemina

Hemisphere of
cerebellum

Impression of
thalamus

Temporal lobe

Vermis cerebelli

Lateral recess of
fourth ventricle

Fasciculus gracilis
Medulla oblongata

FIG. 353. — Dorsal view of the brain from a 100 mm. fetus (Kollmann).

cortex forms the hippocampus (Figs. 345 and 349). The lateral fissure
(of Sylvius) makes its appearance also in the third month (Fig. 3^2),
but its development is not completed until after birth. The cortex over-
lying the corpus striatum laterally develops more slowly than the sur-
rounding areas and is thus gradually overgrown by folds of the parietal
and frontal lobes (fronto-parietal operculum) and of the temporal lobe
(temporal operculum). The area thus overgrown is the insula (island
of Reil) and the depression so formed is the lateral fissure (of .Sylvius) (Fig.
355). Later, frontal and orbital opercula are developed ventro-laterally
from the frontal lobe. These are not approximated over the insula until
after birth. The frontal operculum is included between the anterior limbs
of the Sylvian fissure, and the extent of its development, which is variable,
determines the form of these limbs.

350

THE MORPHOGENESIS OF THE CENTRAL NERVOUS SYSTEM

Median olfactory
gyms

Middle olfactory

gyrus

Diagonal gyrus

C erebellum

Insula

Lat. olfactory gyrus

Gyrus ambiens
Cyrus semilunaris

Oliva

FIG. 354. — Ventral view of the brain of a i op mm. fetus to show the rhinencephalon (Kollmann)

Sulcus postcentralis-

Sukus centralis

Inferior
frontal
sulcus

Occipital
pole

Superior temporal gyrus Middle temporal gyrus

FIG- 355- — Lateral view of the right cerebral hemisphere from a seven months' fetus

(Kollmann).

THE BRAIN

35*

In fetuses of six to seven months, four other depressions appear which
later form important landmarks in the cerebral topography. These are:
(i) the central sulcus, or fissure of Rolando, which forms the dorso- lateral
boundary line between the frontal and parietal lobes (Fig. 355); (2) the
parieto-occipital fissure, which, on the median wall of the cerebrum, is
the line of separation between the occipital and parietal lobes (Fig. 356) ;
(3) the calcarine fissure, which includes the cuneus between itself and the
parieto-occipital fissure and marks the position of the visual area of the
cerebrum; (4) the collateral fissure on the ventral surface of the temporal
lobe, which produces the inward bulging on the floor of the posterior horn

Corpus cattosum
Cyrus cinguli

Side. corp. callosi
Splenium

Parieto-occipital fissure

Space of

septum

pellu-

cidum

Rostral

lamina

Parol-

factory

area

Cuneus

Olfactory lobe

Optic nerve

Fissura rhinica
Temporal lobe

FIG. 356. — Median surface of the right cerebral hemisphere from a seven months' fetus

(Kollmann).

of the ventricle known as the collateral eminence. The calcarine fissure
also affects the internal wall of the ventricle, causing the convexity termed
the calcar avis (hippocampus minor) .

Simultaneously with the development of the collateral fissure, appear
other shallower depressions known as sulci. These have a definite arrange-
ment, and, with the fissures, mark off from each other the various func-
tional areas of the cerebrum. The surface convolutions between the
depressions constitute the gyri and lobules of the adult cerebrum.

Histogenesis of the Cerebral Cortex. — In the wall of the pallium are
differentiated the three primitive zones typical of the neural tube: the
ependymal, mantle, and marginal layers. During the first two months

352 THE MORPHOGENESIS OF THE CENTRAL NERVOUS SYSTEM

the cortex remains thin and differentiation is slow. At eight weeks,
neuroblasts migrate from the ependymal and mantle zones into the mar-
ginal zone and give rise to layers of pyramidal and other cells typical of
the cerebrum. The differentiation of these layers is most active during
the third and fourth months, but probably continues until after birth
(Mellus, 1912). From the fourth month on, the cerebral wall thickens
rapidly, owing to the development: (i) of the fibers from the thalamus
and corpus striatum; (2) of endogenous fibers from the neuroblasts of
the cortex. The fibers form a white, inner medullary layer surrounded
by the gray cortex. Myelination begins shortly before birth (Flechsig),
but some fibers may not acquire their sheaths until after the twentieth
year. As the cerebral wall increases in thickness the size of the lateral
ventricle becomes relatively less, its lateral diameter especially being
decreased.

Anomalies. — There are numerous types of defective neural tube development — most
the result of arrest. These usually involve the bony investments as well, and produce
conspicuous malformations.

The more or less extensive failure of the neural groove to close produces cranioschisis
(acrania) , or rachischisis, depending on whether the region of the head or vertebral column
is affected. If the cleft contains a sac -like protrusion of the membranes, the condition is
known as menhigoccele; if the neural wall alone protrudes, it is encephaloccele (brain) or
myeloccele (spinal cord) ; if, as is most common, both are involved, it is meningo-encephalo-
ccele, or meningo-myeloccele. Such a hernial condition of the spine is often called spina
bifida and is most frequent in the lumbo-sacral region, where the sac may become the size
of a child's head.

An excessive fluid content in the brain cavities causes both brain and skull to enlarge,
producing hydrocephaly.

CHAPTER XIII
THE PERIPHERAL NERVOUS SYSTEM

THE nerves, ganglia, and sense organs constitute the peripheral
nervous system. The peripheral nerves consist of bundles of myelinated
and unmyelinated nerve fibers, and aggregations of nerve cells, the ganglia.
The fibers are of two types : afferent fibers, which' carry sensory impulses
to the central nervous system, and efferent fibers, which carry motor im-
pulses away from the nervous centers. The peripheral efferent fibers of
both brain and spinal cord take their origin from neuroblasts of the basal
plate. Typically they emerge ventro-laterally from the neural tube.
Those arising from the spinal cord take origin in the mantle layer, con-
verge, and form the ventral roots of the spinal nerves. The efferent fibers
of the brain take origin from more definite nuclei and constitute the
motor components of the cerebral nerves. The peripheral afferent fibers
originate from nerve cells which lie outside the neural tube. Those
sensory nerve cells related to the spinal cord and to the brain stem caudal
to the otic vesicle are derived from the ganglion crest, the origin of which
has been described (Chapter X, p. 302).

X-XI gang, crest
XI fibers

^=^

FIG- 357- — Reconstruction of an embryo of 4 mm., showing the development of the cerebro-
spinal nerves (Streeter). X 17. Cr-6, Cervical spinal nerves.

A. THE SPINAL NERVES

The spinal nerves are segmentally arranged and each consists of
dorsal and ventral roots, spinal ganglion, and nerve trunks. In embryos
of 4 mm. the ventral roots are already developing as outgrowths of neuro-
blasts in the mantle layer of the spinal cord (Fig. 357). The spinal ganglia
are represented as enlargements along the ganglion crest and are connected
by cellular bridges.

In 7 mm. embryos (five weeks old) the cells of the spinal ganglia begin
to develop centrally directed processes which enter the marginal zone of

23. 353

354

THE PERIPHERAL NERVOUS SYSTEM

the 'cord as the dorsal root fibers (Fig 358). These fibers course in the
dorsal funiculi and eventually form the greater part of them. Peripheral
processes of the ganglion cells join the ventral root fibers in the trunk
of the nerve (Fig. 360). At 10 mm. (Fig. 359) the dorsal root fibers
have elongated and the cellular bridges of the ganglion crest between the
spinal ganglia have begun to disappear. In transverse sections at this

___ ^ IX- X-XI gang, crest

1 ^x /3^7^

?*^»»^-^\ ^ v /">! /

Ophthal. div.

Sup. max. div.
M. masticatorius
Inf. max. div.

S.I.

D.I.

L.I

FIG. 358. — Reconstruction of a 6.9 mm. embryo, showing the development of the dorsal root
fibers from the spinal and cerebral ganglia* (Streeter). X 16.7.

stage (Fig. 325 and 360) the different parts of a spinal nerve may be seen.
The trunk of the nerve, just ventral to the union of the dorsal and ventral
roots, gives off laterally the dorsal, or posterior ramus, the fibers of which
supply the dorsal muscles. The ventral ramus, continuing, gives off
mesially the ramus communicans to the sympathetic ganglion, and divides
into the lateral and ventral (anterior) terminal rami. The efferent fibers

THE SPINAL NERVES

355

of these rami supply the muscles of the lateral and ventral body wall, and
the afferent fibers end in the integument of the same regions.

At the points where the anterior and lateral terminal rami arise,
connecting loops may extend from one spinal nerve to another. Thus, in
the cervical region superficial and deep nerve plexuses are formed. The

Gang, acusticum Vesicula auditiva
Gang, semilunare n. V : / Gang, radicis n. £X
Cerebellum j N.VI; < \ \Gang. petrosum

Gang, redicis n. X

A*. Ill
N.IV —

N. Jrontalis

N. nasociliaris

N. maxillaris
N. mandibularis '
Gang, geniculatum

Diaphragma "'
Hepar
I Co.

N. tibialis
N. peroneus '*

Gang. Froriep
,-N. hypoglossus

I.C.

-.-— N. XI

- Gang, nodos.

N. desc. cerv.
... Rami hyoid.
(Ansa hypoglossi)
N. Musculoculan.
'' N. axillaris
' ' N. phrenicus

- - N. medianus
'~N. radialis
"N. ulnaris

1 Th.

Tubus digest*

. R. posterior
R. terminalis lateral i

IS i R terminalis anterior

N.femorali \ \IL.
N obturator '•• Mesonephros

Nn. ilioing. et hypogastr.

12.

FIG. 359. — Reconstruction of the nervous system of a 10 mm. embryo (Streeter). X

deep cervical plexus forms the ansa hypoglossi and the phrenic nerve
(Fig- 359).

The Brachial and Lumbo-sacral Plexuses. — The nerves supplying the
arm and leg also unite to form plexuses. In embryos of 10 mm. (Fig. 359)
the trunks of the last four cervical nerves and of the first thoracic are united
to form a flattened plate, the anlage of the brachial plexus. From this

356

THE PERIPHERAL NERVOUS SYSTEM

plate nervous cords extend into the intermuscular spaces and end in the
premuscle masses. The developing skeleton of the shoulder splits the
brachial plexus into dorsal and ventral laminae. From the dorsal lamina
arise the musculo- cutaneous, median, and ulna nerves; from the ventral
lamina, the axillary and radial nerves.

In 10 mm. embryos the lumbar and sacral nerves that supply the leg
unite in a plate-like structure, the anlage of the lumbo-sacral plexus
(Fig. 359). The plate is divided by the skeletal elements of the pelvis and
femur into two lateral and two median trunks. Of the cranial pair, the
lateral becomes the femoral nerve; the median, the obturator nerve. The

Dorsal root

Somatic sensory neuron
Visceral sensory neu

Spinal cord
Visceral motor neuro

Somatic motor m
Dorsal ramus

Marginal layer

Epcndymal layer
Mantle layer

Ventral terminal division of / \ \ d t

spinal nerve /
Ramus communicans Sympathetic ganglion

FIG. 360. — Transverse section of a 10 mm. embryo, showing the spinal cord, spinal nerves and
their functional nervous components. Diagrammatic.

caudal pair constitutes the sciatic nerve; the lateral trunk will be the
peroneal nerve, the median trunk the tibial.

Save for the neurons from the special sense organs (nose, eye, and ear)
that form a special sensory group, the neurons of the peripheral nerves,
both spinal and cerebral, fall into four functional groups (Fig. 360).

(1) Somatic afferent, or general sensory, with fibers ending in the
integument of the body wall.

(2) Visceral afferent, or sensory, with fibers ending in the walls of the
viscera.

(3) Somatic efferent, or motor, with fibers ending on voluntary muscle
fibers.

(4) Visceral efferent, or motor: (a) with fibers ending about sympa-
thetic ganglion cells, which in turn control the smooth muscle fibers of

THE CEREBRAL NERVES

357

the viscera and blood vessels (spinal nerves) ; or (6) with fibers ending
directly on visceral muscle fibers (mixed cerebral nerves).

B. THE CEREBRAL NERVES

The cerebral nerves of the human brain are twelve in number. They
differ from the spinal nerves: (i) in that they are not segmentally ar-
ranged, and (2) in that they do not all contain the same types of nervous
components. Classed according to the functions of their neurons they
fall into three groups:

VISCERAL SENSORY AND
SOMATIC MOTOR MOTOR.

III. Oculomotor. V. Trigeminal.

IV. Trochlear. VII. Facial.

VI. Abducens. IX. Glossopharyngeal.

SPECIAL SOMATIC SENSORY.
I. Olfactory.
II. Optic.
VIII. Acoustic.

XII. Hypoglossal.

X. Vagus complex, including
XI. Spinal Accessory.

It will be seen: (i) that the nerves of the first group are purely sen-
sory, corresponding to the general somatic afferent neurons of the spinal
nerves; (2) that those of the somatic motor group are purely motor and
correspond to the somatic efferent neurons of the spinal nerves; (3) that
those of the third group are mixed in function and correspond to the vis-
ceral components of the spinal nerves.

I. THE SPECIAL SOMATIC SENSORY NERVES

i. The Olfactory Nerve, though purely sensory, has no ganglion. Its
nerve cells lie at first in the olfactory epithelium of the nose and are of the
bipolar type (fourth week). From
these cells peripheral processes de-
velop and end directly at the surface
of the olfactory epithelium (Fig.
361). Central processes grow to-
ward the olfactory lobe and form
the strands of the olfactory nerve.
They end in the glomeruli of the
olfactory bulb in contact with the
dendrites of the mitral cells, or
olfactory neurons of the second
order. Some olfactory cells migrate

from the epithelium, with which, however, they retain peripheral con-
nections. Such bipolar cells, found along the entire course of the nerve,
resemble ordinary dorsal ganglion cells. The olfactory nerve fibers are
peculiar in that they remain unmyelinated. Nerve fibers from the

"Olfactory tract
-Mitral cell

Glomerulus

-Cribriform plate
-Olfactory nerve fiber

\~Olfactory epithelium

FIG. 361. — Diagram of the relations of the
fibers in the olfactory nerve.

358 THE PERIPHERAL NERVOUS SYSTEM

epithelium of the vestigial vomero-nasal organ (of Jacobson) also end in
the olfactory bulb.

When the ethmoidal bone of the cranium is developed, its cartilage, as
the cribriform plate, forms around the strands of the olfactory nerve.

The ganglionated n. ierminalis courses in close association with the
olfactory nerve. Its unmyelinated fibers end in the epithelium of the
vomero-nasal organ and of the nose. Although evidently a distinct nerve
its significance is obscure.

2. The Optic Nerve is formed by fibers which take their origin from
neuroblasts in the nervous layer of the retina. The retina is differentiated
from an evagination of the wall of the fore-brain (Fig. 343), hence the
optic nerve is not a true peripheral nerve, but belongs to the central
system of tracts. The neuroblasts from which the optic nerve fibers
develop constitute the ganglion cell layer of the retina (Fig. 381). During
the sixth and seventh weeks these cells give rise to central processes
which form a nerve fiber layer on the inner side of the retina. The optic
fibers converge to the optic stalk and grow through its wall back to the
brain. The cells of the optic stalk are converted into a neuroglia frame-
work and the cavity is obliterated. In the floor of the fore-brain, at the
• boundary between telencephalon and diencephalon, the fibers from the
median half of each retina at about the end of the second month cross to
the opposite side, and this decussation constitutes the optic chiasma
(from Greek letter x. or 'chi ') . The crossed and uncrossed fibers constitute
the optic tract which rounds the cerebral peduncles laterally and dorsally
(Fig. 354). Eventually, the optic fibers end in the lateral geniculate body,
thalamus, and superior colliculus.

Efferent fibers, terminating in the inner reticular layer of the retina,
are also present. In certain fishes where their function has been studied,
these fibers resemble visceral efferent components (Arey, 1916).

8. The Acoustic Nerve is formed by fibers which grow from the cells of
the acoustic ganglion. The origin of these cells is unknown, though they
appear in 4 mm. embryos just cranial to the otic vesicle (Fig. 358). The
cells become bipolar, central processes uniting the ganglion to the tuber-
culum acusticum of the myelencephalon and peripheral fibers connecting it
with the wall of the otocyst.

The acoustic ganglion is differentiated into the vestibular and spiral
ganglia (Fig. 362) . The ganglion elongates and is subdivided into superior
and inferior portions in 7 mm. embryos. The superior part supplies
nerves to the utriculus and to the ampullae of the anterior and lateral semi-
circular canals. Part of the inferior portion supplies nerves to the sacculus
and to the ampulla of the posterior semicircular canal, and this portion,
together with the entire pars superior, constitutes the vestibular ganglion.

THE CEREBRAL NERVES

359

,'N. vestib.---

4 mm. 7 mm

Pars. sup.

' •*•""'''• "\N ''

N. each.

-•- N.vestib-

R. amp. sup.

R. amp. lot.

R. amp. sup.

-R. amp. lot.

LATERAL VIEW

MEDIAN VIEW

FIG. 362. — The development of the acoustic ganglia and nerves. The vestibular ganglion is
finely stippled, the spiral ganglion coarsely stippled (Streeter).

360 THE PERIPHERAL NERVOUS SYSTEM

The greater part of the pars inferior is, however, differentiated into the
spiral ganglion, the peripheral fibers of which innervate the hair cells of
the spiral organ (of Corti) in the cochlea. The spiral ganglion appears- in
9 mm. embryos and conforms to the spiral turns of the cochlea, hence its
name. Its central nerve fibers form the cochlear division of the acoustic
nerve. This is distinctly separated from the central fibers of the vestibular
ganglion which constitute the vestibular division of the acoustic nerve, the
fibers of which are equilibratory in function. The pars inferior of the
vestibular ganglion becomes closely .connected with the n. cochlearis, and
thus in the adult it appears as though the sacculus and posterior ampulla
were supplied by the cochlear nerve.

n. THE SOMATIC MOTOR NERVE

The nerves of this group, consisting of the three nerves to the eye
muscles and the n. hypoglossus, are purely motor nerves, the fibers of
which take origin from the neuroblasts of the basal plate of the brain stem,
near the midline. They are regarded as the homologues of the ventral
motor roots of the spinal cord, but they have lost their segmental arrange-
ment and are otherwise modified. The nuclei of origin of these nerves are
shown in Fig. 364.

12. The Hypoglossal Nerve is formed by the fusion of the ventral root
fibers of three to five precervical nerves. Its fibers take origin from neuro-
blasts of the basal plate and emerge from the ventral wall of the myelence-
phalon in several groups (Figs. 357 and 364). In embryos of five weeks
(7 mm.) the fibers have converged ventrally to form the trunk of the nerve
(Fig. 358). Later they grow cranially, lateral to the ganglion nodosum,
and eventually end in the muscle fibers of the tongue (Fig. 359). The
nerve in its development unites with the first three cervical nerves to form
the ansa hypoglossi.

