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BtOLOGY
LIBRARY

TEXT-BOOK.

OJ THE

EMBRYOLOGY OF MAN AND MAMMALS

TEXT-BOOK

OF THE

EMBRYOLOGY or MAN AND MAMMALS

BY

DR. OSCAR HERTWIG

Professor extraordinarily of Anatomy and Comparative Anatomy, Director of the If. Anatomical
Institute oj the University of Berlin

TRANSLATED FROM THE THIRD GERMAN EDITION

BY

EDWARD L. MARK, PH.D.

Hersey Professor of Anatomy in Harvard University

339 <fj0uws iw ibt fet ajtfc 2 Si

LONDON: SWAN SONNENSCHEIN & CO., LIM.
NEW YORK: THE MACMILLAN CO.

1901

Of

BifotOGY/

BA
G

FIBST EDITION, October 1892.
SECOND EDITION, January 1898.
THIRD EDITION, J/arcA 1901.

TRANSLATOR'S PREFACE.

THE rapidly increasing recognition of the importance of Embryology
in all morphological studies makes it desirable that the most valuable
text-books upon the subject, in whatever language, be made available
for those who are beginning its study. Although the English-reading
student already has at command a number of text-books upon this
subject, it is evident to any one familiar with HERTWIG'S Lehrbuch der
Entwicklungsgeschichte des Menschen und der Wirbelthiere that this
work covers the field of Vertebrate Embryology in a more complete
and satisfactory way than any book heretofore published in English.

Two important objects to be accomplished in a text-book are :
first, a clear and methodical exposition of the well-established facts
of the science; and, secondly, such a presentation of unsettled
questions as shall stimulate the reader to further inquiry and re-
search. I believe it is far too common for the second of these aims
to be overlooked. The present work fulfils both requirements in an
eminent degree, and in its historical surveys exhibits an exceptional
fairness of treatment, notwithstanding the author has been one of
the foremost contestants in several of the fields reviewed. The
summaries which follow the discussions of the several topics serve a
useful purpose in directing attention to the more important conclu-
sions drawn from each subject.

I have aimed to give a clear and accurate reproduction of the
author's ideas ; while I have endeavored — not always successfully —
to avoid awkward renderings and German idioms, I have preferred
to err on the side of a too literal rather than a too liberal translation.
There are a few points that demand a brief explanation. The German
word Anlage has heretofore been variously rendered into English
by rudiment, origin, beginning, basis, foundation, etc., while some
writers, recognising the inadequacy of any of these words to express
the idea, have incorporated the German word itself in their English.

The Anlage of a structure is its beginning or its undifFerentiated
state — the object in a simple condition which is destined to be

followed by a more complicated one. The use of rudiment in this
sense is undesirable, because, in the interest of scientific accuracy, it
is important to restrict its meaning, as in German, to a structure
which is not destined to become more complicated, but which may have
been, either ontogenetically or phylogenetically, even more highly
developed than it now is. Origin and beginning are abstract terms,
whereas Anlage is more frequently used in the concrete ; basis and
foundation (Grundlage) convey a wrong impression — that of the sub-
stratum upon which the structure is erected. The need of a new
word, which shall be used in the sense of Anlage, is evident. I
suggest the adoption of an already existing word,— fundament, — used
at present only in a sense with which the proposed usage will not
produce confusion. This word has been uniformly employed in the
present translation, and the reader will see how readily and naturally
it lends itself to this use. Fundament would thus bear the same
relation to foundation that Anlage does to Grundlage.

I have also departed from authorised usage by sometimes employ-
ing for Bindegewebe and Stiitzgewebe the term sustentative (in a
mechanical sense) tissue, instead of connective tissue. My reason
for this is the narrower meaning of connective as compared with
sustentative.

In deference to a custom still followed in Human Anatomy, the
author, in describing the relative positions of parts, has very generally
used anterior and posterior for dorsal and ventral, etc. Instead of
converting these expressions into terms which are independent of the
temporary position of the organism, as I should have preferred, it
has seemed better to indicate the direction by a bracketed word in
those cases where a misunderstanding was most likely to occur. It
has of course not been necessary to repeat this after each term of
direction, but only after the first one of a series, the reader's atten-
tion being thus sufficiently directed to the matter to prevent any
misconception.

The rapid advances in Embryology make it impossible for a book
two years old to be a faithful reflection of the science of to-day in all
its branches ; there are some topics in which even radical changes
must be recognised. I have thought best, however, to reproduce the
book as it left the hands of its author, and to content myself with
calling the reader's attention to some of the topics in which the most
important advances have been made, such as the metamerism of the
head, and the plan and metamorphoses of the vessels of the visceral
arches.

TRANSLATOR'S PREFACE. vii

I aia under very great obligations to my colleague, Dr. C. B.
Davenport, for kind assistance and valuable criticism, but for which
many defects of the translation would have been overlooked. I am
also indebted to Drs. T. G. Lee, H. B. Ward, and W. McM. Wood-
worth for aid in reading portions of the proof.

a. L. MARK.

CAMBRIDGE, MASS.

AUTHOR'S PREFACE

TO THE FIRST EDITION.

" Die Entwickelungsgeschichte 1st der wahre Lichttrager fiir Untersuchungen
iiber organische Korper."— C. E. v BAER, "Ueber Entwickelungsgeschichte
derThiere"(Bd.L, S.231).

THE Embryology of Animals, although one of the youngest shoots
of morphological research, has, nevertheless, grown up in the course
of sixty years, along with the cell-doctrine and that of the tissues, to
a vigorous and stately tree. The comprehension of the structure of
organisms has been extended in a high degree by numerous develop-
mental investigations. The study of the human body has also derived
great advantage from the same. In the newer anatomical text-
books (GEGENBAUR, SCHWALBE) Embryology is receiving more and
more attention in the description of the separate systems of organs.
To what extent many things may be more clearly and attractively
described in this manner is best shown by a comparison of the des-
criptions of brain, eye, heart, etc., in the older and the more recent
anatomical text-books.

Although it is generally recognised that Embryology constitutes " a
foundation-stone of our comprehension of organic forms," neverthe-
less the attention which its importance warrants is not yet given to
it ; it is especially true that it has not become as extensively as it
should be a component of well-rounded medical and natural-history
instruction, to which it is indispensable. The cause of this is
perhaps in part to be sought in the fact that in student-circles the
study of Embryology is often held to be especially difficult and a
comprehension of it to be laborious. And thus many do not venture
into this apparently obscure realm.

But ought the development of an organism to be really more
difficult to comprehend than the complicated finished structure 1

To a certain extent this was the case at a time when the most
divergent and contradictory opinions prevailed concerning many of
the most important processes of development, such as the formation
of the germ-layers, the pro to vertebrae, etc., which the lecturer had to

AUTHOR'S PREFACE TO THE FIRST EDITION. ix

take into account, and when many processes were not yet understood
in their essence and their significance. But, thanks to the results of
Comparative Embryology, the number of the unintelligible processes
has been every year diminished, and in the same ratio the study of
Embryology even for the beginner has been rendered easier.

At least, it is not in any way an essential feature of the process
of development that it should be more difficult to understand than
the structure of the completed form. For every development begins
with a very simple condition, from which the more complicated is
gradually derived and by which it is explained.

Inasmuch as I have for twelve years pursued the study of Embry-
ology with especial interest, both in annually recurring academic
lectures and in a series of scientific investigations, the desire has
been awakened in me to acquire for Embryology a broader and more
secure foundation in education, and to procure for it admission into
larger circles of medical men and well-educated naturalists. As the
result of this there has come into existence the book which is before
us, in which the especial problem has been to make the complicated
structure of the human body more intelligible through the knowledge
of its development.

For the solution of this problem I have in the present text-book
placed the comparative method of investigation in the foreground. I
do not thereby find myself in any way in opposition to another
direction of embryological research, which places the objective point
in the physiological or mechanical explanation of the form of the
animal body. Such a direction I hold to be fully warranted, and I
believe that, instead of being opposed to a comparative-morphological
direction, it can be of the most permanent value to it in the solution
of its problems. One will find that I have here given full attention
to the mechanico-physiological explanation of forms. Compare the
sections on cell-division and Chapter IV., " General Discussion of the
Principles of Development," in which the laws of unlike growth and
the processes of the formation of folds and evaginations are treated.

In the presentation of the separate processes of development, in
the main the important things only have been selected, the sub-
sidiary left out, in order thus to make the introduction into
embryological study easier. In the case of fundamental theories
I have gone into their history extensively, because .it is of great
interest, and under certain circumstances operates as a stimulus,
for one to see in what way the state of a scientific question for the
time being has been attained. In pending controversial questions.

s AUTHOR'S PREFACE TO THE FIRST EDITION.

I have, it is true, employed chiefly as the foundation of my pre
sentation the views which appear to me the most entitled to
acceptance, but have not left unmentioned opposing conceptions.

Numerous figures in the text, as well as some colored plates, will
contribute materially to the easier comprehension of the various
developmental processes.

I submit, then, this text-book to physicians and to students of
medicine and the natural sciences, with the desire that it may
promote and facilitate the study of Embryology in wider circles, and
that it may thereby contribute to a deeper insight into the structure
of our own bodies.

OSCAR HERTWIG.
JENA, October 1886.

AUTHOR'S PREFACE

TO THE SECOND EDITION.

THE friendly reception which the " Text-book of the Embryology
of Man and Mammals " has found, is an indication of the increased
interest which this branch of Morphology now meets with.

Even more than a year ago, after the first part of the text -book
appeared and while the second part was in the press, the necessity of
preparing a second edition became evident.

In this edition fundamental changes have not been* undertaken ;
the text has, however, undergone an expansion in some places, owing
to the attention given to several works which have recently appeared.
This has been the case with the section on the first developmental
processes of the egg (WEISMANN, BLOCHMANN) ; that on the origin of
the vascular system (E/ABL, RUCKERT) ; that on the development of
the foetal membranes (DuvAL, OSBORN) ; and that on the human
placenta (KASTSCHENKO, WALDEYER, HUGE).

As the second part of the text-book has just appeared, it has been
possible to incorporate it in the second edition without alteration.

It has, furthermore, seemed to me expedient in the second edition
to distribute at the ends of the several chapters the synopses of the
literature, which in the first edition were brought together at the close
of the whole work. Finally, there has been added an index of
subjects, by which a more rapid orientation concerning the separate
topics will be facilitated; this will increase the usefulness of the
work.

May the book in this form make for itself new friends, not only
among students of medicine and the natural sciences, but also with
all those who have a fondness for and a comprehension of studies
in' natural science.

OJSCAE HERTWIG.
JENA, February 1888.

AUTHOR'S PREFACE

TO THE THIRD EDITION.

IN the two yeais which have elapsed since the appearance of the
second edition of this text-book, our knowledge of the embryology of
Vertebrates has experienced many important enrichments, thanks ta
the numerous investigations which are annually published. There-
fore, as the problem of preparing a third edition of the text-book
confronted me, I was compelled to make extensive changes in
many places. Thus the second and third chapters, concerning the
processes of fertilisation and cleavage of the egg, have undergone
expansion, owing to the presentation of the important discoveries
which have been made on the the egg of Ascaris megalocephala. I
have given an entirely new wording to the ninth chapter on the
development of connective substance and blood, also to the
sections on the origin of the urinary organs and the development of
the peripheral nervous system, and, finally, to the account of the
development of the heart and the venous system. Also at other
places one will often recognise the hand of improvement.

The third edition has been essentially improved by the addition of
thirty new figures, which I have taken from the investigations of
VAN BENEDEN, BOVERI, DUVAL, FLEMMING, HERMANN, His, BORN,
GEGENBAUR, NAGEL, VAN WIJHE, GRAF SPEE, BONNET, and KEIBEL.
Through the friendliness of Professor VAN BENEDEN I was also put
in a position to employ for my text-book three figures out of his
hitherto unpublished extensive work on the development of the
germinal layers of the Rabbit. By means of the increase in the
number of figures I hope that I have been able to render still easier
the comprehension of many of the processes of development.

And so I close the preface to the third edition by expressing
my thanks to all those who have rendered me friendly aid, and
especially to the publisher, who in the further equipment of the
text-book has met my wishes with the greatest willingness.

OSCAR HERTWIG.
BERLIN, March 1890.

CONTENTS.

PAGE

INTRODUCTION 1

MANUALS AND TEXT-BOOKS . ....... 4

PART FIRST.

CHAPTER I.

DESCRIPTION OF THE SEXUAL PRODUCTS 7

THE EGG-CELL 7

THE SEMINAL FILAMENTS 19

Historical 23

SUMMARY 27

CHAPTER II.
THE PHENOMENA OF THE MATURATION OF THE EGG AND THE

PROCESS OF FERTILISATION . . 30
THE PHENOMENA OP MATURATION . . . . . . .30

Historical .... 35

THE PROCESS OF FERTILISATION ....... 37

Historical 45

SUMMARY ...... . . 46

CHAPTER III.

THE PROCESS OF CLEAVAGE . 51

Historical 69

SUMMARY ... 72

CHAPTER IV.

GENERAL DISCUSSION OF THE PRINCIPLES OF DEVELOPMENT 76

CHAPTER V.

THE DEVELOPMENT OF THE TWO PRIMARY GERM-LAYERS

(GASTR^A-THEORY) 84

CHAPTER VI,

THE DEVELOPMENT OF THE TWO MIDDLE GERM -LAYERS

(CCELOM-THEORY) 106

SUMMARY 142

CHAPTER VII.

HISTORY OF THE GERM-LAYER THEORY ...... 145

CHAPTER VIII.

DEVELOPMENT OF THE PRIMITIVE SEGMENTS . . . .161
SUMMARY . . 169

XIV . CONTENTS.

CHAPTEE IX. PAGE

DEVELOPMENT OF CONNECTIVE SUBSTANCE AND BLOOD (THE

PARABLAST- AND MESENCHYME-THEORIES) . . 170

Historical 189

SUMMARY 191

CHAPTER X.

ESTABLISHMENT OF THE EXTERNAL FORM OF THE BODY . 194
SUMMARY ..206

CHAPTER XI.

THE FCETAL MEMBRANES OF REPTILES AND BIRDS . . - .206
SUMMARY 220

CHAPTER XII.
THE FCETAL MEMBRANES OF MAMMALS ...... 221

SUMMARY - . . .238

CHAPTER XIII.

THE FCETAL MEMBRANES OF MAN ...... .241

(1) THE CHORION . . . . . . *..... . .248

(2) „ AMNION . . .v . ... 250

(3) „ YOLK-SAC . . . . . . .... 251

(4) „ DECIDUJS . ......... 252

(5) „ PLACENTA . 258

(6) „ UMBILICAL CORD 268

SUMMARY . 272

PART SECOND.

CHAPTER XIV.
THE ORGANS OF THE INNER GERM-LAYER. THE ALIMENTARY

TUBE WITH ITS APPENDED ORGANS . . . . .281
I. THE FORMATION OF THE MOUTH, THE THROAT-, GILL-, OR

VISCERAL CLEFTS, AND THE ANUS . . . . "... 282
II. THE DIFFERENTIATION OF THE ALIMENTARY TUBE INTO

SEPARATE REGIONS, AND FORMATION OF THE MESENTERIES 295
III. THE DEVELOPMENT OF THE SEPARATE ORGANS OF THE ALL-

MENTARY TUBE . . I .,.. . . . . 304

A. The Organs of the Oral Cavity : Tongue, Salivary Glands, and

Teeth .304

S. The Organs arising from the Pharynx 313

(1) The Thymus ..... . .314

(2) „ Thyroid Gland . . , 317

(3) „ Lungs and Larynx . . . . . . 320

C. The Glands of the Small Intestine . . ... . .324

(1) The Liver . . . . . . . . .324

(2) , Pancreas . . .. , . . . . .332
SUMMARY . . 333

CONTENTS. XV

CHAPTER XV. PAGE

THE ORGANS OF THE MIDDLE GERM-LAYER . . . .341
L THE DEVELOPMENT OF THE VOLUNTARY MUSCULATURE . . 342

A. The Primitive Segments of the Trunk 342

B. „ Head-Segments 351

II. THE DEVELOPMENT OF THE URINARY AND SEXUAL ORGANS . 353

(«) The Pronephros and the Mesonephric Duct .... 353

(b) „ Mesonephros (Wolffian Body) 359

(c) „ Metanephros (Kidney) ....... 367

(d) „ Miillerian Duct 369

(e) „ Germinal Epithelium . 374

(/) „ Ovary 374

(#) „ Testis 382

(/*) ,, Metamorphosis of the Different Fundaments of the Uro-

genital System into their Adult Condition .... 385

A. In the Male (Descensus testiculorum) .... 387

B. „ „ Female ( „ ovariorum) .... 393
(i) The Development of the External Sexual Parts . . . 397

III. THE DEVELOPMENT OF THE SUPRARENAL BODIES . . . 403
SUMMARY 405

CHAPTER XVI.
THE ORGANS OF THE OUTER GERM-LAYER 416

I. THE DEVELOPMENT OF THE NERVOUS SYSTEM .... 416

A. The Development of the Central Nervous System . . . 416
(a) The Development of the Spinal Cord . . . .418
(&) „ „ „ Brain 421

(1) Metamorphosis of the fifth Brain-Vesicle . . . 427

(2) v „ fourth „ „ 429

(3) „ „ third „ „ 430

(4) ., „ second „ „ 431
Development of the Pineal Gland (Epiphysis cerebri) 432

„ Hypophysis (Pituitarj**Body) . 436

(5) „ „ Fore-Brain Vesicle . . .439
JB. The Development of the Peripheral Nervous System . . 449

O) „ „ Spinal Ganglia 449

(ft) „ „ Peripheral Nerves . . . .452

(0) „ „ Sympathetic System .... 462

SUMMARY 463

II. THE DEVELOPMENT OF THE SENSORY ORGANS .... 467

A. The Development of the Eye . . . . . .467

O) The Development of the Lens 471

Vitreous Body . . . .474
„ ,, Secondary Optic Cup and the

Coats of the Eye . . .476

(d-) „ „ ,, Optic Nerve . . . .484

(e) „ „ „ Accessory Apparatus of the Eye 486

XVI CONTENTS.

PAGE

SUMMARY . 489

B. The Development of the Organ of Hearing .... 490

(a) The Development of the Otocyst into the Labyrinth . 491
(&) ., „ „ Membranous Ear-Capsule into

the Bony Labyrinth and the
Perilymphatic Spaces . 498

(c) „ M „ Middle and External Ear . . 505
SUMMARY 510

C. The Development of the Organ of Smell 511

SUMMARY ^ . . 518

III. THE DEVELOPMENT OF THE SKIN AND ITS ACCESSORY ORGANS 520

(a) The Skin ' . . . .520

(5) ,. Hair 522

O) „ Nails .526

(d) „ Glands of the Skin . . . ... , .528

SUMMARY . 531

CHAPTER XVII.
THE ORGANS OF THE INTERMEDIATE LAYER OR MESENCHYME 538

I. THE DEVELOPMENT OF THE BLOOD-VESSEL SYSTEM . . . 542

A. The first Developmental Conditions of the Vascular System. . 542

(a) Of the Heart ... 542

(&) Vitelline Circulation, Allantoic and Placental Circulation 548

B. The further Development of the Vascular System up to the

Mature Condition 553

(a) The Metamorphosis of the Tubular Heart into a Heart

with Chambers . . 553

(&) The Development of the Pericardial Sac and the Dia-
phragm , -. . • . 566

(c) Metamorphoses of the Arterial System . 570

(d) „ ,, ., Venous .-. .... 577
SUMMARY . 588

II. THE DEVELOPMENT OF THE SKELETON 593

A. The Development of the Axial Skeleton . . , . ' . 593

(a) The Development of the Vertebral Column . . . 596

(&) „ „ „ Head -Skeleton . . . .603

I. Bones of the Cranial Capsule . . . . . 619

II. „ „ Visceral Skeleton . . . .' .622

(c) Concerning the Relation of the Head-Skeleton to the

Trunk-Skeleton 627

E. The Development of the Skeleton of the Extremities . . 635

(a) Pectoral and Pelvic Girdles 638

(&) Skeleton of the Free Extremity . , . . .640
(c) Development of the Joints ...... 644

fiUMMABY 4 .... 647

APPENDIX TO LITERATURE . . 658

INTRODUCTION.

THE history of the development of the individual, or Ontogeny
(Embryology), is the science of the growth of an organism ; it de-
scribes the morphological changes which an organism passes through
from its origin in the ovum up to its complete maturity, and presents
these in their natural connection. We can regard the fertilisation
of the egg-cell as the beginning of the process of development for
Vertebrates, as it also is for all the rest of the higher animals.

In giving an account of the changes of the egg-cell, which begin
with fertilisation, one may choose between two different methods.

According to one method a particular organism is made the basis
of the account, and one describes the changes which its germ under-
goes from the moment of fertilisation onward, from hour to hour,
and from day to day. It is in this way that the embryology of the
Chick has been worked out by C. E. VON BAER in his classical paper,
and by FOSTER AND BALFOUR in their " Elements of Embryology."
This method has the advantage that the reader acquires a view of
the total condition of an organism in the separate stages of its
development.

A book of that kind is especially suitable for such persons as
desire to acquaint themselves, by their own observation, with the
embryology of a single animal, as, for example, the Chick, by
repeating the investigations of others. It is, on the contrary, less
adapted to those who wish to acquire a connected view of the
development of the separate organs, as the eye, the heart, the brain,
etc. For the formation of these will of course be treated of at different
places in describing younger and older embryos. In order to procure
a general survey of the course of development of an organ, the
reader must consult various places in the text-book, and collect for
himself what relates to the subject.

For beginners, and for the needs of theoretical instruction ir
Embryology, the second method commends itself, in which the separate
organs are considered in succession, each for itself, and the changes
which a single organ has to pass through during development are

1

2

INTRODUCTION.

set forth connectedly from beginning to end. It is in this way that
KOLLIKER'S " Embryology of Man and the Higher Animals" is written.

The second method is, moreover, the only one applicable when the
problem is to investigate in a comparative way the development of
several organisms, and to fill up the gaps which exist in our know-
ledge of one by that which we know concerning nearly related
animals. But it is precisely in this position that we find ourselves
when we wish to acquire a survey of the development of the hurnar>
body. An account which should limit itself to that which we know-
about Man would exhibit numerous and extensive gaps. For up to
the present the eye of man has not seen how the human ovum is
fertilised, how it divides, how the germ-layers are formed, or how
the establishment of the most important organs is effected. It is
especially the period of the first three weeks, during which the
greatest variety of fundamental processes of development take place,,
concerning which we know next to nothing ; there is also little
prospect that a change will soon occur in this regard. The time
will therefore perhaps never come when a complete embryology of
Man in the strict sense of the word will be possible.

However, the existing gaps can be filled out in another manner,
and one which is entirely satisfactory. The study of the most widely
differing Vertebrates teaches us that they are developed according
to a common plan, that the first processes of development agree
in all really important points, and that the differences which we
encounter here and there are produced by causes of a subordi-
nate kind, as, e.g., by the egg's possessing a greater or less amount
of yolk.

When we see that the establishment of the central nervous system,,
of the eye, of the spinal column, of the viscera, etc., takes place in
Mammals on the whole just as it does in Amphibia, Birds, and
Reptiles, the conclusion is near at hand, and justified, that Man
afso in his development is no excf ptlon to this general phenomenon.
Thus in the study of Embryology we are naturally led to the com-
parative, method. What, owing to the nature of the difficulties, we
cannot learn directly about the development of Man, we seek to
deduce by the investigation of other Vertebrates.

In earlier decennia the Hen's egg wa^ the favorite object, and it
i-s upon this that we possess the most numerous and most complete
series of observations. During the last twenty years research has
also been directed to Mammals, — in the investigation of which the
greatest difficulties have to be surmounted, — as well as to Reptiles,

INTRODUCTION. 3

Amphibia, Fishes, etc. Only through the observation of such various
objects has insight been acquired into many processes, which in their
essence remained unintelligible to us from the study of the Chick
alone. For it was thus that one first learned to distinguish the
important from the accessory and unimportant, and to understand
the laws of development in their generality.

In this text-book, therefore, I shall not confine myself to a single
object, such as the egg of the Hen or the Rabbit, but from more
general comparative standpoints shall endeavour to present what,
through extensive series of investigations, we have thus far recognised
as the rule in regard to the real nature of the processes of fertilisa-
tion and cleavage, the formation of the germ layers, etc.

However, let no one expect a text-book of comparative Embryo-
logy. The purpose and the problem is first of all to learn to com-
prehend the development and the structure of the human body.
What we know about that has been placed before everything else,
and the embryology of the remaining Vertebrates has been cited, and,
as it were, fully utilised, only in so far as was necessary for the
purpose indicated.

In the division of the embryological material proposed by us, ac-
cording to the separate systems of organs, there is a long series of
processes, with which the development begins, which do not permit
of an arrangement, because at the beginning the fundaments of
definite, afterwards differentiated organs, are not recognisable in the
germ. Before there is any formation of organs, the egg is divided
into numerous cells, and these then arrange themselves into a few
larger complexes, which have been called the germ-layers, or the
primitive organs of the embryo. Further, in the higher Verte-
brates there are formed certain organs, which are useful only during
embryonic life, and are subsequently lost — namely, the foetal mem-
branes and fcetal appendages. All of the processes of that nature
we shall treat of connectedly, and by themselves. In accordance
with this, we can divide our theme into two main sections, the first
of which will deal with the initial processes of development and the
embryonic membranes, the second with the origin of the separate
systems of organs. In order to facilitate for the advanced a more
thorough study, and a penetration into embryological literature, a
survey of the more important original works is given at the close of
the separate chapters. On the other hand, text-books of Embryo-
logy may be mentioned in this place. [Compare also the larger
monographic works cited at the end of the book.]

MANUALS AND TEXT-BOOKS.

Valentin, G. Handbuch der Entwicklungsgeschichte des Menschen mit

vergleichender Kiicksicht der Entwicklung der Saugethiere und Vogel.

Berlin 1845.
Bischoff. Entwicklungsgeschichte der Saugethiere und des Menschen.

Leipzig 1842.

Hathke, H. Entwicklungsgeschichte der Wirbelthiere. Leipzig 1861.
Kolliker, A. Entwicklungsgeschichte des Menschen und der hoheren Thiere.

Academische Vortrage. Leipzig 1861. 2. ganz umgearbeitete Auflage.

Leipzig 1879.
Kolliker, A. Grundriss der Entwicklungsgeschichte des Menschen und der

hoheren Thiere. 2. Auflage. Leipzig 1884.
Schenk. Lehrbuch der vergleichenden Embryologie der Wirbelthiere. Wien

1874.
Haeckel, E. Anthropogenic oder Entwicklungsgeschichte des Menschen.

Leipzig 1874. Dritte Auflage. 1877.
Foster, M., and F. M. Balfour. The Elements of Embryology. Part I.

(Chick.) London 1874. 2nd edit, by Adam Sedgwick and Walter Heape

1883. German translation by Kleinenberg. Leipzig 1876.
His, W. Unsere Korperform und das physiologische Problem ihrer Ent-

stehung. Leipzig 1875.
Balfour, F. M. A Treatise on Comparative Embryology. London 1880, -81,

2 vols. German translation by Dr. C. Vetter. Jena 1881.
Homiti, Q-. Lezioni di embriogenia umana e comparata dei vertebrati. Siena

1881, -82, -88.

Preyer, W. Specielle Physiologic des Embryo. 1883, -84.
Hoffmann, C. K. Grondtrekken der vergelijkende Ontwikkelingsgeschie-

denis van de gewervelde Dieren. Leiden 1884.
Duval, M. Atlas d'Embryologie. Paris 1888.

PAET FIRST,

CHAPTER I.
DESCRIPTION OF THE SEXUAL PRODUCTS.

EGG-CELL AND SEMEN-CELL.

IN most animals, and without exception in all Vertebrates, the
development of a new being can take place only when reproductive
elements, produced by two sexually different individuals, — the egg
by the female, and the seminal corpuscle or seminal filament by th§
male, — are at the proper time brought - into union as the result of
the procreative act.

The egg and the seminal filament are simple elementary parts or celts,
which are produced in special glandular organs, the egg-cells in the
ovary of the female, and the semen-cells in the testis of the male.
After the beginning of sexual maturity at definite periods, they
detach themselves within the sexual organs from their union with
the remaining cells of the body, and form, under suitable conditions
of development, among which the union of the two sexual cells is
the most important, the starting-point for a new organism.

First of all, therefore, we have to acquaint ourselves with the
peculiarities of the two kinds of sexual products.

1. The Egg-cell.

The egg is by far the largest cell of the animal body. At a time
when nothing was known of its cell-nature, its separate components
were given special names, which remain in use even at the present
time. The contents were called egg-yolk, or vitellus ; the cell-nucleus
was called vesicula germinativa, or germinative vesicle, discovered by
the physiologist PURKINJE ; the nuclear corpuscles, or nucleoli, were
called germinative spots, or maculce germinativce (WAGNER) ; and,
finally, the cell-membrane was called the yolk-membrane, or mem-
brana mtellina. All these parts vary in not unimportant ways from

8

EMBRYOLOGY.

the ordinary condition of the protoplasm and nucleus of most animal
cells.

The vitellus (figs. 1 and 3 n.-d) rarely appears homogeneous, mucila-
ginous, and translucent, like the protoplasm of most cells; it is
ordinarily opaque and coarsely granular. This results from the
fact that the egg-cell, during its development in the ovary, stores
up in itself nutritive materials, or reserve stuffs. These consist of
fat, of albuminous substances, and of mixtures of the two, and
are described, according to their form, as larger and smaller yolk-
spherules, yolk-plates, etc. Later, when the process of development
is in progress, they are gradually used up in the growth and for
the increase of the embryonic cells. The fundamental substance

of the egg, in which the reserve stuff's
just now referred to are imbedded, is
protoplasm, physiologically the most in-
teresting and important of substances,
because in it take place, as we infer
from many phenomena, the essential
life-processes.

We must therefore distinguish in
the yolk, in accordance with the sug-
gestion of VAN BENEDEN, (1) the egg-
protoplasm, and (2) the yolk-substance.
or deutoplasm, which is of a chemi-
cally different nature, and is stored
up in the former.
When the deposition of reserve materials takes place to a great
degree, the really essential substance, the egg-protoplasm, may
become almost entirely obscured by it (figs. 3, 4). The protoplasm
then fills up the small interstices between the closely packed yolk-
globules, yolk-cakes, or lamellae, as mortar does those between the
stones in masonry, and appears in sections only as a delicate net-
work, in the smaller and larger meshes of which lie the yolk-elements.
Only at the surface of the egg is the egg-plasm constantly present
as a thicker or thinner continuous cortical layer.

The germinative vesicle usually occupies the middle of the egg.
It is the largest nuclear structure in the animal body, and its
diameter generally increases with the size of the egg.

The germinative vesicle (figs. 1, 2) is separated from the yolk by
a firm membrane, which may often be distinctly demonstrated, and
which surrounds various in eluded components : nuclear liquid (Kern-

Fig. 1. — Immature egg from the ovary
of an Echinoderm. The large ger-
minative vesicle shows a germinative
dot, or nucleolus, in a network of
filaments, the nuclear network.

DESCRIPTION OF THE SEXUAL PRODUCTS.

saft), nuclear network, and nudeoli. The nuclear liquid is more
fluid than the yolk, in the fresh condition usually as clear as water,
and when coagulated by the addition of reagents, absorbs only
a little or no coloring matter. It is traversed by a network
of delicate filaments (kn), which attach themselves to the nuclear
membrane. In this network are enclosed nudeoli, or germinative
spots (&/), small, for the most part spherical, homogeneous, lustrous
structures, which consist of a substance akin to protoplasm — nuclear
substance or nuclein. Nudein is distinguishable from protoplasm —
in addition to certain other chemical reactions' — especially by the
fact that it absorbs with great
avidity pigments such as car-
mine, hsematoxylin, aniline,

etc., on account of which it has JSQ£FJ0 <^lSs33^---- *»

also received from FLEMMING
the name chromatin.

The number of the nudeoli
in the germinative vesicles of
different animals is highly
variable, but it is tolerably
constant for each species;
sometimes there is only a

, , T Fig. 2.— Germinative vesicle of a Frog's egg that

single nucleolus present is 8till 8mall ^ immature. It 8hows very

(fig. 1), Sometimes there are numerous mostly peripheral germinative spots

„ (A/), in a fine nuclear network (kn). m, Nu-

several or even very many of clear membrane.

them (fig. 2kf). Accordingly

one may with AUERBACH distinguish uninucleolar, plurinucleolary

and multinucleolar germinative vesicles.

At their surfaces eggs are surrounded by protective envelopes, the
number and condition of which are exceedingly variable throughout
the animal kingdom as well as among Vertebrates. It is best to
divide them, as LUDWIG has done, according to their method of
origin, into two groups, into the primary and the secondary egg-
membranes. Primary egg-membranes are such as have been pro-
duced either by the egg itself or by the f ollicular cells within the ovary
and the egg-follicle. Those produced by the yolk of the egg are
called vitelline membrane ; those formed by the f ollicular epithelium,
chorion. All which take their origin outside of the ovary, as a
result of secretions on the part of the wall of the oviduct, &re to be
designated as secondary egg-membranes.

In their details the eggs of the various species of animals differ

1 0 EMBRYOLOGY.

from each other in a high degree, so that they must really be con-
sidered as the most characteristic for the species of all the kinds
of animal cells. Their size, which is due to a greater or less ac-
•cumulation of deutoplasm, varies so extensively that in some species
the egg-cells can be only barely recognised as minute dots, whereas
in others they attain the considerable dimensions of a Hen's egg, or
even of an Ostrich's egg. The form is usually globular, more rarely
•oval or cylindrical. Other variations arise from the method in
which protoplasm and deutoplasm are constituted and distributed
within the limits of the egg ; there are in addition the differences of
the finer structure of the germinative vesicle and the great variability
<of the egg-membranes.

Some of these conditions are of great significance from their in-
:fluence on the manner of subsequent development, They have been
employed as a basis for a classification of the various kinds of eggs.

It is most expedient to divide eggs into two chief groups, — into
simple and into compound 'eggs, — the first of which is divisible into
several sub-groups.

A. Simple Eggs.

Simple eggs are such as are developed in an ovary out of a single
germinal cell, The eggs of all the Vertebrates and most of the
Invertebrates belong to this group.

In this chief group there occur, according to the manner in which
protoplasm and deutoplasm are distributed within the egg, three
modifications, which are of very great importance in the determination
of the first processes of development.

In the simplest case the deutoplasm, which ordinarily is present
only to a limited amount in the correspondingly small egg, is more
or less uniformly distributed in the protoplasm (fig. 1). In other
cases there has arisen out of this original condition, in conjunction
with an increase in the bulk of the yolk-material, an inequality in
the distribution of the two egg-substances previously distinguished.
The egg-plasma has accumulated in greater abundance at certain
regions of the egg -territory, and the deutoplasma at other regions.
Consequently, a contrast has arisen between portions of the egg-cell
which are richer, and those which are poorer, in protoplasm. A
further accentuation of this contrast exercises an extraordinarily
broad and profound influence on the first processes of development,
which take place in the egg after fertilisation. That is to say,
the changes, which further on are embraced under the process of

DESCRIPTION OF THE SEXUAL PRODUCTS.

11

A.P

cleavage, make their appearance only at the region of the egg
which is richer in protoplasm, whereas the region which is more
voluminous and richer in deutoplasm remains apparently quite
unaltered, and is not divided up into cells. By this means the
contrast, which was already present in the unsegmented egg,
becomes during development disproportionately greater and more
obvious. The one part undergoes changes, is divided into cells, and
out of these produces the individual organs ; the other part remains
more or less unaltered, and is gradually employed as nutritive
material. Following the example of REICHERT, the part of the
yolk which is richer in protoplasm, and to which the developmen-
tal processes remain confined,
has been designated formative
yolk, and the other nutritive
yolk.

The unequal distribution of
formative yolk (vitellus forma-
tivus) and of nutritive yolk
(vitdlus nutritivus) within the
egg is accomplished in two dif-
ferent ways.

In the one case (fig. 3) the
formative yolk is accumulated
at one pole of the egg as a, flat
germ-disc (k.sc/i). Inasmuch as
its specific gravity is less than
that of the nutritive yolk (n.d)
collected at the opposite pole, it
is always directed upward, and

it spreads itself out on the yolk just like a drop of oil on water. In
this case, therefore, the egg has undergone a polar differentiation ;
when at rest it must always assume a definite position, owing to the
unequal weight of the two poles. The dissimilar poles are distin-
guished : the upper, lighter pole, with the germ-disc, as the animal
(A.P); the under, heavier and richer in yolk, as the vegetative pole
(V.P). The polar differentiation of eggs is often encountered in
Vertebrates, and is especially prominent in the classes of Bony
Fishes, Reptiles, and Birds.

In the second case (fig. 4) the formative yolk (b.d) is accumulated
over the whole surface of the egg, and surrounds the centrally placed
nutritive yolk (n d) as a uniformly thick, finely granular cortical

V.P

Fig. 3. — Diagram of an egg with the nutritive
yolk in a polar position. The formative
yolk constitutes at the animal pole (A.P) A
germ-disc (k.sch), in which the germinative
vesicle (it. 6) is enclosed. The nutritive yolk
(n.eZ) fills the rest of the egg up to the
vegetative pole (V.P).

12

EMBRYOLOGY.

b.d
n.d

iii— fc.ft

Tig. 4.— Diagram of an egg with the nutri-
tive yolk in the centre. The germinative
vesicle (fc.ft) occupies the middle of the
nutritive yolk (n.d), which is enveloped
in a mantle of formative yolk (b.d).

layer. The egg exhibits central differentiation, and therefore does
not assume a constant position when at rest. As in the former case
the yolk was polar in position, so here it is central. Such a condition

is .never encountered in Verte-
brates, but it is characteristic of
Arthropods.

In order to distinguish the three
modifications, BALFOUR has made
use of the expressions alecithal,
telolecithal, and centrolecithal. He
calls those eggs alecithal in which
the deutoplasm, in small amount,
is uniformly distributed through
the protoplasm ; telolecithal, those
in which it is accumulated at the
vegetative pole \ centrolecithal,
those in which the accumulation of
deutoplasm has taken place at the

centre. In what follows, we shall speak of (1) eggs with uniformly
distributed yolk, (2) eggs with polar deutoplasm, and (3) eggs with
central deutoplasm.

It is now expedient to illustrate what has just been said by typical
examples, and for this purpose the eggs of Mammals, Amphibia,
Birds, and Arthropods have been selected. We shall also frequently
recur to these in the presentation of the subsequent phases of develop-
ment.

The egg of Mammals and of Man is exceedingly small, since it mea-
sures on the average only 0*2 mm. in diameter. It is for this reason
that it was not discovered until the present century — in 1827, by CARL
ERNST VON BAER. Previously the much larger GRAAFIAN follicle
of the ovary, in which the smaller true egg is enclosed, had been
erroneously taken for the latter. The Mammalian egg (fig. 5) con-
sists principally of a finely granular protoplasmic substance, which
contains dark, fat-like spherules and granules (deutoplasm), and
which is turbid and opaque in proportion to the amount of these.
The germinative vesicle (k.b) contains a large germinative dot (&•/),
located, together with a few smaller accessory dots, in a nuclear
network (k.n). The egg-membrane is called zona_ pelludda, (z.p),
because it surrounds the yolk as a relatively thick and clear layer. It
is a primary membrane, for it is formed within the GRAAFIAN follicle,
by the follicular cells. Under high magnification the zona pellucida

DESCRIPTION OF THE SEXUAL PRODUCTS.

13

sj^O&y&^sagjgl

3?il§iMSii

Tig. 5. — Egg from a Rabbit's follicle which was 2 mm. in diameter, after WALDEYER. It is
surrounded by the zona pellucida (z.p), on which there rest at one place follicular cells (/.z).
The yolk contains detitoplasmic granules (d). In the germinative vesicle (£.6) the nuclear
network (k.n) is especially marked, and containe a large germinative dot (k.f),

(z.p) appears radially striate, since it is traversed by numerous pore-
canals, into which, as long as the egg remains in the GRAAFIAN follicle,
very fine projections of the follicular cells (f.z) penetrate. These
fuse with the egg-plasm, and are probably concerned in the nutrition
<ind growth of the contents of the egg. (RETZIUS.)

The human ovum is wonderfully like the egg of Mammals in size,
in the condition of its contents, and the nature of its membranes.
However, it always can be distinguished by means of special, though
trifling, characteristics, as the careful investigations of NAGEL have
shown. Whereas in the Rabbit lustrous, fat-like spherules render
the yolk cloudy, the human ovum retains its transparency during
all stages of development, so that one may recognise most ac-
.curately all its structural details, even on the living object. The
yolk is divided into two layers. The inner layer contains principally
deutoplasm, which produces in this case, contrary to most of the
Mammals, only a slight cloudiness ; it consists in part of feebly
lustrous, in part of highly refractive fragments, some coarser, some
finer ; but it is not possible to recognise the mutual boundaries of

14

EMBRYOLOGY.

the individual components, as is the case in other Mammals and
lower animals, where one distinguishes with great ease granules
and distinct drops. The outer layer or peripheral zone of the yolk is
more finely granular and still more transparent than the central
part, and contains the gerrnmative vesicle with a large gerrninative
dot, in which NAGEL was able to observe amoeboid motions. The
zona pellucida is remarkably broad ; it is striate, and is separated
from the yolk by a narrow (perivitelline) space. There are two or
three layers of follicular cells attached to the periphery of the egg
when it is set free from the GRAAFIAN follicle. The long diameters
of these cells are arranged in a radial direction around the egg, as
is general in Mammals, and it is due to this circumstance that they
have received the name corona radiata, introduced by BISCHOFF..
The human egg without the follicular epithelium measures, on the
average, O17 mm. in diameter.

The eggs of many. Worms, Molluscs, Echinoderms, and Ccelenterates
agree with the Mammalian egg in their size, and in the method in
which protoplasm and deutoplasm are uniformly distributed through,
the egg.

The eggs oj Amphibia, which were cited as the second example,
foim a transition from simple eggs, with uniform distribution of
yolk-material, to eggs with -distinctly expressed and externally
recognisable polar differentiation. Already these have deposited in
themselves a large amount of deutoplasm, and have thereby acquired
a very considerable size. The Frog's egg, for example, is stuffed
full of closely compacted, fatty-looking yolk-lumps (Dotterscholleii)
and yolk-plates. The egg protoplasm is in part distributed as a
network between the little yolk-plates ; in part it forms a thin
cortical layer at the surface of the egg. Upon closer examination
however, the beginning of a polar differentiation is most distinctly
recognisable even here. It manifests itself in this way : at one
pole, which at the same time appears black on account of a deposit
of superficial pigment, the yolk-plates are smaller and enveloped in
more abundant egg-plasm ; and also, nrobably as a consequence of
this, slight differences in specific gravity are distinguishable between
the pigmented and the unpigmented, or the animal and the vegetative,
halves of the egg.

The germinative vesicle (fig. 2) lies in the middle of the immature
egg, is exceedingly large, even visible to the naked eye, and multi-
nucleolar, inasmuch as there are a hundred or more large germinative
dots (kf) distributed irninediatplv under the nuclear membrane.

DESCRIPTION OF THE SEXUAL PRODUCTS.

15-

k.b k.sch

The envelopes exhibit, in comparison with the Mammalian egg, an
increase in number, for to the zona pellucida (zona radiata), which
is produced in the follicle, there is subsequently added still another,
a secondary envelope. This is a thick, viscid, gelatinous layer,
which is secreted by the wall of the oviduct, and which becomes
swollen in water.

The polar differentiation, taken, as it were, in the very process
of developing in the 'case of the Amphibia, is found sharply expressed
in our third example, the Bird 's egg.

In order to form a correct picture of the condition of the egg-cell
in the case of the Hen, or of any
other bird, we must seek it while
still in the ovary, at the moment
when it has finished its growth,
and is ready to be set free from the
follicle. It is then ascertained that
only the spheroidal yolk, the so-
called yellow of the egg, which in
itself is an enormously large cell
(fig. 6a), is developed in the botryoidal
ovary. It is enclosed in a thin but
tolerably firm pellicle (d.h), the
vitelline membrane, the rupture of'
which is followed by an extrusion of the soft pulpy contents. By
careful examination one will discover upon the latter a small white
spot, the germinative disc (k.sch), or discus proligerus, also called scar
or cicatricula. It has a diameter of about 3 or 4 mm., and consists
of formative yolk, — a finely granular protoplasm with small yolk-
spherules, — which alone is involved in the process of cleavage. In
the flattened germinative disc is also found the germinative vesicle,
fig. 6a (k.b) and fig. 6b (x), which is likewise somewhat flattened and
lenticular.

The remaining chief mass of the egg-cell is nutritive yolk, which-
is composed of numberless yolk-spherules united by slight traces of
egg-plasm, as though by a cement. Information concerning its finer
structure is to be gained from thin sections through the hardened
egg, which should be cut perpendicularly to the germinative disc.
According to differences in staining and in elementary composition,
there are now to be distinguished the white and the yellow nutritive
yolk (fig. 6a).

The white yolk (w.d) is present in the egg cell only in a small.

Fig. 6a.— Egg-cell (yolk) of the Hea
taken from the ovary, k.sch, Germina-
tive disc ; i. 6, germinative vesicle ;
ic.d, white yolk", g.d, yellow yolk
d.h, vitelline membrane.

16

EMBRYOLOGY.

quantity ; it forms a thin layer over the whole surface, the white
yolk-rind ; secondly, it is accumulated in somewhat greater quantity
under the germinative vesicle, for which it at the same time forms a
bed or cushion (PANDER'S nucleus) ; and, thirdly, from this region it

Pig. 6b.— Section of the germ-disc of a mature ovarian Hen's egg still enclosed in the capsule,
after BALFOUR.

«, Connective-tissue capsule of the egg ; 6, epithelium of the capsule, on the inside of which lies
the vitelline membrane reposing upon the egg; c, granular substance of the germinative
disc ; w.y, white yolk, which passes imperceptibly into the finely granular substance of the
disc ; x, germinative vesicle enclosed in a distinct membrane, but shrivelled up ; y, space
originally occupied by the germinative vesicle, but made empty by its shrivelling up.

penetrates in the form of a mortar-pestle into the very centre of the
yellow yolk, where it terminates in a knob-like swelling (latebra,
PURKINJE). Upon boiling the egg, it is less coagulated, and remains
softer than the yellow yolk. In the coagulated condition the latter
discloses upon sections a lamellated condition, in that it consists of
smaller and larger spherical shells, which envelope the latebra.

The two kinas of yolk also differ from each other in respect to
the condition of their elementary particles. The yellow yolk
consists of soft plastic spherules (fig. 7 A) from 25 to 100 //, in
diameter, which acquire a punctate appearance from the presence
of numerous exceedingly minute granules. The elements of the
white yolk are for the most part smaller (fig. 7 B), and likewise
spherical, but contain one or several large highly refractive granules.

Fig, 7.— Yolk-elements from the Fowl's egg, after BALFOUR. A, Yellow yolk ; B, white yolk.

At the boundary between the two kinds of yolk there are present
spherules which effect a transition between them.

The freshly laid Hen's egg (fig. 8) has a different appearance
from that of such an ovarian egg. This results from the fact ihat
there is deposited around the yolk, when it detaches itself from

DESCRIPTION OF THE SEXUAL PRODUCTS. 17

the ovary and is taken up by the oviduct, several secondary en-
velopes derived from the wall of the oviduct, viz., the white of the
egg, or the albumen, the shell-membrane, and the calcareous shell.
Each of these parts is formed in a special region of the Hen's oviduct.
The latter is divided into four regions : (1) A narrow ciliated
initial part, into which the liberated egg is received, and where it
is fertilised by the spermatozoa already accumulated there ; (2) a

Fig. 8.— Diagrammatic longitudinal section of an unincubated Hen's egg, after ALI.EN THOMSON.
(Somewhat altered.)

b.l. Germ-disc ; w.y. white yolk, which consists of a central flask-shaped mass and a number of
concentric layers surrounding the yellow yolk (y.y.) ; v.t. vitelline membrane ; x. a somewhat
fluid albuminous layer, which immediately envelopes the yolk ; w. albumen composed of
alternating layers of more and less fluid portions ; ch.l. chalazse ; a.ch. air chamber at the
blunt end of the egg — simply a space between the two layers of the shell-membrane ; i.t.m.
inner, s.m. outer layer of the shell-membrane ; s. shell.

glandular region, covered with longitudinal furrows, from which
the albumen is secreted and spread around the yolk in a thick layer ;
(3) a somewhat enlarged part, covered with small villi, the cells
of which secrete calcareous salts, and thus cause the formation of
the shell; (4) a short narrower region, through which the egg
passes rapidly, and without undergoing any further change, when
being deposited.

The envelopes furnished in succession by the oviduct have the
following composition : —

The white of the egg, or albumen (w), is a mixture of several
materials: according to chemical analyses, it contains 12% albumen,

2

18 EMBRYOLOGY.

1-5% fat and other extractive materials, 0*5% salts (potassic chloride,
sodic chloride, sulphates, and phosphates), and 86% water. It
surrounds the yolk in several layers of varying consistency. There
is a layer quite closely investing the latter, which is firmer and
especially noteworthy because it is prolonged into two peculiar
spirally twisted cords, the chalazce (ch.l), which consist of a very
compact albuminous substance, and which make their way through
the albumen to the blunt and to the pointed poles of the egg

The albumen is enclosed by the thin but firm shell-membrane (s.m)
(membrana testae), which is composed of felted fibres. It may be
separated into two lamellae — an outer, which is thicker and firmer,
and an inner, which is thinner and smooth. Soon after the egg is
laid the two layers separate from each other at the blunt pole, and
enclose between them a space filled with air (a.cli), — the so-called
air-chamber, which continues to increase in size during incubation r
and is of importance for the respiration of the developing Chick.

Finally, the shell, or testa (s), is in close contact with the shell-
membrane ; it consists of an organic matrix (2%), in which 98% cal-
careous salts are deposited. It is porous, being traversed by small
canals, through which the atmospheric air may gain entrance to the
egg. The porosity of the calcareous shell is an absolute necessity f 01
the normal development of the egg, since the vital processes in the
protoplasm can take place only when there is a constant supply of
oxygen. If the porosity of the shell be destroyed, either by soaking
it in oil or closing its pores with varnish, the death of the incubated
egg ensues in a very short time.

B. Compound Eggs.

Compound eggs are found only in a few subdivisions of the
invertebrated animals, as in the Cestodes, Trematodes, etc. ; they
are noteworthy in this respect, that they are produced by the
union of numerous cells, which are formed in two different glands
of the sexual apparatus of the female, — in the germariurn and in
the vitellarium. In the germarium is developed the egg-cell in the
restricted sense. This is always very small, and consists almost
exclusively of egg-plasm. When this cell at its maturity is set free
from its surroundings and comes into the sexual outlets, it is obliged
to pass the opening of the vitellarium] here there are associated
with it a number of yolk-cells, which, owing to deposition of reserve
material in the protoplasm, appear turbid and coarsely granular^

DESCRIPTION OF THE SEXUAL PRODUCTS. 19

and which constitute the dower that is given by the maternal
organism to the developing germ on its way. Thereupon the whole
is enclosed in one or several secondary egg-membranes, and now|
constitutes the compound egg, in which, however, the developmental
processes manifest themselves exclusively on the simple germ cell ;
it is that alone which is fertilised and segments, while the yolk-cells
gradually degenerate and are employed as nutritive material. Thus
in this case also, upon closer examination, the general law, that the
descendent organism takes its origin from a single cell of the maternal
body, suffers no exception.

2, The Seminal Filaments.

In contrast with eggs, which are the largest cells of the animal
body, the sperm-cells or sperm-filaments (spermatozoa) are the
smallest elementary parts ; they are accumulated in great multitudes
in the seminal fluid of "the male, but can be recog-
nised in it only by the aid of high magnification,
being, for the most part, slender motile filaments. ^ A— £

Inasmuch as every cell consists of at least two
parts, namely, nucleus and protoplasm, we must
look for these parts in this case also. We shall
take for description the spermatozoa of Man.

In Man the seminal filaments (fig. 9) are arbout
0*05 mm. long. One may distinguish as head (k)
a short but thick region, which marks the anterior
end, as tail a long thread-like appendage (s), and
between the two a so-called middle piece (ra). seen in two dif-

The head (k) has the form of an oval plate, '™* P08itions-

f \ I Each consists of a

which is slightly excavated on both surfaces, head (k), a mid-
and is somewhat thinner toward the anterior end. ^ ^ece :rrt)> an
Seen from the side (£) it presents a certain re-
semblance to a flattened pear. Chemically considered, it consists of
nuclear substance (nuclein or chromatin), as microchemical reactions
show. To the head is united, by means of a short* part called the
middle piece (m), the long thread-like appendage (s), which is com-
posed of protoplasm, and is best compared to a flagellum, because,
like the latter, it executes peculiar serpentine motions in virtue of
its contractile properties. By means of these motions the sper-
matozoon moves forwards in the seminal fluid with considerable
velocity.

20 EMBRYOLOGY.

The spermatozoa have often been designated — and it seems
to us with entire justice— as cilia te, or still better as flagellate,
cells.

The spermatozoa of the remaining Vertebrates have a similar
structure to that of Man ; on the whole, the diversity of form which
is encountered in the comparative study of the egg-cell in the animal
kingdom is wanting here.

That spermatozoa are in reality metamorphosed cells cannot be
more clearly demonstrated than by their development. According
to the extended observations of LA. V ALETTE and others, each
spermatozoon is formed from a single seminal cell or spei matid, and,
to be more precise, the head w formed from the nucleus, the contractile
filament from the protoplasm.

The metamorphoses which take place in the development have
been investigated with the greatest detail by FLEMMING and
HERMANN in the case of Salamandra maculata, the spermatozoa of
which are characterised by their very great size. The individual
spermatozoon here consists of : (1) a very long head, which has the
form of a finely pointed skewer, and takes up stains with avidity ;
(2) a short cylindrical middle piece, which differs from the first part
in chemical properties also ; (3) the motile caudal filament, which in
the Salamander exhibits the additional peculiarity that it is provided
with a contractile undulating membrane. Of these three regions
the skewer-like head, and probably also the middle piece, arise from
the nucleus of the spermatid, whereas the contractile filament is
differentiated out of the protoplasm. In the development of the
head the nucleus of the seminal cell is seen to become more and
nore elongated (fig. 10 A, B); at first it takes the form of a pear
{fig. 10 A k); then it grows out into an elongated cone (fig. 10 B k),
the base of which serves as the point of attachment for the middle
piece (mst). The cone becomes elongated and narrowed into a rod
(fig. 11 A, B), which is finally converted into the characteristic form
of a skewer. With this elongation of the nucleus the chromatic
network becomes more and more dense, and at last assumes a quite
compact and homogeneous condition, as in the mature spermatozoon.
The fundament (Anlage) of the middle piece (figs. 10, 11, A, £, mst)
makes its appearance early — when the nucleus begins to elongate —
at that end of the nucleus which was called its base, in the form of
a small oval body, which at first takes up stains like the head, but
afterwards loses this property. Its first appearance demands still
further elucidation.

DESCRIPTION OF THE SEXUAL PRODUCTS.

21

Why are the male sexual cells so small and thread-like, and so
differently constituted from the eggs?

The dissimilarity between the male and the female sexual cells is
explained by the fact that a division of labor has arisen between the
two, inasmuch as they have adapted themselves to different missions.

Fig. 10 A and B, — Initial stages of the metamorphosis
of the seminal cell into the seminal filament,
after HERMANN.

A, Seminal cell with pear-shaped nucleus ; B, seminal
cell with cone-shaped nucleus ; sz, seminal cell ; k,
nucleus with chromatin network, and nucleoli (n) ',
mst, bod> out of which the middle piece is developed ;
r, ring-like structure, which is in contact with the
middle piece, and is claimed to have relation to the
formation of the spiral membrane of the filament ;
f, caudal appendage of the seminal filament.

Fig. 11 A and B.— Two terminal
stages in the metamorphosis
of the seminal cell into
the seminal filament, after
FLEMMINO.

k, Nucleus, which has become
elongated to form the head
of the spermatozoon ; mst,
its middle piece ; /, its
caudal filament.

The female cell has assumed the function of supplying the substances
which are necessary for that nutrition and growth of the cell proto-
plasm which a rapid accomplishment of the process of development
demands. It has therefore, while in the ovary, stored up in itself
yolk-substance, reserve material, for the future ; and consequently
has become large and incapable of motion. But inasmuch as it
is necessary for the accomplishment of a process of development
that union with a second cell from another individual should take
place, and since non-motile bodies cannot unite, theiefore the male
element has been suitably modified to meet this second requirement.

22 EMBRYOLOGY.

For the purpose of locomotion and in order to make possible the
union with the non-motile egg-cell, it has become metamorphosed
into a contractile filament, and has rid itself completely of all
substances, as, for example, yolk-material, which would interfere
with this principal requirement. At the same time it has assumed
the form best adapted for passing through the envelopes with
which, as a means of protection, the egg is surrounded, and for
penetrating the yolk.

The conditions especially in the vegetable kingdom confirm the
accuracy of this interpretation. There are plants of the lowest
forms in which the two copulating sexual cells are entirely alike,
both being small and motile ; and there are other related species in
which a gradual differentiation is brought about by the fact that
one of the cells becomes richer in yolk and incapable of motion,
while the other becomes smaller and more active. From this it is
evident that the stationary egg must now be sought out by the
migratory cell.

A few physiological statements may be in place in this connection.
In comparison with other cells of the animal body, and especially
in comparison with the eggs, the seminal filaments are characterised
by greater duration of life and power of resistance, a fact which is
frequently of importance for the success of fertilisation. The mature
spermatozoa, after they are set free from their connection with
other cells, remain for months in the testes and vasa deferentia
without losing their fertilising power. They also appear to remain
active for a long time after having been introduced into the sexual
passages of the female, perhaps for several weeks in the case of Man.
For some animals this is demonstrable to a certainty. For example, it
is known that the semen of Bats remains alive in the uterus of the
female during the whole winter ; and in the case of the Fowl it is
known that fertilised eggs can be laid up to the eighteenth day after
the removal of the Cock.

In the presence of external influences semen shows itself to be
much more resistent than the egg-cell, which is easily injured or
killed. For example, when semen is frozen and then thawed out,
the motion of the seminal filaments comes back again. Many salts,
if they are employed not too strong, have no deleterious influence.
Narcotics in strong concentration, and when employed for a long time,
make the filaments motionless, without immediately killing them,
because after removal of the injurious substance they can be revived.

DESCRIPTION OF THE SEXUAL PRODUCTS. 23

Very weak alkaline solutions stimulate the motions of seminal
filaments ; on the contrary, acids, even when they are very dilute,
produce death. Accordingly the motion becomes more lively in all
animal fluids of alkaline reaction, whereas in acid solutions it soon
dies out.

HISTORY. — The discovery that egg and seminal filament are simple cells is
of far-reaching import for the comprehension of the whole process of develop-
ment. In order to appreciate this to its full extent, it will be necessary to
make a digression into the historical field. Such a digression will acquaint us
with some fundamental transformations, which have affected our conception of
the essentials of developmental processes.

In the last century, and even in the beginning of the present, ideas about the
nature of the sexual products were very indistinct. The most distinguished
anatomists and physiologists were of opinion that eggs agreed in their structure
in every particular with the grown-up organism, and therefore that they
possessed from the beginning the same organs in the same position and con-
nection as the latter, only in an extraordinarily diminutive condition. But in-
asmuch as it was not possible, with the microscopes of the time, actually to see
and demonstrate in the eggs at the beginning of their development the assumed
organs, recourse was had to the hypothesis that the separate parts, such as
nervous system, glands, bones, etc., must be present, not only in a very diminu-
tive, but also in a transparent condition.

In order to make the process more intelligible, the origin of the blossoms of
plants from their buds was cited as an illustrative example. Just as already
in a small bud all the parts of the flower, such as stamens and coloured petals,
are enveloped by the green and still unopened sepals, — just as the parts grow
in concealment and then suddenly expand into a blossom, so also in the de-
velopment of animals it was thought that the already present but small and
transparent parts grow, gradually expand, and become discernible. The doctrine
which has just been outlined was consequently called the Theory of unfolding,
or evolution. However, a more appropriate designation for it is the one intro-
duced during recent decennia— ^reformation theory. For the characteristic
feature of this doctrine is, that at no instant of development is there anything
new formed, but rather that every part is present from the beginning, or is
preformed, and consequently that the very essence of development — t/te be-
coming— is denied. " There is no such thing as becoming ! " is the way it is
expressed in the " Elements of Physiology " by HALLER. " No part in the animal
body was formed before another ; all were created at the same time."

As the necessary consequence of a rigid adherence to the pref ormation theory,
it follows, and indeed was formulated by LEIBNITZ, HALLER, and others, that
in any germ the germs of all subsequent offspring must be established or
included, since the animal species are developed from one another in un-
interrupted sequence. In the extension of this box-within-box doctrine
(Einschachtelungslehre) its expounders went so far as to compute how many
human germs at the least were concentrated in the ovary of mother Eve, and
thereby arrived at the number 200,000 millions.

The evolution theory offered a point of attack for a scientific feud, inasmuch
as every individual among the higher organisms is developed by means of the
cooperation of two separate sexes. When, therefore, the seminal filament as

24 EMBRYOLOGY.

well as the animal egg became known, there soon arose the actively discussed
question, whether the egg or the seminal filament was the preformed germ.
Decennium after decennium the antagonistic camps of the ovists and of the
animalculists stood opposed to each other. Those who followed the latter
thought they saw, with the aid of the magnifying glasses of the times, the
spermatozoa of man actually provided with a head, arms, and legs. The
animalculists recognised in the egg only a suitable nutritive soil, as it were,
which was necessary to the growth of the spermatozoon.

Jn the face of such doctrines there dawned a new period for Embryology,
when in 1759 CASPAE FEIEDEICH WOLFF in his doctor's dissertation opposed
the dogma of the evolution theory, and, casting aside preformation, laid down
the scientific principle that what one could not recognise by means of his
senses was certainly not present preformed in the germ. At the beginning, so he
maintained, the germ is nothing else than an unorganised material eliminated
from the sexual organs of the parent, which gradually becomes organised, but
only during the process of development, in consequence of fertilisation. Ac-
cording to WOLFF, the separate organs of the body differentiate themselves
one after another out of the hitherto undifferentiated germinal material. In
individual cases he endeavoured, even at this time, to determine more exactly,
by means of observations, the nature of the process. Thus C. F. WOLFF was
the founder of the doctrine of epigenesis, which, through the discoveries of the
present century, has proved to be the right one.*

WOLFF'S doctrine of unorganised germinal matter has been compelled since
then to give way to more profound knowledge, thanks to the improved optical
aids of recent times, and to the establishment of the cell-theory by SCHLEIDEN
and SCHWANX. A better insight into the elementary composition of animals
and plants was now acquired, and especially into the finer structure of the
sexual products, the egg-cell and the seminal filament.

So far as regards the egg-cell, a series of important works began with
PUEKINJE'S investigation of the Hen's egg in 1825, in which the germinative
vesicle was described for the first time. This was soon (1827) followed by
C. E. v. BABE'S celebrated discovery of the Mammalian egg, which had been
hunted for, but always without success. Extensive and comparative investiga-
tions into the structure of the egg in the animal kingdom were published in
1836 by E. WAGNEE, who also discovered at the same time in the germinative
vesicle the germinative dot (macula germinativa).

With the establishment of the cell-theory there naturally arose the question
as to how far the egg was in its structure to be regarded as a cell, — a question
which was for years answered in widely different ways, and which even now
from time to time is brought up for discussion in an altered form. Even at that
time SCHWANN, albeit with a certain reservation, expressed it as his opinion that
the egg was a cell, and the germinative vesicle its nucleus; but others, his co-
temporaries (BISCHOFF and others), regarded the germinative vesicle as a cell,

* Historical presentations of the theory of evolution and the theory of
epigenesis, which are worth the reading, have been given by A. KIECHHOFF
in his interesting paper, " CASPAE FEIEDEICH WOLFF. Sein Leben und seine
Bedeutung Mr die Lehre von der organischen Entwicklung." Jcnalsclie Zeit-
schrift fur Medicin und Naturwissenschaft, Bd. IV., Leipzig, 1868; and by W.
His, " Die Theorien der geschlechtlichen Zengung." Archiv filr Anthropclogic,
Bd. IV. u. V.

DESCRIPTION OF THE SEXUAL PRODUCTS. 25

and the yolk as a mass of enveloping substance. A unanimity of views in this
matter was brought about only after the general conception of " cell " had
received in Histology a more precise definition. This was due especially to
more accurate knowledge of the processes of cell-formation gained through
the works of NAGELI, KOLLIKER, REMAK, LEYDIG, and others.

The interpretation of eggs with separate formative and nutritive yolk, and
with partial cleavage, occasioned especial difficulty. Two antagonistic views
in this matter have existed for a long time. According to one view, eggs with
polar nutritive yolk (the eggs of Reptiles, Birds, etc.) are compound structures,
which cannot be designated as simple cells. Only the formative yolk, together
with the germinative vesicle, is comparable with the Mammalian egg ; the
nutritive yolk, on the contrary, is something new, superposed upon the cell
from without, a product of the follicular epithelium. The spherules of the
white yolk are explained as uninuclear and multinuclear yolk-cells. The
formative and nutritive yolk together are comparable with the entire contents
of the GRAAFIAN vesicle of Mammals. H. MECKEL, ALLEN THOMSON,
ECKER, STRICKEE, His, and others, have expressed themselves in favour of this
view with slight modifications in the details.

According to the opposite view of LEUCKART, KOLLIKER, GEGENBAUR,
HAECKEL, VAN BENEDEN, BALFOUR, and others, the Bird's egg is just as truly
a simple cell as the egg of a Mammal, and the comparison with a GRAAFIAN
follicle is to be rejected. The yolk never contains enclosed cells, but only
nutritive components. As KOLLIKER, especially in opposition to His, has
shown, the white-yolk spherules contain no structures comparable with genuine
cell-nuclei ; and therefore cannot be interpreted as cells. As GEGENBAUR
already in 1861 sharply formulated it : " The eggs of Vertebrates with partial
cleavage are on that account essentially no more compound structures than
those of the remaining Vertebrates; they are nothing else than enormous
cells peculiarly modified for special purposes, but which never surrender this
their real chaiacter." There would be no change in this interpretation, even
if it should prove to be that the yolk was formed in part from the follicular
epithelium, and was set free from the latter as a sort of secretion. In that
event we should have to do with a special method of nutrition of the egg, the
cell-nature of which cannot on that account be called in question.

Various components of the yolk have received special names. REICHERT
first distinguished as formative yolk the finely granular mass, which, in the
Bird's egg, contains the germinative vesicle, and forms the germ-disc, because
it alone undergoes the process of cleavage, and produces the embryo. The
other chief mass of the egg he called nutritive yolk, because it does not
break up into cells, and because subsequently, enclosed in a yolk-sac, it is
consumed as nutritive material. Afterwards His introduced for these the
names chief germ and accessory germ (Haupt- und Neberikevm).

AVhereas the nomenclature of REICHERT and His is applicable only to eggs
with polar arrangement of nutritive yolk, VAN BENEDEN (1870) has undertaken
the division of the substance of the egg from a more general standpoint. He
distinguishes between the protoplasmic matrix of the egg, in which, as in
every cell in general, the vital processes take place, and the reserve and
nutritive materials, which are stored up in the protoplasm in the form of
granules, plates, and balls, and which he designates as deutoplasm. Every
egg possesses both components, only in different proportions, in varied forms
and distribution. BALFOUR has selected this latter condition as a basis for

26 * « EMBRYOLOGY.

division ; and has consequently made the three groups of alecithal, telolecithal,
and centrolecithal eggs, for which I have selected the designation eggs with
little or uniformly distributed yolk, eggs with polar, and eggs with central
yolk.

In recent times investigation has been directed to the finer structure of the
germinative vesicle, in which KLEINENBEKG (1872) was the first to observe a
special protoplasmic nuclear trestle (Kerngerilsf) or nuclear network, which since
then has been shown by numerous researches to be a constant structure. In
the case of the germinative dot I have myself designated two chemically and
morphologically distinguishable substances as nuclein and paranuclein, the
investigations concerning the importance and the role of which in the develop-
ment of the egg are not yet concluded.

The history of the spermatozoa begins with the year 1677. A student in
Leyden, HAMM, in the microscopic examination of semen, saw the briskly
moving bodies, and communicated his observation to his teacher, the celebrated
microscopist LEEUWENHOECK:, who instituted more accurate investigations,
and published them in several papers, which soon attracted general attention.
The sensation caused was all the greater becausa LEEUWENHOECK declared the
seminal filaments to be the preexisting germs of animals, and maintained that
at fertilisation they penetrated into the egg-cell and grew up in it. Thus
arose the school of animalculists.

After the refutation of the preformation theory, it was thought that no
importance was to be ascribed to the seminal filaments in fertilisation, it
being held that it was the seminal fluid that fertilised. Even during the first
four decennia of the present century, the seminal filaments were almost
universally held to be independent parasitic creatures (spermatozoa) com-
parable with the Infusoria. Even in JOH. MULLER'S " Physiology " (1833-40)
occurs this statement : " Whether the semen-animalcules are parasitic animals,
or animated elements of the animals in which they occur, cannot for the
present be answered with certainty."

The settlement of the question was accomplished by comparative histological
investigations of the semen in the animal kingdom, and by physiological
experiment.

In two essays — " Beitriige zur Kenntniss der Geschlechtsverhaltnisse und
der Samenfliissigkeit wirbelloser Thiere," and "Bildung der Samenfaden in
Blaschen " — KOLLIKEB showed that in many animals, e.g., in the Polyps, the
semen consists of filaments only, the fluid being entirely absent ; and that in
addition the filaments are developed in cells, and consequently are themselves
elementary parts of animals. KEICHERT discovered the same to be true in
Nematodes. By means of physiological experiment it was recognised that
seminal fluid with immature and motionless filaments, and likewise mature but
filtered semen, did not fertilise. This was decisive for the view that the
seminal filaments are the active part in fertilisation, and that the fluid, which
is added thereto in the case of the higher animals under complicated sexual
conditions, "can be regarded only as a menstruum for the seminal bodies
which is of subordinate physiological significance."

Since then our knowledge (1) of the finer structure, and (2) of the develop-
ment of the seminal filaments, has made further advances. So far as regards
the first point, we have learned, especially through the works of LA VALETTE
and SCHWEIGGER-SEIDEL, to distinguish between head, middle piece, and

DESCRIPTION OP THE SEXUAL PRODUCTS.

tail, and to know their different chemical and physical properties. The view
expressed by KOLLIKER, that ordinarily the seminal filaments were the
metamorphosed and elongated nuclei of the seminal cells, underwent a modifi-
cation. According to the researches of LA VALETTE, only the head of the
seminal filament arises from the nucleus, the tail, on the contrary, from the
protoplasm of the spermatid. Finally FLEMMING brought forward convincing
proof that it is only the chromatin of the nucleus that is metamorphosed into
the head of the seminal filament. Important investigations concerning the
development of the seminal filaments in various animals have recently been
made by VAN BENEDEN ET JULIN, PLATNER, HERMANN, and others.

SUMMARY.

The most important results of this chapter may be briefly sum-
marised as follows : —

1. Male and female sexual products are simple cells.

2. The seminal filaments are comparable to flagellate cells. They
are usually composed of three portions, head, middle piece, and
contractile filament.

3. The seminal filament is developed out of a single cell, the
spermatid ; the head, and probably also the middle piece, from the
nucleus ; the contractile filament from the protoplasm.

4. The egg-cell consists of egg-plasm and yolk-particles, which are
reserve material (deutoplasm), imbedded in it.

5. The quantity and distribution of the deutoplasm in the egg-cell
is subject to great variation, and exercises the greatest influence on
the course of the first processes of development.

(a) The deutoplasm is small in amount, and uniformly, dis-

tributed in the egg-plasm.

(b) The deutoplasm is present in greater quantity, and, in

consequence of unequal distribution, is more densely
accumulated either at one pole of the egg or in its middle.
(Polar and central deutoplasm.)

(c) In eggs with polar deutoplasm (eggs with polar differentia-

tion) the pole with more abundant deutoplasmic contents
is designated as the vegetative, the opposite one as the
animal pole.

(d) In the case of eggs with polar differentiation, the more

abundant protoplasm of the animal pole may be sharply
differentiated as germ-disc (formative yolk) from the
portion which is richer in deutoplasm (nutritive yolk).
The developmental processes take place only in the
formative yolk, while the nutritive yolk remains on the
whole passive.

EMBRYOLOGY.

6. Eggs may be divided into several groups and sub-groups ac-
cording to their development from cells of the ovary alone, or from
cells of the ovarium and vitellarium, as well as according to the
distribution of the deutoplasin, as exhibited in the following
scheme : —

I. Simple eggs. (Development from cells of the ovary.)

A. Eggs with little deutoplasm uniformly distributed through

the egg (alecithal*). (Amphioxus, Mammals, Man.)

B. Eggs with abundant and unequally distributed deutoplasm.

(1) Eggs with polar differentiation (telolecithal), with deuto-

plasm having a polar position, with animal and
vegetative poles. (Cyclostomes, Amphibia.)

(2) Eggs with polar differentiation, which are distinguished

from the preceding sub-group by the fact that with
them there has been effected a still sharper segregation
into formative yolk (germ-disc) and nutritive yolk —
into a part which is active during development and a
part that is passive. (Eggs having polar differentia-
tion with a germ-disc. Fishes, Reptiles, Birds.)

(3) Eggs having central differentiation with central deuto-

plasm (centrolecithal) and superficially distributed
formative yolk (blastema, KeimJtaut). (Arthropods.)

II. Compound eggs. (Double origin from cells of the ovarium

and vitellarium.)

IiITERATUKE.

Baer, C. E. von. De ovi mammalium et hominis genesi epistola. Lipsiae

1827.
Beneden, Ed. van. Recherches sur la composition et la signification de

1'ceuf. Mem. cour. de 1'Acad. roy. Sci. de Belgique. T. XXXIV. 1870.
Bischoff. Entwicklungsgeschichte des Kanincheneies. 1842.
Flemming. Zellsubstanz, Kern- und Zelltheilung. Leipzig 1882.
Frommann, K. Das Ei. Realencyclopadie der gesammten Heilkunde. 2.

Auflage.
Gegenbaur, C. Ueber den Bau und die Entwicklung der Wirbelthiereier mit

partieller Dottertheilung. Archiv f. Anat. und Pbysiol. 1861.
Guldberg. Beitrag zur Kenntniss der Eierstockseicr bei Echidna. Sitzungsb.

d. Jena. Gesellsch. (1885), p. 113.
Hensen. Die Physiologic der Zeugnng. Hermann's Handbuch der Physio-

logie. Bd. VI. Theil II. Leipzig 1881.

* The translator has been accustomed for several years to use the word
homolecithal instead of alecithal, heterolecithal being employed as a coordinate
term to embrace telolecithal and centrolecithal eggs.

LITERATURE* 29

Hertwig, Oscar. Beitriige zur Kermtniss der Bildung. Befruchtung und

Theilung des thierischen Eies. Morphol. Jahrb. Bde I. III. IV. 1875,

-77, -78.
His, W. Untersuchungen iiber die erste Anlage des Wirbelthierleibes. I.

Die Entwicklung des Hiihnchens im Ei. Leipzig 1868.
Kleinenberg. Hydra. Leipzig 1872.

Leuckart, R. Article " Zeugung " in Wagner's Handworterbuch der Physio-
logic, Bd. IV. 1853.
Leydig, Fr. Beitriige zur Kenntniss des thierischen Eies ira unbefruchteten

Zustand. Zool. Jahrbucher. Abth. f. Anat. Bd. III. (1888), p. 287.
Iiudwig, Hubert. Ueber die Eibilduug im Thierreiche. Wiirzburg 1874.
Uagel, W. Das menschliche Ei. Archiv f. mikr. Anat. Bd. XXXI. 1888.
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1825.
Retzius. Zur Kenntniss vom Bau des Eierstockeies und des Graaf'schen

Follikels. Hygiea Festband 2. 1889.
Schwann. Mikroskopische Untersuchunge • iiber die Uebereinstimmung in

der Structur und dem Wachsthum der Thiere und Pflanzen. 1839. Engl.

transl. by H. Smith. London 1847.
Thomson, Allen. Article " Ovum " in Todd's Cyclopaedia of Anatomy and

Physiology. Vol. X. 1859.

Wagner, R. Prodromus hist, generationis. Lipsiae 1836.
Waldeyer, W. Eierstock und Ei. Leipzig 1870.
Waldeyer, W. Eierstock u. Nebeneierstock. Strieker's Handbuch der

Lehre v. den Geweben. 1871. Engl. transl. New York 1872.

Benecke, B. Ueber Reif ung und Bef ruchtung des Eies bei den Fledermausen.

Zool. Anzeiger (1379), p. 304.
Beneden, Ed. van, et Charles Julin. La spermatogenese chez 1'Ascaride

megalocephale. Bull, de 1'Acad. roy. Sci. de Belgique. T. VII. (1884),

p. 312.
Eimer. Ueber die Fortpflanzung der Fledermause. Zool. Anzeiger (1879),

p. 425.
Engelmann. Ueber die Flimmerbewegung. Jena. Zeitschr. f. Med. und

Naturwiss. Bd. IV. (1868), p. 321.
Flemming, W. Beitriige zur Kenntniss der Zelle und ihrer Lebenserschein

ungen. II. Theil. Archiv f. mikr. Anat. Bd. XVIII. 1880.
Flemming, W. Weitere Beobachtungen iiber die Entwicklung der Spermato-

somen bei Salamandra maculosa. Archiv f. mikr. Anat. Bd. XXXI.

1888.
Hermann. Beitriige zur Histologie des Hodens. Archiv f. mikr. Anat. Bd.

XXXIV. 1889.
Hertwig, Oscar, und Richard Hertwig. Ueber den Befruchtungs- und

Theilungsvorgang des thierischen Eies unter dem Einfluss ausserer Agen-

tien. 1887.
Kdlliker. Physiologische Studien iiber die Samenfliissigkeit. Zeitschr. f.

wiss. Zoologie. Bd. VII. (1856), p. 201.
Kolliker. Beitriige zur Kenntniss der Geschlechtsverhaltnisse und der

Samenflussigkeit wirbelloser Thiere, etc. Berlin 1841.

30

EMBRYOLOGY.

Kolliker. Die Bildung der Samenfaden in Blaschen. Denkschr. d. Schweizer.

Gesellsch. f. Naturwiss. Bd. VIII. 1847.
Nussbaum, M. Ueber die Veranderungen der Geschlechtsproducte bis zur

Eifurchung. Archiv f. mikr. Anat. Bd. XXIII. 1884.
Reichert. Beitrag zur Entwickelungsgeschichte der Samenkorperchen bei

den Nematoden. M tiller's Archiv. 1847.
Schweigger-Seidel. Ueber die Samenkorperchen und ihre Entwicklung.

Archiv. f. mikr. Anat. Bd. I. 1865.
Valette St. George, von La. Article " Hoden," Strieker's Handbuch der

Lehre von den Geweben. Engl. trans. Nero York 1872.
Valette St. George, von La. Spermatologische Beitrage. Archiv f. mikr.

Anat. Bde. 25, 27, 28. 1885, -86.

Waldeyer. Ban und Entwicklung der Samenfaden. Anat. Anzeiger (1887),
345. (Full list of the literature on Spermatozoa.)

CHAPTER II.

THE PHENOMENA OF THE MATURATION OF THE EGG AND
THE PROCESS OF FERTILISATION.

1. The Phenomena of Maturation.

EGGS, such as have been described in the previous chapter, are
not yet capable of development, even if they have acquired the
normal size. Upon the addition of mature semen they remain
unfertilised. In order that they may be fertilised they must first
pass through a series of changes, which I shall group together as
the phenomena of maturation.

The maturation-phenomena begin with changes of the germinative
vesicle, which have been followed out the most carefully on the
small transparent eggs of invertebrated animals, such as the
Echinoderms and Nematodes (the maw-worm of the horse). The
germinative vesicle gradually moves from the middle of the egg —
the egg of an Echinoderm may serve as the basis of the description
— towards its surface, shrivels a little (fig. 12.4), in that fluid escapes
from it into the surrounding yolk, its nuclear membrane disappears,
and the germinative dot becomes indistinct and breaks up into small
fragments (fig. 12 B kf). During this degeneration of the germinative
vesicle a nuclear spindle (fig. 1 2 B sp) is formed, as can be recognised
only after appropriate treatment with reagents ; there arises out of
parts of the germinative dot, or out of a part of the nuclear substance
of the germinative vesicle, a nuclear spindle (fig. 12 B sp), — a form

MATURATION OF THE EGG, AND PROCESS OF FERTILISATION. 31

of the nucleus which one encounters in the animal and vegetable
kingdoms in stages preparatory to cell-division.

The nuclear spindle, the more precise structure of which will be
described later, in discussing the process of cleavage, pursues still
further the direction already taken by the germinative vesicle, until
it touches with its apex the surface of the yolk, where it assumes a
position with its long axis in the direction of a radius (fig. 137 sp).
A genuine process of cell-division soon takes place here, which is to
be distinguished from the ordinary cell-division only by this, that
the two products of the division are of very unequal size. To be

kb

Fig. 12.— Portions of eggs of Asterias glacialis. They show the degeneration of the germinative
vesicle.

In figure A it begins to shrivel, in that a protuberance of protoplasm (x), with a radial structure
inside of it, penetrates into its interior, and dissolves the membrane at that point. The
germinative dot (Jcf) is still visible, but separated into two substances, nuclein (nit) and
paranuclein (pn).