That the hypoglossal is a composite nerve, homologous with the ventral roots of the
spinal nerves, is shown: (i) by the segmental origin of its fibers; (2) from the fact that its
nucleus of origin is a cranial continuation of the ventral gray column, or nucleus of origin
for the ventral spinal roots; (3) from the fact that in mammalian embryos (pig, sheep, cat,
etc.) rudimentary dorsal ganglia are developed, one of which at least (Froriep's ganglion)
sends a dorsal root to the hypoglossal. In human embryos Froriep's ganglion may be pres-
ent as a rudimentary structure (Figs. 359 and 363), or it may be absent and the ganglion of
the first cervical nerve may also degenerate and disappear. In pig embryos Prentiss (1910)
has found one to four accessory ganglia (including Froriep's) from which dorsal roots ex-
tend to the root fascicles of the hypoglossal nerve (Fig. 121).

3. The Oculomotor Nerve originates from neuroblasts in the basal
plate of the mesencephalon (Fig. 339 B). The fibers emerge as small
fascicles on the ventral surface of the mid-brain in the concavity due to the

THE CEREBRAL NERVES 361

cephalic flexure (Figs. 359 and 364). The fascicles converge, form the
trunk of the nerve, and end in the premuscle masses of the eye. The
nerve eventually supplies all of the extrinsic muscles of the eye save the
superior oblique and external rectus. A branch also passes to the ciliary
ganglion. In the chick embryo, bipolar cells migrate along the fibers of
the oculomotor nerve to take part in the development of the ganglion.
The ciliary ganglion of human embryos is derived entirely from the semi-
lunar ganglion of the trigeminal nerve.

4. The Trochlear Nerve fibers take their origin from neuroblasts of the
basal plate, located just caudal to the nucleus of origin of the oculomotor
nerve (Fig. 364). They are directed dorsally, curve around the cerebral
aqueduct, and, crossing in its roof, emerge at the isthmus (Fig. 339 A).
From their superficial origin, each is directed ventrally as a slender nerve
which connects with the anlage of the superior oblique muscle of the eye

(Fig. 359).

6. The N. Abducens takes origin from a nucleus of cells in the basal
plate of the myelencephalon, located directly beneath the fourth neuro-
mere of the floor of the fourth ventricle (Figs. 359 and 364). The con-
verging fibers emerge ventrally at a point caudal to the future pons, and, as
a single trunk, course cranially, mesial to the semilunar ganglion, finally
ending in the anlage of the external rectus muscle of the eye. Vestigial
rootlets of the abducens and hypoglossal nerve tend to fill in the gap be-
tween these two nerves, according to Bremer and Elze.

III. THE VISCERAL MIXED NERVES

The nerves of this group, the trigeminal, facial, glossopharyngeal, and
vagus complex (vagus plus the spinal accessory), are mixed in function.
The trigeminal nerve, beside its visceral nerve components, contains also
numerous somatic sensory neurons which supply the integument of the
head and face.

The facial, glossopharyngeal, and vagus nerves are essentially visceral
in function. Their sensory fibers, chiefly of the visceral type, supply the
sense organs of the branchial arches and viscera. A few somatic sensory
fibers, having the same origin and course in the myelencephalon, supply
the adjacent integument.

5. The Trigeminal Nerve is largely sensory. Its semilunar ganglion, a
derivative of the ganglion crest, is the largest of the whole nervous system,
but very early is distinct from the other cerebral ganglia (Fig. 358).
It arises laterally at the extreme cranial end of the hind-brain. Central
processes from its cells form the large sensory root of the nerve that enters
the wall of the hind-brain at the level of the pontine flexure (Fig. 359).
These fibers fork and course cranially and caudally in the alar plate of the

362

THE PERIPHERAL NERVOUS SYSTEM

myelencephalon. The caudal fibers constitute the descending spinal tract
of the trigeminal nerve, which extends as far caudal as the spinal cord
(Fig. 364). The peripheral processes separate into three large divisions,
the ophthalmic, maxillary, and mandibular rami, and supply the integu-
ment of the head and face, and the epithelium of the mauth and tongue.
The motor fibers of the trigeminal nerve arise chiefly from a dorsal
motor nucleus that lies opposite the point at which the sensory fibers enter
the brain wall (Fig. 364). In the embryo these fibers emerge as a sepa-

Gang. jugulare N, 10

Accessory root ganglia

Gang, super.ius N. 9

Gang, nodosum, N. 10
N. laryng. sup.

Gang. Froriep.
A7, ticcessorius

Rod. dors.

Inter-gang, bridge

N. hypoglossus

N. vagus
FIG. 363. — Reconstruction of the cerebral nerves of an embryo of 10.2 mm. (Streeter). X 16.7.

rate motor root, course along the mesial sideof thesemilunar ganglion, and,
as a distinct trunk, supply the premuscle masses which later form the
muscles of mastication. From the chief motor nucleus, a line of cells
extending cranially into the mesencephalon constitutes a second source of
origin for motor fibers. In the adult, the motor fibers form a part of the
mandibular division of the nerve.

7. The Facial Nerve is largely composed of efferent motor fibers that
supply the facial muscles of expression. In 10 mm. embryos these fibers
arise from a cluster of neuroblasts in the basal plate of the myelencephalon,
located beneath the third rhombic groove or neuromere (Fig. 364). The
fibers from these cells course laterally, and emerge just mesial to the acous-
tic ganglion . The motor trunk then courses caudally and is lost in the tissue
of the hyoid visceral arch, tissue which later gives rise to the muscles of
expression (Fig. 359). The sensory fibers of the facial nerve arise from the

THE CEREBRAL NERVES

363

cells of the geniculate ganglion, which are in turn derived from the ganglion
crest (Streeter). This ganglion is present in 7 mm. embryos (Fig. 358),
located cranial to the acoustic ganglion. The centrally directed processes
of the geniculate ganglion enter the alar plate and form part of the solitary
tract. The peripheral fibers in part course with motor fibers in the chorda
tympani, join the mandibular branch of the trigeminal nerve, and end in
the sense organs of the tongue. Other sensory fibers form later the great
superficial petrosal nerve, which extends to the spheno-palatine ganglion.

The motor fibers of the facialis at first course straight laterad, passing
cranial to the nucleus of the abducens. The nuclei of the two nerves later

Nucl. motor. n,X (amblguui)

Nud. n. hypogloMl

N. »c«s»oriu« v—--

FIG. 364. — Reconstruction of the nuclei of origin and termination of the cerebral nerves in an
embryo of 10 mm. The somatic motor nuclei are colored red (Streeter). X 30.

gradually shift their positions, that of the facial nerve moving caudad and
laterad, while the nucleus of the abducens shifts cephalad. As a result, the
motor root of the facial nerve in the adult bends around the nucleus of the
abducens, producing the genu, or knee, of the former. The two together
produce the rounded eminence in the floor of the fourth ventricle known as
the facial colliculus.

9. The Glossopharyngeal Nerve takes its superficial origin just caudal
to the otic vesicle (Figs. 358, 363 and 365). Its few motor fibers arise
from neuroblasts in the basal plate beneath the fifth neuromeric groove.
These neuroblasts form part of the nucleus ambiguus, a nucleus of origin
which the glossopharyngeal shares with the vagus (Fig. 364). The motor

364 THE PERIPHERAL NERVOUS SYSTEM

fibers course laterally beneath the spinal tract of the trigeminal nerve
and emerge to form the trunk of the nerve. These fibers later supply
the muscles of the pharynx.

The sensory fibers of the glossopharyngeal nerve arise from two gan-
glia, a superior, or root ganglion, and a petrosal, or trunk ganglion (Figs.
359 and 365). These fibers constitute the greater part of the nerve and
divide peripherally to form the tympanic and lingual rami to the second
and third branchial arches. Centrally, these fibers enter the alar plate of
the myelencephalon and join the sensory fiberr of the facial nerve coursing
caudally in the solitary tract.

10, ii. The Vagus and Spinal Accessory.— The vagus, like the hypo-
glossal, is composite. It represents the union of several nerves which supply
the branchial arches of aquatic vertebrates (Figs. 359 and 365). The more
caudal fascicles of motor fibers take their origin in the lateral gray column
of the cervical cord as far back as the fourth cervical segment. These
fibers emerge laterally, and, as the spinal accessory trunk (in anatomy a dis-
tinct nerve), course cephalad along the line of the neural crest (Figs. 358,
359 and 365). Other motor fibers take their origin from the neuroblasts
of the nucleus ambiguus of the myelencephalon (Fig. 364). Still others
arise from a dorsal motor nucleus that lies median in position. The
fibers from these two sources emerge laterally as separate fascicles and
join the fibers of the spinal accessory in the trunk of the vagus nerve.
The accessory fibers soon leave the trunk of the vagus and are distributed
laterally and caudally to the visceral premuscle masses which later form
the sterno-cleido-mastoid and trapezius muscles of the shoulder (Fig. 359).
Other motor fibers of the vagus supply muscle fibers of the phayrnx and
larynx.

As the vagus is a composite nerve, it has several root ganglia which
arise as enlargements along the course of the ganglion crest (Figs. 359
and 365). The more cranial of these ganglia is the ganglion jugular e. The
others, termed accessory ganglia, are vestigial structures and not segmen-
tally arranged. In addition to the root ganglia of the vagus, the ganglion
nodosum forms a ganglion of the trunk (Fig. 365). The trunk ganglia of
both the vagus arid glossopharyngeal nerves are believed to be derivatives
of the ganglion crest, their cells migrating ventrally in early stages.

The central processes from the neuroblasts of the vagus ganglia enter
the wall of the myelencephalon, turn caudal ward, and, with the sensory
fibers of the facial and glossopharyngeal nerves, complete the formation of
the solitary tract. The peripheral processes of the ganglion cells form the
greater part of the vagus trunks after the separation from it of the spinal
accessory fibers.

THE CEREBRAL NERVES

365

In aquatic vertebrates, special somatic sensory fibers from the lateral line organs
join the facial, glossopharyngeal, and vagus nerves, and their ganglion cells form part
of the geniculate, petrosal, and nodose ganglia. In human embryos the organs of the
lateral line are represented by ectodermal thickenings, or placodes, which occur tempo-

Gang, jugular e N. 10 Accessory root ganglia

Gang, superius N. 9

Gang, petrosum N
N. tympanicus

Br. to carotid plexus
N. glossopharyngeal

N. hypoglossus

N.laryng.sup./ m
Gang, nodosum N. 10 "-

Gang. Froriep

N. accessorius

Sympathetic trunk

FIG. 365. — A reconstruction of the peripheral nerves in an embryo of 17.5 mm. (Streeter).

X 16.7.

rarily over these ganglia. The nervous elements supplying these vestigial organs have
completely disappeared.

Segmentation of the Vertebrate Head. — The vertebrate head undoubtedly consists
of fused segments. This was suggested to the earlier workers by the arrangement of
the branchial arches (branchiomerism), and by the discovery, in the embryos of lower ver-
tebrates, of so-called head cavities, homologous with mesodermal segments. (Note also
the presence of neuromeres, p. 334.)

366 THE PERIPHERAL NERVOUS SYSTEM

Assuming that the branchiomeres are portions of the primary head segments — and
there are recent observations which tend to disprove this — their segmentation is still not
comparable to thlat of the trunk, for the branchial arches are formed by the segmentation of
splanchnic mesoderm, tissue which in the trunk never segments. The branchial arches,
therefore, represent a different sort of metamerism.

Only the first three head cavities persist. These form the eye muscles, innervated by
the third, fourth, and sixth cerebral nerves respectively. All the remaining muscles of the
head are derived from the branchiomeres. From what has been said, it is evident that one
cannot compare the relation of the cranial nerves to the branchiomeric muscles with the
relation of a spinal nerve to its myotomic muscles. For this reason, the cerebral nerves
furnish unreliable evidence as to the primitive number of cephalic segments. Various
investigators have set this number between eight and nineteen.

C. THE SYMPATHETIC NERVOUS SYSTEM

The sympathetic nervous system is composed of a series of ganglia
and peripheral nerves, the fibers of which supply gland cells and the smooth
muscle fibers of the viscera and blood vessels. It is also known as the
autonomic system, for it has a certain degree of independence of the central
nervous system.

The sympathetic ganglion cells are^derived from the cells of the gan-
glion crest. In fishes, discrete cellular masses become detached from the
spinal ganglia. At an early stage (6 to 7 mm.) in human development, on
the contrary, certain cells of the ganglion crest (and neural tube; Kuntz,
1910) migrate ventrally along the nerve roots and give rise to a series of
ganglia, which, in the region of the trunk, are segmentally arranged (Fig.
360).

The cells which are to form the ganglia of the sympathetic chain
migrate ventrally in advance of the ventral root fibers and take up a posi-
tion lateral to the aorta (Fig. 325). These sympathetic anlages are at
first distinct, but at 9 mm. unite with each other from segment to seg-
ment, forming a longitudinal ganglionated cord. After the formation of
the primitive rami communicaates by root fibers from the spinal nerves,
centripetal processes from the sympathetic cells grow back and join the
trunks of the spinal nerves. The visceral, spinal fibers later become mye-
linated and constitute the white rami; the sympathetic, centripetal fibers
remain unmyelinated and form separately the gray rami. Nerve fibers
appear in the paired longitudinal cords, which were at first purely cellular,
in such a manner that segmental masses of cells (sympathetic ganglia) be-
come linked by fibrous, commissural cords. The more peripheral ganglia
(cardiac and cceliac) and the sympathetic ganglia of the head may be found
in 1 6 mm. embryos (Fig. 366).

In the head region the sympathetic ganglia are not segmentally ar-
ranged, but are derived from cells of the cerebrospinal ganglia that mi-
grate to a ventral position (Fig. 365). These cells likewise give rise to nerve

THE SYMPATHETIC NERVOUS SYSTEM

367

fibers which constitute longitudinal commissures and connect the various
ganglia of the head with the ganglionated cord of the trunk region. The
small, cranial sympathetic ganglia are probably all derived from the anlage
of the semilunar ganglion (Fig. 366). The ciliary ganglion is related by a
ramus communicans to the ophthalmic division of the trigeminal nerve and

FIG. 366. — The sympathetic system in a 16 mm. human embryo (Streeter in Lewis and
Stohr). X 7. The ganglionated trunk is heavily shaded. The first and last cervical, thoracic,
lumbar, sacral and coccygeal spinal ganglia are numbered, a., Aorta; ace., accessory nerve;
car., caro'tid artery; cil., cilliary ganglion; coe., cceliac artery; Ht., heart; nod., nodose gang-
lion; ot., otic ganglion; pet., petrosal ganglion; s-m., submaxillary ganglion; s.mes., superior
mesenteric artery; sph-p., spheno-palatine ganglion; spl., splanchnic nerve; St., stomach.

receives fibers from the oculomotor nerve. Its cells are apparently de-
rived \ entirely from the semilunar ganglion. The spheno-palatine, sub-
maxillary, and otic ganglia probably take their origin from migrating cells
of the semilunar ganglion, but as they are connected with the geniculate
ganglion of the facial nerve it is possible that the latter contributes to
their formation also. The spheno-palatine ganglion is connected directly

368 THE PERIPHERAL NERVOUS SYSTEM

with the semilunar ganglion by two communicating rami. The submaxil-
lary ganglion is intimately related through the mandibular division of the
trigeminal nerve to the semilunar ganglion, while the otic ganglion is
united to the latter by a plexus and is related to the glossopharyngeal nerve
through its tympanic branch.

The 'cervical ganglia lose their segmental arrangement and represent
the fusion of from two to five ganglia of the cervical and upper thoracic
region. The more distally located prevertebral ganglia (of the cardiac,
cceliac, hypogastric, and pelvic plexuses) are derived from cells of the neural
crest which migrate to a greater distance ventrally (Fig. 366). The vis-
ceral ganglia (of the myenteric and submucous plexuses, and the pre verte-
bral cardiac plexus as well, are derived by Kuntz chiefly from migratory
cells from the hind-brain and from the vagus ganglia.

The sympathetic nerve cells give rise to a,xons and dendrites, and are
thus typically multipolar cells. Their axons possess a neurilemma sheath,
but remain unmyelinated.

D. THE CHROMAFFIN BODIES AND SUPRARENAL GLAND

Certain cells of the sympathetic ganglia, instead of becoming neurons,
are transformed into peculiar gland cells ; these produce an important inter-
nal secretion which affects the blood pressure. The secretion formed by
these cells causes them to stain brown when treated with chrome salts,
hence they are called chroma ffin cells. Cells of this type, derived from the
ganglionated cord of the sympathetic system, give rise to structures
known as chroma ffin bodies. Chromafrin derivatives of the cceliac plexus,
together with mesenchymal tissue, also form the anlage of the suprarenal
gland.

The Chromaffin Bodies of the ganglionated cords are rounded, cellular
masses partly embedded in the dorsal surfaces of the ganglia (Fig. 367).
At birth they may attain a diameter of i to i . 5 mm. In number they vary
from one to several for each ganglion.

Similar chromafrin bodies may occur in all the larger sympathetic
plexuses. The largest of these structures, found in the abdominal sym-
pathetic plexuses, are the aortic chromaffin bodies (of Zuckerkandl) .
These occur on either side of the inferior mesenteric artery, ventral to the
aorta and mesial to the metanephros. At birth they attain a length of
9 to 12 mm. and are composed of cords of chromaffin cells intermingled
with strands of connective tissue, the whole being surrounded by a con-
nective-tissue capsule. After birth the chromaffin bodies degenerate, but
do not disappear entirely.

THE CHROMAFFIN BODIES AND SUPRARENAL GLAND

369

The Glomus Caroticum. — Associated with the intercarotid sympathetic
plexus is a highly vascular chromaffin body known as the carotid gland.
Its anlage has been first observed in 20 mm. embryos.

The Suprarenal Gland is developed from chromaffin tissue, which
become its medulla, and from mesodermal tissue that give rise to its cortex.
In an embryo of 6 mm. the anlage of the cortex begins to form from ingrow-
ing buds of the peritoneal mesothelium. At about 9 mm. the glands are

FIG. 367. — Section through a chromaffin body in a 44 mm. human fetus (after Kohn). X 450.
P, Mother chromaffin cells; sy, sympathetic cells; b, blood vessel.

definite organs and their vascular structure is evident (Fig 201). The
cellular elements of the cortex are at first larger than the chromaffin cells
that give rise to the medulla. The anlages of the glands early project
from the dorsal wall of the ccelom between the mesonephros and mes-
entery; here they become relatively huge organs (Figs. 221, 232 and 233).
The differentiation of the cortex into its three characteristic layers is not
completed until between the second and third years. The inner reticular
zone is formed first, next the fasciculate zone, and last the glomerular zone
(50 mm.).