In figure B the germinative vesicle (£6) is entirely shrivelled, its membrane is dissolved, and
only small fragments of the germinative dot (kf) remain. In the region of the protoplasmic
protuberance of figure A there is a nuclear spindle (,«p) in process of formation.

more exact, therefore, we have to do here with a cell-budding. At
the place where the nuclear spindle touches the surface with one of
its extremities the yolk arches up into a small knob, into which
half of the spindle itself advances (fig. 13/7). The knob thereupon
becomes constricted at its base, and with the half of the spindle —
from which subsequently a vesicular nucleus is again formed — is
detached from the yolk as a very small cell (fig. 13 777 rkl). Here-
upon exactly the same process is repeated, after the half of the
spindle which remains in the egg, without having previously entered
into the vesicular quiescent stage of the nucleus, has restored itself
to a complete spindle (fig. 13 IV).

There now lie close together on the surface of the yolk two
spherules, which consist of protoplasm and nucleus, and therefore
have the value of small cells (fig. 13 V rkl, rW), and which are
often to be identified in an unaltered condition, even after the
egg has been divided into a number of cells. They were already

32

EMBRYOLOGY.

known in earlier times under the name of direction bodies, or
polar cells. They have acquired the latter name because, in the case
of eggs in which an animal pole is to be distinguished, they always
arise at that pole. After the conclusion of the second process of
budding, one half of the spindle, the other half of which was employed
in the formation of the second polar cell, is left in the cortical layer

Fig. 13.— Formation of the polar cells in Asterias glacialis.

In figure /. the polar spindle (sp) has advanced to the surface of the egg. In figure //. there has
been formed a small elevation (rkl), which receives a half of the spindle. In figure ///. the
elevation is constricted off, forming a polar cell ()•£'). Out of the remaining half of the
previous spindle a second complete spindle (sp~) has arisen. In figure IV. there bulges forth
beneath the first polar cell a second elevation, which in figure V. has become constricted off
as the second polar cell (?-&2). Out of the remainder of the spindle is developed (figure VI.)
the egg-nucleus (ek),

of the yolk (fig. 13 Fand VI ek). From this arises a new, small,
vesicular nucleus, which consists of a homogeneous, tolerably fluid
substance without distinctly segregated nucleoli, and attains a
diameter of about 13 /x. From the place of its formation it usually
migrates slowly back again toward the middle of the egg (fig. 14 ek).
The nucleus of the mature egg (fig. 14 ek) has been designated by
me as Egg nucleus, by VAN BENEDEN as female pronucleus. It is not
to be confounded with the yerminative vesicle of the unfertilised egg.
Compare the figures of the immature egg (fig. 15) and the mature
egg (fig. 14) of an Echinoderm, both of which are drawn with the
same magnification. The germinative vesicle is of very considerable
size, the egg-nucleus remarkably small : in the case of the former
one distinguishes a clearly developed nuclear membrane, a nuclear
network, and a nucleolus ; the latter is almost homogeneous, without

MATURATION OF THE EGG, AND PROCESS OF FERTILISATION. 33

nucleolus, and not separated from the protoplasm by any fixed
membrane. Similar distinctions in the condition of the germinative
vesicle and the egg-nucleus recur throughout the animal kingdom.

The formation of polar cells, and the accompanying metamorphosis
of the germinative vesicle into such an extraordinarily reduced egg-
nucleus, is a phenomenon of very wide, probably, indeed, of general
occurrence. Polar cells have been observed throughout the Ccelen-
terates, Echinoderms, Worms, and Molluscs. In the ripening of the
eggs of Arthropods, according to the earlier observations, they
appeared never to be present; but recently they have been found in

(Fig. iy Fig. 15.

Fig. 14.— Mature egg of an I chinoierm. It encloses in the yolk the very small homogeneous-

egg-nucleus (at).
Jig. 15. — Immature egg from the ovary of an Echinoderir.

numerous species by a number of observers, especially by BLOCHMANN
and WEISMANN. Among Vertebrates polar cells are always en-
countered in Cyclostomes and Mammals, whereas in Fishes and
Amphibia they have been identified only in some cases, and in Reptiles
and Birds not at all as yet. They arise either some time before or
else during fertilisation.

In the case of Mammals (Rabbit and Mouse) the process has been
very carefully investigated by VAN BENEDEN, and recently by TAFANI.
Severa. weeks before the rupture of the GRAAFIAN follicle the ger-
minative vesicle ascends to the surface of the egg ; some days before
that epoch it there disappears, and at the place where it disappeared
there are formed the egg-nucleus and, under the zona pellucida, one
or two (TAFANI) polar cells. The egg after it has escaped from the
ovary always exhibits egg-nucleus and polar cells.

Also in the case of Fishes, Amphibia, Reptiles, and Birds, whose

3

34 EMBRYOLOGY.

eggs are of considerable size and with few exceptions opaque, the
germinative vesicle, distinguished by its numerous nucleoli, undergoes
a regressive metamorphosis. As has been followed step by step in
Teleosts by OELLACHEE, and in Amphibia by the author, it always
ascends from the middle of the yolk to its surface, and in
fact without exception to its animal pole : in the case of the
Frog (fig. 16 kb) this occurs many weeks before the beginning
of maturation. Here immediately under the vitelline membrane,
it becomes flattened to a disc-like body, being at the same time
somewhat shrunken. Further changes, which it is very difficult
to follow in detail, take place in a comparatively short time;
these occur in the case of the Amphibia at the time when the

Fig. 16. — Frog's egg in process of ripening.

The germinative vesicle (kb), with numerous germinative dots (i/), lies quite at the surface of
the animal pole as a flattened lenticular body.

eggs are detached from the ovary. For if one examines eggs which
have already escaped into the abdominal cavity, or have entered the
oviduct, it is uniformly found that the germinative vesicle with its
dots has disappeared. In this case, too, there are subsequently
formed from a part of the chromatic substance of the germinative
vesicle two polar cells and an egg-nucleus, as has been proved by the
fine investigations of HOFFMANN for some species of Teleosts, of
O. SCHULTZE for several Amphibia (Siredon, Triton), and of KAST-
SCHENKO for certain Selachians.

WEISMANN and BLOCHMANN have discovered a very interesting fact
in the Arthropods. In eggs, namely, which develop parthenogenetic-
ally (in summer eggs of Polyphemus, Bythotrephes, Moina, Leptodora,
and Daphnia, as well as in Aphidse) only a single polar cell is elimin-
ated, whereas in eggs which require fertilisation for their further
development there are always two formed. At present, however,
this contrast cannot be established as a general law. For PLAINER
found that in the case of Liparis dispar there are formed in
parthenogenetic eggs, as well as in those which are fertilised, two
polar cells, the first of which again divides. BLOCHMANN arrived at
the same result from the investigation of unfertilised eggs of bees,
from which drones are developed.

MATURATION OF THE EGG, AND PROCESS OF FERTILISATION. 35

Although the researches oil the phenomena of maturation of
the egg in animals still present numerous gaps, nevertheless it
can be regarded as already well-established, that eggs with a germi-
native vesicle are never capable of fertilisation, that the germinative
vesicle is without exception dissolved, and that there is formed out of
components of it (as regards the details there are still many processes
to be more carefully studied) a very small egg-nucleus. During the
metamorphosis there arise, probably without exception, polar cells.

The polar differentiation of many eggs rich in yolk, which was
pointed out in the first chapter, may be brought into causal connection
with the phenomena of maturation. -Without exception the animal
pole is the part of the egg-sphere to which the germinative vesicle
ascends, and where the polar cells are subsequently formed. That
the protoplasm is accumulated here in greater quantity is in part
referable to the fact that it comes to the surface of the egg along
with the nucleus, which most certainly furnishes a centre of attrac-
tion for the protoplasm.

The insight into the phenomena of the maturation of the egg, as they have been
connectedly presented in the preceding pages, has been acquired only by many
roundabout ways and after the removal of many misconceptions. As early as
the year 1825 PURKINJE, the discoverer of the germinative vesicle in the Hen's
egg, found that in eggs which were taken from the oviduct this vesicle had
disappeared, and from this concluded that it was ruptured by the contractions
of the oviduct, and that its contents (a lympha generatrix) were mingled with
the germ. Whence the name vesicula germinativa. Similar observations were
made on this and other objects by C. E. v. BAER, OELLACHER, GOETTE,
KLEINENBERG, KOWALEVSKY, REICHERT, and others. But on the other hand
the positive statements were made for many eggs (by JOH. MULLER for
Entoconcha mirabilis ; by LEYDIG, GEGENBAUR, and VAN BENEDEN for
Rotifers, Medusae, etc.) that the germinative vesicle did not disappear, but
remained and gave rise by direct division at the time of segmentation to the
daughter-nuclei.

There were therefore in previous decennia two opposing parties : the one
asserted the continuance of the germinative vesicle and its division during the
process of cleavage ; the other maintained that the egg-cell in its development
passed through a condition ivithout nucleus, and again acquired a nucleus in
consequence of fertilisation.

The controversial points were cleared up by investigations which BUTSCHLI
and the author had undertaken at the same time.

I showed in my first " Beitrage zur Kenntniss der Bildung, Befruchtung
und Theilung des thierischen Eies,'' that in all the older writings there
had been no distinction made between the nucleus of the immature, the
mature, and the fertilised egg, but that these nuclei had been of ten confounded
and held to be identical, and I first established the differences between germi-
native vesicle, egg-nucleus, and cleavage-nucleus, the latter being the names
which were introduced by me. In addition I showed that the disappearance

36 EMBRYOLOGY.

of the germinative vesicle and the origin of the egg-nucleus preceded fertilisa-
tion, and thus I distinguished between the phenomena of maturation and
fertilisation of the egg-cell, which generally had been interchanged and con-
founded. I also endeavoured to make it probable that the egg-nucleus
descended from the germinative vesicle, and in fact from a nucleolus of the
vesicle, and defended the thesis that the egg during its maturation did not
pass through a non-nuclear condition. In this I fell into an error : I overlooked,
like all previous observers, the connection between the formation of the polar
cells and the disappearance of the germinative vesicle, — & process which it was
the more difficult to establish in the object which I studied because it takes
place in the ovary.

The excellent investigations of BtiTSCHLi, which brought the changes of the
germinative vesicle into connection with the formation of the polar cells, now
made their appearance, supplementing my results. The polar cells were
discovered in the year 1848 by FR. MULLER and LOVEN, and were named by
the former directive vesicles (Richtungsblaschen), because they always lie at
the place where subsequently the first cleavage-furrow makes its appearance.
Their wide distribution in the animal kingdom had also been established by
many investigators ; BtiTSCHLi was the first, however, to direct attention to
the peculiar processes which take place in the yolk, in the interpretation of
which he, nevertheless, committed several errors. He maintained that the
whole germinative vesicle is converted into a spindle-shaped nucleus, which
moves to the surface, and, while becoming constricted in the middle, is thrust
outside by the contractions of the yolk in the form of two directive bodies.
By this process the egg became non-nuclear, and again acquired a nucleus-
only in consequence of fertilisation.

In two further articles on the Formation, Fertilisation, and Cleavage of the
Animal-Egg, I modified the teachings of BtfTSCHLi, and brought them into
unison with my previous investigations, inasmuch as I pointed out that
the germinative vesicle is not as such directly converted into the nuclear
spindle, but in part is dissolved : that the spindle takes its origin from the
nuclear substance in a manner which it is very difficult to investigate ; that
the polar cells are formed, not by the elimination of the spindle, but by a
genuine process of division or budding ; that in consequence of this the egg is
not destitute of a nucleus even after the constricting off of the second polar
cell, but that the egg-nucleus arises from the half of the divided polar spindle
which remains in the yolk, and therefore, in its ultimate derivation, from
components of the germinative vesicle of the immature egg.

Soon afterwards BUTSCHLI also interpreted the development of the directive
bodies as cell-budding, likewise GIARD and also FOL, who has produced a
very extensive and thorough investigation on the phenomena of the maturation
of the egg in animals. Recently VAN BENEDEN, supported by researches on
Nematodes, has combatted the interpretation of the process as cell-budding;
however, BOVERI and O. Z ACHARIAS, who have established a complete agreement
between the formation of directive bodies and the process of cell-division in
the case of the Nematodes also, are unable to subscribe to his conclusion in.
this matter.

As a new advance is to be recorded the discovery by WEISMANN and by
BLOCHMAXN, that in eggs which are developed parthenogenetically only a
single polar cell arises.

If the original obscurity on the morphological side, in which the phenomena.

MATURATION OF THE EGG, AND PROCESS OF FERTILISATION. 37

of the maturation of the egg were enveloped, has been in general cleared up,
the same is not the case if we inquire after its physiological meaning. That
the germinative vesicle undergoes a regressive metamorphosis into component
parts is easily comprehensible, for a firm membrane and a rich accumulation
of nucleo plasm certainly cannot be necessary to the interaction of protoplasm
and active nuclear substance in the processes of division. Its dissolution is,
as it were, the preliminary requirement for the renewed activity of the nuclear
contents. But what function shall one ascribe to the polar cells ?

Concerning this several hypotheses have been proposed.

BALFOUR, SEDGWICK MINOT, VAN BENEDEN, and others, are of opinion
that the immature egg, like every other cell, is originally hermaphroditic, and
that by the development of polar cells it rids itself of the male constituents of
its nucleus, which afterwards are replaced by fertilisation. BALFOUB thinks
that, if no polar cells were formed, parthenogenesis must normally occur.

WEISMANN, supported by his discovery in the case of eggs developing
parthenogenetically (p. 34), ascribes a different function to the first and the
second polar cells. He distinguishes in the germinative vesicle two different
kinds of plasma, which he designates ovogenetic and germinal plasma.
He maintains that by the formation of the first polar cell the ovogenetic
plasma is eliminated from the ovum ; by that of the second polar cell, half
of the germinal plasma. In the latter case the ejected germinal plasma must
be replaced by fertilisation.

These hypotheses appear to me upon closer examination to present many
vulnerable points. To me appears more promising an interpretation of
BtiTSCHLi, who compares the egg, as had already often been done, to the
mother-cell of spermatozoa. Just as the latter gives rise to many spermatozoa,
so also the egg must have once possessed the capability of dividing itself into
many eggs. In the formation of the polar cells, which are eggs that have
become rudimentary, as it were, there has been preserved a trace of these
original conditions. Also BOVERI regards the polar cells as abortive eggs.
I have likewise always conceived of the conditions in this manner.

2. The Process of Fertilisation.

The union of egg-cell and spermatic cell is designated as the process
of fertilisation. This process is to be observed, sometimes with great
difficulty, sometimes with considerable ease, according to the choice of
the animal for experimentation. The investigator ordinarily en-
counters great difficulties in cases where the ripe eggs are not laid, but
where a part, if not the whole, of their development is effected within
the sexual ducts of the maternal organism. In such cases the fertili-
sation also must evidently take place in the ducts of the female sexual
apparatus, into which the semen is introduced in the act of
copulation.

An internal fertilisation takes place in nearly all Vertebrates
except the greater part of the Fishes and many Amphibia. Usually the
egg and the spermatozoa meet, in the case of Man and Mammals, in

EMBRYOLOGY.

the beginning of the oviduct ; likewise in the case of Birds they meet
in the first of the four regions previously (p. 17) distinguished, and
at .a time when the yolk is not yet surrounded with its albuminous
envelope and calcareous shell.

In contrast to internal fertilisation stands external fertilisation,
which is the simpler and more primitive method, and which occurs in
the case of many Invertebrates that live in the water, as well as
ordinarily in Fishes and Amphibia. In this method, while male and
female keep near together, both kinds of sexual products, which are
for the most part produced in great number, are evacuated directly
into the water, where fertilisation takes place outside of the maternal

Fig. 17 A, B, C.— Small portions of eggs of Asterias glacialis, after FOL,

The spermatozoa have already penetrated into the gelatinous envelope which covers the eggs. In
A there begins to be raised up a protuberance toward the most advanced spermatozoon. In
B the protuberance and spermatozoon have met. In C the spermatozoon has penetrated
into the egg. A vitelline membrane, with a crater-like orifice, has now been distinctly
formed.

organism. The whole procedure is therefore much more easily observ-
able. The experimenter has it within his power to effect fertilisation
artificially, and thus to determine precisely the point of time at which
egg and semen are to meet. He needs only to collect in a watch-glass
containing water ripe eggs from a female, likewise in a second watch-
glass ripe semen from a male, and then to mingle the two in a
suitable manner. In this way artificial fertilisation is extensively
practised in fish-breeding. For the purpose of scientific investigation
the selection of the particular species of animal is of the greatest
importance. It is manifest that animals with large opaque eggs do
not commend themselves, whereas those species are especially suit-
able whose eggs are so small and transparent that one can observe
them under the microscope with the highest powers, and at the same
time pass in review every least speck. Many species of Echinoderms

MATURATION OF THE EGG, AND PROCESS OF FERTILISATION. 39

are in this respect most excellent objects for investigation. Conse-
quently it was by means of them that an accurate insight into the
processes of fertilisation was first secured. They may therefore serve
in the following account as the foundation of our description.

If ripe eggs with egg-nucleus are removed from the ovary into a
watch-glass containing sea -water, and a small quantity of seminal
fluid is added, a very uniform result is obtained, since in the course
of five minutes every one of many hundreds or thousands of eggs is
normally fertilised, as can be accurately observed by means of high
magnification.

Although spermatozoa attach themselves to the gelatinous envelope

Fig. 18.— Fertilised egg of a Sea-urchin.

The head of the spermatozoon which penetrated has been converted into a sperm-nucleus (sk)

surrounded by a protoplasmic radiation, and has approached the egg-nucleus (ek).
Fig. 19. — Fertilised egg of a Sea-urchin.
The sperm-nucleus (sk~) and the egg-nucleus (efc) have come close to each other, and both are

surroxinded by a protoplasmic radiation.

of an egg in great numbers, — many thousands of them when con-
centrated seminal fluid is employed, — still only a single one of them
is concerned in fertilisation, and that is the one which by the lash-
like motion of its filament first approached the egg. Where it strikes
the surface of the egg with the point of its head the clear superficial
expanse of the egg-protoplasm is at once elevated into a small knob
that is often drawn out to a fine point, the so-called receptive promin-
ence (Empfangnisshugel), or cone of attraction. At this place the
seminal filament, with pendulous motions of its caudal appendage,
bores its way into the egg (fig. 17 A, B). At the same time a fine
membrane (fig. 71 (7) detaches itself from the yolk over the whole
surface, beginning at the cone, and becomes separated irom it by
an ever-increasing space. The space probably arises because, in
consequence of fertilisation, the egg-plasma contracts and presses

40

EMBRYOLOGY.

out fluid (probably the nuclear fluid which was diffused after the
disappearance of the germinative vesicle).

The formation of a vitelline membrane is in so far of great signi-
ficance for the fertilisation, as it makes the penetration of another
male element impossible. No one of the other spermatozoa swing-
ing to and fro in the gelatinous envelope is able after that to get
into the fertilised egg.

The one which has penetrated thereupon undergoes a series of
changes. The contractile filament ceases to vibrate, and soon dis-
appears ; but out of the head — which, as was previously stated, is
derived from the nucleus of a sperm-cell (spermatid), and consists of
nuclein — there is soon developed a very small spheroidal or oval

corpuscle, which afterwards becomes
somewhat larger, the semen- or
sperm-nucleus (fig. 18 sk). This
slowly moves deeper into the yolk,
whereupon it exerts an influence
upon the surrounding protoplasm.
For the latter is arranged radially
around the sperm -nucleus (sk), so
that there is formed a radiate
figure, which is at first small, but
afterwards becomes more and more
sharply expressed and more ex-
tended.

Now an interesting phenomenon
begins to hold the attention of the observer (figs. 18, 19, 20). Egg-
nucleus and sperm-nucleus mutually attract each other, as it were,
and migrate through the yolk toward each other with increasing
velocity. The sperm-nucleus (sk), enveloped in its protoplasmic radia-
tion, changes place more rapidly than the egg -nucleus (ek). Soon the
two meet, either in, or at least near, the middle of the egg (fig. 19) ;
become surrounded by a common radiation, which now extends
through the whole yolk-substance ; are firmly juxtaposed, and then
mutually flattened at the surface of contact ; and finally fuse with
each other (fig. 20 fk). The product of their fusion is the first
cleavage-nucleus (fk), which undergoes the further alterations leading
to cell-division.

This whole interesting process of fertilisation has consumed in the

present object of investigation the short time of about ten minutes only.

The phenomena of fertilisation discovered in the Echinoderms were

Fig. 20.— Egg of a Sea-urchin immediately
after the close of fertilisation. Egg-nucleus
and sperm-nucleus are fused to form the
cleavage-nucleus (fk), which occupies the
centre of a protoplasmic radiation.

MATURATION OF THE EGG, AND PROCESS OF FERTILISATION. 41

soon observed, either completely or at least partially, in numerous other
animals also — in Coelenterates and Worms (NUSSBAUM, VAN BENEDEN,
CARNOY, ZACHARIAS, BOVERI, PLAINER), and in Molluscs and Verte-
brates. As regards the last, it has been possible to follow accurately
in the case of Petromyzon the penetration of a single spermatozoon
into the egg through a special preformed micropyle in the vitelline
membrane (CALBERLA, KUPFFER, BENECKE, and BOHM). Likewise in
the Amphibia, proof has been brought forward that after fertilisation
a sperm-nucleus is formed at the animal pole, and that, surrounded by
a pigmented area, derived from the cortex of the yolk, it moves to-
ward another more deeply imbedded nucleus (egg-nucleus), and fuses
with it (O. HERTWIG, BAMBEKE, BORN). In Mammals the fertilisa-
tion takes place in the beginning of the oviduct. Evidence has also
been produced in their case that after the liberation of the polar
cells two nuclei are temporarily to be seen in the egg-cells, and that
these unite in the centre of the egg to form the cleavage-nucleus
(VAN BENEDEN, TAFANI).

This is the proper place in which to mention briefly the so-called
micropyle. In many animals (Arthropods, Fishes, etc.) the eggs are
enclosed before they are fertilised in a thick firm envelope, which
is impenetrable for spermatozoa. Now, in order to make fertilisation
possible, there are found in these cases at a definite place on the egg-
membrane sometimes one, sometimes several, small openings (micro-
pyles), at which the spermatozoa accumulate in order to glide into
the interior of the egg.

The egg of Nematodes has for several years rightly played an
important role in the literature of the process of fertilisation. Bat
this is especially true for the egg of the Maw-worm of the Horse
(Ascaris megalocephala), which VAN BENEDEN has made the subject
of a celebrated monograph. It is an excellent object, in so far
as it not only can be had for study everywhere and at all seasons of
the year, but also allows one to follow step by step, in the most
accurate manner, the penetration and subsequent fate of the sper-
matozoon. Since, moreover, the process of fertilisation in Ascaris
megalocephala presents many peculiarities in its details, an extended
presentation of them is both warranted and desirable.

In the case of this Worm, in which the sexes are separate individuals,
there is a copulation, and the fertilisation of the egg takes place within
the sexual passages of the female. In one region, which is expanded
into a kind of uterus, mature spermatic bodies are met with in great
numbers. The appearance of these differs greatly from that which

42 EMBRYOLOGY.

the male seminal elements ordinarily present in the animal kingdom r
for they are apparently motionless ; are comparable in form to a cone,
a conical ball, or a thimble (fig. 21) ; and consist in part of a
granular substance (b), in part of a homogeneous lustrous substance
(/), and of a small spherical body of nuclear substance (k), which is
imbedded in the granular substance at the base of the cone.

When the small naked eggs enter into the region designated as-
uterus, fertilisation takes place at once. One spermatic body, which
can execute feeble amreboid motions with its basal end (SCHNEIDER),
attaches itself to the surface of the yolk (fig. 22 ak). Where contact
with the egg first takes place, there is formed, exactly as in the
Echinoderms, a special cone of attraction. Here the spermatic

body, without essential change of form, gradually

glides deeper into the yolk, until it is completely

enclosed therein (fig. 23).

While the two sexual products are thus externally

fused, the egg itself is not yet ripe, because it still
Fig. 21.— Spermatic possesses the germinative vesicle (fig. 22 kb], but

body of Ascaris .. ,11-

megaiocephaia, " now promptly begins to enter upon the matura-

after VAN BENE- tion stage by preparing to form the polar cells.

t, Nucleus ; 6, base The germinative vesicle, which is of small size in

of the cone, by the case of the Maw-worm of the Horse, loses its

which the attach . .

ment to the egg sharp delimitation trom the yolk, moves toward

takes place; /, ^^ surface of the egg which is opposite to the

lustrous substance . Ol

resembling fat. cone or attraction (figs. 23, 24), and is gradually

converted into a nuclear spindle (sp), the origin
of which may be traced upon this object with considerable precision.
The most important part of the process consists in the formation,
out of the chromatic substance, of numerous short, rod-like pieces
(figs. 23, 24, c/i), which form directly the chromatic elements of
the spindle, the chromosomes (WALDEYER). As in the case of the
Echinoderms, there then arise at the surface of the yolk two small
polar cells (fig. 25 pz); as in that case, a vesicular egg-nucleus
(fig. 25 ei) arises from the half of the second polar spindle which
remains in the peripheral portion of the yolk.

Meanwhile the spermatic body has moved farther and farther
from the place of its entrance into the egg (figs. 22, 23, sk), and
finally comes to lie in the middle of the yolk (fig. 24 sk), approxi-
mately in the position occupied by the germinative vesicle before its
migration to the surface. During this period the spermatic body
has gradually lost its original form and its sharp delimitation ; out

MATURATION OF THE EGG, AND PROCESS OF FERTILISATION. 43

of its nuclear substance, which was described as a small, deeply
stainable spherule, there arises a vesicular nucleus (fig. 25 sk), which
acquires the same size and condition as the egg-nucleus.

Fig. 22.

Fig. 23.

Fig. 22.— An egg of Ascaris megalocephala just fertilised, after VAX BENEDEN.

sk, Spermatic body, with nucleus, which has entered the egg ; /, fat-like substance of the
spermatic body ; kb, germinative vesicle.

Fig. 23.— A stage of a fertilised egg of Ascaris megalocephala. somewhat older than that of

fig. 22, after VAN BENEDEN.
.;/,-, Spermatic body, which has penetrated deeper into the cortex of the yolk ; sp, polar spindle

which has arisen from the germinative vesicle ; ch, chromosomes of the spindle.

After the rapid and continuous accomplishment of these processes,
the egg of the Worm usually enters on a longer or shorter period of

Fig. 25.

Fig. 24.— A still older stage of development, following that of fig. 23, of the egg of Ascaris

megalocephala, after BOVERI.
up, Polar spindle, which has ascended to the surface of the yolk ; ch, 2 x 4 chromosomes;

ak, spermatic nucleus, which has migrated into the middle of the egg.

Fig. 25.— Egg of Ascaris megalocephala in preparation for the process of cleavage, after

. E. VAN BENEDEN.
2>2, Two polar cells which have arisen from the polar spindle (sp~) of fig. 24 by a repetition

of the process of budding ; ei, egg-nucleus ; sk, spermatic nucleus already preparing to

divide ; ch, nuclear loops or chromosomes.

rest. It now presents (compare fig. 25, which represents a stage
already further developed) at its surface within the vitelline mem-
brane two polar cells (pz), and in its interior two large vesicular
nuclei, the spermatic nucleus (sk) and the egg-nucleus (ei), the

44 EMBRYOLOGY

latter of which has come close up to the former, without, however,
fusing with it. A union of the male and female nuclear substances
into a common nuclear figure takes place in the case of the Maw-
worm, when the process of egg-cleavage is beginning.

The processes of fertilisation just described can be designated as
typical for the animal kingdom. But they appear to recur in exactly
the same manner throughout the vegetable kingdom also, as has
been shown by the thorough investigations of STRASBURGER. We
are therefore in a better position now than formerly to advance a
theory of fertilisation based upon an important array of facts : —

In fertilisation clearly demonstrable morphological processes take
place. Of these the important and essential one is the union of two
cell-nuclei which have arisen from different sexual cells, a female egg-
nucleus and a male spermatic nucleus. These contain the fructifying
nuclear substance, which is an organised body and comes into activity
as such in fertilisation.

Recently the attempt has been made to expand the fertilisation
theory into a theory of transmission. Important reasons may be urged,
as appearing to indicate that the fructifying substance is at the
same time the bearer of the transmissible peculiarities. The female
nuclear substance transmits the peculiarities of the mother, the male
nuclear substance the peculiarities of the father, to the nascent creature.
Perhaps there is in this theory a morphological basis for the fact
that offspring resemble both progenitors, and in general inherit from
both equally numerous peculiarities.

If we accept these two theories, the nucleus, which, despite its
<xmstant presence, previously had to be described as a problematic
structure of unknown significance, acquires an important role in the
life of the cell. It seems to be the cell's especial organ of fertilisation
and transmission, inasmuch as there is stored within it a substance
(idioplasma of NAGELI) which is less subject to cell metastasis.

In connection with the consideration of the process of fertilisation
may be permitted a slight digression to the realm of pathological
phenomena.

As follows from numerous observations in both the animal and
vegetable kingdoms, in the normal course of fecundation only a single
spermatic filament penetrates into an egg, when the encountering
sexual cells are entirely healthy. But with an impaired condition of
the egg -cell, superfetation by means of two or more seminal filaments
(polyspermia) takes place.

Superfetation may be produced artificially, if by way of experiment

MATURATION OF THE EGG, AND PROCESS OF FERTILISATION. 45

one injures the egg-cell. This may be accomplished either by
exposing it temporarily to a lower or a higher temperature, and
thus producing cold-rigor or heat-rigor, or by affecting it with
chemical reagents, — chloroforming it, or treating it with morphine,,
strychnine, nicotine, quinine, etc., — or by doing violence to it in a
mechanical way, such as shaking it. It is interesting to observe how,
with all of these means, the degree of superfetation is, to a certain
extent, proportional to the degree of the injury ; how, for example, a
small number of spermatozoa penetrate into eggs which have been
slightly affected with chloral, whereas a greater number penetrate
those which have been more strongly narcotised.

In all unfertilised eggs the whole course of development becomes
abnormal. But whether, as claimed in FOL'S hypothesis, the origin
of double and of multiple organisms is referable respectively to the
penetration of two and many spermatozoa, must still be regarded as
doubtful. Certainly the question suggested richly deserves to be still
more thoroughly tested experimentally.

HISTORY. — The facts here given concerning the theory of fecundation are
acquisitions of very recent times. To omit the older hypotheses, it was
generally assumed up to the year 1875 that the spermatozoa penetrate in great
numbers into the substance of the egg, but that they there lose their activity
and become dissolved in the yolk.

I succeeded in my study of the eggs of Toxopneustes lividus in finding
an object in which all the internal phenomena of fertilisation may be
determined with ease and certainty, and in establishing (1) that inconsequence
of fertilisation the head of a spermatic filament surrounded by a stellate figure
makes its appearance in the cortex of the yolk, and is metamorphosed into a
small corpuscle, which I called spermatic nucleus ; (2) that within ten minutes
egg-nucleus and spermatic nucleus copulate ; (3) that normally fertilisation is
accomplished by only a single spermatic filament, whereas in pathologically
altered eggs several spermatozoa may penetrate. I was therefore able at that
time to announce the proposition, that fertilisation depends upon the fusion of
two sexually differentiated cell-nuclei.

A few months later, VAN BENEDEN announced that in the case of Mammals
the segmentation-nucleus arises from the fusion of two nuclei, — as had
previously been observed by AuERBACHand BUTSCHLI in the case of numerous
other objects,— and expressed the conjecture that one of them, which has at
first a peripheral position, might in part result from the substance of the
spermatozoa, which, in great numbers, as he maintained, fuse and become
commingled with the cortical portion of the yolk. An advance was soon after
this made by FOL, who investigated with the greatest detail the eggs of
Echinoderms at the very moment of the penetration of a spermatic filament
into the egg, and discovered the formation of a cone of attraction. Since
then it has been established by means of numerous researches (those of
SELENKA, FOL, HERTWIG, CALBERLA, KUPFFER, NUSSBAUM, VAN BENEDEN..
EBERTH, FLEMMING, ZACHARIAS, BOVERI, PLATNER, TAFANI, BOHM, and.

46 EMBRYOLOGY.

others) that in other objects also, and in other branches of the animal kingdom,
the processes of fertilisation take place in essentially the same manner. At
the same time the comprehension of the processes of fertilisation was
essentially advanced, especially by the works of VAN BENEDEN on the egg
of Ascaris megalocephala, to which have been added the important investiga-
tions of BOVEEI and others on the same object. STEASBUEGEB has established
in a series of excellent researches the identity of the processes of fertilisation
in the animal and vegetable kingdoms.

Finally, the phenomena of fertilisation were utilised simultaneously by
STEASBUEGEE and myself for the foundation of a theoiy of heredity, in our
endeavor to prove — what others (KEBEE, HAECKEL, HASSE) had previously
expressed as a conjecture — that the male and the female nuclear substances
are the bearers of the peculiarities which are transmitted from parent to
offspring. KOLLIKER, Roux, BAMBEKE, WEISMANN, VAN BENEDEN, BOVERI,
and others have since expressed themselves in a similar manner.

SUMMARY.

1. At maturation the germinative vesicle gradually rises to the
animal pole of the egg, and thereby undergoes a regressive meta-
morphosis (degeneration of the nuclear membrane and the fibrous
network, mingling of the nuclear fluid — Kernsaft — with the proto-
plasm).

2. A nuclear spindle (polar spindle or direction-spindle) is de-
veloped out of remnants of the germinative vesicle, principally,
indeed, out of the substance of the germinative dot, which breaks
up into chromosomes.

3. At the place where the spindle encounters the surface of the
yolk with one of its ends, there are formed two polar cells or direction-
bodies (Richtungskorper) by means of a process of budding, which is
repeated.

4. At the second budding, half of the nuclear spindle remains in
the cortex of the yolk, and is metamorphosed into the egg-nucleus.
The egg is then ripe.

5. In the case of eggs which develop parthenogenetically (Arthro-
poda), ordinarily only one polar cell is formed.

6. At fertilisation only a single spermatozoon penetrates a sound
egg (formation of a cone d 'attraction, detachment of a vitelline mem-
brane).

7. The head of the spermatozoon is converted into the spermatic
nucleus, around which the neighbouring protoplasmic particles are
radially arranged.

8. Egg-nucleus and spermatic nucleus migrate toward each other,
and in rncfct instances immediately fuse to form the segmentation-

LITERATURE. 47

nucleus ; in many objects they remain for a considerable time near
each other, but not united, arid only later are together metamorphosed
into the segmentation-spindle.

9. In some animals fertilisation of the egg takes place only after
completion of its maturation, but in others it is inaugurated at the
very beginning of maturation, so that the two phenomena overlap
each other.

10. Fertilisation theory. Fertilisation depends on the copulation
of two cell-nuclei, which are derived from a male cell and a female
cell.

11. Theory of heredity. The male and female nuclear substances
contained in the spermatic nucleus and the egg-nucleus are the
bearers of the peculiarities which are transmissible from parents to
their offspring.

LITERATURE.

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Blochmann. Ueber die Reifung der Eier bei Ameisen und Wespen. Fest-
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48 EMBRYOLOGY.

Blochmann. Ueber die Zahl der Richtungskorper bei befruchteten un«».

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Bd. XXIX. 1877.
Calberla. Befruchtungsvorgang beim Ei von Petromyzon Planeri. Zeitschr.

f. wiss. Zoologie. Bd. XXX. 1878, p. 437.
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globules polaires de 1'Ascaris megalocephala. 1886. And La Cellule.

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thier. Eizelle. Biol. Centralblatt, Bd. III. 1884, pp. 641, 678.
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1877, pp. 1-86.

Hertwig, Oscar. Weitere Beitrage, etc. Morphol. Jahrb. Bd. III. 1877.
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Kastschenko. Zur Frage iiber die Herkunft der Dotterkerne im Selachierei.

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THE PROCESS OF CLEAVAGE. 51

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CHAPTER III.
THE PROCESS OF CLEAVAGE.

FERTILISATION is in most instances immediately followed by further
development, which begins with the division of the egg-cell — the
simple elementary organism — into an ever-increasing number of
small cells — the process of cleavage. We shall begin the study of
cleavage with a very simple case, and here also choose as a foundation
for the presentation of the subject the egg of an Echinoderm and
the egg of the common Ascaris of the Horse.

In the living egg of the Echinoderm the cleavage-nucleus (fig. 26
fk), which arose from the fusion of egg-nucleus and spermatic
nucleus, is at first spheroidal, and lies exactly in the middle of the
egg, where it forms the centre of a radiation which affects the
whole yolk-mass ; but it soon begins to be slightly elongated, and
at the same time to become less and less distinct, so that with the
living object one might be misled into assuming that it had been
completely dissolved. Before this, very regular changes in the dis-
tribution and arrangement of the protoplasm around the nucleus
have taken place. The monocentric radiation resulting from fer-
tilisation is divided. The two newly formed radiations thereupon
move to the poles of the elongated nucleus. At first small and in-
significant, they rapidly extend, and finally each occupies a half of
the egg (fig. 27), and the rays of the two systems meet at a sharp
angle in the median plane of the egg.

Just in proportion as the two radiations become more distinct,
there arises, within the granular yolk, as the starting-point and

EMBRYOLOGY.

centre of the radiations, a figure, which may be appropriately com-
pared (fig. 27) with a dumb-bell. It arises by the accumulation of a
large amount of homogeneous protoplasm around the poles of tho
elongating nucleus, forming the two ends of the dumb-bell; the
poles may be regarded as if they were two centres of attraction.
The non-granular streak, representing the handle of the dumb-bell,
is the nucleus, which has meanwhile undergone a peculiar metamor-
phosis and has become indistinct.

A more accurate knowledge of the nuclear metamorphosis may be
got by employing suitable reagents and dyes. By means of inter-
mediate stages, which may be disregarded here, thero arises out of

Fig. 27.

Pig. 26 — Egg of a Sea-urchin immediately after the conclusion of fertilisation, fk, Cleavage-
nucleus.

Tig. 27. — Egg of a Sea-urchin in preparation for division. The nucleus is no longer to be seen ;

there has arisen in its place a dumb-bell figure.
Both figures are drawn from the living object.

the vesicular nucleus the nuclear spindle (fig. 31 J2), which is a
typical structure for cell-division throughout the organic world.
Tnis (sp) consists of two substances, both of which, in my opinion,
are derived from the quiescent condition of the nucleus — namely,
(1) of a non-chromatic substance, which does not show affinity for any
dyes, and (2) of the stainable nuclein or chromatin. The non-chromatic
substance forms extraordinarily fine, and therefore at times scarcely
discernible, " spindle-fibres" which are united into a bundle, and
give rise to a spindle by the convergence of their ends to points. The
chromatin, on the contrary, has assumed the form of small individual
granules or chromosomes, which correspond in number with the
spindle-fibres, and are so arranged that each granule adjoins a
spindle-fibre at its middle point. In its totality, therefore, it con-
stitutes at the middle of the spindle a plate composed of individual

THE PROCESS OF CLEAVAGE.

granules— the nuclear plate of STRASBURGER. That which in the case
of the Sea-urchin ordinarily appears as a chromatic granule is found,
upon the employment of the highest magnifying powers, — but
especially in the study of objects (fig. 28 A) more suitable for this
purpose, — to be a small Y-shaped loop. The number of the loops or
chromosomes appears to be very definite, and subject to law for each
species of animal.

At the tips of the spindle there may be demonstrated, in addi-
tion, two special and exceedingly minute bodies, one of which
occupies the exact centre of each of the two previously mentioned
systems of rays ; they are, in fact, to be regarded as the cause of the-

i W :

•--—..•-• - ^ ^$$<- .

i. m '»:*.!—'''

Fig. 28.— Diagram of nuclear division, after RABL.

lu figure A one sees the spindle, composed of delicate non-chromatic fibres, with the protoplasmic
radiations at its tips and the chromatic loops at its middle. The splitting of the filaments
of the latter has already taken place. In figure B the daughter-loops resulting from the
fission have moved apart in opposite directions. In figure C they begin to arrange themselves
in a regular manner into two groups of loops. In figure D the groups of daughter-loops lie
near the two poles of the spindle.

latter. Inasmuch as during the elongation qf the nucleus they are
to be found at each of its two poles, they may be especially designated
as polar corpuscles [or centrosomes\. During the whole process of the
division of nucleus and cell-body, it appears as though a directing
influence belongs to the two polar corpuscles.

Important changes in the1 nuclear loops of the spindle take place
during later stages of the process of division. Each loop is split
lengthwise into two l^Lghter-loops (fig. 28 A), as discovered by
FLEMMING and as confirmed since then by numerous other investi-
gators (STRASBURGER, HEUSER, VAN BENEDEN, RABL, and others).
These daughter-loops soon move apart toward the opposite ends of
the spindle (figs. 28 B, C; see also the explanation of the figures), and
approach very closely to the polar corpuscles at their tips (fig. 28 1)}

Thus by a complicated jjocess a division of the stainable nuclear
substance into similar halves is brought about. As the immediate

EMBRYOLOGY.

Consequence of this the protoplasmic parts of the cell also begin at
this time to be divided into halves by means of the process of cleavage,
which is already recognisable externally. There is formed at the
surface of the egg (fig. 29 A), in a plane passing between the two
groups of loops through the middle of the spindle perpendicular
to its long axis, a circular furrow, which rapidly cuts deeper and
deeper into the substance of the egg, and in a short time divides
it into two equal parts. Each of these contains half of the spindle

Fig. 29 A.— Egg of a Sea-urchin at the moment of division.

A circular furrow cuts into the yolk and halves it in a plane which is perpendicular to the
middle of the nuclear axis and to the long axis of the dumb-bell.

B.— Egg of a Sea-urchin after its division into two cells.

In each resultant of the di vision a vesicular daughter-nucleus has arisen. The radial arrange-
ment of the protoplasm begins to become indistinct.
Both figures are drawn from the living object.

with half of the loops, half of the dumb-bell, and a protoplasmic
radiation.

The resulting halves of the egg, still surrounded in common by the
vitelline membrane, then closely apply to each other the surfaces
resulting from the division, and become so flattened that each one of
them forms approximately a hemisphere (fig. 20 E). Internally,
however, nucleus and protoplasm enter upon a brief transitory resting
stage. There is developed out of the half of the nuclear spindle
with its daughter-loops a vesicular homogeneous daughter-nucleus
like the first, but in the protoplasm the radial arrangement becomes
less and less distinct and at last entirely disappears.

The egg of the common Maw-worm of the Horse is also a very
instructive object for the study of the process of cleavage, as it was
for the study of fertilisation, for it allows a still deeper insight into
this process. As has already been stated, the egg-nucleus and the

THE PROCESS OF CLEAVAGE. 55

spermatic nucleus remain for a time separate, even after they have
approached each other. After a brief period of rest both of them
begin to exhibit simultaneously the changes which precede the for-
mation of the nuclear spindle. In each the chromatic substance is
metamorphosed into a fine thread, which is arranged within the
nuclear membrane in numerous windings. Each filament is there-
upon divided into two equally large coiled loops, the chromosomes
{fig. 25 ch). Now the two vesicular nuclei lose their delimitation
from the surrounding yolk, in which there arise at a little distance
from each other two polar corpuscles [centrosomes], surrounded by a
system of rays, which is at first faint, but subsequently becomes
more distinct. Between the two centrosomes, the method of whose
development no one has as yet succeeded in observing, there are
formed spindle-fibres, and the four loops (chromosomes), set free by
the dissolution of the two nuclear membranes, so arrange themselves
that they lie upon the outside of the spindle at its equator.

In the case of the egg of the Maw-worm, therefore, the union of the
two sexual nuclei, which terminates the act of fertilisation, takes
place only at the time of the metamorphosis to form the cleavage-
spindle, in which metamorphosis they take an equal share. In conse-
quence of this remarkable deviation from the ordinary course of the
process of fertilisation, VAN BENEDEN has been able to establish the
interesting and important fact that half of the chromosomes of the
first cleavage-spindle are derived from the egg-nucleus, and half from
the spermatic nucleus, and that consequently they may be distin-
guished as female and male chromosomes. Since in this instance, just
.as in nuclear division ordinarily, the four loops are split lengthwise
and then move apart toward the two polar corpuscles (centrosomes),
there are formed two groups of four daughter-loops each, of which
two are of male origin and two of female. Each group is then meta-
morphosed into the quiescent nucleus of the daughter-cell. This
furnishes incontestable proof, that to each daughter-nucleus in each
half of the egg, ivhich arises as the result of the first cleavage, there is
transmitted exactly the same amount of chromatic substance from the
egg-nucleus as from tJie spermatic nucleus.

The first division is followed after a brief period of rest by the
second, this by the third, the fourth, etc., during which are repeated
the same series of changes in nucleus and protoplasm that have just
been described. Thus in quick succession the 2 first daughter-cells
are divided into 4, these into 8, 16, 32, 64, etc. (fig. 30), until
there has resulted a large spheroidal mass, wliich has received the

56 EMBRYOLOGY.

name morula or mulberry -sphere, because the cells protrude as small
elevations at its surface.

During the second and third stages of cleavage there is easily
recognisable a rigidly observed order in the direction which the planes
of cleavage sustain to each other. The second plane of cleavage always
halves the first and cuts it perpendicularly ; the third plane, again, is-
perpendicular to the first two, and passes through the middle of the
nxis formed by their intersection. If one regards the ends of this
axis as the poles of the egg, the first two planes of division may be
designated as meridional, the third as equatorial.

This uniformity is caused by the mutual relation which subsists
between nucleus and protoplasm, in which connection the two follow-
ing laws are to be noted : (1) The plane of division always cuts the
axis of the spindle perpendicularly at its centre. (2) The position of

Fig. 30.— Various stages of the process of cleavage, after GEGENBAUR.

the axis of the nuclear spindle in turn depends on the form and differ-
entiation of the protoplasmic body which envelops it, and in such a
manner that the two poles of the nucleus take the direction of the greatest
protoplasmic masses. Thus, for example, in a sphere in which the
protoplasm is uniformly distributed, the centrally situated spindle
may come to lie in any radius ; but in an ovoid protoplasmic body,
only in the longest diameter. In a circular protoplasmic disc the
nuclear axis lies parallel to its surface in any diameter whatever of
the circle, but in an oval disc, as before, in the longest diameter
only.

Let us return now, after these general remarks, to the case under
consideration. Each daughter-cell forms at the close of the first seg-
mentation a hemisphere. According to the rule, the daughter-spindle
cannot assume a position perpendicular to the flat surface of the
hemisphere, but must lie parallel to it, so that a division into two
quadrants must result. At the next segmentation the axis of the
spindle must coincide with the long axis of the quadrant, whereby
this becomes divided into two octants.

THE PROCESS OF CLEAVAGE. 5/

There are some important deviations from the process of division
just described, which affect the form of the cleavage products, although
leaving unaltered the finer processes relating to the nucleus. The
deviations are induced, as we shall show more in detail in the in-
dividual cases, by the variation in the amount of deutoplasm contained
in the eggs, and by the previously described variability in its distribu-
tion. One may appropriately separate the various forms of the-
process of cleavage into two classes, and each class into two sub-
classes, although the forms merge into one another by means of
transitional conditions.

To the first class we assign such eggs as are completely divided
into segments by the process of cleavage. The cleavage itself we-
designate as total ; and according as the segments are of equal or un-
equal size, we distinguish as subdivisions equal cleavage and unequal
cleavage.

With total is contrasted partial cleavage. This occurs in the
case of eggs which are provided with very abundant deutoplasm,.
and are consequently of considerable size, and in which, at the same
time, the previously described separation into formative yolk and
nutritive yolk has been distinctly established. In this case the for-
mative yolk alone undergoes a process of cleavage, whereas the chief
mass of the egg, the nutritive yolk, remains undivided, and in general
unaffected, by the processes of embryonic development ; hence the
name partial cleavage. This, in turn, is resolvable into the two sub-
types of discoidal and superficial cleavage, according as the forma-
tive yolk rests as a disc upon the nutritive yolk, or envelops the
latter as a thick cortical layer. REMAK has designated eggs with
total segmentation as holoblastic, those with partial segmentation as
meroblastic.

We may therefore present the following scheme of cleavage : —

I. TYPE-
TO tal cleavage : ~\

(#) Equal cleavage Holoblastic eggs.

(J) Unequal cleavage J
II. TYPE—

Partial cleavage : "|

(«) Discoidal cleavage Meroblastic eggs.

(&) Superficial cleavage J

Ia- Equal Cleavage.

In the general consideration of the process of cleavage we have
already become acquainted with the phenomena of equal segmenta-

58 EMBRYOLOGY.

tion. It remains to be added to what has been previously said, that
this t"-ne is most frequent in the case of Invertebrates, and is to be
encountered among Vertebrates only in the cases of Amphioxus and
Mammals. With the latter, however, there early appears a slight
difference in the size of the segments ; this has induced many
investigators to designate the cleavage of Amphioxus and Mammals
as unequal also. If I have not followed this suggestion, it is
because the differences are of a trivial nature, because the nucleus
in the egg-cell, and also in its segments still occupies a central
position, and because the different methods of cleavage are in
general not sharply definable, but connected by transitional con-
ditions.

Concerning Amphioxus, HATSCHEK states that at the eight-cell stage
four smaller and four larger cell are to be distinguished, and that
from that time forward in all the subsequent stages there is to be
observed a difference in size, and that the process of cleavage takes
place in a manner similar to that which will be subsequently
described for the Frog's egg. The egg of the Rabbit, concerning
which we have the painstaking investigations of VAN BENEDEN,
•divides at the very outset into two segments of slightly different
size j moreover, from the third stage of division onward there occurs
n difference in the rapidity with which the divisions follow each
other in the different segments. After the four cleavage-spheres
have been divided into eight, there is a stage with twelve spheres ;
this is followed by another with sixteen, and afterwards another with
twenty-four.

P- Unequal Cleavage.

As a basis for the description of unequal cleavage we may employ
the Amphibian egg, the structure of which has already been con-
sidered. As soon as the egg of the Frog or Triton is deposited in
the water and is fertilised, and while the gelatinous envelope is
swelling up, its black pigmented hemisphere or animal half becomes
directed upward, because it contains more protoplasm and small
yolk-spherules, and is specifically lighter. The want of uniformity
in the distribution of the various components of the yolk also induces
an altered position of the segmentation-nucleus. \Whereas the latter
.assumes a central position in all cases in which the deutoplasm is
uniformly distributed, it invariably alters its location whenever
one half of the egg is richer in deutoplasm and the other richer in
protoplasm ; it then migrates into the more protoplasmic territory.

THE PROCESS OF CLEAVAGE. 5'J

In the case of the Frog's egg, consequently, we find it in the black
piginented hemisphere, which is turned upward.

When in this case the nucleus prepares to divide, its axis can no
longer assume the position of any and every radius of the egg. In
consequence of the want of uniformity in the distribution of the
protoplasm, the nucleus comes under the influence of the more
protoplasmic pigmented part, which rests on the more deutoplasmic
portion like an inverted cup, and, on account of its less specific
gravity, floats at the surface, and is spread out horizontally. But
in a horizontal protoplasmic disc the nuclear spindle comes to occupy
a horizontal position (fig. 31 A sp). Consequently the plane of
division must be formed in a vertical direction. A small furrow now

p

pr

Fig. 31. — Diagram of the division of the Frog's egg.

A, Stage of the first division. B, Stage of the third division. The four segments of the second
stage of division are beginning to be divided by an equatorial furrow into eight segments.
P, pigmented surface of the egg at the animal pole ; pr, the part of the. egg which ia richer
in protoplasm ; d, the part which is richer in deutoplasm ; sp, nuclear spindle.

begins to show itself — at the animal pole first, because the latter is
more under the influence of the nuclear spindle, which lies nearer
to it, and because it contains more protoplasm, from which proceed
the phenomena of motion during division. The furrow gradually
deepens downward, and cuts through to the vegetative pole.

By the first act of division we get two hemispheres (fig. 32 2), each
of which is composed of a quadrant richer in protoplasm and directed
upward, and another poorer in protoplasm and directed downward.
By this means both the position of the nucleus and the direction of
its axis are again determined, when it prepares for the second
division. According to the rule previously laid down, the nucleus is
to be sought in the quadrant which contains the more protoplasm ;
the axis of the spindle must take a position parallel to the long
axis of the quadrant, and must therefore come to lie horizontally

GO

EMBRYOLOGY.

The second plane of division is consequently, like the first, vertical,
and cuts the latter at right angles.

After the conclusion of the second segmentation the Amphibian
egg consists of four quadrants (fig. 32 4), which are separated from
one another by vertical planes of division and possess two dissimilar
poles, — one richer in protoplasm, lighter, and directed upwards ; the
other richer in yolk, heavier, and directed downwards. In the case of
equal segmentation we saw that at the stage of the third segmentation
the axis of the nuclear spindle becomes parallel to the long axis of
the quadrant. The same thing occurs here also, although in a some-
what modified manner. On account of the greater accumulation of
protoplasm in the upper half of the quadrant, the spindle cannot, as-

Fig. 32. — Cleavage of Rana temporaria, after ECKER.

The numbers placed above the figures indicate the number of segments present in the corre-
ponding stage.

in the case of equal segmentation, lie in the middle of it, but must
lie nearer to the animal pole of the egg (fig. 315 sp). Moreover, it
is exactly vertical, because the four quadrants of the Amphibian egg
are definitely oriented in space on account of the difference in specific
gravity of their halves. In consequence of this the third plane
of division must be horizontal, and must also lie above the equator of
the egg-sphere more or less toward its animal pole (fig. 32 8). The
segments are very unlike both in size and composition ; and this is
the reason why this form of segmentation has been called unequal.
The four upper segments are smaller and contain less yolk, the four
lower ones are much larger and richer in yolk. They are also
distinguished from each other as animal cells and vegetative cells,
according to the poles near which they lie.

In the course of farther development, the distinction between
animal and vegetative cells constantly increases, for the richer the
cells are in protoplasm the more quickly and the more frequently

THE PROCESS OF CLEAVAGE. 61

do they divide. At the fourth stage the 4 upper segments are first
•divided by vertical furrows into 8, and then after an interval the
4 lower ones are divided in the same manner, so that the egg is now
composed of eight smaller and eight larger cells (fig. 32 16). After
a short resting stage the eight upper segments are again divided, this
time by a horizontal furrow, and somewhat later a similar furrow
divides the eight lower segments also (fig. 32 32). In the same
manner the 32 segments are divided into 64 (fig. 32 64). In the
stages which follow this, the divisions in the animal half of the egg
are still more accelerated relatively to those of the vegetative half.
While the 32 animal cells are divided into 128 segments by two
divisions which follow each other in quick succession, there are
still found in the lower half only 32 cells which are preparing
for cleavage. It thus comes to pass that, as the final result of the
process of cleavage, there exists a spheroidal mass of cells with entirely
dissimilar halves, — an upper, animal half with small, pigmented
cells, and a vegetative half with larger, clear cells, containing more
abundant yolk.

From the nature of the progress of unequal cleavage, as well as
from a series of other phenomena, one may lay down a general law,
first formulated by BALFOUB, that the rapidity of cleavage is pro-
portional to the concentration of protoplasm in the segment. Cells
which are rich in protoplasm divide more rapidly than those in which
protoplasm is more scanty and deutoplasm more abundant.

As we have seen, the Frog's egg, by reason of the difference in
specific gravity between its animal and vegetative halves, by reason
of the heterogeneous pigmentation of its surface, by reason of thfe
unequal distribution of protoplasm and deutoplasm, and by reason or
the eccentric position of its. nucleus, allows us to pass fixed and easily
determinable axes through its spherical body. On this account it is
an especially favourable object upon which to determine the question
whether the egg allows one to recognise in the position of its parts,
<3ven before fertilisation, immediately after the same, and during the
process of cleavage, fixed relations to the organs of the fully developed
organism. This question has been tested by means of ingenious
experiments, especially by PFLUEGER and Roux, by the latter in his
" Beitrage zur Entwicklungsmechanik des Embryo."

These have resulted in determining that the first cleavage plane of
the egg corresponds to the median plane of the embryo, so that it
separates the material of the right half of the body from that of the
left. Secondly, according to Royx, the position of the head- and tail-

C2

EMBRYOLOGY.

ends of the embryo may be determined in the fertilised egg. That
half of the egg, namely, through which the spermatic nucleus
migrates to reach the egg-nucleus, becomes the tail-end of the
embryo ; the opposite half becomes the head-end. Every egg,
however, can be fertilised in any meridian whatever, as was demon-
strable experimentally, and thereby the tail-end of the embryo may
be located at any chosen position in the egg. Thirdly, the plane
in which the two sexual nuclei meet each other (copulation-plane)
corresponds with the first plane of segmentation.

IIa- Partial Discoidal Cleavage.

The Hen's egg serves us as the classical example for the description
of discoidal segmentation. In this instance the whole process of

Fig. SZ.— Surface view of the first stages of cleavage in the Hen's egg, after COSTE.
«, Border of the germ-disc ; b, vertical furrow ; c, small central segment ; d, large peripheral
segment.

cleavage takes place while the egg is still in the oviduct, during the
period in which the yolk is being surrounded by the albuminous
envelope and the calcareous shell. It results simply in a cleavage of
the germ-disc of formative yolk, whereas the greater part of the
egg, which contains the nutritive yolk, remains unsegmeiited, and
becomes subsequently enclosed in an appendage to the embryo, — the
so-called yolk-sac, — and is gradually consumed as nutritive material.
Just as in the case of the pigmented, animal half of the Frog's eggr
so also in the case of the Hen's egg, turn it in whatever direction
one will, the germ-disc floats on top, because it is the lighter part.
As in the Frog's egg the first plane of cleavage is vertical and begins-
at the animal pole, so in the case of the Hen's egg (fig. 33 A)
a small furrow (b) makes its appearance in the middle of the disc,
and advances from above downward in a vertical direction. But

THE PROCESS OF CLEAVAGE. 63

whereas in the case of the Frog's egg the first plane of cleavage cuts-
through to the opposite pole, in the case of the Hen's egg it divides
only the germ-disc into two similar segments, which like two buds
rest upon the undivided yolk-mass with a broad base, by means of
which they still have a physical connection with each other. Soon after
this, there is formed a second vertical furrow, which crosses the first
at right angles, and likewise remains limited to the germ-disc, which
is now divided into four segments (fig. 33 B).

Each of the four segments is again divided into halves by a radial
furrow. The segments thus formed correspond to sectors, which
meet in the centre of the germ-disc with pointed ends, and have

Fig. 34.— Section through the germ-disc of the Hen's egg during the later stages of segmentation

after BALFOUR.
The section, which represents rather more than half the breadth of the blastoderm (the middlt

line is at c), shows that the segments of the surface and of the centre of the disc are smallei

than those below and toward the periphery. At the border they are still very large. One of

the latter is indicated at a.
a, Large peripheral cell ; b, larger cells of the lower layers ; c, middle line of the blastoderm ;

e, boundary between the blastoderm and the white yolk, w.

their broad ends turned toward the periphery. The apex of each of
the segments is then cut oft* by a cross furrow, i.e., by one which is
parallel to the equator of the egg (fig. 33 C), in consequence of which
there are formed smaller central (c) and larger peripheral (d) seg-
ments. Since from this time forward radial furrows and those that
are parallel to the equator make their appearance alternately, the germ-
disc is subdivided into more and more numerous segments, which are
so arranged that the smaller lie at the centre of the disc, — therefore
immediately around the animal pole, — the larger toward its periphery.
With the advancing cleavage the smaller segments are entirely con-
stricted off from the underlying yolk, whereas the larger peripheral
ones still remain at first in continuity with it (fig. 34). In this way
we finally get a disc of small embryonic cells, which, toward the
middle, are arranged in several superposed layers.

•64 EMBRYOLOGY.

Tho layer of yolk which immediately adjoins the periphery of the
cellular disc, and which is very finely granular and especially rich in
protoplasm, still merits particular consideration, for in it lie isolated
nuclei (fig. 35 nx), the much-discussed yolk-nuclei or parablasi-nuclei
{the " merocytes " of RUCKERT). In the case of the Chick they are
less striking than in Teleosts and Selachians, in which they have
been accurately investigated by BALFOUR, HOFFMANN, RFCKERT,
and KASTSCHENKO. Formerly these were held to arise spontaneously
(free formation of nuclei) in the yolk, an assumption which in itself
is very improbable, since, according to our present knowledge, the
free formation of nuclei does not appear to occur anywhere in

Jfig. 35. — Section through the germ-disc of- a Pristiurus embryo during segmr n';ation, after

BALFOUR.
n, Nucleus; nx, modified nucleus prior to division; nx', modified nucleus in the yolk; f,

furrows which appear in the yolk adjacent to the germ-disc.

either animal or vegetable kingdom. Consequently the yolk-nuclei
are now rightly held to be derived from the cleavage-nuclei. They
are probably produced even at an early period, when the first-formed
segments, which remain, as we have seen, for a long time in connection
with the yolk, begin to be constricted off from the latter. This
probably takes place in the following manner : there arise in the
segments nuclear spindles, the halves of which go into the completely
isolated embryonic cells at the time of their separation from the
yolk, while the remaining halves go into the underlying yolk-layer,
and are there converted into vesicular yolk-nuclei.

Their number subsequently increases by means of indirect division,
as is established by the fact that in sections nuclear spindles have
been observed in the yolk-layer (fig. 35 nx').

While, on the one hand, there is an increase in the member of the
yolk-nuclei, so, on the other hand, there is also a diminution in their

THE PROCESS OF CLEAVAGE. 65

number, as is asserted by several authors (WALDEYER, RUCKERT,
BALFOUR, etc.). This takes place by the constricting off of nuclei
and surrounding protoplasm, which go to enlarge the cellular disc.
We may, with WALDEYER, designate these as secondary cleavage-cells,
and regard the whole process as a kind of supplementary segmentation.

By means of this a part of the voluminous yolk-material continues
to be gradually individualised into cells. These annex themselves to
the border of the germ-disc, which with their aid increases in extent
and grows over a continually increasing territory of the unsegmented
yolk-sphere. In still later stages of development, long after the
cellular germ-disc has been differentiated into the germ -layers, the
supplementary segmentation continues to go on at the margin of the
disc in the neighbouring yolk-mass, and to furnish new cell-material.
Therefore the layer which encloses the yolk-nuclei forms an important
connecting link between the segmented germ and the unsegmented
nutritive yolk; I shall come back to this subject later.

The appearance of merocytes and the supplementary cleavage
which proceeds from them are phenomena which are induced by the
vast accumulation of yolk-material, and which allow the latter to be
divided up into cells, even though the process is a slow one.

The eggs of Selachians (KASTSCHEXKO, KUCKERT) deviate a little
from the usual method of partial cleavage in meroblastic eggs,
and in a manner which recalls to a certain extent the processes
of superficial cleavage, which are to be treated of later. The
cleavage-nucleus, namely, is divided into two nuclei, these again
into four and even a greater number, without an accompanying
division of the germ -disc into a corresponding number of segments.
In this case, therefore, there arises at first a multinuclear proto-
plasmic mass, — a plasmodium, — in which the nuclei are distributed at
regular intervals. Subsequently furrows appear, generally in great
numbers and all at once, by means of which the germ-disc becomes
divided into cells from the centre to the periphery. Some of the
nuclei always remain in the periphery outside the territory of
cleavage, here undergo further division, migrate out of the germ-
disc into the surrounding nutritive yolk, and constitute the yolk-
nuclei or merocytes. These cause and maintain in the yolk for
a long time the process of supplementary cleavage.

When we institute a comparison between partial and unequal
cleavage, — for the descriptions of which we have made use of the eggs
of the Hen and the Frog, — it is not difficult to derive the former
from the latter, and to find a cause for the origin of the former.

5

66 EMBRYOLOGY.

It is the same as that which produced unequal cleavage from
equal cleavage ; it is the great accumulation of nutritive yolk,
the inequality in the distribution of the egg-substances which
goes hand in hand with it, and the alteration in the position
of the cleavage-nucleus. The process of differentiation, which
is still in a stage of transition in the case of the Frog's egg, is
carried to an extreme in the case of the Hen's egg. Protoplasmic
substance was already abundantly accumulated at the animal pole in
the former case, but in the latter it is still more concentrated, and
at the same time has become differentiated from the nutritive yolk
as a disc enclosing the segmentation-nucleus. The yolk, accumulated
to an enormous extent at the opposite pole, is, in consequence of this
separation, relatively poor in protoplasmic substance, which only
scantily fills the interstices between the large yolk- spheres.

Inasmuch as the phenomena of motion during the process of
division emanate from the protoplasm and nucleus, whereas the
deutoplasm remains passive, the active substance in the case of mero-
blastic eggs can no longer master the passive substance and cause it to
participate in the cleavage. Even in the case of the Frog's egg a
preponderance of the animal pole during cleavage is observable;
within its territory the nucleus lies, the radial figures of the proto-
plasm appear, and the first and second planes of division begin to
arise, whereas they cut through at the vegetative pole last of all ;
moreover the process of division during the later stages takes place
there with greater rapidity, so that a distinction arises between the
smaller animal cells and the larger vegetative ones. In the case of
the Hen's egg, the preponderance of the animal pole is still further
increased, and the contrast with the vegetative pole is most sharply
expressed. The cleavage-furrows not only begin there, but they
remain restricted to the territory immediately surrounding it. Thus
we get on the one hand a disc composed of small animal cells, on the
other an immense undivided yolk-mass, which corresponds to the
larger vegetative cells of the Frog's egg. The yolk-nuclei enclosed in
the periphery of the germ-disc are equivalent to the nuclei of the
vegetative cells of the Frog's egg.

IP- Partial Superficial Cleavage.

The second sub-type of partial cleavage is prevalent in the phylum
of Arthropods, and occurs in centrolecithal eggs, where a central
yolk-mass is enclosed in a cortical layer of formative yolk. Manifold

THE PROCESS OF CLEAVAGE. 67

variations are possible here, as well as transitions to equal and un-
equal cleavage. When the course pursued is quite typical, the
segmentation-nucleus, surrounded by a mantle of protoplasm, lies in
the middle of the egg in the nutritive yolk ; here it is divided into
two daughter-nuclei, without the occurrence of a corresponding division
of the egg-cell. The daughter-nuclei, in turn, undergo division into
4, these into 8, 16, 32 nuclei, etc., while the egg as a whole still
remains unsegmented. Subsequently the nuclei move apart, the
greater number gradually migrate to the surface, and penetrate into
the protoplasmic cortical layer, where they arrange themselves at
uniform distances from each other. It is only at this stage that
the process of egg-segmentation takes place, for now the cortical layer
is divided into as many cells as there are nuclei in it, while the central
yolk remains undivided. The latter is therefore suddenly enclosed in
a sac formed of small cells — a blastoderm (Keimhaut). Instead of
a polar (telolecithal) yolk, we have a central (centrolecithal) yolk.
Ordinarily yolk-nuclei or merocytes remain behind in the yolk, as in
the meroblastic eggs of Vertebrates.

Now that we have become acquainted with the various forms of the
process of segmentation, it will be expedient to dwell for a moment
on its results. According as the process of cleavage takes place
by one or the other of the four methods described, there arises
a mass of cells with corresponding characteristics. From equal
segmentation there arises a spherical germ with cells approximately
uniform in size (Amphioxus, Mammals) (fig. 30, p. 56) ; from un-
equal segmentation, as well as from discoidal, there is produced^
form of the germ with polar differentiation. This manifests itself in
the first case (Cyclostomes, Amphibia) in the production of small
cells at the animal pole and large yolk-laden elements at the opposite,
vegetative pole (fig. 32 64, p. 60). In the other case (fig. 35, p. 64)
the vegetative pole is occupied by an unsegmented yolk-mass, in
which at definite regions nuclei are found (Fishes, Reptiles, and
Birds). Finally there is developed from superficial cleavage a germ
composed of a mantle of cells, which envelops an unsegmented yolk-
mass in which also there are nuclei (Arthropods).

The multicellular germ undergoes further changes, sometimes in
the earlier stages of the cleavage-process, sometimes only in the later
stages, in that a small, fluid-filled cleavage-cavity is developed in its
centre, by the separation of the embryonic cells. At first small, this

68

EMBRYOLOGY.

Fig. 36. — Blastula of Amphioxus, after HATSCHEK.
h, Segmentation-cavity ; az, animal cells ; dz, cells
with abundant yolk.

cavity increases more and more in size, so that the surface
of the whole germ is augmented, and the cells which were at

first central come to the
surface.

Different names have been
given to the solid and to the
hollow mass of cells. A
morula or mulberry -sphere
is spoken of as long as the
segmentation-cavity is either
wanting or only slightly de-
veloped. But when a larger
cavity has been formed, as
is almost always the case
toward the end of the
cleavage-process, the germ
is called a blastula or blas-

tosphere (Keimblase). The latter in turn exhibits a four-fold
variation of form, according to the abundance of yolk in the
original egg and the method of the antecedent segmentation.

In the simplest case (fig. 36) the wall of the blastula is only one
layer thick ; the cells are of uniform size and cylindrical, and are
closely united to one another
to form an epithelium (many
of the lower animals, Am-
phioxus). In the case of
lower, aquatic animals the
blastulse at this stage aban-
don the egg-envelopes, and,
since their cylindrical cells
develop cilia at the surface,
swim about with rotating
motion in the water as ciliate
spheres or blastospheres.

In eggs with unequal seg-
mentation the blastula is
ordinarily formed of several
layers of cells, as in the case of the Frog and Triton, and at
the same time it exhibits in different regions different thicknesses
(fig. 37). At the animal pole the wall is thin ; at the vegetative
pole, on the contrary, it is so much thickened that an elevation,.

— fh

'. dz

Fig. 37.— Blastula of Triton tseniatus.
fh, Segmentation-cavity ; rz, marginal zone ; dz, cells
with abundant yolk.

THE PROCESS OF CLEAVAGE.

69

composed of large yolk-cells, protrudes from this side far into the
cleavage-cavity, thus considerably diminishing it.

The eggs with partial discoidal segmentation (fig. 38) are modified
most of all, and are therefore scarcely to be recognised as blastula?.
In consequence of the immense accumulation of yolk on the ventral
(vegetative) side, the cleavage-cavity (B) is extraordinarily constricted,
and is still preserved only as a narrow fissure filled with albuminous
fluid. Dorsally its wall consists of the small embryonic cells (kz) result-
ing from the process of cleavage, which are accumulated in several
superposed layers; at the surface they join each other closely,
deeper they lie more loosely associated. The floor of the cleavage-
cavity is formed of a yolk-mass, scattered through which are
to be found the
yolk-nuclei or dlf

merocytes (dk),
which likewise
result from the
cleavage-p r o c e s s.
It is to be seen
that they are espe-
cially numerous at
the place of tran-
sition from the
germ-disc to the
yolk -mass.

This nucleated

yolk-mass very evidently corresponds to the large vegetative cells
which constitute the floor of the cleavage-cavity in the case of the
Amphibian egg (fig. 37).

In the case of superficial cleavage there is formed, strictly speaking,
no blastula, since the place where the segmentation-cavity should be
developed is filled with nutritive yolk. The latter either remains
»msegmented or is subsequently divided, as in the Insects, into in-
dividual yolk-cells.

Fig. 38.— Median section through a germ-disc of Pristiurus in the

blastula stage, after RUCKERT.
S, Cavity of the blastula ; kz, segmented germ ; dk, finely granular

yolk with yolk-nuclei.

HlSTOBY OF THE PROCESS OP CLEAVAGE.

The investigation and right comprehension of the process of cleavage have
been attended with manifold difficulties. A voluminous literature has arisen
on this subject. We limit ourselves to pointing out the most important dis-
coveries and the chief questions which have been discussed.

The first observations on the process of segmentation were made on the
Frog's egg. Aside from short statements by SWAMMEEDAM and ROSEL VON

70 EMBRYOLOGY.

EOSENHOF, it was PREVOST ET DUMAS who were the first to describe, in 1824,
the manner in which regular furrows arise on the Frog's egg, and how by
means of these the whole surface is divided into smaller and smaller areas.
According to the French investigators, the furrows were restricted to the sur-
face of the egg. However, only a few years later, RUSCONI (1826) and C. E.
V. BAER recognised that the furrows visible at the surface correspond to
fissures which extend through the whole mass of the yolk, and divide it into
separate parts. Even in his time VON BAER rightly characterised the whole
process of segmentation, in which he discerned the first impulse of life, as an
automatic division of the egg-cell, but subsequently he abandoned this, the
right path, since he sought for the meaning or! division in the dictum : that
"all yolk-masses are subject to the influence of the fluid and volatile
components of the fertilising material."

In the next decennary there followed numerous discoveries of the process of
segmentation in other animals. During this period acquaintance was also
gained with partial segmentation. After KUSCONI and VOGT had seen it in
the case of fish eggs, KOLLIKER gave, in the year 1844, the first detailed
description of it as seen in the eggs of Cephalopods, and four years later
COSTE described it in the Hen's egg.

The question of the significance of the cleavage-process has engaged the
earnest attention of investigators, and has given rise to many controversies.
The discussion first took a definite turn upon the establishment of the cell-
theory. The question was, to determine whether and in what manner cleav-
age was a process of cell-formation. Although there were already many
observations on the division of eggs, SCHWANN himself took no definite posi-
tion on this question. The views of other investigators were at variance for
years. There was a difference of opinion as to whether the egg or the ger-
minative vesicle was a cell, whether the segments resulting from cleavage
possessed a membrane or not, and whether these segments were to be regarded
as cells or not. In the earlier literature the germinative vesicle and the
nuclei of the cleavage-spheres were often designated as embryonic cells, and
the surrounding yolk-mass as an enveloping sphere. The difficulty of com-
prehending the process of segmentation was also aggravated by the false
doctrine of free cell -formation from an organic matrix— the cytoblastema —
founded by SCHWANN. It remained for a long time a controverted point
whether the tissue-cells of the adult organism were the direct descendants of
the segmentation-spheres, or whether they arose at a later period by means
of free cell-formation from cytoblastema. After NAGELI on the botanical
side had adopted the right course, it was the service of KO"LLIKER, KEICHERT,
KEMAK, and LEYDIG to have paved the way to a comprehension of cleavage,
and to have shown that free cell-formation does not take place, but that all
cellular elements arise in uninterrupted sequence from the egg-cell.

As far as regards the different kinds of cleavage, KOLLIKER designated
them as total and partial. VAN BENEDEN has given in his " Recherches sur
la composition et la signification de 1'ceuf " a more exhaustive review of the
subject, and has also expounded in a clear way the signification of the
deutoplasm for the different kinds of cleavage. Subsequently HAECKEL mate-
rially simplified the categories of segmentation recognised by VAN BENEDEN,
and proposed in his " Anthropogenic " and in his paper " Die Gastrula und die
Eif urchung " the classification of the methods of cleavage on which is based
the scheme previously given, and according to which total cleavage is divided

THE PROCESS OF CLEAVAGE. 71

into equal and unequal, and partial into discoidal and superficial. At the
same time HAECKEL endeavoured to derive the different methods of cleavage
from one another, and apropos of this directed attention to the important role
of the nutritive yolk.

The processes which take place within the yolk have eluded observation
and a correct interpretation even more than the external phenomena of cleav-
age, so that it is only in the most recent times that we have acquired a satis-
factory insight into them. It is true that the problem, as to what part the
nucleus plays in segmentation, has had the uninterrupted attention of investi-
gators, but without any solution having been found. For years there were in
the literature two opposing views : sometimes one of them, sometimes the
other, attained temporarily greater currency. According to one view— which
was almost universally adopted by the botanists, and was defended on the
zoological side principally by EEICHERT, and even recently by AUERBACH—
the nucleus disappears before every division, and is dissolved, to be afterwards
formed anew in each daughter-segment; according to the other view the
nucleus, on the contrary, is not dissolved, but is constricted, becomes
dumb-bell-shaped, and is divided into halves, and thereby induces cell-division.
This view was taught especially by such zoologists and anatomists as C. E.
v. BAER, JOH. MULLER, KOLLIKER, LEYDIG, GEGENBAUR, HAECKEL, VAN
BENEDEN, and others, who were supported by the observations which they
had made on transparent eggs of the lower animals.

Light was first thrown on the disputed question at the moment when suit-
able objects were studied with the aid of higher magnifications, and especially
with the employment of modern methods of preparation (fixing and staining
reagents).

The works of FOL, FLEMMING, SCHNEIDER, and AUERBACH on the cleavage
of the eggs of various animals mark a noteworthy advance. They still main-
tained, it is true, that the nucleus is dissolved at the time of cleavage, but they
gave a detailed and accurate description of the striking radiation which arises
in the yolk upon the disappearance of the nucleus, and which during the
constriction of the egg soon becomes visible in the region of the daughter-
nuclei.* SCHNEIDER observed parts of the spindle-stage.

Soon after this a more exact insight into the complicated and peculiar
nuclear changes was obtained by means of three investigations, which were
carried out independently and simultaneously on different objects, and were
published in rapid succession by BUTSCHLI, STRASBURGER, and the author.
It was definitely established by these observations that there is no dissolution
of the nucleus at the time of division, but a metamorphosis, such as has been
described in the preceding pages. At the same time I likewise proved that the
egg-nucleus is not a new formation, but is derived from parts of the germinative
vesicle. From this resulted the important doctrine that, just as ill cells, so also
all nuclei of the animal organism are derivatives in an uninterrupted sequence,
the one from tlie egg-cell and tJie other from its nucleus. (Omnis cellula e cellula,
omnis nucleus e nucleo.) Through these researches there was furnished for the

* Eadiating structures had already been observed in the yolk before this,
but in an incomplete manner, by different authors — by GRUBE in the Hiru-
dinea, by DERBES and MEISSNER in the Sea-urchin, by GEGENBAUR in Sagitta,
by KROHN, KOWALEVSKY, and KUPFFER in Ascidians, by LEUCKART in Nema-
todes, by BALBIANI in Spiders, and by OELLACHER in the Trout.

72 EMBRYOLOGY.

first time a scheme of nuclear division and cell-division, which has since
proved to be correct in all essentials, even though it has undergone important
improvements and additions at the hands of FOL, FLEMMING, VAN BENEDEN,
and RABL.

FOL published an extended monographic investigation of the process of
cleavage, which he had observed in many invertebrated animals. FLEMMING,
starting with nuclear division in tissue-cells, distinguished with great acumen
the non-chromatic and the chromatic parts of the nuclear figure, the non-
stainable nuclear spindle-fibres, and the stainable nuclear filaments and loops,
which are located upon the surface of the former. He made the interesting-
discovery concerning the latter, that they become split lengthwise. Lignt
was soon thrown upon this peculiar phenomenon, when HEUSER, VAN BENEDEN,
and RABL, independently of each other, discovered that the halves of the split
filaments moved apart toward the poles of the nucleus, and furnished the
fundament for the daughter-nuclei. VAN BENEDEN at the same time made
the additional and important observation on the egg of Ascaris megalocephala,
that of the four chromatic loops, which are constantly to be observed in the
case of the cleavage-nucleus, two are derived from the chromatic substance
of the spermatic nucleus, the other two from the chromatic substance of the
egg-nucleus; and that, in consequence of the longitudinal splitting, each
daughter-nucleus receives at the time of division two male and two female
nuclear loops. In addition there have appeared many other recent works
of value on the process of cleavage by NUSSBAUM, RABL, CARNOY, BOVERI,
PLATNER, and others.

Within the last few years PFLtiGER has endeavored to prove by interesting
experiments that gravitation exercises a determining influence on the position
of the planes of cleavage. BORN, Roux, and the author, on the contrary,
thought they were able to explain division from the organisation of the egg-
cell itself. In the author's article, " Welchen Einfluss tibt die Schwerkraft
auf die Theilung der Zellen ? " he recognised the causes which determine the
various directions of the planes of division, (1) in the distribution of the
lighter egg-plasm and the heavier deutoplasm, and (2) in the influence which
the spatial arrangement of the egg-plasm exercises on the position of the
nuclear spindle, and that which the position of the latter exercises upon the
direction of the plane of cleavage.

SUMMARY.

1. In the process of cleavage the internal and the external pheno-
mena of segmentation are to be distinguished from each other.

2. The internal phenomena of cleavage find expression in changes
(a) of the nucleus, (6) of the protoplasm.

3. The nucleus while in the process of division consists of a non-
chromatic and a chromatic nuclear figure. The non-chromatic figure
is a spindle composed of numerous fibres. The chromatic figure is
formed of bent, V-shaped nuclear filaments (chromosomes), which lie
upon the surface of the middle of the spindle. At the two ends of
the spindle there is found a special polar corpuscle [centrosome].

THE PROCESS OF CLEAVAGE 73

4. The division of the nucleus takes place in the following manner :
the nuclear filaments split lengthwise, and their halves move apart
in opposite directions toward the ends of the spindle, and are there
converted into vesicular daughter-nuclei.

5. The protoplasm arranges itself around the ends of the spindle
in filaments having the form of a stellate figure (an aster), so that
a double radiation or an amphiaster arises in the egg.

6. The external phenomena of cleavage consist in the division of
the egg-contents into individual parts, the number of which corre-
sponds to that of the daughter-nuclei. They exhibit various modifica-
tions, which are dependent on the arrangement and distribution of
the egg-plasm and the deutoplasm, as is to be seen from the fol-
lowing scheme of segmentation.

Scheme of the Various Modifications of the Process

of Cleavage.
I. Total Cleavage. (Holoblastic eggs.)

The eggs, which for the most part are small, contain a small or
moderate amount of deutoplasm, and are completely divided into
daughter-cells.

1. Equal Cleavage.

This takes place in eggs with meagre and uniformly distributed
deutoplasm (alecithal). By the process of cleavage there are formed
segments which, in general, are of uniform size. (Amphioxus, Mam-
malia.)

2. Unequal Cleavage.

This occurs in eggs in which a more abundant deutoplasm is un-
equally distributed, being concentrated toward the vegetative pole,
and in which the cleavage-nucleus is located nearer the animal and
more protoplasmic pole. Usually the segments become unequal in
size only with and after the third act of division. (Cyclostomes,
Amphibia.)

II. Partial Cleavage. (Meroblastic eggs.)

The eggs, which are often very large, ordinarily contain con-
siderable quantities of deutoplasm. In consequence of the unequal
distribution of this, the egg- contents are separated into a formative
yolk, in which alone the process of cleavage is manifested, and a
nutritive yolk, which remains undivided, and is used up during
embryonic development for the growth of the organs.