The chromaffin cells of the medulla are derived from the cceliac plexus
of the sympathetic system. In embryos of 15 to 19 mm. (Fig. 368),
masses of these cells begin to migrate from the median side of the supra-
renal anlage to a central position, and later surround the central vein

370

THE PERIPHERAL NERVOUS SYSTEM

which is present in embryos of 23 mm. The primitive chromaffin cells
are small and stain intensely. They continue their immigration until
after birth.

Anomalies. — Portions of the suprarenal anlage may be separated from the parent
gland and form accessory suprarenals. As a rule, such accessory glands are composed
only of cortical substance; they may migrate some distance from their original position,
accompanying the genital glands. In fishes the cortex and medulla persist normally as
separate organs.

•sy */

M

---.J,

^•*fM&B93SSs:&

y>''~:

' • •' .;*/*'* ' 'l* ~*' •'* * ' "" ^"^ x

" <

J I

O1'

FIG. 368. — Transverse section through the right suprarenal gland of a 15.5 mm. human embryo
(after Bryce). sy, sy', Groups of chromaffin sympathetic cells migrating into the gland.

E. DEVELOPMENT OF THE SENSE ORGANS

The sense cells of primitive animals, such as worms, are ectodermal
in"origin and position. Only those of the vertebrate olfactory organ have
retained this primitive relation. During phylogeny the cell-bodies of all
other such primary sensory neurones migrated inward to form the dorsal
ganglion (Parker), hence their peripheral processes either end freely in the
epithelium or appropriate new cells to serve as sensory receptors (taste;
hearing).

DEVELOPMENT OF THE SENSE ORGANS 371

The nervous structures of the sense organs consist of the general sense
organs of the integument, muscles, tendons, and viscera, and of the special
sense organs, which include the taste buds of the tongue, the olfactory
epithelium, the retina of the eye, and the epithelial lining of the ear
labyrinth.

I. GENERAL SENSORY ORGANS

Free nerve terminations form the great majority of all the general
sensory organs. When no sensory corpuscle is developed, the neurofibrils
of the sensory nerve fibers separate and end among the cells of the epithelia.

Lamellated corpuscles first arise during the fifth month as masses of
mesodermal cells clustered around a nerve termination. These cells in-
crease in number, flatten out, and give rise to the concentric lamellae
of these peculiar structures. In the cat these corpuscles increase in num-
ber by budding.

The tactile corpuscles, according to Ranvier, are developed from mes-
enchymal cells and branching nerve fibrils during the first six months
after birth.

II. TASTE BUDS

The anlages of the taste buds appear as thickenings of the lingual
epithelium in three month fetuses. The cells of the taste bud anlage
lengthen and later extend to the surface of the epithelium. They are
differentiated into the sensory taste cells, with modified cuticular tips, and
into supporting cells. The taste buds are supplied by nerve fibers of the
seventh, ninth, and tenth cerebral nerves; the fibers branch and end in
contact with the periphery of the taste cells.

In the fetus of five to seven months, taste buds are more widely dis-
tributed than in the adult. They are found in the walls of the vallate,
fungiform, and foliate papillae of the tongue, on the under surface of the
tongue, on both surfaces of the epiglottis, on the palatine tonsils and arches,
and on the soft palate. After birth many of the taste buds degenerate,
only those on the lateral walls of the vallate and foliate papillae, on a few
fungiform papillae, and on the laryngeal surface of the epiglottis persisting.

III. THE OLFACTORY ORGAN

The olfactory epithelium arises as paired thickenings or placodes of
the cranial ectoderm (Fig. 369 A). The placodes are depressed to form
the olfactory pits, or fosses, about which the nose develops (Fig. 89).

In embryos of 4 to 5 mm. (Fig. 369) the placodes are sharply marked
off from the surrounding ectoderm as ventro-lateral thickenings near the
top of the head. They are flattened and begin to invaginate in embryos

372

THE PERIPHERAL NERVOUS SYSTEM

of 6 to 7 mm. In 8 mm. embryos the invagination has produced a distinct
fossa, surrounded everywhere, save ventrally, by a marginal swelling.

The later development of the olfactory organ is associated with that
of the face. It will be remembered (p. 146) that each first branchial arch
forks into a maxillary and mandibular process. Dorsal to the oral
cavity is the fronto-nasal process of the head, lateral to it the maxillary
processes, and ventral to it are the mandibular processes (Fig. 97). With

Fore-brain

Vomero-nasal organ

Tekncephalon
Nasal fossa

Lot. nasal process
Med. nasal process
Maxillary process

Nasal fossa

Epithelial plate

FIG. 369. — Sections through the olfactory anlages of human embryos. A, 4.9 mm. (X 20);
5,6.5 mm. (X 13); C, 8.8mm. (X I3);£>and£, 10 mm. (A , B and C from Keibel and Elze).

the development of the nasal pits, the fronto-nasal process is divided into
paired lateral nasal processes and a single median frontal process, from which
are differentiated later the median nasal processes, or processus globulares
(Fig. 370). The nasal pits are at first grooves, each bounded mesially by
the median frontal process and laterally by the lateral nasal process and
the maxillary process (Fig. 3 70 A). The fusion of the maxillary processes
with the ventro-lateral ends of the median frontal process converts the
nasal grooves into blind pits, or fossae, shutting them off from the mouth
cavity (Fig. 370). Thus, in embryos of 10 to 12 mm. the nasal fossa has
but one opening, the external naris, and is separated from the mouth cavity
by an ectodermal plate (Fig. 369 D, E).

DEVELOPMENT OF THE SENSE ORGANS

373

When the ventro-lateral ends of the median frontal process enlarge
and become the median nasal processes they fuse with the lateral nasal
processes and reduce the size of the external nares (Pig: 370 B). Exter-
nally, the nares are now bounded ventrally by the fused nasal processes.
The epithelial plates which separate the nasal fossae from the primitive
mouth cavity become thin, membranous structures caudally, and, rup* ur-
ing, produce two internal nasal openings, the primitive choance (Fig. 153).
Cranially, the epithelial plate is split by ingrowing mesoderm of the maxil-
lary process and median nasal process which replaces it, thereby forming
the primitive palate (Fig. 369 D). The primitive palate forms the lip and

Nasal septum

Ext. naris

Oral cavity

Maxillary
process

Mandibl

Med. nasal process

Oral cavity

FIG. 370. — Two stages in the development of the jaws and nose. A, Ventral view of the end
of the head of a 10.5 mm. human embryo (after Peter) ; B, of an 1 1.3 embryo (after Rabl).

the premaxillary palate. The nasal fossae now open externally through
the external nares and internally into the roof of the mouth cavity through
the primitive choanas.

Coincident with these changes, the median frontal process has be-
come relatively smaller, and that portion of it between the external nares
and the nasal fossas forms the nasal septum (Fig. 370). As the facial re-
gion grows and elongates, the primitive choanae becomes longer and form
slit-like openings in the roof of the mouth cavity. By the development
and fusion of the palatine processes (described on p. 148) the dorsal por-
tion of the mouth cavity is separated off and constitutes the nasal passages
(cf. Figs. 371 and 372). The nasal passages of the two sides for a time
communicate through the space between the hard palate and the nasal

374

THE PERIPHERAL NERVOUS SYSTEM

septum. Later, the ventral border of the septum fuses with the hard
palate and completely separates the nasal passages (Fig. 372). The
nasal passages of the adult thus consist of the primitive nasal fossae plus a
portion of the primitive mouth cavity which has been appropriated second-
arily by the development of the hard palate. . The passages of the adult
thus open caudally by secondary choance into the cavity of the pharynx.

Olfactory epithelium
V omero-nasal organ

Inferior cone,
Palatine process

Dental lamina

Cartilage of nasal
sept ion

Cartilage of vomero-
nasal -organ

Naso-lacrimal duct

— Tongue

. Meckel' s cartilage

FIG. 371. — Transverse section through the nasal passages and palatine processes of a 20 mm.
human embryo. In the nasal septum is a section of the vomero-nasal organ (of Jacobson).
X 30.

Part of the epithelium which lines the nasal fossae is transformed into
the sensory olfactory epithelium (Fig. 371). The remainder covers the
conchae and lines the vomero-nasal organ (of Jacobson), the ethmoidal
cells, and the cranial sinuses.

The Vomero-nasal Organ (of Jacobson) is a rudimentary epithelial
structure which first appears in 8.5 to 9 mm. embryos on the median wall
of the nasal fossa (Fig. 369 C, E). The groove deepens and closes cau-
dally to form a tubular structure in the cranial portion of the nasal septum
(Fig. 371). During the sixth month it attains a length of 4 mm. Nerve
fibers, arising from cells in its epithelium, join the olfactory nerve, and it
also receives fibers from the n. terminalis. In late fetal stages it often
degenerates, but may persist in the adult (Merkel, Mangakis). Special

DEVELOPMENT OF THE SENSE ORGANS

375

cartilages are developed for its support (Fig. 371). The organ of Jacob-
son is not functional in man, but in many animals evidently constitutes a
special olfactory organ.

§j£r~ Olfactory epithelium

Ethmo-turbinal I
Nasal septum

JJS — Naso-lacrimal duct
Maxillo-turbinal

FIG. 372. — Transverse section through the nasal passages of a 65 mm. humar retus. X 14.

The Conchae are structures which are poorly developed in man.
They appear on the lateral and median walls of the primitive nasal fossae.
The inferior concha, or maxillo-turbinal, is developed first in human

Horizontal ethmoid plate

•Lateral lamella

Hard pal

FIG. 373. — Right nasal passage of a fetus at term (after Killian). /, Maxillo-turbinal; II-VI,
ethmo-turbinals. The slight elevation at the left of / and // is the naso-turbinal.

embryos (Figs. 371 and 372). It forms a ridge along the caudal two-
thirds of the lateral wall and is marked off by a ventral groove which
becomes the inferior nasal meatus (Fig. 373). The naso-turbinal is very

376 THE PERIPHERAL NERVOUS SYSTEM

rudimentary and appears as a slight elevation dorsal and cranial to the
inferior concha (Fig. 373). Dorsal to the inferior concha arise five ethmo-
turbinals, which grow progressively smaller caudally. According to
Peter, the ethmo-turbinals arise on the medial wall of the nasal fossa, and,
by a process of unequal growth, are transferred to the lateral wall (Fig.
372). Accessory conchae are also developed (Killian).

In adult anatomy, the inferior concha forms from / (Fig. 373), the middle concha from
II, and the superior concha from /// and I V.

In addition to the ridges formed by the conchae, there are developed in the grooves
between the ethmo-turbinals the ethmoidal cells. After birth the frontal recess (located
between / and //, Fig. 373) gives rise to the frontal sinus. During the third month the
maxillary sinus grows out from the inferior recess of the same groove. The most caudal
end of the nasal fossa becomes the sphenoidal sinus, which, as it increases in size, invades
the sphenoid bone. These cells and sinuses form as excavations of the bone which become
lined with simultaneously advancing epithelial evaginations.

The cells of the olfactory epithelium acquire cilia, but only a small area, representing
the primitive epithelial invagination, functions as an olfactory sense organ. The olfactory
cells of this area give rise to the fibers which constitute the olfactory nerve (cf. p. 357).

IV. THE EYE

The anlage of the human eye appears in embryos of 2.5 mm. as a
thickening and evagination of the neural plate of the fore-brain. At this
stage the neural groove of the fore-brain has not closed (Figs. 324, 330
and 382). At 4 mm. the optic vesicles are larger, but still may be con-
nected by a wide opening with the brain cavity (Fig. 374 A, B). In
the section shown in Fig. 374 C, the optic vesicle is attached to the ventral
brain wall by a distinct optic stalk (cf. Fig. 343)..

The thickening, flattening, and invagination of the distal and ventral
wall of the optic vesicle gives rise to the optic cup (Fig. 374 B-D). The
area of invagination also extends ventrally along the optic stalk and pro-
duces a groove known as the chorioid fissure (Figs. 331, 375 and 377).
At the same time that the optic vesicle is converted into the optic cup,
the ectoderm overlying the vesicle thickens, as seen in Fig. 3 74 B, forming
the lens plate, or optic placode. This plate invaginates to form the lens
pit, the external opening of which closes in embryos of 6 to 7 mm. (Fig.
374 D), producing the lens vesicle, which at first remains attached to the
overlying ectoderm.

The invagination of the optic vesicle is a self-governed process. On the contrary,
contact of the optic vesicle with the overlying ectoderm stimulates the latter to lens forma-
tion, even in regions that normally never differentiate a lens (Lewis, 1907). It is possible,
however, for a lens to arise independently of this contact stimulus (Stockard, IQIO)

DEVELOPMENT OF THE SENSE ORGANS

377

In an embryo of 10 mm. (Fig. 376) the essential plan of the eye is
foreshadowed. The lens vesicle has separated from the ectoderm, which
will form the epithelium of the cornea. The lens vesicle in earlier stages

Anlage of lens

Fore-brain

Optic vesicle

Optic vesicle

Optic stalk Optic vesicle

Retinal layer

Lens vesicle

FlG. 374. — vStages in the early development of the human eye. A, B, 4 mm. (X 27); C, 5 mm.
(X 23); D, 6.25 mm. (X 18); (after Keibel and Elze).

(Fig. 374 D) is closely applied to the inner wall of the optic cup, but now
it has separated from it, leaving a space in which the vitreous body de-
velops. The inner retinal layer of the optic cup has become very thick

Diencephalon — £;

'rystalline lens
'Chorioid fissure

Optic stalk

FIG. 375. — The optic stalk, cup and lens of a human embryo of 12.5 mm. Thechorioid fissure
has not yet extended along the optic stalk (from Fuchs, after Hochstetter). X 9°-

and is applied to the outer layer, so that the cavity of the primitive optic
vesicle is nearly obliterated (Fig. 376). Pigment granules have begun
to appear in the outer layer of cells to form the pigment layer of the retina.

378

THE PERIPHERAL NERVOUS SYSTEM

Mesenchyma Lens vesicle Vitreous body Optic stalk Optic recess of brain

Epithelium of cornea Pigment layer of retina Nervous layer of retina

FIG. 376. — A transverse section through the optic cup, stalk and lens of a ro mm. human

embryo. X 100.

'Epithelial layer of lens Pigment layer of the retina
Ectoderm

Nervous layer of retina

horioid fissure

'Central artery
Vitreous body
Layer of lens fibers

Mesenchyme

FIG. 377. — Transverse section passing through the optic cup at the level of the chorioid
fissure. The central artery of the retina is seen entering the fissure and sending a branch to
the proximal surface of the lens; from a 12.5 mm. human embryo. X 105.

DEVELOPMENT OF THE SENSE ORGANS

379

Epithelial layer

Mesenchymal tissue surrounds the optic cup and is beginning to make
its way between the lens vesicle and the ectoderm. Here, the anterior
chamber of the eye develops' later as a cleft in'the mesoderm. The dis-
tal mesenchymal tissue .(next the ectoderm) forms the substqntia propria
of the cornea and its posterior epithelium, while the proximal mesen-
chyma (next the lens) differentiates into tbe, vascular capsule of the lens.
The mesenchyme surrounding the optic cup is continuous with that which
forms the cornea; later it gives rise to the sclerotic layer, to the chorioid
layer, and to the anterior layers of the ciliary body and iris.

Both the inner and outer layers of the optic cup are continued into
the optic state, as seen in Fig.
376. This is due to the trough-'
like invagination of the ventral
wall of the" optic stalk, the
chorioid fissure, when the optic
vesicle is transformed into the
optic cup (Fig. 375). Into the
chorioid fissure grows the central
artery of the retina, carrying
with it into the posterior cavity
of the eye a small amount of
mesenchyme (Fig. 377).
Branches from this vessel ex-
tend to the posterior surface
of the lens and supply it with
nutriment for its growth. At a
later stage the chorioid fissure
closes, so that the distal rim of
the optic cup forms a complete
circle.

The lens vesicle, and its early development from the ectoderm, have
been described. Its proximal wall is much thickened in 10 mm. embryos
(Fig. 376), and these cells form the lens fibers which will soon obliterate
the cavity of the vesicle, as in embryos of 15 to 17 mm. (Fig. 378). The
cells of the distal layer remain of a low columnar type and constitute
the epithelial layer of the lens. When the lens fibers attain a length of
o.i 8 mm. they cease forming new fibers by cell division. New fibers
thereafter arise from the cells of the epithelial layer at its equatorial
line of union with the lens fibers. The nuclei are arranged in a layer,
convex toward the outer surface of the eye, but they later degenerate,
the degeneration beginning centrally. Lens sutures are formed on the
proximal and distal faces of the lens when the longer, newly formed,

Lens fibers

Ectoderm

FIG. 378. — Section through the lens and corneal
ectoderm of a 16 mm. pig embryo. Xi4O.

380 THE PERIPHERAL NERVOUS SYSTEM

peripheral fibers overlap the ends of the shorter, central fibers. By an
intricate but orderly arrangement of fibers these sutures are later trans-
formed into lens-stars of three, and finally of six or nine rays (Fig. 379).
The structureless capsule of the lens is probably derived from the lens cells .
The lens, at first somewhat triangular in cross section, becomes nearly
spherical at three months (Fig. 379).

Anterior epithelium
of cornea

Raphe between
the fused lids

Posterior epithelium
of cornea

Vitreous
body

FIG. 379. — Section through the distal half of the eyeball and eyelids of a 65 mm. human fetus.

X 35-

The origin of the vitreous body, whether ectodermal or mesodermal,
has long been in doubt. Modern evidence apparently points to its deri-
vation from both sources.

It is certain that vitreous tissue is formed before mesenchyma is present in the cavity
of the optic cup. Szily (1908) regards this primitive vitreous body as a derivative of both
retinal and lens cells, it forming a non-cellular network of cytoplasmic processes which are
continuous with the cells of the lens and retina. With the ingrowth of the central artery
of the retina, from which the artery of the lens passes to the proximal surface of the lens
and branches on it, a certain amount of mesenchymal tissue invades the optic cup, and this
tissue probably contributes to the development of the vitreous body (Fig. 377).

DEVELOPMENT OF THE SENSE ORGANS 381

The mesenchyma accompanying the vessels to the proximal surface
of the lens, and that on its distal surface, give rise to the vascular capsule
of the lens (Fig. 377). On the distal surface of the lens this is supplied by
branches of the anterior ciliary arteries and is known as the pupillary mem-
brane; the vessels disappear and the membrane degenerates just before
birth. The artery of the lens also degenerates, its wall persisting as the
transparent hyaloid canal. Fibrillas extending in the vitreous humor
from the pars ciliata of the retinal layer to the capsule of the lens persist as
the zonula ciliaris, or suspensory ligament of the lens.

Differentiation of the Optic Cup. — We have seen that of the two layers
of the optic cup, the outer becomes the pigment layer of the retina. Pig-
ment granules appear in its cells in embryos of 7 mm. and the pigmentation
of this layer is marked in 12 rr.m. embryos (Fig. 377).

Com cell
Rod cell

Rod cell
Fiber of Miiller

Amacrine cell
Ganglion cell
Optic fibers^

—External limiting
membrane

•Layer of rod and cone
cells

Internal limiting
membrane

FIG. 380. — Section of the nervous layer of the retina from a 65 mm. human fetus. At the left
is shown diagrammatically the cellular elements of the retina according to Cajal. X 440.

The inner, thicker layer of the optic cup, the retinal layer proper, is
subdivided into a distal zone, the pars cceca, which is non-nervous, and
into the pars optica, or the true nervous portion. The line of demarcation
between the pars optica and the pars caeca is a serrated circle, the ora
serrata. By the development of the ciliary bodies the blind portion of the
retinal layer, the pars caeca, is differentiated into a pars ciliaris and pars
iridica retina. The former, with a corresponding zone of the pigment
layer, covers the ciliary bodies. The pars iridica forms the proximal layer
of the iris and blends intimately with the pigment layer in this region, its
cells also becoming heavily pigmented (Fig. 379).

The pars optica, or nervous portion of the retina, begins to differen-
tiate proximally and the differentiation extends distally. An outer cellular
layer and an inner fibrous layer may be distinguished in 12 mm. embryos

382

THE PERIPHERAL NERVOUS SYSTEM

(Fig. 377). These correspond to the cellular layer (ependymal and mantle
zones) and marginal layer of the neural tube. In fetuses of 65 mm. (C R)
the retina shows three layers, large ganglion cells having migrated in
from the outer cellular layer of rods and cones (Fig. 380). In a fetus of
the seventh month all the layers of the adult retina may be recognized
(Fig. 381). As in the wall of the neural tube, there are differentiated in
the retina supporting tissue and nervous tissue. The supporting elements,
or fibers of Muller, resemble ependymal cells and are radially arranged

(Figs. 380 and 381). Their
terminations form internal
and external limiting mem-
branes.

The neuroblasts of the
retina differentiate into an
outer layer of rod and cone
cells, the visual cells of the
retina, which are at first
unipolar (Fig. 381). In-
ternal to this layer are
layers of bipolar and mul-
tipolar cells. The inner
layer of multipolar cells
constitutes the ganglion
cell layer. Axons from

Pigment layer
Rods and Cones

Outer nuclear layer

Outer reticidar layer
Inner nuclear layer

Inner reticular layer
Ganglion cell layer

Nerve fiber layer
Fibers of Midler

'Internal limiting membrane
FIG. 381. — Section through the pars optica of the retina
from a seven months' fetus. X 440.

these cells form the inner
nerve fiber layer of optic
fibers. These converge to
the optic stalk, and, in
embryos of 15 mm. grow
back in its wall to the brain. The cells of the optic stalk are converted
into neuroglia supporting tissue and the cavity in the stalk is gradually
obliterated. The optic stalk is thus transformed into the optic nerve (cf .
P- 358).

The Sclerotic and Chorioid Layers, and their Derivatives. —After the
mesenchyme grows in between the ectoderm and the lens (Fig. 377), the
lens and optic cup are surrounded by a condensed layer of mesenchymal
tissue, which gives rise to the supporting and" vascular layers of the eye-
ball. By condensation and differentiation of its outer layers, a dense layer
of white fibrous tissue is developed, which forms the sclera. This cor-
responds to the dura mater of the brain. In the mesenchyme of 25 mm.
embryos, a cavity appears distally which separates the condensed layer of
mesenchyme, continuous with the sclerotic, from the vascular capsule of

DEVELOPMENT OF THE SENSE ORGANS 383

the lens (Fig. 379). This cavity is the anterior chamber of the eye and sepa-
rates the anlage of the cornea from the lens capsule.

An inner layer of mesenchyme, between the anlage of the sclerotic and
the pigment layer of the retina, becomes highly vascular during the sixth
month. Its cells become stellate in form and pigmented, so that the tissue
is loose and reticulate. This vascular tissue constitutes the chorioid layer,
in which course the chief vessels of the eye. The chorioid layer corresponds
to the pia mater of the brain. Distal to the ora serrata of the retinal layer,
the chorioid is differentiated into: (i) the vascular folds of the ciliary
bodies; (2) the smooth fibers of the ciliary muscle; (3) the stroma of the
iris. The proximal pigmented layers of the iris are derived. from the pars
iridica retinae and from a corresponding zone of the pigment layer. Of
these, the pigment layer cells give rise to the sphincter and dilator muscles
of the iris. These smooth muscle fibers are thus of ectodermal origin.

The Eyelids appear as folds of the integument in 20 mm. embryos.
The lids come together and the epidermis at their edges is fused in 33 mm.
embryos (Fig. 379). Later, when the epidermal cells are cornified, sepa-
ration of the eyelids takes place. A third, rudimentary eyelid, corespond-
ing to the functional nictitating membrane of lower vertebrates, forms the
plica semilunaris. The epidermis of the eyelids forms a continuous layer
on the inner surfaces, known as the conjunctiva, which in turn is continuous
with the anterior epithelium of the cornea.

The Eyelashes, or cilia, develop like ordinary hairs and are provided
with small sebaceous glands. In the tarsus, or dense connective-tissue
layer of the eyelids, which lies close to the conjunctival epithelium, there
are developed about 30 tarsal (Meibomian) glands. These arise as in-
growths of the epithelium at the edges of the eyelids, while the latter are
still fused.

The Lacrimal Glands appear in embryos of about 25 mm., according
to Keibel and Elze. They arise as five or six ingrowths of the conjunctiva,
dorsally and near the external angle of the eye. The anlages are at first
knob-like, but rapidly lengthen into solid epithelial cords. They begin to
branch in 30 mm. embryos. At stages between 50 and 60 mm. (C R),
additional anlages appear which also branch.

In 38 mm. (C R) embryos, a septum begins to partition the gland into orbital and pal-
pebral portions. This septum is complete at 60 mm. (C R), the five or six anlages first de-
veloped constituting the peripheral orbital part. Lumina appear in the glandular cords in
fetuses of 50 mm. (C R) by the degeneration of the central cells. Accessory lacrimal glands
appear a month before term. The lacrimal gland is not fully differentiated at birth, being
only one-third the size of the adult gland. In old age marked degeneration occurs.

The N ' aso-lacrimal Duct arises in 12 mm. embryos as a ridge-like
thickening of the epithelial lining of the naso-lacrimal groove (Fig. 149);

384

THE PERIPHERAL NERVOUS SYSTEM

which, it will be remembered, extends from the inner angle of the eye to
the olfactory fossa. This thickening becomes cut off, and, as a solid cord,
sinks into the underlying mesoderm (Schaeffer). Secondary sprouts, grow-
ing out from this cord to the eyelids, form the lacrimal canals. A lumen,
completed at birth, appears during the third month (Fig. 372).

Anomalies. — Lack of pigment in the retina and iris is usually associated with general
albinism. If the chorioid fissure fails to close properly, there results a gaping, and hence
unpigmented, defect, or coloboma, in the iris, ciliary body, or chorioid. In cyclopia, a
single median eye replaces the usual paired conditon. All intergrades exist from closely
approximated, separate eyes to perfect unity. The mode of genesis, whether from the
fusion of separate eyes or from the inhibited separation of a common anlage into its
bilateral derivatives, is in dispute. In cases of cyclopia the nose is usually a cylindrical
proboscis,-, situated above the med'an eye.

V. THE EAR

The human ear consists of a sound-conducting apparatus and of a
receptive organ. The conveyance of sound is the function of the external
and middle ears. The end organ proper is the inner ear, with the auditory

Hind-brain

A caustic ganglion A uditory placode

Otic vesicle

ptic vesicle

FIG. 382. — Two stages in the early development of the internal ear (after Keibel and Elze)«
A, Horizontal section through the open neural tube of a 2 mm. human embryo, (X 27); B,
through the hind-brain of a 4 mm. human embryo (X 33).

apparatus residing in the cochlear duct. Besides this acoustic function
the labyrinthine portion of the inner ear acts as an organ of equilibration.
The Inner Ear. — The epithelium of the internal ear is derived from the
ectoderm. Its first anlage appears in embryos of 2 mm. as a thickened
ectodermal plate, the auditory placode (Fig. 382 A). These are developed,
dorsal to the second branchial grooves, at the sides of the hind-brain
opposite the fifth neuromeres (Fig. 383). The placodes are invaginated

DEVELOPMENT OF THE SENSE ORGANS

385

to form hollow vesicles which close in the embryos of 2.5 to 3 mm., but
remain temporarily attached to the ectoderm (Fig. 382 B).

The auditory vesicle, or otocyst, when closed and detached, is nearly
spherical, but approximately at the point where it was attached to the

Ectoderm

Wall of hind-brain

Neur. 5

FIG. 383. — Four sections through the right otic vesicle of a 4 mm. human embryo (after
Keibel and Elze). X about 30. r.e., Endolymphatic recess; o.v., otic vesicle; Neur. 1 4,
Neur. 5, neuromeres.

ectoderm a recess, the ductus endolymphaticus, is formed. The point of
origin of this recess is shifted later from a dorsal to a mesial position (Figs.
384 and 385 a). The endolymph duct corresponds to that of selachian
fishes, which remains per-
manently open to the ex-
terior. In man, its ex-
tremity is closed and dilated
to form the endolymph sac
(Fig. 385 /)•

In an embryo of about
7 mm. the vesicle has
elongated, its narrower
ventral process constitut-
ing the anlage of the
cochlear duct (Fig. 385 a).
The wider, dorsal portion
of the otocyst is the vest-
ibular anlage, which shows
indications dorsally of the
developing semicircular

Wall of mydencephalon

Endolymph duct

Vestibular anlage

Cochlear anlage

FIG. 384. — Right half of a transverse section through
the hind-brain and otic vesicles, showing the position
of the endolymph duct. From a 6.9 mm. human
embryo (His).

canals. These are formed

in ii mm. embryos as two

pouches — the anterior and posterior canals from a single pouch at the

dorsal border of the otocyst, the lateral canal later from a lateral out-

pocketing (Fig. 385 c}. Centrally, the walls of these pouches flatten and

fuse to form epithelial plates. In the three plates thus produced canals

are left peripherally, communicating with the cavity of the vestibule.

300 THE PERIPHERAL NERVOUS SYSTEM

Soon, the epithelial plates are resorbed, leaving the semicircular canals as
in Fig. 385 d, e. Dorsally, a notch separates the anterior and posterior
canals. Of these canals, the anterior is completed before the posterior.
The lateral canal is the last to develop.

In a 20 mm. embryo (Fig. 385 e) the three canals are present and the
cochlear duct has begun to coil like a snail shell. It will be seen that the
anterior and posterior canals have a common opening dorsally into the
vestibule, while their opposite ends, and the cranial end of the lateral canal,
are dilated to form ampullae. In each ampulla is located an end organ, the
crista ampullaris, which will be referred to later. By a constriction of its
wall the vestibule is differentiated into a dorsal portion, the utriculus, to
which are attached the semicircular canals, and a ventral portion, the sac-
culus, connected with the cochlear duct (Fig. 385 e, /). At 30 mm. the
adult condition is nearly attained. The sacculus and utriculus are more
completely separated, the canals are relatively longer, their ampullae more
prominent, and the cochlear duct is coiled about two and a half turns
(Fig. 385 /). In the adult, the sacculus and utriculus become completely
separated from each other, but each remains attached to the endolymph
duct by a slender canal that represents the prolongation of their respective
walls. Similarly, the cochlear duct is constricted from the sacculus, the
basal end of the former becomes a blind process, and a canal, the ductus
reuniens, alone connects the two.

The epithelium of the labyrinth at first is composed of a single layer of
low columnar cells. At an early stage, fibers from the acoustic nerve grow
between the epithelial cells in certain regions and these become modified
to produce special sense organs. These end organs are the cristce ampullares
in the ampullae of the semicircular canals, the maculcs acusticcs in the
utriculus and sacculus, and the spiral organ (of Corti) in the cochlear duct.

The cristae and maculae are static organs, or sense organs for main-
taining equilibrium. In each ampulla, transverse to the long axis of the
canal, the epithelium and underlying tissue form a curved ridge, the crista.
The cells of the epithelium are differentiated into: (i) sense cells, with
bristle-like hairs at their ends; and (2) supporting cells. About the bases
of the sensory cells branch nerve fibers from the vestibular division of the
acoustic nerve. The maculae resemble the cristae in their development save
that larger areas of the epithelium are differentiated into cushion-like end
organs. Over the maculae, concretions of lime salts may form otoconia
which remain attached to the sensory bristles.

The true organ of hearing, the spiral organ, is developed in the basal
epithelium of the cochlear duct, basal having reference here to the base
of the cochlea. The development of the spiral organ has been studied
carefully only in the lower mammals. According to Prentiss (1913), in

endolymph

vestib.
pouch "

qroove

c.sc.post., absorpt.foci

I at groove

"f. 307™. lateral.

FIG. 385.— Six stages in the development of the internal ear (Streeter). X 25. The
figures show lateral views of models of the left membranous labyrinth — a at 6.6 mm. ; b, at 9
mm. ; c at 1 1 mm. ; d at 13 mm. ; e at 20 mm. ; and / at 3o'mm. The colors yellow and red are
used to indicate respectively the cochlear and vestibular divisions of the acoustic nerve and its
ganglia, absorp. focus, Area of wall where absorption is complete; crus, crus commune; c.sc.lat.,
ductus semicircularis lateralis; c.sc.post., ductus semicircularis posterior; c.sc.sup., ductus semi-
circularis superior or anterior: cochlea, ductus cochlearis; each, pouch, cochlear anlage; endolymph.,
appendix endolymphaticus; sacc., sacculus; sac. endol., saocus endolymphaticus; sinus ut. lat.,
sinus utriculi lateralis; utric., utriculus.

DEVELOPMENT OF THE SENSE ORGANS 387

pig embryos of 5 cm. the basal epithelium is thickened, the cells becoming
highly columnar and the nuclei forming several layers. In later stages,
7 to Q cm., inner and outer epithelial thickenings are differentiated, the
boundary line between them being the future spiral tunnel (Fig. 386 A).
At the free ends of the cells of the epithelial swellings there is formed a
cuticular structure, the membrana tectoria, which appears first in embryos
of 4 to 5 cm. The cells of the inner (axial) thickening give rise to the
epithelium of the spiral limbus, to the cells lining the internal spiral sulcus,
and to the supporting cells and inner hair cells of the spiral organ (Fig.
386 B, C). The outer epithelial thickening forms the pillars of Corti,
the outer hair cells, and supporting cells of the spiral organ. Differentia-
tion begins in the basal turn of the cochlea and proceeds toward the apex.
The internal spiral sulcus is formed by the degeneration and metamorphosis
of the cells of the inner epithelial thickening which ie between the labium
vestibulare and the spiral organ (Fig. 386 B, C). These cells become
cuboidal, or flat, and line the spiral sulcus, while the membrana tectoria
loses its attachment with them. The membrana tectoria becomes
thickest over the spiral organ, and in full term fetuses is still attached to
its outer cells (Fig. 386 Q.

Hardesty (1915), on the contrary, asserts that the membrana tectoria is not attached
permanently to the cells of the spiral organ.

From what is known of the development of the spiral organ in human embryos, it
follows the same lines of development as described for the pig. It must develop relatively
late, however, for, in the cochlear duct of a newborn child figured by Krause, the spiral
sulcus and the spiral tunnel are not yet present.

The mesenchyme surrounding the labyrinth is differentiated into a
fibrous membrane directly surrounding the epithelium, and into the
perichondrium of the cartilage which develops about the whole internal
ear. Between these two is a more open mucous tissue which largely
disappears, leaving the perilymph space. The membranous labyrinth is
thus suspended in the fluid of the perilymph space. The body labyrinth
is produced by the conversion of the cartilage capsule into bone. In the
case of the cochlea, large perilymph spaces form above and below the cochlear
duct. The duct becomes triangular in section as its lateral wall remains
attached to the bony labyrinth, while its inner angle is adherent to the
modiolus. The upper perilymph space is formed first and is the scala
vestibuli; the lower space is the scala tympani. The thin wall separating
the cavity of the cochlear duct from that of the scala vestibuli is the
vestibular membrane (of Reissner). Beneath the basal epithelium of the
cochlear duct, a fibrous structure, the basilar membrane, is differentiated
by the mesenchyme. The modiolus is not preformed as cartilage, but

THE PERIPHERAL NERVOUS SYSTEM

n. cock.

FIG. 386. — Three stages in the differentiation of the basal epithelium of the cochlear duct
to form the spiral organ (of Corti), internal spiral sulcus and labium vestibulare. A, Section
through the cochlear duct of an 8.5 cm. pig fetus (X 120); B, from a 20 cm. fetus (X 140);
C, from a 30 cm. fetus (near term) ( X 140). ep.s.sp., Epithelium of spiral sulcus; h.c., hair cells;
i.ep.c., inner epithelial thickening; i.h.c., inner hair cells; i.pil., inner pillar of Corti; lab. vest.,
labium vestibulare; limb, sp., Hmbus spiralis; m.bas., basilar membrane; nt.tect., membrana
tectoria; m.vest., vestibular membrane; n.coch., cochlear division of acoustic nerve; o.ep.c.,
outer epithelial thickening; o.h.c., outer hair cells; s.sp., sulcus spiralis; sc.tymp., scala tympani;
sf.H., stripe of Hensen; t.sp. spiral tunnel.

DEVELOPMENT OF THE SENSE ORGANS

389

Malleus

Br. arch. I
(Meckel's cartil

Tympa

Slopes

is developed directly from the mesenchyme as a membrane bone. The
development of the acoustic nerve has been described on p. 358 with the
other cerebral nerves.

The Middle Ear. — The middle ear cavity is differentiated from the
first pharyngeal pouch which appears in embryos of 3 mm. The pouch
enlarges rapidly up to the seventh week, is flattened horizontally, and
is in contact with the ectoderm (Fig. 168). During the latter part of the
second month, in embryos of 24 mm., the wall of the tympanic cavity is
constricted to form the auditory (Eustachian) tube. This canal lengthens
and its lumen becomes slit-like during the fourth month. The tympanic
cavity is surrounded by loose areolar connective tissue in which the
auditory ossicles are developed and
for a time are embedded. Even in
the adult, the ossicles, muscles, and
chorda tympani nerve retain a
covering of mucous epithelium con-
tinuous with that lining the tympanic
cavity. The pneumatic cells are
formed at the close of fetal life.