74 EMBllYOLOGY.

1. Discoidal Cleavage.

This takes place in eggs with nutritive yolk in a polar position
The process of cleavage remains confined to the formative yolk
accumulated at the animal pole, which has the form of a disc and
contains only a small amount of deutoplasm. There is formed, con-
sequently, a cellular disc. (Fishes, Reptiles, Birds.)

2. Superficial Cleavage.

This occurs in the case of eggs with central yolk. In typical
cases the nucleus alone, which occupies the middle of the egg, under-
goes repeated division. The numerous daughter-nuclei which arise
in this manner migrate into the layer of protoplasm which invests
the central nutritive yolk, and the ' protoplasm is thereupon divided
into as many segments as there are nuclei lying in it. There is
formed a germ-membrane (Keimhaut). (Arthropods.)

7. Eggs with total cleavage are designated as holoblastic, eggs
with partial cleavage as meroblastic.

8. The direction and position of the first cleavage-plane are strictly
conformable to laws which are founded in the organisation of the
cell ; they are determined by the following three factors : —

First factor. The cleavage-plane always divides the axis of the
nucleus which is preparing for division perpendicularly at its middle.

Second factor. The position of the axis of the nucleus during
division is dependent upon the form and differentiation of the en-
veloping protoplasm.

In a protoplasmic sphere the axis of the nuclear spindle, occupying
the centre of the sphere, can lie in the direction of any radius what-
ever ; but in an oval protoplasmic body, only in the longest diameter.
In a circular disc the nuclear axis lies parallel to its surface in
any diameter of the circle, but in an oval disc only in the longest
diameter.

Third factor. In the case of eggs of unequal segmentation, which,
in consequence of their unequally distributed, polar deutoplasm,.
are geocentric, and therefore assume when in equilibrium a parti-
cular position, the first two planes of cleavage must be vertical, and
the third must be horizontal and placed above the equator of the
sphere.

LITERATURE. 75

.IiITERArURE.

In addition to the writings cited in the second chapter see : —

Auerbach. Organologische Studien. Heft I. und Heft II. , Breslau 1874.
Baer, C. E. von. Die Metamorphose des Eies der Batrachier. MUller

Archiv. 1834.
Born, G. Ueber die Furchung des Eies bei Doppelbildungen. Breslauer

iirztl. Zeitschr. 1887. Nr. 15.
Coste. Histoire generate et particuliere du developpement des corps organises.

1847—1859.
Flemming. Ueber die ersten Entwicklungserscheinungen am Ei der Teich-

muschel. Archiv f. mikr. Anat. Bd. X. p. 257. 1874.
Flemming^ Beitrage zur Kenntniss der Zelle und ihrer Lebenserscheinungen.

Archiv f. mikr. Anat. Bd. XVI. p. 302. 1878.
Flemming. Neue Beitrage zur Kenntniss der Zelle. Archiv f. mikr. Anat.

Bd. XXIX. p. 389. 1887.
Fol, H. Die ersteEntwicklungdesGeryonideneies. Jena. Zeitschr. Bd.VIL

1873.
Fol, H. Sur le developpement des Pteropodes. Archives de Zoologie exper

et gen. T. IV. and V. 1875-76.

Gasser. Eierstocksei u. Eileiterei des Vogels. Marburger Sitzungsb. 1884.
Haeckel, E. Die Gastrula und Eifurchung. Jena. Zeitschr. Bd. IX. 1875.
Heape, Walter. The Development of the Mole, the Ovarian Ovum, and

Segmentation of the Ovum. Quart. Jour. Micr. Sci. Vol. XXVI. pp. 157

174. Vol. XXVII. pp. 123-63. 1886.

Kolliker. Entwicklungsgeschichte der Cephalopoden. Zurich 1844.
Leydig, Fr. Die Dotterfurchung nach ihrem Vorkommen in d. Thiervvelt

und nach ihrer Bedeutung. Oken's Isis. 1848.
Pfltiger, E. Ueber den Einfluss der Schwerkraf t auf die Theilung der Zellen.

Arch. f. d. ges. Physiol. Bd. XXXI. p. 311. 1883.
Pfluger, E. 2. Abhandlung. Bd. XXXII. pp. 1-71. 1883.
Prevost et Dumas. 2me Mem. sur la Generation. Ann. des sci. nat.

T. II. pp. 100, 129. 1824.

Rabl. Ueber Zelltheilung. Morphol. Jahrb. Bd. X. p. 214. 1885.
Rauber, A. Furchung u. Achsenbildung bei Wirbelthieren. Zool. Anzeiger,

p. 461. 1883.
Rauber, A. Schwerkraf tversuche an , Forelleneiern. Berichte der naturf .

Gesellsch. zu Leipzig. 1884.
Reichert. Der Furchungsprocess und die sogenannte Zellenbildung urn

Inhaltsportionen. Miiller's Archiv. 1846.
Remak. Sur le developpement des animaux vertebres. Comptes rendu?.

T. XXXV. p. 341. 1852.
Roux. Ueber die Zeit der Bestimmung der Hauptrichtungen des Frosch-

embryo. Leipzig 1883.

Roux. Ueber die Bedeutung der Kerntheilungsfiguren. Leipzig 1883.
Roux. Beitrage zur Entwicklungsmechanik des Embryo. Nr. 4. Archiv f.

mikr. Anat. Bd. XXIX. p. 157. 1887.
Roux. Die Entwicklungsmechanik der Organismen, eine anatomische Wis-

senschaft der Zukunft. Wien 189C.
Rusconi. Sur le developpement de la grenbuille. Milan 1828.

76 EMBRYOLOGY.

Salensky, "W. Befruchtung und Furchung des Sterlet-Eies. Zool. Anzeiger.

Nr. 11. 1878.
Sarasin, C. F. Keifung u. Furchung des Keptilieneies. Arbeiten a. d.

zool.-zoot. Inst. Wurzburg. Bd. VI. p. 159. 1 883.
Schneider. Untersuchungen tiber Plathelminthen. Jahrb. d. oberhessischen

Gesellsch. f. Natur- u. Heilkunde. 1873.
Strasburger. Zellbildung und Zelltheilung. 3. Aufl. Jena 1875.

CHAPTER IV.

GENERAL DISCUSSION OF THE PRINCIPLES OF DEVELOP-
MENT.

A SIMPLE principle has exclusively controlled the embryonic pro-
cesses hitherto considered. By means of the cleavage of the egg-
substaiice, or cell-division, alone the originally simple elementary
Organism has been converted into a cell-colony. This presents the
simplest conceivable form, inasmuch as it is a hollow sphere, the
wall of which is composed of one or several layers of epithelial cells.
But the principle of cell-division is not adequate for the production,
out of this simple organism, of more complicated forms with dissimilar
organs, such as the adult animals are ; further progress in develop-
ment can be brought about from this time forward only by the
supervention of two other principles, which are likewise simple ;
namely, the principle of unequal growth in a cell-membrane, and
the principle of the division of labour, together with the histological
differentiation connected with it.

Let us consider first the principle of unequal growth. When in a
cell-membrane the individual elements continue to divide uniformly,
the result will be either a thickening or an increase in the surface of
the membrane. The former takes place when the plane of division
has the same direction as the surface of the membrane, the latter
when it is perpendicular to the surface. With the increase in the
extent of surface the cells which were at first present are uniformly
and gradually crowded apart by the introduction of the new daughter-
cells, inasmuch as they are soft and plastic, and are joined together
only by means of a soft cementing substance. Were we to assume
that only such a growth took place in the case of the blastula during
its further development, nothing else could come of it except an ever
larger and thicker-walled hollow sphere of cells.

GENERAL DISCUSSION OF THE PRINCIPLES OF DEVELOPMENT. 77

The operation of an unequal growth of the surface produces quite
another result. When in the middle of a membrane the cells of a
single group within a short time repeatedly undergo " division " by
vertical planes, they will be suddenly compelled to claim for themselves
muclT greater surface, and they will consequently exert a vigorous
pressure, due to growth, upon the cells in their vicinity, and will
tend to push them apart. But in this case a separation of contiguous
cells, such as takes place with gradual and uniformly distributed
interstitial growth, will be impossible ; for the surrounding cells,
remaining in a passive condition, will constitute, as it were, a rigid
frame, as His has expressed it, around the extending part, which, in
consequence of accelerated growth, demands an increased area. It
must therefore secure room for itself in another manner, and increase
its surface by abandoning the level of the passive part through
the formation of a fold in either one direction or the other. The
fold will be still further increased, and forced farther from the
original level, if the increased activity of the process of cell-division
in it continues. Thus by means of unequal growth there has now
arisen out of the originally uniform membrane a new recognisable
part, or a special organ.

When the folding membrane encloses a cavity, as is the case with
the blastula, there are two cases conceivable in the formation of folds.
In the first place, the membrane may be folded into the interior of
the body, a process which in embryology is called invagination or
involution. Secondly, there may arise by evagination a fold, which
projects free beyond the surface of the body.

In the first case numerous variations in the details are possible, so
that the most various organs, as, e.g., the glands of the animal body,
parts of the sensory organs, the central nervous system, etc., .are
formed.

In the origin of glands a small circumscribed circular part of a
cellular membrane is infolded as a hollow cylinder (fig. 39 1 and 4),
towards the interior of the body, into the underlying tissue, and by
continuous growth may attain considerable length. The invagina-
tion develops into either the tubular or the alveolar form of gland
(FLEMMING). If the glandular sac possesses from its mouth to its
blind end nearly uniform dimensions, we have the simple tubular
gland (fig. 39 x), — the sweat glands of the skin, LIEBERKUHN'S glands
of the intestine. The alveolar form of gland differs from this in that
the invaginated sac does not simply increase in length, but expands
somewhat at its end (fig. 39 5, db], while the other part remains

78

EMBRYOLOGY.

db

(ft

Tig. 39.— Diagram of the formation ->f glands.

1, Simple tubular gland ; 2, branched tubular gland ; 3,

branched tubular gland with anastomosing branches ;

4 and 5, simple alveolar glands ; a, duct ; db, vesicular

enlargement ; 6, branching alveolar gland.

narrow and tube-like and serves as its duct (a). More complicated
forms of glands arise, when the same processes to which the simple

glandular sac owes its origin are repeated on the wall of the sac

12 345 e when on a small

tract of it a more
vigorous growth
again takes place,
and a part begins
to grow out from
the main tube as a
lateral branch' (fig.
39 2 and 6). By
numerous repetitions
of such evaginations,
the originally simple
tubular gland may
acquire the form of
a much - branched
tree, upon which we
distinguish the part

formed first as trunk, and the parts which have arisen by outgrowths
from it as chief branches and branchlets of first, second, third, and
fourth order, according to their ages and correlated sizes. According
as the lateral outgrowths remain tubular or become enlarged at their
tips, there arise either the compound tubular
glands (fig. 39 2) (kidney, testis, liver), or the b

compound alveolar glands (fig. 39 6) (sebaceous
glands of the skin, lungs, etc.).

Again, the invaginating part of an originally
ilat membrane assumes other forms in the pro-
duction of sense organs and the central nervous
system. For example, the part of the organ of
hearing which bears the nerve terminations —
the membranous labyrinth — is developed out of
a small tract of the surface of the body, which
becomes depressed into a small pit (fig. 40) in
consequence of its acquiring an extraordinary
vigor in growth. The edges of the auditory
pit then grow toward one another, so that this is gradually con-
verted into a little sac, which still opens out at the surface of the
body by means of a narrow orifice only (fig. 40 a). Finally, the

Fig. 40. — Diagram of the
formation of the audi-
tory vesicle.

a, Auditory pit ; b, audi-
tory vesicle, which has
arisen by a process of
constriction, and still
remains connected with
the outer germ-layer by
means of a solid stalk
of epithelium.

GENERAL DISCUSSION OF THE PRINCIPLES OF DEVELOPMENT. 79

narrow orifice closes. Out of the auditory pit there has arisen a
closed auditory sac (6), which then detaches itself completely from its
parent tissue, the epithelium of the surface of the body. Afterwards,
simply by means of the unequal growth of its different regions, by
means of constrictions and various evaginations, it acquires such an
extraordinarily complicated form, that it has justly received the
name of membranous labyrinth, as will be shown in detail in another
chapter.

The development of the central nervous system may serve as
the last example of invagination. Spinal cord and brain take their
origin at an early epoch from the layer of epithelial cells which limits
the outer surface of the body of the embryo. A narrow band of this
epithelium lying along the axis of the back becomes thickened, and is
distinguished from the thinner part of the epithelium, which produces
the epidermis, as the medullary plate (fig. 41 A mp). Inasmuch as
the plate grows more rapidly than its surroundings, it becomes in-
folded into a gutter which is at first shallow, the medullary groove.
This becomes deeper as a result of further increase of substance. At
the same time the edges (fig. 41 B inf), which form the transition
from the curved medullary plate to the thinner part of the cellular
membrane, become slightly elevated above the surrounding parts, and
constitute the so-called medullary folds. Subsequently these grow
toward each other, and become so apposed that the furrow becomes
a tube, which still remains temporarily open to the outside by means
of a narrow longitudinal fissure. Finally, this fissure also disappears
(fig. 41 C) ; the edges of the folds grow together ; the closed medullary
tube (n), like the auditory vesicle, then detaches itself completely
along the line of fusion (suture) of the cell-membranes of which it
was originally a component part and becomes an entirely independent
organ (n).

Let us now examine somewhat more closely the mechanism of the
fusion and detachment of the neural tube.

The two medullary folds are each composed of two layers, which
are continuous with each other at the edge of the fold, — the thicker
medullary plate (mp), which lines the furrow or tube, and the thin-"
ner epidermis (ep), which has either a more lateral or a more super-
ficial position. When, now, the folds come into contact, they fuse,
not only along a narrow edge, but over so extensive a tract that
epidermis is joined to epidermis, and that the edges of the medullary
plate are joined to each other. The medullary tube thus formed,
and the continuous sheet of epidermis that stretches across it, are by

80

EMBRYOLOGY.

means of an intermediary cell-mass still in continuity along the suture
produced by the concrescence. But a separation soon takes place

mp

•• ep

Fig. 41— Cross sections through the dorsal halves of three Triton larvae.

A, Cross section through an egg in which the medullary folda (m/) begin to appear.

B, Cross section through an egg whose medullary furrow is nearly closed.

C, Cross section through an egg with closed neural tube and well-developed primitive segments.
mf, Medullary folds; mp, medullary plate; n, neural tube (spinal cord); ch, chorda;

cp, epidermis, or corneal layer; ml-, middle germ-layer; mk\ parietal, nifc2, visceral sub-
division of the middle germ-layer ; U; inner germ-layer ; ush, cavity of primitive segment.

along this line, inasmuch as the intermediary band of substance
becomes narrower and narrower, and one part of it unites with the

GENERAL DISCUSSION OF THE PRINCIPLES OF DEVELOPMENT. 81

epidermis, while the other part is annexed to the medullary tube. Thus
in the formation of the suture processes of fusion and of separation
occur almost simultaneously, a condition which often recurs in the
case of other invaginations, as in the constricting off of the auditory
vesicle, the vesicle of the lens, etc.

The neural tube having once become indepsndent is subsequently
segmented in manifold ways by the formation of foldings, in conse-
quence of inequalities in the rate of surface growth, especially in its
anterior enlarged portion, which becomes the brain. There are
formed out of this by means of four constrictions five brain-vesicles,
which lie in succession one after
another; and of these the most an-
terior, which becomes the cerebrum
with its complicated furrows and con-
volutions of first, second, and third
order, serves as a classical example
when one desires to show how a
highly differentiated organ with com-
plicated morphological conditions may
originate by the simple process of
folding.

In addition to imagination the second
method in the formation of folds,
which depends upon a process of eva~
gination, plays a no less important
part in the determination of the
form of animal bodies, giving rise to
protuberances of the surface of the body, which may likewise
assume various forms (fig. 42). As a result of exuberant growths
of small circular territories of a cell-membrane there arise rod-
like elevations, resembling the papillae on the mucous membrane
of the tongue (c), or the fine villi (a) in the small intestine (villi
intestinales), which are so closely set that they give a velvety ap-
pearance to the surface of the mucous membrane of the intestine.
Just as the tubular glands may be abundantly bran< hed, so tufted
villi are here and there developed out of simple villi, sinc3 local
accelerations of growth cause the budding-out of latf ral branches of
a second, third, and fourth order (fig. 42 b). We rt call the external
tufted gills of various larvae of Fishes and Amphibia, which project
out from the neck-region free into the water, or the villi of the
chorion in Mammals, which are characterised by still more numerous

6

Fig. 42.— Diagram of the formation of

papillae and villi.
o, Simple papilla ; 6, branched papilla

or tufted villas ; c, simple papilla,

the connective-tissue core of which

runs out into three points.

82 EMBRYOLOGY.

branchings. The formation of the limbs is also referable to such
a process of external budding.

When the growth of the membrane takes place along a line,
the free edges form ridges or folds directed outward, such as
the valves of KERKRING or the gill-plates on the gill-arches of
Fishes,

From the examples cited it is clearly to be seen how the greatest
variety of forms may be attained by the simple means of invagina-
tion and evagination alone. At the same time, the forms may be
modified by two processes of subordinate importance, by separations
and by fusions which affect the cell-layers. Vesicular and sac-like
cavities acquire openings by the thinning out of the wall at a place
where the vesicle or sac lies near the surface of the body, until there
is a breaking through of the separating partition. Thus in the
originally closed intestinal tube of "Vertebrates there are formed the
mouth-opening and the anal opening, as well as the gill-clefts in
the neck-region.

The opposite process — fusion — is still more frequently to be
observed. It allows of a greater number of variations. We have
already seen how the edges of an invagination may come in
contact and fuse, as in the development of the auditory vesicle,
the intestinal canal, and the neural tube. But concrescence may
also take place over a greater extent of surface, when the facing sur-
faces of an invaginated membrane come more or less completely into
contact, and so unite with each other as to form a single cell-mem-
brane. Such a result ensues, for example, in the closure of the
embryonic gill-clefts, in the formation of the three semicircular
canals of the membranous labyrinth of the ear, or, as a pathological
process, in the concrescence of the surfaces of contact of serous
cavities. Moreover fusions may take place between sacs which come
in contact with their blind ends, as very often occurs in the com-
pound tubular glands (fig. 39 3). Of the numerous lateral branches
which sprout out from the tubule of a gland, some come in contact
at their ends with neighboring branches, fuse with them, and
establish an open communication with them by the giving way
of the cells at the place of contact. It is by this means that
branched forms of tubular glands pass into the net-like forms to
which the test is and the liver of Man belong.

In addition to the formation of folds in epithelial layers, which
under a great variety of modifications determine in general the
organisation of the animal body, there were mentioned, as a second

GENERAL DISCUSSION OF THE PRINCIPLES OF DEVELOPMENT. 83

developmental principle, of fundamental significance, division of labor
•and the histological differentiation associated with it. In order to
understand fully the significance of this principle in development,
we must proceed from the thesis that the life of all organic bodies
expresses itself in a series of various duties or functions. Organisms
take to themselves substances from without ; they incorporate in their
bodies that which is serviceable, and eliminate that which is not
(function of nutrition and metastasis) ; they can alter the form of
their bodies by contraction and extension (function of motion) ; they
are capable of reacting upon external stimuli (function of sensibility) ;
they possess the ability to bring forth new organisms of their own
kind (function of reproduction). In the lowest multicellular organisms
each of the individual parts discharges in the same manner as the
others the enumerated functions necessary for organic life ; but the
more highly an organism is developed, the more do we see that its
individual cells differentiate themselves for the duties of life, — that
some assume the function of nutrition, others that of motion, others
that of sensibility, and still others that of reproduction, — and that with
this division of labor is likewise joined a greater degree of com-
pleteness in the execution of the individual functions. The
development of a specialised duty likewise leads invariably to an
altered appearance of the cell : with the physiological division of
labor there always goes hand-in-hand a morphological or histological
differentiation.

Elementary parts which are especially concerned in the duties of
nutrition are distinguished as gland-cells ; again others, which have
developed the power of contractility to a greater extent, have
become muscle-cells, others nerve-cells, others sexual cells, etc. The
Cecils which are concerned in one and the same duty are for the most
part associated in groups, and constitute a special tissue.

Thus the study of the embryology of an organism embraces chiefly
two elements : one is the study of the development of form, the
second the study of histological differentiation. We may at the
same time add that in the case of the higher organisms the morpho-
logical changes are accomplished principally in the earlier stages of
development, and that the histological differentiation takes place in
the final stages.

A knowledge of these leading principles will materially facilitate
the comprehension of the further processes of development.

84

EMBRYOLOGY.

CHAPTER V.

DEVELOPMENT OF THE TWO PRIMARY GERM-LAYERS.
( G A STRJ4A- THE OR Y. )

THE advances which are brought about during the next stages in
the development of the blastula depend primarily upon processes of
folding. By these means there arise larval forms, which are at first
composed of two, and afterwards of four epithelial membranes, or
germ-layers.

The larval form which is composed of two germ-layers is called the
gastrula. It possesses an important developmental signification,
because, as HAECKEL has shown in his celebrated Gastrsea -Theory,
it is to be found in each of the six chief branches of the animal
kingdom, and thus furnishes a common starting-point from which
along diverging lines the separate animal forms may be derived.
As with blastulse, so in the case of the gastrula four different
kinds can be distinguished, according to the abundance and the
method of distribution of the yolk. Starting from a simple funda-
mental form, three further modifications have arisen, all of which,

with the exception
of a single one which
is characteristic of
many Arthropods,
are to be encoun-
tered within the
phylum of Verte-
brates.

The simplest and
most primitive form?
with the considera-
tion of which we
have to begin, is
found only in the
development of Am-
phioxus lanceolatus.
As has been previously shown, its blastula is composed of cylin-
drical cells, which are closely joined into a single-layered epithelium
(fig. 43). At one place, which may be designated as the vegetative pole

AP

Fig. 43.— Blastula of Amphioxus lanceolatus, after HATSCHEK.
fh, Cleavage-cavity ; az, animal cells ; rz, vegetative cells ;
AP, animal pole ; F7>, vegetative pole.

DEVELOPMENT OF THE TWO PRIMARY GERM-LAYERS.

85

ak

ltd

Fig. 44. — Gastrula of Amphioxus lanceolatus. after

HATSCHEK.
ak, Outer germ-layer ; ik, inner germ-layer ; u,

blastopore, or mouth of archenterou (tid).

(VP), the cells (vz) are somewhat larger and more turbid, owing to
the yolk-granules lodged in them. The process of the formation of
the gastrula commences at this place. The vegetative surface begins
at first to be flattened, and
then to be pushed in toward
the middle of the sphere.
By the advance of the
invagination the depression
grows deeper and deeper,
while the cleavage-cavity be-
comes to the same degree
diminished in size. Finally,
the invaginated portion (fig.
44 ik) comes in contact with
the inner surface of the un-
invaginated portion (ak) of
the blastula, and completely
obliterates the cleavage-
cavity. As a result there has been formed out of the hollow
sphere with a single wall a cup-shaped germ with double walls—
the gastrula.

The cavity of the gastrula, which results from the invagination and
is not to be confounded with the cleavage-cavity which it has sup-
planted, is the primitive intestine (archenteron) (ud), or the intestino-
body cavity (coelenteron). This opens to the outside through the
primitive mouth (mouth of the archenteron, blastopore) (u).

Inasmuch as the names primitive intestine and primitive mouth
might easily give rise to erroneous conceptions, let it be remarked, in
order to preclude from the start such an event, that the cavity and
its external opening which arise by this first invagination are not
equivalent to the intestine and mouth of the adult animal. The
archenteron of the germ, it is true, furnishes the fundament for the
intestinal tube, but there are also formed out of it a number of other
organs, the chief of which are the subsequently formed thoracic and
abdominal cavities. The future destination of the cavity will there-
fore be better expressed by the term " ccelenteron." Finally, the
primitive mouth is only an evanescent structure among vertebrated
animals; later it is closed and disappears without leaving a trace, while
the permanent or secondary mouth is an entirely new structure.

The two cell-layers of the cup, which are continuous with each
other at the edge of the blastopore, are called the two primary

86 EMBRYOLOGY.

germ-layers, and are distinguished according to their positions as the
outer (ak) and the inner (ik). Whereas in the blastula the individual
cells differ only a little from one another, with the process of gastru-
lation a division of labor begins to assert itself, a fact which may
be recognised in the case of the free-swimming larvse of Inver-
tebrates. The outer germ-layer (ak) (also called ectoblast or ectoderm)
serves as a covering for the body, is at the same time the organ of
sensation, and effects locomotion when cilia are developed from the
cells, as is the case with Amphioxus. The inner germ-layer (ik]
(entoblast or entoderm) lines the coelenteron and provides for nutri-
tion. The cell-layers thus stand in contrast to each other both as
regards position and function, since each has assumed a special duty,
In view of this fact they have been designated by C. E. VON BAER
as the two primitive organs of the animal body. They present us
with a very instructive, because very simple, illustration of the
manner in which two organs originate from a single fundament.
By invagination the undifferentiated cells of the surface of the
blastula are brought into different relations to the outer world, and
have consequently been compelled to follow different courses in their
development, and to adapt themselves to special duties corresponding
to the new relations.

The separation of the embryonic cell-material into the two primi-
tive organs of VON BAER is of decisive significance for the whole
subsequent course of the development of the individual cells. For a
very definite portion of all the ultimate organs of the body is refer-
able to each of the two primitive organs. In order to put this im-
portant condition in the proper light at once, let it be stated that the
outer germ-layer furnishes the epithelial covering of the body, the
epidermis with the glands and hair, the fundament of the nervous
system, and that part of the sense organs which is functionally most
important. On this account the older embryologists imposed upon it
the name of dermo-sensory layer. The inner germ-layer, on the
contrary, is converted into the remaining organs of the body — into
the intestine with its glands, into the body-cavity, into the muscles,
etc. ; by far the greater mass of the body, therefore, is differentiated
out of it, and it has to pass through the most numerous and the most
trenchant metamorphoses.*

* The practice of distinguishing the outer and the inner germ-layers as animal
and vegetative, which was formerly in vogue and is followed even now, is not
proper, and ought therefore to be given up. For the transversely striped muscu-
lature of the body, which belongs to its animal organs, does not arise from

DEVELOPMENT OF THE TWO PRIMARY GERM-LAYERS.

87

Larval forms quite like that of Amphioxus have also been observed
in the case of Invertebrates belonging to the phyla of Ccelenterata,
Echinodermata, Vermes, and Brachiopoda. For the most part they
quit the egg-envelope, even in the gastrula stage, to swim about in
the water by means of their cilia ; and they can now take nutritive
substances — small infusoria, algse, or remnants of larger animals —
through the primitive mouth
into the digestive cavity, and
make use of them in the fur-
ther growth of their bodies.
Likewise the substances
which are not serviceable be-
cause indigestible are ejected
from the body through the
same orifice. In the case
of the higher animals the
ingestion of food is not only
impossible at this time, but
also superfluous, because the
egg and the embryonic cells
arising from it still contain
yolk-granules, which are
gradually consumed.

The modifications which gastrulation undergoes in the Amphibia are
easily referable to the simpler conditions in Amphioxus. In the case
of the Water- Salamander, which is to serve as an illustration in
this description, one half of the blastula (fig. 45), which is called
the animal half, is thin-walled and composed of small cells, which
lie in two or three layers one above another, and in the case of
the Frog contain black pigment. The other, or vegetative half (dz),
exhibits a greatly thickened wall, composed of much larger, more
deutoplasmic, polygonal cells (dz), which, loosely associated in several
layers, cause a protuberance into the cavity (fh) of the blastula,
which is proportionally diminished in size. Where the differentiated
halves meet, a transition is effected by means of cells, forming what
GOETTE has designated marginal zone (rz). Inasmuch as the specific
gravity of the animal half is much less than that of the opposite
half, it is without exception directed upward in water. The former

the outer germ-layer, as, in consequence of false observations, was formerly
believed, but rather from the primary inner germ-layer, as has now been esta-
blished by many observations.

— dz

Fig. 45.— Blastula of Triton taeniatus.
fh, Cleavage-cavity ; dz, yolk-cells ; rz, marginal
zone.

88

EMBRYOLOGY.

\.

Fig. 46. Egg of Triton, which is
developing into a gastrula, seen
from the surface.

u, Primitive mouth (blastopore).

constitutes the thinner roof, the latter the highly thickened floor, of
the excentrically placed cleavage-cavity.

When the gastrula begins to be developed, the invagination
takes place on one side in the marginal zone (fig. 46 u), and is

distinguishable externally by means of
a sharp, afterwards horseshoe-shaped
furrow, which is bounded on one side
by small cells, which in the case of
the Frog contain black pigment, on
the other side by large unpigmented
elements. At the fissure-like blasto-
pore there are infolded into the interior
of the blastula (fig. 47 u) along its
dorsal lip (dl) small cells, along its
ventral lip (vl) the large deutoplasmio
elements of the vegetative half; the

former constitute the roof, the latter the floor, of the crelenteron (ud).
The latter appears in the first stages of the invagination simply as
a narrow fissure alongside the capacious cleavage-cavity (fh) ; soon,
however, it causes a com-
plete obliteration of this
cavity, the f undus of the
invagination becoming
enlarged into a broad
sac, while the entrance
always remains narrow
and fissure-like. Since
the co3lenteron of the
Amphibia was first ob-
served by the Italian
investigator, RUSCONI, it
is ordinarily mentioned
in the older writings as
RUSCONI'S digestive
cavity, and the blasto-
pore likewise as the
RUSCONIAN anus.

At the close of the process of invagination the whole yolk-mass, or
the vegetative half of the blastula, has been taken into the interior
to form the lining of the ccelenteron, being at the same time over-
grown by a layer of small cells (fig. 48). Tn the case of the Frog the

fit —

Fig. 47.— Longitudinal [sagittal] section through an egg
of Triton at the beginning of gastrulation.

ak, Outer germ-layer ; ik, inner germ-layer ; fh, cleavage-
cavity ; iid, coelenteron ; u, blastopore ; dz, yolk-
cells ; dl and vl, dorsal and ventral lips of the
coelenteron.

DEVELOPMENT OF THE TWO PRIMARY GERM-LAYERS.

89

Fig. 48.— Sagittal section through an egg of Triton after

the end of gastrulation.
ok, ik, dz, dl, vl, ud, as in fig. 47 ; d, vitelline plug ;

ink, middle germ-layer.

whole surface of the germ, with the exception of a small place about
as large as the head of a pin, which corresponds to the blastopore,
now appears black, because the small cells are deeply pigmented. At
the place excepted a part of the unpigmented yolk-mass protrudes
through the blastopore
and closes the entrance to
it as if with a stopper (d),
by reason of which it
bears the significant name
of vitelline plug.

Of the two germ-layers
of the gastrula the outer
subsequently becomes re-
<luced in thickness in the
case of the Water-Sala-
mander to a single layer
of regularly arranged
cylindrical cells, whereas
in the case of the Frog it
is composed of two or

three layers of small, in part cubical, deeply pigmented elements.
The inner germ-layer in the roof of the ccelenteron likewise consists of
small (in the Frog, pigmented) cells, but in the floor it is composed
of large yolk-cells, which, heaped together in many layers, pro-
duce an elevation that projects far into the coelenteron and partly
fills it. For this reason the gastrula in Amphibia is compelled
to adopt in water a definite' position of rest, because the yolk-inass,
being the heavier part, always assumes the lowest position (fig. 48).

The germ of the Amphibia is already a bilaterally symmetrical
body. The thickened, yolk-containing wall of the gastrula becomes
the ventral side of the adult animal ; the opposite wall, or roof of
the coalenteron, becomes the dorsum. The blastopore indicates, as
the sequel shows, the posterior end, the opposite part the head-end.
There may therefore be passed through the gastrula a longitudinal,
a dorso- ventral, and a transverse axis, which correspond with the
axes of the adult animal. This bilateral symmetry, which appears
so early in the Amphibia, is solely attributable to the accumulation
of yolk- material, and to the piling up of it on the ventral side of the
•ccelenteron.

The development of Amphibia furnishes us with a transitional
•condition, which is serviceable for the comprehension of the much

90

EMBRYOLOGY.

dk H

more highly altered form which the gastrula acquires in the case of
eggs with partial cleavage in the classes of Selachii, Teleosts, Reptiles,
and Birds.

The conditions are the most readily intelligible in the case of the
Selachians. That which we have described in the blastula of the
Amphibia as the roof of the cleavage-cavity is in the blastula of

the Selachians a
small disc of em-
bryonic cells (fig.
49 kz), continuous
at its margin with
the extraordi-
narily voluminous
yolk - mass (dk),
which contains
nuclei, although it
is not divided up
into cells. This
yolk-mass corre-
sponds to the
yolk-cells of the

Amphibia, and, like the latter, forms the floor of the cleavage-cavity
(B). Germ-disc and yolk thus together constitute a sac with an

Fig. 49. Median section through a germ-disc of Pristiurua in the
blastula stage, after R{JCKERT. The posterior end of the
embryo lies at the right. B, Cleavage-cavity ; dk, yolk-nuclei ;
kz, germ-cells ; V and //, front and hind margins of the germ-
disc.

Fig, 50. — Median section through a germ-disc of Pristiurus, in which the gastrular invagination

has begun, after RUCKERT.
v.d, First rudiment of the coelenteron ; B, cleavage-cavity ; dk, yolk-nuclei ; fd, finely granular

yolk ; gd, coarsely granular yolk ; V and H, front and hind margins of the germ-disc.

almost obliterated cavity (J3), and with walls differing in thickness
and in differentiation. A very small part of the wall, the germ-disc,
consists of cells. The much larger and thicker portion is yolk-mass,
which in the vicinity of the cavity contains nuclei, but is not divided
into cells.

As in the Amphibia, so here, the gastrulation begins at what

DEVELOPMENT OF THE TWO PRIMARY GERM-LAYERS. 91

is subsequently the hind end (H) of the embryo, at a region in the
zone of transition or margin of the germ-disc, in which the most
superficial cells have assumed the cylindrical form, and are closely
joined together (fig. 49). The margin of the disc is folded in
(fig. 50) toward the cleavage-cavity (.#), so that a small ccelen-
teron (ud), shown in the accompanying section, and a fissure-
like blastopore are distinctly recognisable. The neighboring yolk
also participates in the imagination, since in the territory of
the zone of transition the yolk-nuclei (dk), enveloped in protoplasm,
become detached from the yolk, grow into the cleavage-cavity along
with the invaginated cells, and contribute to the formation of the
inner germ-layer in a similar manner to that in which, in the case of
the Amphibia, the vegetative cells at the lower lip of the blastopore
are carried in with the invagination into the cleavage-cavity. The
cleavage-cavity (B) is being continually encroached upon by the in-
growth of the cells originally in its roof, which form a continuous
layer projecting from behind forward. Consequently in the Sela-
chians also the germ-disc becomes two-layered as the result of the
invagination. It lies so close upon the yolk, that the ccelenteron
appears at most as a fissure. Moreover, the invagination in the
Selachians does not remain limited to one region of the original
margin of the germ-disc, but soon stretches itself out over its whole
posterior perimeter. The blastopore then appears as a large semi-
circular or horseshoe-shaped fissure at the future posterior end of the
embryonic fundament.

The enormous volume of the yolk causes an important difference
between the gastrulation of the Selachii and that of the Amphibia.
In the case of the latter the mass of the yolk-cells was quite rapidly
carried in with the invagination, and employed in the formation of
the ventral wall of the ccelenteron. In the Selachians the taking
up of the yolk into the interior of the body ensues only at a slow
rate (in a manner to be more accurately explained later), so that for
a long time only the dorsal side of the gastrula consists of two cell-
layers, whereas the ventral wall is formed by the yolk-mass.

The eggs of Teleosts are very nearly related to those of Selachians
in their whole method of development. The same cannot be said
to be true to the same extent for the eggs of Reptiles and
Birds. The latter, indeed, also belong to the meroblastic type,
since they have developed a large amount of yolk, and in consequence
undergo partial segmentation; but in the formation of the germ-
layers, they exhibit many peculiarities, so that they require a separate

92

EMBRYOLOGY.

treatment. In Birds and Reptiles the investigation is accompanied
with greater difficulties than in the Selachians. Particularly the
development of the germ-layers in the Chick, notwithstanding the
fact that the best investigators have given it their attention, has
for a long time been the subject of very divergent descriptions. At
the present moment, however, the main facts in the case have been
established for the Bird's egg also by the very recent and excellent
work of DUVAL, and upon this as a basis the gastrulatiori in Birds is
easily to be correlated with that of the Vertebrates hitherto described.
Since the Bird's egg has played such an important role in the history
of embryology, and has even been called a classical object for investiga-
tion, it appears necessary to go briefly into the conditions which it
presents in the gastrula-stage, and in connection therewith to consider
some of the important results drawn from the study of the eggs of
Reptiles.

The blastula arises and the germ-layers begin to be developed out
of it while the Bird's egg tarries in the terminal region of the
oviduct.

The blastula arises in a manner which was first correctly described
by DUVAL. When by tl*e process of segmentation a small disc of

as been formed,

latter a narrow fissure,
^e cleavage-cavity (fig.

.)> and tne ceU"

material is separated
into an upper layer (dw)
and a lower layer (vw),
which are continuous

with each other at the
margin of the disc. The
upper layer Consists of

fully isolated cleavage-

spheres, which are flattened at their surfaces of contact and arranged
into an epithelium-like layer. They correspond to the thin-walled
half of the blastula in Triton (fig. 45), which has already been
designated as the animal half. The lower layer is composed of
larger cleavage-spheres, which are still in great part continuous
by means of their lower halves with the white yolk (wd), which
is spread out beneath the germ-disc and is known as PANDER'S
nucleus. Yolk-nuclei (merocytes) are also found here in great

Fig. 51.— Section through the germ-disc of a freshly laid

unfertilised Hen's egg, after DUVAL.
fh, CJeavage-cavity ; wd, white yolk ; vw, lower cell-layer ;

die, upper cell-layer of the blastula.

DEVELOPMENT OF THE TWO PRIMARY GERM-LAYERS. 93

numbers, especially around the whole periphery of the germ-disc.
Since they increase in number by nuclear division, and since
some of them, enveloped in protoplasm, become detached from the
yolk, they contribute to the continuous growth of the germ-disc, a
process which has already (p. 65) been described as supplementary
cleavage. The lower cell-layer, t6gether with the whole yolk-mass
with its free nuclei, must be compared to the vegetative half of the
blastula of Triton (fig. 45 dz).

The gastrulation proceeds from the posterior margin of the germ-
disc, and begins even some time before the egg is laid. The study
of it is coupled with great difficulties, and demands, most of all,
that, in the investigation of the disc by means of sections, one should
be accurately informed concerning the position of its anterior and
posterior margins. The orientation is essentially facilitated by the
fact that, in the case of every Hen's egg, with rare exceptions, the
side toward which the front end of the embryo is directed can be
stated accurately before opening the shell. This results from the
following rule established by KUPFFER, ROLLER, GERLACH, and DUVAL.

When one so places an egg in front of him that the blunt pole is
turned to the left, the more pointed one to the right, then a line
uniting the two poles divides the germ-disc into a half on the side
toward the observer, which becomes the hind end of the embryo, and
a forward half, which is developed into the head-end. By taking
into account this rule, one can establish a difference on the germ-
disc even during the process of cleavage. In the anterior region the
cleavage takes place more slowly than in the posterior half. Con-
sequently larger embryonic cells are found in front, smaller and
more numerous ones behind (OELLACHER, KOLLIKER, DUVAL).

The difference between anterior and posterior becomes more evident
at the beginning of gastrulation. If one now examines carefully the
thickened margin of the germ-disc (Eandwulst of German writers,
bourrelet blastodermique of DUVAL). it is seen that the disc is limited
in front and on the sides by a notched and indistinct boundary,
but behind, on the contrary, by a sharper contour. The latter
is caused by the fact that the marginal ridge, in consequence of a
more vigorous growth of the cells, has become thickened and more
opaque, and has assumed a whiter colour. It is distinctly recognisable
from its surroundings as a whitish crescentic figure (fig. 52 A s)..
Often there is also observable in the crescent a narrow furrow, the
crescentic groove (Sichelrinne, KOLLER), by means of which the germ-
disc acquires a still sharper limitation behind.

94

EMBRYOLOGY.

DUVAL has proved by means of sections, part of which was made in
a transverse direction, and part in the sagittal, that the Bird's egg is
now in the gastrula stage. Especially instructive are the two median

hi vl ud ak ik

II II

Fig. 52 A.— The unincubated germ-disc of a Hen's egg, after ROLLER.
d, Yolk ; ksch, germ-disc ; s, crescent ; V and H, anterior and posterior margins of the germ-disc.

B. — The germ-disc of a Hen's egg during the first hours of incubation, after KOLIKR.
d, Yolk ; ksch, germ-disc ; Es, embryonal shield ; s, crescent ; sk, knob of the crescent ; V and H,
anterior and posterior margins of the germ-disc.

sections, figs. 53 and 54. As is to be seen at once in fig. 53, which re-
presents the somewhat younger stage, the crescentic groove described
as occupying the posterior part of the marginal ridge (vl) is continued
in the form of a narrow fissure (ud). Whereas in the blastula stage

(fig. 51) the lower cell-
ed I i(r«tk dk i i

layer passed over con-
tinuously into the white
yolk, it is now sharply
separated from it as far
as the fissure extends.
In fig. 53 this separation
has been completed only
in the posterior half of
the germ-disc; in the
anterior half, on the con-
trary, embryonic cells
(dk) and yolk are still
continuous. However,
in the somewhat older

stage (fig. 54) the connection is terminated in this region also,
since the fissure (ud) has extended itself nearly to the anterior
margin of the disc (vr). In consequence of this process the part of
the white yolk which lies beneath the fissure has become destitute of
cells and nuclei, with the exception of the marginal territory, where,

Fig. 53.— Longitudinal section through the germ-disc of an
unincubated egg of the Siskin (Carduelis spinus). after
DUVAL.

ak, Outer , ik, inner germ-layer ; u-d, white yolk ; dk, yolk-
nuclei ; ud, ccelenteron ; vl, anterior lip, hi, posterior lip
at the place of invagination (crescentic groove or blastopore).

DEVELOPMENT OF THE TWO PRIMARY GERM -LAYERS.

95

especially behind (hi) the crescentic groove, free nuclei are constantly
to be found keeping up the supplementary cleavage.

Owing to the appearance of the new fissure (subgerminal cavity)
(fig. 53 ud), the cleavage-cavity (fig. 51 fh) is almost completely
obliterated. The two cell-layers of the
blast ula-stage (fig. 51 dw, vw), described as
lying one above and one below the cleavage-
cavity, have come close together (figs. 53
and 54), being separated from each other
by only a narrow fissure. In the upper
layer (ok) the cells have assumed a cubical,
and at a somewhat later stage a cylindrical,
form, and constitute a compact epithelial
membrane. The lower layer (ik) is composed
of larger roundish and loosely arranged cells
in several layers. The former is the primary
outer germ -layer, the latter the inner layer.
In the region of the posterior marginal
ridge (vl), where the cells are at the same
time engaged in more active proliferation,
the two layers are continuous with each
other.

The highly important processes, by means
of which are produced the conditions repre-
sented in figs. 53 and 54, present many points
of comparison with the ga stimulation of the
Selachians and Amphibia. We can conceive
that the newly appearing fissure has arisen,
as in the case of the germ- disc of Pristiurus
(fig. 50), by an infolding, in such a way that,
as in the former case, cells grow inward from
the posterior marginal ridge; and that at
the same time, at the deep part of the in-
vagination, the cells which are originally
continuous with the yolk (fig. 53 dk) detach
themselves from the latter, and are employed for the increase of the
inner germ layer.

If tl is explanation is correct, the fissure (ud) which now exists be-
tween the inner germ-layer and the floor of the yolk corresponds to
the ccelenteron, as GOETTE and RAUBER have already rt marked, and
as DUVAL has for the first time demonstrated ; moreover, the cres-

96

EMBRYOLOGY.

centic groove (fig. 52 s) corresponds to the blastopore ; the thickened
portion of the marginal ridge (fig. 53 vl) which lies in front of the
crescentic groove, within whose territory the two primary germ-
layers are continuous with each other, is the anterior or dorsal lip of
the blastopore ; and the yolk (hi) which lies behind the crescentic
groove, and which at this early stage contains numerous free nuclei,
may be designated as the posterior or ventral lip of the blastopore.

The develop-

v ment of the

coelenteron is
the cause of
the gradual re-
duction of the
cleavage - cav-
ity, and of its
persisting only
as a narrow fis-
sure separating
the primary
germ-layers.

The points of
comp arison
with the gas-
trula of Triton
(fig. 47) are
made evident
as soon as we
replace the
mass of yolk-
cells with un-

segmented yolk, and imagine nuclei imbedded in the latter in the
region of the ventral lip of the blastopore.

Through the exposition given by DUVAL, it appears to me that the
contest concerning the origin of the two primary germ-layers in
Birds has been happily settled. For a long time there have existed
on this very question two irreconcilable views.

According to the older view, to which many investigators still cling,
the germ-disc which results from the process of cleavage is divided by
fission into an upper and a lower layer (PANDER, VON BAER, REMAK,
KOLLIKER, His, and others). According to the other one (HAECKEL,
GOETTE, RAUBER, DUVAL, and others), the lower layer has arisen by

\

Fig. 55.— Embryonic fundament of Lacerta agilis, after KUPFFER.
If, Area pellucida ; df, area opaca ; «, blastopore ; s, crescent ; es, em-
bryonic shield. V, anterior, H, posterior end.

DEVELOPMENT OF THE TWO PRIMARY GERM-LAYERS. 97

an infolding. Only by means of the theory of infolding can be ex-
plained the different conditions of the anterior and posterior margins
of the germ-disc, the more active cell-growth in the territory of the
crescent, the existence of a crescentic groove, and the continuity
of the two primary germ-layers which is demonstrable in that
region. Only by means of this theory, finally, is the relation of
Birds to the lower classes of the Vertebrates made possible.

The discoveries which KUPFFER UND BENECKE have made in their
investigations of Reptiles, which are so closely related to Birds, also
contribute to the elucidation of the pending controversy. In the case
of Lacerta agilis (fig. 55), Emys europaea, etc., there is found, as in
the case of the Hen at a corresponding stage of development, at the
boundary of the pellucid and opaque areas of the posterior end of
the germ-disc, an exuberant cell-growth in the form of a crescent ($).
In the middle plane and slightly in front of this crescent there is
to be seen a small, transversely placed, fissure-like opening (u\ which
leads into a blind sac and is comparable to the crescentic groove.
KUPFFER rightly interprets the opening as the blastopore, which is
enclosed between an anterior and a posterior lip, and the cavity as
the coelenteron. He also draws a comparison between the corre-
sponding structures in Birds and Reptiles.*

Let us now direct our attention to the succeeding developmental
stages of the germ-disc of the Chick. These consist, chiefly, in
a constant increase of the superficial extent of the disc.

In the freshly laid, unincubated egg (fig. 54) the outer germ-layer
(ah) is composed of a single sheet of closely united cylindrical cells ;
the inner layer (ik), on the contrary, consists of a two-layered to
three-layered bed of somewhat flattened elements, which are only
loosely associated.

Under the influence of incubation the superficial extension of the
germ-disc makes rapid advances (fig. 56). In this process the outer
germ-layer (ok) outstrips the inner, and terminates in a region of the

* In the interpretation of the manner in which the invagination takes place
in the case of the eggs of Reptiles and Birds, I differ from other investigators
who also maintain that a gastrulation takes place (GOETTE, HAECKEL,
RAUBER, BALFOUE, and others). They regard the whole margin of the germ-
disc as the blastopore, at which the outer germ-layer bends over to become
continuous with the inner layer. According to my interpretation, the invagina-
tion occurs at a small circumscribed place of the margin. The blastopore is
from the beginning surrounded by cells both on its anterior and its posterior lip.
The relation of the blastopore as well as that of the germ-layers to the yolk
will be more fully dealt with hereafter.

7

98

EMBRYOLOGY.

yolk where the latter
has not yet undergone
division into entodermic
cells. In the form of
its cells it is, in every
respect, in sharp con-
trast with the inner
layer. While the ecto-
dermic cells (fig. 56 afy
attain their greatest
height in the middle
of the germ-disc, they
gradually decrease in
height toward the mar-
gin, and undergo a
transition into cubical
and finally into flat-
' tened elements (fig. 57).
The reverse is the case
with the inner germ-
layer ; the latter ha&
now become converted in
the middle of the germ-
disc (fig. 56 ik) into a
single layer of much
flattened scale-like cells,
which are closely united
into a thin membrane.
Toward the periphery
they become somewhat-
larger and more poly-
gonal (fig. 57), and here,
at some distance inside
the free margin of the
outer germ-layer, they
become merged in the
white yolk (dw), which
is abundantly provided
with yolk-nuclei (dk) in
the region of the transi-
tion. This region of the

DEVELOPMENT OF THE TWO PRIMARY GERM-LAYERS.

99

,1k

yolk is designated as the yolk-wall (vitelline rampart). It serves
for the augmentation of the inner germ-layer, in that the free
nuclei increase in number by division, and keep up the process of
supplementary cleavage already mentioned.

During incubation the liquefaction of the yolk makes further pro-
gress (fig. 56) and leads to the formation of a depression (ud), which
continually increases in depth and breadth, and over which the germ-
disc arches like a watch-glass. Upon examination from the surface
its middle, as far as the fluid reaches under it, appears clear and
translucent, whereas the marginal area, which lies upon the opaque
yolk, appears dark. Such a distinction is still more observable when
one detaches the whole
germ-disc from, the yolk,
for in the region of the
fluid-filled space the thin
and transparent germ-
layers come off easily and
clean from their substra-
tum, whereas at the rim,
from the point where the
inner germ-layer merges
with the yolk-wall out-
ward, turbid yolk-substance remains clinging to the germ-disc. For
a long time the middle, clear, circular area has been designated
in embryology as the clear germinal area (area pellucida), and the
more cloudy, ring-like rim as the opaque germinal area (area opaca).

In the next chapter I shall treat more in extenso of the important
changes which take place — up to the time when the egg is laid
and during the first hours of incubation — in the vicinity of the
crescentic groove and the anterior lip of the blastopore, because they
are connected with the development of the middle germ-layer.

It is still more difficult than in the case of the Chick to interpret
in its details the development of the germ-layers in Mammals, and to
refer it back to the gastrulation of the other Vertebrates. Especial
service has been rendered through the painstaking investigation of
these conditions : in the earlier times by BISCHOFF, in later years by
HENSEN, LIEBERKUHN, VAN BENEDEN, KOLLIKER, and HEAPE. The
object of investigation which has been made use of in this work, and
which we shall employ as the basis of our description, has usually
been the Rabbit ; besides this, the Bat and the Mole have also been
employed.

Fig. 57. — Section through the margin of the germ-disc
of a Hen's egg that had been incubated for six
hours, after DUVAL.

ak, Outer germ-layer ; dz, yolk-cells ; dk, yolk-nuclei ;
dw, yolk-wall.

100

EMBRYOLOGY.

While the Mammalian egg is gradually impelled through the
oviduct toward the uterus by the ciliary motion of the epithelium, it
becomes converted by the cleavage process into a spherical mass of
small cells (fig. 58 A). Then there arises within it, by the secretion
of a fluid, a small fissure-like cleavage-cavity (fig. 58 £). The germ
has consequently entered upon the vesicular or bias tula stage. The
wall of the blastula, or vesicula blastodermica, is composed of a
single layer of polygonal cells, arranged, as has been known since
BISCHOFF'S works, in mosaic, with the exception of a small region,
where the wall, as in the case of the Amphibian blastula, is thickened
by an accumulation of somewhat more granular and darker cells,

Fig. 58.— Optical sections of a Rabbit's egg in two stages immediately following cleavage, after
ED. v. BENEDEN. Copied from BALFOUR'S ' ' Comparative Embryology."

A , Solid cell-mass resulting from cleavage.

B, Development of the blastula by the formation of a cleavage-cavity in the cell-mass. (According

to VAN BENEDEN'S interpretation, ep is epiblast ; hy, hypoblast ; bp, blastopore.)

which produce a knob-like elevation that projects far into the
cleavage-cavity.

A peculiarity preeminently characteristic of the further develop-
ment of Mammals is that here, as in no other Vertebrate, the
blastula increases enormously in size (fig. 59), by the accumulation
of fluid which contains much albumen and produces a granular
coagulum upon the addition of alcohol ; it soon acquires a diameter
of 1*0 mm. Of course, with these processes of growth the zona
pellucida is altered and distended into a thin membrane. A gela-
tinous layer (zp) already secreted by the oviduct envelops the
latter.

In Rabbits' eggs which are a millimetre in diameter the wall of
the blastula has become very thin. The mosaic- like cells arranged
in a single layer have become very much flattened. Also the knob

DEVELOPMENT OF THE TWO PRIMARY GERM-LAYERS.

101

of cells, which projects into the cleavage-cavity, has become meta-
morphosed and has spread itself out more and more in the
form of a disc-like plate, which is continuous at its attenuated
margins with the thin
wall of the blastula.
The further .processes
of development take
place principally ' in
this plate. Its most
superficial cells are
flattened out to thin
scales, such as also
form the wall of the
blastula elsewhere ; its
remaining elements,
on the contrary, ar-
ranged in from two
to three superposed
layers, are larger and

Fig. 59.— Rabbit's egg, 70-90 hourg after fertilisation, after
Ep. v. BENEDEN. Copied from BALFOUR'S " Comparative
Embryology."

bv, Cavity of the blastula ; zp, [gelatinous layer surrounding
the] zona pellucida ; ep, hy, as in Fig. 58.

richer in protoplasm.

Up to this time the
embryo of the Mammal
is in the blastula stage.
It still consists everywhere of a single germ-layer. For the view
which has been advanced by many persons, that the germ-disc in this

Fig. 60.— Cross section through the almost circular germinal area of a Rabbif s egg 6 days and 9

hours old (diameter 0'8 mm.), after BALFOUR.
ak, Outer, ik, inner germ-layer. The section shows the peculiar character of the upper layer with

a certain number of flattened superficial cells. Only about half of the whole breadth of the

germinal area is repressnted.

stage of development is already in the two-layered condition, and that
the outer layer of flat cells constitutes the outer germ-layer and the
more protoplasmic cells lying under it the inner germ-layer, is, in my
opinion, untenable. Opposed to this are, first, the fact that the flat-
tened and the thicker cell-layers are firmly joined together and
are not separated from each other even by the narrowest fissure,
and, secondly, the further course of the development.*

* Holding to this interpretation, I am of course also unable to agree with a
view of VAN BENEDEN'S, according to which the gastrulation takes place at the

102

EMBRYOLOGY.

Two germ-layers first appear in eggs
which have already attained a diameter of
more than 1 mm. and are about five days
old. At the place where the cell plate pre-
viously lay, one sees by inspection from the
surface a whitish spot, which is at first
round, but later becomes oval or pear shaped.
It is generally designated at this stage as
area embryonalis, or as embryonic spot. It
consists of two germ-layers (fig. 60), which
are separated by a distinct fissure, and may
be detached from each other. The inner
germ-layer (ify is a single sheet of greatly
flattened cells. The outer germ-layer (ak),
on the contrary, is considerably thicker, and
shows that it is composed of two sheets of
cells : (1) a deeper layer of cubical or round-
ish, larger elements, and (2) a superficial
layer of isolated flatter cells, which were first
accurately described by RAUBER, and which
have been named after him RAUBER'S layer.
Toward the margins of the embryonic spot
the outer layer becomes thinner and pos-
sesses only a single layer of cells ; these are
continuous with the large flattened elements
which, as we have seen, alone constitute the
greater part of the wall of the sac in the
blast ula stage. The inner germ-layer is
at first developed on only a small part of
the wall of the sac — at the embryonic spot
and its immediate vicinity; it terminates
with a free notched margin, where there
are to be found loosely associated amoeboid
cells, which by their increase in number and
migration probably cause the further growth

end of the first stages of cleavage. He interprets in the originally solid
sphere of cells (fig. 58 A) the darker and larger centrally located elements
(Jiy) as entoderm, the layer of smaller and clearer cells (ep) surrounding the
latter as ectoderm, and a small vacuity in this investing layer as the blastopore
(&p). I, on the contrary, believe that the gastrulation takes place in the
manner described on page 104.

s

DEVELOPMENT OF THE TWO PRIMARY GERM-LAYERS. 103

of the layer. This on older eggs slowly spreads itself from the
embryonic spot toward the opposite pole, and thereby the whole
blastodermic vesicle gradually becomes two-layered. While this is
taking place, changes also proceed at the embryonic spot, which has
become oval and somewhat larger. RAUBER'S layer disappears*
(fig. 61) ; the underlying cubical or spherical cells have become
cylindrical and more closely crowded together. Each of the primary
germ-layers is now composed of a single layer of cells.

The two accompanying figures, which represent in two different
positions a Rabbit's egg seven days old, will serve for the illustration
of these conditions. In looking down from above (fig. 62 A) one sees
the embryonic spot (ag), now become oval. It is produced exclusively
by a definitely limited thickening of the outer germ-layer, and indi-
cates the place at which the cells are cylindrical ; in that respect it
corresponds to the embryonic shield of reptilian and avian embryos,
and is not to be confounded with the cell-plate (fig. 59), which was
described as a thickening of the one-layered blastula. In looking at
it from the, side (fig. 62 B} one can distinguish on the blastula three
regions : (1) the embryonic spot (ay); (2) a region which includes the
tipper half of the vesicle and reaches to the line ge, in which the wall
is still composed of two layers, but in which the cells of both thr*
outer and inner germ-layers are very much flattened ; and (3) a third
portion lying below the line ge, where the wall is composed exclusively
of the outer germ-layer.

There now arises the important question, in what manner the two-
layered condition in Mammals arises out of the single-layered form.
One has reason to expect that gastrulation takes place here in
the same way as with the remaining Vertebrates, by means of an
invagination or an ingression of cells which proceeds from a definite
territory of the thickened cell-plate of the blastula ; in this con-
nection attention must be directed to the posterior end of the
embryonic spot.

When the embryonic spot has acquired a pear-shaped appearance
(fig. 63), there is at its posterior end a somewhat less transparent,
because thickened, place (hw), which KOLLIKER has designated
the terminal ridge (Endwulst). It is comparable with the opacity

* Two views are held concerning the manner in which EAUBER'S layer
disappears. According to BALFOUR and HEAPE, the flat cells become meta-
morphosed into cylindrical cells, which are interposed between the other
cylindrical cells ; according to KOLLIKER, on the contrary, they disintegrate
and disappear.

104

EMBRYOLOGY

at the posterior margin of the germ-disc of Reptiles and Birds, when
their gastrulation begins. An invagination proceeding from this

point, such as DUVAL has
established for the Chick,
is unfortunately not as
yet proven with sufficient
certainty in the case
of Mammals ; the origin
of the two-layered stage
is also still involved in
obscurity.

However, there are in
the literature some observa-
tions, which, fragmentary
as they are, appear to me
to be worthy of special
regard.

At the stage at which
the blastula has become
for a certain distance two-
layered (fig. 62), there has
been discovered by HEAPE
in the case of the Mole, by
SELENKA in the Opossum,
and by KEIBEL in the
Rabbit, at one place of
the embryonic spot (pro-
bably in the region just
described as terminal ridge),
a small opening (fig. 64 u),
which is possibly to be in-
terpreted as blastopore and
to be compared with the
crescentic groove of Birds.
Here the two primary germ-
layers are continuous with
each other, and from here, as well as from the primitive streak, the
middle germ-layer takes its origin. I assume that, beginning at
this place, the lower germ-layer has in a still earlier stage been
developed by an infolding of a small territory of the single-layered
blastula (fig. 59).

Fig. 62.— Blastula of the Babbit 7 days old without the
outer egg-membranes. Length 4'4 mm. After
KOLLIKER. Magnified 10 diametei-s.

Seen in A. from above, in B from the side.

ag, Embryonic spot (area embryonalis) ; gc, the line
up to which the blastula is two-layered.

DEVELOPMENT OF THE TWO PRIMARY GERM-LAYERS.

105

One circumstance is especially characteristic of the gastrulation of
Mammals : that the invaginating
membrane is not a closed blind sac,
but possesses a free margin, with
which it grows along on the inner
surface of the outer germ-layer,
until it has completely lined the
blastodermic vesicle. The reader
will please compare with this the
statements on page 102. But the
absence of a ventral closure becomes
intelligible, when we imagine that
the yolk-mass, which constitutes in
meroblastic eggs or in Amphibian
eggs the floor of the ccelenteron,
has degenerated and wholly disap-
peared. In this case ccelenteron
and cleavage-cavity become one
and the same, as is the case with
Mammals.

Moreover we are induced to as-
sume that in the eggs of Mammals a
regressive metamorphosis of origin-
ally abundant yolk-contents must have taken place, on account of
many phenomena in their development, which would be unintelligible

Fig. 63.— Pear-shaped embryonic spot of a
Babbit's egg: 6 days and 18 hours old,
after KOLLIKER.

ps, Short primitive streak ; hw, crescent-
shaped terminal ridge ; V, anterior,
H, posterior end.

it

Fig. 64.— Median section of the embryonic fundament of a Mole's egg through that part in

which tke primitive streak has begun to lie formed, after HEAPE.
u, Blastopore ; ok, outer, ik, inner germ-layer ; V, anterior, H, posterior end.

without this assumption. These phenomena will be considered more
at length in a subsequent chapter.

106 EMBRYOLOGY.

CHAPTER VI.

DEVELOPMENT OF THE TWO MIDDLE GERM-LAYERS.
( CCEL OM-THEOR Y. ) *

AFTER the completion of the gastrula stage the processes of develop-
ment become more and more complicated, so that the attention of the
observer from this time on must be directed to a series of changes
which take place at the same time and in various parts of the
embryo. For a transformation now ensues, due to the simultaneous
folding of both the inner and outer germ-layers, whereby four new
chief organs of the vertebrate body are called into existence. Out
of the inner primary germ-layer arise (1) the two middle germ -layers,
which enclose between them the body-cavity ; (2) the secondary en-
toderm or entoblast (Darmdriisenblatt), which lines the secondary
intestine of vertebrated animals ; and (3) the fundament of the axial
skeleton, the chorda dorsalis, or notochord. At the same time there
is developed from the outer germ-layer, as its only system of organs,
the fundament of the central nervous system. Since these four pro-
cesses in the development are in part most intimately involved in
one another, they cannot b£ separated in their treatment.

Here again we have to do with a problem which is one of the
most difficult in the embryology of vertebrated animals — the
history of the development of the two middle germ-layers. Not-
withstanding a voluminous literature which has grown out of this
theme, there are many conditions, especially among the higher
classes of Vertebrata, which are not yet explained in an entirely
satisfactory mannqr. We shall therefore enter somewhat more
minutely into this topic, which, like the question as to the origin of
the two primary germ-layers, possesses a fundamental significance
for the comprehension of the organisation of Vertebrates.

The presentation of what follows will be essentially facilitated, if
we allow ourselves a short digression into the history of the develop-
ment of the Invertebrata, and take under consideration a case in which
the middle germ-layers and the body-cavity are established in a
manner similar to that which obtains in the case of Vertebrata,
but which is easier to investigate arid to understand. Such an

* In figs. 66-89 the individual germ-layers are represented in different depths
of shade, so as to make their relations to one another more evident. The
middle germ-layer is darkest.

DEVELOPMENT OF THE TWO MIDDLE GERM-LAYERS.

107

example is presented to us in the development of arrow-ivorms
(Sagittal) or Chcetognatha, concerning which observations have been
published by KOWALEVSKY, BUTSCHLI, and the author.

After the process of cleavage there arises a typical blastula, which
after some time is converted into a typical gastrula. While the
latter elongates, two folds of the inner germ-layer arise at the bottom
of the coslenteron, and grow up parallel to each other (fig. 65).

ak

Fig. 65.

BALFODR'S

Fig. 65.— A stage in the development of Sagitta, after KOWALEVSKY, from

" Comparative Embryology."
Optical longitiidinal section through a gastrula at the beginning of the formation of the

body-cavity.
in, Mouth ; al, alimentary cavity ; pv, body-cavity ; bl.p, blastopore.

Fig. 66. —Optical cross section through a larva of Sagitta.

The ccelenteron is separated by means of two folds, which protrude from its ventral wall (V),

into the intestinal canal proper and the two lateral body-cavities (Ih), all of which are still

in communication with one another on the dorsal side (Z)).
D, Dorsal side ; V, ventral side ; ak, outer, ik, inner germ-layer ; mfc1, parietal, mk'*, visceral

middle layer ; Ih, body-cavity.

They grow larger and larger, and at the same time stretch over on to
the ventral wall of the larva. From here the free edges finally grow
on the one hand up to the dorsal wall, on the other up to the
blastopore, and thereby completely divide the cceleriteron into a
middle and two lateral spaces (fig. 66 Ih), which for a time communi-
cate with each other near the blastopore and along the subsequent
dorsum (D) of the embryo. After a short time this communication
is lost ; the blastopore becomes closed, and the edges of the folds
fuse with the adjacent surfaces of the ccelenteron. Of the three
cavities the middle becomes that of the permanent intestinal tube, the
two lateral ones (Ih) become those of the two body-cavity sacs which

1 08 EMBRYOLOGY.

separate the intestine from the wall of the body. They appropri-
ately take the name enteroccel, since they are formed from the ccelen-
teron by a process of constriction, and are genetically distinguishable
from other cavities which arise in other animals between the wall of
the intestine and that of the body by simple splitting, and to which
is given the nsnne Jissicoel or schizoccel.

By the process of infolding the number of the germ-layers in Sagitta
has been increased from two to three. The primary inner germ-layer
is thereby divided into (1) a cell-layer (ik) which lines the intestinal
tube, and (2) a cell-layer which serves to enclose the two body-cavities
(mk1 and mk2). The first is designated as the secondary inner germ-
layer or entoblast, the second as the middle germ-layer (mesoblast).
One part of the latter is adjacent to the
outer germ-layer, the other part to the
intestinal tube ; accordingly the division
is carried still further — into a parietal
(mk1) and a visceral layer (mk2) of the meso-
blast. For the sake of brevity the former
may be called the parietal (mk1), the latter
the visceral (mk2) middle layer. Conse-

\ ' ' / •«'

quently, one may now speak of two middle
Fig. 67.-Diagrammatic cross sec- qerm-lay ers instead of one. the total number

tion through a younj Sagitta. y J .

dM, Dorsal, vM, ventral mesen- of the germ-layers being, naturally, raised

tery •; dh, intestinal cavity; fy this from three to four.

Ih, body-cavity; ak, outer, ik, y J J

inner germ-layer ; mk1, parietal, In regard to the course of the further

devel°Pment ft may be stated that> whil*

the larva elongates into a worm-like body,
the two body-sacs (fig. 67 Ih) are increased to a greater extent
than the intestinal tube (ah) which they embrace. They everywhere
crowd the latter away from the wall of the body, grow around it
from above and below, where their thin walls come into direct con-
tact. By the fusion of the two body-sacs along their surfaces of
contact there are formed two delicate membranes, a dorsal (dM)
and a ventral (vM ) mesentery, by means of which the intestinal tube
is attached to the dorsal wall and to the ventral wall of the
trunk.

Processes very similar to those of Sagitta occur in the development
of Vertebrata also, but in the latter case they are combined with
the development of the neural tube and the chorda dorsalis. In the
presentation of these we shall proceed as in the foregoing chapter,
which treated of the formation of the gastrula, and consider separately

DEVELOPMENT OF THE TWO MIDDLE GERM LAYERS.

109

the processes in Amphioxus, Amphibia, Selachians, Birds, and Mam-
mals, since they differ somewhat from one another.

The history of the development oj Amphioxus lanceolatus is very in-
structive. The gastrula elongates, whereby the ccelenteron is turned
a little towards the future dorsal surface, and here terminates in the
blastopore, which marks the future hind end of the worm-shaped
body. Then the dorsal surface becomes somewhat flattened ; the
cells in this region increase in height, become cylindrical, and form
the medullary or neural plate (fig. 69 mp). By a slight infolding of
the latter, there arises a medullary groove, which forces downward
the roof of the

ccelenteron in ik dh u^ush n ush mk cn

the form of a
ridge (ch). At
the place where
the thickened
medullary
plate joins the
small-celled
part of the
outer germ-
layer, or the
horn-layer (hb),
an interruption
in the continu-
ity now takes place, and the epidermis grows over the curved
neural plate from both sides, until its halves meet in the middle
line and fuse. Thus there arises along the back of the embryo
(fig. 70) a canal, the lower wall of which is formed by the curved
medullary plate (mp), and the upper wall by the overgrowing epi-
dermis (ak). It is only at a later stage that the medullary plate in
Amphioxus, lying under the epidermis, is converted into a neural tube
(fig. 72 n) by the bending up of its edges and their fusion. As the
fundament of the nervous system becomes differentiated, it extends
so far toward the posterior end of the embryo, that the blastopore,
which is located there, still falls within its territory, and with the
closure of the neural tube is included within the end of the latter.
In this manner it occurs that neural tube and intestinal tube, as
KOWALEVSKY first observed, are now, by means of the blastopore,
in continuity (fig. 68 cn) at the posterior end of the body. The two
together constitute a canal composed of two arms, the form of which

Fig. 68.— Optical longitudinal [sagittal] section through an embryo of
Amphioxus with five primitive segments, after HATSCHEK.

V, Anterior, H, posterior end ; ik, inner, mk, middle germ-layer ; dh,
intestinal cavity ; n, neural tube ; cn, neurenteric canal ; us1, first
primitive segment ; «*A, cavity of primitive segment.

110

EMBRYOLOGY.

is comparable with a siphon. The upper arm, which is the neural
tube, continues, for a time, to open to the outside world at its

anterior end. The bent por-
tion of the siphon, or the
blastoporic region, by means
of which the neural and the
intestinal tube are united, is
called canalis neurentericus
(fig. 68 en), a structure which
we shall again encounter in
the development of the re-
maining Vertebrata.

Simultaneously with the
neural tube are developed

Fig. 69.-Cross section of an Amphioxus embryo, in ,1 , vnirffffp fiprm Ifiiifir*

which the first primitive segment is being formed, G ^ ™>^a>y&

after HATSCHEK. and the chorda dorsollS (fig*.

ak, Out»r, ik, inner, mk, middle germ-layer ; hb,

hb —

eft

mt

at

epidermis ; mp, medullary plate ; cht chorda ;
*, evagination of the ccelenteron.

ale —-a

69 and 70). At the front
end of the embryo there
arise in the roof of the

ccelenteron close to each other two small evaginations, the body-sacs
(mk), which grow dorsally and laterally at either side of the
curved medullary groove.
These are slowly enlarged,
since the process of evagina-
tion progresses from the an-
terior toward the posterior
end of the larva, and finally
reaches the blastopore. The
narrow strip of the wall of
the ccelenteron which is found
between them and separating
them (its limits marked by
two stars * * in figs. 69 and
70), and which lies under

Fig. 70. — Cross section of an Amphioxus embryo,
in which the fifth primitive segment is i»
process of formation, after HATSCHEK.

ak, Outer, ik, inner, mk, middle germ -layer ; mp,
medullary plate ; ch, chorda ; *, evaginatiou
of the coelenteron ; dh, intestinal cavity ; lh,.
body-cavity.

the middle of the medullary
groove, represents the funda-
ment of the chorda (ch).

The primary inner germ-
layer therefore has now undergone division into four different parts :
(1) the fundament of the chorda (ch), (2) and (3) the cells (mk) which
line the two body-sacs (lh) and represent the middle germ-layer, and

DEVELOPMENT OF THE TWO MIDDLE GERM-LAYERS.

Ill

(4) the remaining part, which, since it is destined to form the bounding
wall of the subsequent intestine (dh), is to be designated as permanent
entoderm (Darmdriisenblatt) (ik).

The succeeding processes of development have as their objective
point the detachment from one another, by means of constriction and
fusion, of the parts which are still in continuity, and the formation
of discrete cavities. The processes of constriction begin at the-
anterior end of the embryo, and progress thence to the blastopore
(figs. 70 and 71). At first the body-sacs become deeper (fig. 70 Ih),

Fig. 72.

Fig. 71. — Cross section through an Amphioxus emhryo with five well-developed primitive seg-
ments, after HATSCHEK.

ak, Outer, ik, inner, mk, middle germ-layer ; mp, medullary plate ; ch, chorda ; dh, intestinal
cavity ; Ih, body-cavity.

Fig. 72. — Cross section through the middle of the body of an Amphioxus embryo with eleven,

primitive segments, after HATSCHEK.
ii, Neural tube ; us, primitive segment. For the meaning of the other letters see Fig. 71.

and then lose their connection with the main cavity (dh) by the close
apposition of the cells which surround the entrances to them (fig. 71).
By this process the margin of the secondary entoderm (ik) comes to-
abut directly 011 the margin of the chordal fundament (ch). The
latter has meanwhile also undergone changes ; the plate-like funda-
ment has become so curved by the elevation of its lateral margins,
that there has arisen a deep chordal groove, which is open along its
ventral side. Subsequently the lateral walls of the groove come into-
close contact, and are thereby converted into a solid rod of cells, which
temporarily shares in the closure of the roof of the secondary intestine,
and appears as a ridge-like thickening of the latter. Then the cell-
rod (ch) becomes detached (fig. 72) from the wall of the intestine ; the-
latter now, for the first time, becomes completely closed in the form
of a tube. To effect this the margins of the entoderm, indicated in-

112 EMBRYOLOGY.

fig. 70 by stars ( * *), grow toward each other under the chorda and
fuse into a median raphe.

The final result of all these processes is shown in the cross section
fig. 72 : the original ccelenteron has become divided into three cavities
— into the ventral permanent intestine (dh), and into the two body-
cavities (Ik), which are situated dorso-laterally to it, and which con-
tinue to increase in size. Between these there has been interpolated
the chorda (ch), upon which the intestine abuts below and the neural
tube (n) above. The cells which have been cut off from the ccelen-
teron by constriction — and which are more deeply shaded in figs. 69
to 72, and enclose the body-cavities (Ih) — constitute the middle
germ-layer (mk). The part which lies in contact with the outer
germ-layer (fig. 72) is recognisable as the parietal middle layer
{mk1) ; the part which is in contact with the neural tube, chorda,
and intestine as the visceral middle layer (mk2).

Inasmuch as the process of differentiation just described begins,
as has been already stated, at the front end of the embryo and
extends slowly step by step toward the hind end, by an examina-
tion of a series of sections one may follow the various stages of
metamorphosis on a single object.

In the description given I have presented the conditions as though
in Amphioxus there arose two simple body-sacs, one on either side
of the intestinal tube. The processes are, however, somewhat more
complicated, for in the case of the embryo of fig. 70 the body-sacs,
while increasing in size posteriorly, undergo further changes in the
anterior region, and through repeated infoldings are divided into
separate compartments, the primitive segments (us), which lie one
behind the other. I content myself with this statement, since for
-didactic reasons I shall defer the treatment of the development of
the primitive segments until I come to a subsequent chapter.

While in the case of Amphioxus lanceolatus there is no doubt but
that the body-cavity and the middle germ-layer are formed by an out-
pocketing of the wall of the coslenteron, opinions upon the origin of the
same parts in the case of the remaining Vertebrata are still very
divergent. This results, in the first place, from the fact that the in-
vestigation, which can be carried out only by means of serial sections,
is coupled with greater technical difficulties, and, secondly, because the
.conditions are somewhat altered, owing to the greater abundance of
yolk in the eggs, and furnish less clear and intelligible views. Where
in the gastrula of Amphioxus a great cavity is present, we see in the
•case of the remaining Vertebrates a great mass of yolk-material

DEVELOPMENT OF THE TWO MIDDLE GERM- LAYERS.

113

collected, and the crelenteron more or less completely filled with it.
Consequently there are formed in these cases for the production cf
the body-cavity no hollow evaginations, but solid cell-growths, iti that
the parietal and the
visceral lamellae of the
middle germ-layer have
the surfaces which in Am-
phioxus bound the body-
cavity pressed together at
the beginning of the de-
velopment and separated
only at a rather late
stage. In order to make
easier the comprehen-
sion of the somewhat

dissimilar appearances p^ ?3 _Diagram to show ^ development of the middle

furnished by an inves- germ- layers and the body-cavity in Vertebrate.

. . , . <» , i Cross section of an embryo in front of the blastopore.

tlgatlOn Of the Separate ^°"8edullary plate; J fundament of the chorda; ale,

classes of Vertebrates, 'outer, ik, inner germ-layer ; mk\ parietal, ml?, visceral

, ., ~ ... lamella of the middle germ-layer; d, yolk-mass; dk,

let US describe first, With yolk-nuclei ; dh, intestinal cavity ; Ih, body-cavity.

the aid of two diagram-
matic figures, how, according to a series of investigations which I
have undertaken, the development of the middle germ-layer and

the body-cavity would take
place in the case of the
vertebrated animals.

One of the diagrams (fig.
73) represents a cross section
in front of the blastopore.
It exhibits the inner germ-
layer (ik) extensively thick-
ened on the ventral side by
the deposition of yolk (d), so
that the crelenteron is re-
Fig. 74.— Cross section oi an Amphioxus embryo. duced to a small cavity (dh).
See explanation of Fig. 70. Jn t^e roof of the CO3lenteron

ak, Outer, ik, inner, mk, middle germ-layer; ch, • i i u

chorda. there lies a single layer of

cells (ch), the fundament of

the chorda, characterised by their cylindrical form. On both sides
of it the inner germ -layer has developed evaginations, the two
body-sacs (Ih), which have grown down some distance between

8

srlfir— a*

114

EMBRYOLOGY.

the yolk-mass and the outer germ-layer. Their wall (ink1 and mka)
is composed of small cubical or polygonal elements, shaded darker
in the diagram. The ccelenteron is distinctly separated by means
of the two coelenteric folds (* *) into a median or intestinal cavity
proper (dh), lying beneath the chordal fundament, and the two narrow
body-sacs (Hi), which communicate with the former only by means
of narrow fissures (* *) at the right and left of the chordal funda-
ment. The figure is easily reducible to the preceding (p. 113) cross
section of an Amphioxus embryo (fig. 74), if we conceive the simple
epithelium on the ventral side of the latter thickened by an accumula-
tion of yolk, and the two
small body-sacs grown
down a certain distance
between yolk-mass and
outer germ-layer.

In the second dia-
grammatic cross section,
which is through the
blastopore (fig. 75), the
coelenteron (ud) is wholl}
filled up with the yolk
mass (d). The body-sac^
(Hi) described in the first
diagram are to be seen
here also, as they crowd
themselves downwards
between yolk and outer
germ-layer. Their walls

are composed of small cells, and the outer or parietal layer (mkl)
merges into the outer germ-layer at the blastopore, while the inner
or visceral layer (m&2) is continuous with the yolk-mass or the inner
germ -layer.

Were the conditions in Vertebrates such as the two diagrams
represent, there could no longer be any doubt in regard to them,
any more than in the case of Amphioxus, that the body-cavity is
developed out of two evaginations of the coelenteron, and that its
Avails constitute the two middle germ-layers. But there is not a
single Vertebrate which presents such clear and convincing evidence.
The distinctness is everywhere diminished, most of all by the
fact that the parts which are to be interpreted as body-sacs no longer
enclose cavities, because their walls are firmly pressed together, in

Fig. 75.— Diagram to show the development of the middle
germ-layers and the body-cavity in Vertebrata.

Cross section through the blastopore of an embryo.

u, Blastopore ; ud, coelenteron ; Ih, body-cavity ; d, yolk ;
ak, outer germ-layer ; mk\ parietal, ml?, visceral
lamella of the middle germ-layer.

DEVELOPMENT OF THE TWO MIDDLE GERM-LAYEES. 115

consequence of the fact that the greater collection of yolk requires
the space for itself. Consequently we find, in place of the body-sacs
exhibited in the diagram, solid masses of cells, for which it remains
to be established that they correspond to the sacs in position and
development.

In order to see what condition would result in consequence of a
disappearance of the body-cavity, we will imagine that in the two
diagrams the parietal and the visceral layers of the body-sacs are
firmly pressed together. In the first diagram (fig. 73) we should
then have a mass several cells thick, which would be everywhere dis-
tinctly separated from the two germ-layers — in between which it had
grown — with the exception of the place indicated by a star, which
marks the entrance to the body-sac ; this is the important region
whence the evagination or the outgrowth of the middle germ-layer
from the inner layer has taken place. At this point the cell-mass is
continuous, on the one side with the fundament of the chorda, on
the other with the entoderm. In the second diagram (fig. 75) we
should likewise see the thick cell-mass everywhere isolated, except in
the vicinity of the blastopore, where a transition to the outer as well
as to the inner germ-layer takes place. If, in addition to this, we
should imagine that the two lips of the blastopore were here pressed
together from right to left, we should have in the middle of the
cross section a thick, many-layered cell-ma^s, which on both sides is
resolved into the three germ-layers, or, in other words, at the blasto-
pore all three germ-layers by their fusion meet together in a single-
mass of cells.

By careful investigation it is, in fact, demonstrable that similar
conditions to those which we have produced by changes in the
diagrams are found in the investigation of the several classes of
Vertebrates. For this purpose we must make sections through three
different regions of the embryo : (1) through the region in front of
the blastopore, (2) through the region of the blastopore itself, and
(3) behind it. The agreement appears most prominent in the develop-
ment oj the Amphibia, among which the Tritons again furnish the
most instructive objects.

When in the case of Triton the gastrulation, with the accompany-
ing obliteration of the cleavage-cavity, is fully completed, the embryo
becomes slightly elongated; the future dorsal surface (fig. 76 Z>)
becomes flattened, and gives rise to a shallow furrow (r), which
stretches from the anterior to the posterior end nearly up to the
blastopore (u). The latter has now assumed the form of a longitu-

11G

EMBRYOLOGY.

dinal fissure. A cross section made through the middle of the
embryo in front of the blastopore (fig. 77) corresponds in every
particular to our first diagram (fig. 73), if wo conceive that the
body-cavity in this case has disappeared. The outer germ-layer (ak)
consists of a single sheet of cells, which on the back of the embryo
are cylindrical, but become shorter toward its ventral side. The
cells enclosed within the outer layer exhibit a differentiation in three
ways, and therefore are subsequently converted into three different

Fig. 70.

Fig. 76.— Egg of Triton with distinctly developed medullary groove, seen from the blastopore,

53 hours after artificial fertilisation.
D, Dorsal, V, ventral region ; u, blastopore ; 7i, elevation between blastopore and medullary

groove (r) ; f, semicircular furrow, which encloses the blastoporal area ; dp, yolk-plug.

Fig. 77.— Cross section of an egg of Triton with feebly expressed medullary groove.
ak, Outer, ik, inner germ-layer ; mkl, parietal, mk*, visceral lamella of the middle germ-layer ;
ch, chorda ; dh, intestinal cavity ; D, dorsal, V, ventral.

organs — into chorda, entoderm, and middle germ-layer. First, there
is to be found on the roof of the ccelenteron (d/i) under the medullary
groove, even close up to the blastopore, a narrow band of long-
cylindrical cells (ch) ; it corresponds in every respect to the funda-
ment of the chorda in our diagram (fig. 73 ch), and in the cross
section through Amphioxus (fig. 74 ch). Secondly, the fundament
of the chorda is flanked on either side by two bands (mkl, mk2) of
small oval cells, which extend downwards to about the middle
of the lateral region of the embryo. They do not share in bounding
the ccelenteron, since a third kind of cells (ik), large and rich in yolk,
lie along their inner surfaces. The latter begin at the margin of

DEVELOPMENT OP THE TWO MIDDLE GERM-LAYERS.

117

the chordal fundament as a single layer, become two layers thick
farther down, and thus merge into the more voluminous accumu-
lation of yolk-cells, which, in all Amphibian embryos, occupy the
ventral side and restrict the gastrula-cavity. They correspond, to
continue with our comparison, with the entoderm, whereas the
small-celled masses, which, starting from the fundament of the
chorda, have crowded themselves out between the entoderm and
the outer germ-layer, are comparable with the cells which in Am-
phioxus and in our diagram form the wall of the body-sacs, or the
middle germ-layer. The
conclusion is therefore jus-
tified and very obvious,
that in Triton the two mid-
dle germ-layers have arisen
in the anterior territory of
the embryonic body by a
process of evagination at
both sides of the chordal
Jundament, just as in Am-
phioxus, except that in one
case the evaginated cell-mass
contains a cavity, in the
other case none,

A cross section through
the blastopore of the Triton
embryo (fig. 78) is to be
•compared with our second
diagram (fig. 75). The

hollow body-sacs of the latter correspond to the solid cell-bands,
which are the fundament of the middle germ-layer. Near the
blastopore (u) they are split into two lamellae. Of these the outer
(mkl) merges, as in our diagram, into the inner layer of the blasto-
poric lip, and becomes continuous at the edge of the blastopore with
the outer germ-layer (ak) ; the inner lamella (mk2), on the contrary,
is connected with the mass of yolk-cells (dz), which lies like a wall in
front of the blastopore and even projects into it as the RUSCONIAN
yolk-plug (dp).

Posteriorly to the blastopore, the middle germ-layer stretches itself
-out for some distance, but here only as a single connected mass.

According to the region from which the middle germ-layer is de-
veloped, we may divide it into two portions, and call that part which

_ dh

Tig. 78.— Gross section through the blastopore of an
egg of Triton with feebly expressed medullary
groove.

ak, Outer, ik, inner germ-layer ; mkl, parietal, mk'*,
visceral lamella of the middle germ-layer; u,
blastopore ; dz, yolk-cells ; dp, yolk-plug ; dh,
intestinal cavity.

116

EMBRYOLOGY.

is produced on both sides of the chorda the gastral mesoderm, ancl
that which arises from the blastopore the peristomal mesoderm
(RABL).

mp

',nf

mp

ak

ink1

Ih

mk*

Fi j. 79. — Three cross sections from a series through an egg on which the medullary ridges begin,
to appear. The sections illustrate the development of the chorda out of the chordal
fundament, and the constricting off of the two halves of the middle germ-layer.

ak, Outer, ik, inner germ-layer ; mkl, parietal, mk*t visceral lamella of the middle germ-layer ;
mp, medullary plate ; mf, medullary folds ; ch, chorda ; Ih, body-cavity.

The further development of the fundaments of mesoderm, chorda,
and intestine, which subsequently become entirely separated from
one another at the places where they now remain in connection ,
causes the agreement with the conditions found in Amphioxus to-

DEVELOPMENT OF THE TWO MIDDLE GERM-LAYERS. 119

appear in stronger relief. The process of separation is introduced
by the curving of the chordal plate, and its conversion into the
chordal groove (fig. 79 A ch). Inasmuch as it is continuous at its
edges with the parietal lamella of the middle germ-layer (mkl), there
arise in the roof of the coelenteron the two small chordal folds, which
enclose between them the chordal groove. Its free margins abut
directly upon the folded edge, where the visceral lamella of the
middle germ-layer (mk*) bends around into the entoderm (ik) to
produce the coelenteric fold.

In the next following stage (fig. 79-6) the thickened medullary
plate, consisting of long cylindrical cells, becomes distinctly marked
off from the now still smaller cubical elements of the ectoderm.
Meanwhile the middle germ-layer begins to detach itself from its
previous connections in the vicinity of the place of evagination ; the
parietal lamella becomes separated from the fundament of the
chorda, the visceral lamella from the entoderm, and thereupon their
detached edges become fused to each other. By means of this pro-
cess the fundament of the body-sac, or of the middle germ-layer,
becomes closed on all sides, and is separated from the other
germ-layers. At the same time the entoderm (ik) and the funda-
ment of the chorda (ch) have come into contact along their free
margins, so that the chorda appears like a thickening of the ento-
derm, and for a time shares in bounding the intestinal cavity on the
dorsal side. This is changed by a second process of detachment.

The fundament of the chorda, now converted into a solid rod,
is gradually excluded from participation in lining the intestine
(fig. 79 C), by the fact that the halves of the entoderm (ik), composed
of large yolk-cells, grow toward each other underneath it, and fuse
in a median raphe.

The closure of the permanent intestine on the dorsal side, the con-
stricting off of the two body -sacs from, the inner germ-layer, and the
origin of the chorda dorsalis are therefore in Amphibia, as in Amphi-
oxus, processes which are most intimately related with one another.
Here, too, constricting off of the parts mentioned begins at the head- end
oj the embryo, and advances slowly toward the posterior end, where
there exists for a long time a zone of growth, by means of which the
increase in the length of the body is effected. Soon after this, the
moment arrives when in the embryos of Triton the body-cavity
becomes visible. For after the detachment of the organs previously
mentioned is completed, the two middle germ-layers at the head-end
of the body, and on both sides of the chorda, separate from each

120

EMBRYOLOGY .

Tig. 80. — Longitudinal [sagittal] section through an advanced em-
bryo of Bombinator, after GOETTE.

m, Mouth ; an, anus ; I, liver ; ne, neurenteric canal ; me, medullary
tube ; ch, chorda ; pn, pineal gland.

other, and thus cause to appear a right and a left body-cavity
(enterocoel), which, according to my interpretation, were not pre-
viously recognisable, simply on account of the intimate mutual

contact of their
walls.

Meanwhile the
medullary plate
has become con-
verted, by the
process of folding
already described,
into the neural
tube (fig. 80 me),
which lies beneath
the epidermis.
Since the neural
tube subsequently

encloses the blastopore, and is thereby in communication with the
intestinal tube (as the preceding longitudinal section of an advanced
embryo of Bombinator most distinctly shows), it follows that there is
also in the Amphibia a structure (fig. 80 ne) corresponding to the
neurenteric canal of Amphioxus (compare fig. 68 en).

More fundamental differences in the development of the middle
germ-layer are
met with in
the eggs of
Fishes, Rep-
tiles, and Birds,
which are more
abundantly
provided with
nutritive yolk
and undergo
partial cleav-
age, and also

in the eggs of Mammals. However, the variations appear in these
cases to be of a subsidiary nature, whereas in the chief points the
unity of the developmental processes for all vertebrated animals has
been the more firmly established the more accurately the individual
stages have been investigated by means of improved methods.

In the presentation of these difficult conditions, we shall describe

vli

Fig. 81 A and B.— Two germ-discs of Hens' eggs in the first hours of

incubation, after ROLLER.
(If, Area opaca ; hf, area pellucida ; s, crescent ; sk, crescent-knob ;

Es, embryonic shield ; pr, primitive groove.

DEVELOPMENT OF THE TWO MIDDLE GERM-LAYERS. 121

first the changes which may be recognised in viewing the germ-disc
from the surface, and to theso shall add, secondly, the more im-
portant results acquired by series of cross sections.

At the posterior margin of the germ-disc of the Chick (fig. 81 A),
which consists of two layers lying on the yolk like a watch-glass, we
had distinguished — not only a short time before incubation, but also
during the early hours of that process — the crescent (s) and the
crescentic groove, and had learned to recognise that this was the
place from which the inner germ-layer arose by a process of folding
under.

When, during the first hours of incubation, the germ-layers grow
out farther on the. yolk, the crescentic groove (fig. 81 1?) is con-
verted into the primitive groove (pr), a structure of far-reaching
significance.

The metamorphosis, according to the excellent researches of DUVAL,
takes place in the following manner : In the middle of the anterior
blastoporic lip, where the outer germ-layer bends over to become
•continuous with the inner, there arises a small notch, which is
•directed forwards (fig. 81 A sk) • this gradually elongates into a
groove (fig. 81-5), corresponding with the future longitudinal axis of
the embryo, and by the following method : the right and the left halves
of the [anterior] blastoporic lip, together with the part which bounds
the first notch, grow toward each other, and come in contact with
€ach other in the median plane, with the same rapidity with which the
•disc increases in super-
ficial extent. For a time, _,. — ...
therefore, the blastopore
has the form of a short />'""""\\
longitudinal groove, :( j;
which, at its posterior '^^^

•end, is bent around into Fig. 82.— Diagrams to elucidate the formation of theprimi-

two Short transversely tive groove, after DUVAL.

The increasing size of the germ-disc in the course of the

placed CreSCentiC horns development is indicated by dotted circular lines. The

{s} Finally these also heavv lines rePresent the crescentic groove, and the

* primitive groove which arises from it by the fusion of

have disappeared ; they, the edges of the crescent.

too, have grown toward

«ach other, toward the median plane, and have thus contributed
largely to the posterior elongation of the primitive groove. By this
remarkable process of growth the whole blastopore is converted from
a transverse fissure into a longitudinal one.

The accompanying diagrams (fig. 82) serve to illustrate this highly

122

EMBRYOLOGY.

important process. The increase which the germ-disc has undergone
during successive stages is indicated by dotted lines. The margin of
the fold, where the upper germ-layer passes over into the lower
layer, or the anterior lip of the blastopore, is denoted by a heavy
black line. In the figures J, B, C, one
observes how, with the increasing extent of
the germ-disc, the right and left halves of
the blastoporic lip come together in the

median plane
in ever-increas-
ing extent, and
form the primi-
tive groove.

In figs. 83
and 84 are pre-
sented instruc-
tive cross sec-
tions through
the primitive
groove in the
first stages of its
development.
The first shows
us the two lips
of the blasto-
pore (fig. 83 ul),
separated by a
small space,
into which
there projects
from below a

small elevation (dp) of yolk-substance,
containing a number of nuclei (merocytes),
comparable with the RUSCONIAN yolk-plug
in the Amphibian larva (fig. 78 dp). At
the lips, the upper germ-layer, a single cell thick, bends around into
the lower germ-layer, composed of loosely associated cells. The
blastopore leads into the coelenteron, which lies between yolk and
germ-disc. In fig. 84 the margins of the two folds have come into
close contact, and have fused to form the anterior part of the primi-
tive streak, above which the primitive groove is still to be found.

DEVELOPMENT OF THE TWO MIDDLE GERM-LAYERS.

When the last remnant of the crescentic groove has been employed
tor the elongation of the primitive groove, the margin of the germ-
disc, which continues all the time to spread itself out uniformly over
the yolk, exhibits everywhere one and the same condition; it has
become at all points a circumcrescence-margin, now that the in-
vagination-margin has detached itself from it as primitive groove.

Fig. 6i

Fig. 86.

Fig. 85.— Surface view of the area pellucida in the blastoderm of a Chick, soon after the

formation of the primitive groove, after BALFOUK.
pr, Primitive streak with primitive groove ; a/, amniotic fold. The darker shading surrounding

the primitive streak indicates the extent of the mesoblast.

Fig. 86.— Surface view of the area pellucida of a blastoderm of 18 hours, after BALFOUR.

The area opaca is omitted ; the pear-shaped outline marks the limit of the area pellucida. At the

place where the two medullary folds are continuous with each other there is to be seen a.

short curved line, which represents the head-fold. In front of it there lies a second line

concentric with it, the beginning of the amniotic fold. A, Medullary folds ; me, medullary

furrow ; prt primitive groove.

When subsequently the pellucid and opaque areas become more dis-
tinctly separated, the primitive groove comes to lie in the posterior
part of the pellucid area. By careful examination of a surface pre-
paration (figs. 85 and 86 pr), one sees that it is bounded, both on the
right side and on the left, by two small folds, which are derived
from the blastoporic lips, and which appear darker and more opaque
because the cells are multiplying rapidly and are more closely
crowded. Since the two primitive folds, or the two blastoporic lips,.

124

EMBRYOLOGY.

lib1

hb"

hb3

mf

pr

Fig. 8?.— Blastoderm of the Chick, incubated 33 hours,
after DUVAL.

The area pellucida (/>/) is surrounded with a portion of the
opaque area (<Jf). The fundament of the nervous
system is nearly closed in front and segmented into
the three brain- vesicles hb1, Jib*, Jib* ; behind, the
medullary furrow (mf) is still open. On either side
of the latter there are six primitive segments (us).
The posterior end of the embryonic fundament is
occupied by the primitive streak and the primitive
groove 0»*).

the primitive streak and its head-process,

are closely in contact
at the bottom of the
groove, and indeed are in
places completely fused^
they together produce
in the pellucid area a
dark streak of sub-
stance, which is about a
millimetre long and O2
mm. broad. With the
earlier embryologists, to
whom it was already
known, we designate
this as the primitive
streak of the germ- disc.
In the vicinity of the
primitive streak there
are to be distinguished
in surface views, now
and during the following
stages of development,
some additional changes,
which are caused by the
beginnings of special or-
gans. In the first place,
there is to be seen in the
anterior region of the
area pellucida, and in
the direct continuation
of the primitive streak,
a narrow, dark streak of
cells, which has been
designated by KOLLIKER
as the head-process of
the primitive streak,
and which gradually in-
creases in length. Se-
condly, there appears an
increasing opacity (fig.
85) in the vicinity of
which afterward stretches

DEVELOPMENT OF THE TWO MIDDLE GERM-LAYERS. 125'

out farther laterally : it is connected with the origin of the middle
germ-layer.

In a still later stage of development (fig. 86), at the beginning of
the second day of incubation, the first fundament of the central
nervous system makes its appearance in the anterior portion of the
germ-disc. Over the head-process there arise at some distance from,
each other the two medullary folds (A), which are continuous with
each other at their anterior ends, and which bound the broad medul-
lary furrow (me) } posteriorly they become less prominent, and they
here embrace between them the anterior end of the primitive streak
(pr). Medullary furrow (me) and primitive groove (pr) must not
be confounded with each other, as occurred in the earlier days of
embryology ; they are two entirely distinct and dissimilar structures,
which exist at the same time, and independently of each other, as
fig. 86 shows.

Primitive streak and primitive groove are preserved for a long
time without undergoing important changes (fig. 87 pr). They
always occupy the posterior end of the embryonic body, which is
characterised by its slightly differentiated condition even in stages
when the development of the separate organs of the body is already
in full progress. On the contrary, the embryonic territory lying in
front of it, which is so small at the time of the appearance of the-
head-process, becomes greatly elongated and, at the same time,
differentiated into the separate organs of the body. This process
of differentiation begins in front, and proceeds posteriorly toward
the primitive groove, just as in Amphibxus and the Amphibia.
The margins of the medullary folds come into contact with each
other and begin to fuse, forming the neural tube (A61, hb2, hbs,
mf), the fusion progressing from the head- toward the tail-end.
There are also to be recognised now in the interior of the body,
at either side of the neural tube, the protovertebrse or primitive
segments (us), which we shall investigate more minutely further
on. The number of these is constantly increased by the growth
which is taking place at the tail-end.

When a large number of primitive segments has arisen, the
primitive groove begins on surface-views to disappear ; for it is sur-
rounded by the medullary folds, and inasmuch as these fuse here as
well as elsewhere, it is enclosed in the terminal part of the neural
tube. A notable condition, and one of great importance for the
interpretation of the primitive groove, has been "discovered at this
stage in the embryos of several species of Birds by GASSER, BRAUN,,

126

EMBRYOLOGY.

*9

HOFFMANN, and others. At the front end of the primitive groove a
narrow canal has arisen, which leads obliquely from the neural tube
•under the entoderm, and unites the two in the same manner in which
the blastopore does in Amphioxus and the Amphibia. A diagram-
matic longitudinal section through the hind end of a Chick (fig. 88)
shows us this important union (n.e), which exactly corresponds to the

condition of
an Amphi-
bian embryo
presented in
fig. 80.

Such a
neurenteric
canal has
been ob-
served still
more dis-
tinctly in
Selac h i a n s
and Reptiles
and at even
e a r 1 i e r
s t a g e s,
whereas in
Teleosts it

-does not come to development on account of special subsidiary
conditions.*

The investigation of the embryonic fundaments of a Mammal fur-
nishes us with views quite similar to those respecting the Chick. When

* In Selachians the blastopore is very early enclosed within the medul-
lary folds, and then assumes the condition of a long-persisting canal-like
passage to the intestinal cavity through the floor of the medullary groove,
and later through that of the neural canal.

In the case of Reptiles, the primitive streak is very short and triangular,
and in many species soon discloses, before other organs have been differentiated,
an opening at its antvivior end which leads to the cavity under the germ-disc,
which is filled with yolk. Subsequently the opening is converted into a canal,
the wall of which is composed of cylindrical cells, and is in continuity above
with the outer germ-layer, and below with the inner germ-layer. Then the
medullary folds, which are being formed in front of the orifice, grow around
it ; the orifice now becomes a genuine neurenteric canal, which in many cases
appears to become obliterated even before the closure of the medullary tube,
but in other cases persists for a long time.

Fig. 88.— Diagrammatic longitudinal section through the posterior end of
an embryo Chick at the time of the formation of the allantois, after
BALFOUR.

The section shows that the neural tube (Sp.c) is continuous at its posterior
end with the post-anal intestine (p.a.g) by means of the neurenteric
canal (n.e). The latter traverses the remnant of the primitive streak
(pr), which is folded over on to the ventral side, ep, Outer germ-layer ;
ch, chorda ; hy, entoderm ; al, allaiitois ; me, middle germ-layer ; an,
the place where the anus will arise; am, amnion ; so, somatopleure ;
sp, splanchnopleure.

DEVELOPMENT OF THE TWO MIDDLE GERM-LAYERS.

127

the embryonic area has assumed an oval form, the opacity at the
posterior end, or the terminal ridge (fig. 63 hw), which was compared
with the crescent of the Bird, elongates into the primitive streak ;
the latter occupies the posterior half of the embryonic area (fig. 89
A pr), and exhibits a distinct groove, that is flanked by a right and a
left ridge-like fold. (Compare with this the Chick as shown in fig. 85.)

Fig. 89 A.— Embryonic fundament of an 8-days Rabbit, after KOLLIKER.
•arg, Fundament of the embryo; pr, primitive streak.

Jig. 89 B — Vascular area (o) and embryonic fundament (ag) of a 7-days Rabbit's egg, after

KOLLIKER.
•o, Vascular area (area opaca) ; ag, embryonic fundament ; pr, primitive groove ; rf, medullary

furrow.

Afterwards there appears in this instance, just as with the Chick, a
narrow opaque streak in the forward prolongation of the primitive
.streak, — its head-process, — and this divides the anterior portion of
the germ into a right and a left half (fig. 90 kf). After some time
there are developed on both sides of the head-process the medullary
folds (fig. 89 B), which bound the broad medullary furrow (rf), and
which, by forming a bow at their anterior ends, become continuous
with each other ; but posteriorly they diverge somewhat from each
other, and embrace the primitive groove (pr). This stage corresponds
to the condition of the Chick, presented in fig. 86.

128

EMBRYOLOGY.

From this time forward the anterior part of the embryonic area
grows in length much more rapidly than the hind part with its
primitive groove ; the latter remains almost unaltered in Mammals
up to late stages of development, and then diminishes in length, not t
only relatively, but also absolutely.

ffo

kf

f \

Fig. 90.

Fig. 91.

Fig. 90.— Germ-disc of an embryo Rabbit with primitive streak, after E. VAN BENEDEN.
pr, Primitive streak ; kf, head-process ; hk, HENSEN'S node ; en, canalis neurentericus.

Fig. 91.— An embryo Rabbit with a part of the area pellucida 9 days after fertilisation,
Magnified 22 diameters. After K'OLLIKER.

ap, .Area pellucid i ; ao, area opaca ; h', medullary plate in the region of subsequent first brain-
vesicle ; h", the same in the region of the subsequent mid-brain, where the medullary furrow
(rf) exhibits a widening; h'", the same in the region of the subsequent third brain-
vesicle ; fcz, fundament of the heart ; stz, trunk zone (Stammzone) ; pz, parietal zone ; pr,
remnant of the primitive streak.

At the same time the embryonic area passes from the oval to a
pronounced guitar-shaped outline. Such an embryo is represented
in fig. 91. The primitive streak (pr) is to be seen at its posterior
end, partly embraced by the medullary folds (rf). The middle germ-
layer is already fully developed, and in the future neck-region three-
pairs of primitive segments have already been differentiated at the
bides of the chorda.

Just as there has been up to this stage an agreement with Birds;

DEVELOPMENT OF THE TWO MIDDLE GERM-LAYERS. 129

and Reptiles in other points, so there also is in the existence of a
neurenteric canal. At a rather early stage there is already noticeable,
at the anterior end of the primitive streak, a small spot, at which,
in consequence of cell-proliferation, a large amount of material is
accumulated. It is known under the name of HENSEN'S node (fig 90
hk). This is important chiefly because a narrow canal, the canalis
neurenterieus (en), passes through it, and leads from the outside into
the interior of the blastodermic vesicle. The presence of this canal
has already been established by several investigators — by VAN
BENEDEN in the Eabbit and the Bat, by BONNET in the Sheep, by
HEAPE in the Mole, and by GRAF SPEE in a young human embryo.
The latter exhibited a still widely open medullary furrow. At the
beginning of the primitive groove there was a wide, roundish,
triangular orifice, which traversed the germ-disc, and was surrounded
by a ring-like elevation corresponding in position to HENSEN'S node.

I have dwelt upon the primitive streak more at length, and have
considered more in detail its first appearance and its topographic
relations to other organs, because from a developmental standpoint
it is a very important structure, and one the significance of which
is still much discussed. For it corresponds to the blastopore of the
lower Vertebrates, and is important as the region from which the
middle germ-layer takes its origin. While I postpone an exposition
of the grounds which warrant us in designating the primitive groove
as blastopore, I shall at once consider the development of the middle
germ-layer. Information concerning this is to be got from cross
sections, which should be made, as in the Amphibians, (1) in front
of the primitive groove, (2) in the region of the groove, and (3) back
of it, both in younger and older embryos.

In embryonic fundaments which have reached the stages repre-
sented in figs. 81 B, 85, and 89, the middle germ-layer is already
begun in the immediate vicinity of the primitive groove, and causes
the opacity which appears upon both sides and in front of it. Cross
sections through the cephalic process of the primitive streak now
allow the establishment of a complete agreement in one fundamental
point between Amphioxus and the Amphibia on the one hand, and
Selachians, Reptiles, Birds, and Mammals on the other.

Along a narrow median streak, in the former groups in front of the
blastopore, in the latter in front of the primitive groove, the embryonic
fundament is composed of only two germ-layers, of which the lower is
destined to become the chorda. At both sides of these regions the two-
layered condition passes abruptly in all Vertebrates into a three-layered

9

130

EMBRYOLOGY.

one, the outer germ-layer being followed by the middle layer, and this
by the inner germ-layer.

-Hip

eh

Fig. 92 A and B.— Cross sections through the germ-disc of a Selachian. Copy after BALFOUR'S

Monograph, PI. IV., Fig. 8a, and PI. IX., Fig. la.
Only the left half of section A is represented.
ak, Outer, ik, inner, mk, middle germ-layer ; ch, chorda ; ;np, medullary plate ; d, yolk.

The conditions in detail assume in Selachians, Birds, and Mammals-
the forms indicated by the accompanying figures (92-95).

In the Selachians the medullary fold is well marked in cross
sections (fig. 92 A mp). Beneath it there lies, as in Amphioxus and
Triton, only a single layer of tall cylindrical cells (ch), the funda-
ment of the chorda ; laterally this merges into a many-layered mass
of small cells, which is soon divided by means of a fissure into two
distinctly separated lamellae — into the middle layer (mk), composed
of small polygonal cells, and into the inner layer (ik), which here
consists of a single layer of tall columnar cells. At the point in-
dicated by a star, the fundament of the chorda and the middle

and inner germ-layers
are continuous with one
another. At a later
stage (fig. 92 B) a se-
paration of the three
fundaments takes place,
as in Triton, and we
then have (1) a round
chord al rod (ch), which
has been formed by in-
folding in the manner
previously described ; (2)
at either side of it the small-celled mass of the middle germ-layer
(mk), divided into halves by the chorda ; (3) the inner germ-layer
(ik), the halves of which, separated in the previous stage, are
now growing under the chorda, and are about to fuse into a single
layer.

ak -

ik

ch

Fig. 93. — Cross section through the blastoderm of a Chick
in which the first traces of the chorda and the medullary
furrow are to be seen, after BALFOUR AND DEIGHTON.

The section passes through the fundament of the chorda
in front of the primitive streak. The part of the
section at the right of the fundament of the chorda is
not figured.

ak, Outer, ink, middle, ik, inner germ-layer ; cJi, fundament
of the chorda.

DEVELOPMENT OF THE TWO MIDDLE GEEM-LAYERS. 131

A similar view is furnished by a cross section through the cephalic
process of the germ of the Chick (fig. 93). Under the outer germ-
layer there is found in the median plane, in front of the primitive
groove, only the fundament of the chorda (ch) ; at the point indicated
by a star it is continued laterally into the small-celled middle germ-
layer, and into the entoderm, which is composed of a single layer of
very much flattened cells.

The same is true for cross sections of Mammals (fig. 94) in corre-
sponding stages of development. Thus, for example, the funda-
ment of the chorda (ch) in the cross section through the embryo of a
Mole figured by HEAPE is a single layer of cylindrical cells ; it has
already become curved into a chordal groove, such as has been repre-
sented in fig. 79 A for Triton. Laterally it is continuous with a
mass of small cells, which is resolved into two layers at the point

Fig. 94. — Cross section through the embryonic area of a Mole which is in about the stage of the

Babbit represented in Fig. 89 B. After HEAPE.
The section passes through the chordal groove (ch) somewhat farther forward than the section

represented in Fig. 97, which has encountered a region that is to be interpreted as the

blastopore.
ait, Outer, mk, middle, ik, inner germ-layer ; ch, fundament of the chorda.

indicated by a star : (1) into the middle germ-layer (mk), composed
of several layers of small cells; and (2) into the inner germ-layer,,
which, as before, appears as a single layer of flattened cells (ik).

In a still more convincing manner VAN BENEDEN has shown, in his
investigations upon the development of Mammals, that conditions
exist in the formation of the middle germ-layer and of the body-
cavity in this class which agree with those in Amphibia. The cross
section (fig. 95) through the germ-disc of the Rabbit, taken from
his work, is especially convincing. It shows the fundament of the
chorda (ch) as a single layer of cylindrical cells, flanked on the right
and left by the middle and inner germ-layers. The middle germ-
layer consists of a parietal (mk1) and a visceral (mk2) lamella of flat
cells, the former of which is continuous with the fundament of the-
chorda, while the latter bends around at the point indicated by a
star to become continuous with the single-layered epithelium of the-

132

EMBRYOLOGY.

inner germ-layer (ik). The place where the bend occurs even pro-
trudes distinctly as a lip into the ccelenteron, as in the case of the
Amphibia. Except for these unions at the sides of the chordal

mkl mk*

ink

Fig. 95.— Cross section through the germ-disc of an embryo Rabbit, after E. VAN BENEDEN.
ak, Outer, ik, inner, mk, middle germ-layer ; ink1, parietal, mk2, visceral lamella of the middle
germ-layer; ch, chorda.

fundament, the middle germ-layer is everywhere sharply separated
by a fissure from the other two germ-layers.*

Further agreement with the conditions which the investigation
of Triton has furnished is afforded by a series of cross sections
through the primitive streak — the obliterated blastopore. In the case of
all Vertebrates, this is the only place in the whole embryonic area where
all three germ-layers, although for only a short distance, are fused with
one another, and cannot be distinguished as separate layers, whereas at
the sides of this region they are separated by distinct fissures.

ink pi' ps mk o,k

Fig. 96. — Gross section through the middle of the primitive streak of a Chick's germ-disc, which
is in the stage of development represented in Fig. 81 B. After ROLLER.

At some distance from the primitive groove is to be seen upon the left side of the figure in cross
section the marginal groove of His. Upon the right side it is as yet little developed.

ak, Outer, ik, inner, mk, middle germ-layer ; pr, primitive groove ; ps, primitive streak ;
gr, marginal groove.

Figure 96 represents a cross section through the embryonic area
of a Chick in which the primitive groove is distinctly developed,

* In the development of Mammals there has been observed at certain stages
under the fundament of the chorda a peculiar structure, the so-called chordal
canal, which is not found in the other classes of Vertebrates. I mention it
here only incidentally, because the publication of VAN BENEDEN'S investiga-
tions will doubtless furnish the desired explanation of its origin and signi-
ficance.

DEVELOPMENT OF THE TWO MIDDLE GERM-LAYERS.

13S

but in which no traces of the medullary folds are to be observed.
The outer germ-layer (ak) is composed of a single layer of tall
cylindrical cells, the inner germ-layer (ik) of a single sheet of
greatly flattened elements. In the space between the two there
penetrates at both sides of the primitive groove a mass of small cells
in many superposed layers, the middle germ-layer (mk). In the
region of the primitive groove (pr) this goes over continuously into
the outer germ-layer, the cells of which are here found in prolifera-
tion, whereas its lateral wings are separated from the outer layer by
a fissure. The lower germ-layer is drawn by ROLLER — from whose
work the accompanying figure is taken — as being everywhere a

ak

mk —

Fig. 97.— Cross section through the embryonic area of a Mole, which is in a stage corresponding

approximately with that of the Rabbit represented in Fig 89 B. After HEAPE.
The section passes through the primitive groove, somewhat behind the one represented in Fig. 94.
ak, Outer, ik, inner, mk, middle germ-layer ; u, primitive groove.

separate sheet of flattened cells. It is clear, however, from other
drawings and descriptions by DUVAL, RABL, and others, as well as
from the accounts in regard to the similar development of Reptiles,
that for a certain distance underneath the primitive groove the
middle germ-layer is as little to be distinguished as a separate
structure from the lower as it is from the upper germ-layer.

Cross sections through the primitive groove of mammalian
embryos are very instructive (fig. 97). According to HEAPE'S inves-
tigations on the Mole, the groove (u) cuts deeply into a mass of
small cells. At this place all three layers are fused together ; and
it is only laterally to this that they are separated by means of
a distinct fissure, and that each is distinguishable by its character-
istic kind of cells — the outer (ak) by its tall, the inner (ik) by its
much-flattened, and the middle (mk) by its small, more spherical
or polygonal cells.

The conditions of the germ-disc of the Rabbit found by VAN.
BENEDEN are especially distinct (fig. 98). At the deep incision

134

EMBRYOLOGY.

of the primitive groove (pr) all three germ-layers are joined to
one another for a certain distance by means of a common cells

mk* mk

ik

Fig. 98.— Cross section through the primitive groove (blastopore) of a Babbit's germ-disc, after

ED. VAN BENEDEN.
ak, Outer, ik, inner, mk, middle germ-layer ; mV, parietal, mk2, visceral lamella of the middle

germ-layer ; ul, lateral lip of the blastopore ; pr, primitive groove.

mass. At the same time one may observe, ' with tolerable dis-
tinctness, how the outer germ-layer (ak) bends around into the
parietal middle layer (mk1) at the primitive fold (ul), while the
visceral lamella (mk2) is continuous with the entoderm (ik), which
is only one cell thick. Indeed, in embryos of Eabbits and Bats, VAN
BENEDEN in some cases observed between the primitive folds, or

mk1 ul

ak

Fig 99. — Gross section through a human germ-disc, with open medullary groove, in the

vicinity of the neurenteric canal (pi-), after GRAF SPEE.
ak, Outer, ik, inner germ-layer; mk1, parietal, mk~, visceral lamella of the middle germ-layer ;

ul, lateral lip of the blastopore ; pr, primitive groove.

blastoporic lips, a structure corresponding to the yolk-plug of
Amphibia.

It is certainly of great general interest that the investigation of
an extraordinarily young human germ-disc at the hands of GRAF
SPEE has furnished a cross section (fig. 99) which is near enough

DEVELOPMENT OF THE TWO MIDDLE GERM-LAYERS. 135

like the one of the Rabbit here figured to be mistaken for it. In
the case of the human embryo, one sees a deep-cutting primitive
groove, and at the easily recognisable blastoporic lip (id) the bend-
ing over of the outer germ-layer (ak) into the parietal lamella (mk1).
The visceral lamella (mk2) is well separated from the latter for some
distance; under the primitive groove it is merged with the inner
germ-layer, the edges of the potential folds of the two sides being
fused into a mass of cells, which forms the floor of the primitive
groove,.

Finally an agreement with the development of the Amphibia is
not wanting in sections which are made through the embryonic
areas of Birds, Reptiles, and Mammals behind the primitive groove.
The middle germ-layer begins to spread itself out backward also,
not, however, as in the anterior part of the embryonic area, in
the form of paired fundaments, but rather as a single continuous
cell-mass. This outgrowth too is united to the two primary
germ-layers only in the region of the posterior end of the primi-
tive streak, being elsewhere distinctly separated from both of
them.

For the completion of the previous account, some statements
about the further growth of the middle germ-layer may now be
added, concerning which cross sections through embryos of various
ages afford evidence. The middle germ-layer spreads itself out
on all sides between the two primary germ-layers, farther and
farther from the place of its first formation — the vicinity of the
primitive groove. At first it is limited to the fundament of the
embryo itself, then it makes its way into the area pellucida, and,
finally, it is encountered in the opaque area. Everywhere and
•constantly in its extension it appears as an entirely independent
layer, at least two cells thick, which is separated from its surround-
ings by fissures. It is found to be united for a short distance with
the inner and outer germ -layers, but only at the primitive groove,
which persists for a long time, — in older embryos even, — as we havo
already learned from surface-views. Even in the stage when the
neurenteric canal traverses the primitive streak, and puts the
ccelenteric cavity (under the entoderm, fig. 100 liy] in communication
with the neural tube, we see the cellular lining of the canal and the
middle germ-layer fused, so that in this region a connection still
exists between all three germinal layers. Compare the accompany-
ing cross sections through embryos of Lacerta muralis.

After the statement of the actual conditions, the questions remain

136

EMBRYOLOGY.

to be answered : (1) What is the meaning of the primitive groove ?
(2) How is the middle germ-layer developed ?

In the interpretation of the primitive groove I place myself, as is
to be seen from what precedes, wholly on the side of those investi-
gators who, like BALFOUR, HATSCIIEK, KUPFFER, HOFFMANN^ VAN
BENEDEN, L. GERLACH, RUCKERT, and others, recognise in it a structure

equivalent to, but somewhat modi-
fied from, the blastopore of lower
Vertebrates, and who compare the
primitive folds to lateral blasto-
poric lips closely pressed together.
In my description of a previous
stage I have already designated
as blastopore the crescentic
groove of Birds (fig. 52 B s}
and the prostoma (fig. 55 u)
of Reptiles, because that is the-

Fig. 100. — Cross sections through the posterior

end of a young embryo of Lacerta muralis,

after BALFOUR.

In figure A the neurenteric canal is cut length-
wise ; in figure B only an evagination of

it, which is directed backward. Since the

sections probably have not cut the chief

axis of the embryo perpendicularly, the

middle germ-layer is fused with the wall

of the canal only on the right side in figure

A, whereas in figure B the connection is
present on both sides.

te, Neurenteric cana ; ep, outer, mep, middle,
hy, lower germ-layer.

place where the lower germ-layer
is infolded. In my opinion both
grooves are identical structures,
which, by changes in position and
form, have been so evolved, the
one from the other, that the
fissure, which was at first trans-
verse, has become converted into a.
longitudinal one. For Reptiles
KUPFFER has established this to-

a certainty. According to his figures in Emys Europsea, e.g., the
transverse depression (u) represented in fig. 101 A is converted at
a later stage into the form shown in the adjacent figure (101 B u).
For the Birds the investigations of DUVAL previously recounted
(p. 121, fig. 82) are convincing. There is also to be taken into
account the additional fact, that even as early as in the
Amphioia an exactly corresponding metamorphosis of the blasto-
pore takes place. As the accompanying cuts (fig. 101 C and D)
show, the blastopore of the Amphibian is, at its first appearance,
a transverse fissure (fig. 101 C u). Then it becomes circular, and
embraces with its lips a protruding portion of the otherwise
enclosed yolk-mass, — the yolk-plug, — becomes narrower, and is
continued forward into a longitudinal groove. Finally it appears,
(fig. 101 D u) as a deep groove' situated at the end of the-

DEVELOPMENT OF THE TWO MIDDLE GERM-LAYERS.

137

medullary furrow, with its small circular opening filled up with a
yolk-plug.

In addition there are three important considerations which may
be urged in support of the interpretation of the primitive groove as
blastopore.

First, the primitive streak, even when an open canal is wanting,
is the only place in the whole germ-disc where a connection between

•A

Fig. 101. A and B.— A portion of a younjer and of an older embryonic fundament of Emya

Europsea, with the prostoma or blastopore (w), after KUPFFER.
«l, Lip of the blastopore.
C and D.— Two eggs of Triton taeniatus seen from the blastopore, one 30 hours, the other SShours^

after artificial fertilisation.
«, Blastopore ; h, elevation between blastopore and dorsal groove ; /, semicircular furrow, which

encloses the blastoporic area ; dp, yolk-plug.

all the germ-layers is constantly present, as at the Amphibian
blastopore.

Secondly, the chief organs of the body, such as the chorda, the
neural tube, and the primitive segments, are developed in front of
the primitive streak in the case of the higher Vertebrates, just as
they arise in front of the blastopore in Amphioxus and the Amphibia.
Both blastopore and primitive streak occupy the posterior end of the
body. The so-called cephalic process of the primitive streak i&
nothing else than the first rudiment of the chorda.

Thirdly, one may still recognise in the openings — canales neu-
renterici — which have been pointed out in the primitive streak at an
earlier or later stage in its development, in the case of Birds, Reptiles,
and Mammals, an indication that an open communication has

138 EMBRYOLOGY.

existed here from the beginning between the inner and the outer
germ-layers ; further, that this communication has disappeared
through the fusion of the blast oporic lips, but that it can be in part
reestablished in consequence of more favorable processes of growth.
At the same time the neurenteric canal, in cases where it reappears
in the primitive streak, effects a very characteristic union between
the posterior ends of the neural and intestinal tubes, in exactly the
same manner in which the blastopore of Amphioxus, the Amphibia,
and the Selachii does (compare fig. 80 with fig. 88 n.e).

In the interpretation of the primitive groove as blastopore I am
compelled to oppose a somewhat different view. Certain investi-
gators (BALFOUR, RAUBER, and others) recognise in the primitive
groove and the crescentic groove of meroblastic eggs only a small
part of the blastopore ; they interpret as the major part of it the
region which is encircled by the whole rim of the germ-disc and is
occupied by the yolk-mass, and to which they give the name yolk-
blastopore.* According to their conception, as also according to
the original assumption of HAECKEL. the two-layered germ-disc is a
flattened-out gastrula, — its blastoporic rim lying upon the yolk-
sphere, — which gradually grows around the yolk, and finally takes
the latter wholly inside itself, just as if it were a ball of food. The
primitive groove is a small detached part of the blastopore, which is
connected with the development of the middle germ-layer. The two
parts become completely separated from each other, and are closed
at different times, each for itself, the yolk-blastopore often late, at
the pole of the yolk-sac which is opposite to the embryo.

Such an assumption of a double blastopore appears to me to be
untenable. / propose that only that place of the germ be designated as
blastopore at ivhich, as in the gastrulation of Ampliioxus and the
Amphibia, there actually occurs an invagination of cells, by means of
which the cleavage-cavity is obliterated. Such a process takes place
in the Selachii only at the crescentic hinder part of the margin of
the germ-disc, in the Reptiles and Birds at the small place designated
as crescentic groove. It is also from this place alone that subse-
quently the development of the middle germ-layer proceeds.

The anterior margin of the germ-disc in Selachians, and, after the
conversion of the crescentic groove into the primitive groove, the whole

* RAUBER has suggested for the various regions which he assumes for the
blastopore the designations prostoma sulcatum lonyitud'male (primitive groove),
prostoma sulcatum falciforme (crescentic groove), and prostoma marginale
(yolk-blastopore).

DEVELOPMENT OF THE TWO MIDDLE GERM-LAYERS.

139

>nargin of the germ-disc in Birds and Reptiles, have an entirely dif-
ferent signification. This margin exhibits a very different relationship
from that of the primitive streak or blastopore ; it is a peculiarity of
meroblastic eggs, which is most intimately associated with the origin
of partial cleavage. It indicates the place at which the segmented
portion of the germ meets the unsegmented portion — the place at
which there lie in the yolk free nuclei, by means of which a supple-
mentary cleavage is kept up until late stages in the process of
development, until, in fact, the time when the two primary germ-
layers have been formed by means of the invagination which
occurs at the blastopore. At the expense of the cell-material, which
is constantly being augmented by supplementary cleavage, the germ-
layers increase in extent at their place of transition into the yolk,
;and thus gradually grow over the unsegmented part. Whereas at
the blastopore an invagination of cells already present takes place, there
ensues at the margin of the germ-disc a formation of new cells, and
thereby an increase of the marginal part and an overgrowth of the
yolk. I therefore propose for it the name circumcrescence-margin
of the yolk-sphere. There can be no such thing as a separate opening
•or a yolk-blastopore, because the yolk is an organic part of the germ,

and is in continuity
with the segmented
part of it by means
of the layer which
contains the yolk-
nuclei.

If we would insti-
tute a comparison be-
tween animals with
meroblastic eggs and
the Amphi bia at a stage
when gastrulation is
not yet completed, then
the blastopore of the
Amphibia, which is
indicated by the letter
u in the accompanying
section through the

ga'strula of a Triton (fig. 102), corresponds to the prostoma of Rep-
tiles, and to the crescentic and primitive grooves of Birds ; the still
•exposed mass of yolk-cells corresponds to the yolk-material which is

Tig. 102.— Longitudinal section through a gastrulaof Triton.
ak, Outer, ik, inner germ-layer ;fh, cleavage-cavity ; ud, ccel-

enteron ; u, blastopore ; dz, yolk-cells ; dt, dorsal, vl,

ventral lip of the ccelenteron.

140 EMBRYOLOGY.

not yet overgrown by germ-layers ; the place marked by a star, at
which in the Amphibia the transition from the small-celled layer
to the mass of yolk-cells occurs, or the marginal zone of GOETTE, is
comparable to the margin of circumcrescence in meroblastic eggs.

In the second place, the question arises : How is the middle germ-
layer of Vertebrates developed ? The answer is : By a process of
folding similar to that in the case of Amphioxus lanceolatus. This
answer is substantiated by the fact that the individual processes in
the development of the middle germ-layer may be correlated with
corresponding processes in Amphioxus.

In view of the fundamental importance of the matter, I formulate
in a synoptic and precise manner in six paragraphs the points in
reference to which it has been possible to establish an agreement in
all Vertebrates.

1. Before the chorda is formed, the germ in all Vertebrates is
composed of two layers in the region of a median streak which lies
in front of the blastopore and primitive groove. It is here composed
of the medullary plate and the fundament of the chorda, which then
shares in bounding the intestinal cavity.

2. At both sides of this median streak the germ is three-layered^
if we regard the middle germ-layer as a single one ; it is four-layered,
if we allow that the latter consists of a parietal and a visceral cell-
layer, which are originally pressed firmly together, and only later
actually separated by the appearance of the body-cavity.

3. In no Vertebrate do the middle germ-layers arise by fission,
either from the outer or the inner germ-layers, because they are
everywhere, except in a very limited region of the germ, sharply
separated from both by means of a fissure.

4. A connection of the middle germ-layers with the neighbouring
cell-layers takes place only : (a) at the blastopore or primitive groove,
where all four (or three) germ-layers are joined together, and (b) at
both sides of the fundament of the chorda.

5. One observes the first fundament of the middle germ-layers at
the region of the germ just mentioned, and sees it spread itself out
from here — i.e., from the periphery of the blastopore or the primitive
groove, and from both sides of the fundament of the chorda
— forward, backward, and ventrad or laterad. In front of the
blastopore it appears in the form of paired fundaments separated by
the fundament of the chorda; behind the blastopore, on the contrary,
as a continuous structure.

6. While the chorda is being developed, the two paired fundaments-

DEVELOPMENT OF THE TWO MIDDLE GERM-LAYERS. 141

of the middle germ-layers detach themselves from the adjacent cell-
layers at the sides where their ingrowth took place, and at the same
time the halves of the permanent entoderm grow together, whereby
the dorsal closure of the intestine is effected.

In view of these facts there is only one explanation at which we
can arrive. If it is certain that the middle germ-layers do not
arise by a fission in loco from either of the primary germ-layers,
then their gradual spreading out from a definite region of the germ
can result only from an ingrowth of cells, which occurs from those
places where a connection with other cell-layers has been demon-
strated. The middle germ-layers draw the principal material for
their growth from cells which, at the blastopore or at the primitive
groove, migrate between the two primary germ-layers.

But this immigration of cells may be interpreted as a process of
infolding of the primary germ-layers, as in the case of Amphioxus.
In the method of the infolding there exists, it is true, one very
striking and apparently important difference between Amphioxus
and the remaining Vertebrates. In Amphioxus the middle germ-j
layer arises as a hollow sac, by means of the folding of the inner
germ-layer — in the remaining Vertebrates as a solid mass of cells.
This undeniable difference is, however, easily explained in the
following manner : In the solid fundaments of the middle germ-
layer a cavity is wanting, because the cellular walls of the sac are
from the beginning firmly pressed together, in consequence of the
yolk-mass which fills the ccelenteron. In addition to other striking
agreements with the conditions in Amphioxus lanceolatus, there are
three pointsof viewwhich in particular commend this interpretation : —

(1) In all vertebrated animals there early arises in the middle
germ-layer a fissure, which is surrounded by cells, often cubical or
cylindrical, having an epithelial arrangement. The parietal and
visceral layers then take the form of epithelial lamellae, as is to be
seen in an especially striking manner in the case of the Selachii at
a very early stage of development. (2) From these epithelial layers
there arise in the adult genuine epithelial membranes, like the
ciliated peritoneal epithelium of many Vertebrates, and, in addition,
glands that in many respects resemble the glands derived from
epithelial membranes [of the other germ-layers] (kidney, testis,
ovary). (3) The objection that the middle germ -layer of Verte-
brates arises as a single cell-mass, and therefore cannot be equi-
valent to two layers of epithelium, loses its weight with every one
who knows the numerous analogous phenomena of development

142 EMBRYOLOGY.

occurring elsewhere, in which organs that should be hollow are at
first developed as solid masses of cells. We shall hereafter cite as
such the solid fundament of the neural tube in Bony Fishes, many
sensory organs and the most of the glandular sacs, which latter
arise as solid buds of epithelial lamellae, and only later, when they
become functionally active, acquire a cavity by the separation of
their cells.

SUMMARY.
A . The Uastula.

1. Out of the mass of cleavage-cells (morula) there is developed
in all Vertebrates a sac-like germ (blastula) with cleavage-cavity.

2. There are four different kinds of blastulse in Vertebrates.,,
according to the amount and distribution of yolk.

(a) In Amphioxus the cleavage-cavity "is very large, and its

wall consists of a single layer of cylindrical cells of
nearly uniform size.

(b) In Cyclostomes and Amphibia the cleavage-cavity is small :

one half of the wall of the blastula is thin, and composed
of one or several layers of small cells ; the other half is
considerably thickened, and formed of large yolk-cells
arranged in many superposed layers.

(c) In Fishes, Reptiles, and Birds (meroblastic eggs) the

cleavage-cavity is small and fissure-like or wanting.
Only its roof or dorsal wall consists of cells (germ-disc) ;
its floor or ventral wall, on the contrary, consists of the
yolk-mass which has not been divided into cells, but
which contains yolk-nuclei in the vicinity of the margin
of the germ-disc.

(d) In Mammals the cleavage-cavity is very spacious, and filled

with an albuminous fluid ; its wall is composed of a single
layer of greatly flattened hexagonal cells, with the
exception of a small thickened place, where larger cells
in several superposed layers cause an elevation which
projects into the cavity.

B. The cup-shaped larva or gastrula with two germ-layers.

1. There is formed out of the blastula, by the imagination of
a portion of its surface, a two-layered form, the beaker-larva or
gastrula.

2. The two layers of the double beaker are the outer and the

DEVELOPMENT OF THE TWO MIDDLE GERM-LAYERS. 143

inner germ-layer (ectoblast, entoblast) ; th*e fissure separating the
two layers is the obliterated cleavage-cavity; the cavity resulting
from the invagination is the coelenteron, its external opening the
primitive mouth (blastopore, prostoma, crescentic groove, primitive
groove).

3. The four kinds of gastrulae correspond to the four kinds of
blastulse.

(a) In Amphioxus the coelenteron is wide, and each germ-

layer is made up of a single sheet of cylindrical cells.

(b) In Cyclostomes and Amphibia the mass of yolk-cells is

accumulated on the ventral wall of the ccelenteron in
the inner germ layer, and causes a protuberance, by
means of which the ccelenteron is reduced to a fissure.

(c) In Fishes, Reptiles, and Birds the process of invagination

remains confined to the germ-disc, since the unsegmented
yolk, on account of its considerable volume, cannot be
mads to share in the invagination. The germ-disc
becomes two-layered by means of an ingrowth of cells-
at the crescentic groove (blastopore). The yolk acquires-
a cellular boundary very slowly and at a late period ;
it is overgrown by the margin of the germ-disc,
when the supplementary cleavage (yolk-nuclei) takes-
place.

The outer germ-layer spreads itself out and envelops
the yolk most rapidly ; then follows the inner, and finally
the middle layer.

(d) In Mammals the inner germ-layer is developed from the

thickened region of the blastula, probably by means of
an invagination, because at a later stage an orifice of
invagination, comparable with the primitive groove of
Birds, or a blastopore, can be demonstrated. At the
beginning of its development the inner germ-layer
terminates below in a free margin, so that the coelen-
teron is for a time closed in on the ventral side by the
outer germ-layer only, a peculiarity which is comparable
with the conditions in Reptiles and Birds, if we conceive
the yolk-material to have disappeared in this instance
before it is completely surrounded by the inner germ-
layer.

4. In Vertebrates the gastrula presents a sharply expressed
trilateral symmetry, so that one can easil distinguish the future-

144 EMBRYOLOGY.

•head- and tail-ends, the future dorsal and ventral sides of the body.
The blastopore (crescentic groove, primitive groove) marks the
posterior end. The ventral side is characterised by being the place
where the segmented or unsegmented yolk-material comes to He.

C. The embryo with four germ-layers and a body-cavity.

1. In all Vertebrates there are formed from the roof of the
ccelenteron two lateral evaginations of the inner germ-layer, by
means of which the cffilenteron is divided into a medial cavity, the
secondary intestine, and two lateral cavities, the two body-sacs.

2. The primary inner germ-layer is resolved in consequence of
this process of evagination into three parts : —

. First, the epithelial lining of the intestinal tube (secondary

inner germ-layer — Darmdriisenblatt).
Secondly, the epithelial lining of the body-cavity, or the middle

germ-layer, in which a parietal and a visceral layer are

distinguishable.
Thirdly, the chorda, which takes its origin from the portion of

the primary inner germ-layer which lies between the

lateral evaginations from the roof of the ccelenteron.

3. Two modifications of the process of evagination can be recog-
nised in the case of Vertebrates.

(a) In Amphioxus the evaginations are small, numerous, and

segmentally arranged; provided from the first with a
cavity ; and, beginning in the f undus of the cffilenteron,
developed toward the blastopore.

(b) In the remaining Vertebrates, instead of hollow sacs, there

grow out from the inner germ-layer two solid masses of
cells : —

(1) In the vicinity of the blastopore (primitive groove,

peristomal mesoblast).

(2) From here forward along the roof of the ccelenteron,

at a slight distance from the median plane, at both
sides of the fundament of the chorda (gastral
mesoblast).

The paired fundaments spread themselves out from
their place of origin between the two primary germ-
layers farther forward and ventralward.

4. The three organs derived from the primary inner germ-layer
(middle germ-layer, fundament of the chorda, secondary inner germ-
layer) are separated from one another by constrictions.

HISTORY OF THE GERM-LAYER THEORY. 145

First, the body-sacs are detached from the fundament of the
chorda and the entoblast, whereupon the edges of the
parietal and visceral lamellae, thus set free, fuse with
each other.

Secondly, the fundament of the chorda is bent into a chordal
groove, and this is converted into a solid rod, which is
completely isolated from the entoblast.

Thirdly, the entoblast closes together into a tube with a dorsal
raphe.

5. The development of the three fundaments, as also that of
various other organs, begins at the head-end of the embryo, and
advances from here toward the blastopore, where for a long time a
continual formation of new parts and an increase in the longitudinal
growth of the body take place.

6. During the development of the middle germ-layer, the blasto-
pore of the Amphibians, Fishes, Reptiles, Birds, and Mammals has
been metamorphosed into a groove occupying the longitudinal axis
of the embryo (primitive groove of the higher Vertebrates).

7. The blastopore and the primitive groove in later stages of
development undergo degeneration, and are not converted into any
organ of the adult. (For the details of this, see Part II.)

8. Before their disappearance the blastopore and primitive groove
are surrounded by the medullary folds and taken into the terminal
part of the neural tube, whereby a direct communication between
neural tube and intestinal tube — the neurenteric canal — is effected.
The two organs, which communicate with each other for a long time,
are later separated by its closure.

CHAPTER VII.
HISTORY OF THE GERM-LAYER THEORY.

THE fundamental facts of the sheet-like structure of the vertebrate
body, which have been treated of in the two preceding chapters, are
epitomised as the doctrine of the germ-layers, or the germ-layer
theory. Since this theory is of the most far-reaching significance
for the comprehension of the evolution of form in animals, and can
be placed side by side with the cell-theory as coequal with the latter,
I devote a separate chapter to its history.

10

146 EMBRYOLOGY.

The very earliest establishment of the germ-layer theory is asso-
ciated with the most celebrated names in the field of embryology :
CASPAR FRIEDRICH WOLFF, PANDER, and CARL ERNST VON BAER.

CASPAR FRIEDRICH WOLFF, the discoverer of the metamorphosis of
plants, who, even before GOETTE, had clearly and distinctly stated
that the various organs of the plant, as, for example, the separate
parts of the flower, have been developed by various modifications of
leaf-like fundaments, also established the metamorphosis of animals,,
for which he endeavoured to found a similar law of development.

He showed in his important work on the formation of the-
intestinal canal of the Chick, that it originally appeared in the egg
as a leaf -like structure, and that this afterwards became folded into*
a groove, and finally converted into a tube.

He conjectured that the remaining systems of organs might arise
in a similar way, and appended to the account of the development of
the intestinal canal the significant assertion : " It appears as though
at different periods, and many times in succession, various systems
might become formed after one and the same type, and as if they
might be on that account similar to one another, even though they
are in reality different. The system which is first produced, which
is first to take on a specific form, is the nervous system. When
this is concluded, then the fleshy mass, which really makes up the
embryo, is formed after the same type; then appears a third, the
vascular system, which certainly ... is not so unlike the first ones
that the form described as common to all systems could not be easily
recognised in it. After this follows the fourth, the intestinal canal,
which, again, is formed after the same type, and appears as a com-
pleted independent whole, similar to the first three."

WOLFF'S article, written in Latin, made no impression on his
contemporaries; it had to be rescued from oblivion by MECKEL,
who published a German translation of it in 1812. It was probably
by means of this translation that the attention of PANDER w7as
directed to WOLFF. PANDER, under the stimulus and direction of
his celebrated teacher, DOLLINGER, further developed the doctrine,
the germ of which was contained in WOLFF'S paper.

In his publication, " Beitrage zur Entwicklung des Hiihnchens
im Ei," issued in the year 1817, PANDER distinguished in the blasto-
derm, as early as the twelfth hour of incubation, two thin separable
lamellae as the serous layer and the mucous layer, and main-
tained that subsequently a third, the vascular layer, was developed
between them. " Whatever noteworthy may subsequently occur,'

HISTORY OF THE GERM-LAYER THEORY. 147

he remarks, "it is never to be regarded as anything else than a
metamorphosis of the blastoderm and its layers, endowed as they are
with an inexhaustible store of formative energy." A few years
later the germ-layer theory reached at the hands of CARL ERNST VON
BAER a preliminary completion, which served for some time. VON
BAER, likewise a pupil of DOLLINGER, had observed in Wurzburg the
beginning of the investigations of his young friend, PANDER. In
laborious studies pursued for many years, BAER followed with
wonderful accuracy the origin of the germ-layers and their meta-
morphosis into the individual organs of the adult body, principally in
the case of the Chick, but also in the case of some other Vertebrates,
and recorded his investigations in his classical work, " Ueber Entwick-
lungsgeschichte der Thiere, Beobachtung und Reflexion," which is
unsurpassable both in observations and in its general standpoints.

BAER differs from PANDER in maintaining that each of the
two primary germ-layers, which he distinguishes as animal and
vegetative, subsequently divides into two sheets. The animal
germ-layer divides itself into dermal lamella and sarcous lamella
(Hautschicht, Fleischschicht), the vegetative into mucous lamella,
and vascular lamella, so that now four secondary germ-layers have
arisen. The individual organs are developed out of the germ-layers
by morphological and histological differentiation.

A further advance beyond that of BAER could not be attained
until, with the establishment of the cell-theory, entirely new points
of view were introduced into morphology and, with improved con-
struction in microscopes, methods of investigation were refined.
It is chiefly REMAK and KOLLIKER who have promoted the germ-
layer theory in this direction.

REMAK took in hand successfully in his noted investigations on
the development of Vertebrates the very important question, how
the originally similar cells of the germ-layers are related to the
tissues of the completed organs. He showed that out of the lowest
of the four germ-layers there proceed only the epithelial and glan-
dular cells of the intestinal tube and its appendages, that from the
uppermost layer the epithelial cells of the epidermis, the sensory
organs, and the nervous tissue arise, whereas the two middle layers
furnish the mechanically sustentative substances and the blood, tho
muscular tissue, and the urinary and sexual organs.

In regard to the manner in which the four secondary germ-layers
arise, REMAK differs from BAER. Out of the two primary germ*
layers he first makes a third one, the middle germ-layer, arise, and

148 EMBRYOLOGY.

indeed he derives it exclusively from the lower germ-layer by a
process of fission. He designates the three layers as the upper or
sensorial, the middle or motor-germinative, and the lower or trophic.
The four secondary germ-layers of VON BAER come into existence
subsequently by a repetition of the fission, whereby the middle germ-
layer is split, at least in its lateral portions (lateral plates), into the
dermo-fibrous layer and the intestino-fibrous layer (Hautfaser- und
Darmfaserblatt), between which arise the thoracic and body-cavities.

REMAK in his account approximates the true state of affairs, as
detailed in the preceding chapters, more nearly than VON BAER ;
however, both made the same mistake of interpreting the formation
of the germ-layers as always a process of disassociation or fission.
That is also the rock on which were wrecked the researches of numer-
ous other investigators, who in the decennary succeeding REMAK
dealt with the important question of the origin of the germ-layers.
It was difficult to decide this question for the higher Vertebrates,
which have been most frequently investigated ; so that very contra-
dictory opinions were expressed relative to the development of the
middle layer — whether it was exclusively from the lower (REMAK),
exclusively from the upper, or from both layers.

This question could be clearly understood only upon the establish-
ment of new general standpoints. These could be acquired only by
the comparative method, and by the study of lower Vertebrates and
the Invertebrates.

Two fundamental processes needed to be better comprehended: —

(1) How are the two primary germ-layers developed ?

(2) How are the two middle germ-layers developed ?

By means of the comparative developmental method, one question
has been brought nearer to a solution in the gastrcea-theory, the other
in the codom-theory.

In the study of the first problem, which was the earlier solved,
HUXLEY and KOWALEVSKY, HAECKEL and RAY LANKESTER, have
shown especial merit. They demonstrated, partly through anato-
mical, partly through embryological studies, that, with the exception
of the Protozoa, the body of every invertebrated animal is constructed
of layers, which may be compared with the primary germ-layers of
Vertebrates.

The highly gifted English zoologist HUXLEY distinguished as early
as the year 1849 two membranes in the Medusae, an outer and an
inner layer, out of which alone their bodies are constructed ; and at
the same time expressed the happy idea that physiologically they

HISTORY OF THE GERM-LAYER THEORY. 149

were equivalent to the serous and the mucous layers of BAER.
Soon after this (1853) ALLMAN introduced for the layers of the
Coelenterates the names, which are now so much employed, ectoderm
and entoderm ; subsequently use was also made of these for designat-
ing the embryonic layers.

The germ-layer theory was promoted to a still greater degree by
the Russian zoologist KOWALEVSKY, who made us acquainted in
numerous excellent detailed investigations with a profusion of
important facts concerning the embryology of Worms, Coelenterates,
Molluscs, Brachiopods, Tunicates, and Arthropods. He produced
evidence that in all the Invertebrates which he investigated two
germ-layers are formed at the beginning of development, and that
in almost all cases, when the process of cleavage is at an end, a
cellular sac arises, and that this, by the infolding of a part of the
wall, becomes converted into a double cup, the cavity of which,
enclosed by two germ-layers, communicates with the outside by
means of an opening. He succeeded in establishing the existence
of this very important cup-shaped larva (gastrula) in many branches
of the animal kingdom.

In this connection should be mentioned the services of several
other embryologists, who at a still earlier period had observed in
isolated cases the cup-shaped larva and its origin by means of
invagination. RUSCONI and REMAK had described the cup-shaped
larva of Amphibia, GEGENBAUR that of the Sagittse or arrow-worms,
MAX SCHULTZE that of Petromyzon.

Whereas KOWALEVSKY by his series of investigations enriched our
knowledge of material facts, HAECKEL first sought to utilise the
same for a general theory, since by the process of morphological
comparison he brought into association hitherto disconnected obser-
vations. Starting from the development and the anatomy of the
Sponges, he compared the layer-like structure of the embryos of all
animals with the layer-like structure of the Coelenterates, and pro-
duced as the fruit of this study the celebrated gastrcea-theory, which,
attacked on many sides at the time of its publication, has now
found in its essential substance general acceptance, and has given
the impetus to numerous investigations. HAECKEL showed that in
the development of the various classes of animals from the Sponges up
to Man a single form of the germ makes its appearance, the gastrula,
which consists of two cell- layers, and that the two cell-layers of
the various embryonic forms are comparable to one another or
homologous. The gastrula in its simplest condition presents, as

150 EMBRYOLOGY.

he endeavored to establish, the form of a double cup with a
ccelenteric cavity and a primitive mouth, but may be greatly
altered, as in the most of the Vertebrates, by the deposition of
yolk-material in the egg, so that the original fundamental form is
scarcely recognisable. Consequently he distinguished, according to
the kind of modification, - different forms of the gastrula, as bell-
shaped, cap-shaped, disc-shaped, and vesicular gastrulce. He made
the various forms arise by a process of invagination from a still
simpler fundamental form, the blastida, which is the final result of
the cleavage process.*

HAECKEL published his excellent gastrsea-thedry in two articles in
iheJenaischeZeitschri/t: (1) " Die Gastrseatheorie, die phylogenetische
Classification des Thierreichs, und die Homologie der Keimblatter,"
(2) " Nachtrage zur Gastrseatheorie."

At the same time with HAECKEL, RAY LANKESTER in England was
led to a similar theory, which he had worked out in a paper full of
new ideas : " On the Primitive Cell-layers of the Embryo as the Basis
of Genealogical Classification of Animals."

Both HAECKEL and LANKESTER failed to point out how the forma-
tion of the gastrula takes place in some of the divisions of Verte-
brates— in Fishes, Reptiles, Birds, and Mammals. Essential service
in the establishment and explanation of numerous questions of detail,
which remained unsettled in the gastrsea-theory, has been rendered
by BALFOUR, VAN BENEDEN, GERLACH, GOETTE, HOFFMANN, KOLLER,
RAUBER, RUCKERT, SELENKA, DUVAL, and others.

Thus through HAECKEL'S gastrsea-theory the following points were
gradually cleared up : (1) The two primary germ-layers, which form
the foundation for the development of both Invertebrates and

* It should be here stated that even OKEN and C. ERNST v. BAER had
set forth, although in a very indefinite manner, the importance of the vesicular
form for the development of the animal body. OKEN was an opponent of the
germ-layer theory of WOLFF. In a criticism of PANDER'S investigations he
exclaimed with emphasis and a certain justice : " The facts cannot be so. The
body arises out of vesicles and never out of layers," and he added the very
pertinent remark : " It appears to me as if it had been entirely forgotten that
the yolk and the yolk-membrane, which is a vesicle, belong essentially to tlie
body of the germ ; that the embryo does not swim upon it like a fish in the
water, nor lie upon it like a funnel on a cask."

In a similar manner BAER remarks, but without further expounding the
relation to the germ-layers : " Since the germ is the undeveloped animal itself,
one can affirm, not without reason, that the simple vesicular form is the
common fundamental form, out of which all animals are developed, not only
ideally, but historically."

HISTORY OF THE GERM-LAYER THEORY. 151

Vertebrates, arise, not through disassociation or fission, but through
infolding of an originally simple cell-layer.* (2) These are com-
parable with one another or homologous, because they are developed
according to the same process, and because the two fundamental
organs of the body, the layer which limits the body externally
{the ectoderm) and the layer which lines the digestive cavity (the
^nfcoderm), arise from them. (3) The intestinal canal of all animals
arises by invagination.

In the question as to the development of the middle germ-layer
HAECKEL remained at the traditional standpoint, and inclined most
to C. E. VON BAER'S view that the parietal lamella arose by fission
from the outer primary layer, and the visceral lamella from the
inner germ-layer. Most embryologists, who worked on the develop-
ment of Vertebrates, entertained, on the contrary, REMAK'S view,
-and made the whole middle germ-layer arise from the inner
by fission.

They regarded the body-cavity as a fissure in the middle germ-
layer, and compared it with other lymphatic spaces, such as occur in
the connective tissue at various places in the body.

The correction of this view was undertaken by various persons
in the same manner as in the case of the primary germ-layers. By
detailed study of the formation of the germ-layers in the Chick
and Mammals, KOLLIKER found that the middle germ-layer did not
simply split itself off from the inner, but that it arose from a limited
region of the blastoderm, namely, from the primitive groove, where
the two primary germ -layers are continuous. He maintained that
from this region it grew out between the two primary germ-layers
as a solid cell-mass, and that subsequently the body-cavity appeared
in it by means of its fission into two layers. This was an essential
advance in the representation of the actual state of affairs.

But a deeper insight into these embryonic processes in Vertebrates
was first acquired in this case also through the study of Invertebrates,
especially through the important discoveries of METSCHNIKOFF and
KOWALEVSKY concerning the formation of the body-cavity in Echino-
derms, Balanoglossus, Chsetognathi, Brachiopods, and Amphioxus.
The former found that in the larvae of Echinoderms and in Tornaria,
the larva of Balanoglossus, the walls of the body-cavity are formed
from evaginations of the intestinal canal. But a still greater sensation

* It is still affirmed by several authors for certain Invertebrates that the
inner germ-layer develops, not by infolding, but by a splitting off or delamina-
tion from the outer germ-layer.

152 EMBRYOLOGY.

was created when KOWALEVSKY in 1871 published his " Embryology of
Sagitta," and showed how the crelenteron of the gastrula was divided
by two folds into three cavities, — into the secondary intestinal cavity
and into the body-cavities : this discovery was afterwards fully con-
firmed by the investigations of BUTSCHLI and the author. After a
short interval, KOWALEVSKY'S account of the development of Sagitta
was followed by his work on Brachiopods, in which he again enriched
science with the new and important fact, that in this class also the
body- cavity was formed in the same way as in the case of the
Chsetognaths. This was followed by his fundamental work on
Amphioxus.

Through the important discoveries made on Invertebrates, HUXLEY,
LANKESTER, BALFOUR, my brother and I were stimulated to
theoretical speculations concerning the origin of the body-cavity
and the middle germ -layer in the animal kingdom.

HUXLEY distinguished three kinds of body-cavity according to their
origin : (1) an enter occel, which arises as in Sagitta, etc., from evagi-
nations of the ccelenteron ; (2) a sckizoccel, which is developed by
means of fission in k mesodermal connective substance lying between
the integument and the intestine ; (3) an epicoel, which is formed by
an invagination of the surface of the body like the perithoracic
space of the Tunicates. The last kind, HUXLEY thinks, may perhaps
correspond to the pleuroperitoneal cavities of the Vertebrates.

LANKESTER makes HUXLEY'S paper his starting-point. He gives
preference to the hypothesis of the common origin of the body-
cavity in all animals until decisive proof of diverse origins is
produced ; and, in fact, he makes the schizocrel arise out of the
enteroccel in the following manner. Evaginations of the ccelenteron
have lost their lumen, and therefore are begun as solid cell-masses,
which only subsequently acquire a cavity. While LANKESTER in
this, as well as in a second publication, overlooks existing differences
in his effort to reduce everything to a single scheme, BALFOUR in
various essays takes more fully into account in his speculations the
actual condition of affairs ; he also limits himself chiefly to the
explanation of the conditions in "Vertebrates. In investigating the
development of Selachians, he made the important discovery that
the middle germ-layer arises from the lateral margins of the primi-
tive mouth, and at first consists of two separate masses of cells,
which grow out forwards and laterally into the space between the
two primary germ-layers. Since in each cell-mass a separate cavity
soon makes its appearance, he designates the body-cavity as from the

HISTORY OF THE GERM-LAYER THEORY. 153

beginning a paired structure, and compares it to the body-sacs
which are developed in Invertebrates by evagination from the
cceleiiteron. BALFOUR justly alleges that the originally solid con-
dition of the two fundaments can have no weight against his inter-
pretation, since in numerous instances organs which ought properly
to contain cavities are developed solid, and subsequently become
hollow, as, for example, in many Echinoderms one encounters solid
cell-masses in place of hollow evaginations of the ccelenteron.

Led by theoretical considerations similar to those of the English
morphologists, my brother and I, by a thorough comparison of de-
velopmental and anatomical conditions, and with due regard to the
morphological and histological structure of organisms, then en-
deavored to bring to a solution this question of the day, — the question
of the development of the body-cavity and the middle germ-layers, —
by systematic investigations (published in " Studien zur Blatter-
theorie "), which extended over Invertebrates and Vertebrates.
The results of these series of investigations were published in two
articles : (1) in the " Ccelomtheorie, Versuch einer Erklarung des
mittleren Keimblattes," and (2) in the " Entwicklung des mittleren
Keimblattes der Wirbelthiere."

In the first paper, in order to prepare the way, we were compelled to
give the term germ-layer a more precise definition. We designated
as such a layer of embryonic cells which are arranged like an
epithelium and serve for the limitation of the surfaces of the body.
At the close of segmentation there is only one germ-layer present ;
namely, the epithelium of the Uastula. The remaining germ-layers
arise from it by the processes of invagination and evagination. The
inner germ-layer is formed by means of gastrulation, the two middle
germ-layers by the formation of the body -cavities, in that two body -sacs
are evaginated from the codenteron, and grow out between and separate
the two primary germ-layers. There are, in the first place, animals
which are formed of two germ-layers, and possess in their bodies only
one cavity, a ccelenteron, produced by invagination (Ccelenterata
and Pseudoccelia). and, secondly, animals with four germ-layers, a
secondary intestine, and a body-cavity derived from the ccelenteron —
an enteroccel. To the two-layered animals belong the Ccelenterates
and the Pseudoccels, but all four-layered animals are Enteroecels.

From this standpoint we endeavored to prove that hitherto there
had been confused under the conception " middle germ-layer " two
things which are genetically, morphologically, and histologically
entirely different.

154 EMBRYOLOGY.

Besides the cell-layers which arose by invagination there had been
•assigned to the middle germ-layer cells which detach themselves
individually from the primary germ-layers, and give rise between
the epithelial layers of the body to the sustentative substances, and
also to the blood, when such exists. Embryonic cells of that kind,
which are formed by emigration into the space surrounded by
the germ-layers, we named the mesenchymatic germ, and the tissue
produced from them mesenchyme. This occurs as well in two-
layered as in four-layered animals. In our opinion a sharp distinction
must be made between the formation of germ-layers, which is
correlated with the morphological differentiation of the body, and
the formation of mesenchyme, — which will especially engage our
attention in one of the next chapters, — if clearness and a uniform
principle are to be introduced into the whole germ-layer theory.

In the second article it was our aim to show that in the Vertebrates
a middle germ-layer is developed by infolding. For that purpose
the development of Amphibia, Fishes, Reptiles, Birds, and Mammals
was compared with the development of Amphioxus, and thus was
acquired the foundation upon which is based the account of the
development of the middle germ-layer given in the preceding chapter.

After the publication of these two papers, there appeared numerous
articles by VAN BENEDEN, DUVAL, HEAPE, HOFFMANN, KOLLIKER,
KOLLMANN, RABL, RUCKERT, STRAHL, WALDEYER, and others, through
which valuable facts concerning the development of the middle germ-
layer in the different classes of Vertebrates have been made known.
In some of these the chief points of view of the ccelom-theory were in
general recognised as correct, attempts were made to modify details,
but especially was the question of the formation of the mesenchyme
of the Vertebrates actively discussed.

The mechanical principle oj the process oj development, by means of
which the germ-layers are formed, and out of these the separate organs,
is appreciated in its full significance by only a few, and in text-books
particularly has not been adequately presented.

Among the founders of the germ-layer theory, PANDER besfc com-
prehended this principle. " The blastoderm," he says in one place,
" forms, exclusively through the simple process of folding, the body
and the viscera of the animal. A delicate thread attaches itself as
the spinal cord to it, and scarcely has this taken place, when the
blastoderm sends the first folds, which themselves necessarily designate
the position of the spinal cord, as an envelope over the exquisite fila-

HISTORY OF THE GERM-LAYER THEORY. 155

merit, thus forming the first foundation of the body. Hereupon it
produces new folds, which, in contradistinction to the first, give shape
to the abdominal and thoracic cavities, together with their contents.
And for the third time it sends out folds to envelop in suitable
membranes the foetus, which is formed out of it and by means of it.
Therefore it need not surprise any one if, in the course of our
narration, so much is said about folds and envelopes." And in
order to avoid misunderstandings he adds in another place the
important statement that "wherever anything is said about the
folds of the skin, one is not to imagine a lifeless membrane, whose
mechanically produced folds would necessarily spread themselves over
the whole surface, without allowing themselves to be limited to a
definite space. The folds which cause the metamorphosis of the skin
are rather themselves of organic origin, and are produced at the
appropriate place, either through increase in the size of the spherules
already present there, or through an accession of new spherules,
without the remaining part of the blastoderm being thereby altered."

PANDER'S successors have expressed themselves concerning the
mechanism of foldings much less clearly ; the most of them, indeed,
not at all. The whole doctrine was in fact condemned by RUDOLPH
WAGNER as positively erroneous. " It will occur to no one," he says
in his "Lehrbuch der Physiologie," "to imagine the three germ-
layers to be like the leaves of a book. No one will entertain the
mechanical conception that the embryo arose by a folding process of
these three layers."

After PANDER. LOTZE was the next to be occupied with the
•" Mechanik der Gestaltbildung," as has been pointed out by EAUBER
in a meritorious history of this topic. He designates "unequal
growth " or " unequal vegetation " as the cause of the changes of
place, which in part only appear to be shif tings, out-pocketings,
imaginations, or extensions, but in part are actually such, being
brought about in this way by mechanical traction and pressure.

In very recent times His has prosecuted the study of embryology
from the mechanico-physiological standpoint more intensely than all
his predecessors, and has also particularly emphasised the signifi-
cance of the process of folding for the formation of the body. The
two principal writings of His in this connection are: "Unter-
suchungen uber die erste Anlage des Wirbelthierleibes " (1868),
•and " Unsere Korperform und das physiologische Problem ihrer
Entstehung " (1874). While I refer for details to the original papers,
I remark that, notwithstanding manifold agreements, I cannot

156 EMBRYOLOGY.

in important points assent to His's view. When, for example,
His (1874, p. 50) seeks to reduce the mechanics of form to the
simple problem of the form-changes in an unequally stretched
elastic plate, in my opinion he overlooks the fact that a plate com-
posed of cells, even if it possess elastic properties, is, nevertheless, a
much more complicated structure, and that the processes of folding
and evagination are primarily produced by the energy of the
growth of special groups of cells, and are therefore not to be com-
pared with the bendings and stretchings of elastic plates. As
PANDER has already emphatically stated, one is not to imagine in
the folding processes a lifeless membrane, but rather the folds are
themselves of organic derivation, called forth at the proper place by
a cell-multiplication at that place. For this reason, too, HAECKEL
in his polemic, " Ziele und Wege der heutigen Entwicklungs-
geschichte," has attacked this method of treating embryology,
introduced by His.

That the morphological differentiation of the animal body primarily
rests upon a process of folding of epithelial lamellae, my brother and
I have endeavored, by means of an abundant series of observations,
to demonstrate in a still more exhaustive manner than our pre-
decessors. In our " Studien zur Blattertheorie " we have, in the first
place, directed attention to the Crelenterates as the animal organisms
in which the principle of the formation of folds is most clearly
shown throughout the whole organisation, even into details; and,
secondly, we have endeavored to establish for Vertebrates that
organs like the body-cavity, chorda, and primitive segments, which
it was claimed arose by a separating and splitting of cell-layers,
likewise come into existence through the typical process of foldings
and constriction.

Finally we have endeavored to point out a physiological cause-
for the unequal growth of a cell-membrane, and have found such in
the Ccelenterates in the unlike functional activity of its various
regions. Parts of a membrane will grow more rapidly and must
become infolded, when in consequence of their position they are
called upon to accomplish more than neighboring regions.

In concluding this historical sketch attention should be called to-
the fact that C. E. VON BAER, in the general discussion of embryo-
logical processes, was the first to distinguish clearly between the
events of morphological differentiation, which take place in the
beginning of development, and those of histological differentiation,
which occur later.

LITERATURE. 157

LITERATURE ON THE DEVELOPMENT AND HISTORY
OF THE GERM-LAYERS.

Balfour. A Comparison of the Early Stages in the Development of Verte-
brates. Quart. Jour. Micr. Sci. Vol. XV. 1875.
Balfour. On the Early Development of the Lacertilia, together with some

Observations on the Nature and Kelations of the Primitive Streak. Quart.

Jour. Micr. Sci. Vol. XIX. 1879.
Balfour. On the Structure and Homologies of the Germinal Layers of the

Embryo. Quart. Jour. Micr. Sci. Vol. XX. 1880.
Balfour and Deighton. A Renewed Study of the Germinal Layers of the

Chick. Quart. Jour. Micr. Sci. Vol. XXII. p. 176. 1882.
Beneden, Ed. van. Kecherches sur 1'embryologie des mammiferes. La

formation des feuillets chez le lapin. Archives de Biologic. T. I. 1880.
Beneden, Ed. van. Untersuchungen iiber die Blatterbildung, den Chorda-
canal und die Gastrulation bei den Saugethieren. Anat. Anzeiger,

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. DEVELOPMENT OP THE PRIMITIVE SEGMENTS. 161

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CHAPTER VIII.
DEVELOPMENT OF THE PRIMITIVE SEGMENTS.

THE more one pursues the development of Vertebrates into later
stages, the more numerous become the changes which simultaneously
appear in the different regions of the embryonic body. We cannot
here undertake to describe step by step the processes which are
^simultaneously accomplished, for by that method the presentation

11

162

EMBRYOLOGY.

would become fragmentary and the comprehension of the separate-
processes would be made more difficult ; but it is necessary, in the
interest of a didactic method, to select from all the manifold pheno-
mena a single process of the development, and to follow it up until
it has come to a preliminary termination.

After the formation of the middle germ-layer two important
processes take place in the embryonic fundament. One process
leads to a division of the middle germ-layers into the two lateral

— mk

ud

Fig. 103.— Amphioxus embryo with five pairs of primitive segments in optical section, afte*

HATSCHEK.

A Seen from the side. B Seen from the dorsum.
In figure B are indicated the openings of the cavities of the primitive segments into the

intestinal cavity, which can be seen by deeper focussing. V, Anterior, H, posterior end ;

ak, outer, ik, inner, mk, middle germ-layer ; dh, intestinal cavity ; n, neural tube ;

en, neurenteric canal; twl, first primitive segment; ush, cavity of primitive segment;

ud, coelenteron.

plates and into two series of cuboidal bodies, which are situated at
the right and the left of the chorda, and which, under an erroneous
interpretation, were formerly called protovertebrce, but for which one
should now substitute exclusively the more accurate name primitive
segments [mesoblastic somites]. The other process, which occurs at
about the same time, at least in the case of the higher Vertebrates,
leads to the origin of those cells from which the sustentative sub-
stances and the blood of Vertebrates are derived.