. The development of the auditory
ossicles has been described by
Broman (1899), with whose general

conclusions most recent workers agree. The condensed mesenchyma
of the first and second branchial arches gives rise to the ear ossicles.
The malleus and incus are differentiated from the dorsal end of the
first arch (Fig. 387). The cartilaginous anlage of the malleus is continuous
ventrally with Meckel's cartilage of the mandible. Between the malleus
and incus is an intermediate disk of tissue, which later forms an articula-
tion. When the malleus begins to ossify, it separates from Meckel's
cartilage. The incus is early connected with the anlage of the stapes,
and the connected portion becomes the crus longum. Between this and
the stapes an articulation develops.

The stapes and Reichert's cartilage are derived from the second
branchial arch (Fig. 387). The mesenchymal anlage of the stapes is
perforated by the stapedial artery, and its cartilaginous anlage is ring-
shaped. This form persists until the middle of the third month, when
it assumes its adult structure and the stapedial artery disappears.

The muscle of the malleus, the tensor tympani, is derived from the first branchial arch;
the stapedial muscle from the second arch. The further fact that these muscles are inner-
vated by the trigeminal and facial nerves, which are the nerves of the first and second arches
respectively, points toward a similar origin for the ear ossicles. These relations strengthen
the general belief in a branchial arch origin.

Br. arch II
(Reichert's cartilage)

FIG. 387. — -Diagram showing the branchial-
arch origin of the auditory ossicles.

390

THE PERIPHERAL NERVOUS SYSTEM

Fuchs (1905), studying rabbit embryos, on the contrary, concludes:- (i) the stapes is
derived from the capsule of the labyrinth; (2) the malleus and incus arise independently
of the first branchial arch.

The External Ear. — The external ear is developed from the first
ectodermal branchial groove and its adjoining tissue. The auricle arises
from six elevations, which appear, three on the mandibular, and three on
the hyoid arch (Fig. 388). Modern accounts of the transformation of
these hillocks into the adult auricle agree in the main.

FIG. 388. — Stages in the development of the auricle. (Adapted in part after His.) A,
II mm.; B, 13.6 mm.; C, 15 mm.; D, adult. I, 2, 3, elevations on the mandibular arch; 4, 5, 6,
elevations on the hyoid arch; of, auricular fold; ov, otic vesicle; I, tragus; 2, 3, helix; 4, 5, anti-
helix; 6, antitragus.

Caudal to the hyoid anlages a fold of the hyoid integument is formed,
t he auricular fold, or hyoid helix. A similar fold forms later, dorsal to the
first branchial groove, and unites with the auricular fold to form with it
the free margin of the auricle. The point of fusion of these two folds
marks the position of the satyr tubercle, according to Schwalbe. Darwin's
tubercle appears at about the middle of the margin of the free auricular
fold, and corresponds to the apex of the auricle in lower mammals. The
tragus is derived from mandibular hillock i ; the helix from mandibular
hillocks 2 and 3 ; the antihelix from hyoid hillocks 4 and 5 ; the antitragus
from hyoid hillock 6. The lobule represents the lower end of the auricular
fold.

DEVELOPMENT OF THE SENSE ORGANS 391

The external auditory meatus is formed as an ingrowth of the first
branchial groove. In embryos of 1 2 to 1 5 mm. the wall of this groove is in
contact dorsally with the entoderm of the first pharyngeal pouch. Later,
however, this contact is lost, and, during the latter part of the second
month according to Hammar, an ingrowth takes place from the ventral
portion of the groove to form a funnel-shaped canal.

The lumen of this tube is temporarily closed during the fourth and fifth months, but
later re-opens. During the third month a cellular plate at the -extremity of the primary
auditory meatus grows in and reaches the outer end of the tympanic cavity. During the
seventh month a space is formed by the splitting of this plate and the secondary, inner por-
tion of the external meatus is thus developed.

The tympanic membrane is formed by a thinning out of the mesodermal
tissue in the region where the wall of the external auditory meatus abuts
upon the wall of the tympanic cavity. Hence it is covered externally
by ectodermal and internally by entodermal epithelium.

INDEX

ABDOMINAL pregnancy, 231
Abducens nerve, 118, 361
Accessor! us nerve, 118
Accessory duct of Santorini, 180

hemiazygous vein, 271
Acoustic nerve, 94, 118, 358
Acrania, 352
Adipose tissue, 286
After pains, 242
After-birth, 74, 242
Alae nasi, 147

Alar plate, 323, 332, 335, 339
Albinism, 294, 295, 384
Allantoic stalk, 68, 98, 122

vessels, 68

Allantois, 59, 66, 69, 76, 85, 99
derivation of, 71, 76
section through, 113
Allelomorphs, 22
Alveoli of pancreas, 180
Alveolo-lingual gland, 154
Ameloblasts, 155
Amitosis, 12
Amnion, origin of, 66, 67, 75

bat, 76

chick, 56, 63, 65

human, 73, 75

pig, /o

Amniotic fluid, 76
Amphiaster, 13

Amphibia, cleavage of ovum in, 26
gastrulation of, 28
origin of mesoderm in, 30
Amphioxus, cleavage of ovum in, 24
gastrulation of, 28
origin of mesoderm in, 30
Ampulla of ductus deferens, 219
Anal membrane, 162, 206
Anaphase of mitosis, 14
Anchoring villi, 238
Angipblast, 40
chick, 43
human, 243
Animal pole, 24
Anlage denned, 3
Ansa hypoglossi, 355, 360
Antihelix, 390
Antitragus, 390
Anus, 99, 145, 162
Aorta, origin of, 256

chick, 41

descending, 41, 47, 48, 50/61, 62, 65,
100, 132, 259, 261

dorsal, 47, 50, 85, 101, 123, 259, 264

pig, 101, 123

ventral, 47, 48, 59, 85, 100, 249, 259
Aortic arches, 61, 62, 123, 261, 263

chick, 59

human, 85, 261

transformation of, 262

85,

Appendicular skeleton, 315
Appendix epididymidis, 219

testis, 220 >

Aqueduct, cerebral, 330, 338
Archenteron, 29, 31, 35
Archipallium, 346
Arcuate fibers, 335
Area opaca, 37, 41

pellucida, 37

scrotal, 227

vasculosa, 243
Areolar tissue, 285
Artemia, 14
Arteries, axillary, 268

basilar, 264

brachial, 268

carotid, 101, 123, 262, 263, 264

cerebral, 264, 266

choroidal, anterior, 266

cceliac, 101, 124, 262, 266

development of, 262

epigastric, 266

femoral, 268

gluteal, 268

hepatic, 179

hypogastric, 267

iliac, 124, 267, 268

innominate, 263

intercostal, 266

interosseous, 268

intersegmental, 101, 123, 259, 262, 264

ischiadic, 268

lumbar, 266

mammary, 266

median, 268

mesenteric, 261, 262, 266
inferior, 124, 262
superior, 124, 261, 262

of extremities, 267

of heart, 85

of lower extremity, 268

of pig, 101, 123

of upper extremity, 267

ovarian, 266

peroneal, 268

phrenic, 266

popliteal, 268

pulmonary, 101, 123, 170, 256, 263

radial, 268

renal, 206, 266

sacral, middle, 267

spermatic, 266

spinal, 264

stapedial, 389

subclavian, 101, 124, 262, 263, 264, 268

suprarenal, 266

ulnar, 268

umbilical, 88, 102, 124, 137, 138, 259, 267

ventral, 101, 124

ventro-lateral, 101, 124

393

394

INDEX

Arteries, vertebral, 124, 264

vitelline, 47, 59, 64, 88, 101, 124, 260, 261,

262

chick, 44

Artificial parthenogenesis, 20
Arytenoid cartilage, 1 68

folds, 119

ridges, 96, 152

swellings, 167

Ascaris megalocephala bivalens, reduction of
chromosomes in spermatogenesis of, 17
univalens, 14
Atrial canal, 251

foramina, 100

septa, 251

valves, 258
Atrio-ventricular bundle, 258

foramen, 251

Atrium, 59, 85, 92, 99, 249, 251
Auditory meatus, external, 92, 114, 148, 391

ossicles, 389

placode, 47, 49, 384

tube, 84, 163, 389

vesicle, 385

Auricle of ear, 148, 390
Auricular fold, 390
Autonomic system, 366
Axial skeleton, 309
Axillary artery, 268

nerve, 356

vein, 275
Axis cylinder, 302
Axon, 302
Azygos vein, 273

BABY, blue, 259
Back, muscles of, 317
Bars, sternal, 311
Bartholin's glands, 228
Basal plate, 239, 240, 323, 332
Basilar artery, 264

membrane, 387
Basilic vein, 275
Basophils, 246
Bertin's renal columns, 203
Bicuspid valves, 123, 258
Bile capillaries, 179

duct, common, 122
Biogenesis, law of, 5
Birds, cleavage of ovum in, 26

gastrulation of, 28

origin of mesoderm in, 32
Birthmarks, 294
Bladder, 145, 206, 208, 209
Blastocoele, 24
Blastoderm, 26
Blast oder mic vesicle, 27
Blastomeres, 24
Blastopore, 29, 31
Blastula, 25

Blood cells, 43, 243, 244
ichthyoid, 244
sauroid, 244

corpuscles, red, 244

white, 245. See also Leucocytes.

elements, monpphyletic theory of origin, 243
polyphylectic theory of origin, 243

islands, 40, 43, 243

Blood, plates, 247

vascular system, pig, 99, 122
vessels, anomalies of, 276
changes at birth, 278
chick, 43, 47, 59
human, 243, 247
pig, 99, 122
primitive, 259
Blue baby, 259
Body cavities, 180

stalk, 73
Bone, cartilage, 287, 288

growth of, 289
cells, 288
destroyers, 288
ethmoid, ossification of, 313
formation, endochondral, 288
perichondral, 288, 289
periosteal, 288
formers, 287
growth of, 289
histpgenesis of, 287
lacrimal, 314
lacunae, 288
marrow, 288
red, 288
yellow, 290
membrane, 287
of skull, 314
nasal, 314

occipital, ossification of, 312
palate, 315
regeneration of, 290
sphenoid, ossification of, 313
temporal, ossification of, 313
zygomatic, 314
Border vein, 275
Bowman's capsule, 199, 200
Brachial artery, 268
plexus, 355
vein, 275
Brachium conjunctivum, 337

pontis, 336
Brain, human, 326
of pig, 117
olfactory, 328
vesicles, primary, 321, 326
Branchial arches, 144, 315
chick, 58
human, 84
pig, 91, 96, 114
skeleton, 315
duct, 163

groove, 56, 57, 91, 144, 162
Branchiomerism, 365
Broad ligaments, 222
Bronchi, primary, of pig, 97, 121

ventral, 168

Bronchial buds, 121, 1 68
Brunner, duodenal glands of, 1 74
Bulbar limb, 249

swellings, 123
Bulbo-urethral glands, 228
Bulbus cordis, 59, 62, 85, 249
Bundle, atrio-ventricular, 258
ground, 325

median longitudinal, 335
Bursa infracardiaca, 161

INDEX

395

Bursa omental, 190

inferior recess of, 191
pharyngeal, 164

C.^CUM, 122, 145, 173, 175, 176

Calcar avis, 351

Calcarine fissure, 351

Calyces of metanephros, 122, 200

Canal, atrial, 251

atrio- ventricular, 251

central, of adult spinal cord, 324

entodermal, 161

Haversian, 289

hyaloid, 381

incisive (of Stenson), 150

inguinal, 222, 223

lacrimal, 384

pleuro- peritoneal, 184

Stenson's, 150
Canaliculi, 288
Capillaries, bile, 179
Capsule, Bowman's, 199, 200

cells, 305

internal, 345

of liver, 193

peri otic, 312

vascular, of lens, 379, 381
Cardiac diverticulum, 121

glands, 172

muscle, 290, 292
Cardinal veins, 125

anterior, 49, 58, 61, 62, 88, 105, 125, 260,

268, 271
common, 58, 62, 88, 100, 105, 125, 260,

268, 271
posterior, 58, 64, 65, 88, 105, 125, 260,

268, 273

Carotid arteries, 101, 123
common, 263
internal, 262, 263, 264

gland, 369

Carpus, ossification of, 316
Cartilage, appositional, growth of, 286

arytenoid, 168

bone, 287, 288
growth of, 289

corniculate, 168

cricoid, 1 68

cuneiform, 168

elastic, 287

fibro-, 287

histogenesis of, 286

interstitial, growth of, 286

hyaline, 287

Meckel's, 315

of larynx, 167

Reichert's, 389

thyreoid, 168, 315
Cauda equina, 326
Caudate lobe of liver, 193

nucleus, 345
Caul, 76, 242
Cavity, body, 180

head, 365

joint, 290

marrow, 290

medullary, 290

oral, 144

Cavity, pericardial, 55, 180, 182

peritoneal, 55, 188

pleural, 55, 184, 188

pleuro-pericardial, 42

pleuro-peritoneal, 180, 184

tympanic, 163, 389
Cell-chain theory of development of "nerve

fibers, 302

Cells, aggregation, 3
blood, 43, 243, 244
ichthyoid, 244
sauroid, 244

bone, 288

capsule, 305

chromafnn, 368, 369

cone, of retina, 382

decidual, 236

division of, 12

enamel, 155
• ependymal, 301, 307, 324

ethmoidal, 313, 376

follicle, 9

ganglion, 305

germ, 7, 209, 214, 301

giant, 247

gland, 296

goblet, 282

hair, 295, 296, 387

interstitial, of testis, 214

mass, inner, 73
intermediate, 53

mastoid, 314

migration, 3

multiplication, 3

muscle, smooth, 290

nerve, 300

neuroglia, 300, 301, 307, 308

rod, of retina, 382

sense, 386

sheath (of axis cylinder), 305

sperm, n

supporting, 371, 387
of neural tube, 307
of spinal ganglia, 305, 306

sustentacular (of Sertoli), 14, 214

taste, 371

Cement of teeth, 157, 158
Centra of vertebrae, 143
Central canal of adult spinal cord, 324

nervous system, 321
chick, 46, 56
human, 82, 321

pig, H7
sulcus, 351
Centrosome, 7
Cephalic flexure, 56, 81, 327

pig, 91
vein, 275

Cerebellum, 117, 336
Cerebral aqueduct, 117, 330, 338
artery, anterior, 264
middle, 264
posterior, 266
cortex, 351

hemispheres, 117, 328, 329, 348
nerves, 117, 357
veins, 271
Cervical duct, 163

396

INDEX

Cervical enlargement, 326
flexure, 327

pig, 9i
ganglion, 368

sixth, 118
sinus, 114

pig, 91
vesicle, 163

Chamber, anterior, of eye, 379, 383
Chick embryos, 37, 45, 56

of fifty hours' incubation, 56
of thirty-eight hours' duration, 45
of twenty hours' duration, 37
of twenty-five hours' incubation, 39
preservation of, 37
study of, 37, 45, 56
Chin, 148
Choanag, 148
primitive, 373
secondary, 374
Chondrification of skull, 312

of vertebrae, 310
Chondrocranium, 312
ossification of, 312
Chorda dorsalis, 309

origin of, 36
gubernaculi, 222, 323
tympani, 363
Chordinae tendineae, 258
Chorioid fissure of eye, 376, 370
layer of eye, 383
plexus, 142, 143, 334, 338, 342
Chorioidal artery, anterior, 266

fissure, 342, 349
Chorion, origin of, 67
chick, 65

frondosum, 235, 237
human, 74
laeve, 235, 237

pig, 70, 72
illi of 73, 74.

233,237
Chromarnn bodies, 368

aortic, 368
Chromosomes, 13
accessory, 23
number of, 13
Cilia, 383
Ciliary bodies, 383
ganglion, 361, 368
muscle, 383
Circulation, fetal, 276
intervillous, 241
portal, 278
vitelline, 48
Circulatory system, 85
Cisterna chyli, 279
Clava, 336

Clavicle, ossification of, 315
Cleavage of ovum, 24
amphibia, 26
Amphioxus, 24
birds, 26
frog, 26
mammals, 27
primates, 28
reptiles, 26
Cleft palate, 151
sternum, 316

Cleft xiphoid process, 316
Clitoris, 145, 226
Cloaca, 85, 98, 173, 206

anomaly of, 209
Cloacal membrane, 85, 161, 206

tubercle, 225
j Closing plates, 58, 62, 97, 119, 162

ring, 239

Coccygeal gland, 281
Cochlear duct, 384, 386
i Coeliac artery, 101, 124, 262, 266

axis, primitive, 266
I Ccelom, 30, 34, 180

chick, 41, 54

human, 180

pleural, 97

Coelomic pouches, 30
i Colic valve, 176
Collateral eminence, 351

fissure, 351
Colliculus, facial, 363

inferior, 338

seminalis, 221

superior, 338
Colomba, 384
Colon, 122, 175, 176
. Column, gray, 324
Columns, muscle, 292

renal, 203

Commissura mollis, 341
Commissure, anterior, 346, 347

gray, 324

hippocampal, 347

of telencephalon, 346

posterior, of labia majora, 226

white, 325

Compact layer, 236, 240
Concealed testis, 225
Conchae, 148, 313, 376
Concrescence, theory of, 32
Cone cells of retina, 382
; Conjunctiva, 383
• Connective tissue, 284
white fibrous, 284
Copula, 96, 119, 151
Coracoid process, 316
Cord, genital, 211

nephrogenic, 198, 202

spermatic, 225

spinal, 322

testis, 213, 214

umbilical, human, 72

of pig, 72
Corium, 294

Cornea, substantia propria of, 379
Corneal tissue, 285
Corniculate cartilages, 168
Corona radiata, 9
Coronary appendages, 193

ligament, 193

sinus, 254, 271

sulcus, 225, 251

Corpora quadrigemina, 330, 338
Corpus albicans, 218

callosum, 346, 348

cavernosa penis, 226

cavernosum urethrae, 226

hemorrhagicum, 218

INDEX

397

Corpus, luteum, 218
spurium, 218
verum, 218

striatum, 329, 341, 345
Corpuscles, blood, red, 244

white, 245. See also Leucocytes.

lamellated, 371

renal, 135, 199, 200

splenic, 281

tactile, 371

thymic, 165
Cortex, cerebral, 351

of cerebral hemispheres, 329

of metanephros, 203

primitive, of cerebral hemisphere, 341
Corti's organ, 360, 386

pillars, 387
Costal processes, 309
Costo-cervical trunk, 266
Cotyledons of human placenta, 241
Cowper's glands, 228
Crantoschisis, 352
Crest, ganglion, 302, 353

inguinal, 222

neural, 302

Cribriform plates, 313
Cricoid cartilage, 168
Crista ampullaris, 386

galli, 313

terminalis, 254
Crura cerebri, 330
Crus longum, 390
Cryptorchism, 225
Cumulus oophorus, 216
Cuneiform cartilages, 168
Cuneus, 336, 351
Cuvier's ducts, 59
Cyclopia, 384
Cystic duct, 122, 177

kidney, 206

Cysts, dermoid, 218, 294
Cytomorphosis, 4
Cytoplasm of ovum, 7

DARWIN'S tubercle, 390
Decidua basalis (serotina), 232, 236,
239

capsularis (reflexa), 232, 237

vera (parietalis), 232, 236
Decidual cells, 236

membranes, 230, 232
separation of, 241

teeth, periods of eruption, 158
Dendrites, 302
Dendrons, 302
Dental canaliculi, 157

lamina, 154

papilla, 154, 156

Pulp, 157

sac, 157, 158
Dentate nucleus, 337
Dentinal fibers of Tomes, 157
Dentine, 156
Derma, 294
Dermatome, 113, 292
Dermoid cysts, 218, 294
Dermo-muscular plates, 53