DEVELOPMENT OF THE PRIMITIVE SEGMENTS.

163

ch-

in this chapter we shall take into consideration the formation of
the primitive segments first in the eggs of Amphioxus and the
Amphibians, and then in those of Fishes, Birds, and Mammals.

In Amphioxus the formation of the primitive segments is more
nearly simultaneous with the development of the middle germ-
layer than in the remaining Vertebrates. As soon as the two-
coelomic sacs begin to grow out from the coelenteron at the front end
of the embryo, there begins a division of them into two rows of
small sacs lying one behind the other (fig. 103 A, J3, us),, and this
( division proceeds from in front backwards. Here again we have
to do with a process of folding, which
repeats itself many times in the same
manner.

The wall of the groove-like coalomic
evagination, composed of cylindrical
cells, becomes, at a little distance from
its head-end, folded transversely to the
longitudinal axis of the embryo ; this
fold grows from above and from the
side downwards into the body-cavity;
in the same manner a second trans-
verse fold is soon formed on either
side of the body at a little distance
behind the first; behind the second
a third, a fourth, and so on, at the
same rate as that at which the em-
bryonal body elongates and the fun-
dament of the middle germ - layer

increases by the progress of the evagination toward the blasto-
pore.

In the embryo represented in fig. 103 five sacs may be counted on
either side of the body. The evagination is taking place at the
region marked mk ; it advances still farther toward the blastopore
and gives rise to a considerable series of primitive segments, the
number of which in a larva only twenty-four hours old has already
increased to about seventeen pairs. The primitive segments exhibit
at first an opening, by means of which their cavities (usK) are in
communication with the intestinal cavity. But these openings soon
begin to be closed in succession, by their margins growing toward
each other and then coalescing : this takes place in the same sequence
as that in which the detachment of the parts takes place, from before

Fig. 104.— Cross section through the
middle of the body of an Amphioxus
embryo with 11 primitive segments,
after HATSCHEK.

ak, Outer, it, inner germ-layer ; mk1,
parietal, mk*, visceral lamella of
the middle germ-layer; us, primi-
tive segment ; n, neural tube ; ch,
chorda ; Ih, body-cavity ; dh, intes-
tinal cavity.

164

EMBRYOLOGY.

backwards. At the same time the primitive segments (fig. 104}
gradually spread out both dorsally and ventrally, while their cells
increase in number and become altered in form. They grow upward
more and more at the side of the neural tube, which has meanwhile
detached itself completely from its matrix, the outer germ-layer.

mf

mp

u»h
A

ml?

Fig. 105 — Two cross sections through a Triton embryo.

A, Cross section through the region of the trunk in which the neural tube is not yet closed an

the primitive segments begin to be constricted off from the lateral plates.

B, Cross section through the region of the trunk in which the neural tube is closed and the

primitive segments have been formed.

mf, Medullary folds ; mp, medullary plate ; n, neural tube ; ch, chorda ; ak, outer, ik, inner
germ-layer ; mJc1, parietal, m/fc2, visceral middle layer ; dh, intestinal cavity ; Ih, body-cavity
ush, cavity of primitive segment ; dz, yolk-cells.

Toward the ventral side they insert themselves between the secondary
intestine and the outer germ-layer.

Finally, it might be further mentioned here that at a still later
stage, as is to be seen on the right side of fig. 104, the dorsal portions
of the primitive segment are constricted off from the ventral. The
former lose their lumina and furnish the transversely striped

DEVELOPMENT OF THE PRIMITIVE SEGMENTS. 165

musculature of the body, but from the cavities of the latter originates
the real unsegmented body-cavity, since the partitions which at
first separate them become thinner, break through, and finally
disappear.

Similar processes take place in a somewhat modified manner in the
case of the remaining Vertebrates.

In the Tritons the middle germ-layer (fig. 105 A) becomes
thickened on both sides of the chorda (ch) and of the fundament of
the central nervous system (ra), which is not yet closed into a tuber
and at the same time there appears a cavity (ush) in its thickened
part, caused by the separation of the visceral and parietal lamellae.
The thickening is not produced by an increase in the number
of the layers of cells, but simply by the fact that the cells
increase in height and grow out into long cylinders, which are
arranged around the cavity like an epithelium. We distinguish
these thickened parts of the middle germ-layer, which lie on either
side of the chorda and the nervous system, as the primitive-segment
plates, from the lateral parts, or the lateral plates. In the territory
of the latter the cells are lower, and ordinarily there is no distinctly
marked cavity between visceral and parietal layer.

Whereas in Amphioxus the process of forming somites extends
itself over the whole of the middle germ-layer, in the case of the
Amphibians, and likewise all the re-
maining Vertebrates, it affects only
the part which is next to the chorda
and the neural tube, leaving the lateral
plates, on the contrary, untouched.
The segmentation begins at the head-
end, and prbceeds slowly toward the
blastopore ; it is accomplished by fold-
ing and constricting off. The epithelial
lamella next to the neural tube and Fig. ioe.— Frontal section through
the chorda, being composed of cylin-
drical cells, is raised up into small ments.
transverse folds, which, separated from °— —
each other by intervals of uniform size, with their cavities
grow into the cavity of the primitive-
segment plate, and give rise to small sacs lying one behind the other
(fig. 106).

Soon afterwards each little sac is constricted off from the lateral
plates (fig. 105 A and £). Consequently one now meets, both in

166 EMBRYOLOGY.

transverse and frontal sections at the right and left of chorda
and neural tube, cubical sacs the walls of which are formed of
cylindrical cells ; these sacs are everywhere surrounded by a fissure-
like space, and they enclose a small cavity (the primitive-segment
cavity), which is a derivative of the body-cavity. From the front
layer of the fold is produced the posterior wall of the newly formed
segment, from its posterior layer the front wall of the remnant of
the primitive-segment plate, or of the sac which is next to be con-
stricted off.

Of the Vertebrates which are developed out of meroblastic eggs, the
Selachians appear to exhibit most clearly the original mode of the
formation of primitive segments. A distinct body-cavity is formed on
either side of the trunk by the separation of the parietal and visceral
lamellae of the middle germ -layer (fig. 110). The dorsal portion of
the cavity, which flanks the neural tube, acquires thickened walls
(trip), and corresponds to the part previously designated as the
primitive-segment plate, which at the same time with the appear-
ance of the body-cavity begins to be divided into primitive segments.
In the anterior part of the body a series of transverse lines of
separation become visible (fig. 195 mpl), the number of which is
continually increased toward the hind end of the body. For a
long time the cavities of the primitive segments, which are sepa-
rated from one another by these transverse furrows, remain in
communication ventrally with the common body-cavity by means
of narrow openings. One may therefore describe this state of
.affairs by saying that the body-cavity is provided toward the back
of the embryo with a series of small sac-like evaginations, which lie
close together one after the other. Afterwards the primitive seg-
ments are entirely constricted off from the body-cavity, and then
their thickened walls come into close contact, and thus cause the
disappearance of the cavities of the segments (fig. Ill mp).

Whereas in the Selachians it is still evident that the formation of
the primitive segments depends upon folding and constricting off, the
process is obscured even to obliteration in the case of Reptiles, Birds,
and Mammals ; this is referable simply to the fact that the two
lamellae of the middle germ-layer remain for a long time firmly
pressed together, only subsequently beginning to separate, and that
they are composed of several layers of small cells. The process of
Balding and constricting of appears here as a splitting up of a solid
cell-plate into small cubical blocks.

The part of the middle germ-layer that is next to the chorda and

DEVELOPMENT OF THE PRIMITIVE SEGMENTS.

167

neural tube appears in a cross section of a Chick embryo (fig. 107)
as a compact mass (Pv) consisting of many superposed small cells f
which, as far as it is not divided up into separate blocks, is designated
-as primitive-segment plate
or protovertebral plate. In
fig. 107 it is still connected
.at the side by means of a
thin isthmus of cells with
the lateral plates, in whose
territory the middle germ-
layers are thinner and sepa-
rated from each other by a
fissure.

In observing the blasto-
.germ from the surface the
region of the primitive-seg-
ment plates, as is to be seen
in the posterior part of a
nine-days-old Rabbit embryo
(fig. 108), appears darker thaji
the region of the lateral plate;
so that the two are dis-
tinguished from each other ;
one is stem-zone (stz), the
other parietal zone (pis).

The development of the
primitive segments is ob-
servable in the Chick at the
beginning of the second day
of incubation, in the Rabbit
at about the eighth day.
Clear transverse streaks ap-
pear in the stem-zone at
some distance from the primi-
tive streak, about in the
middle of the embryonic

fundament, both on the right and the left of the chorda and neural
tube (fig. 108). They correspond to transverse fissures, by means
•of which the primitive- segment plates are divided into the small
and solid cubical primitive segments (uw). In the nine-days-old
Rabbit embryo represented in fig. 108 these plates are resolved in

168

EMBRYOLOGY.

a I

front into eight pairs of primitive segments (uw), whereas in the
hind end of the embryonic area they still have the form of a con-
tinuous mass of cells, the
stem-zone (stz), which in sur-
face-views appears darker
than its surroundings.

In a somewhat more ad-
vanced stage the primitive
segment, which probably se-
cretes at the same time fluid r
develops in its interior, as
in the case of the Amphibia
and Selachii, a cavity, around
which the cells group them-
selves in a radial manner.
This cavity, too, is at first in
communication laterally with
the fissure of the body-cavityy
until the primitive segment
has been fully constricted
off.

In Vertebrates, besides the
trunk-region, a part of the
head-region of the embryo is
also affected by this process
of segmentation which we
have been considering. We
must therefore speak in the
one case of head-segments,
and in the other of trunk-
segments. Up to the present
time the number and condi-
tion of the head-segments have
been made out (by BALFOUR,
MILNES MARSHALL, and VAN
WIJHE) most accurately for

Fig. 108.— Rabbit embryo of the ninth day, seen
from the dorsal side, after KOLLIKER. Magnified
21 diameters.

The stem-zone (stz) and the parietal zone (pz) are
to be distinguished. In the former 8 pairs of
primitive segments have -been established at the
side of the chorda and neural tube.

ap, Area pellucida ; rf, medullary groove ; vh, fore
brain ; ab, eye-vesicle ; mh, mid brain ; hh, hind
brain ; uw, primitive segment ; stz, stem-zone ;
pz, parietal zone ; h, heart ; ph, pericardial part
of the body-cavity ; vd, margin of the entrance to
the head-gut (vordere Darmpforte), seen through
the overlying structures ; of, amniotic fold ; vo,
vena omphalomesenterica.

the Selachians. In this in-
stance there are nine pairs of hollow head-segments. In the higher
Vertebrates such segments although fewer in number, have also
been described; however, the less sharply differentiated structures
of the latter demand still further investigation.

DEVELOPMENT OF THE PRIMITIVE SEGMENTS. 169"

But, in any event, the accurate study of the earliest embryonic
segmentation of the body into a large number of metameres yields
this result of the highest importance for the general morphology of
the Vertebrate body, that the head not less than the trunk represents
a segmented portion of the body and has in no wise been produced
from a single primitive segment.

SUMMARY.

1. In Vertebrates the middle germ-layers immediately after
their origin are differentiated into several fundaments by processes
of folding and constricting off.

2. The process of differentiation in the middle germ-layer exhibits-
two modifications.

(a) In Amphioxus the middle germ-layers are, at the time of

their first appearance, completely separated into primitive-
segments lying one behind the other.
It is only later that each primitive segment is divided into a

dorsal portion (the real primitive segment) and a ventral

portion.
The dorsal portion, or primitive segment proper, furnishes the

transversely striped musculature of the trunk.
The ventral segments form the body-cavity, which is at first

segmented, but afterwards with the disappearance of the

partitions becomes a single cavity.

(b) In all other Vertebrates the fundaments of the middle

germ-layers are divided first into a dorsal and a ventral
region — into the primitive-segment plates and the lateral'
plates.

The lateral plate remains unsegmented. The body-cavity, which
becomes visible in it by separation of the parietal and
the visceral lamellae of the middle layer, is from th&
beginning on each side of the body a single space.

The primitive-segment plate alone is divided into successive
primitive segments.

3. The segmentation of the middle germ-layers also extends over
the future head-region of the embryo. One therefore distinguishes —

(a) Head-segments, the number of which amounts to nine ;

(6) Trunk-segments, the number of which is constantly being
increased during the development of the posterior trunk-
region.

170 EMBRYOLOGY.

CHAPTER IX.

DEVELOPMENT OF CONNECTIVE SUBSTANCE AND BLOOD.
(THE NESENCHYME-THEORY.)

WITH the question of the origin of connective or mechanically sus-
tentative substance and blood we enter a very difficult field, the
cultivation of which has now been taken in hand successfully by many
persons. Here also we shall acquaint ourselves with a simple case
from the development of Invertebrates, before we begin with the
•conditions in Vertebrates, which are more difficult to comprehend.

In Co3lenterates and Echinoderms there is developed between the
germ-layers, which are composed of epithelial cells, a sustentative
tissue. It consists of a homogeneous jelly, in which are scattered a

Tig. 109.— Two stages of development of Holothuria tubulosa, in optical section (after SELENKA),
from BALFOUB.

A, Blastosphere-stage at the end of cleavage.

B, Gastrula-stage.

mr, Micropyle; fl, chorion; s.c, segmentation-cavity, in which gelatinous substance is early
secreted as a gelatinous core; bl, blastoderm; ep, outer, hy, inner germ-layer ;, ms,
amoeboid cells arising from the inner germ-layer ; a.e, coelenteron (archenteron).

few isolated spheroidal or stellate cells, which are capable of changing
position by virtue of their amoaboid motion. It is usually developed
very early ; in the Echinoderms, for example, as early as the blastula-
stage (fig. 109).

Into the cavity of the blastula (A) a homogeneous soft substance, the
jelly-core (s.c), is secreted by the epithelial cells. Into this jelly there
migrate from the epithelium, and indeed from the particular region
which at the time of gastrnlation is infolded (fig. 109 B) as the

DEVELOPMENT OF CONNECTIVE SUBSTANCE AND BLOOD. 171

inner germ-layer (hy), numerous cells (ms), which loose their epi-
thelial character^ and send out processes in the manner of lymph-
corpuscles. They soon distribute themselves as migratory cells
•everywhere in the jelly.

In the gastmla -stage and subsequently, the cell-containing jelly
between the outer and the inner germ-layers represents a third sheet,
which is distinguished from the latter histologically, and, according
to the definition previously given, cannot be designated as a middle
germ-layer ; for by that definition we understand the term to be
limited to a sheet of embryonic cells, having an epithelial arrange-
ment and bounding a surface. The jelly-like sheet is a product of
the germ-layers, which may be distinguished from them by the name
mesenchyme or intermediate layer (Zwischenblatt).

Once formed, the mesenchyme continues to grow as an independent
tissue, in that the cells which at first migrated into the jelly at a
definite stage of development, to which one may give the name
mesenchyme-germ, continue to increase uninterruptedly by means of
cell-division. In its growth it penetrates into all the interstices
which arise when the germ-layers, as happens in many Coelenterates,
produce the most complicated structures by the formation of folds and
evaginations ; it furnishes everywhere a support for the epithelial
layers which repose upon it. At the same time some of the mesen-
chyme-cells can alter their original histological character as simple
trophic or nutritive cells of the intermediate substance. Thus here
and there they differentiate contractile substance at their surface,
and become, as is to be seen in Ctenophores arid Echinoderms, smooth
muscle-cells, the ends terminating either in one fine point, or
dividing themselves into several processes, as is more frequently the
case with Invertebrates.

In Vertebrates also, after the two primary germ-layers have arisen,
a process similar to that which we have just considered appears to
lead to the formation of connective tissue and blood, two tissues
which correspond morphologically and physiologically to the mesen-
chyme of Invertebrates.

In the first two editions of the " Lehrbuch " I set forth that the
whole mesenchyme-question in the Vertebrates was still in a nascent
condition, that the account therefore presented nothing final, but
bore in many respects the character of the provisional. Since that
time an essential advance has been made in this field. Thanks to
the investigations of HATSCHEK and EABL, of RUCKERT, ZIEGLER, and
VAN WIJHE, we have acquired more accurate explanations concerning

172 EMBRYOLOGY.

the origin of the connective substances ; the question of the origin*
of the vascular endothelium and of the blood, on the contrary, is
one that is less cleared up. This determines me to treat the two-
questions separately in the following account.

A. The Origin of the Connective Tissues.

Selachian embryos appear to be the most suitable objects on
which to trace the origin of the connective substances. Here the
middle germ-layer serves as the matrix for the mesenchymatic tissue.
At the time when the primitive segment is still connected below with
the lateral plates, and when the body-cavity is visible in the latter,
there appears a cell-growth at the lower border of each primitive
segment on the side which is directed toward the chorda. It is ordi-
narily designated as sclerotome. It contains at first a small evagi-
nation of the body-cavity (fig. 258 A sic). At the restricted place-
designated, which is marked off from its surroundings, and which
recurs on each primitive segment, cells in large numbers (fig. 110
sk) individually detach themselves from the epithelial layer, remove
by active migration from their place of origin, like the mesen-
chymatic cells of Invertebrates, and distribute themselves in th&
space which is limited on the one side by the inner wall (mp)
of the primitive segment, and on the other by the chorda (ch)
and the neural tube (nr).

At the time of their appearance the ameboid cells are separated
by only a small amount of inter-cellular substance : they increase
rapidly in number, and thereby soon crowd chorda, neural tube, and
primitive segment farther apart (fig. 111). The segmental arrange-
ment which the growths exhibit at their first appearance (fig. 195 Vr)
very early ceases to exist, since by their extension they become fused
together into a continuous sheet.

The mesenchyme, which thus grows forth out of the middle germ-
layer on both sides of the chorda, furnishes the foundation for the
whole axial skeleton ; it produces the skeletogenous tissue by the-
growing toward each other and the fusion of the masses which are-
formed on the right and left sides. As fig. Ill shows, the mesen-
chyme (sk) grows around the chorda (ch) both dorsally and ventrally,
and envelops it with a connective-tissue sheath, which is continually
becoming thicker. In the same manner it encloses the neural tube
(nr) and forms the membrana reuniens superior of the older embryo-
legists, the foundation out of which subsequently the connective-

DEVELOPMENT OF CONNECTIVE SUBSTANCE AND BLOOD.

173

tissue envelopes of the neural tube and the vertebral arches with
their ligaments are differentiated.

Conditions similar to those of Selachians are also to be observed,

Fig. 110.

Fig. 111.

Figs. 110 and 111.— Diagrams of cross sections through younger and older Selachian embryos
to illustrate the development of the principal products of the middle germ-layer. After VAN
WIJHE, with some changes.

Tig. 110.— Cross section through the region of the pronephros of an embryo, in which the
myotomes (mp) are in process of being constricted off.

Tig. 111. — Gross section through a somewhat older embryo, in which the myotomes have just
been detached.

-nr, Neural tube ; ch, chorda ; ao, aorta ; sch, subnotochordal rod ; mp, muscle-plate of the
primitive segment ; w, zone of growth, at which the muscle-plate bends over into the cutis-
plate (cp) ; vb, portion connecting the primitive segment with the [walls of the] body-cavity,
out of which are developed, among other things, the mesonephric tubules uk (fig. Ill) ;
sk, skeletogenous tissue, which arises as an outgrowth from the median wall of the con-
necting portion (vb) ; vn, pronephros ; mkl, parietal, mk*, visceral middle layer, from the
walls of which mesenchyme is developed ; Ih, body-cavity ; ik, entoderm ; h, cavity of the
primitive segment ; uk, mesonephric tubulei arisen from the connecting portion vb of the
diagram 110 ; uk1, place where the mesonephric tubule has detached itself from the" primitive
segment ; ug, mesonephric duct, with which the mesonephric tubule has united on the left
side ; tr, union of the mesonephric tubule with the body-cavity (nephridial funnel) ; mes1,
mes*, mesenchyme. which has arisen from the parietal and visceral lamellae of the middle
layer respectively.

although less distinctly, in Reptiles, Birds, and Mammals ; they
have been described by REMAK, KOLLIKEB, and others, and have been
brought into connection with the formation of the vertebral column.
The primitive segments, which are at first solid, soon acquire a
small cavity (fig. 116), around which the cells are arranged into a

174 EMBRYOLOGY.

continuous epithelium. Then a part of the wall of the primitive
segment lying at its lower and median angle begins to grow with
extraordinary rapidity, and to furnish a mass of embryonic connective
tissue, which spreads itself around the chorda and neural tube in the
manner previously described. The dorsal and lateral parts of the
primitive segment (fig. 116 ms), which subsequently loses its cavity,
are not involved in this growth ; out of them arise principally the
fundaments of the trunk-musfculature. This part is consequently
now distinguished as muscle-plate (ms).

Mesenchyme arises from three other places of the middle germ-
layer besides the primitive segments — from the visceral lamella, from
the parietal lamella, and finally from that wall of the primitive
segment which is turned toward the epidermis and has been given
by RABL the name cutis-plate. Here also the conditions are best
followed in Selachii.

Individual cells migrate out from the visceral lamella (Darm-
faserblatt), which in early stages is composed partly of cubical,,
partly of cylindrical cells (fig. 110 mW), and distribute themselves
upon the surface of the entodermic layer ; they are found at places
where no trace of a vessel is observable. They furnish the
mesenchyma of the intestinal wall, which is ever becoming more
abundant, and which is subsequently converted partly into connective
tissue, partly into the smooth muscle-cells of the tunica muscularis
(fig. Ill mes*).

A similar process is repeated in the parietal lamella (Haut-
faserblatt). Emigrating cells produce between the epithelium of
the body-cavity and that of the epidermis an intermediate layer of
mesenchyme-cells (fig. 110 ink1, fig. Ill mes1).

An important region for the production of connective tissue is,
finally, the cutis-plate, i.e., the epithelial layer of the original primi-
tive segment which is in contact with the epidermis (fig. 110 cp).
The process occurs here later than at the other places mentioned,
and begins with an active cell-growth, which gradually leads to a
complete disintegration of the epithelial lamella. " The disintegra-
tion," as RABL remarks, " proceeds in such a manner that the cells,
which hitherto exhibited an epithelial character, separate them-
selves from one another, and thereby lose their epithelial character."
It is probably from this part of the mesenchyme that the corium is
derived.

That the mesenchyme-cells scattered between the epithelial lam-
ellae are capable of executing extensive migrations, after the fashion

DEVELOPMENT OF CONNECTIVE SUBSTANCE AND BLOOD. 175

of migratory cells, is perhaps best shown in the investigation of
transparent embryos of Bony Fishes. " One sees distinctly," thus
WENKEBACH describes it, ^how the cells by means of amoeboid
motions, and of sometimes extraordinarily long protoplasmic pro-
cesses, move themselves about independently in the body of the em-
bryo and upon the yolk, which is not yet clothed with hypoblast,
and creep toward definite places, as if they acted voluntarily and
consciously." By virtue of this peculiarity, the mesenchyme-cells
actively penetrate into all larger and smaller fissures which exist
between the germ-layers and the fundaments of organs which have
arisen from them. Everywhere they form a filling and connecting
mass between these structures, which afterwards acquires a still
greater importance as the bearer of blood- and lymph-courses as well
as nerves.

In comparison with the earlier editions of the " Lebrbuch," I have here
given an essentially different presentation of the development of the mesen-
chyme. Formerly, supported by the investigations of His, WALDEYEK, KOLL-
MANN, and others on meroblastic eggs, I thought it necessary to refer the
chief source of the mesenchyme to a limited territory of the germ, to the area
opaca, and made the cell-material arise by delamination from the entodermic
layer, especially from the yolk-wall. But now I assume a manifold origin from
various regions of the middle germ-layer. Thus I come back again to an in-
terpretation which I had already propounded as probable in " Die Ccelomtheorie "
(p. 80) and "Die Entwickelung des mittleren Keimblattes " (p. 122),— to the
interpretation, namely, that mesenchyme-germs in Vertebrates are perhaps
formed by an emigration of cells at several distinct places at the same time.
Whether this or that be the real mode, the essence of the mesenchyma-theory
is not thereby affected, for the essential part of that theory consists in this,,
that it establishes in the earliest development of tissue a contrast between
the epithelial germ-layers and a packing tissue, produced by a dissolution of
the epithelial continuity, which spreads itself out between the germ-layers,,
and soon appears as an independent structure.

Indeed, with this theory as a basis, it would not be surprising if the pro-
duction of mesenchy matic tissue should not be limited simply to the middle germ-
layer, and if the entoderm by the contribution of cell-material should participate
in its formation.

B. The Origin of the Vascular Endothelia and the Blood.

The question of the origin of the tissues represented in the above
heading is one of the most obscure in the realm of comparative
embryology. The very investigators who have endeavored most
recently and with the most reliable methods to elucidate this matter
do not hesitate to emphasise the uncertainty in the interpretation
of the conditions presented to them. Even the lowest Vertebrate^
which is distinguished by the greater simplicity of its structure, and

176 EMBRYOLOGY.

by the greater ease with which all its processes of development are
understood, has failed us in this question. For HATSCHEK, who
knows the development of Amphioxus better than any one else, de-
signates the blood-vessels as the only system of organs concerning
which he was unable to arrive at a clear understanding.

Consequently in the field now to be examined there are many
views and observations which in part stand in the most direct
antagonism to each other. To give a comprehensive review of them
is not possible without the greatest fulness, which would be contrary
to the plan of this Text-book; I therefore limit myself, first, to
giving a survey of the various possibilities by which the origin of
the vessels and the blood might take place, and, secondly, to present-
ing a series of observations which have been made on Selachians,
Birds, and Mammals ; still it is always to be kept in mind that
much remains doubtful here, and that coming years may bring about
many a change in our interpretations.

According to one view, the vascular cavities are developed out of
fissure-like spaces between the germ-layers which remain unoccupied at
the time the fundament of the mesenchyme is produced. These cavities
acquire a boundary in this way : the neighboring mesenchyme-cells
begin to penetrate into them, and then unite into a vascular endo-
thelium. " The system of blood-vessels and that of lymphatic vessels,"
observes ZIEGLER, " are produced in their first fundaments from
remnants of the primary body-cavity (the space between the primary
germ-layers), which at the general distribution of the formative
tissue (mesenchyma) remain behind as vessels, lacunae, or interstices,
and are enclosed by that tissue and incorporated in it." The formed
elements [corpuscles] arise at separate places in the blood-courses
by the growth and detachment of mesenchymatic cells.

According to another view, the vessels are constructed in this
manner : cells in the mesenchymatic tissue arrange themselves in
rows, and these cell-cords become hollowed out; thereby the more
superficial cells furnish the endothelial wall, whereas the remaining
cells become blood-corpuscles. The blood-vessels are therefore nothing
else than cavities which have been secondarily produced in the
mesenchymatic tissues by means of their own cells. Both views
agree in this, that they cause the group of sustentative substances
to be brought into genetic connection with the blood, and the latter
to figure as a product of the metamorphosis of the mesenchyma.

Moreover, both views may present variations in the details,
according as they ascribe to the mesenchyme a different origin and

DEVELOPMENT OF CONNECTIVE SUBSTANCE AND BLOOD. 177

make it arise either out of the middle germ-layer alone, or out of
the entoblast alone, or by the migration of cells out of both layers
and their union into a single fundament. Still other variations
result from the first fundament of the blood-course being some-
times referred to a limited territory of the germ, sometimes to several
places. Thus, for the meroblastic eggs of B?rds, the area opaca is
designated by some observers as the place where vessels and blood
are first formed. From here they grow out as it were at first into the
embryonic body proper. The opposite is reported of Bony Fishes, in
which the first vessels, heart, aorta, caudal veins, and sub-intestinal
veins, together with blood-corpuscles, arise earliest in the embryonic
body itself, whereas they appear on the yolk only subsequently.
Finally, for the Selachians a local origin of the vessels is maintained
both for the area opaca and also for the embryonic body in the
restricted sense.

In opposition to the two views hitherto presented, a third view
assumes a separate origin for the connective substances on the one
hand, and for the vascular endothelium and the blood on the other.
Whereas the former are produced by the emigration of cells from the
middle germ-layer, the vascular endothelium is maintained to arise
from cells of the entoblast. It is held that an endothelial sac is
formed (perhaps by constriction) as an independent fundament,
which by budding gives rise to the whole vascular system.

After this brief survey of the various possibilities concerning the
origin of the blood-course, I turn to a description of certain con-
ditions, concerning the signification of which it must be admitted
that the views are also often very divergent.

The area opaca of the meroblastic eggs of Fishes, Reptiles, and
Birds has always played an important role in the literature on the
question of the origin of the blood. Notwithstanding the frequency
with which it has been investigated, the researches concerning it
cannot be regarded as concluded. It is from this standpoint that. I
beg the reader to judge what follows.

In the case of the Chick, on which especially we shall base our
account, the opaque area is composed of only the two primary germ-
layers at the time when the middle germ-layer begins to be formed
from the region of the blastopore by the production of folds.

The outer germ-layer, as has already been described in Chapter V.,
has in general a simple structure, since it is composed of a single
layer of small cubical cells. The inner germ-layer (fig. 56 ik and
fig. 112), on the contrary, alters its condition the more we approach

12

178

EMBRYOLOGY.

the margin of the disc. In the area pellucida and in the immediately
surrounding parts it appears as a single layer of greatly flattened
cells, and is separated from the yolk-floor by a cavity filled with an
albuminous fluid ; in the opaque area it reposes directly upon the
yolk ; its cells here become higher, cubical, or polygonal, and finally
it terminates with a greatly thickened marginal zone, the previously
mentioned yolk- wall (dw). This is the important region of the germ
with which we now have especially to deal.

The yolk-wall consists in the Chick partly of embryonic cellsr
which are separable from one another, partly of yolk-material

in which are enclosed
numerous large and!
small nuclei enveloped
in protoplasm (the me-
rocytes), as at the final
stages of the process of
cleavage.

Such free nuclei have-
also been demonstrated
with perfect certainty
in the marginal terri-
tory of the yolk during

the course of the formation of the germ-layers in Selachians,.
Teleosts, and Reptiles (KUPFFER, HOFFMANN, RUCKERT, STRAHL,.
SWAEN).

The most accurate description of the yolk-nuclei has been given by
RUCKERT for the eggs of Selachians (fig. 113). They are present in
this case at the marginal portion of the germ-disc, embedded in the*
yolk in not inconsiderable numbers, and are remarkable for their
size, sometimes reaching a diameter ten-fold as great as that of an
ordinary nucleus (&1, &*). From the protoplasm enveloping the
nucleus k* there proceeds a richly branched network of processes.
In the interstices of the net are lodged yolk-elements (d) in great
numbers, from the size of the ordinary yolk-plates down to the finest
granules. The former are often in process of disintegration. One
may conclude from this, as well as from other phenomena, that a
vigorous consumption of deutoplasm is taking place at the margin of
the germ. This deutoplasm is taken up as nutritive material by the
protoplasmic net surrounding the nucleus, and employed by means of
intra-cellular digestion for its growth. Consequently one also sees the
yolk-nuclei in active increase.

Fig. 112.— Section through the margin of the germinal
disc of a Hen's egg incubated for six hours, after DUVAL.

ok, Outer germ-layer ; dz, yolk-cells ; dk, yolk-nuclei ;
div, yolk-wall.

DEVELOPMENT OP CONNECTIVE SUBSTANCE AND BLOOD.

179

Toward the surface of the yolk small clusters of nuclei (fig. 113 k)
arise out of the large deeper-lying yolk-nuclei. From these there
are finally produced genuine cells of the germ (z), by the small nuclei
surrounded by a layer of protoplasm detaching themselves from
the yolk, as it were by an act of supplementary cleavage. " Since the
merocytes thus on
the one hand un-
interruptedly take
up nutritive ma-
terial out of the
yolk, and on the
other continually
surrender it in the
form of cells to the
germ-layers of the
nascent embryo,
they present an
important link
between the latter
and the yolk"
(RUCKERT.)

The views of
investigators on
the significance

of the yolk- wall and of the merocytes enclosed in it are very divergent.
Indeed there is unanimity only in this, that the yolk-wall contributes
to the increase of the lower germ-layer by single cells becoming in-
dependent and attaching themselves at the margin to the elements
which already have an epithelial arrangement. On the other
hand it appears less certain how far the yolk-wall is concerned in
the formation- of the blood. According to the observations of His,
DISSE, RAUBER, KOLLMANN, RUCKERT, SWAEN, GENSCH, HOFFMANN,
and others, it does share in this process during a limited period
of development in the case of Selachians, Teleosts, Reptiles, and
Birds.

In the Selachians the anterior margin of the germ-disc is the first
to be metamorphosed into a vascular zone. RUCKERT could find
here numerous and unequivocal indications that the previously
described peculiar cell-elements of the yolk (merocytes) provided
with large nuclei contribute to the formation of blood-islands, in
that they break up into clusters of small cells, detach themselves

Fig. 113.— Yolk-nuolei (merocyte») from Pristiurus, lying underneath
the germ-cavity B, after RUCKERT.

z, Embryonic cells ; k, superficial clear nuclei ; klt deeper nuclei ;
k*t marginal nuclei rich in chromatin, largely freed from th»
surrounding yolk, in order to show the processes of the proto-
plasmic mantle ; d, yolk-plates.

180 EMBRYOLOGY.

from the yolk-containing part of the lower germ-layer, and become
differentiated on the one hand into the migratory cells of the first
blood-vessels, and on the other into the blood-corpuscles. RUCKERT
further maintains that the material destined for the production of
blood is supplemented by means of cells freshly cleft off from the
yolk.

SWAEN remarks with the same positiveness, "Les premiers ilots
sanguins se developpent aux depens des elements de Thypoblaste. Ces
derniers constituent a la fin de ce developpement les parois de cavites
vasculaires closes et les cellules sanguines qui les remplissent."
Likewise GENSCH makes the large cells in the yolk responsible for
the formation of the blood in the case of the Bony Fishes. HOFF-
MANN also finds in Reptiles that the blood and the endothelial
wall of the vessels, as well as the spindle-shaped cells which lie
between the vessels, are a product of the inner germ-layer, and
that they appear at definite places of the germ-disc at a time
when the middle germ-layer has not yet been formed in those
regions.

Finally, it is stated concerning the germ of the Chick that at the
end of the first day of incubation the cells in the yolk-wall have
become very numerous, through the multiplication of the nuclei
enclosed in the latter, and that afterwards the abundance of the
cells diminishes. For part of the cells which have been formed
by the active proliferation now detach themselves from the yolk-
wall, get into the space between the outer and inner germ-layers,
and there produce a third independent layer, which is continually
increasing in thickness, whereas the remaining part becomes modi-
fied into an epithelium of large cylindrical cells containing yolk-
granules. This middle layer is judged by several investigators to
be an independent fundament of the germ, and has in this sense
been described by His as parablast, by DISSE and others as vascular
layer, by RAUBER as desmohcemoUast, and by KOLLMANN as marginal
germ or acroblast.

All of these accounts need still more precise confirmation, since
they have often been called in question, even up to most recent
times. Thus K^LLIKER has always defended the position that
not only the connective substances, but also the vessels and the
blood, are products of the middle germ-layer, and are generated by it
in its peripheral regions. KASTSCHENKO, in his study of the Selachii,
could not convince himself that the merocytes have special import-
ance in the formation of blood and vessels, but was not, however,

DEVELOPMENT OF CONNECTIVE SUBSTANCE AND SLOOP* 181

willing to deny it. So much the more positively do WENKEBACH
and ZIEGLER, on the strength of their investigations on Teleosts,
express themselves against the mode of blood-formation given by
GENSCH. According to ZIEGLER, the blood-corpuscles are developed
in the blood-vessels of the embryonic body itself. The free nuclei
of the yolk, the merocytes, on the contrary, it is maintained, do not
share in the formation of embryonic tissues, but, in adaptation to
the function of resorbing the yolk, undergo peculiar modifications,
which " cause the frequently affirmed but never proved production
of blood-corpuscles [by them] to appear improbable."

Under this condition of affairs, I must regard the question of the
source of the cell-layer in which, in the region of the opaque area,
the formation of blood takes place as not yet ready for final
judgment.

So far as regards the further changes, by means of which the
cell-layer under consideration is converted into connective substance
and blood, on the whole I subscribe, in this difficult field of in-
vestigation, to KOLLIKER'S representation.

At the end of the first day of incubation, the masses of cells which
lie between the inner and the outer germ-layers arrange themselves
in cylindrical or irregularly limited cords, which join themselves to-
gether into a close-meshed network ; they are the first fundaments
both of the vessels and also of their contents, the blood. In the
spaces of the net are to be found groups of indifferent cells, which
afterwards become embryonic connective tissue, and which are the
Substanzinseln (fig. 114) of authors.

At the beginning of the second day of incubation, the solid funda-
ments of the vessels become more distinct, in proportion as they
become bounded superficially by a special wall, and acquire
an internal cavity. The wall of the vessels is developed out of
the most superficial cells of the cords, and is composed during the
first days of incubation of a single layer of very much flattened
polygonal elements, on account of which the first vessels of the
embryo are often designated as endothelial tubes (fig. 114 and
fig. 115 gw).

The cavity of the vessel is probably formed by the penetration of
fluid into the originally solid cord from its surroundings, thus forming
the plasma of the blood, by which the cells are pressed apart and to
the sides. The cells then constitute here and there thickenings of
the wall, and project into the fluid-filled cavities as elevations of
loosely united spherical elements (fig. 114, Blood-islands). Conse-

182

EMBRYOLOGY.

quently the vessels which are just becoming permeable are very
irregular, since narrow places and wider ones, often provided

with evagina-

tions, alternate

Blood-island

Wall of blood-

Blood-island

Blood-vessel

Wall of blood-
vessel

Substanzinseln
Blood-vessel

Jig. 114.— A portion of the vascular area of the germ-disc of an embryo
Chick, in which 12 primitive segments are developed, after DISSE.

One sees the more darkly shaded blood-coxmes, in which lie the
"blood-islands," the centres whence the blood-corpuscles arise-
The clear spaces in the vascular network, the walls of which are
formed of flat endothelial cells, are the "substance-islands"
(Substanzinselu).

one another,
and since
the vessels
are sometimes
wholly excava-
ted, fluid-filled,
endothelial
tubes, and
sometimes re-
main more or
less impassable,
owing to the
variously
formed cell ag-
gregates which
project from
the wall.

The aggrega-
tions of cells
themselves are
simply the
centres where
the formed com-
ponents of the
blood are pro-
duce d . The
small spherical
nucleated cells,
which still en-
close dark yolk-
granules, be-
come at first
homoge n e o u s

by the dissolution of the latter, and then, owing to the formation
of the coloring matter of the blood in them, they take on a slightly
yellowish color, which gradually becomes more intense.

DEVELOPMENT OF CONNECTIVE SUBSTANCE AND BLOOD.

183

If one at this time examines a blastoderm which has been removed
from the yolk, the zone in which the formation of blood takes place
appears flecked with more or less intensely colored blood-red spots,
some of which are roundish, others elongated, and others branched.
The spots are known as the blood-points or blood-islands of the blasto-
derm (fig. 114). From these formative areas the superficial cells
now detach themselves and enter the blood -fluid as the isolated red
blood-corpuscles. Here, as well as in the blood-islands, they multiply
by means of cell-division, during which the nucleus is metamorphosed
into the well-known spindle-figure.

As REMAK first showed, divisions of blood-cells are to be observed
in the Chick in great numbers up to the sixth day of incubation,
whereas they later become more rare, and then wholly disappear.
Also in the case of Mammals and of Man (FoL) the first embryonic

Fig. 115.— Cross section through a portion of the vascular area, after DISSE.

ak, Outer, ik, inner germ-layer ; mkl, parietal, mk*, visceral lamella of the middle germ-layer ;
Ih, extra-embryonic body-cavity ; gw, wall of blood-vessel formed of endothelium ; bl, blood-
cells ; g, vessels.

blood-corpuscles, which are at this time provided as in the other Verte-
brates with a genuine cell-nucleus, possess the power of division.

In proportion as blood-corpuscles still further detach themselves
from the blood-points, the latter become smaller and smaller, and
finally disappear altogether ; but the vessels without exception then
contain, instead of a clear fluid, red blood with abundant formed
elements (fig. 115 bl).

Subsequently there occur changes in the Substanzinseln, which lead
to the formation of embryonic connective substance. The germinal
cells, at first spheroidal, separate farther from one another, at the
same time secreting a homogeneous inter-cellular substance; they
become stellate (fig. 116 sp\ and send out processes by means of
which they are united into a network, which stretches all through
the gelatinous secretion ; other cells apply themselves to the endo-
thelial tubes of the vessels.

184

EMBRYOLOGY.

After the formation of vessels and blood is completed, the territory
of the area opaca, in which the processes just described take place,
is sharply delimited at its periphery (fig. 117) in all meroblastic eggs,
as well as in those of Mammals. Tor the close network of blood

vessels ends abruptly at its periphery in a broad, circular, marginal
vein (the vena or sinus terminalis, S.T.).

Beyond the sinus terminalis, there is formed on the yolk neither
blood nor blood-vessels. Nevertheless, the two primary germ-layers
spread themselves out laterally over the yolk still farther, the-
outer layer more rapidly than the inher, until they have grown
entirely around it.

DEVELOPMENT OF CONNECTIVE SUBSTANCE AND BLOOD. 185-

We must therefore now distinguish in the opaque area (Plate I.,
fig. 2, page 213) two ring-like areas, the vascular area (gh) and the
yolk-area (dh), area vasculosa and area vitettina. Since, moreover.

sx.

Fig 117.— Diagram of the vascular system of the yolk-sac at the end of the third day of
incubation, after BALFOUR.

The whole blastoderm has been removed from the egg and is represented as seen from below.
Therefore what is really on the left appears on the right, and vice vtrsd. The part of the
area opaca in which the fine vascular network has been formed is sharply limited at the
periphery by the sinus terminalis, and represents the vascular .area ; outside of it lies the
yolk-area. The immediate vicinity of the embryo is destitute of a vascular network, and ia
designated now, as at an earlier stage, by the name area pellucida.

H Heart; AA, aortic arches; Ao, dorsal aorta, L.Of.A, left, R.Of.A, right vitelline artery;
S.T, sinus terminalis ; L.Of, left, R.Of, right vitelline vein ; S. V, sinus venosus ; D.C, ductus-
Cuvieri ; S.Ca.V, superior, V.Ca, inferior cardinal vein. The veins are drawn in outline,
the arteries in solid black.

the area pellucida is still recognisable, being traversed by only a few
chief trunks of blood-vessels leading to the embryo, the body of the-
embryo is enclosed altogether by three zones or areas of the extra-
embryonic part of the germ-layers.

Up to the present we have pursued the formation of blood in the
opaque area. But how do the vessels in the body of the embryo-

186 EMBRYOLOGY.

itself arise ? Here, too, the uncertainty of our present knowledge is
to be emphasised.

According to the representation of His, to which KOLLIKER also
adheres, and which the author himself has made the foundation of
his account in the first edition of this Text-book, blood-vessels in the
embryo are not independently formed, but take their origin from
those already existing in the opaque area. According to His, the
germ of the blood and connective substances, originally a peripheral
fundament, makes its way from the opaque area at first into the
pellucid area, and from there into the body of the embryo itself,
and is distributed everywhere in the spaces between the epithelial
germ-layers and the products that have arisen by constriction from
them. Into the spaces migrate first of all amo3boid cells, which
send out in front of them branched processes ; on the heels of these
follow endothelial vascular shoots.

At variance with the teachings of His are noteworthy investiga-
tions of recent date, — not only the previously mentioned accounts of
the manifold origin of the connective substances from the middle
germ-layers, but also particularly the more recent observations con •
cerning the independent origin of vessels and the endothelial sac of
the heart in the body of the embryo itself. (RUCKERT, ZIEGLER,
MAYER, RABL, KASTSCHENKO, and others.)

For Selachian embryos the question, whether the repository of
the material for the blood-vessels of the embryo is to be sought
exclusively on the nutritive yolk, is, as RUCKERT remarks, to be
answered definitely in the negative. The vessels arise in the embryo
itself within the territory of the mesenchyme, from cells which
are sometimes loosely, sometimes compactly arranged (RtiCKERT,
MAYER).

RUCKERT derives the cells that form the vessels from two different
sources, partly from the inner germ-layer of the yolk-wall, partly
from the adjoining mesoblast, and their double origin appears to
him a natural process of development, in so far as the two layers
which bound the first vessels also furnish the material for their walls.

To the same purport are the accounts concerning the formation
of the endothelial sac of the heart. At first it consists of a rather
irregular mass of cells, in which there appear separate cavities, that
gradually unite to form a single cardiac space. The cell-material
of the fundament of the heart is developed in situ ( RUCKERT, ZIEGLER,
MAYER, RABL, and of the earlier investigators GO"TTE, BALFOUR,
HOFFMANN) from the wall of the bounding germ-layers; however,

DEVELOPMENT OF CONNECTIVE SUBSTANCE AND BLOOD. 187

uncertainty prevails as to whether the inner germ-layer alone,
or the middle, or both, are concerned in the production of the
fundament.

When once the first vessels have been formed, they grow further
independently, and continually give rise to new lateral branches by
means of a kind of budding process.

It can be observed that from the walls of vessels that are already
hollow, solid, slender sprouts go out, which are formed of spindle-
shaped cells, and by means of cross-branches join others to form a
network. The youngest and most delicate of these sprouts consist
of only a few cells arranged in a row, or indeed of only a single one,
which, reposing upon the endothelial tube like a knob, is drawn
out into a long protoplasmic filament. Into the solid sprout there
now projects from the already completed vessel a small evagination,
which gradually elongates and at the same time enlarges into a
tube, the wall of which is formed of the separated cells of the funda-
ment. The formation of blood-corpuscles no longer takes place in this
process, all the cells of the sprout being employed to form the wall of
the vessel. Since out of the vessels thus produced new sprouts
are formed, and so on, the fundaments of the vessels spread them-
selves out everywhere in the spaces between the germ-layers and
the organs which have by constrictions been formed from them.

There are, moreover, two different opinions about the manner in which the
sprouting takes place. Are the solid vascular shoots formed exclusively by
growth of cells in the wall of the endothelial tube, or do neighboring con-
nective-tissue cells take part in their formation ? While EABL holds to the
proposition that new vascular endothelia always take their origin from such as
are already in existence, KOLLIKER, MAYER, and KUCKERT make statements
which appear to prove that the endothelial vascular tubes both continue to
grow by themselves alone, and also to elongate through the participation of
the connective-tissue cells of the surrounding tissue.

In the preceding pages we have endeavored to show in detail
how in Vertebrates the material of the cleavage- cells is differen-
tiated into the separate fundamental or primitive organs. As such
we must designate the outer and the inner germ-layers, the two
middle germ-layers, and the mesenchyme or intermediate layer.

In order properly to estimate at once the significance and the rdle
of these fundamental organs, we will glance at the final result of the
process of development — propound the question, What organs and

188 EMBRYOLOGY.

tissues take their origin in the separate germ-layers and the mesen-
chyme ? A definite answer to this question is possible, except on a
few points concerning which the accounts of the different observers
are still contradictory, and which therefore will be indicated by a
mark of interrogation.

From the outer germ-layer arise : the epidermis, the epidermoidal
organs, such as hair and nails, the epithelial cells of the dermal
glands, the whole central nervous system with the spinal ganglia,
the peripheral nervous system (?), the epithelium of the sensory
organs (eye, ear, nose), and the lens of the eye.

The primary inner germ-layer is differentiated into : —

1. The secondary inner germ-layer, or entoblast ;

2. The middle germ -layers ;

3. The fundament of the chorda ;

4. The germ of the mesenchyme, which forms the intermediate
layer.

The entoblast (Darmdriisenblatt) furnishes the epithelial lining
of the whole intestinal canal and its glandular appendages (lung,
liver, pancreas), the epithelium of the urinary bladder, and th&
taste buds.

The middle germ-layers undergo extremely various metamorphoses
after having been differentiated into primitive segments and lateral
plates.

From the primitive segments are derived the striated, voluntary
muscles of the body and a part of the mesenchyme.

From the lateral plates arise the epithelium of the pleuroperitoneal
cavity ; the epithelium of ovary and testis (primitive ova, mother-
cells of the spermatozoa) ; in general, the epithelial components of
the sexual glands and their ducts, as well as those of the kidney and
ureter ; and finally mesenchymatic tissue.

The fundament of the chorda becomes the chorda dorsalis, which in
the higher Vertebrates is reduced, during later stages of development,
to insignificant remnants.

The mesenchyme-germs, which produce the intermediate layer, un-
dergo manifold differentiations, for they spread themselves out in
the body between the epithelial components as the intermediate mass.
From them are derived ; the multiform group of sustentafcive (con-
nective) tissues (mucous tissue, fibrillar connective tissue, cartilage^
bone), vessels (?) and blood (?), the lymphoid organs, the smooth,
involuntary muscles of the vessels, of the intestine, and of various
other organs.

DEVELOPMENT OF CONNECTIVE SUBSTANCE AND BLOOD. 189

HISTORY OF THE PARABLAST- AXD MESENCHYME-THEORIES.

The older investigators, as, for example, REMAK, grouped together all the
•cells which are inserted between the two primary germ-layers under the
common name of the middle germ-layer, and assumed for them a common
origin. To this conception His opposed in the year 1868 in " Die erste Ent-
wicklung des Hiihnchens im Ei " his " parablast-theory" in which, influenced
principally by histogenetic considerations, he distinguished two fundaments
of different origin, an archiblastic and &parablastic.

As archiblastic fundament he designated the part of the middle germ-layer
which lies in the body of the embryo itself, the axial cord (Achsenstrang) and
the animal and vegetative muscle-plates, and he made them arise by de-
lamination from the primary germ-layers, and therefore ultimately from the
embryonic cleavage-cells.

He gave the name parablastto a peripheral fundament, lying originally outside
the embryo, which is the source of all the connective substances, the blood and
the vascular endothelium, and which grows from the margin, or more speci-
fically from the opaque area, into the body between the archiblastic tissues.

The division of the middle germ-layer into archiblast (chief germ) and
parablast (accessory germ), proposed by His and carried out in several of his
writings, found at the time no approbation, and encountered decided and
successful opposition, especially on the part of HAECKEL. because the correct
views contained in the doctrine were obscured and covered up by peculiar
conceptions about the origin of the parablast. The parablast, it was claimed,
is not derived from the egg-cell, but from the white yolk, a product of the
granulosa-cells, which, according to the earlier teachings of His, penetrate
into the primordial ovum in great numbers and become the white yolk-cells
and the yellow spherules. But the granulosa-cells in turn, it was maintained,
arise from the connective tissue (leucocytes) of the mother ; consequently
after their migration into the egg they are capable of producing again
only connective tissue and blood.

His thought it was necessary to assume a fundamental difference between
chief germ and accessory germ ; the former alone had experienced the influence
of fertilisation, since it alone was descended from cleavage-cells, whereas the
latter, since it issued from the white yolk (a derivative of the maternal con-
nective tissue), was " purely a maternal dower."

RAUBER, in a short communication, accepted the conclusions of His, in so
far as he also assumed a common origin for blood and connective tissue, a
special " haemo-desmoblast," but differed from him in that he derived them
from the cleavage-cells.

GOETTE (1874) is also to be mentioned in this connection, since he maintained
that the blood is developed out of yolk-cells, which break up into clusters of
smaller cells (Amphibia and Birds).

Proceeding from other standpoints, and induced by observations on In-
vertebrates, my brother and I were led in our Coelom-Theory (1881) to a result
similar to that of His, namely, that two entirely different structures had been
hitherto embraced under the expression middle germ-layer, and that it was
necessary to introduce in the place of the old indefinite conception two new
and more precise ones, " middle germ-layer in the restricted sense " and " mesen-
chyme-germ" But our conception, notwithstanding many points of agree-
ment, took in detail a form very different from the doctrine of His.

190 EMBRYOLOGY.

All fundaments of the animal body are derived from embryonic cells, which
have been produced from the egg-cell by the process of cleavage. The dis-
tinction between middle germ-layer and mesenchyme-germ is to be sought
in another direction than in that indicated by His. The middle germ-layers
are sheets of embryonic cells, having an epithelial arrangement, which arise by
a process of folding from the inner germ-layer, just as the latter does by a fold-
ing of the blastula (compare the historical part of Chapter VII.). The mesen-
chymatic germ, on the contrary, embraces cells, which have been individually
detached from epithelial union in the inner germ-layer, and furnish the founda-
tion for connective substance and blood by spreading themselves out in the
system of spaces between the epitlielial germ-layers.

After the appearance of the Ccelom-Theory, His entered again into an
explanation of his parablast-theory, and modified it in his paper, " Die Lehre
vom Bindesubstanzkeim," in so far as he no longer laid weight on the
question whether the fundament of the connective substance was derived from
the segmented or the unsegmented germ.

The theory of the double origin of the middle germ-layers, established by-
His and by us in different ways, met with opposition on the part of KOLLIKER
who held to the older interpretation ; but by many others it was accepted ;
attempts were made further to confirm and also to modify it by KUPFFER,
DISSE, WALDEYER, KOLLMANN, HEAPE, and others, who defended the existence
of a special connective-tissue germ.

KUPFFER and his followers furnished important observations concerning
the presence of yolk-nuclei in a definite zone of the embryonic fundament, and
their relation to the formation of blood in Fishes and Eeptiles.

HOFFMANN and KUCKERT showed that the yolk -nuclei do not arise by free
[spontaneous] formation of nuclei, but are descendants of the cleavage-nucleus.

DISSE investigated the germ-wall of the Hen's egg.

KOLLMANN named the cells which migrate out between the germ-layers
poreuts (Poreuten), and the whole fundament the acroblast.

Finally, WALDEYER endeavored to derive the connective-tissue germ from
a special part of the cleavage-material, which he divided into an archiblast
and a parablast.

According to WALDEYER'S theory, the cleavage of the eggs of all those
animals in which there is any blood and connective substance does not take
place uniformly up to the end, but one must distinguish a primary and a
secondary cleavage. " The former divides the egg, so far as it is in any way
capable of cleavage, into a number of cells, which are ready for the production
of tissues. These then form the primary germ-layers. A remnant of im-
mature cleavage-cells (in the case of holoblastic eggs), or of egg-protoplasm,
which is not yet converted into the cell-form (in meroblastic eggs), is left
remaining. Neither the immature cells, nor the protoplasm still unconverted
into cells, enter for the present into the integrating condition of the germ-
layers. On the contrary, it is only afterwards that there is effected on this
material a further formation of cells, the secondary cleavage. The immature
cells of the holoblastic eggs, over-loaded with nutritive yolk, divide them-
selves, or, if one prefers, ' cleave ' themselves further, or the parts which are
most richly provided with protoplasm constrict themselves off from the
eggs, whereas the remnant of the nutritive material is consumed, — the
unformed remnants of the protoplasm (germ-processes) of meroblastic eggs
become divided up into cells. The cell-material thus secondarily acquired

DEVELOPMENT OF CONNECTIVE SUBSTANCE AND BLOOD. 191

migrates in between the primary germ-layers, and becomes blood and connec-
tive substance."

According to the recent investigations of EABL, ZIEGLER, VAN WIJHE,
KiiCKERT, and others, the mesenchyme is produced from various regions of
the middle germ-layer. A participation of the inner germ-layer in the forma-
tion of the blood-vessels is rendered probable.

SUMMARY.

1. Besides the four germ-layers, which have the form of
epithelial lamellae, special germs are developed in the higher
Vertebrates for the sustentative substances and the blood, — the
mesenchyme-germs. The latter together make up the intermediate
layer.

2. The mesenchyme-germs arise by cells detaching themselves
from epithelial union with the germ-layers, and penetrating as
migratory cells into the fissure between the four germ-layers (the
remnant of the original cleavage-cavity) and spreading themselves out
in this space.

3. Germ-layers and mesenchyme -germ (intermediate layer) ex-
nibit a difference in the method of their origin: the former are
developed by foldings of the wall of the blastula, the latter by emi-
gration of isolated cells from definite territories of the germ-layers.

4. Mesenchyme-germs arise from the wall of the primitive segment,
from the cutis-plate, and at certain regions of the parietal and!
visceral lamellae of the middle germ-layer.

5. Blood-vessels are developed both in the body of the embryo
itself, in a manner which still remains to be accurately determined,
and also in the territory of the area opaca of meroblastic eggs.

6. The source of the cells from which the vessels and blood of
the opaque area arise is at present a matter of controversy.

7. In the formation of vessels in the opaque area the following
phenomena are to be regarded : —

(a) The embryonic cells of the intermediate layer arrange-

themselves : —

First into a network of cords, and

Secondly into the substance-islands (Substanzinseln).

(b) There are developed out of the cell-cords, at the same time

with the secretion of the fluid portions of the blood, the
endothelial wall of the primitive blood-vessels and their
cellular contents, the blood-corpuscles (blood-islands).

(c) The Substanzinseln become embryonic connective substance

192 EMBRYOLOGY.

(d) The place where blood-vessels and connective substance at

first arise in the opaque area is sharply limited at the
periphery by a circular vessel, the sinus terminalis.

(e) Since the outer and the inner germ-layers further con-

tinue to spread themselves out over the yolk after the
development of the intermediate layer, the body of the
embryo becomes surrounded by three areas : —
First by the area pellucida,
Secondly by the vascular area ending in the sinus

terminalis,

Thirdly by the yolk-area, which is coextensive with
the margin of the overgrowth.

8. The red blood-corpuscles of all Vertebrates possess in the
earliest stages of development the power of increase by means
of division. The red blood-corpuscles of Mammals have at this
time a nucleus.

9. The following table gives a survey of the fundamental organs
of the embryo, and the products of their further development : —

I. Outer Germ-layer.

Epidermis, hair, nails, epithelium of dermal glands, central nervous
system, peripheral nervous system, epithelium of sensory organs, the
iens. •

II. Primary Inner Germ-layer.

1. Entoblast, or secondary inner germ-layer.

Epithelium of the alimentary canal and its glands, epithelium
of urinary bladder.

2. Fundament of the chorda.

3. The middle germ-layers.

A. Primitive Segments.

Transversely striped, voluntary muscles of the body. Parts
of the mesenchyme.

B. Lateral Plates.

Epithelium of the pleuroperitoneal cavities, the sexual cells
and epithelial components of the sexual glands and their
outlets, epithelium of kidney and ureters. Parts of the
mesenchyme.

4. Mesenchyme- germ.

Group of the connective substances, blood-vessels and blood,
lymphoid organs, smooth involuntary muscles.

LITERATURE. 193

LITERATURE.

Afanasieff. Ueber die Entwickelung der ersten Blutbahnen im Huhner-

embryo. Sitzungsb. d. k. Akad. d. Wissensch. Wien, matb.-nat. 01. Bd. 53.

Abth. 2, p. 560. 1866.
Balfour. The Development of the Blood-vessels of the Chick. Quart. Jour

Micr. Sci. Vol. XIII. 1873, p. 280.
Disse. Die Entstehung des Blutes und der ersten Gefasse im Hiihnerei.

Archiv f . mikr. Anat. Bd. XVI. 1879.
Gasser. Der Parablast und der Keimwall der Vogelkeimscheibe. Sitzungsb.

d. naturwiss. Gesellsch. Marburg. 1883.
Gensch. Die Blutbildung auf dem Dottersack bei Knochenfischen. Archiv

f. mikr. Anat. Bd. XIX. 1881.
Gensch. Das secundare Entoderm und die Blutbildung beim Ei der Knochen-

fische. Inaugural-Dissertation. Konigsberg 1882.

Hatschek. Ueber den Schichtenbau von Amphioxus. Anat. Anzeiger. 1888.
His, W. Der Keimwall des Huhnereies und die Entstehung der parablas-

tischen Zellen. Zeitschr. f. Anat. u. Entwicklungsg. 1876, p. 274.
His, W. Die Lehre vom Bindesubstanzkeim (Parablast). Riickblick nebst

kritischer Besprechung einiger neuerer entwicklungsgeschichtlicher Ar-

beiten. Archiv f. Anat. u. Physiol. Anat. Abth. 1882.
Klein. Das mittlere Keimblatt in seinen Beziehungen zur Entwicklung der

ersten Blutgefasse und Blutkorperchen im Huhnerembryo. Sitzungsb. d.

k. Akad. d. Wissensch. Wien, math.-naturw. 01. Bd. 63. Abth. 2, p. 339.

1871.
Kblliker, A. Ueber die Nichtexistenz eines embryonalen Bindegewebskeims

(Parablast). Sitzungsb. d. phys.-med. Gesellsch. Wurzburg 1884.
Kolliker, A. Kollmann's Akroblast. Zeitschr. f. wiss. Zoologie. Bd. XLL

1885, p. 155.
Kolliker, A. Die embryonalen Keimblatter und die Gewebe. Zeitschr. L

wiss. Zoologie. Bd. XL. 1884, p. 179.
Kollmann, J. Der Randwulst u. der Ursprung der Stutzsubstanz. Archiv

f . Anat. u. Physiol. Anat. Abth. 1884.
Kollmann, J. Ein Nachwort. Archiv f. Anat. u. Physiol. Anat. Abth

1884.
Kollmann, J. Der Mesoblast und die Entwicklung der Gewebe bei WirbeL

thieren. Biol. Centralblatt. Bd. III. Nr. 24, 1884, p. 737.
Kollmann, J. Gemeinsame Entwicklungsbahnen der Wirbelthiere. Archiv

f. Anat. u. Physiol. Anat. Abth. 1885.
Kupffer. Ueber Laichen und Entwickelung des Ostseeherings. Jahresbericht

der Comm. fiir wissensch. Untersuchung der deutschen Meere. 1878.
Lankester, Ray. Connective and Vasif active Tissues of the Leech. Quart.

Jour. Micr. Sci. Vol. XX. 1880.
Mayer, P. Ueber die Entwicklung des Herzens und der grossen Gef assstamme

bei den Selachiern. Mittheil. a. d. zool. Station Keapel. Bd. VII. 1887,.

p. 338.
Rabl, C. Ueber die Bildung des Herzens der Amphibien. Morphol. Jahrb.

Bd. XII. 1886.

Rabl, C. Theorie des Mesoderms. Morphol. Jahrb. Bd. XV. 1889.
Rauber. Ueber den Ursprung des Blutes und der Bindesubstanzen. Sitzungsb.

d. naturf. Gesellsch. Leipzig. 1877.

13

194 EMBRYOLOGY.

Kuckert, J. Ueber den Ursprung des Herzendothels. Anat. Anzeiger.

Jahrg. II. Nr. 12. 1887.
Hiickert, J. Ueber die Entstehung der endothelialen Anlagen des Herzens

und der ersten Gefassstamme bei Selachierembryonen. Biol. Centralblatt.

Bd. VIII. 1888.
Strahl. Die Anlage des Gefasssy stems in der Keimscheibe von Lacerta agilis.

Sitzungsb. d. Gesellsch. z. Befbrd. d. ges. Naturwiss. Marburg. 1883, p. 60.
Strahl. Die Dottersackwand und der Parablast der Eidechsen. Zeitschr. f.

wiss. Zoologie. Bd. XLV. 1887.
TTskow. Die Blutgefasskeime und deren Entwicklung bei einem Hiihnerei.

Mem. de 1'Acad. imper. des Sci. St. Petersbourg. Se>. VII. T. XXXV.

Nr. 4. 1887.
"Waldeyer. Archiblast und Parablast. Archiv f. mikr. Anat. Bd. XXII.

1883, pp. 1-77.
Wenckebach. Beitrage zur Entwieklungsgeschichte der Knochenfische,

Archiv f. mikr. Anat. Bd. XXVIII. 1886, p. 225.
Ziegler. Der Ursprung der mesenchymatischen Gewebe bei den Selachiern.

Archiv f. mikr. Anat. Bd. XXXII. 1888.
Ziegler. Die Entstehung des Blutes bei Knochenfischembryonen. Archiv f.

mikr. Anat. Bd. XXX. 1887.

CHAPTER X.
ESTABLISHMENT OF THE EXTERNAL FORM OF THE BODY.

AFTER having investigated in the preceding chapters the fundamental
organs of the body of vertebrated animals, or the germ-layers, and
their first important differentiations into neural tube, chorda, and
primitive segments, as well as the origin of the blood and connective
tissues, it will be our next undertaking to make ourselves acquainted
with the development of the external form of the body, and with the
development of the embryonic membranes, the latter being intimately
connected with the former.

There exists an extraordinary difference in these respects between the
lower and higher Vertebrates. When the embryo of an Amphioxus
has passed through the first processes of development, it elongates,
becomes pointed at both ends, and already possesses in the main
the worm-like or fish-like form of the adult animal. But the higher
we ascend in the series of Vertebrates, the more are the embryos,
when they attain the stage of development corresponding to the
Amphioxus embryo, unlike the adult animals: at this stage they
assume very singular and strange forms, inasmuch as they become
surrounded by peculiar envelopes and are provided with various
appendages, which subsequently disappear.

ESTABLISHMENT OF THE EXTERNAL FORM OF THE BODY. 195

The difference is referable, first of all, to the more or less extensive
accumulation of nutritive yolk, the significance of which for the
nascent organism is twofold.

From a physiological point of view, the nutritive yolk is a rich
source of energy which alone makes it possible for the embryological
processes to take place in uninterrupted sequence, until at length an
•organism, with an already relatively high organisation, begins its
independent existence.

From a morphological point of view, on the other hand, the yolk plays
the role of ballast, which exerts a restrictive and modifying influence
on the direct and free development of those organs which are en-
trusted with the reception and elaboration of it. Even at the very
beginning of development we could see how the cleavage-process and
the formation of the germ-layers were retarded, altered, and to a certain
extent even suppressed by the presence of yolk. In what follows we
shall again have occasion to point out the same thing, — how, owing
to the presence of yolk, the normal formation of the intestinal canal
and of the body can be attained only gradually and by a circuitous
process.

In the second place, the great difference which the embryos of
Vertebrates present is produced by the medium in which the eggs
undergo development. Eggs which, like those of water-inhabiting
Vertebrates, are deposited in the water, are developed in a more
simple and direct manner than those which, provided with a firm
shell, are laid upon the land, or than those which are enclosed in
the womb up to the time of the birth of the embryos.

In the two latter cases the growing organism, attains its goal only
by very indirect ways. At the same time with the permanent organs
there are also developed others which have no . significance for the
post-embryonic life, but which serve during the egg-stage of exist-
ence either for the protection of the soft, delicate, and easily injured
tody, or for respiration, or for nutrition. These either undergo
regressive metamorphosis at the end of embryonic life, or are cast
•off at birth as useless and unimportant structures. But inasmuch as
they are developed out of the germ-layers, they are also properly to
be regarded as belonging immediately to the nascent organism — as
being its embryonic organs, and as such they too are to be treated in
morphological descriptions.-

The extensive material which has to be mastered in this cori-r
aiection I shall present grouped into two parts.

In the first part we shall inquire how the embryo overcomes the

196

EMBRYOLOGY.

obstacle which it encounters in the presence of the yolk and acquires
its ultimate form.

In the second and likewise more extensive part we must concern
ourselves more minutely with the embryonic enveloping structures
and appended organs, which subserve various purposes.

The collection of yolk-material disturbs the course of development
least in the case of the Amphibia. The latter therefore stand,
as it were, midway between Amphioxus with direct development

and the remaining Verte-
brates, and constitute a>
transition between them.
In the Amphibia the yolk
shares in the process of
cleavage; after the close of
this process it is found ac-
cumulated for the most part
in the large yolk-cells which
form the floor of the blastula
(fig. 45) ; at the time of the
differentiation into germ-
layers it is taken up into the
ccelenteron, which it almost
completely fills (fig. 47); after
the formation of the body-
sacs the large yolk-cells lie
in a similar manner in the

ventral wall of the intestine proper (fig. 118 yti). Here they are in
part dissolved and employed for the growth of the remaining parts
of the body, in part they share directly in the formation of the
epithelium of the ventral wall of the intestine.

In consequence of the presence of the great accumulation of yolk-
cells, the Amphibian embryo acquires a shapeless condition at a time
when the Amphioxus larva has already become elongated and fish-
like. The body, which is spherical during gastrulation, later becomes-
egg-shaped, owing to its elongation. Thereupon the head-end and
the tail-end begin to be established at the two poles as small eleva-
tions (figs. 118 and 80). The middle or trunk-part lying between
the latter becomes somewhat incurved along its dorsal region, in>

Fig. 118. — Diagrammatic longitudinal section through
the embryo of a Frog, after GOETTE, from BALFOUR.

nc, Neural tube ; x, communication of the same with
blastopore and coelenteron (al) ; yk, yolk-cells ; m,
middle germ-layer. For the sake of simplicity the
outer germ-layer is represented aa if composed of
a single layer of cells.

ESTABLISHMENT OF THE EXTERNAL FORM OF THE BODY. 197

•which neural tube, chorda, and primitive segments are developed, so
that the cephalic and caudal elevations become joined by means of
•a concave line. The ventral side of the trunk-region, on the con-
trary, is greatly swollen and bulges out ventrally and laterally like
a hernia, since it is filled with yolk-cells. This swelling is therefore
called the yolk-sac.

In the further progress of development the embryo continually
-acquires a more fish-like shape. The anterior and the posterior
ends of the body, especially the latter, increase greatly in length,
and the middle of the trunk becomes thinner, for with the consump-
tion of the yolk-material the yolk-sac becomes smaller and finally
•disappears altogether, its walls being incorporated into the ventral
wall of the intestine and that of the body.

The interferences in the normal course of development become greater
in the same ratio as the yolk increases in amount, as it does in the
-case of the meroblastic eggs of Fishes, Reptiles, and Birds. With
the latter the yolk is no longer broken up into a mass of yolk-cells,
as in the case of the Amphibia ; it participates in the process of
cleavage, but only to a slight extent, inasmuch as nuclei make their
way into the layer of yolk which is adjacent to the germ, and, sur-
rounded by protoplasm, continue to increase in number by division.
The gastrula-form is altered until it becomes unrecognisable; only
a small part of its dorsal surface consists of cells, which are
arranged into the two primary germ-layers, whereas the whole
ventral side, where in the Amphibia the yolk-cells are found, is an
imsegmented yolk-mass.

Thus we acquire in the case of the Vertebrates mentioned a
peculiar condition; the embryo, if we regard the yolk as not
^belonging to the body, appears to be developed from layers that are
spread out flat instead of from a cup-like structure (Plate I., fig. 1,
page 213). Moreover we see even a greater distinction effected
between the dorsal and ventral surfaces of the egg during develop-
ment than was the case with the Amphibians. The fundaments of
all important organs, the nervous system, the chorda, the primitive
segments (Plate I., figs. 2, 8), are at first produced exclusively on the
former, whereas on the ventral side few and unimportant changes only
are to be observed. These consist principally in the extension of the
germ-layers, which spread out farther ventrally, grow over the yolk-
mass (Plate I., figs. 2-5), and form around it a closed sac consisting
of several layers. This circumcrescence of the unsegmented yolk by
the germ-layers is accomplished, on the whole, very slowly, the more

198

EMBRYOLOGY.

voluminous the accumulated yolk-material, the more time it requires :;
thus, for example, in the case of Birds it is completed at a very late
stage of development, when the embryo has already attained a high
state of perfection (Plate I., fig. 5).

In the case of meroblastic eggs, the part of the germ-layers
on which the first fundaments of the organs (neural tube, chorda,
primitive segments, etc.) appear has been distinguished as the
embryonic area from the remaining part, or the extra-embryonic area.
The distinction is both fitting and necessary ; but the names might
have been more appropriate than " embryonic and extra-embryonic,"
since obviously everything that arises from the egg-cell, and con-
sequently even that

-Ew* which originates in'

the extra-embryonic
area, must be rec-
koned as belonging
to the^embryo. The
differentiation into
two areas persists in
the course of further
development, and be-
comes expressed still
more sharply (fig.
119). The embryonic
area, by means of the
folding of its flattened
layers into tubes,

alone forms the elongated, fish-like body which all Vertebrates a1
first exhibit; the extra-embryonic area, on the contrary, become*
a sac filled with yolk (ds), which, like an enormous hernia, is united
to the embryo (Em) by means of a stalk (st) attached to its belly,
sometimes even while the embryo is still remarkably smalL

We must now explain more minutely the details of the processes
of development which take place in this connection : first the
metamorphosis of the flattened embryonic area- ssto the fish-like
embryonal body, and secondly the formation of the yolk-sac.

In the presentation we shall adhere chiefly to the Hen's egg, but
for the time being we shall leave out of consideration the formation
of the embryonic membranes.

The body of the Chick is developed by a folding of the flattened
layers, and by the constricting off of the tubular structures thus formed-

Fig. 119. — Advanced embryo of a Shark (Pristiurus), after

BALFOUR.
Em, Embryo ; ds, yolk-sac ;'st, stalk of the yolk-sac ; av, arteria

vitellina ; vv, vena vitellina.

ESTABLISHMENT OF THE EXTERNAL FORM OF THE BODY.

199

from the area pellucida. The beginning of the process of folding is
recognisable upon the surface of the blastoderm by means of
certain furrows, the marginal grooves (Grenzrinnen) of His. These
appear earlier in the anterior than in the posterior region of the
embryonic fundament, in correspondence with the law previously
enunciated, according to which
the anterior end of the body
anticipates in development the
posterior end.

At first that part of the

embryonic fundament which is ll'lf'i^^'miiii'i'i'lil11 I "9S?iiiS( «• <•.

destined to become the head is
marked off by means of a cres-
centic groove (fig. 120). In the
case of the Chick this is indicated
during the first day of incubation,
at a time when the first trace
of the nervous system becomes
visible. It lies immediately in
front of the curved anterior end
of the medullary ridges, with its
concavity directed backward.

At a later stage the embryonic
area is marked off laterally. In

the case of the embryo Seen from Fig. 120.-Surface-view of the area pellucida of
~ • r- -mi • 1-1 a blastoderm of 18 hours, after BALFOUR.

the sufiace in ng. 121, in which In front of the primit.ive groove (pr) lies the

medullary furrow (me), with the medullary
ridges (A). These diverge behind and fade
out on either side in front of the primitive
groove ; anteriorly, on the contrary, they are

continuous with each other, and form an arch
behind a curved line, which represents the
anterior marginal groove. The second curved
line, lying in front of and concentric with the
first, is the beginning of the,amniotic fold.

the neural tube is already partly
closed and segmented into three
brain-vesicles, and in which six
pairs of primitive segments are
laid down, there may be re-
cognised at some distance from
these primitive segments two

dark streaks, the two lateral marginal grooves. They become
less distinct in passing from before backward, and wholly disappear
at the end of the primitive groove.

Finally, the tail-end of the embryo is marked off by the posterior
marginal groove, which like the anterior is crescentic, but has its
concavity directed toward the head.

In this manner a small part of the germ-layers, which alone is
required for the construction of the permanent body, is separated by a

200

EMBRYOLOGY.

continuous marginal furrow from the much more extensive extra-
embryonic area, which
serves for the formation
df of evanescent organs like
the yolk-sac and the em-
bryonic membranes.

The marginal grooves
are formed by the infold-
ing of the outer germ-layer
and the parietal middle
layer, which are together
called the somatopleure, and
in such a manner that the
ridge of the original small
fold is directed downward
toward the yolk (Plate I.,
fig. 8 sf). The space en-
closed by the two folded
layers is the marginal
groove (gr). As we have
distinguished on the latter
several regions, which are
developed at different times,
so must we here distinguish
the corresponding folds,
and we consequently speak
of a head/old, a tail-
fold, and the two lateral
folds.

The kead/old appears,
first of all, even on the
first, but more distinctly
on the second, day of in-
cubation. By means of
it the head-end of the
embryonal fundament is
formed and separated from
the extra-embryonic part
of the germ -layers. At
the moment of its origin it is turned directly downward toward the
yolk; but the more it enlarges, — whereby the anterior marginal

pr

Tig. 121.— Blastoderm of the Chick, incubated 33 hours,
after DUVAL.

One sees the pellucid area, hf, surrounded by a portion
of the opaque area, df. The fundament of the nervous
system is closed anteriorly and segmented into three
brain-vesicles, hb1, hb*, hb3; behind, the medullary
fold mf is still open. On either side of it lie six
primitive segments, us. The posterior end of the
fundament of the embryo is occupied by the primitive
streak with the primitive groove, pr.

ESTABLISHMENT OF THE EXTERNAL FORM OF THE BODY.

201

groove is deepened into a pit, — the more its ridge is turned back-
wards.

Two diagrammatic longitudinal sections, one of which is shown in
£g. 122, the other on Plate I., fig. 11, may serve to illustrate this
process.

In fig. 122 there is shown, projecting above the otherwise smooth
flat surface of the germ-layers, a small protuberance, which encloses
the anterior end of the neural tube (N.C) and the simultaneously
forming intestinal tube (Z>), and which has arisen by the formation
•of the fold F.So. The upper sheet of the fold, by directing itself

N.C

Tig. 122.— Diagrammatic longitudinal section through the axis of an embryo Bird, after

BALFOUR.
The section represents the condition when the head-fold has begun, but the tail-fold is still

wanting.
JF.So, Head-fold of the somatopleure ; F.Sp, head-fold of the splanchnopleure, forming at Sp the

lower wall of the front end of the mesenteron ; D, cavity of the fore gut ; pp, pleuroperitoneal

cavity ; Am, fundament of the anterior fold of the amnion ; N.C, neural tube ; Ch, chorda ;

A, B, C, outer, middle, inner germ-layer, everywhere distinguished by different shading;

Ht, heart.

backwards, furnishes the ventral wall of the cephalic elevation ; the
lower sheet forms the floor of the marginal groove.

In the second figure, in which there is represented a diagrammatic
longitudinal section through an older embryo, the head-fold (kfl) has
extended still farther backward. The head has thereby become
longer, since its under surface has increased in consequence of the
advance in the process of folding.

Whoever desires to make this process, which is very important for
-the comprehension of the construction oi animal forms, clearer and
more intelligible, may do so with the help of an easily constructed
model. Let him stretch out his left hand on a table, and spread flat
•over the back of it a cloth, which is to represent the blastoderm ;
then let him fold in the cloth with his right hand by tucking it a
little way under the points of his left fingers. The artificially pro-
duced fold corresponds to the head-fold previously described. The

202 EMBRYOLOGY.

points of the fingers, which by the tucking under of the cloth have-
received a covering on their lower sides, and which project above
the otherwise flattened cloth, are comparable to the cephalic eleva-
tion. In addition we can represent the backward growth of the
head-fold by tucking the cloth still farther under the left fingers
toward the wrist.

The hinder end of the embryo develops in the same manner as the
front end, only somewhat later (compare fig. 11, Plate I.). Corre-
sponding to the posterior marginal groove (gr), the tail-fold is so formed
that its ridge is directed forward and that it grows toward the head-fold.

Where in surface-views of the blastoderm the lateral marginal
grooves are to be seen (fig. 121), one recognises on cross sections the
lateral folds (Plate I., fig. 8 sf). They grow at first directly from
above downwards, thus producing the lateral walls of the trunk.
Afterwards their margins bend somewhat toward the median plane
(Plate I., fig. 9s/), thereby approaching each other, and in this way
gradually draw together to form a tube (Plate I., fig. 10). By their
infolding the trunk acquires its ventral wall.

In order to avoid misconceptions, let it be further remarked that
only at the beginning of their formation are head-, tail-, and lateral,
folds somewhat separated from one another, but that when they
are more developed they are merged into one another, and thus are
only parts of a single fold, which encloses the fundament of the embryo
on all sides.

As the separate parts of this fold increase, they grow with their
bent margins from in front and from behind, from right and from
left, toward one another, and finally come near together in a small
territory, which corresponds approximately with the middle of the
surface of the embryo's belly, and is designated on the figure of the
cross section through this region (Plate I., fig. 10) by a ring-like line
(hn). Thus a small tubular body is formed (Plate I., fig. 3), which lies
upon the extra-embryonic area of the blastoderm and is united to it
by means of a hollow stalk (hn). The stalk marks the place where
the margins of the folds, growing toward one another from all sides,
have met, but a complete constricting off of the embryonic territory
from the extra-embryonic does not take place.

We can also represent these conditions, if, in the previously men-
tioned model, we in addition fold in the cloth that covers the tips
of the fingers along the sides of the hand and the wrist, and then,
carry the circular fold thus artificially formed still farther under,,
even to the middle of the palm. Then the cloth forms around the

ESTABLISHMENT OF THE EXTERNAL FORM OF THE BODY. 203

hand a tubular sheath, which is continuous at one place by means
of a connecting cord with the flattened remaining portion of the
cloth.

A process similar to the externally visible one just described, by
which the lateral and ventral walls of the body are produced from
the sheet-like fundaments, takes place at the same time within the
embryo in the splanchnopleure. There are developed from it, as
from the somatopleure, an anterior, a posterior, and two lateral
intestinal folds.

First, at the time when the head is differentiated (fig. 122), the
part of the splanchnopleure corresponding to it (F.8p.) is folded
together into a tube, the so-called cavity of the fore gut or head-gut (D).

The same process repeats itself on the third day of incubation at
the posterior end of the embryonal fundament, where, upon the
appearance of the caudal part (Plate I., fig. 11), there is formed
within it and out of the splanchnopleure the cavity of the hind gut.

Both parts of the intestine at first terminate with blind ends
directed toward the outer surface of the body. At the head-end
the mouth-opening is still wanting, at the posterior end the anus.
When, however, one raises the blastoderm with the nascent embryo
from the yolk, and examines it from the under side, the anterior
and posterior portions of the intestinal canal exhibit openings (vdpf
and hdpf). through which one can look from the yolk-side into the
blind-ending cavities. One of these is called the anterior, the other
the posterior, intestinal portal or intestinal entrance (Plate I., fig. 11
vdpf and hdpf).