237,

Dermo-myotome, 284, 292
Descending tract of fifth nerve, 335, 362
Determination of sex, 23
Dextrocardia, 259
Diaphragm, 188, 189

anlage of, 63

anomalies of, 195
Diaphragmatic hernia, 195
Diaphysis, 289
Diaster, 14

Diencephalon, 56, 82, 93, 117 327, 338
Differentiation of embryo, 3

of tissues, 4

Digestive canal, chick, 47, 57
human, 82
pig, 6 mm., 95

glands, human, 83
Dilator muscles of iris, 383
Discs, intercalated, 292

intervertebral, 310
Dissecting instruments, 139
Dissections, lateral, of viscera, 140

median sagittal, 142

pig embryos, 139

ventral, 145
Diverticulum, cardiac, 12 1

hepatic, 98, 121, 176

Meckel's, 81, 176

of ileum, 176

of Nuck, 22">

of pharyns al pouches, 96
Double monsters, 21
Ducts, branchial, 163

cervical, 163

cochlear, 384, 386

common bile, 122

Cuvier's, 59

cystic, 122, 177

Gartner's, 219

Ebner's, 153

genital, 209, 211, 219

hepatic, 122, 177

interlobular, 179

mesonephric, 99, 122, 200, 211

milk, 297

Mullerian, 211

naso-lacrimal, 383

pancreatic, 180

papillary, 202

para-urethral, 228

pronephric (primary excretory), 85, 198

thoracic, 279

thyreoglossal, 166

vitelline, 161

Wolffian, 85, 99
Ductuli abberantes, 219

efferentes, 200, 219
Ductus arteriosus, 263, 278

choledochus, 122, 177

deferens, 219

endolymphaticus, 385

epididymidis, 219

reuniens, 386

venosus, 104, 126, 270, 278
Duodenal glands (of Brunner), 174
Duodeno-hepatic ligament, 193
Duodenum, 121, 173, 174
Dyads, 16

398

INDEX

EAR, 384

auricle of, 148, 390
external, 114, 138, 384, 390
inner, 384
internal, 47
middle, 384, 389
Ebner's ducts and glands, 153
Ectoderm, 3, 28, 29

formation of, 28

Ectodermal derivatives, histogenesis of, 293
Ectopic pregnancy, 231
Ectoplasm, 284

Efferent ductules of epididymis, 200, 219
Elastic cartilage, 287

tissue, 285
Eleidin, 294
Ellipsoids of spleen, 281
Embryos, chick, 37, 45, 56

of thirty-eight hours' duration, 45
of twenty hours' duration, 37
of twenty-five hours' duration, 39
preservation of, 37
study of, 37, 45, 56
human, 70

crown-rump length, 89
estimated age, 89
of Coste, 80
of Dandy, 78
of Eternod, 79
of His, 2.5 mm., 80
4.2 mm., 82
Normentafel, 86, 87
of Kromer, 78
of Mall, 78
of Peter, 74, 76
of Spee, 74
of Thompson, 79
pig, 6 mm., 91

10 mm., transverse sections, 127
10 to 12 mm., 114
dissection of, 139
transverse sections of 6 mm., 105
whole, for study, 139
Eminence, collateral, 351
Enamel cells, 155
layer, 155
organs, 154
P«lp, 155

Encephalocoele, 352
Encephalon, 82

Endocardial cushions, 100, 132, 133, 251
Endocardium, 133, 249

chick, 43

Endochondral bone formation, 288
Endolymphatic sac, 385
Endoplasm, 284
Endothelium, 55
Enlargement, cervical, 326

lumbar, 326
Entoderm, 3, 28, 29

formation of, 28
Entodermal canal, 161
epithelium, 172

histogenesis of, 282
Eosinophils, 246
Ependymal cells, 301, 307, 324
layer, 61, 128, 307, 322, 333
zone, 301

Epicardium, 43, 100, 133, 249
Epidermis, 293

anomalies of, 294
Epididymis, 219

efferent ductules of, 200, 219
Epigastric arteries, 266
Epigenesis, 2

Epiglottis, 96, 119, 144, 151, 167
Epiphysis (pineal gland), 142, 289, 310, 330,

338

Epiploic foramen (of Winslow), 137, 191
Epispadias, 230
Epistropheus, 310
Epithalamus, 330
Epithelia, 3
Epithelial bodies, 120, 165

sheath, 156
Epithelium, 55

basal, of cochlear duct, 386

entodermal, 172
histogenesis of, 282

olfactory, 130

respiratory, 169

stratified, 293
Epitrichium, 294, 295, 296
Eponychium, 299
Epoophoron, 200, 219
Erythroblasts, 244, 245
Erythrocytes, 244
Erythroplastids, 244
Esophagus, 83, 96, 97, 121, 144, 170
Ethmoid bone, ossification of, 313
Ethmoidal cells, 313, 376
Ethmo-turbinals, 376
Eustachian tube, 163, 389

valve, 254

Excretory duct, primary, 54, 65, 198, 200
Expression, muscles of, 320
Extra-embryonic mesoderm, 73

structures, 66

Extra-uterine pregnancy, 231
Extremities, arteries of, 267

muscles of, 318

veins of, 275
Eye, chick, 45, 47, 48, 61

human, 82, 376

anomalies of, 384 .

pig, 9i

Eyelashes, 383
Eyelids, 383

FACE, development of, 146
Facial colliculus, 363

nerve, 94, 118, 362, 363
Falciform ligament, 136, 181, 193
False hermaphroditism, 230
Fasciculi proprii, 325
Fasciculus cuneatus, 325

gracilis, 325
Femoral artery, 268

nerve, 356

vein, 275

Femur, ossification of, 316
Fertilization, 20, 21

of human ovum, 21

of mouse ovum, 20

significance of, 22
Fertilizin, 20

INDEX

399

Fetal circulation, 276
membranes, human, 73

pig. 7°
Fetus, 88

relation of, to placenta, 241
Fibrils, horn, 298
Fibro-cartilage, 287
Fibula, ossification of, 316
Filament, axial, of spermatozoon, 12
spiral, of spermatozoon, 12
terminal, of spermatozoon, 12
Filiform papillae, 153
Filum terminale, 326
Fingers, supernumerary, 316
Fissure, calcarine, 351

chorioidal, 342, 349, 376, 379

collateral, 351

great longitudinal, 341

hippocampal, 346, 349

lateral, 349

of Rolando, 351

parieto-occipital, 351

Sylvian, 349

ventral median, 325
Fixation of pig embryos, 139
Flagellum of spermatozoon, 12
Flexure, cephalic, 56, 81, 327

cervical, 327
Pig, 9i

iliac, 176

pontine, 327
Flocculus, 336
Floor plate, 322, 324, 332
Foliate papilla?, 1 53
Follicle cells, 9
Follicles, Graafian, 9, 216

primordial, 216

vesicular, 216
Fontanelles, 314
Foramen, atrio- ventricular, 100

caecum, 153, 166

epiploic (of Winslow), 137, 191

interatrial, 100, 251

interventricular, 117, 258, 329, 342
closure of, 258

mandibular, 315

Monro's, 342

of Winslow, 137, 191

ovale, 100, 122, 251, 256

section through, 133
Fore-brain, chick, 41, 44, 46, 48, 61

human, 326
Fore-gut, chick, 40, 41, 42, 50, 57

human, 83, 161, 162

pig, 95

Fore-skin, 226
Fornices of vagina, 221
Fornix, 346, 347
Fossa, incisive, 150

olfactory, 371, 372

ovalis, 256

supratonsillar, 163

tonsillar, 163
Frenulum prepucii, 226
Frog, cleavage of ovum in, 26
Frontal operculum, 349

sinus, 376
Fronto-nasal process, 372

Fronto-parietal operculum, 349
Froriep's ganglion, 95, 118, 360
Fundus of uterus, 200
Fungiform papillae, 153
Funiculi of spinal cord, 325
Furcula of His, 167

GALL bladder, 122, 177
Ganglion, 353
accessory, 364
cell layer, 382

of retina, 358
cells, 305
cervical, 368
ciliary, 361, 368
crest, 302, 353
Froriep's, 95, 118, 360
geniculate, 94, 118, 363
habenulae, 338
jugular, 94, 118
nodose, 95, 118, 364
otic, 368

petrosal, 94, 118, 364
prevertebral, 368
root, 94, 364
semilunar, 94, 118, 361
sphenopalatine, 367
spinal, 52, 1 1 8, 302

supporting cells, 305, 307
spiral, 358, 359
submaxillary, 368
superior, 94, 118, 364
sympathetic, 305, 366
trunk, 364
vagus accessory, 1 1 8
vestibular, 358
visceral, 368
Gartner's ducts, 219
Gastric glands, 172
Gastro-hepatic ligament, 193
Gastro-lienic ligament, 192
Gastrula, 29
Gastrulation, 28
of amphibia, 29
of Amphioxus, 29
of birds, 29
of mammals, 29
of reptiles, 29
Geniculate bodies, 329

ganglion, 94, 118, 363
Genital cord, 2 1 1
ducts, 209, 211, 219
eminence, 116, 225
fold, 99, 122, 145, 198, 209
glands, 99, 145, 198, 209

and mesonephric tubules, transtormation

of, 219

swellings, 225
Genitalia, external, 225

anomalies of, 230
internal, ligaments of, 222
Germ cells, 7, 209, 214, 301

primordial, 209
layers, 2, 3

derivatives of, 55
origin of, 24
plasm, continuity of, 5
Germinal disc, 26

4co

INDEX

Gestation, period of, 90

Giant cells, 247

Gill slits, 56

Glands, accessory genital, 228

alveolo-lingual, 154

Bartholin's, 228

Brunner's, 174

bulbo-urethral, 228

cardiac, 172

carotid, 369

cells, 296

coccygeal, 281

Cowper's, 228

duodenal (of Brunner), 174

Ebner's, 153

gastric, 172

genital, 99, 145, 198, 209

and mesonephric tubules, transformation
of, 219

haemal, 280

intestinal, 174

lacrimal, 383
accessory, 383

lymph, 280

mammary, 116, 297
rudimentary, 292
supernumerary, 297

Meibomian, 383

parathyreoid, 84, 120, 165

parotid, 153

pineal, 142, 289, 310, 330, 338

prostate, 228

salivary, 153

sebaceous, 295

sublingual, 154

submaxillary, 154

sudoriparous, 296

suprarenal, 145, 368, 369

sweat, 296

tarsal, 383

thymus, 120

thyreoid, 120, 166

urogenital, 146

uterine, of pregnancy, 236

vestibular, 228
Glans clitoridis, 226

penis, 226

Glomerulus, 135, 196, 199
Glomus caroticum, 369

coccygeum, 281

Glossppharyngeal nerve, 94, 118, 363, 364
Glottis, 96, 119, 152, 167
Gluteal artery, 268

vein, 275
Goblet cells, 282
Gonads, 85

Graafian follicle, 9, 216
Granular layer of cerebellum, 337

leucocytes, 246
Granules, pigment, 294
Gray column, 324

commissures, 324

rami, 366
Groove, laryngo-tracheal, 66

neural, 299

primitive, 32

rhombic, 334

urethral, 226

Ground bundles, 325
Growth of embryo, 3
Gubernaculum testis, 223, 224
Gyrus dentatus, 346
hippocampi, 346

H^MAL glands, 280
Haemopoiesis, 243
Hair, 294

anomalies of, 296

bulb, 295

cells, 295, 296, 387

papilla, 295

shaft of, 295

sheath, 295
Hare lip, 148
Haversian canal, 289
Head cavities, 365

fold, 39

muscles of, 319

process, 33, 34, 37, 39

vertebrate, segmentation of 365
Heart, anomalies of, 259

chick, 43, 47, 50

descent of, 259

human, 85, 247, 248

pig, 92, 99, 122, 145

primitive, chick, 43

ventricle of, 59
Helix, 390

hypid, 390

Hemiazygos vein, 273
Hemispheres, cerebral, 117, 328, 329, 348
Henle's loop, 204
Hensen's knot, 32, 37, 52
Hepatic artery, 179

diverticulum, 98, 121, 176

duct, 122, 177

vein, 270

common, 100

Heredity, Mendel's law of, 22
Hermaphroditism, 221, 230

false, 221, 230
Hernia, diaphragmatic, 195

inguinal, 225

umbilical, 72, 174, 176
Hind-brain, chick, 42, 46, 50, 61

human, 82, 326

Hind-gut, 57, 66, 85, 95, 161, 162
Hippocampal commissure, 347

fissure, 346, 349
Hippocampus, 346, 349

minor, 351
His, furcula of, 167
Histogenesis, 282

denned, 4

of bone, 287

of cartilage, 286

of ectodermal derivatives, 293

of entodermal epithelium, 282

of mesodermal tissues, 283

of muscle, 290

of nervous tissue, 299
Historical, i
Horn fibrils, 298

gray, 324

greater, of hyoid bone, 315

lesser, of hyoid bone, 315

INDEX

4OI

Horse-shoe kidney, 206
Howship's lacunae, 288
Human embryos, 70

crown-rump length, 89

estimated age, 89

of Coste, 80

of Dandy, 78

of Eternod, 79

of His, 2.5 mm., 80
4.2 mm., 82
Normentafel, 86, 87

of Kromer, 78

of Mall, 78

of Peters, 74, 76

of Spec, 74

of Thompson, 79
Humerus, ossification of, 316
Hyaline cartilage, 287
Hyaloid canal, 381
Hydramnios, 76
Hydrocephaly, 352
Hymen, 220/221,
Hyoid arch, 92

helix, 390

Hyomandibular cleft, 92
Hypermastia, 297
Hyperthelia, 297
Hypertrichosis, 296
Hypogastric artery, 267
Hypoglossal nerve, 95, 118, 153, 360
Hypophysis, 58, 61, 339
anterior lobe of, 61
posterior lobe of, 117
Hypospadias, 230
Hypothalamus, 330
Hypotrichosis, 296

ICHTHYOID blood cells of Minot, 244
Ichthyosis, 294
Ileum", 85

diverticulum of, 176
Iliac arteries, 124, 267, 268

flexure, 176

veins, 275

Ilium, ossification of, 316
Implantation of ovum, 231
Incisive canals (of Stenson), 150

fossa, 150
Incus, 315, 389
Infundibulum, 330, 339
Inguinal canal, 222, 223

crest, 222

fold, 220, 222

hernia, 225
Inner cell mass, 73

epithelial mass of gonad, 209
Innominate artery, 263
Instruments, dissecting, 139
Insula, 349

Interatrial foramen, 100, 251
Intercalated discs, 292
Intercostal arteries, 266
Interlobular ducts, 179
Intermediate cell mass, 41, 53
Interosseous artery, 268
Intersegmental arteries, 101, 123, 259, 262, 264

fiber tracts, 335

veins, 273

Interstitial cells of testis, 214

lamellae, 289

Interventricular foramen, 117, 258, 329, 342
closure of, 258

septum, 123, 258

sulcus, 258
Intervertebral discs, 310

muscles, 317

Intervillous circulation, 241
Intestinal glands, 174

loop, 144, 173

portal, 40, 42, 50, 66, 84
Intestine, human, 83, 85, 170, 173
anomalies of, 176

pig, 98, 122

villi of, 174
Introduction, I
Iris, 381, 383

muscles of, 383
Ischiadiac vein, 273

artery, 268

Ischium, ossification of, 316
Island of Reil, 349
Islands, blood, 43, 243

of pancreas, 1 80
Isolecithal ova, 23
Isthmus, 117, 328, 330

JACOBSON'S organ, 358, 374

Joint cavity, 290

Joints, 290

Jugular ganglion, 94, 118

sacs, 279

veins, 125, 271

KERATIN, 298
Keratohyalin, 294
Kidney, anomalies of, 206

calyces of, 122

cystic, 206

horse-shoe, 206

human, 200

tubules of, 122, 202, 203
Knot, primitive (of Hensen), 37, 52

LABIA majora, 226

minora, 226, 227
Labyrinth, membranous, 47
Lacrimal bone, 314

canals, 384

glands, 383
accessory, 383

groove, 92
Lacuna?, bone, 288

Howship's, 288
Lamella?, concentric, 289

interstitial, 289

periosteal, 289
Lamellated corpuscles, 371
Lamina perpendicularis, 313

terminals, 329, 342, 346
Langhans' layer, 239
Lanugo hair, 296
Laryngeal nerves, recurrent, 264
Laryngo-tracheal groove, 166
Larynx, 166, 167

cartilage of, 167

muscles of, 320

4O2

INDEX

Larynx, ventricles of, 167
Law, Mendel's, of heredity, 22

of biogenesis, 5

of recapitulation, 5
Layer, chorioid, of eye, 383

compact, 236, 240

enamel, 155

ependymal, 128, 307, 322, 333

epitrichial, 296

ganglion cell, 382
of retina, 358

germ, origin of, 24

granular, 337

Langhans' 239

mantle, 128, 322, 324

marginal, 128, 322, 325

medullary, 337

molecular, 337

nerve fiber, 382

nervous, of retina, 128

of retina, 382

pigment, of retina, 128, 377, 381

retinal, 377, 381

sclerotic, of eye, 382

spongy, 236, 239
Lecithin, 7
Lemniscus, 338

median, 335

Lens of eye, chick, 47, 48
human, 376
fibers of, 379

pupillary membrane of, 381
suspensory ligament of, 381
vascular capsule of, 379, 381
pig, 9i

pit, 376

plate, 376

vesicles, 61, 376, 379
Lens-stars, 380
Lenticular nuclei, 345
Lesser peritoneal sac, 135, 190
Leucocytes, 245

granular, 245

mast, 246

mononuclear, large, 245

non-granular, 245

polymorphonuclear, 245
Ligament, broad, 222

coronary, 193

duodeno-hepatic, 193

falciform, 136, 181, 193

gastro-hepatic, 193

gastro-lienic, 192

lieno-renal, 192

of internal genitalia, 222

of liver, 193

of testis, 222

proper, of ovary, 222

round, 220, 222

spheno-mandibular, 315

stylo-hyoid, 315

suspensory, of lens, 381
Ligamentum arteriosum, 278

labiale, 222

ovarii, 211

scroti, 222

teres, 271, 278

testis, 211, 223

Ligamentum umbilicale medium, 209

venosum, 270, 278
Limbus ovalis, 254
Limiting membranes of retina, 382
Line, lateral, 365

milk, 297

Lingual tonsil, 164
Linguo-facial vein, 105
Lip, 373

hare, 148

rhombic, 334
Liver, anlage of, 59, 64, 176

anomalies of, 179

caudate lobe of, 193

cords, 135

human, 83, 176

ligaments of, 193

lobules of, 179, 193

pig, 92, 95, 98, 121

quadrate lobe of, 193

sinusoids of, 59, 64, 177, 268
Lobes of cerebrum, 348
Lobule of ear, 390
Lobules of liver, 179, 193
Lobuli epididymidis, 219
Lumbar arteries, 266

enlargement, 326

veins, 275

Lumbo-sacral plexus, 355
Lung buds, 84
Lungs, human, 83, 166, 168
anomalies of, 170
apical buds, 168
changes at birth, 170
stem buds, 168

pig, 97, 121
Lunula, 298
Lymph glands, 280

sacs, 278, 280
Lymphatic system, 278
Lymphatics, origin of, 278

peripheral, 279
Lymphocytes, small, 245
Lymphoid tissue of spleen, 281

MACULA acusticae, 386
Magma reticulare, 73
Mall's pulmonary ridge, 185
Malleus, 315, 389

muscles of, 389
Mammals, cleavage of ovum in, 27

gastrulation of, 29

origin of mesoderm in, 34
Mammary arteries, 266

glands, r 1 6, 297
rudimentary, 297
supernumerary, 297
Mammillary bodies, 330, 341, 347

recess, 330, 341
Mandibular arch, 92

foramen, 315

nerve, 118, 362

process, 81, 82, 92, 114, 146, 315, 372
Mantle layer, 128, 322, 324
Manubrium, 311
Marginal layer, 128, 322, 325

sinus, 241

zone, 301

INDEX

403

Margo thalamicus, 327
Marrow, bone, 288
red, 288
yellow, 290

cavity, 290

Massa intermedia, 341
Mast leucocytes, 246
Mastication, muscles of, 319
Mastoid cells, 314

process, 314
Maturation, 14

of human ovum, 20

of mouse ovum, 18

significance of, 22
Maxillas, 315
Maxillary nerve, 118, 362

process, 81, 82, 92, 114, 146, 315, 372

sinus, 376

Maxillo-turbinal anlage, 375
Meatus, external auditory, 92, 114,

. 391

inferior nasal, 375
Meckel's cartilage, 315

diverticulum, 81, 176
Meconium, 176
Median artery, 268

longitudinal bundle, 335

nerve, 356
Mediastinum, 169

of ovary, 215

testis, 214

Medulla oblongata, 82, 330
Medullary cavity, 290

layer, 337

sheath, 305

velum, 330, 337
Megakaryocytes, 247
Meibomian glands, 383
Melanism, 294
Membrana tectoria, 387
Membrane, anal, 162, 206, 294

basilar, 387

bone, 287

bones of skull, 314

cloacal, 85, 161, 206

decidual, 230, 232

separation of, at birth, 241
tympanic, 120, 391

limiting, of retina, 382

obturator, 316

pericardial, 188

peridental, 158

pharyngeal, 161

pleuro-pericardial, 183, 184, 185, 186

pleuro-peritoneal, 183, 184, 185, 186

pupillary, 381
Reis:

leissner's, 387

synovia!, 290

tympanic, 391

urogenital, 162, 206

vestibular, 387

vitelline, 7

Membranous labyrinth, 47
Mendel's law of heredity, 22
Meningoccele, 352
Meningoencephalocoele, 352
Meningomyeloccele, 352
Menstruation, 10, 230

Menstruation, uterus during, 230
Mesamoeboids, 243, 244
Mesencephalon, 80

chick, 46, 48, 62

human, 326, 330, 337

pig, 94, 117
Mesenchyma, 3

chick, 42, 53, 55

human, 283
Mesenteric arteries, 124, 261, 262, 266

inferior, 124, 262

superior, 124, 261

veins, 268

superior, 102, 103, 127, 268
Mesentery, 95, 98, 122, 135, 180, iSi

anomalies of, 195

dorsal, 83, 193
: Mesocardium, 181

dorsal, 49, 249

148, Mesocolon, 181, 194, 195
Mesoderm, 3, 28

amphibian, 30

Amphioxus, 30

birds, 32

extra-embryonic, 35, 73

intra-embryonic, 35

mammal, 34

origin of, 30

primary, 28

•reptiles, 30

somatic, 54, 71, 170

splanchnic, 54, 71, 170, 171, 366

Tarsius, 35
Mesodermal segments, 2, 42, 53, 65,

tissues, histogenesis of, 283
Mesoduodenum, 181, 194
Mesogastrium, 181

Mesonephric duct, 51, 54, 65, 99, 122, 200,
211, 219

fold, 198

tubules, 198, 219

and genital glands, transformation of, 219
Mesonephros, 54, 85, 92, 95, 99, 122, 145, 196,

198

Mesorchium, 2 1 1
Mesorectum, 181, 195
Mesothelium, 55, 283

peritoneal, 172
Mesovarium, 211
Metameres, 2
Metamerism, 2
Metanephrps, 64, 99, 122, 145, 196, 200

and umbilical arteries, section through, 138

calyces of, 200

collecting tubules, 200, 202

cortex, 203

pelvis, 200

tubules, 200, 202

ureter, 200

Metaphase of mitosis, 13
Metatarsus, ossification of, 316
Metathalamus, 329

Metencephalon, 82, 94, 117, 327, 328, 336
Methods of study, 5
Mid-brain, 82, 327

chick, 44, 46, 48
Mid-gut, 57, 161
Migration, cell, 3

404

INDEX

Milk ducts, 297
line, 1 1 6, 297

teeth, periods of eruption, 158
witch, 297

Minot's ichthyoid blood cells, 244
Mitochondria, 7
Mitosis, 12

phases of, 12-14

significance of, 22
Mitotic figure, 13
Mitral valve, 258
Moderator muscles, 258
Modiolus, 387
Molecular layer, 337
Moles. 294
Monaster, 13

Mononu clear leucocytes, large, 245
Monophyletic theory of origin of blood ele-
ments, 243

Monro's foramen, 342
Mons pubis, 225
Monsters, double, 21
Montgomery's rudimentary mammary glands,

297

Morula, 24

Motor nerves, somatic, 360
Mouse ovum, fertilization of, 20

maturation of, 18
Mouth, pig, 6 mm., 95
Miiller's fibers, 382

tubercle, 209, 221
Mullerian ducts, 211

transformation of, 220
Multiplication, cell, 3
Muscles, 316

anomalies of, 320

cardiac, 290, 292

ciliary, 383

columns, 292

dilator, of iris, 383

histogenesis of, 290

intervertebral, 317

moderator, 258

of back, 317

of expression, 320

of extremities, 318

of head, 319

of larynx, 320

of malleus, 389

of mastication. 319

of neck, 317

of pharynx, 320

of tongue, 320

of trunk, 317

papillary, 258

plate, 60, 62, 65

skeletal, 290, 291

smooth, 290

sphincter, of iris, 383

stapedial, 389

sterno-cleido-mastoid, 364

thoracp-abdominal, 317

trapezius, 364
Muscular system, 316
Musculocutaneous nerve, 356
Myelencephalon, 82, 94, 117, 328, 330, 333
Myelin, 305

development of, 325

Myelin sheath, 305

Myeloccele, 352

Myelocytes, 245, 246

Myoblasts, 291, 292

Myocardium, 43, 100, 133, 249, 258

Myofibrillag, 292

Myotomes, 2, 292

changes in, during formation of adult mus
cles, 317

chick, 53

294
Nail fold, 298, 299

human, 298
Nares, external, 373
! Nasal bone, 314

meatus, inferior, 375

passages, 373

processes, 147, 372, 373

septum, 313, 373
Naso-lacrimal duct, 383
Naso-turbinal anlage, 375
Navel, 72

Neck, muscles of, 317
Neopallium, 346
Nephrogenic cords, 198, 202

tissue, 122, 138, 202, 203
Nephrostome, 196
Nephrotome, 196

chick, 41, 53, 65
Nerve, abducens, 118, 361

accessorius, 118

acoustic, 94, 118, 358

axillary, 356

cells, 300

cerebral, 117, 357

facial, 94, 1 1 8, 362, 363

femoral, 356

fibers, 300

cell-chain theory of development, 302
layer, 382

glossopharyngeal, 94, 118, 363, 364

hypoglossal, 95, 118, 153, 360

mandibular, 118, 362

maxillary, 118, 362

median, 356

motor somatic, 360

musculocutaneous, 356

obturator, 356

oculomotor, 94, 118, 330, 360

olfactory, 357

ophthalmic, 118, 362

optic, 117, 358, 382

peroneal, 356

petrosal, superficial, 118, 363

phrenic, 355

radial, 356

recurrent laryngeal, 264

sciatic, 356

sensory, somatic, 357

somatic, motor, 360
sensory, 357

spinal, i'i8, 353

accessory, 95, 118, 364
efferent fibers of, 302

terminal, 358

tibial, 356

INDEX

405

Nerve, trigeminal, 94, 118, 361

trochlear, 118, 330, 361

ulnar, 356

vagus, 95, 1 1 8, 361, 364

visceral mixed, 361
Nervous layer of retina, 128

system, 93, 117
central, 321
chick, 46, 56
human, 82, 321
peripheral, 353
sympathetic, 366

tissue, histogenesis of, 299
Neural crest, 52, 94, 302
chick, 42

folds, 39, 41, 42

groove, 39, 299

plate, 299

tube, 39, 41, 66, 299, 332
anomalies of, 352
origin of, 30
supporting cells of, 307
Neurenteric canal, 32, 33, 34, 78
Neurilemma, 305
Neuroblasts, 301

differentiation of, into neurones, 301

of retina, 382
Neurofibrillae, 302
Neuroglia cells, 300, 301, 307, 308

fibers, 300, 301, 307, 308
Neurokeratin, 305, 308
Neuromeres, 47, 107, 117, 334
Neurons, 302

afferent, 302

concept, 301

differentiation of neuroblasts into, 301
Neuropores, 41, 321

anterior, 44
Neutrophils, 246
Nipple, 297
Node, primitive. (See Knot.)

of Ranvier, 305
Nodose ganglion, 95, 118, 364
Nodulus cerebelli, 336
Normoblasts, 244
Nose, 371
Notochord, 34, 39, 309

chick, 41, 65

origin of, 30, 36
Notochordal canal, 34

plate, 31, 33, 37, 39, 66
Nuclear zone, 301
Nuclei pulposi, 36, 309
Nucleolus, 7
Nucleus ambiguus, 364

caudate, 345

cuneatus, 335

dentate, 337

gracilis, 335

lenticular, 345

of pons, 336

olivary, 335

receptive, 335

red, 338

ruber, 338

terminal, 335
Nuck's diverticula, 225
Nymphae, 227

OBEX, 334

Oblique vein of left atrium, 271

Obturator membrane, 316

nerve, 356

Occipital bone, ossification of, 312
Oculomotor nerve, 94, 118, 230, 360
Odontoblasts, 157
Olfactory apparatus, 346

brain, 328

epithelium, 130

fossa, 371, 372

lobe, 346

nerve, 357

organ, 371

pits, 114,371,372

pig, 9i

placodes, 372

stalk, 346

tracts, 346
Olivary nucleus, 335
Omental bursa, 190

inferior recess of, 191
Omentum, 136, 171, 181, 191, 192
Oocyte, 1 8

primary, 1 8
Oogenesis, 8, 17 '
Oogonia, 18
Operculum, 349
Ophthalmic nerve, 118, 362

vein, 271
Optic chiasma, 329, 358

cup, 57, 114, 327, 376, 381

nerve, 117, 358, 382

placode, 376

recess, 330, 343

stalks, 48, 61, 376

tract, 358

vesicles, 41, 44, 46, 48, 61, 343
Ora serrata, 381
Oral cavity, 144
Orbital operculum, 349
Organ, Corti's, 360, 386

Jacpbson's, 358, 374

spiral, 360, 386, 387

vomero-nasal, 358, 374
Os coxae, 316
Ossicles, auditory, 389
Ossification of carpus, 316

of chondrocranium, 312

of clavicle, 315

of ethmoid bone, 313

of femur, 316

of fibula, 316

of humerus, 316

of ilium, 316

of ischium, 316

of metatarsus, 316

of occipital bone, 312

of patella, 316

of phalanges, 316

of pisiform, 316

of pubis, 316

of radius, 316

of skull, 312

of sphenoid bone, 313

of tarsus, 316

of temporal bone, 313

of tibia, 316

4o6

INDEX

Ossification of ulna, 316

of vertebrae, 310
Osteoblasts, 158, 287, 288
Osteoclasts, 288
Ostium abdominale, 2 1 1

.vaginae, 221
Otic ganglia, 368

vesicle, 47

Otocyst, 47, 57, 62, 82, 94, 385
Ovarian arteries, 266

pregnancy, 231

vein, 275
Ovary, 215

anomalies, 218

compared with testis, 218

descent of, 223

mediastinum, 215

proper ligament of, 222

septula, 215

stroma of, 216
Ovulation, 10

Ovum, cleavage of, 24. See also Cleavage of
ovum.

human, 7

fertilization of, 21

implantation of, 231

isolecithal, 24

maturation of, 14, 17, 18

mouse, fertilization of, 20

segmentation of, 24. See also Cleavage of
ovum.

structure of, amphibian, 7
bird, 7
monkey, n

telolecithal, 24

PALATE bones, 315

cleft, 151

development of, 148

premaxillary, 373

primitive, 373

soft, 150
Palatine processes, lateral, 148

tonsil, 84, 1 20, 163
Pallium of cerebral hemispheres, 329

of cerebrum, 341
Pancreas, alveoli of, 180

human, 83, 179

accessory duct of, 180
anomalies of, 180

islands of, 180

pig, 98, 122
Pancreatic duct, 180
Papillae, dental, 154, 156

hair, 295

of tongue, 153

renal, 202
Papillary ducts, 202

muscles, 258
Paradidymis, 200, 219
Parathyreoid gland, 84, 120, 165
Paraurethral ducts, 228
Parietal pleura, 170
Parietals, 314

Parieto-occipital fissure, 351
Parolfactory area, 346
Paroophoron, 200, 219
Parotid glands, 153

Pars caeca, 381

ciliaris, 381

intermedia, 340

iridis retinae, 381

lateralis of sacrum, 311

optica, 381

hypothalamica, 339

radiata, 203

tuberalis, 340

Parthenogenesis, artificial, 20
Patella, ossification of, 316
Peduncles of cerebrum, 338
Pelvis, renal, 200, 202
Penis, 145

Perforated space, 346
Pericardial cavity, 49, 55, 1 80, 182
chick, 55, 62

membrane, 188

Perichondral bone formation, 288, 289
Perichondrium, 286
Peridental membrane, 158
Periderm, 293
Perilymph space, 387
Periosteal bone formation, 288

lamellae, 289
Periosteum, 288
Periotic capsule, 312
Peripheral lymphatics, 279

nervous system, 353
i sinus, 280
Peritoneal cavity, 55, 188
chick, 55

mesothelium, 172

sac, 136

lesser, 135^36, 190
Peritoneum, 135

Permanent teeth, development of, 158
Peroneal artery, 268

nerve, 356
Petrosal ganglion, 94, 118, 364

nerve, superficial, 118, 363

sinus, 273
Pfliiger's tubes, 216
Phalanges, ossification of, 316
Phallus, 145, 225
Pharyngeal bursa, 164

membrane, 44, 47, 48, 82, 161

plate, 44

pouches, 47, 62, 96, 119, 162

tonsil, 164

Pharyngopalatine arches, 150
Pharynx, human, 83

muscles of, 320

pig, 95, 118
Philtrum, 148
Phrenic artery, 266

nerve, 355
Pia mater, 128
Pig embryos, 114
6 mm., 91
10 to 12 mm., 114
dissection of, 139
transverse sections of 6 mm., 105
of 10 mm., 127

fetal membranes, 70
Pigment granules, 294

layer of retina, 128, 377, 381
Pillars, anterior, of fornix, 347

INDEX

407

Pillars of Corti, 387

Pineal body or gland, 142, 289, 310, 330, 338

Pisiform, ossification of, 316

Pituitary body, 339

Placenta, accessory, 242

human, 75, 230, 232, 235, 237
cotyledons of, 241
intervillous spaces of, 241
position of, 242
relation of fetus to, 241
vessels of, 241

praevia, 242

succenturiate, 242
Placentation, 242
Placodes, 365

auditory, 384

olfactory, 371

optic, 376

Plasm, germ, continuity of, 5
Plate, alar, 323, 332, 335, 338

basal, 239, 240, 323, 332

blood, 247

closing, 58, 62, 97, 119, 162

cribriform, 313

floor, 322, 324, 332, 338

lens, 376

neural, 299

notochordal, 31, 37

roof, 322, 332, 338

urethral, 225
Pleura, parietal, 170

visceral, 170

Pleural cavity, 55, 62, 184, 188
chick, 55

ccelom, 97
Pleuro-pericardial cavity, 42

membranes, 183, 184, 185, 186
Pleuro-peritoneal canal, 184,

cavities, 180, 184

membranes, 183, 184, 185, 186
Plexus, brachial, 355

chorioid, 142, 143, 334, 338, 342

lumbo-sacral, 355
Plica semilunaris, 383

venae cavae, 105, 136, 190, 193, 273

vein of, 273
Polar bodies, 17
Polocytes, 17
Polydactyly, 316

Polymorphpnuclear leucocytes, 245
Polyphyletic theory of origin of blood ele-
ments, 243
Polyspermy, 20
Pons, 117, 330

nucleus of, 336
Pontine flexure, 327
Popliteal artery, 268
Portal circulation, 278

intestinal, 40, 42, 50, 66, 84

vein, 102, 127, 268, 270
Postanal gut, 98
Postbranchial bodies, 165
Postnatal development, 4
Preformation, doctrine of, 2
Pregnancy, abdominal, 231

duration of, 89

ectopic, 231

extra -uterine, 231

Pregnancy, ovarian, 231

tubal, 231

uterine glands of, 236

uterus during, 230
Premaxillary palate, 373
Premyelocytes, 244, 245, 246
Prepucium, 226
Prevertebral ganglia, 368
Primary excretory ducts, 54, 65, 198, 200
Primates, 70