Between the two portals the middle region of the intestinal canal
remains for a long time as a leaf -like fundament. Then by its
becoming somewhat bent downwards (Plate I., figs. 9 and 2) there
arises under the chorda dorsalis an intestinal groove (dr\ which lies
between fore and hind gut. Owing to the further increase of the
lateral intestinal folds (df), the groove becomes deeper and deeper,
and finally, by the approximation of the edges of the folds from in
front, from behind, and from both sides, becomes closed into a tube
in the same manner as the wall of the body.

At only one small place, which is indicated by the ring-like line
dn in Plate I., figs. 3 and 10, the folding and constricting-off process
is not completed, and here the intestinal tube too remains con-
tinuous, by means of a hollow stalk, with the extra-embryonic part
of the splanchnopleure, which encloses the yolk.

The pai't of the germ-layers which is not employed in the formation

204

EMBRYOLOGY.

of the embryo furnishes in the case of the Reptiles and Birds the
yolk-sac and certain embryonic membranes. I shall speak of the
development of these in the next chapter.

The fate of the extra-embryonic area of the blastoderm in Fishes
is more simple, since there is formed from it only a sac for the
reception of the yolk.

Fig. 123 exhibits the embryo (Em) of a Selachian, which has
arisen by the infolding of a small area of the germ-layers in the

manner described for

Era> the Chick. All the

remaining part of
the egg has become
a great yolk-sac (ds),
which is united with
the middle of the
belly by means of a
long stalk.

The Teleosts (Plate
I., fig. 6) show us
transitions from this
(Pristiurus), after condition to one in
which the yolk-sac,
as in Amphibians,
is not separated by

a stalk from the mesenteron, but represents only a capacious
enlargement of the latter and of the belly-wall.

Let us now examine more carefully the structure of the yolk-sac.
As has been remarked already, all four of the germ-layers spread
themselves out one after another around the unsegmented yolk-mass
of meroblastic eggs (Plate I., figs. 6 and 7). As in the embryonal
body the two middle germ-layers separate from each other and allow
the body-cavity to appear between them, so, too, at a later stage
the same process occurs in the extra-embryonic area. Throughout
the region of the middle germ-layer there is formed a narrow
fissure, for which the name " extra-embryonic body-cavity," or
blastospheric coelom (cavity of the blastoderm, KOLLIKER), would be
most suitable. It separates the envelope of the yolk into two layers,
of which the inner is the immediate continuation of the intestinal
wall (splanchnopleure), the outer, on the contrary, that of the body-
wall (somatopleure). Therefore, to be exact, we have before us a
double sac formed around the yolk, which we can distinguish as

Pig. 123.— Advanced embryo of a Shark

BALFOUR.
Em, Embryo ; ds, yolk-sac ; st, stalk of the yolk-sac ; av, arteria

vitellina ; vv, vena vitellina.

ESTABLISHMENT OF THE EXTERNAL FORM OF THE BODY. 205

intestinal yolk-sac and dermal yolk-sac. The former is simply a,
hernia-like e vagina tion of the intestinal canal, and, like it, is
composed of three layers : —

(1) The intestine-glandular layer (ik), — the entoblast or secondary
entoderm, which encloses the yolk ;

(2) The visceral middle layer, or the pleuroperitoneal epithelium
(m*») ; and

(3) The intermediate layer (Zwischenblatt), in which have been
developed the vitelline blood-vessels, which at the beginning of the
circulation of the blood have to conduct the liquefied nutritive
material from the yolk-sac to the places of embryonic growth.

The dermal yolk-sac is, as a continuation of the body-wall, likewise-
composed of three layers — the epidermis (ak), the parietal middle
layer (mkl), and the connective-tissue intermediate substance
(Zwischensubstanz) .

It has already been stated that the constricting-off of the yolk-sac
from the embryonal body is quite variable in extent, and can go so-
far that the connection between the two is kept up only by mean&
of a narrow stalk. A more careful examination shows that in the
latter case the stalk itself is composed of two narrow tubes one
within the other (Plate I., fig. 7), of which the outer unites the
dermal yolk-sac (hs) to the ventral wall of the body, and the inner
the intestinal yolk-sac to the intestinal canal. The former is called
the dermal stalk, the latter the intestinal stalk (dn) or vitelline
duct, ductus vitello-intestinalis. The place of attachment of the
dermal stalk in the middle of the ventral surface of the embryo is
called the dermal navel (hn) ; the corresponding place of attachment
of the intestinal stalk to the wall of the intestine the intestinal
navel (dn). The embryonic body-cavity opens out between the two,
and is continuous with the fissure between dermal and intestinal
yolk-sac — with the "extra-embryonic body-cavity" or the blasto-
spheric ccelom (Ui2).

The ultimate fate of the yolk-sac in the Fishes is the same as in.
the Amphibia. It is still employed, even in the extreme case of the
Selachians, for the formation of the wall of the intestine and that
of the body. The more its contents are liquefied and absorbed,
the more the yolk-sac shrivels. When the intestinal yolk-sac has
become very small, it is drawn into the body-cavity and finally
serves to close the intestinal navel, just as the dermal yolk-sac upon
its disappearance closes up the dermal navel. With the lower
Vertebrates a shedding of the embryonic parts has not yet come into-

206 EMBRYOLOGY.

existence. The next chapter will explain what becomes of tho
yolk-sac in the case of Reptiles and Birds.

SUMMARY.

1 . In the case of Vertebrates whose eggs contain little yolk, the
embryo after the development of the germ-layers takes on an
•elongated, fish-like form.

2. In eggs with abundant yolk the body of the vertebrated animal
is produced by only a small region of the germ-layers (the embryonic
fundament); the far greater extra-embryonic area is employed for
the formation of a yolk-sac and of embryonic membranes (the latter
only in Reptiles and Birds).

3. The separate layers of the embryonic fundament constrict them-
selves off from the extra-embryonic territory, and at the same time
become folded into tubes — the somatopleure into the tubular body-
wall, the splanchnopleure into the intestinal tube (head-fold, tail-fold,
lateral folds, intestinal groove, intestinal fold).

4. The extra-embryonic territory of the germ-layers remains in
•continuity with the two tubes by means of a stalk-like connection.

5. In Fishes the extra-embryonic territory of the germ-layers
becomes the yolk-sac, which is composed of two sacs, the intestinal
and the dermal yolk-sacs, separated from each other by a pro-
longation of the embryonal body-cavity.

6. The place where the dermal yolk-sac is attached to the belly -
wall of the embryo by a stalk-like prolongation is called the dermal
navel or umbilicus ; the corresponding place of attachment of the
intestinal yolk-sac to the middle of the intestinal canal is the
intestinal navel or umbilicus.

7. In Fishes the yolk-sac after resorption of the yolk-material,
accompanied by the phenomena of shrivelling, is employed for the
closure of the intestinal and dermal navels.

8. In Reptiles and Birds the extra-embryonic region furnishes,
in addition to the yolk-sac, several other embryonic membranes,
which, complicate the development.

CHAPTER XI.

THE FCETAL MEMBRANES OF REPTILES AND BIRDS.
As has already been stated, the course of development in all animals
which do not deposit their eggs in water — in Reptiles, Birds, and
Mammals — is unusually complicated, owing to the appearance of

THE F(ETAL MEMBRANES OF REPTILES AND BIRDS.

207

special egg-envelopes (embryonic or foetal membranes). Some of
them, according to their origin, are to be referred to the extra-
•embryonic area of the germ-
layers, and indeed to that part
which in Fishes is employed for
the yolk-sac. They arise from
folds, which grow around the
embryo while it is still small,
and furnish a double envelope
for it.

The egg- envelopes (embryonic
membranes) of Reptiles and
Birds, which exhibit almost
identical conditions, and the
consideration of which we shall
take up first, are more simply
constituted than those of Mam-
mals. In the case of the former
there are associated with the
yolk-sac, in the possession of
which they agree with the
Amphibia and Fishes, three
additional embryonic appen-
dages, the amnion, the mem-
•brcvna serosa (or briefly Derosa),
and the allantois. They are
partly laid down at an early
period, at the time when the'
embryonic body is converted -

into tubes by the infolding of the germ-layers and is thereby con-
stricted off from the yolk-sac.

The Chick shall again serve as a basis for our description.

Fig. 124.— Surface-view of the pellucid area of
. a blastoderm of a Chick of 18 hours, after

BALFOUR.

In front of the primitive groove, pr, lies the
medullary furrow surrounded by the medullary
folds. Immediately in front of these one sees
a curved line, the head-fold, and in front of
it a. second curved line running concentric
with it, the anterior fold of the amnion.

1. The Amnion, the Serosa, and the Yolk-Sac.

The amnion is a structure the appearance of which is recognisable
remarkably early in the Chick. At the time when one recognises
the semicircular head-fold at the anterior end of the incipient embryo
(fig. 124), by the growth of which the head of the embryo is marked
off, there is already present, at a short distance from it, a second fold
running parallel to it. This is the anterior fold of the amnion, a

208

EMBRYOLOGY.

product of the extra-embryonic part of the ectoderm and of the
parietal mesoderm united with it.

The two infoldings, which lie near to each other, have opposite

Fig. 125.— Diagrammatic longitudinal section through the axis of an embryo Bird, after

BALFOUR.
The section represents the condition when the head-fold is already formed, but the tail-fold i»

still wanting.
F.So, Head -fold of the somatopleure ; F.Sp, head-fold of the splanchnopleure, forming at Sp

the floor of the anterior part of the intestine. For the remaining references see fig. 122,

p. 201.

directions (fig. 125). While the head-fold (F.So) advances with its
margin toward the yolk, the anterior fold of the amnion (Am), sepa-
rated from it by the marginal groove, rises externally above the

Fig. 126. — Diagrammatic longitudinal section through the posterior end of an embryo Chick at

the time of the formation of the allantois, after BALFOUR.
tp, me, hy, Outer, middle, and inner germ-layers ; ch, chorda ; Sp.c, neural tube ; n.e, neurenteric

canal ; p.a.g, post-anal gut ; pr, remains of the primitive streak folded toward the ventral

side ; al, allantois ; an, point where the anus will be formed ; p,c, perivisceral cavity ;

am, amnion ; so, somatopleure ; sp, splanchnopleure.

plane of the blastoderm. At the time when the head is being formedr
the amnion enlarges rather rapidly (Plate I., fig. 1 1 vaj), and grows over
and around the head in a cap-like fold, the rim of which is directed
backwards. At the end of the second day of incubation it already

THE F(ETAL MEMBRANES OF REPTILES AND BIRDS.

209

covers the anterior part of the head like a thin transparent veil, and
is therefore called the cephalic sheath.

In like manner, but at a somewhat later stage, there arise at the
tail-end and at both sides of the embryo the posterior and lateral
folds of the amnion. Tlie posterior fold is still very inconspicuous even

at the time when the head is covered with the veil-like pellicle
(Plate I., fig. 11 haj). It enlarges slowly, and under the name of
caudal sheath covers over the posterior end of the body (fig. 126 am).
The lateral folds of the amnion are elevated externally to the lateral
marginal grooves (fig. 127 om), and project in the opposite direction
from those lateral folds by the bending in of which the lateral and
ventral walls of the embryo are produced. By this means the rim

14

210 EMBRYOLOGY.

of the fold is carried farther and farther from the siiunchnopleure
(sp), which remains spread out flat over the yolk. In this way the
extra-embryonic part of the body-cavity, or the cavity of the blasto-
derm (KOLLIKER), increases in extent in the vicinity of the embryo.
When the lateral folds of the amnion have grown up to the dorsal
surface of the embryo (Plate I., fig. 9 saf), they begin, by the bending
over of their edges inedianwards, to form the so-called lateral
sheaths.

Inasmuch as the folds of the amnion, which are called by special
names, become, when they are in full development, continuous, and are
only parts of a single ring like fold, the embryo eventually becomes
surrounded on all sides as though by a high wall. With further
enlargement, the amniotic sheaths then bend together over the back
of the embryo from in front and behind, and frcun the right and
the left (Plate I., figs. 2, 3, and 10, af, vaf, haf), come together
with their edges in the median plane, and then fuse with each other
along a line, the amniotic suture, which closes from in front back-
wards (Plate I., fig. 10), except that at one very small place near
the tail-end the closing is interrupted for a considerable time, and
a small opening is preserved.

The fusion of the amniotic folds takes place in the same manner
as the fusion of the medullary folds described on page 79. Each
fold (Plate I., figs. 3 and 10) consists of two layers, an inner and an
outer one, which are continuous at the margins of the folds, and are
separated by a fissure, which is a portion of the extra-embryonic
body-cavity. At the amniotic suture the corresponding layers of
the folds of both sides fuse, and hand in hand with this a separa-
tion of the inner from the outer layers takes place (Plate I., fig. 4).
As a result of this there have 'now arisen two envelopes over the
back of the embryo, an inner and an outer one, the amnion (A) and
the serosa (S).

The amnion is the product of the inner layer of the folds (Plate I.,
fig. 10 ifb). It forms a sac which immediately after its origin is
closely applied about the embryo, and which encloses a very small
amniotic cavity filled with fluid.

The serous membrane (serosa), which is derived from the outer
layer of the folds (afb, Plate I., fig. 10), lies as a very delicate trans-
parent membrane closely applied to the amnion, and thus encloses
the embryo in still another envelope.

If we now glance back at the conditions described in the previous
chapter, and compare the development of Fishes with that of Reptiles

THE F03TAL MEMBRANES OF REPTILES AND BIRDS. 211

and Birds, it is to be seen that a considerable complication has arisen
in the case of the latter. Whereas in Fishes the extra-embryonic
area of the somatopleure becomes exclusively the dermal yolk-sac, in
Reptiles and Birds two sacs have arisen out of it by a process of
folding. The influences producing this folding appear to be clear.

Since the egg is enclosed in firmly applied envelopes, the embryonic
body, when it is formed by the folding together of the germ-layers,
cannot rise from the yolk-sac ; it therefore comes to lie in a depres-
sion of the latter. There is the more reason for the occurrence of
this because the embryo at the beginning of development is exces-
sively small in comparison with the yolk, and because the yolk-layers
immediately underlying it become liquefied and absorbed. With
the sinking of the body into the yolk (Plate I., figs. 2 and 3), the
parts which in Fishes become the simple dermal yolk-sac (Plate I.,
figs. 6 and 7) fold in around it on all sides as amniotic folds, and
enclose it the more completely the deeper it sinks into the yolk.

The preceding account of the development of the amnion is made some-
what schematic in a single point. That is to say, the anterior fold of the
amnion is developed so early, that the middle germ-layer has not yet been
.able to spread out as far as the anterior part of the embryonic area. The in-
folding, therefore, in this region involves only the outer and inner germ-layers,
which are still closely united. This condition is changed somewhat later,
when the middle germ-layer has grown into the region of the anterior fold of
the amnion, and has there split into a visceral and a parietal layer. The process
has not yet been followed out in detail in series of longitudinal sections. But
at all events we must assume that the entoblast, which is united with the
visceral middle layer,' retracts from the anterior fold of the amnion and
again spreads out flat, as is represented in diagrammatic figure 11 (Plate I.). In
this manner the anterior amniotic fold, which in the meantime has become
greatly enlarged, now consists of the outer germ-layer and the parietal middle
layer, as is the case from the beginning with the subsequently arising posterior
and lateral folds of the amnion.

We now have to enter still more particularly upon the further
relations of amnion and serosa.

Up to the end of embryonic development the amniotic sac remains
in continuity with a small region on the ventral side of the embryo,
which is called the dermal umbilicus. In figs. 3, 4, 5, and 10
(Plate I.) this place is indicated by means of a circular line (7m).
Here the primitive layers of the body- wall are continuous with the
corresponding layers of the amnion, as, for instance, the epidermis of
the body with an epithelial layer lining the amniotic cavity. The
dermal umbilicus of Reptiles and Birds corresponds therefore with

212 EMBRYOLOGY.

the structure of the same name in embryo Fishes (Plate I., fig. 7 hn),
for it is at this point that the dermal yolk-sac is continuous by means
of its stem-like elongation with the walls of the belly. As in the
Fishes, it surrounds an opening (Plate I., figs. 7 and 5 hn) which unites
the portion of the body-cavity lying within the embryo (lhl) with
the extra-embryonic part lying between the embryonic membranes
(Mi2). Furthermore, the stalk of the yolk-sac or vitelline duct,
which is continuous with the embryonic intestine, and which is
indicated in the above-mentioned figures of Plate I. by the small
circle dn, passes through the opening.

The amniotic sac affords an additional special advantage to the
embryos of Reptiles and Birds in that an albuminous saline fluid, the
liquor amnii, collects in its cavity. In it the delicate, easily injured
embryo composed of plastic cells floats, as it were, and is able to
move.

The amniotic sac is small at the beginning of its development, but
enlarges with each day of incubation, since it keeps pace with the
growth of the embryo and encloses a larger and larger amount of
amniotic fluid.

At the same time its wall becomes contractile. Certain cells in its
somatic mesoderm develop into contractile fibres, which in the Chick
give rise to rhythmic movements from the fifth day of incubation
onward. One can observe these while the egg-shell remains intact,
if one holds the egg toward a source of bright light, and for this
purpose makes use of the ob'scope constructed by PREYER. In this
manner it can be determined that the amiiion. executes about ten
contractions in a minute, which, beginning at one pole, proceed to
the opposite end, like the contractions of a worm. Thus the amniotic
fluid is set in motion, and the embryo oscillates or rocks regularly
from one end to the other. The rocking of the embryo, as PREYER
expresses it, becomes more and more obvious in the later days
of incubation, since" the contractions of the amnion become more
energetic.

The serosa (S) is a wholly transparent, easily ruptured membrane^
which is closely applied to the vitelline membrane. It consists of two
thin cell-layers, which take their origin from the outer germ-layer
and the parietal middle layer, and like them are distinguished by
blue and red lines in the diagram. The serous membrane is origin-
ally present as a separate structure only in the region of the amnion
and of the embryo (Plate I., fig. 4), as far as the body-cavity is formed
in the middle germ-layer. It then enlarges to the same extent as the

face, p. 213.

PLATE I

Swan, tSomenschein & Co.

THE FOZTAL MEMBRANES OF REPTILES AND EIEDS. 213

yolk becomes overgrown and as the vascular area extends farther
downwards. Parietal and visceral middle layers separate more and
more from each other, until finally (in the Chick toward the end of
incubation) a separation re suits over the entire periphery of the yolk-
sphere. Figs. 3, 4, and 5, Plate I., show stages in this process. In
the last figure, which represents the condition on about the seventh
day of incubation, the extra-embryonic part of the body-cavity has
already become very considerable ; the serous envelope is, with the
exception of a small place at the vegetative pole of the yolk, every-
where formed as a separate structure.

In connection with this the wall of the yolk-sac also becomes
changed. Whereas at the beginning of the overgrowth it embraces
for a considerable distance all the germ-layers, after the separation
of the serosa it is composed exclusively of entoderm and the visceral
middle layer.

EXPLANATION OF THE FIGURES ON PLATE I.

Figs. 1-5 are diagrammatic representations of cross and longitudinal sections
through the Hen's egg at different stages of incubation. They are intended to
illustrate how the body of the Chick is developed out of the embryonic funda-
ment, and how the yolk-?ac, the amnion, the serosa, and the allantois arise out
of the extra-embryonic area of the germ-layers.

For the sake of clearness the embr3Tonic fundament, and later the embryo,
are represented much too large in relation to the yolk.

In order more easily to distinguish the different parts from one another
different colors have been selected for them. The yolk is represented in
yellow, the entoderm green, the outer germ-layer blue, and the middle germ-
layer, together with the mesenchyme, red. The black dots indicate the limit
to which the outer and inner germ-layers have grown over the yolk in the
different stages ; the red dots mark the boundary for the time being of the
middle germ-layer, which after the development of the blood-vessels ends in
the sinus terminalis.

The references apply to all of the figures.

ak, Outer germ-layer (blue).

mw, Medullary ridges or folds.

N, Neural tube.

(if, Amniotic fold.

vaf, haf, saf, Anterior, posterior, and lateral

amniotic folds.
A, Amnion.
ah, Amniotic cavity.
•S, Serous membrane (Serosa).
hn, Dermal umbilicus.
tf, Lateral folds. */',#", Head-fold; a/6, ifb, I marginal vein.

outer and inner limbs of fold. I dm, vm, Dorsal and ventral mesentevit

dg, Vitelline duct.

al, Allantois.

ds, Intestinal sac.

dn, Intestinal umbilicus.

mi', Middle germ-layer (red).

ink1, Parietal lamella of the same or parietal

middle layer.
ink a, Visceral lamella of the same or visceral

middle layer.
st, Lateral limit of the same, sinus terminalis,

iJc, Inner germ-layer (green).
in-, Its margin of overgrowth.
dr, Intestinal groove.

Ih, Body-cavity. lhl, Embryonic, lh~, extra-
embryonic part of the same.

214 EMBRYOLOGY.

Fig. 1. — Cross section through a Hens egg on the second day of incubation.

The germ-layers are spread out flat over the yolk ; the middle one is less
extensive than the other two. The first blood-vessels have developed, and
terminate with the marginal vein (st) at the edge of the middle germ-layer.
One now distinguishes therefore the vascular area, which extends to the red
dotted line (.«£), and external to it the yolk-area (dh), which terminates with
the black dotted line (ur), the edge of overgrowth of the outer and inner
germ-layers.

Fig. 2. — Cross section through a Hen's egg on the third day of incubation.

The outer and inner germ-layers are spread out over half of the yolk.
The yolk-area (dh~) terminates with the black dotted line (wr), the edge of
overgrowth.

The middle germ-layer, with the vascular area, which is now well developed,
has also grown over the yolk as far as the line st (the sinus terminalis). In
the middle germ-layer the body-cavity has become distinct in the embryonic
region (W) and in its immediate vicinity (7A-), the parietal (mkl) and visceral
middle layers (mfc) having separated from each other.

The embryonic fundament begins to be constricted off from the extra-
embryonic part by a process of folding and to constitute the trunk. The lateral
folds (sf) have grown downwards for a certain distance, thus giving rise to
the lateral walls of the trunk, whereas ventrally the body is still open. Corre-
sponding to these lateral folds («/"), the lateral intestinal folds (df) have
arisen on the splanchnopleure, and bound the intestinal groove (dr).

The embryo in process of being constricted off has sunk into a depression of
the more and more liquefied yolk, and becomes partly enveloped by the somato-
pleure of the extra -embryonic area of the germ -layers, the lateral folds of
the amnion (of) having already encircled the sides of the embryonic body.

Fig. 3 shows a longitudinal section through the stage represented in cross
section in fig. 2. (Third day of incubation.}

The head-end of the body is entirely constricted off from the blastoderm.
It encloses the cephalic portion of the intestine (Kopfdarmhohle). The tail-
end is only slightly differentiated. The anterior fold of the amnion (yaf) has
invested the head, the posterior fold (haf) the tail (cephalic sheath, caudal
sheath).

The middle of the trunk is still wide open ventrally. The place where
the body-wall passes over into the folds of the amnion, and which is indicated
in the diagram by the ring 7m, is called the dermal umbilicus.

The splanchnopleure has become closed into a tube anteriorly and pos-
teriorly (the cephalic and pelvic portions of the intestinal cavity) ; in the
middle the tube is still open ventrally, and by means of the vitelline duct (dg)
is continuous with the yolk- sac (ds). The place of transition indicated by
the ring dn is the intestinal umbilicus. Theallantois (al) grows out as a small
vesicle from the ventral wall of the pelvic portion of the intestinal cavity into
the body-cavity of the embryo.

THE F(ETAL MEMBRANES OF REPTILES AND BIRDS. 215

Fig. 4. — Longitudinal section through a Hen's egg at the beginning of the

fifth day.

After the fusion of the amniotic folds, the embryo, together with the amniotic
cavity (ah), is enveloped in the amniotic sac. The serous membrane (8) has been
developed from the outer layer of the amniotic folds. By further separation
of the middle germ -layers the extra-embryonic part of the body-cavity (ZA2)
has enlarged, and the allantois (al) has grown into it.

With the exception of a third of its surface, the yolk has become overgrown
by the outer and inner germ-layers, as far as the line ur. The vascular area
has extended to the line st. The cephalic portion of the intestinal cavity has
opened into the amniotic cavity by means of the newly arisen mouth (ra).

Fig. 5. — Longitudinal section through a Hens egg on'tlie seventh day of
incubation.

By the enlargement of the extra-embryonic body-cavity the serous membrane
(serosa) has entirely separated from the yolk-sac, with the exception of a small
area. The outer and the inner germ-layers have now grown over the yolk on all
sides ; the middle germ-layer with the vascular area has extended farther
downwards. The amniotic cavity, in which the embryo floats, has become
much extended by the increase of the amniotic fluid. The allantois has
enlarged considerably, and forms a sac, which connects with the hind gut
by means of a narrow stalk (urachus). The sac extends out into the extra-
embryonic body-cavity between amnion, yolk-sac, and serous membrane, more
particularly on the right side of the embryo.

Fig. 6 represents a diagrammatic cross section through an embryo Fish.

The dorsal part is already far advanced in development and encloses the
neural tube (N), the chorda (c/i), the aorta (ao), and the primitive segments.
The ventral side is greatly distended by the considerable yolk-mass (d). The
latter lies in an enlargement of the intestinal canal, the intestinal yolk-sac ;
this is separated from the enlarged dermal yolk-sac by means of a narrow
fissure, the body-cavity (l/t).

Fig. 7. — Diagrammatic longitudinal section through a Selachian embryo.

The yolk-sac has been partly constricted off from the body of the emoryo ;
it still remains united to its ventral side, but only by means of a narrow stalk (st),
which consists of two tubes, one within the other, the intestinal stalk (vitelline
duct) and the dermal stalk. The yolk-sac communicates with the embryonic
intestinal canal by means of the vitelline duct. The point of transition is
called the intestinal umbilicus (dn). The point of attachment of the dermal
stalk to the belly of the embryo is the dermal umbilicus (7m). The space
between dermal and intestinal umbilicus (hn and dn) serves to put the body
cavity of the embryo (lhl) in communication with the body-space (lhz) between
the dermal and intestinal volk-sacs.

216 EMBRYOLOGY

Figs. 8, 9, 10, 11. — Diagrammatic cross and longitudinal sections through
embryo Chicks of different ayes.

Fig. S.—Half of a cross section through an embryo Chick oj two days, after

KOLLIKEE.

The embryonic body, in which the neural tube (JV), chorda (ch), primitive
segment with its cavity (ush), primitive aorta (ao), and the fundament of the
primitive kidney (un) are to be seen, is marked off from the extra-embryonic
region of the germ-layers by the marginal groove (gr). The body-wall begins
to be developed, owing to the somatopleure having given rise to the lateral fold
(sf), the ridge of which is directed toward the yolk. External to it the lateral
fold of the amnion (saf) rises in an opposite direction.

Fig. 9. — Cross section of an embryo Chick at the beginning of the third day,

after KOLLIKEE.

The lateral folds (sf) have grown farther downward, and have completed the
body-wall. The lateral folds of the amnion (saf) likewise have risen up farther
toward the back of the embryo. The splanchnopleure has folded in to
form the groove dr. The dotted line hn indicates the still broad dermal
umbilicus, the line dn that of the intestinal umbilicus.

Fig. 10. — Cross section through the trunk of a five-days embryo Chick in the
region of the umbilicus, after KEMAK.

By an approximation of the lateral folds, the body-wall has been completely
formed up to the region enclosed by the line hn, in which the body-cavity still
possesses an opening, and communicates with the extra-embryonic portion of
the body-cavity. At the line hn, the dermal umbilicus, the body-wall bends
over into the folds of the amnion (a/), which have grown over the back of the
embryo, and are about to fuse along their edges. At the dermal umbilicus
(dn) the intestinal tube (d) passes over into the yolk-sac, which is not
represented.

Fig. 11. — Diagrammatic longitudinal section through an embryo Chick.

The head is already fully differentiated from the blastoderm by the process
of folding, the tail-portion is less completely separated ; the former encloses
the cephalic portion of the intestinal cavity (kd), which is in connection with
the yolk-sac by means of the anterior intestinal portal (v.dj>f). The pelvic
portion of the intestinal cavity, which shows the first traces of the allantois
(al), communicates backwards and above with the neural tube by means of the
neurenteric canal (en), and toward the yolk-sac by means of the posterior
intestinal portal (h.dpf). The head-end is already partly ensheathed by the
anterior amniotic fold (vaf), whereas at the tail-end the posterior amniotic fold
(haf) is just beginning to be elevated.

THE F(ETAL MEMBRANES OF REPTILES AND BIRDS. 217

2. The Allantois.

While the development of the amnion is still going on, there is
formed in Reptiles and Birds an embryonic organ of no less import-
ance, the allantois, or urinary sac. It has two different functions
to perform at the same time. In the first place it S3rves, as its
name implies, for the reception of the excretory products which are
furnished during embryonic life by the kidney and primitive kidney ;
and secondly, by virtue of the abundance of blood-vessels and the

Fig. 128.— Diagrammatic longitudinal section through the posterior end of an embryo Chick at
the time of the formation of the allantois, after BALFOUR.

The section shows that the neural tube, Sp.c, is continuous at its posterior end with the hind
gut, p.a.g, by means of the neurenteric canal, n.e. The latter passes through the remains of
the primitive streak, pr, which is folded over toward the ventral side, ep, Outer germ-layer ;
ch, chorda: hy, entoderm (hypoblast) ; al, allantois ; r,ie, middle germ-layer; an, the point
where the anus will arise ; am, amnion ; so, somatopleure ; sp, splanchnopleure.

superficial position that it acquires, it is the most? important organ of
respiration.

The allantois takes its origin from the posterior portion of the
hind gut, which is afterwards designated as the cloaca, and in the
Chick the first traces of it can be recognised even at the end of
the second day, at a time when the walls of the hind gut are still
in the process of formation. It appears in this instance as a small
caecal evagination (al) on the anterior wall of the splanchnopleure
(hy) (fig. 128; Plate I., fig. 3 al).

The evagination is lined by the entoderm, and is covered exter-
nally by a growth of the splanchnic mesoderm. It enlarges rapidly
into a vesicle, which grows out into the body-cavity (Plate I., fig. 4 al).
At the same time the blind end enlarges, whereas the proximal part,
where it passes over into the hind gut, becomes narrow and elongated
into a hollow stalk, the urinary duct or urachus.

218 EMBRYOLOGY.

On the fourth day the urinary sac is so enlarged that it can
no longer find room in the embryonic part of the body- cavity, and
therefore forces itself into the extra-embryonic portion 'of it between
the intestinal and dermal portions of the umbilical stalk (Plate I.,
fig. 5 al). Here it comes into the space between the yolk-sac (ds) and
amnion (A ) ; then it comes in contact with the inner surface of the
serosa (S), and spreads out under it for a considerable distance over
the right side~of ~the embryonic body.

In regard to the subsequent fate of the embryonic membranes in the
Uhick, it is to be noticed that up to the middle of incubation, i.e., up
to about the eleventh day, they continue to develop in a progressive
direction, but that from this time onward certain regressive processes
commence, which later become more and more apparent.

In the first period (fifth to eleventh day) the1 following changes
are effected in the yolk-sac, the amnion, the allantois, etc. The
vascular area spreads out, in the manner before described, over a
greater area in the wall of the yolk-sac, which still retains a
considerable size. On the seventh day it covers about two-thirds
(Plate I., fig. 5), and on the tenth three-fourths of the yolk-sac. At
the same time the marginal vein becomes indistinct, and the sharp
separation from the non-vascular portion ceases.

The contents of the yolk-sac have become fluid by chemical
changes of the yolk-mass. The serosa (S) is raised from its surface
as far as the vascular area has extended, owing to the enlargement
of the extra-embryonic body-cavity. At the same time the allantois
(Plate I., fig. 5 al) has grown into the intermediate space. This has
enlarged so much by the tenth day that it leaves uncovered only a
small portion of the yolk-sac and amnion. It has lost still more
of its sac-like character ; for between its outer layer, which almost
everywhere is closely applied to the inner surface of the serosa, and
its inner layer, adjoining the amnion and yolk-sac, there is found only
an insignificant intermediate space filled with urine.

The allantois, moreover, has by this time become a very vascular
organ and is nourished by the umbilical vessels, which will engage
our attention in a subsequent chapter devoted to the vascular system.
The network of blood-vessels is densest in its outer layer, which
spreads out at the surface of the egg ; it serves to maintain here the
processes of embryonic respiration, since carbonic acid is given off from
the superficially circulating blood and oxygen is taken up. The latter

THE FCETAL MEMBRANES OF REPTILES AND BIRDS.

is acquired in part directly through the egg-shell and in part out of
the air chamber (fig. 8 a.ch) situated at the blunt pole of the egg,
which is in contact with a large part of the allantois.

Finally, in addition to respiration, the allantois serves for the
resorption of the albumen, which becomes more and more thickened
during incubation, and compressed into a lump at the pointed pole of
the egg. It grows over the albumen and envelops it in a sac, the epi-
thelial surface of which arose from the serosa, which was evaginated
at the same time with the growing allantois. There are developed on
the inner surface of the sac highly vascular villi, which sink into the
albumen, and have been described as a placenta by DUVAL, who has
called attention to these conditions.

The air chamber also has undergone modifications during incuba-
tion, and, at the same time with the acquisition of air, has increased
in size by the separation of the two layers of the shell-membrane in
which it is enclosed (fig. 8, p. 17).

Finally, the amnion, which at the beginning of its development is
rather closely applied to the embryo, has enlarged and become a sac
(Plate I., fig. 5 A) entirely filled with amniotic fluid. Its rhythmical
contractions already described become most active and powerful on
the eighth day, and from that time forward to the end of incubation
diminish in frequency and in force.

As a result of all these processes of growth, the embryo with its
appendages now demands a much larger space than at the beginning
of incubation. It acquires this in the following manner. The
albumen which surrounds the yolk diminishes considerably, since it
disappears, especially its fluid portion, partly by evaporation to the
exterior, partly also by resorption on the part of the embryo. The
vitelline membrane has become ruptured by the enlargement.

In the second period, which we have reckoned from the eleventh
to the twenty-first day, or to the hatching of the Chick, retrogressive
metamorphoses are most prominent.

These assert themselves first of all on the yolk-sac. As the result
of the vigorous sucking up of its contents it becomes more and more
flaccid, so that its wall begins to lie in folds. It now becomes
entirely separated from the serosa, since the extra-embryonic body-
cavity has extended all around it, and thereupon it is drawn closer to
the wall of the belly by the shortening of the umbilical stalk. On
the nineteenth day of incubation it begins to slip into the peritoneal
cavity through the dermal umbilicus, which has now become very
narrow, whereby it takes on an hour-glass shape during its passage

220 EMBRYOLOGY.

through the ventral wall. It is here employed to help in the closure
of the intestinal wall.

The amnion undergoes regression, inasmuch as the fluid diminishes
and almost entirely disappears, until the membrane is again closely
applied to the body of the embryo. The -albumen, too, is almost
entirely consumed. The allantois alone continues to increase, and
finally grows around so completely on the entire inner surface of the
serosa that its edges come together and fuse with one another into
a sac entirely enclosing the embryo and the amnion. It adheres so
firmly to the serosa that a separation is no longer possible.

The urine] likewise diminishes toward the end of incubation, arid
finally, like the amniotic fluid, has entirely disappeared. As the
result of this, there are found in the allantois precipitates of uric
salts, which become more and more abundant.

Amnion and allantois finally undergo complete retrogressive meta-
morphoses. Inasmuch as the Chick, shortly before hatching, breaks
through the surrounding membranes with its bill, it begins to take
in directly the air contained in the air chamber, which has become
larger. A result of this is that the circulation in the allantois
is retarded and finally ceases altogether. The afferent umbilical
vessels disappear. Amnion and allantois die away, dry up, and then
separate from the dermal umbilicus, which closes on the last day
before hatching, and when the Chick leaves the egg-shell they are
stripped off with it as useless remains.

SUMMARY.

1. In Reptiles and Birds the embryo during its development sinks
into the underlying yolk, which has become liquefied, and becomes
enveloped by folds of the extra-embryonic area of the somatopleure,
the anterior, posterior, and lateral folds of the amnion (cephalic
sheath, caudal sheath, lateral sheaths).

2. As the result of the folding processes two sacs arise around
the embryonic body, the amnion and the serous membrane (serosa).

3. The amnion is united at the dermal umbilicus with the belly
of the embryo.

4. The dermal umbilicus encloses an opening through which the
embryonic and extra-embryonic portions of the body-cavity are in
connection.

5. The stalk of the yolk-sac passes through the dermal umbilicus
in order to attach itself to the intestine at the intestinal umbilicus.

THE FCETAL MEMBRANES OF MAMMALS. 221

6. The allantois is evaginated from the ventral wall of the
posterior tract of the hind gut (cloaca), grows as a pedunculated sac
(1) into the body-cavity, and (2) through the dermal umbilicus into
the extra-embryonic part of the same, extends out from here 011
all sides between the amnion and serosa, and by virtue of its great
vascularity functions as an organ of respiration.

7. At the end of embryonic development the constantly diminish-
ing yolk-sac, after the consumption of the yolk, slips through the
open dermal umbilicus into the body-cavity, and is employed in the
closure of the intestinal umbilicus.

8. Amnion, serosa, and that part of the allantois which has
grown out beyond the embryonic body, are cast off as useless struc-
tures at the dermal umbilicus, which becomes closed.

CHAPTER XII.
THE FCETAL MEMBRANES OF MAMMALS.

IN their early stages of development the foetal membranes of
Mammals present an extraordinary correspondence with those of
Reptiles and Birds (fig. 129). We find a yolk-sac (UV) with abun-
dant capillaries, an amnion (am), a serous menJbrane or serosa (sz),
and an allantois (ALC) ; we find that, in the same way as before,
the embryo is developed out of a small region of the blastula, and is
constricted off in the same way from the extra-embryonic area, with
which it remains united only by means of a dermal and intestinal
yolk-stalk.

The correspondence becomes a striking one and stimulates to
further reflection, when we take into consideration that the develop-
mental processes enumerated are primarily evoked by means of the
accumulation of yolk-material in the eggs of Reptiles and Birds, and
that the eggs of most Mammals lack almost entirely the yolk, are of
very small size, undergo total segmentation, and in all these respects
resemble more the eggs of Amphioxus.

Why, then, does the mammalian germ nevertheless undergo
metamorphoses which in other cases are only the result of the
accumulation of yolk 1 Why is there developed a yolk-sac that
contains no yolk, with a system of blood-vessels that is designed for
the resorption of yolk 1

222 EMBRYOLOGY.

For the explanation of these conditions we must have recourse
to an hypothesis which can be formulated about as follows : —

The Mammalia must have descended from animals which possessed
large eggs with abundant yolk, which were oviparous, and in ivhich
consequently the embryonic membranes were developed in the same way
as in Reptiles and Birds. The loss of the yolk-contents from the eggs
of these animals must have been a supplementary event, which began
at the time when the eggs were no longer deposited outside, but were

Tig 129.— Diagram of the foetal membranes of a Mammal, after TURNER.

pc, Zona pellucida with villi (prochorion) ; sz, serous membrane ; E, outer germ-layer of the
embryo ; am, amnion ; AC, anmiotic cavity ; M, middle germ-layer of the embryo ; H, inner
germ-layer of the same; UV, yolk-sac (vesicaumbilica'is); ALC, allantoic cavity ; al, allantois.

developed in the uterus. For by this change there was found a new
and more productive, because unlimited, source of nourishment for the
developing germ in substances which were secreted by the walls of the
uterus from the maternal blood. There was therefore no more need of
a dower of yolk. But the enveloping structures, which were originally
called into existence by the presence of yolk-contents in the eggs,
were retained, because they were still of use in many other relations,
and because, through a change of function, they became subservient
to uterine nourishment and correspondingly underwent changes.

THE POSTAL MEMBRANES OP MAMMALS. 223

Three facts can be cited in favour of this hypothesis.

In the first place, in the lowest classes of Mammals, as in the
Monotremes and Marsupials, the eggs are larger than in placenta!
animals, They are characterised by a large quantity of yolk,
which, as in Ornithorhynchus for instance, is deposited in closely
compacted spheres of varying size and fat-like lustre. In this par-
ticular they form a transition to the eggs of Reptiles and Birds.

Secondly, it has been observed that the Monotremes, the lowest
division of the Mammalia, are oviparous, like Birds and Reptiles.
Quite recently two investigators, HAACKE and CALDWELL, have made
the interesting discovery that Echidna and Ornithorhynchus, instead
of giving birth to living young, as was hitherto assumed, lay eggs
which are nearly two centimetres in diameter, and enveloped in a
parchment-like shell, and which they carry about with them in their
brood-pouch or mammary pocket.

Thirdly, the fcetal membranes of Marsupials, which next to the
Monotremes are to be considered as the lowest Mammals, remain
permanently in a condition which corresponds to that of Reptiles
and Birds, although the development takes place in the uterus. As
we know through OWEN, the embryo, which is enclosed in a capacious
amnion, possesses a very large vascular yolk-sac, which extends out to
the serosa, and in addition a small allantois and a serosa. The latter
lies closely applied to the walls of the uterus, but without being
intimately united with it. Probably, therefore, after resorption of
the yolk, substances which have been secreted by the uterus are
taken up by the blood-capillaries of the yolk-sac. Thus a kind of
intra-uterine nutrition begins to be established in the Marsupials;
but otherwise the embryo with its envelopes lies in the cavity of the
uterus, like the Avian or Reptilian embryo with its membranes in
the firm egg-shell.

Having established the hypothesis, already expressed by various
authors, that the eggs of Mammals must originally have contained
more yolk, let us turn to a more exact description of the foetal
membranes. As regards the first stages of development, let us begin
with the Rabbit, because! its embryology has been the most thoroughly
investigated; then, in order to facilitate our understanding of the
structure of the human placenta, we shall show in a brief sketch how,
in the class of Mammalia, in various ways more intimate anatomical
and physiological relations are developed between the mucous mem-
brane of the uterus xand the embryonic membranes. We shall treat
of the foetal membranes of Man in a special chapter.

224

EMBRYOLOGY.

When, in the Eabbit, the ovum, which has reached the uterus,
has here become metamorphosed into the blastula already described,
it is still enveloped by the zona pellucida. This in the meanwhile
has been distended into a thin pellicle (prochorion), which is subse-
quently destroyed.

The blastula, or blastodermic vesicle, expands rapidly, and from
the fifth to the seventh day grows from 1-5 mm. to 5 mm. in diameter.

In consequence
of this increase
in size the pro-
chorion on the
seventh and
eighth days is
so closely ap-
plied to the in-
ner surface of
the uterus that
it becomes more
and more diffi-
cult, an d finally
impossible, to
detach the eggs
without injury.
For by the rup-
turing of the
prochorion,
which adheres
to the walls of
the uterus, the
delicate blas-
tula, which is
in close contact

with it, generally becomes injured and torn open, and thereupon
collapses, owing to the escape of its contents. The latter have also
suffered changes which make the investigation more difficult, having
increased in consistency until they equal in density the albumen
of the Hen's egg.

During the process of attaching itself, the embryonic fundament,
which at first is round, increases in size and takes on a more elon-
gated form. On the seventh day it becomes oval (fig. 130 ag), then
pear-shaped, and on the eighth day acquires a more and more marked

\

Fig. 130.— Embryonic fundament of the ovum of a Rabbit of seven days,

from KOLLIKER.
o, Vascular area (area opaca) ; ag, embryonic fundament ; pr, primitive

streak ; rf, dorsal furrow.

THE FCETAL MEMBRANES OF MAMMALS.

225

ffo

i

sole-like form; meanwhile it grows to a length of about 3'5 mm.
(%. 131).

As has been already described in the previous chapter, at this
time the middle germ-layer spreads out in the embryonic fundament,
the medullary groove (figs. 130 and 131 rf), the chorda, and a
number of primitive segments are formed,
and, on the eighth day, the first trace of
the vessels and blood appears in the vas-
cular area (o). On the ninth and tenth
days the embryonic fundament is by a
process of folding converted into the body
of the embryo, and is constricted off from
the remaining part of the blastodermic
vesicle, out of which at the same time
various foetal membranes begin to be de-
veloped. The initial stages of all these
processes are the same in Mammals as in
Birds and Reptiles, so that we can express
ourselves very briefly in describing them.
We shall connect the description with the
diagrammatic drawings which KOLLIKER
has made, and which have found a place
in many text-books (fig. 132, 1-5).

Diagram 1 shows a blastodermic vesicle
which in the Rabbit would correspond to
about the seventh or eighth day. It is
still enclosed from without by the very
much attenuated vitelline membrane (d),
which is now also called prochorion, since
in many Mammals flakes and shreds of
albumen have been precipitated on its
outer surface out of the fluid secreted by
the mucous membrane of the uterus. The
inner germ-layer (i) — which in a slightly

younger blastula, such as is represented in figure 62 B, reaches only
to the line ge, and still leaves uncovered a third of the inner surface
of the sphere — has now entirely grown around to the vegetative pole.
The middle germ-layer (m) is in full process of development, and
embraces about a fourth part of the surface of the sphere/ A small
portion of this three-layered region contains the embryonic fundament,
which would be in about that stage of development which we have

15

Fig. 131. — Embryonic fundament
of a Rabbit of nine days with
a portion of the area pellucida,
from KoflLiKER.

Ap, Area pellucida ; ao, area opaca ;
h', h", h'", medullary plate in
the region of the first, second,
and third cerebral vesicles ; stz,
stem -zone (Stammzone) ; pz,
parietal zone ; rf, dorsal f urrow ;
pr, primitive streak.

226

EMBRYOLOGY.

Fig 182.— Five diagrammatic figures illustrating the development of the foetal egg-membranes

of a Mammal, after KOLLIKER.
figures 1 to 4 the embryo is represented in longitudinal section.

(1) Ovum with zona pellucida, blastula, embryonic area, and embryonic fundament.

(2) Ovum in which the yolk-sac and the amnion are beginning to develop.

(3) Ovum in which, by the fusion of the amniotic folds, the amniotic sac and the serous mem-
brane are formed, and the allantois makes its appearance.

(4) Ovum with serous membrane, which has developed villi, with a large allantois and an
embryo, in which the t>ral and anal openings have arisen.

(5) Diagrammatic representation of a young human ovum, in which the vascular layer of the

allantois has become applied to the serous membrane on all sides, and lias grown into its
villi. The serous membrane from this time forward takes the name of chorion. The cavity

THE F(ETAL MEMBRANES OF MAMMALS. 227

before us in the surface-view in figure 130. It is ovate, and shows
the primitive streak (pr) in the posterior half, and in front of it a
deep dorsal furrow (rj) ; tne extra-einbryonic part of the middle
germ-layer can be designated as the vascular area (o), since the first
traces of the formation of the vessels and the blood are noticeable
in it.

In the much further developed embryo figured in diagram 2 (at
about the ninth day in the Rabbit) the middle germ-layer has spread
out over about the third part of the blastula, and now encloses an
easily distinguishable body-cavity, since the* parietal and visceral
middle layers have separated from each other in the embryonic
as well as extra-embryonic regions. It extends as far as the place
marked st, where the sinus terminalis is found as the outer limit of
the now clearly defined vascular area.

The embryonic fundament is in the act of being constricted off from
the blastodermic vesicle. The head- and tail-ends of the embryo, by
foldings of the separate layers, have been elevated from the area
pellucida in the same way as in the Chick. As there, a cephalic
and pelvic part of the intestinal tract (fore and hind gut) have
arisen, witb an anterior and posterior intestinal portal, which open
toward the cavity of the blastodermic vesicle.

At the same time occurs the development of the amnion, which
was first recognised in the Mammalia by BAER and BISCHOFF. On the
diagrammatic section one sees that the extra-embryonic body-cavity
has become very capacious, in that the outer germ-layer with the
closely applied parietal middle layer has risen up in the vicinity of
the embryo and formed itself into the folds ks and ss. The anterior
fold of the amnion (ks) has bent over the head, and the posterior
fold (ss) over the tail. The two sheaths lie so close to the embryo
in the Mammalia, that in looking from the surface they are not
easily recognised, especially as they are extraordinarily transparent.
On the third diagram the amniotic folds have greatly enlarged, and
have grown toward each other over the back of the embryo till their

of the allantoi^ has diminished and the yolk-sac has become very small, but the amniotic
cavity is in the act of increasing.

d, Vitelline membrane (zona pellucida) ; d', villi of the same ; sh, serous membrane [serosa] ;
ch, chorion ; ch.z, villi of the chorion ; am, amnion ; ks, ss, cephalic and caudal folds of the
amnion ; a, outer germ-layer ; a', the same in the extra-embryonic region of the blastula ;
m, middle germ layer ; m', the same in the extra-embryonic region ; dd, inner germ-layer ;
i, the same in the extra-embryonic region ; df, vascular area ; st, sinus terminalis ; kh, cavity
of the blastula, which later on becomes the cavity of the yolk-sac (ds) ; dg, stalk of the yolk-
sac (vitelline duct) ; al, allantois ; e, embryo ; r, space between chorion and amnion. extra-
embryonic part of the body-cavity, filled with albuminous fluid ; vl, ventral body- wall ;
hh, pericardial cavity.

228 EMBRYOLOGY.

edges are in mutual contact. The closure of the sac takes place in
a somewhat different manner from that of the Chick. Instead of
meeting in a longitudinal suture, the edges of the amniotic folds
meet, in the Rabbit at least, approximately in the middle of the back
in a small spot, where for a considerable time a circular opening in
the sac is retained. The outer layer of the amniotic fold, which in
diagram 3 is still in connection with the amniotic sac at the point of
fusion, but which later entirely separates from it, represents, as in
the Chick, the serosa. It first appears as an independent structure
in the vicinity of the embryo, whereas farther downwards it is still
firmly united with the entoblast, and together with it constitutes the
wall of the original blastula, which is here only two-layered.

In the third diagram, furthermore, we can recognise the first
trace of the allantois (al), which grows out from the anterior
wall of the hind gut in the manner already described (p. 217), and
which in the Rabbit is seen as early as the ninth day in the form of
a small, pedunculated, exceedingly vascular sac.

The fourth diagram shows the development of the foetal membranes
much further advanced. The prochorion has become ruptured by
the distension of the entire blastodermic vesicle, and is no longer
recognisable as a separate membrane. What we see on the outside
is the serosa, which has been changed in a striking manner. In the
first place, it has become completely detached from the .amnioii ;
however, it should be remarked in this connection that in certain
Mammals, and especially in Man, a stalk uniting the two membranes
is retained for a considerable time at the amniotic suture. Secondly,
the serosa is everywhere separated from the yolk-sac, and loosely
surrounds the embryo and its remaining membranes as a thin sac.
This condition has been brought about in the following manner : the
middle germ-layer, which in diagram 3 had grown over only one half
of the original blastula, has now spread over the other half also, and
has become divided into its two layers. By this means the extra-
embryonic part of the blastula is now completely split, as in the Chick,
into an outer sac, the serosa, and the yolk-sac, separated from it
only by the body-cavity.

Moreover, there exist in this respect differences among the
Mammalia, since in some the serosa remains to a greater or less
extent permanently united with the yolk-sac. This . is the case, for
example, in the Rabbit.

In the Rabbit, in which the yolk-sac at first fills the greater part of the
blastodermic vesicle, the middle germ-layer spreads out over that half of the

THE FCETAL MEMBRANES OF MAMMALS.

229

yolk-sac only which is turned toward the embryo. There is developed in it
a system of capillaries, which ends abruptly in a marginal vein. The other
half of the yolk-sac is without vessels, and is everywhere firmly united with the
serosa. When, after the resorption of its contents, the yolk-sac commences to
shrivel, it begins to take on a mushroom-like form (fig. 133 ds\ owing to the
folding in of the vascular half (fd) against the non- vascular part (ed"), which
is fused with the serosa (*&). It remains united with the umbilicus of the
embryo by means of an elon-
gated intestinal stalk (or
vitelline duct), which is com-
parable to the stalk of the
mushroom.

The space (r) which is
produced in the blastodermic
vesicle by the shrinking of
the yolk-sac does not become
filled out by compensating
growths of the amnion (a)
and allantois (a?), both of
which remain small. There-
fore a large amount of fluid
collects between the separate
fcetal membranes. The space
filled with fluid is none other
than the extra-embryonic part
of the body-cavity, which in
the Babbit, as in no other
Mammal, is highly developed.
The allantois (al~) hangs freely
in this space as a stalked
vesicle, a part of its surface
having applied itself to that
portion of the serosa (*/<•)
which is not united with the
yolk-sac, and which is circum-
scribed by the sinus termi-
nalis (st). It is gradually

metamorphosed into an organ of nutrition for the embryo, the placenta (pi),
inasmuch as it receives a rich supply of blood through the vessels of the
allantois, the umbilical vessels.

Subsequently the remaining surface of the blastodermic vesicle, over which
the umbilical vessels do not extend, also becomes vascular. This is due to the
fact that the albuminous fluid still contained in the mushroom-like yolk-sac
becomes entirely absorbed, and that consequently its outer non-vascular and
inner, invaginated vascular walls come to lie on each other and to fuse into
a single membrane. In this manner the blastodermic vesicle in the Babbit
becomes provided with blood on its entire surface, but from two different
sides — the placental portion from the vessels of the allantois, and the larger
part of the surface from the degenerating vitelline vessels.

In regard to the formation of the amnion in the Babbit, upon which VAN
BEXEDEN ET JULIN have made very thorough investigations, it is to be added

Fig. 133.— Diagrammatic longitudinal section through
the ovum of a Rabbit at an advanced stage of
pregnancy, after BISCHOFF.

e, Embryo ; a, amnion ; u, urachus ; al, allantois with
blood-vessels ; sh, subzonal membrane ; pi, villi of the
placenta ; fd, vascular layer of the yolk-sac ; ed, ento-
blast of the yolk-sac ; ed', ed", inner and outer lamellae
of the entoblast which lines the flattened cavity of the
yolk-sac ; ds, cavity of the yolk-sac ; st, sinus termi-
nalis; r, the space between amnion, allantois, and
yolk-sac that is filled with fluid.

$30 EMBRYOLOGY.

that the middle germ-layer is wanting in the region of the anterior amniotic fold
to a greater degree in this case than in the Chick. The anterior amniotic fold
therefore consists during a considerable period of only the two primitive germ-
layers, closely joined together. VAN BENEDEN has therefore given to. the
cephalic sheath, as long as the inner germ-layer takes part in its formation,
the name of proamnion. Later on, however, a separation of the amnion from
the entoblast takes place also in the head-region in the Rabbit.

Finally, in our fourth diagram, still a third change has appeared in
the serosa. By rapid growth of the epithelium large numbers of
small evaginations or villi have arisen on its outer surface. On this
account the name of chorion or villous layer has been applied to it
when these changes have been completed. It should also be added
here that in the development of the villi uniformity among all Mammals
by no means prevails. In the lowest orders (Monotremes, Marsupials)
the. surface of the blast odermic vesicle remains almost smooth, as in
Reptiles and Birds. In them, therefore, the serosa is permanently
retained during embryonic life, whereas in other Mammalia it is
transformed into a villous membrane. By reason of these differences
KOLLIKER has divided Mammals into Mammalia achoria and
Mammalia choriata.

On the other embryonic membranes of fig. 132, 4, it is principally
changes in size only that have been effected. The yolk-sac (ds), over
the entire surface of which the vitelline vessels now spread, has
become considerably smaller, and is continuous with the embryonic
intestine by means of a long Blender stalk, the vitelline duct (dg).
The amniotic sac (am) has already enlarged and is filled with fluid,
the liquor amnii. Its walls are continuous at the umbilicus with
the ventral wall of the embryo. The allantois (al) has become a
vascular pear-shaped sac, which has grown out between the dermal
stalk and umbilicus into the extra -embryonic part of the body-cavity,
and soon after reaches the serosa.

The accurate representation of an embryo Dog of twenty-five days
(fig. 134) affords us, better than the diagram (fig. 132, 4), a view of
the connection of the two vascular sacs, the allantois and yolk-sac,
with the intestinal canal.

The embryo is removed from the chorion and amnion. The
ventral belly-wall is partly removed, and thereby the dermal um-
bilicus, which about this time has become rather narrow, has been
destroyed. The intestinal canal, now to be seen in its entire length,
is already converted throughout into a tube (d) ; near its middle it is
continuous, by means of a short vitelline duct, with the yolk-sac (ds),

THE FCETAL MEMBRANES OF MAMMALS.

231

which was cut open in the process of preparation. The allantois (al)
is attached to the very end of the intestinal canal by means of the
attenuated stalk-like urachus.

Up to this stage the correspondence in the development of the embry-
onic membranes in Mammals, Birds, and Reptiles is clear. But from
now on the course of development in the Mammalia becomes more
and more divergent, since one portion of the embryonic membranes

rig. 134.— Embryo Dog of 25 days, extended and seen from in front. Magnified 25 diameters.
After BISCHOFF.

d, Intestine ; ds, yolk-sac ; al, allantois, urinary sac ; un, primitive kidney ; I, the -two lobes of
the liver, with the lumen of the omphalomesenteric vein between them ; ve, he, anterior and
posterior appendages ; h, heart ; m, mouth ; au, eye ; g, olfactory pit.

enters into closer relations with the mucous membrane of the uterus,
and is thus converted into an organ of nutrition for the embryo. In
this manner a compensation is provided for the loss of the yolk.

The interesting adaptations for intra-uterine nutrition — they have
been studied especially by the English anatomist TURNER in a
series of profound comparative-embryological works — present very
great differences in the separate orders of Mammalia : sometimes
they are of a simple kind, at other times they are more com-

232 EMBRYOLOGY.

plicated organs, which have been designated as the after-birth, or
placenta. Since a knowledge of them will facilitate our compre-
hension of the human placenta, we shall consider them somewhat at
length.

It is most expedient to distinguish three different modifications in the
way in which the surface of the blastodermic vesicle comes into relation
with the mucous membrane of the uterus, and accordingly to divide the
Mammals into three groups.

In one the serosa is retained nearly in its simple primitive condition,

In the second it is transformed into a villous layer or chorion, and

In the third a placenta arises out of one or more portions of the chorion.

To the first group belong, among the Mammalia, only the Mono-
tremes and the Marsupials, whose embryonic membranes are in the
main constituted like those of Birds and Reptiles. Ordinarily in the
Marsupials the serosa retains its smooth surface. Inasmuch as it
lies in close contact with the vascular mucous membrane of the uterus,,
it can absorb nourishment from the latter and transmit it to the
deeper-lying embryonic parts.

In the second group of Mammals an improvement in the intra-
uterine nourishment is effected by important changes in the organisa-
tion of the serosa, which is converted into a villous layer or choriQn.

In the first place, it is provided with blood-vessels by the allantois,
which grows out into contact with it, and whose connective-tissue
layer, containing the ramifications of the umbilical vessels, grows
over its entire inner surface.

Secondly, the epithelial membrane begins to grow out info folds
and villi, into which there soon penetrate vascular outgrowths of the
connective-tissue layer. By this process a larger resorbing surface
is provided.

Thirdly, the mucous membrane of the uterus and the chorion
unite more intimately and firmly with each other, while the former
also increases its surface and acquires pits and depressions into which
the processes of the latter penetrate.

All these changes have simply the purpose of facilitating and
rendering more perfect the interchange of materials between the
tissues of the mother and those of the offspring.

We meet with membranes thus constituted in the Suidae, the
Perissodactyla, Hippopotamidse, Tylopoda, Tragulidse, Sirenia, and
Cetacea. In the Pig, which shall serve as an example, the blasto-
dermic vesicle, in adaptation to the form of the uterus, is transformed
into a spindle-shaped sac. The inner embryonic appendages, the

THE FOZTAL MEMBRANES OF MAMMALS. 233

yolk -sac and allantois, are also drawn out in the same manner into
two long tapering ends.

On the entire surface of the chorion, with the exception of the
two ends of the sac, there have arisen rows of very vascular pads,
which radiate from separate smooth round spots of the membrane,
and are covered at their edges with small simple papillae. The
mucous membrane of the uterus is exactly fitted into the elevations
and depressions of the chorion. There are also found on it circular
smooth places similar to those of the chorion, which are further
noteworthy from the fact that it is only on them that the tubular
uterine glands open out. At birth the interlocking surfaces of
contact separate from each other without any loss of substance on
the part of the mucous membrane of the uterus ; for the pads and
small papillae are easily withdrawn from the depressions which serve
for their reception.

In the third group a special organ, the placenta, or after- birth,
has been developed for the purpose of intra-uterine nutrition^ Its
origin was brought about by separate portions of the chorion having
assumed different characters, owing to the unequal size and distri-
bution of the villi.

One part exhibits a condition in which the villi are entirely gone
or much stunted, so that the surface of the membrane feels smooth ;
moreover, it possesses few blood-vessels or is entirely destitute of them.

Another part of the chorion contains, closely packed together, villi
which are extremely long and covered with many ramifying lateral
branches ; furthermore, it receives large blood-vessels, which approach
the tufts of villi and distribute their terminal capillaries t© the finest
lateral ramifications of the latter; finally, it has entered into the
most intimate relations with the mucous membrane of the uterus.
Wherever the latter comes in contact with the tufts of villi it
is much thickened, very vascular, and in a state of active growth.
It encloses numerous branched cavities of varying size, into which
the villi of the chorion exactly fit.

The entire structure is called a placenta, in which the part of the
chorion which is covered icith villi is distinguished as the placenta
fvetalis, and the part of the mucous membrane of the uterus which is
united with and adapted to the latter as the placenta uterina. Both
parts together constitute an organ for the nutrition of the embryo.

The term placenta has often been extended to the kind of chorion
which is evenly covered with small villi, such as exists in the
Suidae, etc., and the designation of diffuse placenta has been created

234

EMBRYOLOGY.

c1

for it. But in the interest of a more precise definition it is advisable

^2 to use the name

only in the re-
stricted sense
in which it has
been employed
in this chapter,
and in other
cases to speak
of a villous
membrane or
chorion only.
The forma-
tion of the pla-
centa presents
in its details
important mo-
difications.

Tig. 135a.-TJterus of a Cow laid open, in the middle of the period of Tha 7?,,™ *
gestation. From BALFOUR, after COLIN. lhe -ttumi-

V, Vagina ; U, uterus ; Ch, chorion ; C\ cotyledons of the uterus ; C2, total nants, in which
cotyledons.

the blastoder-

mic vesicle is drawn out into two tips, as in the Pig, present a
special typ e
(fig.!35a). On w
their chorion
(Ch) have been
developed very
many small
foetal placentae
((72),whichhere
are also called
cotyledons. The
number of the
latter is ex-
ceedingly vari-
able in the
different spe-
cies, from sixty

Fig. 135b.— Cotyledon of a Cow, the foatal and maternal parts half
detached from each other. After COLIN, from BALFOUR.

u, Uterus; Cl, maternal part of the cotyledon (placenta uterina);
Ch, chorion of the embryo; C*. foetal part of the cotyledon
(chorion frondosum or placenta foetalis).

to one hundred
in the Sheep
and Cow, and only from five to six in the Doe. They are united with

THE FOETAL MEMBRANES OF MAMMALS. 235

corresponding thickenings of the uterine mucous membrane, the
placentae uterinse (C1), though only in a loose manner, so that a little
pulling is sufficient to produce a separation, and to draw the chorionio
villi out of the depressions which serve for their reception, as one
draws the hand out of a glove. In fact, in the preparation which
serves as the basis of our figure 135a the cotyledons of offspring and
mother (C2 and Cl) are separated from each other, since the uterus
( U) has been opened by means of an incision and drawn back from
the chorion (Ch) for a little distance.

Figure 135b shows a single cotyledon of figure 135a somewhat
larger than the natural size. The wall of the uterus (u) is drawn
back a little from the chorion (Ch). As a result of this, the maternal
•((71) and foetal parts (C2) of the cotyledon are partially separated
from each other. On the placenta uterina (C1) one perceives many
small pits, on the placenta fcetalis (C2) the closely packed dendritically
branching chorionic villi, which have been withdrawn from the
pits.

As the diagrammatic section figure 136 teaches, the foetal and
maternal tissues abut immediately on each other. The villi are
covered with flattened cells, and the depressions of the mucous
membrane are lined with cylindrical cells ; the latter develop within
them granules of fat and albumen ; they disintegrate in part, and
thereby contribute to the formation of a milky fluid, the so-called
uterine milk, which can be pressed out of the placenta uterina and
serves for the nutrition of the foetus. It is to be noticed also that
in the Ruminants the uterine glands have openings on the mucous
membrane only between the cotyledons.

In all other Mammals that are provided with a placenta the
intergrowth of the foetal and maternal .tissue is still more intimate.
At the same time there is formed in this way such a close union,
that a separation of the chorion without injury to the mucous membrane
of the uterus is now no longer possible. At birth therefore a more or
less considerable superficial layer of the mucous membrane of the uterus
is cast off with the foetal placenta. The part that is cast off is called
the caducous membrane, or the decidua.

In accordance with HUXLEY'S proposal, all Mammals in which, in
consequence of the special growth of the placenta, such a membrane
is formed are now grouped together as Mammalia deciduata, or
briefly Deciduata, in contradistinction to the remaining Mammals —
the InoVsciduata, the formation of whose placentae has just been
•discussed.

236

EMBRYOLOGY.

In the Mammalia with a decidua we must distinguish two sub-
types of placenta, a ring-like and a disc-like, a placenta zonaria and
a placenta discoidea.

The placenta zonaria is characteristic of the Carnivora. The
blastodermic vesicle in this case generally has the shape of a cask.
With the exception of both poles, which retain a smooth surface, the
chorion is covered with numerous villi arranged in a girdle -shaped
zone ; the villi are furnished with lateral branches, like a tree.

The branched villi of the chorion sink into the thickened mucous

Fig. 136.— Diagrammatic representation of the finer structure of the placenta of a Cow, after

TURNER.
F, Foetal, M, maternal placenta ; V, villus ; e, epithelium of the chorionic villus ; e', epithelium

of the maternal placenta ; d, foetal, d', maternal blood-vessels.

Fig. 137. — Diagrammatic representation of the finer structure of the placenta of a Cat, after
TURNER. Explanation of letters as in fig. 13C.

membrane of the uterus in various directions, so that in sections
there arises the appearance of an irregular interlacing (fig. 137).
However, according to the concurrent accounts of TURNER and
ERCOLANI, there is no penetration into the uterine glands in this case,
any more than in the case of the Indeciduata.

The epithelium (e') of the maternal mucous membrane (M ) persists
and forms a boundary between the villi ( V) and the maternal blood-
vessels (d'), which latter have enlarged to cavities from three to four
mites as wide as the foetal capillaries (d). This enlargement of the

THE FCETAL MEMBRANES OF MAMMALS.

237

maternal blood-passages is full of significance for the formation of
the placenta in the Deciduata as opposed to that of the Indeciduata.

The second form, the discoid placenta, is characteristic of the
Rodentia, the Insectivora, the Chiroptera and Prosimiae, the Apes and
Man. Here the portion of the chorion devoted to the formation of
the placenta is small ; but in compensation for this the tufts of villi
(fig. 138 F) are very highly developed; the union between placenta
uterina(Jf)and placenta
foetalis (F) is most in-
timate ; the maternal
blood-spaces (d1), in the
case of the Apes and
Man at least, are, as no-
where else, enormously
distended, so that the
villi of the chorion (F)
appear to sink directly
into them and to be
bathed immediately by
the maternal blood.

Since we shall occupy
ourselves more at length
in the next chapter
with the human pla-
centa, which belongs to
this type, these few
remarks may suffice for
the time being.

I close this section
with a reference to the
high systematic signifi-
cance of the embryonic
accessory organs of Ver-
tebrates. They present,
as we have seen, such
great and striking dif-
ferences in the separate

Fig. 138. — Diagrammatic representation of the finer struc-
ture of the human placenta according to the hypothesis
of TURNER.

F, Foetal, M, maternal placenta; e', epithelium of the
maternal placenta; d, foetal, d', maternal blood-
vessels ; F, villus ; ds, decidua serotina of the human
placenta; t, t, trabeculae of the serocina running to
the foetal villi ; ca, convoluted artery which sinks into
the blood-space d' ; up, one of the utero-placental veins
conveying blood from the latter; x, a continuation
over the villus of maternal tissue— lying outside the
epithelial layer e' — which represents either the endo-
thelium of the maternal blood-vessels or a delicate
connective tissue pertaining to the serotina, or both
together. The layer e' consists, at all events, of ma-
ternal cells derived from the serotina. The foetal
» epithelial layer is no lonper to be seen on the villi of
the completely formed human placenta.

classes, that the utilisa-
tion of them for systematic purposes which has been made by
MILNE- ED WARDS, OWEN, and HUXLEY was natural.

All lower Vertebrates, Amphioxus, Cyclostomes, Fishes, Dipnoi

238 EMBRYOLOGY.

and Amphibia, either possess no accessory organs at all, or only
an evagination of the intestinal tube, the yolk-sac. The embryos
of Reptiles, Birds, and Mammals, on the contrary, are further
enclosed in two fugitive membranes characteristic of embryonic
life, the amnion and serosa. They have therefore been grouped
together as amniotic animals or Amniota, and the classes first
mentioned have been contrasted with them as non -amniotic animals
or Anamnia.

Among the amniotic animals a further separation into two groups
can be made : on the one side are the egg-laying Reptiles and Birds,
which HUXLEY unites into the Sauropsida ; on the other side
Mammals, in which (with the exception of the Monotremes) the
eggs develop in the uterus, and the young are further nourished
after birth by the secretions of milk-glands.

In the Mammalia the fo3tal membranes, inasmuch as they unite
with the mucous membrane of the uterus to form an organ of nutrition,
take on a still more complicated character, and present modifications
which in turn can readily be utilised for systematic purposes.

In Monotremes and Marsupials the outer embryonic membrane
retains an almost smooth surface, as in Reptiles and Birds ; in all
other Mammals there arise on the surface of the chorion villi, which
grow into the maternal mucous membrane. OWEN has designated
the one as Implacentalia, the other as Placeiitalia. The terms
Achoria and Choriata introduced for these by KOLLIKER are better.

In the Choriata the union of the villi witn the mucous membrane
is either loose or firm ; corresponding to this there is either no
detachable layer of the mucous membrane of the uterus formed,
no decidua, or such a structure arises as the result of close inter-
growth of the placenta uterina and placenta foetalis. Thus we have
the Mammalia indeciduata and the Mammalia deciduata. In each
division there are again two sub-types in the formation of villi. In
the Indeciduata the villi are either evenly distributed over the
surface, or they are united into more or less numerous groups
(placentae or cotyledons), which are separated from one another by
smooth tracts of the chorion. In a part of the Deciduata the
placenta is girdle-shaped, in another part disc-shaped.

SUMMARY.

1. In the Mammalia there is developed, in the same way as in
Reptiles and Birds, a yolk-sac, an amnion, a serosa, and an allantois.

2. Excepting in the Monotremes and Marsupials, the serosa is
metamorphosed into a chorion, in that it puts forth villi, and in that

THE F(ETAL MEMBRANES OF MAMMALS 2391

the connective-tissue layer of the allantois, which is provided with
the umbilical blood-vessels, spreads out on its inner surface and
penetrates into the villi.

3. In a part of the Mammalia certain regions of the serous
membrane, where the villi grow more vigorously and put forth
lateral branches, and sink into corresponding depressions of the
mucous membrane of the uterus, are converted into a placenta (when
many of them have arisen on one chorion they are called cotyledons).

4. On the placenta one distinguishes :—

(a) A placenta foetalis, i.e., that part of the chorion which has

developed the tufts of villi.

(b) A placenta uterina, i.e., that part of the mucous membrane

of the uterus which has proliferated and is provided with
depressions for the reception of the placenta foetalis.

5. Fcetal and maternal parts of the placenta can become more
firmly united with each other ; the result is that at birth a larger
or smaller tract of the mucous membrane of the uterus is also cast
off, and is known as the caducous membrane, or the decidua.

6. According to the character of the embryonic membranes, the
following divisions of Vertebrates may be established : —

I. Anamnia, animals without an amnion.

(Amphioxus, Cyclostomes, Fishes, Amphibia.)
II. Amniota, animals with an amnion (with yolk-sac, amnion,.
serosa, and allantois).

A. Sauropsida. Egg-laying, anmiotic animals.
(Reptiles and Birds.)

B. Mammalia. In all of them, except the Monotremes, the

eggs are developed in the uterus.

(a) Achoria. The serosa develops no villi, or only a few.

(Monotremes, Marsupials.)

(b) Choriata. The serosa becomes the villous membrane

(chorion).

'(1) With evenly distributed villi.
., .. (Perissodactyla, Suidse, Hippopotamidae, Tylopoda,.

.M i t 1 Ii 1 1 1 H 1 K 1 m t . -t s-v . \

Tragulidse, Cetacea, etc.)

, . , (2) Placentalia. The serosa is at intervals metamor

deciduata. x '

phosed into a placenta.

a. Numerous cotyledons. (Ruminantia.)
C /?. Placenta zonaria. (Carnivora.)

,.,,-! y. Placenta discoidea. ([Man,] Apes, Rodents, In-
I sectivores, Bats.)

240 EMBRYOLOGY.

LITERATURE.

Beneden, van, et Charles Julin. Recherches sur la formation des

annexes foetales chez les Mammiferes (Lapin et Cheiropteres). Archives

de Biologic. T. V. 1884.
•Caldwell, "W. H. Eierlegen der Monotremen. Referat in Schwalbe's

Jahresbericht, p. 507. 1886.
Caldwell, W. H. On the Arrangement of the Embryonic Membranes in

Marsupial Animals. Quart. Jour. Micr. Sci. Vol. XXIV. p. 655. 1884.
HJdwards, Milne. Le$ons sur la physiologie et 1'anatomie comparee de

1'homme et des animaux. Pans 1870.
Eschricht. De organis quae nutrition! et respirationi foetus mammalium

inserviunt. Hafniae 1837.
•Godet. Recherches sur la structure intlme du placenta du lapin. Inaugural

Dissertation. Ncuveville 1877.
Haacke, W. Meine Entdeckung des Eierlegens der Echidna hystrix. Zool.

Anzeiger, p. 647. 1884.
Hoffmann, C. K. Ueber das Amnion des zweiblatterigen Keimes. Archiv

f. mikr. Anat. Bd. XXIII. p. 530. 1884.
Kblliker. Entwicklungsgeschichte des Menschen und der hoheren Thiere,

pp. 261-3 and 360, 361. 1879.
Mauthner, Julius. Ueber den miitterlichen Kreislauf in der Kaninchen-

placenta mit Riicksicht auf die in der Menschenplacenta bis jetzt vorge-

fundenen anatomischen Verhaltnisse. Sitzungsb. d. k. Akad. d. Wissensch.

Math.-naturw. Classe. Bd. LXVII. Abth. 3. 1873.
Milne-Edwards. See Ed wards,. Milne.
Osborn, H. F. Observations upon the Foetal Membranes of the Opossum

and other Marsupials. Quart. Jour. Micr. Sci. Vol. XVIII. 1883.
Osborn, H. F. The Foetal Membranes of the Marsupials.' Jour. Morphol.

Vol. I. 1887.
Owen, R. Description of an Impregnated Uterus and of the Uterine Ova ot

Echidna hystrix. Ann. and Mag. Nat. Hist. Vol. XIV. p 373. 1884.
Slavjansky. Die regressiven Veranderungen der Epithelialzellen in clei

serosen Hiille des Kanincheneies. Berichte iiber die Verhandl. d. k.

sachsischen Gesellsch. d. Wissensch. Leipzig. Math.-phys. Classe. Bd.

XXIV. pp. 247-52. 1872.
Strahl, H. Die Dottersackwand u. der Parablast der Eidechse. Zeitschr. f.

wiss. Zoologie. Bd.'XLV. p. 282. 1887.
Turner. On the Placentation of the Apes with a Comparison of the Structure

of their Placenta with that of the Human Female. Philos. Trans. Pioy. Sci.

London. Vol. CLXIX. Part I. 1878.
Turner. Some General Observations on the Placenta with especial reference

to the Theory of Evolution. Jour. Anat. and Physiol. 1877.
Virchow, Hans. Ueber das Epithel des Dottersackes im Hiihnerei. Disser-
tation. Berlin 1875.
Waldeyer, W. Die Placenta von Inuus nemestrinus. Sitzungsb. d. k.

preuss. Acad. d. Wissensch. Berlin. 1889.
Numerous citations of the literature on the foetal membranes of Mammals are

to be found in Hoffmann : Grondtrekken der vergelijkende ontvvikkelings-

creschiedenis, etc. 1884.

THE FOETAL MEMBRANES OF MAN. 241

CHAPTER XIII.
THE FCETAL MEMBRANES OF MAN.

THE investigation of the first stages in the development of man,
which are accomplished during the first four weeks of pregnancy, is
coupled with extraordinary difficulties. Only very exceptionally does
the embryologist come into possession of young human ova, whether
found in the uterus at the time of dissection, or coming into the
hands of a physician as the result of miscarriage. In the latter case
the ova have often been "dead for a long time in the uterus, and
consequently are in '"pt-pcess of "decomposition. Finally, a good
preservation and an accurate investigation of such small and
delicate objects demand no slight degree of skill.

This accounts for the fact that we do not possess in the case of
Man a single observation upon the process of fertilisation or that of
cleavage, upon the formation., of the^ germ-layers, or upon the first
establishment of the form* ofrtHe, body, the foetal membranes, and a
large number of other organs. Concerning this whole period we
are dependent upon the conclusions which are furnished by the
development of other Mammals. Thus we assume that fertilisation
normally takes place in the enlarged beginning of the oviduct
(Fallopian tube) ; that the seminal elements, which remain alive in
the female sexual organs perhaps for days or weeks, here await the
ovum as it emerges from the ovary ; that the ovum already segmented
enters into the cavity of the uterus, attaches itself in the mucous
membrane, and during the first weeks of pregnancy gives rise to the
germ-layers, the outer form of the body, and the foetal membranes,
according to the well-known rules for other Mammals.

A little, although very scanty, information has been acquired,
but this concerns only the second arid subsequent week. A small
number of ova have been described in the literature, which for the
most part come from miscarriages, and the age of which has been
estimated at from twelve to fifteen days. The blastodermic vesicles
measured 5 to 6 mm. in diameter. Here belong two ova described
by ALLEN THOMSON, and those by SCHRODER v. D. KOLK, HENNIG,
REICHERT, BREUSS, BEIGEL UND LOWE, as well as the cases published
by AHLFELD, KOLLMANN, FOL, and GRAF SPEE.

Upon critical comparison of the discoveries, there are two facts
which we can regard as established.

First. At the end of the second week the blastodermic vesicle

16

242

EMBRYOLOGY.

(blastula) no longer lies free in the cavity of the uterus, but is
enclosed in a special capsule produced by the growth of the mucous
membrane. Hitherto no one has had the opportunity to make
observations concerning the formation of this capsule. Following
an hypothesis of SHARPEY, which has been somewhat modified by

Dv

~±g. 139.— Diagrammatic section through the grwid human uterus, from WIEDEUSHEIM.

U, Uterus ; UH, cavity of the same ; Tb, Fallopian tube ; DC, cecidua vera ; Dr, decidua reflexa, ,
Pu, .placenta uterina (decidua serobiiia) ; Pf. placenta foe tails or choriou frondo3um (CUj) ',
Chi, chorion laeve ; A (on black background), cavity of the amnion filled with amniotie
fluid ; Z>, yolk- (umbilical) vesic'e ; in the embryo one sees the r.mbilical vessels (Al) ; t tho
livcjr traversed by the vera nmbilicalis ; //, the Jieavt ; A, the aorta; ci and cs, the vena
cava ii,ferior and superior ; p, vena pottaruui. »

KEICHERT, it is now generally assumed that the ovum upon its
entrance into the uterus imbeds itself in a depression of the mucous
membrane, which is thrown into ridges and is in process of being
metamorphosed into the decidua. The margins of the depression
soon grow around the blastula on all sides, and fuse together to form
a, closed foetal capsule. The fusion takes place at a point diametrically

THE F(ETAL MEMBRANES OF MAN. 243

opposite the attachment, and is described as resembling a cicatrix.
It is destitute of blood-vessels, whereas these, as well as uteirne
glands, are present in the remaining portion of the overgrowing
mucous membrane. The blastula lies in this receptacle now, and
even into the beginning of the second month, loosely enclosed ; after
opening the capsule the blastula can be removed easily and without
injury.

Whereas in other Mammals only that part of the uterine mucous
membrane which contributes to the formation of the placenta is cast
off, in the case of Man there occurs a much more extensive ecdysis
of the most superficial layer, namely, over the whole inner surface of
the uterine cavity. Here, too, the part which is cast off is designated
as deciduous membrane or decidua, and three regions are distinguish-
able (fig. 139) — the part which is thrown around the blastula as
decidua reflexa (Dr), the part which forms the floor of the depression
in which the ovum has established itself as decidua serotina (Pu), and
the remaining portion as decidua vera (Dv).

In the retiexa we become acquainted with a structure which in
this complete form occurs only in the case of Man and the Apes,
whereas beginnings of such a structure are also found in other
groups, as, e.g., in the Carnivores. Since the foetal capsule does not
at first completely fill the uterus, there remains between reflexa and
vera a space filled with mucus.

A second and in many respects astonishing result is, that even
in very young and small blastodermic vesicles, as all discoveries
agree in showing, a well-developed chorion with abundant villi is
fcegun.

The villi are either distributed over the whole surface of the ovum,
or, as in REICHERT'S case (fig. 140 A and B), they leave two opposite
poles of the blastula free. They attain a length of one millimetre,
and in part have the form of simple cylindrical elevations ; in part
they already possess lateral branches. At no place have they fused
with the decidua. Like the chorion itself, they consist of two layers
— of a superficial epithelial layer, derived from the serosa, concern-
ing which AHLFELD and KOLLMANN have made very definite and
reliable statements, and of a layer of embryonic gelatinous tissue,
which extends into the axis of the villi and already appears to bear
here and there blood-vessels.