. cleavage of ovum in, 27
Primitive choanae, 373

folds, 32

groove, 32, 37, 39, 52

heart, chick, 43

knot or node, 32, 37, 52

palate, 373

pit, 32

segments, 2, 41

streak, 32, 37, 41, 52
Primordial follicles, 216
Proamniotic area, 40, 44
Process, coracoid, 316

costal, 309

fronto-nasal, 372

lateral nasal, 147, 372
palatine 148

mandibular, 81, 82, 92, 114, 146, 315, 372

mastoid, 314

maxillary, 81, 82, 92, 114, 146, 315 372

median nasal, 147, 372, 373
palatine, 148

nasal, 147, 372, 373

styloid, 314, 315

vermiform, 176

xiphoid, 3 1 1
cleft, 316

Processus globulares, 372
Pronephric ducts, 198

tubules, 51
Pronephros, 53, 196
Pronucleus, 18, 20
Prophase of mitosis, 13
Prosencephalon, 326

chick, 46

Prostate gland, 228
Prostatic utricle, 220
Pubis, ossification of, 316
Pulmonary arteries, 101, 123, 170, 256, 263

ridge, 185

vein, 123, 170, 256
Pulp, dental, 157

enamel, 155

Pupillary membrane, 381
Pyloric sphincter, 172
Pyramids of kidney, 202

QUADRATE lobe of liver, 193

RACHISCHISIS, 352
Radial artery, 268

nerve, 356

Radius, ossification of, 316
Ramus angularis, 270

arcuatus, 270

communicans, 354, 366

dorsal, 354

gray, 366

408

INDEX

Ramus lateral, 354

posterior, 354

terminal, 354

ventral, 354

white, 366

Ranv-ier's nodes,- 305
Rathke's pouch, 58, 6l, 83, 95, 128, 162
Recapitulation, law of, 5
Receptive nucleus, 335
Recess, inferior, of omental bursa, 191

lateral, 334

mammillary, 330, 341

optic, 330, 343

Rectum, 122, 138, 145, 176, 206
Red blood corpuscles, 244

bone marrow, 288

nucleus, 338
Reference, titles for, 6
Regeneration of bone, 290
Reichert's cartilage, 389
Reil's islands, 349
Reissner's membrane, 387
Renal artery, 206, 266

columns, 203

corpuscles, 135, 199, 200

papillae, 202

pelvis, 200, 202

tubules, 122, 202, 203, 204

veins, 275
Reptiles, cleavage of ovum in, 26

gastrulation of, 29

origin of mesoderm in, 30
Respiratory epithelium, 169
Rete ovarii, 215, 218

testis, 214, 218
Reticular formation, 335

tissue, 165, 284
Retina, layers of, 382

nervous layer, 128

pigment layer of, 128, 377, 381
Retinal layer, 381

of optic cup, 377
Retroperitoneal sac, 278
Rhinencephalon, 328, 341, 346
Rhombencephalon, 82, 326

chick, 46
Rhombic grooves, 334

lip, 334

Rhomboidal sinus, 41, 46, 52
Ribs, 309, 311
Ridge, pulmonary, 185
Rod cells of retina, 382
Rolando's fissure, 351
Roof plate, 322, 332, 338
Roots, spinal, dorsal, 305
Round ligament, 220, 222

SAC, dental, 157, 158
Sacculus, 386
Saccus vaginalis, 224
Sacral artery, middle, 267
Sacrum, pars lateralis of, 311
Sagittal dissections, median, 142

sinus, superior, 271
Salivary glands, 153
Santorini. duct of, 180
Saphenous vein, 275

Sarcolemma, 292
Sarcoplasm, 292
Sarcostyles, 292
Satyr tubercle, 390
Sauroid blood cells, 244
Scala tympani, 387

vestibuli, 387

Scapula, ossification of, 316
Sciatic nerve, 356
Sclerotic layer of eye, 382
Sclerotome, 113, 283
Scrotal area, 227
Scrotum, 228

ligament of, 223
Sebaceous gland, 295
Sections, "chick, fifty hours, 56
thirty-eight hours, 45
of twenty hours' duration, 37
twenty-five hours, 39

pig, 6 mm., 105
10 mm., 127

Seessel's pouch, 36, 83, 95, 162
Segmental zone, 66

Segmentation of ovum, 24. See also Cleavage
of ovum.

of vertebrate head, 365
Segments, mesodermal, 2, 42, 53, 64, 65

primitive, 2, 41
Semilunar ganglion, 94, 118, 361

valves, 258
Seminal vesicle, 219
Sense cells, 386

organs, chick, 46, 56

human, 82, 370
Sensory nerves, somatic, 357

organs, general, 371
Septa placentae, 241
Septum, atrial, 251

interventricular, 123, 258

median, of adult spinal cord, 324,^325

membranaceum, 258

nasal, 313, 373

pellucidum, 346

primum, 100, 122, 251, 278

scroti, 227

secundum, 123, 251, 278

spurium, 252

transversum, 63, 64, 84, 116, 118, 144, 176,

181-186

Sertoli, sustentacular cells of, 14, 214
Sex, determination of, 23
Shaft of hair, 295
Sheath cells, 305

epithelial, 156

hair, 295

medullary, 305

myelin, 305

Shoulder-blade, ossification of, 316
Sinus, cavernosus, 271

cervical, 91, 114

coronary, 254, 271

frontal, 376

marginal, 241

maxillary, 376

peripheral, 280

petrosal, 273

rhomboidal, 41, 46, 52

sagittal, superior, 271

INDEX

409

Sinus, sphenoidal, 376

transverse, 271

urogenital, 122, 206, 213

venosus, 59, 62, 100, 122, 249, 250, 254

valves of, 122, 250, 252, 254
Sinusoids, 88

of liver, 59, 64, 177, 268
Situs viscerum inversus, 195
Skeletal muscle, striated, 290, 291

system, 309
Skeleton, 309

anomalies of, 316

appendicular, 315

axial, 309

branchial arch, 315
Skull, 311

chondrification of, 312

membrane bones of, 314

ossification of, 312
Smooth muscle, 290
Solitary tract, 363, 364
Soma, 5
Somatic mesoderm, 54, 71

motor nerves, 360

sensory nerves, 357
Somatop'leure, 30, 34, 54, 65, 66
Somites, 2
Sperm cells, 1 1
Spermatic artery, 266

cord, 225

veins, 275
Spermatids, 15
Spermatocyte, primary, 14

secondary, 15
Spermatogenesis, 14
Spermatogonia, 14, 214
Spermatozoon, n
Sphenoid bone, ossification of, 313
Sphenoidal sinus, 376
Spheno-mandibular ligament, 315
Spheno-palatine ganglia, 367
Sphincter muscle of iris, 383

pyloric, 172
Spina bifida, 352
Spinal accessory nerve, 95, 118, 364

arteries, 264

cord, 322

primitive segments, section through, 113

ganglia, 52, 118, 302

supporting cells, 305, 307

nerves, 118, 353

efferent fibers of, 302

roots, dorsal, 305

tract, descending, of trigeminal nerve, 362
Spiral ganglia, 358, 359

limbus, 387

organ, 360, 386, 387

sulcus, 387

tunnel, 387
Spireme, 13

Splanchnic mesoderm, 54, 71, 170, 366
Splanchnopleure, 30, 35, 54, 66
Spleen, 192, 280
Splenic corpuscles, 281
Spongioblasts, 301, 306, 307
Spongy layer, 236, 239
Stapedial artery, 389

muscle, 389

Stapes, 315, 389
Stenson's canal, 150
Sternal bars, 311

Sterno-cleido-mastoid-muscle, 364
Sternum, 311

cleft, 316

Stoerck's loop, 204
Stomach, 83, 97, 121, 171
Stompdaeum, 57, 82, 162
Stratified epithelium, 293
Stratum corneum, 294

germinativum, 293

granulosum, 216, 217, 294

lucidum, 294
Stroma of ovary, 216
Study, methods of, 5
Stylo-hyoid ligament, 215
Styloid process, 314, 315
Subcardinal veins, 105, 125, 116, 273
Subclavian arteries, 101, 124, 262, 263, 264
268

veins, 125, 271, 275
Sublingual gland, 154
Submaxillary ganglia, 368

gland, 154

Substantia propria of cornea, 379
Sudoriparous glands, 296
Sulcus, central, 351

coronary, 225, 251

interventricular, 258

limitans, 323, 330, 332, 339

of cerebrum, 351

spiral, 387
Superfetation, 21
Supporting cells, 371, 387
of neural tube, 307
of spinal ganglia, 305, 306

tissue, 284

Supracardinal veins, 273
Suprarenal artery, 266

gland, 145, 368, 369
accessory, 370

vein, 27_s

Supratonsillar fossa, 163
Suspensory ligament of lens, 381
Sustentacular cells (of Sertoli), 14, 214
Sweat glands, 296
Sylvian fissure, 349
Sympathetic ganglia, 305, 366

nervous system, 366
Synovial membrane, 290

TACTILE corpuscles, 371
Tasnia, 334
1 Tail bud, 56

fold, 56

gut, 98

of caudate nucleus, 345
Tarsal glands, 383
Tarsius, origin of mesoderm in, 35
Tarsus, 383

ossification of, 316
i Taste buds, 153, 371

cells, 371
! Teeth, anlages of, 156, 158

anomalies of, 160

cement of, 157

decidual, periods of eruption, 158

4io

INDEX

Teeth, dental lamina of, 154
papilla, 154, 157
pulp, 157
sac, 157

dentine, 157

development of, 154

enamel, 154, 156

milk, periods of eruption, 158

odontoblasts, 157

permanent, 158

of vertebrates, 160

permanent, periods of eruption, 158, 159
Tegmentum, 330
Tela chorioidea, 328, 338
Telencephalon, chick, 56

commissures of, 346

human, 82, 327, 341

pig, 93, II?
Telolecithal ova, 24
Telophase of mitosis, 14
Temporal bone, ossification of, 313

operculum, 349
Tendon, 285
Tensor tympani, 389
Teratpmata, 218
Terminal nerve, 358

nucleus, 335

ramus, 354

ventricle, 326
Testis, 213

anomalies of, 218, 225

compared with ovary, 218

concealed, 225

cords, 213, 214

descent of, 223

intermediate cords of, 213

interstitial cells of, 214

ligament of, 222

mediastinum, 214

tubuli contorti, 214
fecti, 214
septula, 215
Tetrads, 15
Thalamus, 143, 329
Thebesian valve, 254
Theca folliculi, 216
Theory of concrescence, 32
Thoracic duct, 279
Thoraco-abdominal muscles, 317
Thymic corpuscles, 165
Thymus, 84, 164

gland, 120

Thyreo-cervical trunk, 266
Thyreoglossal duct, 119, 166
Thyreoid anlage, 62, 97

cartilage, 168, 315

gland, 120, 166

human, 83, 84, 166
.pig, 95- 97

Tibia, ossification of, 316
Tibia! nerve, 356

veins, 275
Tissue, adipose, 286

areolar, 285

connective, 284
white fibrous, 284

corneal, 285

differentiation of, 4

Tissue, elastic, 285

lymphoid, of spleen, 281

nervous, 299

reticular, 165, 284

supporting, 284
Titles for reference, 6
Toes, supernumerary, 316
Tomes, dentinal fibers of, 157
Tongue, anomalies of, 153

muscles of, 320

of pig, 119, 144, 151

papillae of, 153
Tonsil, 163

anomalies of, 164

lingual, 164

palatine, 84, 120, 163

pharyngeal, 164
Tonsillar fossa, 163
Touch-pads, 299
Trabeculae carnae, 258
Trachea, human, 83, 84, 166, 168

pig, 97, 121, 144

Tract, descending, of fifth nerve, 335
Tractus solitarius, 335
Tragus, 390
Trapezius muscle, 364
Triangular ligaments, 193
Tricuspid valves, 123, 258
Trigeminal nerve, 94, 118, 361
Trochlear nerve, 118, 330, 361
Trophectoderm, 27, 73, 74, 232
Trophoderm, 232, 233
Tubal pregnancy, 231
Tuber cinereum, 330, 341
Tubercle, cloacal, 225

Darwin's, 390

Muller's, 209, 221

satyr, 390
Tuberculum acusticum, 358 •

impar, 84, 95, 119, 151
Tubular heart, 248
Tubules, mesonephric, 198, 219

and genital glands, transformation of, 219

renal, 122, 202, 203, 204
Tubuli contorti, 214

recti, 214

septula, 215
Tunica albuginea, 213, 214

externa, 218

interna, 218

vaginalis, 224
Turbinate anlages, 144
Twins, development of, 21
Tympanic cavity, 163, 389

membrane, 120, 391

ULNA, ossification of, 316
Ulnar artery, 268

nerve, 356

Ultimobranchial body, 120, 165
Umbilical arteries, 88, 102, 124, 137, 138, 259,

267
cord, human, 72

of pig, 72

hernia, 72, 174, 176
veins, 259, 261, 268, 271
human, 88
pig, 104, 126

INDEX

411

Umbilical vessels, 72
Umbilicus, 72
Unguiculates, 70
Ungulates, 70
Urachus, 209-

Ureter, 122, 138, 202, 208, 209
Urethra, 145, 206, 227
Urethral groove, 226

plate, 225
Urogenital ducts, 146

fold, 198, 209

glands, 146

membrane, 162, 206

opening, 225

organs, 85, 145

sinus, 122, 206, 213

system, 99, 122, 196
Uterine glands of pregnancy, 236

tubes, 220

Utero-vaginal anlage, 220
Uterus, 220, 221

anomalies of, 221

bicornis, 211

cervix of, 220

during menstruation, 230
pregnancy, 230

fetalis, 221

fundus of, 220

gross changes in, 242

growth of, 221

infantalis, 221

ligaments of, 222, 223

masculinus, 220

planifundus, 221
Utricle, prostatic, 220
Utriculus, 386
Uvula, 150

VAGINA, 220, 221

anomalies of, 221

fornices of, 221

masculina, 220
Vagus ganglia, accessory, 1 1 8

nerve, 95, 118, 361, 364
Vallate papillae, 153
Valves, atrio-ventricular, 258

bicuspid, 123, 258

colic, 176

Eustachian, 254

mitral, 258

of coronary sinus, 254

of inferior vena cava, 254

of sinus venosus, 122, 250, 252, 254

semilunar, 258

Thebesian, 254

tricuspid, 123, 258
Vascular system, 243
Vasculogenesis, 247
Vegetal pole, 24
Veins, accessory hemiazygos, 271

anterior cardinal, 49, 58, 61, 62, 8
125, 260, 268, 271

axillary, 275

azygos, 273

basilic, 275

border, 275

brachial, 275

cardinal, 125

105,

Veins, cardinal anterior, 49, 58, 61, 62, 88, 105,

160, 268, 271

common, 58, 62, 88, 100, 105, 125, 260,
268, 271
left, 100
right, 100
posterior, 58, 64, 65, 88, 105, 125, 260,

268, 273
cephalic, 275
cerebral, 271
common cardinal, 58, 62, 88, 105, 125, 260,

268, 271
left, 100
right, 100

development of, 268
femoral, 275
gluteal, 275
hemiazygos, 273
hepatic, 270

common, 100
iliac, 275

intersegmental, 273
ischiadic, 273
jugular, 125, 271
linguo-facial, 105
lumbar, 275

mesenteric, superior, 102, 103, 127, 268
oblique, 2 71
of extremities, 275
of heart; 88
of' lower extremity, 275
of pig, 102, 125
of plica venae cavae, 273
ophthalmic, 271
ovarian, 275

portal, 102, 127, 268, 270
posterior cardinal, 58, 64, 65, 88, 105, 125,

260, 268, 273
pulmonary, 123, 170, 256
renal,275
saphenous, 275
spermatic, 275

subcardinal, 105, 125, 126, 273
subclavian, 125, 271, 275
supracardinal, 273
suprarenal, 275
tibial, 275

umbilical, 259, 261, 268, 271
human, 88
pig, 104, 126
vitelline, 51, 64, 88, 100, 126, 183, 259, 261,

268

chick, 41, 42, 43
left, 100
right, 100

Velum, medullary, 330, 337
Vena anonyma, left, 271

right, 271
capitis lateralis, 271

medialis, 271
cava, inferior, 103, 105, 122, 126, 190, 273

superior, 271
portas, 268, 270
Ventral arteries, 101, 124

ramus, 354
Ventricle, fifth, 346
first, 329
fourth, 117, 330

412

INDEX

Ventricle, lateral, 117, .329

of heart, 59, 85, 92, 99, 249, 251, 258

of larynx, 167

second, 329

terminal, 326

third, 117, 329, 341
Ventricular limb, 249
Ventro-lateral arteries, 101, 124
Vermiform process, 176
Vermis cerebelli, 336
Vernix caseosa, 76, 294
Vertebrae, 309, 310

chondrification of, 310

ossification of, 310

pig, centra of, 143

variations in number, 316
Vertebral arch, 310

arteries, 124, 264

Vertebrate head, segmentation of, 365
Vesicle, auditory, 385

blastodermic, 27

brain, primary, 321, 326

cervical, 163

lens, 61, 376, 379

optic, 44, 46, 48, 61, 343

otic, 47

seminal, 219
Vesicular follicles, 216
Vestibular anlage, 385

ganglia, 358

glands, 228

membrane, 387
Vestibule, 221
Villi, anchoring, 238

of chorion, 73, 74, 233, 237

of intestine, 1 74

origin of, 74
Viscera, lateral dissections, 140

pig, dissections of, 93
Visceral ganglia, 358

mixed nerves, 361

pleura, 170

Vitelline arteries, 47, 59, 64, 88, 101, 124, 260,
261, 262

| Vitelline arteries, chick, 44
circulation, 48
duct, 161
membrane, 7

veins, 51, 64, 88, 100, 126, 183, 259, 261, 268
chick, 41, 42, 43
left, 100
right, ioo

Vitello-umbilical trunk, 88, 259
Vitreous body of eye, 380
Vocal cords, 167
Vomer, 314
Vomero-nasal organ, 358, 374

WHITE blood corpuscles, 245. See also Leuco-
cytes.

commissure, 325

fibrous connective tissue, 284

rami, 366

Whole embryos for study, 139
Winslow's foramen, 137, 191
Wirsung, duct of, 180
Witch milk, 297
Wolffian ducts, 85, 99

XIPHOID process, 311
cleft, 316

YELLOW bone marrow, 290
Yolk, 7

sac, 67, 68, 69, 70, 79

stalk, 67, 68, 79, 81, 122, 161, 173

ZONA pellucida, 7
Zone, ependymal, 301

marginal, 301

nuclear, 301

segmental, 66
Zonula ciliaris, 381
Zuckerkandl's bodies, 368
Zygomatic bone, 314

802

This book is DUE on the last date stamped below

JAN 23 1930
SEP- * 0

OCT 10

(? DE

KOV !

5 «**

JS 3 W35

JAN 2 11935
FEB4

JUN 1 7 1935

Form L-9-15m-ll,'27

MAY

1 6 mi

DEC 2 1 1349

JAN 3 0 1954

|U ' g

ftfC-Dc
Bmoo OCT2"5 19

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JUN18

OCT2419?3;

973

000429752 9

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