Unfortunately we have learned nothing from investigations of
these youngest of all human embryos concerning the structures
within the chorion, — the remaining foetal membranes and the

244 EMBRYOLOGY.

fundament of the embryo itself. Either the ova were already more
or less pathologically altered, or the contents were considerably
damaged in consequence of the method of preservation and by the
preparation. At all events with other investigators one, I think,
may conclude from the condition of the chorion that the embryo
must have been in an advanced stage, in which germ-layers, yolk-
sac, and amnion were already formed.

This assumption is all the more reasonable, since well-developed
embryos from blastodermic vesicles which were only a few milli-
metres larger have been described by COSTE, ALLEN THOMSON, His,
and others. In these cases the head-end of the embryo only is
rather sharply differentiated from the yolk-sac, which is continuous
with the fundament of the intestine throughout nearly its entire

Fig. 140.— The human ovum at an early stage of development.

A and B, Front and side views of a human ovum of 12 to 13 days, figured by REICHERT. e, The

part designated by REICHERT as embryonic spot. From QUAIN'S " Anatomy."
C, An ovum of 4 to 5 weeks, showing the general character of the villous membrane before the

formation of the placenta. A part of the wall of the ovum is removed in order to show the

embryo in situ. After ALLEN THOMSON, from KOLLIKER'S " Entwicklungsgeschichte des

Menschen, etc."

length. The neural canal is not yet closed, but the amnion never-
theless is completely developed, and in fact lies almost in contact
with the embryonal body ; at its posterior end it is connected with
the chorion by means of a short cord, which is connected with th&
fundament of the allantois and has been named the belly-stalk
(Bauchstiel) by His.

Also in the only slightly older embryo of COSTE (fig. 141) — in which
the neural tube is closed, the body distinctly segmented (us), the
head provided with visceral arches (vb), behind the latter the
heart (h) recognisable, and the yolk-sac (ds) further constricted off—
a short belly-stalk (bst) is present. It is composed of the amnion
(am1) drawn out to a point and of a connective-tissue cord, which
arises from the ventral surface of the embryo out of the intestinal
cavity of the pelvic region, encloses at its attached end a small cavity

THE FCETAL MEMBRANES OF MAN.

245

- h

x- am

(the allantois), and conducts the allantoic blood-vessels from the
pelvic portion of the intestine to the chorion.

This cord is a characteristic structure for the human embryo, the
significance of which is still in dispute. KOLLIKER and His have
given somewhat different explanations of it. KOLLIKER brings the
cord into relation with the development of the allantois. He makes
the fundament of this important embryonic appendage arise, as in
other Mammals, from the hind gut of the embryo, and approach the
serosa as a thick vascular connective-tissue growth lined with a narrow,
short epithelial
tube, without
previously de-
veloping inside
itself a large
epithelial sac.
He also main-
tains that the
connective-
tissue part of
the short allan-
toic cord, or
bell y-s talk,
grows around
on the whole
inner side of
the serosa, and
into the epi-
thelial villi.

His regards
as unwar-
ranted " the

assumption, in opposition to the actual state of affairs, that the
human embryo at first separates itself from, the part of the blasto-
dermic vesicle which is employed for the chorion, and subsequently
unites with it again by means of the fundament of the allantois."
He does not admit that the fundament of the embryo in Man is
ever wholly constricted off from the chorion, as in the remaining
Mammals, and he recognises in the belly-stalk " the bridge of
connection between the fundament of the embryo and the
chorionic part of the original blastodermic vesicle, which has
never been severed." According to . him the allantois in the

Fig. 141.— Human embryo with yolk-sac, amnion, and belly-stalk of
15 to 18 days, aftei COSTE, from His ("Menschliche Embryonen").

His has untwisted somewhat the posterior end of the body in com-
parison with the original figure, in order to bring into view the
right side of the end of the body, the left side being represented
in COSTE'S fig. 4. The chorion is detached at am1, am, Amnion ;
am1, the point of attachment of the amnion to the chorion drawn
out to a tip ; bst, belly-stalk ; Sch, tail-end ; us, primitive seg-
ment ; dg, vitelline blood-vessels ; ds, yolk-sac ; h, heart ; vb,
visceral arch.

246 EMBRYOLOGY.

human embryo has nothing to do with the development of the
belly-stalk.

Neither of these two explanations seems to me entirely satisfactory.
According to my view, the structure under consideration may be
explained in a manner which is not only in complete harmony with
the facts of the case, but also reconciles the views of KOLLIKER and
His.

As COSTE'S embryo appears to show, the origin of the belly-stalk is
connected in the first place with a somewhat irregular formation of the
amnion. It follows from the fact that the latter is drawn out
posteriorly to a point (fig. 141 am1), the apex of which reaches to the
chorion, that its closure in the human embryo takes place at the
extreme posterior end of the body, and that at the same time a union
with the chorion is retained at the place of closure. The fundament
of the embryo therefore remains in connection with the chorion, not
directly, as His maintains, but only indirectly by means of the
amnion.

In the second place, the allantois, the somewhat eccentric develop-
ment of which in the case of Man is perhaps intimately connected
with the above-mentioned peculiarity in the formation of the amnion,
takes part in the formation of the belly-stalk. It is therefore proper
in this connection to enter somewhat more fully into the allantois-
question in Man, so actively discussed during the last decade.

Since in other Mammals the allantois (fig. 142 al) has the form of
a large stalked sac. which grows out from the navel till it comes in
contact with the sero?a (sz), and carries to it, along with connective
tissue, the umbilical vessels, attempts have been made ever and anon
to discover such a structure in the case of human embryos also. The
proof of its existence in Man appeared to be furnished by a premature
embryo, on which KRAUSE described a spherical, sac-like allantois.

The embryo of KRAUSE presented, however, in many respects
such deviations from other known human embryos of the corre-
sponding stage as to cause the statements to be accepted on the part of
many persons with great reservation, and to permit the suggestion
of His, that in this case it was not after all a human embryo.

Upon critical examination of the facts relating to the question,
I am likewise of the opinion that in the case of Man a stage of
development with a free allantoic sac protruding out of the body-cavity
is not reached.

As results from the fine investigations of human embryos by His,
the belly-stalk is found upon cro?s section to be composed of : —

THE FCETAL MEMBRANES OF MAN. 247

(1) The pennant-like prolongation of the amnion ;

(2) Beneath this, abundantly developed embryonic connective
tissue ;

(3) The fundament of the allantois, which has the form of a very
narrow passage with epithelial lining ;

(4) The umbilical blood-vessels, of which the arteries lie close
upon the allantoic duct, while the veins run nearer to the amnion.

To the question, How have these parts arisen ? that appears to me

Fig. 142.— Diagram of *he foetal membranes of a Mammal, after TURNER.

pc, Zona pellucida with villi (prochorion) ; sz, serous membrane ; am, amnion AC, amniotic

cavity ; £, outer germ-layer ; M, middle germ-layer ; H, inner germ-layer ; UV, yolk-^ac

(vesica umbilicalis) ; al, allantois; ALC, allantoic cavity.

the most natural answer which permits of being harmonised with
the known conditions in other Mammals. Now, such an agreement
is possible upon the following assumption.

Very early, when the hind gut begins to be formed, there arises
on its ventral side as a fundament of the allantois a knob composed
of many cells, and containing only a small evagination of the ento-
dermic layer. The allantoic knob does not, however, grow free into
the body-cavity, as in the remaining Mammals (fig. 142 al). but ex-
tends along the ventral wall of the embryo, and, from the place where
this is reflected off to form the amnion, along the ventral wall of the

248 EMBRYOLOGY.

latter (fig. 141 am1) up to its place of attachment to the chorion.
The evagination of the entodermic layer meantime becomes elongated
into the narrow allantoic duct ; the more voluminous connective -
tissue growth carries with it the umbilical blood-vessels to the
chorion, then spreads itself out on the inner surface of the latter
in the well-known manner, and penetrates into the villi of the
serosa.

The allantois, therefore, in its development, instead of growing
out free to the serosa, makes use of the already existing connection
between the latter and the embryo established by the pennant-like
elongation of the amnion (am1). But this mode of development
perhaps results from the fact that the posterior end of the embryo
in Man, as fig. 141 shows, is closely attached to the serosa at the
place of the amniotic suture, whereby the allantois has only a short
distance to grow in order to reach the serosa.

Finally, the early appearance of the allantois will become intel-
ligible to us, if we remind ourselves that organs of great physiological
importance have in general the tendency to an accelerated develop-
ment, and that in the series of Mammals the provisions for the
nutrition of the embryo by means of a placenta have become more
and more complete.

While there is still much obscurity about the first stages of Man's
development, we possess more satisfactory insight into the changes
which the embryonic membranes in Man undergo from the third
week onward.

From this point forward we shall examine each separate embryonic
membrane by itself : first the structures that are developed from
the blastodermic vesicle — (1) the chorion, (2) the amnion, (3) the
yolk-sac ; then (4) the deciduse which are produced by the mucous
membrane of the uterus ; and finally (5) the after-birth (placenta)
and (6) the umbilical cord.

1. The Chorion.

During the first weeks of pregnancy the whole surface of the
chorion is covered with villi (fig. 1325, p. 226, and fig. 140), and
provided with terminal branches of the umbilical blood-vessels. After
its growth has proceeded for a time uniformly, there begin to appear —
from the beginning of the third month onward — differences between
the part which lies directly against the wall of the uterus that is
destined to become the decidua serotina and the remaining greater

THE FCETAL MEMBRANES OF M AX.

249

part, which has become overgrown by the decidua reflexa (fig. 143).
While on the latter the villi (z1) cease to grow, on the former they
increase enormously in size and take the form of long, and at the
base thick, tree-like, branching structures («), which, united into
tufts, project
far beyond the
surface of the
membrane that
bears them,
and grow into
pits of the ma-
ternal mucous
membrane (ds).
This part, to
which we shall
give more par-
ticular atten-
tion at the
time of inves-
tigating the
mature pla-
centa, is there-
fore distin-
guished as
chorion fron-

dosum from the remaining larger part, the chorion Iceve or the
smooth chorion.

The expression " smooth chorion " is, strictly speaking, not quite
applicable. Of the villi which are at first everywhere developed,
some afterwards remain preserved on the chorion laeve, especially in
the vicinity of the placenta. They grow into the decidua reflexa,
effecting a firm union with it (fig. 143 «').

At the same time a second distinction between chorion frondosum
and chorion Iseve is developing. In the territory of the latter the
blood-vessels arising from the umbilical arteries begin to dwindle,
whereas the former becomes more and more abundantly supplied
with blood-vessels, and finally alone receives the terminal distribution
of the umbilical arteries. Thus the one region becomes destitute of
vessels, while the other becomes extraordinarily vascular, and the
nutritive organ for the embryo.

Histologically the chorion laeve, which upon examination from the

Fig. 143.— Diagrammatic section through the gravid human uterus with

contained embryo, after LOXGET, from BALFOUB.
al, Stalk of the allantois ; nb, umbilical vesicle ; am, anmion ; eh

chorion ; ds, decidua serotina ; du, decidua vera ; dr, decidua

reflexa ; I, Fallopian tube ; c, cervix uteri ; u, uterus ; z, villi of

the foetal placenta ; z?, villi of the chorion laeve.

250 EMBRYOLOGY.

surface appears thin and translucent, consists of (1) a connective-tissue
membrane, and (2) an epithelial covering, which is identical with the
original serosa.

The connective-tissue membrane possesses at first the character of
embryonic mucous tissue, and exhibits therefore branched stellate cells
in a homogeneous matrix. Subsequently the mucous tissue is con-
verted, as at other places in the body, into fibrous connective tissue.

The epithelium of the diorion consists in the first months, according
to the statements of KASTSCHENKO and SEDGWICK MINOT, of two
layers — a superficial one, in which no cell -boundaries are visible
(protoplasmic layer), and a deeper one, in which the individual cells
are distinctly separated. Additional particulars are given in the
description of the placenta.

The embryonic adjuncts enclosed within the chorion — the amnion
and yolk-sac — undergo in Man during pregnancy the following
changes.

2. The Ainnion.

The amnion (am) immediately after its origin lies close on the
surface of the embryo (fig. 144), but soon becomes distended by the
accumulation of fluid, the liquor amnii, in its cavity (fig. 1325). It
increases to a much greater extent than in other Mammals, in which
it is often found to be smaller than the allantoic sac (compare the
foetal membranes of the Rabbit, fig. 133). Finally, in Man it Jills
out the entire blastodermic vesicle, since it everywhere applies itself
(fig. 143 am) closely to the inner wall of the chorion (ch).

Its wall is rather thin and translucent, and also consists, like the
chorion, of an epithelial and a connective-tissue layer.

The epithelium, derived from the outer germ-layer of the embry-
onic fundament, lines the amniotic cavity within, and is continuous
with the epidermis of the embryo at the dermal navel ; at the place
of transition it is composed of layers ; but elsewhere it is a single sheet
of pavement cells. The connective-tissue layer is thin and at the
navel continuous with the corium.

The amniotic or fatal water is slightly alkaline, and contains about
1% solid constituents, among which are found albumen, urea, and
grape-sugar. Its volume is greatest in the sixth month of pregnancy,
and it often attains a weight of not less than a kilo [2-2 Ibs. avoir-
dupois] ; then it diminishes to about one-half that amount at the
time of birth, and in the same ratio as the embryo by its increased
growth demands for itself more room. Under abnormal circumstances

THE FCETAL MEMBRANES OF MAN.

251

the secretion of amniotic water can become much greater, and can,
by a considerable distension of the amnion, lead to conditions which
have been called dropsy of the amnion, or hydramnion.

Sch

3. The Yolk-Sac.

The yolk-sac or the umbilical vesicle (vesicula umbilicalis) in Man
pursues the opposite course of development from that of the ever-
increasing
amnion, and
shrivels to a
structure that
easily escapes
observation.

Iri human
foetuses of the
second and
third week (fig.
144) the yolk-
?ac (ds] fills
somewhat more
than half of the
blastod e r m i c
vesicle and is
not constricted
off from the in-
testine, which
still has the
form of a
groove.

In somewhat older embryos it is seen to be connected by means of
a thick static or vitelline duct with the middle of the rudimentary
intestine, now converted into a tube. It is supplied with blood by
the vasa omphalomesenterica.

During the sixth week the vitelline duct or ductus omphalomesen-
tericas has grown out into a long, narrow tube, which sooner or later
loses its cavity and is converted into a solid epithelial cord. It
terminates in the small egg-shaped umbilical vesicle (figs. 139 D and
143 nb). Since the amnion, in consequence of a greater accumulation
of fluid, now fills the whole blastodermic vesicle (fig. 143), it has
enveloped both the vitelline duct and the neck of the allantois (al).

Fig. 144.— Human embryo with yolk-sac, amnion, and belly-stalk of
15 to 18 days, after COSTE, from His (" Menschliche Embryonen ").

His has untwisted somewhat the posterior end of the body in com-
parison with the original figure, in order to bring into view the
right side of the end of the body, the left side being represented in
COSTE'S fig. 4. The chorion is detached at am1, am, Amnion ; am1,
the point of attachment of the amnion to the chorion drawn out to
a tip ; bst, belly-stalk ; Sch, tail-end ; iw, primitive segment ; dg,
vitelline blood-vessels ; ds, yolk-sac ; h, heart ; vb, visceral arch.

252

EMBRYOLOGY.

and, as it were, surrounded them with a sheath (amniotic sheath).
The structure thus produced, the umbilical cord, f uniculus umbilicalis,
is now the only means of connection between the embryo, which
floats free in the amniotic fluid, and the wall of the blastodernric
vesicle. Its attachment to the latter always coincides with the place
where the placenta is developed.

By the enlargement of the amnion the umbilical vesicle is crowded
out to the surface of the blastodermic vesicle, where it is enclosed
between amnion (am) and chorion (ch), at some distance from the
place where the umbilical cord is attached. It continues to exist
here up to the time of birth, although in a very rudimentary condition.
It is only by painstaking examination that it is to be found, usually

several inches away from the

GI.U --nOr7nnf~l/If~irir~ margin of the placenta. Its

longest diameter measures only
from 3 to 10 millimetres. It
was on this account that the
older text-books of anatomy,
physiology, and embryology
contained the statement
that in Man the vesicula
umbilicalis disappeared as a
useless structure ; this idea
prevailed until the constancy
of its presence was demon-
strated by B. SCHULTZE.

M -

Fig. 145.— Cross section through the mucous mem-
brane of the uterus, after KUNDRAT UND ENGEL-

MANN.

Gl.u, Uterine glands ; M, muscular layer of the
uterus.

4. The Deciduae.

The deciduce or caducous

foetal membranes take their origin from the mucous membrane of the
uterus, the structure of which is greatly altered during pregnancy.

In the unmodified condition the mucous membrane is a soft layer
about a millimetre thick, which reposes directly and immovably upon
the musculature (M ) of the uterus, which does not possess a submucosa
in this region (fig. 145). It is traversed by numerous tubular uterine
glands (glandulse utriculares, Gl.u), which begin at the surface with
small orifices and pass directly downward in a sinuous course close
to one another until they reach the musculature (M), where they
terminate, often after dichotomous division.

Mucous membrane and glands are lined with ciliate cylindrical cells.
The connective tissue that separates the glands embraces an extra-

THE FOZTAL MEMBRANES OF MAN. 253

ordinary abundance of cells, some of which are spindle-shaped, others
roundish.

From the beginning of pregnancy the mucous membrane undergoes
very profound changes, which affect all parts. Concerning these we
possess accurate observations, which relate to every month of preg-
nancy, by KUNDRAT UND ENGELMANN, as well as by LEOPOLD and
SEDGWICK MINOT.

We take up in succession (1) the decidua vera, (2) the decidua
reflexa, and (3) the decidua serotina or placentalis, the part which
enters into the formation of the placenta.

(1) Decidua vera. As LEOPOLD remarks, with the beginning of
pregnancy the mucous membrane constantly increases in thickness,
until it becomes 1 cm. or more thick, up to the time, indeed, when
the growing ovum attaches itself completely to the walls of the
uterus, therefore approximately up to the end of the fifth month.
From that time forward there begins, as it were, a second stage, in
which, under the pressure of the growing foetus, it again becomes
thin and finally is only 1 to 2 mm. thick. Meanwhile both the
glands and the tissue between them undergo changes.

During the first stage the uterine glands, which at the beginning
are tubes of uniform calibre, increase in size, especially in their
middle and deeper parts (fig. 146) ; whereas at their open end
they are rectilinear and drawn out lengthwise, deeper down
they take a spiral course and are covered with e vagina tions and
pocketings.

Upon sections therefore one can now distinguish two layers in the
decidua vera : —

(1) An outer more compact layer (C), possessing more abundant
ceils, and

(2) A deeper ampullar or spongy layer (/Sp).

In the former one sees the glands as elongated, parallel canals.
In consequence of a great growth of the inter-tubular tissue they
are separated from one another farther than at first ; they begin at
the surface with enlarged funnel-shaped pits (tr). The surface of a
mucous membrane stripped off from the musculature has, as KOLLIKER
states, a sieve-like appearance, due to the enlarged orifices of the glands.

In the spongy layer (/Sp) one encounters irregular, lobed
cavities (dfi) one above another, the capacity of which continually
increases up to the middle of pregnancy, and which are finally
separated from one another by thin septa and cords of the matrix-
tissue only. The appearance is explained by the fact that in the

254

EMBRYOLOGY.

Jf

middle of their course the
glands are highly tortuous
and have enlarged and be-
come pocketed.

The dilate cylindrical epi-
thelium at the surface of the
mucous membrane of the
uterus gradually disappears
entirely ; it is destroyed as
early as the end of the first
month of pregnancy (MINOT).
In the glands it undergoes
fundamental changes. In
the first months all the cavi-
ties are still lined with it, a
condition which, on account
of the increase in the size of
the cavities, presupposes an
active cell-growth. Mean-
while the originally elongate
cylindrical cells are in part
converted into small cubical,
in part into small flat struc-
tures, except in the portions
of the glands which adjoin
the muscular membrane.
The cells here preserve more
or less their normal form up
to the end of pregnancy, and
subsequently serve for the
regeneration of tlie epithelial
lining of the mucous mem-
brane of the uterus.

In the fourth and fifth

Fig. 146.— Cross section through the
mucous membrane of a uterus at the
beginning of pregnancy, after KUND-
RAT UNO EXUELMAXX.

C, Compact layer ; Sp, spongy layer ;
M, musciilature of the uterus : tr,
funnel-shaped mouths of the uterine
Clam's; e, enlarged region; dh, am-
pullae produced by the wine ings and
evagiitations of the Avowing- glands.

THE F(ETAL MEMBRANES OF MAN.

255

months one still finds all cavities up to the mouth of the glands
lined with a thin layer of cubical or flat epithelial cells.

Likewise in the first stage there occurs in the inter- glandular

Itift

tissue an active process of growth, especially in the upper compact
layer. In this there are formed spheroidal structures, 30 to 40 /x
in diameter, which have been called decidual cells by FRIEDLANDER.
In many places they lie so close together that, as a consequence
.and because of their form, they appear very similar to an epitheliumr

256 EMBRYOLOGY.

They are also found in the spongy layer, but in the cords and septa
they are more elongated and spindle-shaped.

In the second stage, from the sixth month forward, in which the
decidua vera becomes much thinner, and under the pressure of the,
growing foetus gradually diminishes from 1 cm. to 2 'mm. in thickness,
many regressive processes take place in the individual parts that have
just been described (fig. 147).

The mouths of the glands, which caused the sieve-like condition of
the inner surface of the decidua, become more and more difficult to
see and finally disappear altogether.

The inner compact layer (C) assumes a uniform, compact, lamellar
condition, since by the pressure the cavities of the glands occupying
it become wholly obliterated, and then by disappearance of the epithe-
lium their walls become fused.

In the spongy layer (Sp) the cavities of the glands (dh) persist,
but, in consequence of the pressure, are converted into fissures, which
are parallel to the wall of the uterus, and are separated by partitions
which in comparison to earlier months of pregnancy have become
very much thinner. The glandular cavities which are adjacent to
the compact layer have lost their epithelium or exhibit cellular debris
(de), swollen bodies, and a slimy mass p?rmeated with fine granules ;
toward the uterine musculature, on the contrary, they possess a well-
preserved epithelium of short cylindrical or cubical cells.

(2) The decidua reflexa (fig. 148 Dr) exhibits close agreement in its
structure with the decidua vera. That it has arisen from the latter
by a process of foldinj may be inferred, as KUNDRAT has rightly
maintained, especially from the circumstance that during the first
months of pregnancy the mouths of uterine glands (glu), at least
at the place of transition to the vera, are found upon both its sur-
faces. The mouths lead into fissures (glu) which are parallel to the
surface of the refiexa and are lined with cuboidal epithelium. In
the inter-glandular tissue there appear the same large, round decidual
cells as in the vera.

From the fifth month forward the space between vera and reflexa
begins to disappear ; both membranes now, after loss of th'eir epithe-
lium, become firmly pressed together, and finally completely fused
with each other (fig. 147). By this process the reflexa, from which
the glandular spaces disappear except in the transitional region,
becomes so extraordinarily thinned that it constitutes [in sections]
only a narrow band, occasionally | mm. broad.

A separation of the two membranes at the close of pregnancy

THE FCETAL MEMBRANES OF MAN.

257

is very difficult, but occasionally it may still be accomplished to some
extent.

Moreover in later months the inside of the decidua reflexa is
firmly fused with the chorion, and since the chorion in its turn is in
contact with the amnion (fig. 147 ch and am), one now comes, by

Fig. 148.— Section through decidua serotina (Dse) at the transition into decidua vera (Dv) and
reflexa (Dr), after KUSDRAT USD EXGELMANX.

M, Musculature of the uterus ; Sp, spongy layer of the decidua vera and serotina ; C, compact
layer of the same ; glu, uterine glands ; sp. fissures in the serotina resulting from growth
of the glands ; dh, ampullarial spaces in the spongy layer produced by growth of the glands.

cutting through the muscular wall of the uterus, and then opening
the foetal membranes, .which are thus pressed together, directly into
the amniotic cavity, in which the embryo lies bathed in the amniotic
fluid.

(3) The third region of the uterine mucous membrane, or the
decidua serotina (fig. 148 Dse), is that part which joins with the

17

258 EMBRYOLOGY.

chorion frondosum to form a nutritive organ for the embryo. —
the after-birth, or placenta.

According to the statements of KUNDRAT and LEOPOLD it under-
goes changes similar to those of the decidua vera. Here also the
uterine glands grow rapidly in its deeper portions (fig. 148) and are
converted into irregular spaces (dh), which are from the beginning,
however, most extended in breadth. Subsequently they are crowded
together still more by the pressure and the growth of the placenta
until they become narrow fissures which lie parallel to the surface
of the uterus.

The glandular epithelia disintegrate to a still greater extent than
in the vera, and by disintegrating and swelling up become detached
from the connective-tissue walls ; only those regions of the glands
which are adjacent to the muscular layer (M) retain their cylindrical
cells.

In this presentation KUNDRAT and LEOPOLD disagree with KOLLIKER
and with TURNER, who likewise, it is true, find great spaces in the
deeper layer of the serotina, but interpret them for the most part
as greatly enlarged blood-vessels, an Assumption according to which
there would exist an important difference between the serotina and
the vera.

In the superficial layer the outlets of the glands must disappear
early, since they become pressed together. Besides, more active cell-
proliferation takes place in the inter-glandular tissue.

Therefore the decidua serotina (fig. 148 Dse) is also converted
into two readily distinguishable layers : —

(1) A deeper spongy layer (8p), in which the detachment of

the placenta subsequently takes place, and

(2) A superficial, more compact layer (C). The latter alone shares

in the formation of the placenta, and is accordingly called
the placenta uterina (or materna). It undergoes from the
second month forward more profound alterations.
We shall become acquainted with these in the description of the
placenta, to which we now pass.

5. The Placenta.

•

The placenta is a very vase alar, and when filled a spongy or doughy,
disc-shaped structure, which at the height of its development mea-
sures 15 to 20 cm. in diameter and is 3 to 4 cm. thick. Its weight
reaches somewhat more than a pound (500 grammes). The surface

THE FOETAL MEMBRANES OF MAN. 259

which is turned toward the embryo is concave (figs. 139 and 143)
and altogether smooth, since it possesses a covering of the amnion
(am) ; the surface which reposes on the wall of the uterus is convex,
after its detachment at birth feels uneven, and is divided by deep
furrows into separate lobes or cotyledons.

The normal position of the placenta is, in the majority of cases,
at the fundus uteri, where it is sometimes developed more to the
left side, sometimes more to the right. Consequently the opening
of one or the other of the Fallopian tubes may be covered and sealed
by it.

In rare cases the placenta, instead of being attached to the fundus,
is united to the wall of the uterus nearer its mouth [os uteri]. This
results from the fact that the fertilised egg, when it passes from the
Fallopian tube into the cavity of the uterus, sinks down farther
owing to abnormal conditions, instead of attaching itself at once to
the mucous membrane.

Occasionally the attachment takes place quite low, in the immediate
vicinity of the inner mouth of the uterus. In this case, as the
placenta with the growth of the foetus extends itself, it grows either
partly or wholly over the mouth of the uterus, and closes it more
or less completely. This anomaly is known as placenta prcevia
(lateralis or centralis) and presents a dangerous condition, because
the regular progress of birth is disturbed.

In consequence of the low position of the placenta perilous bleeding is pro-
duced, either during pregnancy, or at least at the beginning of labor pains,
because the placenta detaches itself from the wall of the uterus prematurely,
whereby large blood-vessels are ruptured and laid open.

In the investigation of the finer structure of the placenta serious
obstacles are encountered, since it is a very soft organ traversed by
numerous capacious blood-vessels. Therefore very contradictory views
still prevail concerning many points which are of the greatest
importance in judging of the structure. It does not appear to me
possible to give at present a final opinion upon these points.

In the description it is best for us to start with the fact that the
placenta, as was previously stated, is composed of two parts, — of one
part which is furnished by the embryo, and another part which is
produced by the mother, — the placenta foetalis and the placenta
uterina (Plate II.).

The placenta foetalis is the part of the chorion (chorion frondosum)
which is thickly covered with much-branched villi. The villi (z),
united into great tufts or cotyledons, elevate themselves from a firm

260 EMBRYOLOGY.

membrane, the membrana chorii (m), in which the chief branches
of the umbilical arteries and veins take their course. They consist
of (1) large main stems (z), which grow straight out from the mem-
brana chorii, and the ends of which (h1) sink into and firmly unite
with the placenta uterina, which faces them, and (2) numerous lateral
branches (/) which arise on all sides at right angles or obliquely,
and which are in turn covered with fine twigs. A small part of
these (h*) also fuse, by means of their tips, with the tissue of the
placenta uterina (LANG HANS), so that a separation of the foetal and
the maternal portions can be accomplished only by forcible detach-
ment. KOLLIKER has therefore appropriately divided the branches
of the chorionic villi into roots of attachment (A1, k2) and free pro-
cesses (/).

To each arborescent chorionic villus there goes a large branch of
an umbilical artery, which, corresponding to the ramifications of the
former, is divided up into branches ; the capillary networks which
arise from this are situated quite superficially immediately under
the epithelium of the villi. From this network the blood is collected
into vessels, leading from the villi, which are again united into a
single chief stem that emerges from the chorionic tuft.

Consequently the vascular system of the placenta fcetalis is entirely
closed. A direct mingling of the foetal and maternal blood cannot
take place in any manner ; on the other hand the prerequisite for
an easy exchange of fluid and gaseous components of the blood
is furnished by the very superficial position of the thin-walled
capillaries.

PLATE II.

Diagrammatic section through the human placenta at the middle of the fifth
month, after LEOPOLD.

The musculature of the uterus is followed by the spongy layer of the decidua
serotina (SJP), in which the separation o£ the placenta takes place at birth
along the line of separation indicated by two heavy marks ; this is followed
by the compact layer ( CS), which is thrown off at birth as the placenta uterina,
and which consists of the (WINKLER'S) basal plate (BP\ closing plate (Schluss-
plattc) (SP), cavernous blood-spaces (?), the arteria advehentes («), and the
marginal sinus. The placenta fcEta.lis has grown into the placenta uterina;
it consists of the membrana chorii (ni) and the villi (z) arising from it ; on
the latter are to be distinguished the roots of attachment (h\ li1} and the free
processes (/). [ej>, Foetal epithelium derived from the serosa.] The chorion
is still covered internally by the amnion. [The foetal part of the placenta is
reproduced in blue, the maternal part in black and brown ; pink indicates the
blood-spaces.]

THE F(ETAL MEMBRANES OF MAN. 261

The connective substance of the chorionic villi is gelatinous tissue
with stellate and spindle-shaped cells in the finer branches ; in the
larger stems it takes on a more fibrillar condition.

The views of investigators are still at variance upon the important
point whether the epithelium of the membrane*, chm*ii and the, villi is
of foetal or maternal origin. KOLLIKER, LANGHANS, LEOPOLD, and
others derive it from the cells of the serosa, whereas ERCOLANI and
TURNER, whom BALFOUR has followed in his text-book, state more
or less explicitly that, although originally the cells of the serosa
cover the villi as an epithelium, during the mutual intergrowth of
the placenta foetalis and the placenta uterina they perish, and are
replaced by proliferating cells of the decidua serotina.

The recent investigations of KASTSCHENKO and SEDGWICK MINOT,
as well as the observations of WALDEYER, KUPFFER, GRAF SPEE,
and KEIBEL, afford much enlightenment on this controversial
subject.

KASTSCHENKO, who has most carefully investigated the epithelium
of the chorion frondosum in the different months of pregnancy,
and with whom recently S. MINOT essentially agrees, can readily
distinguish two layers: (1) a cell-layer (LANGHANS), which lies
immediately upon the gelatinous substance of the villi and the
connective-tissue membrana chorii, and in which the limits of some
of the cell-territories may be made out, and (2) a multinuclear
protoplasmic layer, in which separate cells cannot be demonstrated
in any manner. These layers are rather sharply contrasted from
each other.

The double-layered chorionic epithelium is already distinctly
present in eggs four weeks old, as is confirmed by KUPFFER, GRAF
SPEE, and KEIBEL. The deeper layer consists of a single sheet of
well-marked cubical cells; the outer layer discloses at the free surface
a striated border, the significance of which is obscure.

In the following months the chorionic epithelium undergoes note-
worthy alterations. The deeper layer becomes thickened in many
places into special cell-patches, in which the elements are much super-
posed. The outer, protoplasmic layer changes still more ; it is
converted into a hyaline, peculiarly lustrous substance, which is
traversed by numerous fissures and spaces, and has therefore received
from LANGHANS the name " canalised fibrin."

There is one conclusion that in my opinion results from these inves-
tigations : the view of TURNER, according to which the chorionic
epithelium is replaced in the course of pregnancy by uterine

262 EMBRYOLOGY.

epithelium, must be abandoned. The chorionic epithelium, which is
derived from the serosa, is preserved ; it constitutes in any event the
deeper layer, composed of epithelial cells, which lies immediately on the
membrana chorii or the gelatinous tissue of the villi. Perhaps there
Jbelongs to it in addition the so-called protoplasmic layer and the
canalised fibrin. However, the source and significance of these
structures, especially the latter substance, appear to me to be less
satisfactorily explained, and to be in need of still further investiga-
tions, in which the question of its origin from the maternal mucosa is
not to be overlooked. For even if TURNER has erred in regard to
the degeneration of the chorionic epithelium, he is probably in the
right in the second point, that the whole surface of the chorion
frondosum is directly invested by a layer of maternal tissue.

The connective-tissue framework of the chorion frondosum, then,
is provided, as I think must be assumed, with a double investment :
(1) with a foetal epithelium, derived from the serosa, and (2) with
a layer, however thin it may be, of maternal tissue.

I shall endeavor to establish this view in now turning to the
discussion of the placenta uterina, the structure of which likewise
presents great difficulties, and is therefore interpreted in very dif-
ferent ways.

The placenta uterina is developed out of the part of i,he uterine
mucosa designated as decidua serotina (fig. 148 Dse). At birth it
detaches itself, like the corresponding part of the decidua vera, from
the inner surface of the womb at the line of separation shown on
Plate II., by the breaking down of the thin connective-tissue septa of
the underlying spongy layer. It then forms a thin membrane of only
O5 to 1 mm. thickness, the basal plate of WINKLER (Plate II. BP},
and forms a complete investment over the placenta foetalis, which
it covers up at the time of the detachment of the foetal membranes.
At the margin it is directly continuous with the vera and reflexa
(fig. H8).

The surface turned toward the wall of the uterus is divided by
deep furrows into separate divisions. Larger and smaller par-
titions, the septa placentae (figs. 139 and 143), corresponding in
position to the furrows, arise from the opposite surface of the mem-
brane and penetrate in between the chorionic villi (fig. 143 z) ; they
always unite a small number of these into a tuft or a cotyledon. If
we imagine the cotyledons wholly removed, there would be formed
in the placenta uterina a corresponding number of irregular com-
partments. These are in turn subdivided into smaller and more

THE FCETAL MEMBRANES OF MAN. 263

shallow compartments by finer connective-tissue outgrowths from
the membrane and the septa.

The edges of the septa do not reach to the roots of the villi in
the middle of the placenta, but only in a narrow peripheral region,
where they come into immediate contact with the membrana chorii
(Plate II. m)t and are joined together underneath it into a thin,
closely applied membrane, which is pierced by the roots of the villi.
This has been called by WINKLER closing plate (Schlussplatte, SP),
by KOLLIKER decidua placentalis subchorialis. Still more appro-
priate is the term employed by WALDEYER, subchorial terminal ring
(Schlussring), because it is thereby stated that the membrane in
question is present only at the margin of the placenta, leaving the
middle area of the chorion free.

The connective-tissue framework of the placenta uterina possesses
in general the properties of the compact, abundantly cellular layer
of the decidua vera and reflexa, but exhibits one peculiarity in the
presence of a very special form of cells, the so-called giant cells.
These are large masses of protoplasm appearing yellowish grey, and
with from ten to forty nuclei ; they begin to develop in the fifth month,
and are found in the after-birth in great numbers ; they lie partly
in the basal plate, partly in the septa, ordinarily in the immediate
vicinity of large blood-vessels ; but they are also found isolated in
the spongy layer of the decidua serotina and even between the
adjacent muscle-bundles of the uterus.

The greatest difficulties in the investigation of the placenta uterina
are caused by its blood-courses. Numerous spirally twisted arterial
stems (Plate II. a) penetrate through the muscular layer of the womb,
and, passing through the spongy layer, reach the basal plate of the
placenta uterina, where their structure undergoes important changes.
For they here lose their muscular layer, and now appear as large
tubes, lined with endothelium only. From the basal plate they
penetrate in part into the septa placentae. From here they are
not to be followed further as closed vessels ; a transition to capillaries
does not take place anywhere. On the contrary, it can be proved that
through openings in the basal plate and the septa they pour their
blood into a system of cavities between the chorionic villi, i.e., into
the intervillous or intraplacental spaces (c). The latter are bounded
on the one side by the membrana chorii (ra) with its villi (z), on the
the other side by the basal plate (BP] with its septa.

The blood is collected from this system of cavernous spaces into
large veins, which are likewise simply tubes lined with endothelium .

264 EMBRYOLOGY.

These are distributed as a network in the septa, as well as in the basal
and closing plates of WINKLER, and they begin with narrow openings,
which connect with the intervillous spaces. At the margin of the
placenta they are joined together, and thereby produce the marginal
sinus (Plate II. ), or the ring-like sinus of the placenta. This, however,
is not to be regarded as a vessel of uniform calibre, but as a system
of irregular spaces joined together.

In virtue of the conditions described, the chorionic villi are directly
bathed by the maternal blood. At the same time, from what has
already been said, it is to be seen that the motion of the blood is
retarded, owing to the great enlargement of the blood-courses, and
that it is irregular, corresponding to the form of the intervillous
spaces. In general the motion of the blood is from the middle and
from the convex side of the placenta, where the arteries chiefly enter,
toward its concave surface and its margin.

The question as to the significance and the origin of the intervillous
Hood-spaces constitutes the key to the comprehension of the structure
of the placenta.

According to one view, which for a long time was the dominant
one in Germany, and is defended by KOLLIKER, LANGHANS, and others,
the intervillous spaces originally have no connection with the maternal
blood-system. Developmentally they are nothing but spaces between
chorion and uterine mucosa, and owe their existence to the fact that
the two structures have not everywhere come in contact, but have
acquired firm connection only by means of the tips of the villi. The
spaces in the earliest stage would be bounded by the epithelium of
the villi and the maternal mucosa. LANGHANS therefore designates
them as placental spaces. According to this view they would acquire
their blood-contents later only, and in this way, as KOLLIKER ex-
presses it : " The proliferating chorionic villi everywhere corrode,
and in part destroy the maternal placental tissue, and thus produce
an opening of their vessels, which must naturally lead to a gradual
penetration of the maternal blood into the intervillous spaces."

This view has been modified by other observers (BBAXTOX HICKS, AHLFELD,
RUGE, and others) to this extent, that the intervillous spaces, even in the
mature placenta, do not normally contain blood nor have connection with
the maternal blood-vessels. The almost universally received views concerning
placental nutrition are thus called in question. The denial of a regulated
blood-circulation has induced the further hypothesis, that a uterine mil*,
as in the Ruminants, is secreted by the cells of the deeidua serotina into the
intervillous spaces, and is taken up by the foetal villi.

THE FCETAL MEMBRANES OF MAN.

265

According to the second diametrically opposite view, which finds its
defenders in VIRCHOW, TURNER, ERCOLANI, LEOPOLD, WALDEYER, and
others, the intervillous spaces are nothing else than the enormously
enlarged capillary blood-vessels of the maternal mucosa. Chorion and
decidua serotina early unite very intimately by means of their sur-
faces, so that no fissures are left between them. The villi grow into
the mucous tissue, the
superficial capillaries of
which enlarge to capa-
cious spaces.

If this view is cor-
rect, the chorionic villi
will necessarily be sur-
rounded on all sides by
thin coverings of ma-
ternal tissue, or, since
a partial degeneration
of the covering would
certainly be possible,
there will of necessity
be at least a stage in. the
development in which
such a covering will be
demonstrable.

ERCOLANI, ROMITI,
and TURNER have in
fact, as has been pre-
viously stated, expressed
themselves to the effect
that probably the epi-
thelial layer resting
upon the connective-
tissue axis of the villi
is not the original chori-
onic epithelium derived from the serosa, but a covering which arises
from the decidua placentalis — a view the untenableness of which has
already been shown.

In the diagram which TURNER has sketched to illustrate his view
of the structure of the human placenta (fig. 149) the real original
villous epithelium is degenerated.

The cell-layer e' is the epithelium of the uterine mucosa, into which

Fig. 149.— Diagrammatic representation of the finer struc-
ture of the human placenta, after TURNER.

F, Placenta foetalis ; M, placenta uterina ; ca, tortuous
artery ; up, vein which conducts the blood away from
the intervillous maternal blood-sinus (d') ; x, a con-
tinuation of the maternal tissue over the villi : this
lies outside the layer e' (the metamorphosed epithelium
of the uterine mucosa), and is probably a connective-
tissue membrane with vascular endothelium ; t, cords
of the placenta uterina, which unite with the tips of
some of the foetal villi (Haftwurzeln) ; ds, decidua
serotina of the placenta.

266 EMBRYOLOGY.

the villous tufts (JF) have grown, and with which the most intimate
contact everywhere prevails. Outside the epithelium TURNER de-
scribes in addition a thin membrane (x), which he interprets as an
exceedingly thin connective-tissue layer, upon which is probably to
be found an endothelial covering which lines the blood- spaces. The
cords indicated by t are connective-tissue strands of the maternal
mucosa, which join the tips of certain foetal villi with the septa
placentae (ds), by which the origin of the so-called attachment-
roots (Haftwurzeln) is explained. The great blood-spaces d' are
simply enormously enlarged, superficially located capillaries of the
mucosa.

The exact determination of the true state of affairs is coupled with
great difficulties.

However, it seems to me that the second of the two hypotheses
cited, according to which the intervillous spaces are the enlarged
maternal capillaries, is the more probable because the more natural,
and the following facts especially appear to me to favor it : —

(1) From a comparative-anatomical point of view it can be main-
tained that in all Mammals where a special adaptation to intra-uterine
nutrition is developed, the epithelial surfaces of the chorion and the
mucous membrane of the uterus lie directly on each other, and with
the increase of surface produced by the formation of folds effect
mutual ingrowth. An intra-placental fissure, such as LANGHANS
and KOLLIKER assume for Man, is found nowhere else among
Mammals. We also see in some instances how the capillaries of
the uterine mucosa become enlarged and acquire attenuated walls
(Rodents, Carnivora, etc.), so that the fcetal villi are almost directly
bathed in maternal blood. The enlargement of the blood-courses in
Man may therefore be regarded as a further elaboration of an already
existing arrangement.

(2) That capillaries become metamorphosed into a cavernous
system is also realised in other parts of the human body (corpora
cavernosa of the sexual organs), whereas the employment of spaces
lying outside the blood-courses as component parts of the vascular
system would be a phenomenon without analogy.

(3) In the placenta uterina the capillaries originally present are
wanting between the arteries and veins, whereas they ought to TDC
demonstrable, if they have not been converted into the intervillous
spaces.

(4) The exposition which LEOPOLD has given of the development
of the placenta in the second month of pregnancy favors the

THE FCETAL MEMBRANES OF MAN. 267

second of the hypotheses cited. " Villi and the tissue of the decidua,"
he says, " become shoved into each other, as one can interlock the
outspread fingers of the two hands. If now the blood-vessels of the
serotina be followed, one will recognise here the greatly enlarged
capillary network of the surface, upon which the egg comes to lie
when it lodges. But its innumerable vessels apparently continue
with the sprouts of the decidua to grow toward the villi, and
become distended and more voluminous ; on the other hand the villi
increase rapidly in size, and thus it is intelligible that the new
branches of the villi, whose stems have, as it were, sucked themselves
fast in the decidua by means of their tips, at once encounter the en-
larged capillaries of the surface, and press forward against these and
break into them."

The weightiest objection that can be brought against this inter-
pretation is the assertion of many investigators that the chorionic
villi are not covered with a mantle of maternal tissue, and that the
inter villous spaces are not lined with vascular endothelium. How-
ever, it is precisely upon this point that more exhaustive and
especially ontological investigations are desirable. For one is not
at liberty to draw conclusions from the conditions of "delivered"
placentae, since degeneration may have taken place. Moreover
TURNER and LEOPOLD claim to have demonstrated endothelia at
certain places of the intervillous spaces. But especially decisive
here appear to me to be, first, the important investigations which
WALDEYER has recently published upon the placental circulation in
Man, and, secondly, KEIBEL'S very noteworthy preliminary commu-
nication upon the embryology of the human placenta.
. WALDEYER has injected the maternal blood-vessels of placentae
which still possessed their normal attachment to the uterus, and has
prepared sections through the hardened organ. He finds that the
intervillous spaces are nothing else than the enormously enlarged
maternal blood-vessels, and that at many places there is still present
outside the villous epithelium a layer of flat cells, which he is inclined
to interpret as vascular endothelium. He appropriately compares
the intrusion of the chorionic villi into the intervillous blood-spaces
with the ingrowth of the arachnoideal villi into the blood-sinus of
the dura mater, carrying before them invaginations of the endothelial
covering of the latter.

KEIBEL has investigated by means of sections a well preserved
and prepared human embryo, which was in about the middle of the
fourth week. He saw the villi (fig. 150 Z), which were provided

268

EMBRYOLOGY.

with numerous secondary sprouts and were clothed in a two-layered
chorionic epithelium, already attached by their tips in the maternal
tissue (attachment villi), and also the, intervillous spaces filled with
maternal blood. But this was distinctly separated from the chorionic
epithelium by a special thin cellular membrane (E). This membrane
consisted of very thin endothelial cells, and was frequently elevated
more or less from the chorionic villi, probably owing to the method
of preparation. KEIBEL justly concludes from the establishment
of the existence of an endothelial membrane that the intervillous
spaces are the enormously dilated maternal capillaries.

Between the chorionic epithelium and the walls of the maternal

chorionic blood-vessels.

cliorionic epithelium,
maternal endothelium. E.

Fig. 150. — Diagram of the structure of the human placenta from an embryo four we3ks oldr
after KEIBEL.

Z, Chorionic villi ; Sp, attachment of the tips of the same in the matercal decidua (Z>) ; C, en-
larged maternal blood-capillaries.

capillaries KEIBEL finds no further remnant of maternal tissue in
the very young ovum. This would indicate an early and complete
disappearance of the uterine epithelium, and would make it probable
that the protoplasmic layer and the canalised fibrin described at
p. 261 are to be derived from the cell-layers of the chorion, a mooted
point concerning which I have been unable to form a definite opinion.
Thus the observations are increasing which favor a special limita-
tion of the intervillous spaces and the existence of a thin layer of
maternal tissue, a vascular endothelium, upon the villi.

6. The Umbilical Cord.

The umbilical cord (funiculus umbilicalis) constitutes the union
between the placenta and the embryonic body (fig. 143). It is a cord

THE F<ETAL MEMBRANES OF MAN. 269

about as thick as the little finger (11-13 mm. or 0*5 inch), and attains
the considerable length of 50 to 60 cm. (20-24 inches). It almost
always exhibits a very pronounced spiral twist, which, regarded from
the embryo, runs usually from left to right.

There are often knot-like thickenings of the umbilical cord, which
may be due to either of two causes. For the most part they are
due to an increased growth here and there in the connective -tissue
matrix of the cord (false knots). More rarely they are formed by
a knotting of the cord, which results from the fact that the embryo,
in the motions which it executes in the amniotic fluid, accidentally
slips through a loop of the cord and then gradually tightens it into
a knot. The thickening then presents, in distinction from the other,
a true knot.

The attachment of the umbilical cord to the placenta ordinarily
takes place in or near its middle (insertio centralis). However,
exceptions to the rule are not rare. Thus one distinguishes in addi-
tion an insertio marginalis and an insertio velamentosa. In the first
case the umbilical cord unites with the margin of the placenta ; in
the second place it does not reach the placenta at all, but attaches
itself at a lesser or greater distance from the margin of the latter,
to the foetal membranes themselves, and sends out from that point
the outspreading large branches of its vessels to the placenta.

Man is distinguished from almost all of the remaining Mammals
by the possession of a long slender umbilical cord. Its condition
in Man results from the great distension of the amniotic sac.
Whereas this at first lies close upon the body of the embryo, it sub-
sequently becomes so distended (compare fig. 144 with fig. 143) that
it fills the whole cavity of the blastodermic vesicle and everywhere
clings closely to the inner surface of the chorion. Owing to this,
the remaining structures — the yolk-sac with its blood-vessels, the
slender canal of the allantois with its connective- tissue envelope, and
the umbilical blood-vessels — which emerge through the dermal navel
of the embryo into the extra- embryonic body-cavity and betake
themselves to the chorion, become more and more hemmed in by
the amnion, and finally are crowded together into a small cord.

At first the umbilical cord is short, since it pursues a straight course
in uniting the navel of the embryo to the foatal membranes ; after-
wards it becomes greatly elongated and folded in the amniotic fluid.

Its structure varies at different times during pregnancy corre-
sponding to the changes which the yolk-sac and the allantois with
their blood-vessels undergo.

270 EMBRYOLOGY.

I shall give a detailed description of its finer structure for the
end of pregnancy only, and shall consider especially the following
parts: (1) the gelatin of WHARTON, (2) the umbilical vessels, (3)
the remnant of the allantois, of the vitelline duct, and of the vasa
omphalomesenterica, (4) the amniotic sheath.

(1) The gelatin of WHARTON forms the common matrix in which
the remaining parts are imbedded. It is a gelatinous or mucous tis-
sue. In this soft gelatinous substance there run strands of connective-
tissue fibrillse and elastic fibres, which are the scantier the younger
the umbilical cord. They are joined together into a network, the
meshes of which are narrower at some places than at others. In
this way there are formed in the gelatin numerous firm peculiarly
differentiated strands. The cells of the gelatinous connective tissue
are partly spindle-shaped, partly stellate elements, the latter with
widely branching processes.

(2) The umbilical blood-vessels consist of two large arteries (art.
umbilicales), which conduct the blood from the embryo to the pla-
centa, and a capacious vena umbilicalis, in which the blood flows back
to the embryo after having traversed the placental circulation. The
two arteries are wound spirally, like the umbilical cord itself, and
are joined to each other by an anastomosis near their entrance
into the placenta. They are very contractile, and exhibit a thick
muscular membrane (tunica muscularis), consisting of circular and
longitudinal fibres.

(3) The canal of the allantois and the vitelline duct, which are
essential components of the umbilical cord during the first months of
pregnancy, subsequently undergo reduction, and are present at the
end of embryonic life only in the form of insignificant remnants,
as has been shown by KOLLIKER, AHLFELD, and HUGE. The canals
lose their lumens; there then exist in the gelatin of WHARTON solid
cords of epithelial cells ; finally, these also disappear in part, so that
only here and there strands and nests of epithelial cells have been
preserved. The vitelline blood-vessels (vasa omphalomesenterica),
which have a role to perform at the beginning of development, soon
become inconsiderable, and diminish more and more in comparison
with the enlarging umbilical blood-vessels. In the mature umbilical
cord they are very rarely to be demonstrated (AHLFELD) ; usually
they have wholly degenerated.

(4) At the beginning of development the amnion forms around
the allantoic canal and the vitelline duct a sheath, which can be
removed. Afterwards the sheath is firmly fused with the gelatin

THE FCETAL MEMBRANES OF MAN. 271

of WHARTON, except at the attachment at the navel, where for a
short distance it may be peeled off as a special thin membrane.

Condition of the Fvetal Membranes during and after Birth.

As a conclusion to the account of the foetal membranes some further
remarks may be in place regarding their history at birth.

At the end of pregnancy, with the beginning of labor pains, the
foetal membranes, which form a fluid-filled sac surrounding the em-
bryo, are ruptured as soon as the contractions of the musculature of
the uterus have reached a certain degree of intensity. The rupture
ordinarily arises at the place where the wall of the sac is pressed out
through the mouth of the uterus (rupture of the amnion). In con-
sequence the amniotic water now flows away.

With the continuation and increase of the pains, the child is next
forced out of the uterus through the rupture in the foetal membranes
— it is born, whereas the placenta and embryonic membranes usually
still remain behind for a short time in the cavity of the uterus.
Immediately after birth the union between child and foetal mem-
branes has to be artificially interrupted, by the tying and cutting oft'
of the umbilical cord at a little distance from the navel.

Finally, the foetal membranes with the placenta are detached from
the inner surface of the uterus, and with renewed pains are discharged
to the outside as the after-birth.

The separation takes place in the spongy layer of the decidua vera,
approximately in the region which is designated as the line of sepa-
ration in the diagram given by LEOPOLD (Plate II.). The after-birth
is composed of both foetal and maternal membranes, which are quite
firmly grown together: (1) the amnion, (2) the chorion, (3) the
decidua reflexa, (4) the decidua vera, (5) the placenta (placenta uterina
and placenta foetalis). Notwithstanding the growing together, a
partial separation of the individual membranes from each other is
still possible.

After birth the inner surface of the uterus is one great surface-
wound, since by the detachment of the placenta and the deciduae
numerous blood-vessels are ruptured. Also during the first days of
childbed fragments of the spongy layer of the decidua vera and
serotina, which remained behind at birth, continue to be detached
from it. Only the deepest layer of the mucosa, that immediately in
contact with the musculature of the uterus, is retained. This still
contains remnants of the cylindrical epithelium of the uterine glands,
as has been already stated. In the course of several weeks it is

272 EMBRYOLOGY.

again converted, by an active process of growth, into a normal mucous
membrane, whereby its superficial epithelium probably arises from
the preserved remnants of the glandular epithelium.

SUMMARY.

1. The human ovum establishes itself ordinarily at the base c
the uterus (fundus uteri), between the mouths of the two Fallopian
tubes, and becomes overgrown by folds of the mucosa and enclosed
in a capsule.

2. The mucous membrane of the uterus is developed into the
maternal envelopes of the ovum, the deciduse, which are distinguished
as decidua serotina, reflexa, and vera.

(a) The decidua serotina is that part of the mucous membrane

upon which the ovum immediately lies after its entrance
into the uterus and on which the placenta is afterwards
developed.

(b) The decidua reflexa is the part that grows around the ovum.

(c) The decidua vera arises from the remaining portions of the

mucous membrane lining the uterus.

3. In the formation of the deciduse or deciduous foetal membranes
the uterine mucosa undergoes profound alterations of structure, and,
accompanied by a rapid growth of the uterine glands and a partial
disappearance of its epithelium, becomes differentiated into an inner
compact and an outer spongy layer.

4. Out of the wall of the blastodermic vesicle, so far as it is not
employed in the formation of the embryo itself, are developed the
fo3tal envelopes of the offspring, which in the main agree with the
foetal envelopes of the remaining Mammals in number and the
method of their development, but which present in detail important
modifications, which are essentially as follows : —

(a) The amnion is closed from before backward, remains united

at the hinder end of the embryo with the serosa (subse-
quently the chorion) by means of a short pointed pro-
longation, and thus contributes to the formation of the
so-called belly-stalk of human embryos.

(b) The allantois does not grow as a free sac into the extra-

embryonic part of the body-cavity, but, in the form
of a narrow canal, shoves itself along the under surface
of the pointed amniotic prolongation to the chorion,
and thus furnishes the chief component of the belly-
stalk.

THE FCETAL MEMBRANES OF MAN. 273

(c) The yolk-sac (umbilical vesicle) is reduced to an exceedingly

small vesicle, and is connected with the embryonic
intestine by means of a long thread-like stalk, the
vitelline duct.

(d) By the enlargement of the amnion, which at length fills the

entire blastodermic vesicle (increase of amniotic fluid),
the canal of the allantois and the vitelline duct, together
with the umbilical and vitelline blood-vessels, become
completely enveloped by the amniotic sheath ; in this
way is formed the umbilical cord (funiculus umbilicalis),
a cord-like connection between the inner surface of the
egg-membrane and the navel of the embryo.
{e) The serosa at a remarkably early period (second week)
develops villi over its whole surface, and by the ingrowth
of the connective tissue of the allantois into the latter it
becomes the villous membrane (chorion).

(/) The villous membrane is differentiated into a chorion laeve
and a chorion frondosum : —

(a) The part which lies in contact with the decidua
leflexa and is firmly united with it by means of
villi which lag behind in growth becomes the chorion
laeve.

(/3) The region which abuts upon the decidua serotina,
and in which the villi grow out into large, much-
branched tufts, is converted into the chorion
frondosum.

5. By the penetration of the villous tufts of the chorion frondosum
into the decidua serotina and their firm union with it, there is formed
an especial organ of nutrition for the embryo, the after- birth, or
placenta.

6. One distinguishes a fatal and a maternal part of the placenta :
(1) the placenta f retails or the chorion frondosum, and (2) the pla-
centa uterina or the original decidua serotina.

(a) The placenta fcetalis consists —

First, of the membrana chorii, in which the chief
branches of the umbilical blood-vessels spread them-
selves out, and to which the umbilical cord is attached,
ordinarily in the middle (insertio centralis), rarely at the
margin (insertio marginalis), still more rarely at a
distance from the margin (insertio velamentosa) ;

Secondly, of bundles of chorionic villi, the " attachment-

18

274 EMBRYOLOGY.

roots " of which are firmly grown together with the-
.uterine mucosa by means of their tips, whereas the
free processes project into the cavernous blood-spaces
of the placenta uteriiia.

(6) The placenta uterina, like the decidua vera, is composed of
a compact layer, which becomes detached at birth (pars
caduca), and a spongy layer, in which tfie separation
takes place, a part remaining behind on the musculature
(pars fixa).

The compact layer (basal plate of WINKLER) sends
partition- walls (septae placentae) between the chorionie
tufts, and thereby divides them into separate bundles,
the cotyledons.

There are interpolated between the arteries and veins —
which run in the basal plate and the septae — enormously
enlarged vascular spaces, in which the villi appear to
hang free.

The vascular spaces are probably extraordinarily
distended maternal capillaries, in which case one may
expect to find the chorionie villi invested by a very thin
layer of maternal tissue (endothelial membrane), as is
maintained by some investigators.

7. At birth the deciduae or caducous membranes become detached
from the uterus along the spongy layer, and together with the foetal
envelopes and the placenta constitute the after-birth.

8. In the first weeks after birth a normal mucosa is developed
out of the remnants of the spongy layer left upon the musculature
and the remnants of the uterine glands, from the epithelium
of which the epithelium of the mucous membrane is probably
regenerated.

LITERATURE.

Ahlfeld, Friedr. Beschreibung eines sehr kleinen menschlichen Eies.
Archiv f. Gynakologie. Bd. XIII. 1878.

Beigel, Herm., und Ludw. Loewe. Beschreibung eines menschlichen
Eichens aus der 2. bis 3. Woche der Schwangerschaft. Archiv f. Gynako-
logie. Bd. XIT. 1877.

Beigel. Der dritt kleinste bisher bekannte menschliche Embryo. Archiv f.
Gynakologie. Bd. XIII. 1878.

Braim, G. Ein Abortivei aus dern 3. Schwangerscbaftsmonat. Centralblatt
f. Gynakologie. Jahrg. XIII. 1889.

Breus, K. Ueber ein menschliches Ei aus der 2. Woche der Graviditat*.
Wiener medicin. Wochenschrift 1877.

LITERATURE. 275

Chiarugi. Anatomie d'un embryon humain de la longueur de mm. 2'6 en

ligne droite. Archives ital. de Biologic. T. VI. 1889.
Coste, M. Histoire gene"rale et particuliere du d^veloppement des corps

organises. Paris 1847-59.

Ecker, A. Icones Physiologicae. Leipzig 1852-59.
Ecker, A. Beitrage zur Kenntniss der ausseren Form jiingster menschlicher

Embryonen. Archiv f. Anat. u. Physiol. Anat. Abtheil. 1880.
Pol, H. Description d'un embryon humain de cinq millimetres et six dixiemes.

Recueil zool. Suisse. Tom. I. p. 357. 1884.
Gottschalk. Ein Uterus gravidus aus der 5. Woche der Lebenden entnom-

men. Archiv f. Gynakologie. Bd. XXIX. p. 488. 1887.
Heinricius. Ueber die Entwicklung und Structur der Placenta beim Hunde.

Archiv f. mikr. Anat. Bd. XXXIII. 1889.
Heinz. Untersuchungen iiber den Bau und die Entwicklung der menschlichen

Placenta. Archiv f. Gynakologie. Bd. XXXIII. p. 413. 1888.
His. Zur Kritik jiingerer menschlicher Embryonen. Archiv f. Anat. u.

Entwicklungsg. Jahrg. 1880.

His. Anatomie menschlicher Embryonen. Leipzig 1880, 1882.
Hofmeier. Zur Anatomie der Placenta. Archiv f . Gynakologie. Bd. XXXV.

p. 521. 1889.
Kastschenko. Das menschliche Chorionepithel und dessen Rolle bei der

Histogenese der Placenta. Archiv f. Anat. u. Physiol. Anat. Abth. 1885.
Keibel. Zur Entwicklungsgeschichte der menschlichen Placenta. Anat.

Anzeiger. Jahrg. IV. 1889.
Kolliker, A. Der W. Krause'sche menschliche Embryo mit einer Allantois.

Ein Schreiben an Herrn Prof. His. Archiv f. Anat. u. Physiol. Anat.

Abth. 1882.
Kollmann. Die menschlichen Eier von 6 mm. Grosse. Archiv f. Anat, u,

Physiol. Anat. Abth. Jahrg. 1879.
Kollmann. Die Korperf orm menschlicher normaler und patholog. Embryonen.

Archiv f. Anat. u. Physiol. Anat. Abth. 1889. Supl.-Bd.
Koster, K. Ueber die feinere Structur der menschlichen Nabelschnur.

Inaugural-Diss. Wiirzbu/rg 1868.

Krause, W. Ueber die Allantois des Menschen. Archiv f . Anat. u. Physiol. 1875,
Krause, W. Ueber zwei friihzeitige menschliche Embryonen. Zeitschr. f.

wiss. Zoologie. Bd. XXXV. 1880.
Krause, W. Ueber die Allantois des Menschen. Zeitschr. f. wiss. Zoologie,

Bd. XXXVI. 1881.
Kundrat, Hans, und G. J. Engelmann. Untersuchungen liber die

Uterusschleimhaut. Medicin. Jahrbiicher. Wien 1873.
Kupffer. Decidua und Ei des Menschen, am Ende des ersten Monats,

Miinchener medic. Wochenschrift. 1888.
Langhans, Th. Zur Kenntniss der menschlichen Placenta. Archiv f.

Gynakologie. Bd. I. p. 317. 1870.

Langhans, Th. Die Lbsung der mutterlichen Eihaute. Archiv f . Gynako-
logie. Bd. VIII. 1875.
Langhans, Th. Untersuchungen liber die menschliche Placenta. Archiv f.

Anat. u. Entwicklungsg. Jahrg. 1877.
Langhans, Th. Ueber die Zellschicht des menschlichen Chorion. Beitrage

zur Anatomie und Embryologie. Festgabe fur Jacob Henle. 1882.
Leopold, G. Studien uber die Uterusschleimhaut wahrend der Menstrua-

276 EMBRYOLOGY.

tion, Schwangerschaft und Wochenbett. Archiv f. Gynakologie. Bd. XI. u.

XII. 1877
Leopold, G. Die Uterusschleimhaut wahrend der Schwangerschaft u. der

Bau der Placenta. Archiv f. Gynakologie. Bd. XI. 1877.
Leopold, G. Ueber den Bau der Placenta. Archiv f. Gynakologie. Bd.

XXXV. 1889.
Loewe, L. In Sachen der Eihaute jiingster menschlicher Eier. Archiv f.

Gynakologie. Bd. XIV. 1879.
Minot, Charles S. Uterus and Embryo. I. Babbit ; II. Man. Jour. Morphol.

Vol. II. 1889.

Osborn. The Foetal Membranes of the Marsupials. Jour. Morphol. Vol. 1. 1887.
Phisalix. Etude d'un embryon humain de 10 millimetres. Archives d.

zoologie exper. et gen. 2me ser. T. VI. 1888.
Reichert. Beschreibung einer f riihzeitigen menschlichen Frucht im blaschen-

formigen Bildungszustande, nebst vergleichenden Untersuchungen iiber

die blaschenfb'rmigen Friichte der Saugethiere und des Menschen.

Abhandl. d. k. Akad. d. Wissensch. Berlin. 1873.
Romiti. Ueber die Structur der menschlichen Placenta. Atti della R. Accad.

dei Filocritici di Siena Vol. III. p. 441. Abstract inSchwalbe's Jahres-

bericht. 1879.
Huge, Carl. Die Eihiillen des in der Geburt befindlichen Uterus. Pp. 113-151

in Karl Schroder. Der schwangere und kreissende Uterus. Bonn 1886
Schultze, B. S. Die genetische Bedeutung der velamentalen Insertion des

Nabelstranges. Jena. Zeitschr. Bd. III. 1867.
Schultze, B. S. Das Nabelblaschen, ein constantes Gebilde in der Nachge-

burt des ausgetragenen Kindes. Leipzig 1861.
Schultze, B. S. Ueber velamentale und placentale Insertion der Nabelschnur.

Archiv f. Gynakologie. Bd. XXX. p. 47. 1887.
Spee, Ferdinand Graf. Beobachtungen an einer menschlichen Keimscheibe

mit offener Medullarrinne und Canalis neurentericus. Archiv f. Anat. u.

Physiol. Anat. Abth. 1889.
Strahl, H. Untersuchungen iiber den Bau der Placenta. Archiv f. Anat. u.

Physiol. Anat. Abth. 1889.
Thomson, Allen. Contributions to the History of the Structure of the

Human Ovum and Embryo before the Third Week after Conception, with

a Description of some early Ova. Edinburgh Med. Surg. Jour. Vol. LII. 1839.
Turner. Observations on the Structure of the Human Placenta. Jour. Anat.

and Physiol. Vol. VII. 1873.
Turner. Some General Observations on the Placenta with Especial Reference

to the Theory of Evolution. Jour. Anat. and Physiol. Vol. XI. 1877.
Turner. On the Placentation of the Apes, with a Comparison of the Structure

of their Placenta with that of the Human Female. Philos. Trans. Roy. Soc.

London. Vol. CLXIX. Pt. II, 1878.
Virchow. Gesammelte Abhandlungen zur wissenschaftlichen Medicin.

Frankfivrt a. M. 1856.
Waldeyer. Ueber den Placentarkreislauf des Menschen. Sitzungsb. d. k.

preuss. Akad. d. Wissensch. Berlin. Heft VI. 3. Febr. 1887.
Walker, A. Der Bau der Eihaute bei Graviditas abdominalis. Virchow's

Archiv f. path. Anat. u. Physiol. Bd. CVII. p. 72. 1887.
"Winkler. Zur Kenntniss der menschlichen Placenta. Archiv f. Gynakologie.

Bd. IV. 1872.

PAET SECOND.

INTRODUCTION TO PART II.

IN the first part of the text-book, which treated of the fundamental
processes of the beginning of development, it was shown how there
were formed from the embryonic cells, the descendants of the
cleavage-process, several cell-layers : the outer, the middle, and the
inner germ-layers, and the intermediate layer which inserts itself into
all the interstices between the former. In the further progress of
development each of these chief layers, which CARL ERNST v. BAER
has called the fundamental organs of the animal body, undergoes
a series of manifold changes, and is in consequence gradually con-
verted into the separate organs of the adult body.

The study of the development of the organs constitutes the theme of
the second part of this text-book.

A division of the extensive material to be presented here is best
undertaken with reference to the separate germ-layers from which
the various organs are derived, as was first attempted by REMAK
in his pioneer work " Untersuchung iiber die Entwicklung der
Wirbelthiere."

But it must be observed at the very outset that the principle of the
classification of organs according to the germ-layers can be carried out
only with certain limitations. For the completed organs of the adult
are ordinarily compound structures, which are not formed out of a
single embryonic layer, but out of two or even out of three. Thus,
for example, a muscle is developed from the middle germ-layer arid
the intermediate layer. The teeth arise from the latter and the
outer germ-layer ; the alimentary canal with its glands contains
•elements from three layers, from the inner and the middle germ-
layers, as well as from the intermediate layer. When, notwith-
standing, these organs are cited as descendants of one germ-layer,
it is for the reason that the various tissues are of unequal value
in the construction and function of an organ, the important com-
ponents being furnished preeminently by one germ-layer. Thus
the structure and the function of the liver or the pancreas are
primarily determined by the glandular cells which are derived from

280 EMBRYOLOGY.

the inner germ-layer, whereas connective tissue, blood-vessels, nerves,
and serous covering, although they also belong to these glands as
a whole, are of less significance, because the characteristic properties
of liver or pancreas do not depend upon them. In the anatomy and
physiology of a muscle the muscular tissue is the more significant
part, in the sensory organs the sensory epithelium.

Guided by such considerations one has a perfect right to designate
the intestinal glands as organs of the inner germ-layer, the muscles,
the sexual and urinary organs as belonging to the middle germ-layer,
and the nervous system together with the sensory organs as products
of the outer germ-layer.

Thus the science of the embryology of organs is divisible into four
main sections — into the science of the morphological products of

(1) the inner germ-layer, (3) the outer germ-layer,

(2) the middle germ-layer, (4) the intermediate layer.

CHAPTER XIV.

THE ORGANS OF THE INNER GERM-LATER.
THE ALIMENTAKY TUBE WITH ITS APPENDED ORGANS.

AFTER completion of the formation of the germ-layers and the first
processes of differentiation described in the tenth chapter, the body
of the vertebrated animal consists of two simple tubes, one within
the other (Plate I., figs. 7 and 10), — the inner, smaller alimentary
tube, and the body-tube separated from the former by the body-
cavity (Ui1), — each of which is composed of more than one of the
primitive cell-layers of the germ.

The alimentary tube, the further development of which will first
engage our attention, is composed of two epithelial layers, — the
entoderm and the visceral portion of the middle layer, which fur-
nishes the epithelial lining of the body -cavity, — separated from each
other by the intermediate layer, which is at this time little developed.
Of the three layers the entoderm is unquestionably the most im-
portant, since the further processes of differentiation primarily
proceed from it, and since the physiological capabilities of the
alimentary canal are determined by the activity of its cells.

The changes which occur in the further course of development are
best divided into three groups. First, the alimentary tube comes
into communication with the surface of the body by means of a large
number of openings, the visceral clefts, the mouth, and the anus.
Secondly, it grows enormously in length, and is at the same time
differentiated into oesophagus, stomach, small intestine and large
intestine, with their peculiarly modified mesenteries and omenta.
Thirdly, numerous organs, which are for the most part concerned
in the duties of digestion, take their origin from the walls of the
alimentary tube.

282

EMBRYOLOGY.

I. The Formation of the Mouth, the Throat- or Gill-Clefts, and

the Anus.

At the beginning of development the alimentary tube opens out to
the surface of the germ by means of the primitive mouth (primitive
groove), which marks the place at which, during the stage of the
blastula, the inner and middle germ-layers have been invaginated
(Chapters V. and VI., figs. 44, 47, 54, 55, 78 u). But this opening
is only a transitory structure.

Located at the future hind end of the embryonic fundament, it

is at first overgrown by the
medullary ridges, and es-
tablishes a temporary union
between the intestinal and
neural tubes, the canalis
neurentericus (figs. 68 en,
80, 88 ne). Afterwards it
becomes entirely closed by
the growing together of
the edges of the primitive
mouth.

It is affirmed by some that in
certain Vertebrates (Petromy-
zon, several Amphibia) the
primitive mouth persists, and
becomes the anus of the adult
animal.

ck

c/*

Fig. 151.— Median section through the head of an
embryo Rabbit 6 mm. long, after MIHALKOVICS.

rh, Membrane between stomodaeum and fore gut,
pharyngeal membrane (Rachenhaut) ; hp, place
from which the hypophysis is developed ; h, heart ;
kdt lumen of fore gut ; ch, chorda ; v, ventricle
of the cerebrum ; v3, third ventricle, that of the
between-brain [thalamencephalon] ; v*, fourth
ventricle, that of the hind-brain and after-brain
[epencephalou and metencephalon,* or medulla
oblongata] ; ck, central canal of the spinal cord.

There arise, however, on
the permanent alimentary
tube, both at its anterior
and posterior ends, new
openings, part of which are unpaired, part paired ; for the wall of the
alimentary tube at several places fuses with the wall of the body,
then becomes thinner, and finally breaks through to the outside.
The unpaired openings are mouth and anus ; the paired ones are the
throat-, gill-, or visceral clefts. The first to be established are the
mouth and the gill-clefts, in the regions of head and neck. These
are of the greatest importance in the external morphology of the

* [Huxley has employed metencephalon and myelencephalon instead of
epencephalon and metencephalon for the fourth and fifth regions of the brain
respectively.]

THE ORGANS OP THE INNER GERM-LAYER.

283

embryo, because with their appearance the head- and neck-regions
become distinguishable.

A. The Development of the Mouth.

In all vertebrated animals the epidermis forms on the under side
of the rudimentary head, which at first has the appearance of a
rounded knob, a small shallow pit (Plate I., fig. 11, and fig. 151),
which meets the blind end of the
fore gut (kd). In the region of
this pit the middle germ-layer
is from the beginning absent
{KEIBEL, CARIUS). Outer and
inner germ-layers meet to form
a thin membrane (fig. 151 rh\
which separates oral sinus or
oral pit [stomodaeum] and fore
gut, and which has been de-
scribed since the time of REMAK
&,s pharyngeal membrane (Rachen-
haut). By its rupture and the
degeneration of the shreds of it
known as the primitive palatal
velum communication with the
•outside is established (Plate I.,
figs. 4 and 7 m).

Mb

Fig. 152.— Human embryo (Lg of His) 2*15 mm.
long, neck measurement.* Drawing from
a reconstruction, . after His (" Menschliche
Embryonen "). Magnified 40 diameters.

Mb, Oral pit (or sinus) ; Ab, aortic bulbus ;
Vm, middle part of the ventricle of heart ;
PC, vena cava superior or ductus Cuvieri ;
Sr, sinus reuniens ; Vu, vena umbilicalis ;
VI, left part of the ventricle ; Ho, auricle of
heart ; D, diaphragm ; V.om, vena omphalo-
mesenterica ; Lb, solid fundament of the
liver ; Lbg, hepatic duct.

In the case of the Chick the oral
pit is observable on the second day
of incubation, the front end of the
embryonic fundament having a short
time previously elevated itself as a
•cephalic knob above the extra-em-
bryonic part of the germ-layers. The rupture of the pharyngeal membrane
takes place on the fourth day. In the case of an embryo Rabbit of nine days
the pharyngeal membrane is not yet ruptured. His has studied in detail this
«arly stage in Man on his embryo " Lg," the age of which he estimates at twelve
•days.

In all amniotic Vertebrates the entrance to the oral pit (fig. 152
Mb) presents a very uniform condition and appears as a large five-

* [It will be seen by an inspection of figure 158 that the longest straight line
which can be drawn through the embryo connects the neck- and rump-regions.
It is this distance which is designated as the neck, or neck-rump, measure-
ment.]

284 EMBRYOLOGY.

sided opening, which is surrounded by Jive ridges. A knowledge of
these is of great importance in studying the history of the formation
of the face.

Of the five ridges one is unpaired, the frontal or naso-frontal
process, a broad, rounded projection which bounds the oral pit above.
Its origin is connected with the development of the central nervous
system, which reaches up to the anterior end of the embryonic
fundament, where it is developed into the cerebral vesicles (fig. 153
gh, zh, mh). Examined by means of a longitudinal section, the
frontal process at this stage, therefore, encloses a large cavity be-
longing to the neural tube, and has the form of a vesicle, which is
composed of three layers, the epidermis, a layer of mesenchyma, and
the thickened epithelial wall of the neural tube. The primary oral
cavity and the fundament of the brain are closely apposed at the
beginning of development ; they are separated by only a thin sheet
of tissue, within whose territory there is subsequently formed, among
other things, the floor of the cranium.

The four remaining ridges are paired structures which surround
the oral sinus upon its sides and below. These are produced by
growths of the embryonic connective tissue, through which large
blood-vessels take their course. They are distinguished according to
their positions as upper-jaw (maxillary) and lower-jaw (mandibular)
processes. The former are on either side in immediate contact with
the frontal process, from which they are separated by a groove only,
the naso-optic furrow, which will be discussed in a subsequent chapter,
and which runs obliquely upward and outward to that region of the
face in which the eye begins its development. The maxillary process
is separated from the mandibular process by an incision which corre-
sponds to the place of the future angle of the mouth. The two
processes of either side together form the pharyngeal arches, or the
membranous jaw-arches.

Before the rupture of the pharyngeal membrane the oral sinus has become
still deeper, but only in its upper part, whereas toward the mandibular arch it
becomes shallow. This condition is connected with curvatures which in all
amniotic Vertebrates as well as Selachians affect that part of the head which
encloses the brain -vesicles and lies above the alimentary tube. For the front
end of the head is bent down toward the ventral side of the embryo, and
finally makes a right angle with the posterior half of the head (fig. 153).
Consequently the place at which the so-called anterior cephalic curvature has
occurred, and at which the posterior and anterior halves of the head bend into
each other, has become an elevation, tt&parietal [or mid-brain'] elevation (Schei-
telhbcker), SH. The latter encloses the middle brain-vesicle (w/i), the future

THE ORGANS OF THE INNER GERM-LAYER.

285

mid-brain. Furthermore the frontal process, in consequence of the curvature,
covers in the oral sinus more and more from above and in front, and thereby
contributes to its depth.

As His has shown for the human embryo, the pharyngeal membrane before
rupturing extends obliquely backward and upward from the mandibular arch,
and becomes firmly attached at the point of curvature hp, where, as a result of
the bending, the anterior and posterior halves of the head meet each other
at right angles. Even after the rupture of the pharyngeal membrane there
is retained, in front of

its attachment, a small gh zh. v* c/ 8H

pit, which constitutes
RATHKE'S pocket (fig.
153 hp).

It is to be noted that
the oral sinus, in front
of the pharyngeal mem-
brane, and the fore gut,
which lies behind it, do
not correspond respec-
tively to the cavities de-
signated in the anatomy
of the adult as oral
cavity and pharynx. But
the region of RATHKE'S
pocket, which belongs
to the embryonic oral
sinus, is in the adult
referred to the pharynx.

In consequence of the
early and complete dis-
appearance of the pha-
ryngeal membrane, it is
no lonc-er possible to
say at what place in the
adult is to be sought
the transition from the

primitive, epidermis-lined oral sinus to the epithelial layer of the alimentary
tube.

B. The Development of the Visceral Clefts.

While the changes described take place in the vicinity of the oral
sinus, several visceral clefts make their appearance immediately
behind the jaw-arches upon either side of the body. They are
developed in the case of Selachians, Teleosts, Ganoids, and Am-
phibia, as well as Amniota, in a rather uniform manner (figs. 154,
155). From the epithelium of the fore gut there are formed deep
outpocketings (sch1 — scA6), which run from above downward on the
lateral wall of the throat parallel to the jaw-arches. They crowd

Fig. 153.— Median sagittal section through the head of a Chick
incubated 4£ days, after MIHALKOVICS.

SH, Parietal [mid-brain] elevation ; sv, lateral ventricle of the
brain ; v3, third ventricle ; v*, fourth ventricle ; Sw, aque-
ductus SYLVII ; gh, cerebral vesicle ; zh, between-brain
[thalamencephalon] ; mfi, mid-brain ; kh, cerebellum ;
zf, pineal process ; hp, hypophysial (or RATHKE'S) pocket ;
ch, chorda ; ba, basilar artery.

286

EMBRYOLOGY.

aside the middle germ-layers, which extend into this region, and
thus grow outward to the surface, where they unite with the epi-
dermis. The latter now become depressed into furrows along the
regions of contact (fig. 154), so that one can distinguish inner, deeper
throat-pockets, and outer, shallower throat- or gill-furrows. The two

are separated from each other
for a time by a very thin clos-
ing membrane, which consists
of two epithelial layers, the
epidermis and the epithelium
lining the fore gut.

The bands of substance
which lie between the suc-
cessive throat-pockets (figs.
154 and 157) are the mem-
branous branchial, throat-, or
visceral arches. They consist
of an axis, which is derived
from the middle germ-layer
and the mesenchyma, and of
an epithelial covering, which
on the side toward the pharynx
is furnished by the inner germ-
layer, on the outside by the
outer germ-layer. They are
designated according to their
sequence as the second, third,
fourth, etc., visceral arches,

inasmuch as the ridge which surrounds the mouth constitutes the
first visceral arch.

In all water-inhabiting Vertebrates which breathe by means of
gills the thin epithelial closing plates break through between the
visceral arches, and indeed in the same sequence as that in which they
arose. Currents of water therefore can now pass from the outside
through the open clefts into the cavity of the fore gut and be employed
for respiration, since they flow over the surface of the mucous mem-
brane. There is now developed in the mucous membrane, upon both
sides of the visceral clefts, a superficial, close network of blood-
capillaries, the contents of which effect an exchange of gases with
tjie passing water. Moreover the mucous membrane becomes f olded>
for the increase of its respiratory surface, into numerous, close-set.

Fig. 154.— Frontal (reconstruction) section of the
oro-pharyngeal cavity of a human embryo
(Bl of His) 4-5 mm. long, neck measurement,
from His " Menschliche Embryonen." Mag-
nified 30 diameters.

The figure shows four outer and four inner visceral
furrows, with the closing plates at the bottom
of them. In the visceral arches separated by
furrows one sees the cross sections of the
second to the fifth aortic arches. By reason
of the greater development of the anterior
visceral arches the posterior ones are already
somewhat pressed inwards.

THE ORGANS OF THE INNER GERM<-LAYER. 287

parallel branchial leaflets, which are provided with the greatest
abundance of capillary blood-vessels. In this manner the most
anterior section of the alimentary canal, which lies immediately
behind the head, has become converted into an organ of respiration
adapted to life in water.

The important differentiation of the alimentary canal into an anterior re-
spiratory chamber and a following nutritive region is possessed by Vertebrates
and Amphioxus in common with certain Invertebrates (Tunicates and
Balanoglossus).

Likewise in the case of the higher (amniotic) Vertebrates both
inner and outer visceral furrows, together with the visceral arches
separating them, are, as has already been stated, formed ; but here
they are never developed into an actually functioning respiratory
apparatus ; they belong consequently in the category of rudimentary
organs. Upon the mucous membrane there arise no branchial leaflets ;
indeed the formation of open clefts is not always and everywhere
achieved, since the thin epithelial closing membranes between the
separate visceral arches are preserved at the bottom of the externally
visible furrows. Upon this point, however, the opinions of the
investigators who have been engaged in the study of the throat- region
in late years are very dissimilar. Whereas His, BORN, and KOLLIKER
maintain that the closing plate does not as a rule rupture, FOL, DE
MEURON, KASTSCHENKO, LIESSNER, and others find that at least the
first two or three visceral clefts are temporarily open. The opening
takes place to a greater extent in Reptiles than in Birds and
Mammals, where it remains limited to a small territory. In the most
posterior visceral pockets there can be no breaking through, because
they are not as deep, and the closing plate is therefore thicker and
contains also a layer of connective tissue. The conditions in Reptiles
and Mammals, as well as the differences in the number of visceral
arches, to be mentioned directly, express separate stages in the
process of regressive metamorphosis, to which the whole visceral
apparatus in the vertebrate series has been subjected.

The number of visceral clefts which actually appear in the separate
classes of Vertebrates is variable. The greatest number is en-
countered among the Selachians, where there may be as many as
six (fig. 155), in a few species indeed seven or eight. In Teleosts,
Amphibia, and Reptiles the number sinks to five. In Birds,
Mammals, and Man (figs. 154 and 157) only four arise. We can
therefore say in general that from the lower to the higher Vertebrates,
a reduction has taken place in the number of visceral clefts which

288

EMBRYOLOGY.

sch1

make their appearance. In view of these phenomena, and guided by
other comparative-anatomical considerations, many investigators
have advanced the hypothesis that in the case of the ancestors of
Vertebrates the fore gut has been pierced by a greater number
of clefts than is now to be observed even in the Selachians, and
further that degraded or metamorphosed remnants of them are still
to be found in the head- and neck-regions.

VAN BEMMELEN has observed in embryos of various Sharks and Skates out-
pocketings of the lateral wall of the throat behind the last visceral arch, and
has interpreted them as radimentary visceral clefts, which no longer succeed
in breaking through (fig. 155 nsd). Subsequently there are developed out of

them, by growth of the epithelium, glan-
dular organs, the supra-pericardial bodies
(BEMMELEN), which are similar in their
structure to the thyroid gland. Also in
the head-region, which lies in front of
the first visceral arch, a reduction and a
metamorphosis of clefts has, according
to the opinion of various observers, taken
place. DOHRN especially has propounded
several hypotheses of this kind, for which,
however, I do not find valid grounds : (1)
that the mouth has arisen by the fusion
of a pair of visceral clefts, (2) that the
olfactory organs are to be referred to the
metamorphosis of another pair of clefts,
— a view which is also shared by M. MAR-
SHALL and several others,— (3) that a dis-
appearance of gill-clefts in the region of
the sockets of the eye is to be assumed,
and that the eye-muscles are to be inter-
preted as remnants of gill-muscles.

nsd

fig, 155. — Diagram of the development of
the thymus, the thyroid gland, and
the accessory thyroid glands, and
their relations to the visceral pockets
in an embryo Shark, after DE MEUROIJ.

-•sch1, schG, First and sixth visceral pockets ;
th, fundament of the thymus ; sd,
thyroid gland ; nsd, accessory thyroid
gland.

In the Chick the visceral furrows
become visible in the course of the

third day of incubation, only three pairs at first, but, at the end of
the sanv» day, a fourth pair is added.

In human embryos the visceral furrows are to be seen most dis-
tinctly (figs. 157, 154) when the embryo has attained a length of
three or four millimetres (His). Outer and inner furrows are in
this case deeply excavated and separated from each other by only a
thin epithelial closing plate; they diminish in length from before
backward. Of the visceral arches which separate them, the first is
the largest, the last the smallest ; seen in frontal section they form
two rows converging below, so that the oro-pharyngeal cavity tapers
funnel-like into the intestinal tube.

THE ORGANS OF THE INNER GERM-LAYER.

289

From the fourth week of development onward the visceral arches
begin to be displaced in relation to one another, owing to a more rapid
growth of the first two than of the following ones (fig. 156). " They
glide over one another," as His remarks, " like the tubes of a telescope,
in such a way that, viewed from the outside, first the fourth arch is
surrounded and covered in by the third, and this in turn by the
second, whereas on the inner surface, that which is turned toward the
pharynx, the fourth arch
lies over the third, the
third over the second." As
a result the length of the
oro-pharyngeal cavity is
relatively less in the older
than in the younger em-
bryos. In consequence of
this unequal growth, which
moreover takes place in an
entirely similar way in the
embryos of Birds and Mam-
mals, there is formed a deep
depression of the surface at
the posterior margin of the
cephalo-cervical region, the
neck-sinus, sinus cervicalis
(EABL) or sinus prcecervi-
calis (His) (figs. 156 and
158 hb). In the depths of
this depression and on its
front wall lie the third
and fourth visceral arches,
which are now no longer
visible from without. The
entrance to the sinus is bounded in front by the second visceral, or
the hyoid, arch (zb). The latter gradually develops a small process
backward, which covers over the cervical sinus and has been justly
compared by RATHKE with the operculum of Fishes and Amphibia.
The opercular process at last fuses with the lateral wall of the body.
Thereby the sinus cervicalis, which corresponds to the cavity beneath
the operculum which in Fishes and Amphibia covers in the real gill-
arches, is closed up.

One easily gets an accurate conception of these important processes

19

Fig. 156.— Frontal reconstruction of the oro-pharyngeal
cavity of a human embryo (K<i of His) 11-5 mm. long,
neck measurement. From His, " Menschliche Em-
bryonen." Magnified 12 diameters.

The upper jaw is seen in perspective, the lower jaw in
section. The last visceral arches are no longer
visible externally, since they have moved into the
depths of the cervical sinus.

290

EMBRYOLOGY.

of growth by comparing fig. 154 with fig. 156 and fig. 157 with
fig. 158.

The development of the visceral clefts and the cervical sinus has also a
practical interest. Sometimes there occur in the neck-region in Man fistulse,
which penetrate variable distances from without inward, and may even open
into the pharyngeal cavity. They result from embryonic conditions, the
cervical sinus having remained partly open. From this sinus a passage may

zb uk

Fig. 157. — Very young human embryo of the fourth week 4 mm. long, neck-rump measurement;
taken from the uterus of a suicide 8 hours after her death, after RABL.

au, Eye ; ng, nasal pit; uk, lower jaw ; zb, hyoid arch; s3, s", third and fourth visceral arches j.
h, protrusion of the wall of the trunk produced by the growth of the heart ; us, boundary
between two primitive segments ; oe, ue, anterior and posterior limbs.

lead, even in the adult, into the pharyngeal cavity, if abnormally the second
visceral cleft has not closed.

C. The Development of the Anus and the Post-anal Gut.

The question concerning the fate of the primitive mouth [blastopore]
and the development of the anus is not yet settled. Many disclosures
are still to be expected from a comparative study of these structures
in the different classes of Vertebrates. According to the common
representation, which appears to me to correspond on the whole
with the real state of affairs, the primitive mouth is a transitory
structure without permanent existence. In all Vertebrates it is-
surrounded, as in Amphioxus, by the growth of the medullary folds,

THE ORGANS OF THE INNER GERM-LAYER.

291

and when these are closed, it no longer leads directly to the outside, but
into the posterior end of the neural tube. It has thereby become
the familiar canalis neurentericus (fig. 159 ne). Neural tube and
intestinal canal together form a U-shaped tube, at the bend of
which the rudiment of the primitive mouth, or primitive groove, is
to be sought.

The anus is a new structure. It arises on the ventral side of the

II U

ok

Fig. 158.- Human embryo of the middle of the fifth week 9 mm. long, neck-rump measurement,

after RABL.
«, Mid-brain [parietal] elevation ; au, eye ; ok, upper jaw ; uk, lower jaw ; zb, hyoidarch ; hb, sinus

cervicalis ; ng, nasal pit ; oe, anterior, ue, posterior limb ; mp, muscle-plates (trunk-segments).

body (fig. 159 an) at some distance in front of the place where the
neural tube bends around into the intestine. Over a small area
the entoderm and the epidermis here grow toward each other,
and, by crowding aside the middle germ-layer, come into contact and
form a thin septum, the anal membrane. Externally this place is
characterised in many animals by a depression of the epidermis, the
anal pit (fig. 159 an). The opening of the intestine to the outside
takes place in most cases at a rather advanced stage of development
by the rupture of the thin anal membrane, which consists of only
two epithelial layers. The process is therefore similar to that by
which the mouth is formed. In one important point, however, there
exists a difference between the opening at the anterior and that at

292

EMBRYOLOGY.

7JC

the posterior end of the body. Whereas the oral sinus comes in
contact with the anterior end of the fore gut, the formation of the
anus does not take place at the posterior end of the embryonic intes-
tine, which is occupied by the primitive mouth [blastopore], but at
some distance in front of it. (Compare also fig. 126, that of the
Chick, in which the region where the anal pit is to be formed is
designated by the letters an.) Consequently in the embryos of
Vertebrates, when the anus has broken through, the embryonic in-
testinal tube is still continued for some distance back of the anus to
the primitive mouth. This portion is designated as the post- anal or
caudal gut (fig. 126 p.a.g.). The latter designation is appropriate,
because the part of the body which lies behind the inus, in which is

enclosed the part
of the intestine
under considera-
tion, becomes the
tail-end of the
embryo.

The post-anal
gut appears to be
established as a
shorter or longer
tract in all Ver-
tebrates ; it has
already been ob-
served in the most

widely different animals by several investigators : first by KOWALEVSKY
in Amphioxus, the Acipenseridse, Selachians, and Teleosts ; then

by GOETTE, BOBRETZKY, BALFOUR, HlS, KoLLIKER, GASSER, BRAUN,

BONNET, and others in the Amphibia, Selachians, Birds (fig. 126
p.a.g.), and Mammals. In the Selachians (Scyllium) the post-anal
section at the time of its greatest development attains about one-
third the length of the whole alimentary canal. It exhibits at its
end a small vesicular enlargement, which communicates with the
neural tube by means of a narrow opening. In an advanced embryo
of Bombinator it is also to be seen well developed, as shown in the
sagittal section fig. 159. It begins at the place marked by an,
at which the epidermis has sunk down to form the anal pit (an) and
at which it has united with the intestine, immediately behind the
mass of yolk-cells collected in the ventral wall of the latter. From
this point it runs backward as a narrow but open tube, and bends

Fig. 159. — Sagittal section through an advanced embryo of

Bombinator, after GOETTE.
m, Mouth ; an, anus ; I, liver ; ne, nexarenteric canal ; me, medullary

tube ; ch, chorda ; pn, pineal gland.

THE ORGANS OP THE INNER GERM-LAYER.

293

around dorsally into the neural tube as the neurenteric canal. Tha
primitive mouth, now closed, formerly lay at the place of bending.

The post-anal gut, sooner or later, undergoes regressive metamor-
phosis in all Vertebrates ; it loses its cavity, becomes a solid epi-
thelial cord, afterwards detaches itself from the anal part of the
intestine and from the neural tube, and then disappears altogether.
Thereby the neurenteric canal, the last remnant of the primitive
mouth, has ceased to exist.

A few still more specific statements, in accordance with the repre-
sentations of STRAHL, KOLLIKER, BONNET, KEIBEL, and GIACOMINI,
concerning the formation of the anus in Mammals, may be mentioned

afm am *>r

Fig. lo&x^Sagittal section through the posterior end of an embryo Sheep 16 daya old and with
5 pairsoT primitive segments, after BONNET.

al, Allantois ; afm, anal membrane ; am, amnion ; ah, amniotic cavity ; dk, outer germ-layer, and
ink1, middle germ- layer, which share in the formation of the amnion ; np, neural plate as
it merges into the primitive streak ; pr, primitive groove in the region of the neurenteric
canal ; ik, inner germ-layer ; mkz, splanchnic portion of the middle germ-layer ; d, alimentary
tube.

in this connection. The first fundament of the anus is demonstrable
even in embryos with few primitive segments. At the posterior end
of the primitive streak — at the anterior end of which the neurenteric
canal is situated — the anal membrane is formed by the disappearance
of the middle germ-layer over a small area and the close contact of
entoderm and epidermis. This, however, takes place so that the
two latter layers always remain separated from each other by a
sharp contour (fig. 160 afm). One might be inclined to regard
this position, at the hindermost end of the primitive streak (pr),
as deviating from the representation just given, according to which
the anus arises on the ventral side of the body somewhat in front of
the neurenteric canal. That is not the case, however, as the further
course of development teaches ; for in meroblastic eggs, in consequence

294

EMBRYOLOGY.

of the previously described process of folding, — by means of which
the body is formed from the flattened-out germ-layers, — the region
which originally lies behind the primitive groove comes to lie ventral
to and in front of the tail-end. At a somewhat later stage than that
shown in fig. 160, the primitive streak in front of the anal membrane
grows outward as a small ridge and subsequently enlarges into the
tail of the Mammal. The neurenteric canal, located in the ridge, is
overgrown by the medullary folds, and upon the complete closure
of the latter is incorporated in the neural tube, as in the case of the
remaining Vertebrates. In the case of Mammals also there is formed

a small caudal gut, which sub-
sequently degenerates. The more
the caudal bud protrudes outward
(fig. 161 sch), the more it projects
over and beyond the anal mem
brane (afm), which constantly
moves farther toward the ventral
side of the body and is now found
between the base of the tail (sch}
and the fundament of the allan-
tois (al). The rupture of the anal
membrane takes place relatively
late ; in the case of Ruminants,
for example, in embryos that are
more than twenty-four days old.
Apparently the anus in Birds
arises in a manner similar to
that in Mammals. According to

the statements of GASSER and KOLLIKER its opening, produced by
the rupture of the anal membrane, occurs on the fifteenth day.

al

Fig. 161.— Sagittal section through the tail-
end of an embryo Sheep 18 days old and
with 23 pairs of primitive segments, after
BONNET.

sch, Tail-bud or terminal ridge ; am, amnion ;
mk1, its mesodermal (somatic) layer ; afm,
anal membrane lying ventral to and in
front of the tail-bud ; al, allantois.

It is asserted for many Vertebrates (Petromyzon, Triton, Salamandra, Kana
temporaria, Alytes) that the primitive mouth is converted directly into the anus
(GASSER, JOHNSON, SEDGWICK, SPENCER, KUPFFER, GOETTE). But since the
development of the posterior part of the body proceeds from the margins of
the primitive mouth (formation of the chorda and of the middle germ-layer),
it would be difficult to understand how, in these cases, the tail-end of the body
and a tail-gut could still be formed. Other investigators (SCHANZ and BONNET)
find that the primitive mouth is divided into two openings — an anterior, which
is incorporated in the hind end of the neural canal (canalis neurentericus,
chorda-blastopore), and a posterior, which becomes the anus (anal blastopore,
anal canal). The statements, which are still contradictory, must be cleared
up by means of comparative investigations.

THE ORGANS OF THE INNER GERM-LAYER. 295

II. Differentiation of the Alimentary Tube into Separate Regions
and Formation of the Mesenteries.

At first the alimentary tube is broadly in contact (fig. 116) with
the dorsal wall of the trunk ; it is united to the chorda (cA), the
neural tube, and the primitive segments by means of a broad tract of
embryonic connective tissue, in which the fundaments of two large
blood-vessels, the primitive aortse (ao), are enclosed. The right and
left portions of the body-cavity are therefore still separated from
•each other on the dorsal side by a considerable distance. The older
the embryo is, the less this distance becomes, until there results a
mesentery, a structure which is established along the whole length of
the intestinal tube, with "exception of the anterior portion, in the
following manner (compare, Plate I., figs. 8 and 9 with fig. 10). The
-alimentary tube recedes from the chorda ; at the same time the broad
tract of connective tissue previously mentioned becomes narrower
from right to left, but elongated dorso-ventrally (fig. 10, Plate I.) ;
the two aortre embraced in it move nearer and nearer together and
finally fuse into a single trunk, which lies in the median plane between
chorda and intestine. After the further advance of this process the
alimentary tube and chorda remain united by means of only a thin
band, which stretches from the front to the hind end of the embryo.
This proceeds from the connective tissue enveloping the chorda,
encloses along its line of origin the aorta, and is composed of three
layers : a connective-tissue lamella, in which blood-vessels run to
the intestine, and two epithelial coverings, which are derived from
the middle germ-layer and are now composed of greatly flattened
-cells.

The differentiation of the alimentary tube into separate non-equivalent
regions lying one behind the other begins with the development of the
stomach. This first becomes distinguishable, at some distance be-
hind the respiratory tract, as a small spindle-shaped enlargement, the
long axis of which corresponds with that of the body (figs. 162 and
163 Mg). Such a condition is attained by the human embryo of the
fourth week. Five successive regions may now be distinguished in
the whole embryonic alimentary tube : the oral cavity, the throat-
cavity with its visceral clefts, which is narrowed into the shape of a
funnel where it merges into [the third region,] the gullet. This is
followed by the spindle-shaped enlargement, the stomach, and the
latter by the remaining portion of the alimentary tube, which still is
more or less broadly connected (Ds) with the yolk-sac. Excepting

296

EMBRYOLOGY.

the first three regions, the whole alimentary tube possesses a
mesentery (mesenterium), the part which is attached to the stomach
being designated by the special name mesogastrium.

In many Fishes and Amphibia this condition is permanent. Even
in the adult the alimentary tube takes only a slightly sinuous course

Fig. 162.

Fig. 163.

Fig. 162.— Alimentary tube of a human embryo (R of His) 5 mm. long, neck measurement. Prom

His, " Menschliche Embryonen." Magnified 20 diameters.
RT, RATHKE'S pocket ; Uk, lower jaw ; Sd, thyroid gland ; Ch, Chorda dorsalis ; Kk, entrance

to larynx ; Lg, lung ; Mg, stomach ; P, pancreas ; Lbg, hepatic duct ; Ds, vitelline duct

(stalk of the intestine) ; All, allantoic duct ; W, Wolffian duct, with budding kidney-duct

(ureter) ; B, bursa pelvis.

Fig. 163. — Alimentary tube of a human embryo (/>'/ of His) 4*25 mm. long, neck measurement.

From His, " Menschliche Embryonen." Magnified 30 diameters.
The abbreviations mean the same as in fig. 162.

through the body-cavity. The stomach appears as a spindle-shaped
enlargement of it.

An alteration is brought about in all higher Vertebrates by
a more or less considerable increase in the length of the tube,
which eventually far exceeds that of the trunk. Consequently
the alimentary tube, in order to find room for itself in the
body-cavity, is compelled to take a tortuous course. In this way

THE ORGANS OF THE INNER GERM-LAYER.

297

certain parts remain near the vertebral column, whereas others,
as a result of the folding, are more distant. The former are
attached by means of a narrow mesentery and are consequently
less movable, the latter by their change in position have drawn
out their suspensorial band into a thin lamella, which sometimes
attains a remarkable breadth and allows a correspondingly increased
freedom of motion.

The processes of development,
which are in part very complicated,
are satisfactorily explained by the ex-
cellent works of MECKEL, JOHANNES
MULLER, TOLDT, and His, even in
the case of human embryos, so that
these may serve as a foundation for
the description.

In human embryos of the fifth
and sixth weeks the posterior sur-
face of the stomach, that which is
turned toward the vertebral column
(fig. 164 gc), is greatly distended;
the anterior wall (kc) on the con-

Fig. 164.— Diagrammatic representation
of the alimentary canal of a six- weeks
embryo of Han, after TOLDT.

sp, (Esophagus ; kc, lesser curvature ;
gc, greater curvature of the stomach ;
du, duodenum ; d1, part of the loop
that will become the small intestine ;
da, part of the loop that will become
the large intestine and begins with
the coecum ; d3, place of connection
with the vitelline duct ; mg, meso-
gastrium ; ms, mesenterium ; m,
spleen ; p, pancreas ; r, rectum ;
ao, aorta ; cl, coeliaca ; mei, mesen-
terica inferior ; ac, aorta caudalis.

trary, which upon opening the
body-cavity is found to be covered
by the already voluminous liver, is
somewhat depressed. Consequently
a line running along the posterior
surface from the entrance of the
stomach (cardia) to its outlet
(pylorus) is much longer than the
corresponding line along the an-
terior surface. The latter becomes
the future lesser curvature (kc) ;

the former, along which the mesogastrium is attached, is the greater
curvature (gc).

The portion of the tube which follows the stomach has become
folded, in consequence of its great increase in length. From the
pylorus the intestinal tube (du) at first runs backward [dorsad] for
a short distance until it is close to the vertebral column, makes a
sharp bend here, and then describes a large loop, the convexity of
which is directed forward [ventrad] and downward [caudad] toward
the navel. The loop consists of two nearly parallel arms (dl and d2)

298 EMBRYOLOGY.

running near each other, between which is stretched the mesentery
(ms), which is likewise drawn out with the loop. One arm (dl) lies
in front and is directed backward, the other (d2) lies behind it and
runs upward, to be again bent near the vertebral column; thence,
supported by a narrow mesentery, it pursues a straight course (r)
backward to the anus. The transition from the first to the second
arm, or the apex of the loop, is imbedded in an excavation in the
fo3tal end of the umbilical cord, and it is there in communication
with the umbilical vesicle by means of the vitelline duct (d3), now
in process of degeneration. At some distance from the origin of
the vitelline duct there is to be seen in the second arm of the loop
a small enlargement and evagination (c£2). This is afterwards de-
veloped into the coecum, and it therefore indicates the important
boundary between the small and large intestine.

In consequence of these first foldings four regions of the intestine
•can be distinguished even now; these are more sharply separated
later. The short portion, running from the stomach to the back-
bone and provided with a small mesentery, becomes the duodenum
{du) ; the anterior [ventral], descending arm (dl), together with the
bend in the loop, furnishes the small intestine ; the posterior [dorsal],
ascending arm is developed into the colon (cZ2), and the terminal
part, embracing the last bend, into the sigmoid flexure and the
rectum (r).

In embryos of the third and following months there occur, in con-
nection with a further increase in length, important changes in the
position of the stomach and the intestinal loops.

The stomach undergoes a double twisting, about two different axes,
and thereby early acquires a form and position (figs. 165 A and B)
which correspond approximately to the permanent condition. First
its longitudinal axis, which unites cardia and pylorus and is in the
beginning parallel with the vertebral column, takes an oblique and
finallv an almost transverse position, in consequence of a rotation
around the dorso-ventral axis. Thereby the cardia moves to the left
half of the body and downwards, but the pylorus more to the light
side and somewhat higher. Secondly, at the same time the stomach
experiences a torsion around its longitudinal axis, by which the
originally left side becomes the front [ventral] and the right the back
[dorsal]. Consequently the greater curvature comes to lie below
[posterior], the lesser above [anterior]. The terminal part of the
oesophagus is also affected by the torsion ; it undergoes a spiral
twisting, by which its left side becomes the front.

THE ORGANS OF THE INNER GERM-LAYER.

299

The embryonic processes of growth in the case of the alimentary tube shed
light on the asymmetrical position of the two nervi vagi, which pass through
the diaphragm, the left on the front side of the CBsophagus to be distributed
to the front side of the stomach, the right on the back side of the oesophagus
to the corresponding surface of the stomach. If we imagine the process of
torsion in case of the ossophagus and stomach to be reversed, the symmetry in
the course and distribution of the vagi will be completely restored.

The torsion of the stomach naturally exercises a great influence on
the mesogastrium, and, as JOH. MULLER was the first to show clearly,

gn

Fig. 165. — Diagram of the development of the human alimentary canal and its mesentery.

A, earlier, £, later stage.

gn, Greater omentum, which is developed from the mesogastrium (fig. 164 mg). The arrow

indicates the entrance to the omentum (bursa omentalis). go, Greater curvature of the

stomach ; gg, ductus choledochus ; du, duodenum ; mes, mesenterium ; me, mesocolon ;

dd, small intestine ; di, large intestine (colon) ; md, rectum ; dg, vitelline duct ; bid, ccepum ;

wf, appendix vermiformis ; k, place where the loops of the intestine cross each other. The

colon with its mesocolon crosses the duodenum.

initiates the development of the greater omentum (omentum majus).
As long as the stomach has a vertical position, its mesentery is a
vertical lamella, which stretches from the vertebral column (fig. 164)
directly to the greater curvature, that is still directed backward
[dorsad]. But in consequence of the torsion it becomes greatly
stretched and enlarged, because its attachment to the stomach must
follow all the displacements of that organ. From its origin at the
vertebral column, it therefore now betakes itself to the left and
downward to become attached to the greater curvature of the
stomach ; it assumes a shape and position of which the reader will
•easily form a correct idea if he mentally combines the diagram of

300

EMBRYOLOGY.

fig. 165 with the cross section shown in fig. 166. In this way there-
is formed a cavity (bursa omentalis, fig. 166 **), separated from the
rest of the body-cavity, which has its opening turned toward the-
right, whose front wall is formed by the stomach and whose back and
lower wall is formed by the mesogastrium (gn1, gn2). In the diagram-
matic figures 165 A and B the entrance to the bursa is indicated by
the direction of the arrows.

The bursa omentalis (fig. 166 **) moreover acquires a still greater extension
from the fact that the liver (I) has by this time grown into a large gland, and is
united to the lesser curvature of the stomach by means of the lesser omentum

(kri), the development of which
we shall treat of later. There-
fore the bursa does not open,
as in the diagram (fig. 165), in
which the liver with its liga-
ments is omitted, at once into-
the common body-cavity at the
lesser curvature of the stomach,
but first into an ante-chamber
(the atrium burses omentalis), or
the lesser omental pocket, which
lies behind the lesser omentunx

Ckn) and the liver (I).
Ten gn1 p gc gn* I

T/ie intestinal loop with,
its mesentery passes through
a no less fundamental twist-
ing around its place of at-
tachment in the lumbar
region than the stomach
does. The descending
and the ascending arms
at first lie side by side.

Then the latter, which becomes the colon (fig. 165), lays itself obliquely
over [ventral to] the former, and crosses the beginning of the small
intestine (k) transversely. Both parts, but especially the small in-
testine, continue from the end of the second month to increase rapidly
in length and to take on a folded condition. Meanwhile the initial
part of the colon, or the coecum (fig. 165 A bid), which exhibits even,
in the third month a curved, sickle -shaped, vermiform appendage,
comes to lie wholly on the right side of the body up under the
liver; from here it runs in a transverse direction across [ventral
to] the duodenum under [caudad of] the stomach to the region of
the spleen, then bends sharply about (flexura coli lienalis) and

Fig. 166. — Diagrammatic cross section through the
trunk of a human embryo in the region of the
stomach and mesogastrium, to show the formation
of the omentum, at the beginning of the third
month, after TOLDT.

nn, Suprarenal bodies ; ao, aorta ; I, liver ; m, spleen ;
p, pancreas ; gn1, origin of the greater omentum
(mesogastrium) at the vertebral column ; gin?, the
part of the mesogastrium which is attached to the
greater curvature (gc) of the stomach ; kn, lesser
omentum ; gc, greater curvature of the stomach.
* Atrium and cavity of the greater omentum.

THE ORGANS OF THE INNER GERM-LAYER. 301

descends to the left pelvic region, where it is continued into the
sigmoid flexure and rectum. Therefore there are distinguishable in
the colon, even in the third month, the ccecum, the transverse and
the descending colon. An ascending colon is still wanting. It is
formed in the succeeding months (fig. 165 B) by the gradual sinking
down of the coecum, which was at first under the liver, until in the
seventh month it is below the right kidney, and from the eighth
month onward descends past the crest of the ilium.

Meanwhile the ccecum has increased in length and toward the
end of pregnancy is a rather large appendage at the place of tran-
sition from the small to the large intestine. It early exhibits a
want of uniformity in development (fig. 165 B bid). The terminal
part, which often embraces more than half its length, does not keep
pace in its growth with the more rapidly enlarging proximal portion ;
the former is designated as the appendix vermiformis, the latter as the
coecum. At the time of birth the vermiform appendage is still not
so sharply differentiated from the coecum as it is a few years later,
•when it has been converted into an appendage of the size of a goose -
quill and 6 to 8 cm. long.

Within the region embraced by the bends of the large intestine,
the small intestine, which is derived from the descending arm of
the loop, is disposed in more and more numerous folds owing to
its extensive growth in length (fig. 165 B).

At first all regions of the intestine from the stomach onward are
so united to the lumbar region of the vertebral column by means of
a common mesentery (mesenterium commune) that they can move
freely (fig. 165 A and £). The mesentery is naturally influenced by
the increase in the length of the intestine, inasmuch as its line of
insertion on the intestine exceeds in length many times the line of
origin at the vertebral column (radix mesenterii), and is thereby laid
into folds like a frill. Such an arrangement of the mesentery is
found to be the permanent condition in many Mammals, as in the
Dog, the Cat, etc.

But in the case of Man, from the fourth month onward, the
arrangement of the mesentery is much more complicated. There
occur changes which may be briefly characterised as processes of
fusion and concrescence of certain portions of the mesenterial lamella
with contiguous parts of the peritoneum, either of the posterior wall
of the body-cavity, or of neighboring organs. They affect the
mesentery of the duodenum and colon, which is always present in
the first half of embryonic development.

302

EMBRYOLOGY.

The duodenum, describing the well-known horseshoe-shaped curve,,
applies its mesentery, in which the beginning of the pancreas is en-
closed, broadly to the posterior wall of the body, and fuses throughout
its whole extent with the peritoneum of the latter; from being
a movable it has become an immovable portion of the intestine
(fig. 167 du).

The large intestine (figs. 165 and 167-4 and B ct) still possesses in
the third month a very broad suspensorium arising from the vertebral
column, which is nothing else than a part of the common mesentery

Fig. 167 A B.— Two diagrams to illustrate the development of the bursa omentalis.

A, earlier, J5, later stage.

zf, Diaphragm ; I, liver ; p, pancreas ; mg, stomach ; gc, its greater curvature ; du, duodenum ;
dd, small intestine; ct,- colon transversum ; *, bursa omentalis; kn, lesser omentum ;
gn\ posterior [dorsal] lamella of the greater omentum, arising from the vertebral column ;
gri>, anterior [ventral] lamella of the same, attached to the greater curvature of the stomach
(gc) ; gn3, the part of the omentum which has grown over the small intestine ; gn*, the
part of the omentum which encloses the pancreas ; mes, mesentery of the small intestine *
msc, mesocolon of the transverse colon.

of the intestine, but which has received the special designation of
mesocolon (msc). In consequence of the previously described twisting
of the primitive loop of the intestine, not only the colon trans-
versum, but also the considerable mesocolon belonging to it, has been
drawn transversely across the end of the duodenum ; for a certain
distance it fuses with the latter and with the posterior wall of the
body, thereby acquires a new secondary line of attachment (fig. 167
msc) running from right to left, and thus appears as a part that has
become detached from the.common mesentery. The colon transversum
(ct) with its mesocolon (msc) now divides the body-cavity into an

THE ORGANS OF THE INNER GERM-LAYER. 305

upper [anterior] part, which contains the stomach, liver, duodenum,
and pancreas, and a lower part, holding the small intestine.

Thus embryology explains the striking condition of the duodenum,
which, in order to pass from the upper to the lower space and to
become continuous with the small intestine, passes underneath [dorsal
to] the transversely outstretched mesocolon (figs. 165 and 167 du).

Also in the case of the suspensorium of the coBcum, and of the
ascending and descending arms of the colon, there occurs a more or
less extensive concrescence with the peritoneum of the wall of the
trunk. Therefore in the adult the parts of the intestine named
sometimes lie with their posterior wall broadly in contact with the
body-wall ; sometimes they are supported by a broader or narrower
mesentery.

There still remain to be described the important changes of the
bursa omentalis, the development of which during the first months of
embryonic life we have already (p. 299) become acquainted with.
The bursa is distinguished, first, by a very considerable growth,
and, secondly, by the fact that it fuses with neighboring organs at
various places. In the beginning it reaches only to the greater
curvature of the stomach (figs. 165, 166), to which it is attached;
but even from the third month onward it enlarges and lays itself over
[ventral to] the viscera which lie below the stomach, at first over the
transverse colon (fig. 167 A gnl, gn2), then over the whole of the
small intestine (fig. 1'67 A gn3). The bursa consists, as far as it has
extended downwards, of two lamellae, which lie close to each other,
separated by only a very narrow space, and are continuous at their
lower margin. Of these the more superficial, the one which is nearer
to the ventral wall of the belly, is attached to the greater curvature
of the stomach (gc) ; the posterior [dorsal] lamella, which lies upon
the intestines, is originally attached to the vertebral column and here
encloses the main part of the pancreas (figs. 167 A p and 166 p). In
the case of many Mammals (Dog) the bursa omentalis remains in
this condition. In Man it begins as early as the fourth month
to undergo fusions (fig. 167 B}. On the left side jof the body the
posterior lamella reposes on the posterior wall of the body over a
large extent of surface, and fuses with it (gn*), so that its line of
attachment to the vertebral column moves laterad up to the origin
of the diaphragm (lig. phrenico-lienale). Farther down it glides over
the upper [anterior] surface of the mesocolon (msc) and over the-
transverse colon (ct) ; it becomes fused with both of them, with the
former as early as the fourth embryonic month. At the time of

304 EMBRYOLOGY.

birth the two lamellae of the portion of the bursa which has grown
over the intestines are, as in many Mammals, separated by a narrow
fissure (fig. 167 B gn*) ; during the first and second years after birth
they ordinarily fuse into a single lamella in which fat is deposited.

/ III. Development of the Separate Organs of the Alimentary Tube.

The simple growth in length, to which is to be referred the for-
mation of the convolutions just described, is only one and certainly
not the chief means by which the inner surface of the intestine is
increased. The latter acquires a much greater addition from the
fact that the inner, originally smooth epithelial layer, which is
derived from the entoblast of the germ, forms evaginations and
imaginations. By invaginations toward the cavity of the intestine
there arise numerous folds, small papillae and villi, which give to the
mucous membrane at most places a velvety structure ; by evagina-
tions toward the outer surface of the tube there are developed
various kinds of larger and smaller glands.

By this simple device, the formation of folds, — the great importance
of which in the determination of form in animals was particularly
set forth in Chapter IV. of Part I., — the mucous membrane acquires
to a much greater extent the ability : (1 ) to secrete digestive fluids',
•and (2) to absorb the nutritive substances that are mechanically and
chemically prepared in the intestine, and to transfer them into the
body-fluids.

I discuss the numerous organs which are produced by the process
of folding according to the regions into which the intestinal tube is
•divided, beginning with the organs of the oral cavity.

A. The Organs of the Oral Cavity : Tongue, Salivary Glands, and Teeth.

(1) The Tongue arises, according to the investigations of His upon
human embryos, out of an anterior and a posterior fundament
<ng. 168).

The anterior fundament appears very early as an unpaired eleva-
tion (tuberculum impar, His) on the floor of the oral cavity in the
space surrounded by the mandibular ridges. It grows a good deal
in width, and its anterior margin projects free over the mandible,
thus forming the body and tip of the tongue. Even as early as the
beginning of the third month some papillae make their appearance
on it (His, KOLLIKER).

The posterior fundament produces the root of the tongue, which,

THE ORGANS OF THE INNER GERM-LAYER. 305

although free from papillae, is richly provided with follicnlar glands.
It is developed out of two ridges in the region where the second and
third visceral arches come together in the median plane. The
anterior and posterior fundaments unite in a V-shaped furrow,
the arms of which diverge in front. The circumvallate papillae are
formed on the body of the tongue along this furrow, which persists
for a long time. Where the two arms of the V meet there is a deep
pit, the foramen co3cum, which His has brought into connection with
the origin of the thyroid glands, which will soon be discussed.

(2) The Salivary Glands are demonstrable even in the second
month. The fundament of the submaxillary appears first in human
embryos at the sixth week

(CHIEVITZ), afterwards the
parotid in the eighth week,
and finally the sublingual.

(3) From a morphological
point of view, the Teeth can
well be designated as the most
interesting structures of the
oral cavity. Their develop-
ment in Man and Mammals
is accomplished in a manner

which is neither simple nor Fi*- 168--Tongue ,of a human embry°P about 2*

mm. long, neck measurement. After His,
easily intelligible; in the "Menschliche Embryonen."

lower Vertebrates, on the con-
trary, it is simpler, and for that reason I shall make use of the latter
as the starting-point of the description. .

The teeth, which in Mammals are attached to the edges of the jaw&
and only bound the entrance to the alimentary tube, possess in the
lower Vertebrates a very wide distribution. For in many species they
not only cover the roof and the floor of the oral cavity and the inner
surface of the branchial arches in immense numbers, as palatal,
lingual, and pharyngeal teeth, but they are also distributed in close-set
rows over the whole surface of the skin, and produce, as in the
Selachians, a strong and at the same time flexible coat of mail.

The teeth are originally nothing else than ossified papillce of the skin
and the mucous membrane, upon the contiguous surfaces of which they
are formed. The development of the dermal teeth in Selachians shows
this in a very convincing manner.

In young Shark embryos, by a proliferation on the part of the sub-
epithelial cells, there are developed on the otherwise smooth surface

20

306

EMBRYOLOGY.

cf the dermis, which comes from the embryonic mesenchyme, small
papillae composed of numerous cells (fig. 169 zp), and these penetrate
into the thick overlying epidermis. The latter also undergoes
changes on its part, which are directed toward the formation of the
tooth ; for those of its cells which immediately cover the papilla
grow out into very long cylindrical forms, and produce an organ the
function of which is to secrete enamel, the so-c&\\ed'£namel-membrane
(fig. 169 sm). vBy means of further growth the whole fundament

sm zp

Fig 169.- Very young fundament of a dermal tooth (a placoid scale) of a Selachian embryo.
zp, Deutal papilla ; sm, enamel-membrane.

next assumes a form which corresponds to the future hard structure
(fig. 170).

Then the process of ossification begins. There is secreted by the
most superficial cells of the papilla (o), the odontoblasl-layer (mem-
brana eboris), a thin layer of dentine (zb), which rests upon the
papilla like a cap. At the same time the enamel- membrane (sm)
begins its secretive activity, and coats the outer surface of the
dentinal cap (zb) with a firm, thin layer of enamel (s). The body of
the tooth is developed and becomes ever firmer and larger by the
subsequent continual deposition of new layers on the first-formed
ones, — on the dentinal cap new dentine from within through the
activity of the odontoblasts ; on the coating of enamel new layers of
enamel from without, through the action of the enamel-membrane.
Thus the structure projects more and more above the level of the

THE ORGANS OF THE INNER GERM-LAYER.

307

skin, and the tip of the tooth finally breaks through the epidermal
covering. The tooth then acquires a still firmer attachment in the
dermis from the fact that, at the surface where the lower margin of
the dentine occurs, salts of lime are deposited in the superficial layers
of the connective tissue (lh2), and thus a kind of connective-tissue
bone, the cementum of the tooth, is produced.

The finished tooth therefore is constructed out of three calcified
tissues, which arise from three separate fundaments. The dentine

Tig. 170.— Longitudinal section through an older fundament of a dermal tooth of a Selachian
embryo.

.«, Epidermis ; e1, the deepest layer of epidermal cells, which are cubical ; sch, mucous cells ;
lh1, the part of the dermis which is composed of connective-tissue lamellae ; lh", superficial
layer of the dermis ; zp, dental papilla ; o, odontoblasts ; zb, dentine ; 8, enamel ; sm, enamel-
membrane.

takes its origin from the odontoblast-layer of the dental papilla (mesen-
chyme), the enamel from the epithelial enamel-membrane (outer germ-
layer), and the cementum from connective tissue in the vicinity by
means of direct ossification. The finished tooth has, moreover,
within it a cavity, which is filled with a vascular connective tissue
(pulp), the remnant of the papilla. When the enamel-membrane
has fulfilled its office it perishes, for in the process of secretion its
cells become shorter and shorter, and are finally reduced to flat scales,
which are afterwards thrown off.

In Selachians the formation of the teeth which occupy the edges
•of the jaws and serve for the comminution of the food differs from
this simple process in one important point ; they take their origin,
not on the free surface of the mucous membrane, but in its
depths (fig. 171). The epithelial tract of the oral mucous membrane

308

EMBRYOLOGY.

which shares in the formation of teeth has sunk deep down in the form
of a ridge (z.l) on the inner surface of the jaw-arches, into the under-
lying loose connective tissue, and now represents a special organ,
distinguishable from its surroundings. This important difference is
produced by the fact that in the development of the teeth of the jaws
more active processes of growth take place, first because these teeth
are much larger than the dermal teeth, and, secondly, because they
are more rapidly worn out and must consequently be more rapidly
replaced by supplementary teeth. As we have often had the oppor-
tunity of observing in the study of the production of morphological
conditions in animals generally, portions of epithelial membranes that

sin zb »

Fig. 171.— Cross section through the lower jaw of a Selachian embryo with fundaments of teeth.
k, Mandibular cartilage ; zl, dental ridge ; zp, dental papilla ; zb, dentine ;'s, enamel ; SHI, enamel-
membrane ; 6, connective-tissue part of the mucous membrane.

grow more rapidly than their surroundings emerge from the latter
and become folded either outward or inward.

The process of the formation of teeth is the same on the dental ridge
itself as upon the free surface of the skin. There are developed on its
outer side, which is turned toward the cartilage of the jaw (k\
numerous papillae (zp), lying alongside of and behind one another,
which grow into the invaginated epithelium just as the dermal
papillae grow into the epidermis. Thus there arise in the depths of
the mucous membrane several rows of teeth, of which the most
superficial anticipate in development those which lie deeper ; the
former are the first to break through the mucous membrane, to
become functional, and, after having been worn out, to be cast off;
they are also the first to be supplanted by reserve teeth, which lie
behind them, and, developing somewhat later, are consequently
younger.

THE ORGANS OF THE INNER GERM-LAYER. 309

Whereas in the Selachians, as well as in the lower Vertebrates
generally, the replacement of teeth by new ones is throughout life an
unlimited process, since new papillae are continually being formed
in the depths of the dental ridge (polyphyodont), it is in the higher
Vertebrates more limited, and in most Mammals occurs only once.
There are formed on the ridge two fundaments (diphyodont), one behind
the other, one for the milk-teeth and a second for the permanent teeth.

In the case of Man the development of the teeth begins as early as
the second month of embryonic life. A ridge (zl) (the enamel-germ of
older authois) grows from the epithelium of the oral cavity both
on the maxillary and mandibular arches — as it also does in other
mammalian embryos (fig. 290) — into the richly cellular embryonic
connective tissue. The region from which this growth into the
depths takes place (fig. 172 A and £) is marked exteriorly by a
groove, which runs parallel to the arch of the jaw, the so-called
dental groove (zf). The head of the human embryo represented in
figure 289 shows this groove at a little distance behind the fundament
of the upper lip.

At first the dental ridge is uniformly thin and separated from its
surroundings by a smooth surface. There is nothing to be seen as
yet of the separate fundaments of the teeth. Then the epithelial
cells on the side of the ridge which is directed outwards begin at
certain places to grow and to produce at regular intervals from one
another as many thickenings as there are to be teeth (fig. 172 A).
In Man, who has twenty milk-teeth, the number of these is ten
in each jaw. The thickenings now assume a flask-shaped form
(fig. 172 J3), and gradually detach themselves from the outer surface
of the epithelial ridge (zl), except at the neck of the flask, which
remains in connection with it at a little distance from its deep edge.
Because these epithelial growths have relation to the secretion of
•enamel, they have received the name of enamel-organs.

In the meantime the connective tissue has taken its first steps
toward the formation of the tooth (fig. 172-4 and .3). At the bottom
of each flask the connective-tissue cells exhibit active growth, and
give rise to a papilla (zp) corresponding in form to the future tooth.
As the papilla of the dermal teeth grow into the epidermis, so this
papilla grows into the enamel- organ, which is thereby made to take
the form of a cap.

Then the special layers from which the formation of dentine and
•enamel proceed are differentiated in both fundaments so far as these
are in mutual contact. At the surface of the papilla (fig. 172 B zp]

310

EMBRYOLOGY.

the cells assume spindle-shaped forms and group themselves into a
kind of epithelial layer, the layer of the dentine-forming cellsl(mem-
brana eboris). On the part of the cap-like enamel-organ the cells of
the deepest layer, which is in immediate contact with the papilla, are
converted into very long cylinders and constitute the enamel-mem-
brane (sm, membrana adamantime). The latter becomes gradually
thinner toward the base of the papilla, where it is continued as a
layer of more cubical elements (se), which forms the boundary at the
surface of the cap separating it from the surrounding connective
tissue. Between these two cell-layers (the inner and the outer
epithelium of KOLLIKER) the remaining epithelial cells of the enamel-
organ undergo a peculiar metamorphosis, and produce a kind of
gelatinous tissue, the enamel-pulp (sp) ; they secrete between them a

Fig. 172 A B.— Two stages in the development of the teeth of Mammals. Diagrammatic sections.

zf, Dental groove ; zl, dental ridge ; zl\ deepest part of the dental ridge, on which are formed
the fundaments of the supplementary teeth ; zp, dental papilla ; sm, enamel-membrane :
sp, enamel-pulp ; se, outer epithelium of the enamel-organ ; zs, dental sac ; k, bony alveolus.

fluid rich in mucus and albumen, and become themselves converted
into stellate cells, which are united to one another by their processes.
and thus form a fine network. The enamel-pulp is most highly
developed in the fifth or sixth month, and then diminishes up to the
time of birth in the same ratio as the teeth increase in size.

The connective tissue immediately enveloping the whole fundament
acquires numerous blood-vessels, from which branches also make their
way into the papilla ; it becomes somewhat differentiated from the
surrounding tissue, and is distinguished as dental sac (fig. 172 B zs).

The soft fundaments of the teeth enlarge up to the fifth month of
embryonic life, and at the same time acquire the particular forms of
the teeth which are to arise from them — those of the incisors, the
canines, and molars. Then the process of ossification begins (fig. 173)
in the same manner as in the dermal teeth. A cap of dentine (zb) is

THE ORGANS OF THE INNER GERM -LAYER.

311

formed by the odontoblasts (o), or dentinal cells ; this cap at the same
time acquires a coating of enamel (s) from the enamel-membrano
(sm) • then there are continually deposited on the first layers new
ones, until the crown of the tooth is completed. Under pressure of
the latter the enamel-pulp (sp) atrophies, and forms only a thin
covering to the tooth at birth. The papilla (zp) is converted into a
mass of connective tissue containing blood-vessels (g) and nerves, and
fills the cavity of
the tooth as the so-
called pulp. The
larger the whole
structure becomes,
the more it raises

up

the

the tissue of

gum,

which

covers the edge of
the jaw, and
causes it to be-
come gradually
thinner. Finally,
it breaks through
the gum soon after
birth, and at the
same time casts
off from its sur-
face the atrophied
remnant of the
enamel-organ.

The time has
now come in which
the third hard sub-
stance of the tooth
is formed, the cementum that envelops the root. So far as the
dentine has received no coating of enamel, the bounding con-
nective tissue of the dental sac (zs) begins, after the eruption of the
teeth, to ossify and to produce a genuine bone-tissue with numerous
SHARPEY'S fibres ; this bony tissue contributes to the firmer union of
the root of the tooth with its connective-tissue surroundings.

The eruption of the teeth ordinarily takes place with a certain degree
of uniformity in the second half of the first year after birth. First
the inner incisors of the lower jaw break through in the sixth to the

Fig. 173.— Section through the fundament of the tooth of a young
Dog.

k, Bony alveolus of the tooth ; zp, dental papilla ; g, blood-vessel ;
o, odontoblast-layer(membrana eboris) ; zb, dentine ; «, enamel ;
sm, enamel-membrane ; zs, dental sac ; sp, enamel-pulp.

312

EMBRYOLOGY.

eighth months ; then in the course of a few weeks those of the upper
jaw follow. The outer [lateral] incisors appear during the period
between the seventh and ninth months, those of the lower jaw, again,
somewhat earlier than those of the upper jaw. The front molars
usually appear at the beginning of the second year, those of the lower
jaw first ; then the gap thus left in the two rows of teeth is filled by
the eruption of the canine or eye-teeth in the middle of the second

year. Finally, the eruption of the
back molars, which may be delayed
into the third year, takes place.

The fundaments of the reserve teeth
make their appearance at the side of
those of the milk-teeth at an extra-
ordinarily early period. They also
take their origin from the epithelial
ridge. As was previously (fig. 172
A and B) stated, the ridge extends
still deeper (zl1) into the underlying
tissue from the place where the
enamel-organs of the milk-teeth
have been differentiated from it
and where they remain united to
it by means of an epithelial cord,
the neck. Here in a short time
there again appear near the edge of
the ridge (fig. 174 sm2, zp?) flask-
shaped epithelial growths and dental
papillae, which lie on the inner
[median] side of the dental sacs of
the milk-teeth. In addition there
are developed at the ends of the

epithelial ridges, in both the right and left halves of the jaw, the
enamel-organs of the posterior grinders (the molar teeth of the
permanent set), which are not subject to replacement, but are
formed once for all. The ossification of the second generation of
teeth begins a little time before birth with the first large molars,
and is followed in the first and second years after birth by that of
the incisors, canines, etc. As a result in the sixth year there are in
both jaws forty-eight ossified teeth, — twenty milk-teeth and twenty-
eight permanent crowns, — as well as four fundaments of wisdom
teeth, which are still cellular.

Tig. 174.— Diagrammatic section to show
the development of the milk-teeth and
permanent teeth in Mammals. Third
stage in the series of which figs. 172
A and B are the first and second.

zf, Dental furrow ; zl, dental ridge ; k,
bony alveolus of the tooth ; h, neck,
by means of which the enamel-organ
of the milk-tooth is connected with the
dental ridge, zl • zp, dental papilla ;
zpa, dental papilla of the permanent
tooth ; zb, dentine ; s, enamel ; am,
enamel-membrane ; a«i2, enamel-mem-
brane of the permanent tooth; sp,
enamel-pulp ; se, outer epithelium of
the enamel-organ ; zs, dental sac.

THE ORGANS OF THE INNER GERM-LAYER. 313

The shedding of the teeth ordinarily begins in the seventh year. It
is initiated by the disorganisation and absorption of the roots of the
milk-teeth, under the pressure of the growing new generation. One
finds here exactly the same appearances as in the atrophy of osseous
tissue, concerning which we have the thorough investigations of
KOLLIKER. There arise on the roots of the teeth the well-known
pits of HOWSHIP, in which large, multinuclear cells, the osteoclasts or
bone-destroyers, are imbedded. The crowns are loosened by surren-
dering their union with the deeper connective-tissue layers. Finally,
when the permanent teeth, owing to the growth of their roots, push
forth out of the alveoli, the crowns of the milk-teeth are thereby
raised up and fall off.

The permanent teeth generally appear in the follow iny order : at
first, in the seventh year, the first [front] molars ; a year later the
middle incisors of the lower jaw, which are followed a little later by
those of the upper jaw ; in the ninth year the lateral incisors are
cut, in the tenth year the first premolars, in the eleventh year the
second premolars. Then in the twelfth and thirteenth years the
canines and the second molars come through. The eruption of the
third molars, or wisdom teeth, is subject to great variation : it may
take place in the seventeenth year, but it may be delayed till the
thirtieth. Occasionally the wisdom teeth never attain a complete
development, so that they are never cut.

B. The Organs arising from the Pharynx : Thymus, Thyroid Gland,
Larynx, and Lung.

Whereas in the water-breathing Vertebrates the visceral clefts
remain throughout life and subserve respiration, they are completely
closed in all Amniota as well as in a part of the Amphibia. The
only exception is in the case of the first cleft, lying between the man-
dibular and the hyoid arches, which is converted into the drum of the
ear (tympanum) and the EUSTACHIAN tube, and thus enters into the
service of the organ of hearing, in connection with which it will
subsequently engage our attention.

However, the remaining visceral clefts do not disappear without
leaving any trace. From certain epithelial tracts of these there
arises an organ of the neck-region which functionally is still proble-
matic, the thymus, the morphology of which has been very essentially
advanced during the last few years.

314

EMBRYOLOGY.

3Ch

(1) The Thymus

has been for several years a favorite object of embryological investiga-
tion, since the time when KOLLIKER
made the interesting discovery that
in mammalian embryos it takes
its origin from the epithelium of a
visceral cleft. This discovery has
since then been corroborated, and
at the same time extended ; for also
in such animals as persistently
breathe by means of gills the
thymus is developed out of epi-
thelial tracts of the open and func-
tionally active gill-clefts.

Let us first examine the original
condition as exhibited by Fishes.
As stated by DOHRN, MAURER, and
DE MEURON, the thymus (tJi) of the
Selachians (fig. 175) and the Bony
Fishes has a multiple origin and is
derived from separate solid epithelial
growths, which take place at the
dorsal ends of all the gill-clefts, and,

indeed, to a greater extent on the anterior than on the posterior ones.

nsd

Fig. 175.— Diagram to show the develop-
ment of the thymus, the thyroid
gland, and the accessory thyroid
glands, and their relations to the
visceral pockets in a Shark embryo,
after DE MEURON.

tch1, sch*, First and sixth visceral pockets ;
tJt, fundaments of the thymus ; sd,
h jroid gland ; nsd, accessory thyroid
gland.

Fig. 176.— Two diagrams [ventral aspect] of the development of the thymus, the thyroid gland
and the accessory thyroid glands, and their relations to the visceral pockets in a Lizard
embryo (A) and a Chick embryo (B), after DE MEURON.

tch1, sch*, First and second visceral pockets ; sd, thyroid gland ; nsd, accessory thyroid gland ;
th, fundament of thymus.

In the Bony Fishes the separate fundaments at an early period, even
before they have detached themselves from their matrix, fuse together

THE ORGANS OF THE INNER GERM-LAYER.

A

315

into a spindle-shaped organ lying
above the insertion of the gill-arches,
which subsequently becomes inde-
pendent, just as it does in Selachians.
The originally epithelial product ac-
quires a peculiar histological char-
acter from being penetrated by
ingrowths of connective-tissue ele-
ments. In the first place lymph -
cells in great quantities migrate in
between the epithelial cells, in a
manner similar to that described by
STOHR as of frequent occurrence in
the territory of mucous membranes.
Secondly, the epithelial growth is
traversed in all directions and cut
up into small portions by connective
tissue, in which lymph-follicles are
formed. The thymus thereby ac-
quires the appearance of a lymphoid
organ, in which the epithelial rem-
nants are still in part preserved,
but only in the form of very small
spherical portions, as the corpuscles
of HASSALL. At a still later stage
of development there arise in the
organ irregular cavities filled with
molecular granules. These are
caused by the disintegration of
lymph-cells and the melting down
of the reticular connective tissue,
which takes place here and there.
In the higher, air-breathing Ver-
tebrates the thymus is derived either
from the epithelium of two or three
clefts or only from the epithelium
of the third visceral cleft, which
becomes closed. The former is the
case with Reptiles (fig. 176 A th)
and Birds (fig. 176 B th), the latter
with Mammals. In Reptiles and

nsd

Fig. 177.— Semidiagrammatic illustra-
tions to show the ultimate position of
thymus, thyroid gland, and accessory
thyroid gland on the neck of the
Lizard (A), the Chick (B), and the
Calf (<?), after DE MEURON.

sd, Thyroid gland ; nsd, accessory thyroid
gland ; th, thymus ; th,1, accessory
thymus ; Lr, trachea ; h, heart ; vj
vena jugularis ; ca, carotid vein.

316

EMBRYOLOGY.

Birds the two fundaments fuse early upon either side of the trachea
into a longish tract of tissue, which in the former is shorter
(fig. 177 A), but in the latter very much elongated (fig. Ill B).

In Mammals it is principally the third visceral cleft which con-
tributes to the formation of the thymus. According to KOLLIKER,
BORN, and KABL this is the only one which comes into considera-
tion, whereas DE MEURON, KASTSCHENKO, and
His give an account which differs from this,
but only in minor details.

The further changes of the fundament of the
thymus in Mammals and in Man may be briefly
summarised as follows. The thymus-sac, which
probably takes its origin from the third visceral
pocket, encloses only a very narrow cavity, but
possesses a thick wall composed of many elon-
gated epithelial cells (fig. 178). It then grows
downward toward the pericardium, and at the
posterior end begins to form, like a botryoidal
gland, numerous rounded lateral branches (c).
(KOLLIKER.) These are frcm the beginning of
their formation solid, whereas the sac-like part
(a), which occupies the neck-region, always
continues to exhibit a narrow cavity.

The budding continues for a long time, and
meanwhile extends to the opposite end of the
originally simple glandular sac, until the whole
organ has assumed the lobed structure peculiar
to it. At the same time an histolcgical meta-
morphosis is also taking place. Lymphoid
connective tissue and blood-vessels grow into
the thick epithelial walls and gradually destroy
the appearance which so resembles a botryoidal
gland. With the increase in the size of the
organ the lymphoid elements coming from the

surrounding tissue predominate more and more ; the epithelial rem-
nants are finally to bo found only in the concentric bodies of HASSALL,
as MAURER has shown for Bony Fishes and as His has undoubtedly
rightly inferred for Man and Mammals. The cavity originally present
and resulting from the invagination disappears, and instead of it
there arise new irregular cavities, probably the result of a breaking
down of the tissue.

.Fig. 178.— Thymus of an
embryo Rabbit of 16
days, after KO'LL.KER.
Magnified.

«, Canal of the thymus ;
b, upper, c, lower end
of the organ.

THE ORGANS OP THE INNER GERM-LAYER. 317

The further history of the thy mm in Man permits the recognition
of two periods, one of progressive and one of regressive development.

The first period extends into the second year after birth. The
thymus of the right side and that of the left move in their growth
close together into the median plane and here fuse into an unpaired,
lobed organ, whose double origin is to be recognised only by the fact
that the organ is ordinarily composed of lateral halves separated by
connective tissue. It lies in front of [ventral to] the pericardium and
the large blood-vessels beneath the breastbone, and is often elongated
into two horns which extend upwards to the thyroid gland.

The second period exhibits the organ undergoing regressive meta-
morphosis, which usually leads to its total disappearance, the par-
ticulars of which can be learned from the text-books of Histology.

(2) The Thyroid Gland

is found on the anterior surface of the neck, and appears to be
developed in almost all classes of Vertebrates in a tolerably uniform,
typical manner from an unpaired and a paired evagination of the
pharyngeal epithelium. We must therefore distinguish unpaired and
paired fundaments of the thyroid gland.

The unpaired fundament has been longest known. There is not
a single class of Vertebrates in which it is wanting, as has been
established especially by the investigations of W. MULLER. It
appears to be an organ of very ancient origin, which shows relation-
ship to the hypobranchial furrow of Amphioxus and the Tunicates.

DOHKN has opposed this hypothesis and has expressed the view, which is also
shared by others, but which lacks proof, that the thyroid gland is the remnant
of a lost gill-cleft of the Vertebrates.

The unpaired thyroid gland arises as a small evagination of the
epithelium of the front wall of the throat in the median plane and
in the vicinity of the second visceral arch. Then it detaches itself
completely from its place of origin, and is converted either into a
solid spheroidal body (Selachians, Teleosts, Amphibia, etc.) or into an
epithelial vesicle having a small cavity (Birds, Mammals, Man, etc.).
The vesicle subsequently loses its cavity.

In Man the development of the unpaired part of the thyroid gland is related
to the formation of the root of the tongue, as His states in his investigations
of human embryos. The previously described ridges lying on the floor of the
throat-cavity in the vicinity of the second and third visceral arches, which unite
in the median plane to form the root of the tongue, surround a deep depression,

318 EMBRYOLOGY.

which is tbe equivalent of the evagination of the pharyngeal epithelium in the
remaining Vertebrates. By the further approximation of the ridges the depres-
sion becomes an epithelial sac, which remains for a long time in communication
with the surface of the tongue by means of a narrow passage, the ductus
thyreoglossus.

The paired fundaments of the thyroid gland were discovered a few
years ago by STIEDA in mammalian embryos, but they have been
more fully investigated by BORN, His, KASTSCHENKO, DE MEURON,
and others in Mammals and other Vertebrates (excepting Cyclo-
stomes). In the Amphibia, as well as in Birds and Mammals
(fig. 176 J3), there are formed, a little while after the appearance of
the unpaired fundament, two hollow evaginations of the ventral
epithelium of the throat behind the last visceral arch and in con-
nection with the last visceral cleft. They come to lie immediately on
either side of the entrance to the larynx. In many Reptiles (fig. 176
A nsd) there- is_ an interesting deviation due to the fact that an
evagination is developed only on the left side of the body, while on
the right it has become rudimentary. Even in the Selachians
(fig. 175), as DE MEURON appears rightly to maintain, paired
fundaments of thyroid glands are present. They are the previously
mentioned supra-pericardial bodies discovered by v. BEMMELEN. These
arise as evaginations of the epithelium of the throat behind the last
pair of gill-clefts near the anterior end of the heart. In all cases
the evaginated portions of the epithelium become detached from
their parent tissue and enclosed on all sides by connective tissue ;
they then undergo a metamorphosis similar to that of the unpaired
fundament of the thyroid gland.

In regard to their ultimate position there exist considerable
differences between the separate classes of Vertebrates. In the
Selachians the supra-pericardial bodies remain far away from the
unpaired thyroid gland, being located in the vicinity of the heart ;
but in the other Vertebrates they move more or less close to the
gland, and have here acquired the name of accessory thyroid glands
(fig. 177 A and B nsd). Finally, in Mammals and Man the approxi-
mation has led to a complete fusion of the unpaired and the lateral,
paired fundaments (fig. 177 C). Together they constitute a horse-
shoe-shaped body that embraces the larynx. It is, however, to be
observed, that at the time of their fusion the lateral fundaments,
in comparison with the median one, are only very small nodules.
Consequently KASTSCHENKO, who is probably in the right, ascribes to
the former an inconsiderable importance for the. development of the

THE ORGANS OF THE INNER GERM-LAYER.

319

whole mass of the thyroid gland, whereas His maintains that they
become in Man the voluminous lateral lobes, and that the unpaired
fundament becomes the small middle part of the organ.

The further development of the thyroid gland is accomplished
in a very similar manner in all Vertebrates. Two stages are
distinguishable.

During the first stage the whole fundament grows out into
numerous cylindrical cords, which in turn push out lateral buds
(fig. 179). By the union of these with one another there is formed a
network, into the interstices of which are distributed branches of the
blood-ve s s e 1 s
together with
embryonic con-
nective tissue.
In the case of
the Chick it is
found that the
thyroid gland
has reached
this stage of de-
velopment on
the ninth day
of incubation,
in the Eabbit
embryo when
it is about six-
teen days old,
in Man in the
second month.

During the second stage the network of epithelial cords is resolved
into the characteristic follicles of the thyroid gland. The cords
acquire a narrow lumen, around which the cylindrical cells are
regularly arranged. Then there are formed on the cords at short
intervals enlargements, which are separated by slight constric-
tions (fig. 180). By the deepening of the constrictions the
whole network is finally subdivided into numerous, small, hollow
epithelial vesicles or follicles, which are separated from one another

* [The elevation caused by the mid-brain may be called the apex or crown
(Scheitel). In later stages the distance between crown and rump is greater
than that between neck and rump, hence the measurement is made from the
crown. Compare foot-note, p. 283.]

MS

Fig. 179.— Right half of the thyroid gland of an embryo Fig 21 5 mm.

long, crown-rump measurement,* after BORN. Magnified 80

diameters.
The lateral (LS) and median (MS) thyroid glands are in process of

fusion, g, Blood-vessels ; tr, trachea.

320

EMBRYOLOGY.

by highly vascular embryonic tissue. Subsequently the follicles
increase in size, especially in the case of Man ; this results from the
epithelial cells secreting a considerable quantity of colloid substance
into the cavity.

A few further details concerning the thyroid gland of Man, for which we are
indebted to His, may be of interest. First, it is to be noted that the lateral
fundaments are considerably more voluminous than the middle part, and that
the future fundamental form of the organ is thus from the beginning pre-
determined. Secondly, some rare anatomical conditions (His) are explained
by the development, such as the ductus lingualis, the ductus thyroideus, and
the glandula suprahyoidea and prsehyoidea. As was previously stated, the
unpaired fundament of the thyroid gland is connected with the root of the
tongue by means of the ductus tbyreoglossus. When the thyroid gland moves

from its place of origin farther
down, this duct becomes elon-
gated into a narrow epithelial
passage, whose external orifice
remains permanently visible as
-the foramen ccecum at the base
of the tongue. The remaining
part usually undergoes degene-
ration, but occasionally some
parts of it also persist. Thus
the foramen ccecum is some-
times elongated into a canal
(ductus lingualis) 2^ cm. long,
that leads to the body of the

Fig. 180.— Section through the thyroid gland of an
embryo Sheep 6 cm. long, after W. MULLEE.

sch, Sac-like fundaments of the gland ; /, glandular
follicles in process of formation ; b, interstitial
connective tissue with Wood-vessels (tf).

hyoid bone. In other instances
the middle part of the thyroid
gland is prolonged upward in
the form of a horn, which is
continued as a tube (ductus

thyroideus) to the hyoid bone. Finally, according to His, the glandular vesicles
now and then to be observed in the vicinity of the hyoid bone— the accessory
thyroid glands, as well as the glandula supra- and prae-hyoidea— are to be
interpreted as remnants of the ductus thyreoglossus.

(3) Lung and Larynx.

The lung with its outlet (larynx and trachea) is developed, like
a lobed gland, out of the O3sophagus in a tolerably uniform manner,
as it appears, for all amniotic Vertebrates. Immediately behind the
unpaired fundament of the thyroid gland (fig. 181 Sd) there arises on
the ventral side of the oesophagus a groove (Kk), which is slightly
enlarged at its proximal end. It is to be seen in the Chick at the
beginning of the third day, in the Rabbit on the tenth day after
fertilisation, and in the human embryo when it is 3'2 mm. long.

THE ORGANS OF THE INNER GERM-LAYER.

321

Ofc

Soon the groove-like evagination becomes separated from the over-
lying portion of the alimentary tube by two lateral ridges; this
furnishes the first indication of a differentiation into oesophagus and
trachea (fig. 181). Then there grow out from the enlarged posterior
«nds of the groove (figs. 181, 163) two small sacs (Lj) toward the two
sides of the body (in the Chick iu the middle of the third day), the
fundaments of the right
and left lung. Enveloped
in a thick layer of em-
bryonic connective
tissue, they are in im-
mediate contact behind
with the fundament of
the heart; laterally they
project into the anterior
fissure-like prolongation
•of the body - cavity.
With this the essential
parts of the respiratory
apparatus are estab-
lished; at this stage
in amniotic Vertebrates
they resemble the simple
sac-like structures which
the lungs of Amphibia
present permanently.

In the further course
of development the fun-
daments of trachea and
03sophagus, which com-
municate by means of a
fissure, become separated
by a constriction which
"begins behind, where the

pulmonary sacs have budded out, and gradually moves forward. The
constricting off is here interrupted at the place which becomes the
entrance to the larynx. The latter is distinguishable in the case of
Man at the end of the fifth week as an enlargement at the beginning
of the fundament of the trachea. It acquires its cartilages in the
eighth or ninth week. Of these the thyroid cartilage arises, according
;to the comparative-anatomical investigations of DUBOIS, from a fusion

21

Fig. 181.— Alimentary tube of a human embryo (R of His)
5 mm. long, neck measurement. From His, " Mensch-
liche Embryonen." Magnified 20 diameters.

RT, RATHKE'S pouch ; Uk, lower jaw ; Sd, thyroid gland ;
Ch, chorda dorsalis; Kk, entrance to the larynx;
Lg, lung ; Mg, stomach ; P, pancreas ; Lbg, primitive
hepatic duct ; Ds, vitelline duct (stalk of the intestine) ;
All, allantoic duct; W, Wolffian duct, with kidney-
duct (ureter) budding out of it ; B, bursa pelvis.

322 EMBEYOLOGY.

of the fourth and fifth visceral arches, whereas the cricoid and ary-
tenoid cartilages, as well as the half-rings of the trachea, are
independent chondrifications in the mucous membrane.

Two stages are recognisable in the metamorphosis of the primitive
lung-sacs of Man and Mammals.

The first stage begins with the elongation of the sac, which is
attenuated at its origin from the trachea, but is enlarged at its
opposite or free end. At the same time — in Man from the end of
the first month (His) — it pushes out, in the manner of an alveolar
gland, hollow evaginations, which grow out into the thick connective-
tissue envelope and enlarge at their ends into little sacs. The first
bud-like outgrowths on the two sides of the body are not symmetrical
(fig. 182), because the left lung-sac produces two, the right three bud-like

enlargements. An im-
'<»• portant feature of the
architecture of the lungs
is thus established from
the beginning, namely,
sp the differentiation of the
right lung into three

Fig. 182.— View of a reconstruction of the fundament of i • r i ^ j * ^

the lungs of a human embryo (Pr of His) 10 mm. long, >6S> an°

neck measurement, after His. left into two.

Ir, Trachea; br, right bronchus; sp, oesophagus; bf, con- mi p ,1 i -ji-

nective-tissue envelope and serous membrane (pleura) im&

into which the epithelial fundament of the lung grows ; is distinctly dichotoniOUS

0, M, U, fundaments of the upper, middle, and lower //. -, Q«j\ T, , i i

lobes of the right lung; 0\ V\ fundaments of the W l$6)' 1* takes place

tipper and lower lobes of the left lung. in the following way :

each terminal vesicle

(primitive lung- vesicle), which is at first spheroidal, becomes flattened.
and indented on the wall (Ib) which lies opposite its attachment.
Thus it becomes divided, as it were, into two new pulmonary vesicles,
each of which is then differentiated into a long stalk (lateral bronchus)
and a spherical enlargement. Inasmuch as such a process of budding
is kept up for a long time, — in Man until the sixth month, — there arises
a complicated system of canals, the bronchial tree, which opens into
the trachea by means of a single main bronchial tube from either
side of the body, and the ultimate branches of which, becoming finer
and finer, terminate in flask-shaped enlargements, the primitive
lung-vesicles. The latter are at first confined to the surface of the
lung, while the system of canals occupies its interior.

During this budding the lungs as they increase in volume
continue to grow downwards into the thoracic cavities, and thereby

THE ORGANS OF THE INNER GERM-LAYER.

323

M

come to lie more and more at the right and left of the heart. With
their ingrowth into the cavities of the chest (fig. 314 brh), they push
before them the serous lining of the latter, and thus acquire their
pleural covering (the pleura pulmonalis, or the visceral layer of the
pleura).

During the second stage the organ, which up to this time has the
typical structure of a botryoidal gland, assumes the characteristic
pulmonary structure. The metamorphosis begins in Man, as
KOLLIKER states, in the sixth month, and comes to a close in the
last month of pregnancy. There now arise close together on the
fine terminal tu-
bules of the bron-
chial tree, on the
alveolar passages,
and on their ter-
minal vesicular
enlargem ents,
very numerous
small evagina-
tions. But in dis-
tinction from the
earlier ones, these
are not constricted
off from their
source of origin,
but communicate
with the latter
by means of wide
orifices, and thus
constitute the air-cells or pulmonary alveoli. Their size is only a
third or fourth as great in the embryo as in the adult ; from this
KOLLIKER concludes that the increase in the volume of the lung
from birth up to complete development of the body is to be attributed
exclusively to the enlargement of the vesicular elements which exist
in the embryo.

The epithelial lining of the lung is variously modified in different
regions during development. In the whole bronchial tree the
epithelial cells increase in height, acquire in part a cylindrical, in
part a cubical form, and from the fourth month onward (KOLLIKER)
have their free surfaces covered with cilia. In the air-sacs, on the
contrary, the cells, which are arranged in a single layer, become

Fig. 183. — View of a reconstruction of the fundament of the lungs
of a human embryo (N of His) older than that of fig. 182.
After His. Magnified 50 diameters.

Ap, Arteria pulmonalis ; Ir, trachea ; sp, resophagus ; Ib, pulmonary
vesicle in process of division ; 0, upper lobe of the right lung
with an eparterial bronchus leading to it ; M, U, middle and
lower lobes of the right lung ; 0', upper lobe of the left lung
with hyparterial bronchus leading to it ; U1, lower lobe of the
left lung.

324

EMBRYOLOGY.

more and more flattened, and in the adult become so thin that
formerly the presence of an epithelial covering was wholly denied.
Then they assume a condition similar to that of endothelial cells ;
as in the case of the latter, their boundaries are demonstrable only
after treatment with a weak solution of silver nitrate.

C. The Glands of the Small Intestine : Liver and Pancreas.
(1) The Liver.

In the section which treats of the liver we must enter upon a dis-
cussion not only of the development of the parenchyma of the gland,
but also of the various hepatic ligaments — the
lesser omentum, the ligamentum suspensorium,
etc.; in fact, we must begin with the latter
because they are developed out of a structure —
a ventral mesentery — which is ontogenetically
older than the liver itself. In view of the
manner in which the body -cavity arises, as a
pair of cavities, such a structure ought to be
found along the whole length of the ventral
side of the alimentary canal in the same manner
as on its dorsal side. Instead of that, it is found
only at the anterior region of the alimentary
canal, along a tract which extends from the
throat to the end of the duodenum.

This ventral mesentery acquires a special
significance, because several important organs
take their origin in it ; in front, the heart,
together with the vessels that bring the blood
back to it — the terminal parts of the venae
omphalomesentericse and of the vena umbili-
calis; immediately behind the latter, the liver with its outlet and
its blood-vessels.

The part which, during an early stage of development, encloses the
heart is called mesocardium anterius and posterius ; we shall return
to it later in considering the development of that organ. The
portion (fig. 184) which joins this behind [caudad] has been hitherto
less regarded by embryologists. Since it stretches from the lesser
curvature of the stomach and the duodenum (du) to the anterior
[ventral] wall of the trunk, it may be especially designated as the
ventral gastric and duodenal mesentery, or, under a more compre-

Pig. 184.— Diagram (view
of a cross section) to
show the original re-
lations of duodenum,
pancreas, and liver,
and of the ligamentous
structures belonging to
them.

H R, Posterior wall of the
trunk ; du, duodenum ;
p, pancreas ; I, liver ;
dms, dorsal mesentery ;
Ihd, ligamentum hepa-
to-duodenale ; Is, liga-
mentum suspensorium
Lepatis.

'

THE OEGANS OP THE INNER GERM- LAYER.

325

umc

Fig. 185.— Cross section through the anterior part of the trunk of an embryo of Scyllium, af tef
BALFOUE.

Between the dorsal and ventral walls of the body, where the attachment of the stalk of the yolk*
sac is cut, there is stretched a broad mesentery which contains numerous cells and completely
divides the body-cavity into a right and a left half. The duodenum (du), lying in tha
mesentery, is twice cut through ; dorsally it gives rise to the fundament of the pancreas
(pan), ventrally to that of the liver (hp.d). Further, the place where the vitelline duct
(umc) emerges from the duodenum is to be seen, sp.c, Neural tube (spinal cord) ; sp.g,
ganglion of posterior root ; ar, anterior root ; dn, dorsally directed nerve springing from the
posterior root ; mp, muscle-plate ; mpl, part of muscle-plate already converted into muscles ;
mp.l, part of muscle-plate which gives rise to the muscles of the limbs ; nl, nervus lateralis ;
ao, aorta ; ch, chorda ; sy.g, sympathetic ganglion ; ca.v, cardinal vein ; sp.n, spinal nerve ;
sd, segmental duct (duct of primitive kidney) ; st, segmental tube (pronephric tubule).

326 EMBRYOLOGY.

hensive title, as ventral alimentary mesentery (Ihd -f Is). It has
been described by KOLLIKER on sections of Rabbit embryos as liver-
ridge (Leberwulst), and by His in his " Anatomie menschlicher
Embryonen " as prehepaticus (Vorleber) ; it has the form of a mass
of tissue rich in cells, which inserts itself between the wall of the
belly and the regions of the intestine previously mentioned. In
cross sections through human and mammalian embryos there are
encountered in it the capacious vense omphalomesentericse. As far
as a mesocardium and a mesogastrium anterius are developed in
Vertebrates, the body-cavity appears even subsequently as a paired
structure.

The cross section through a Selachian embryo (fig. 185) shows this
distinctly. The duodenum (du) is enclosed in the connective-tissue
mesentery, which reaches from the aorta (ao) to the front [ventral]
wall of the trunk ; dorsally the pancreas (pan) is budded forth from
its wall, ventrally the liver (hp.d).

The liver begins to be developed very early in the ventral me-
sentery (liver-ridge or prehepaticus), and in this exhibits, as will
appear later, two modifications, which are, however, unessential ; for
sometimes it appears in the form of a single, sometimes as a paired
evagination of the epithelial lining of the ventral wall of the duo-
denum.

The first is the case, for example, in the Amphibia and Selachii.
In Bombinator (fig. 159), as GOETTE has shown, the liver arises as a
broad ventrally directed evagination of the intestine, which lies im-
mediately in front of the accumulation of yolk-material. The liver
remains permanently in this simplest form in the case of Amphioxus
lanceolatus, in which it is located immediately behind the gill-region
as an appendage of the intestinal canal.

In the case of Birds and Mammals, on the contrary, the funda-
ment of the liver is from the beginning double. As has been known
since the investigations of REMAK, in the case of the Chick (fig. 186)
on the third day of incubation, two sacs (I) grow out of the ventral
wall of the duodenum immediately behind the spindle-shaped
stomach (St). They grow into the broad cell-mass of the ventral
mesogastrium (the Leberwulst), one passing forward to the left, the
other backward to the right, and thereby embrace from above the
vena omphalomesenterica on its way to the heart. The process in
Mammals is somewhat different. According to the observations of
KOLLIKER in the case of the Rabbit, the primitive hepatic tube of
the left side is forme:! in the embryo of ten days, to which a right

THE OEGANS OF THE INNER GERM-LAYER.

327

duct is added in the course of another day. Also in the case of
human embryos 4 mm. long His demonstrated that at first there is
only a single hepatic duct, and that some time afterwards a second
appears (fig. 163 Lbg).

In the further course of development both the unpaired and the
paired hepatic fundaments are metamorphosed quite rapidly into
a tubular gland with numerous branches ; this acquires a special
character, differing from that of simple tubular glands, owing to
the fact that the tubes early become joined together to form a fine
network, since the primitive hepatic tubes send out numerous
lateral buds, which in some Vertebrates
(Amphibia, Selachii) are from the be-
ginning hollow, in others (Birds, Mam-
mals, Man) solid. Imbedded in the
embryonic connective substance of the
ventral mesogastrium, they grow out in
the former case into hollow tubes, in
the latter into solid cylinders. These
in turn are soon covered with corre-
sponding lateral processes, and so on.
Inasmuch as these grow toward one
another, and where they meet (fig. 187 Ic)
fuse, there arises a close network of
hollow glandular canals or solid hepatic
cylinders in the common connective-
tissue matrix.

Simultaneously with the epithelial
network there is formed in its meshes
a network of blood-vessels (g). From
the vena omphalomesenterica, which,

as previously stated, is embraced by the two hepatic tubes, there
grow out numerous shoots, and these by forming lateral branches
unite with one another in a manner corresponding to that of the
hepatic cylinders.

The liver of the Chick is found to be in this condition on the sixth
day. It has become even now a rather voluminous organ, and is
composed, as in the case of Mammals and Man, of two equally
large lobes, each of which has arisen from one of the two primitive
hepatic ducts by budding. The two lobes produce on the ventral
mesentery two ridges, one of which projects into the left body-cavity
and one into the right (fig. 184).

Fig. 186.— Diagrammatic view of the
alimentary canal of a Chick on
the fourth day, after GOETTE.

The heavy line indicates the inner
germ-layer, the shaded portion
surrounding it the splanchnic
portion of the mesoblast. Ig,
Lung ; St, stomach ; p, pancreas ;
I, liver.

328

EMBRYOLOGY.

A further increase in the size of the liver is due to the fact that
from the hepatic cylinders united into a network new lateral
branches grow forth and undergo anastomosis, whereby new meshes
are being continually formed.

Herewith the essential parts of the liver are present in the fun-
dament : (1) the secretory liver-cells and the bile-ducts, (2) the
peritoneal covering and the suspensory apparatus, both of which are

Pig. 187.— Section through the fundament of the liver of a Chick on «he sixth day of incubation.

Slightly enlarged.
Ic, Network of hepatic cylinders ; lcl, hepatic cylinder cut crosswise ; g, blood-vessels ; gw, wall

of the blood-vessel (endothelium) ; bl, blood-corpuscles ; bf, peritoneal covering of the liver.

derived from the ventral mesentery. The changes in these parts
which lead to the permanent condition are now to be considered.

The epithelium of the ducts and the secretory liver-parenchyma
are derived from the two hepatic tubes and from the network of
hepatic cylinders, — products of the entoblast.

The parts of the two primitive liver- tubes first formed become ih&
right and left ductus hepatici. In Birds and Mammals these open
at first, as we have seen, into the duodenum close together ; then at
their place of entrance there is formed a small evagination of the-

THE ORGANS OF THE INNER GERM-LAYER. 329

duodenum, which receives the two ductus hepatici. The evagination
gradually increases to a long single canal, the bile-duct or ductus
choledochus, the result of which process is that the whole liver is
farther removed from its source of origin.

By an evagination either of the ductus choledochus or of one of
the two ductus hepatici, the gall-bladder with its ductus cysticus is
established. In Man it arises from the ductus choledochus, and is
present as early as the second month.

The network of hepatic cylinders, which are sometimes hollow,
sometimes solid, is metamorphosed in two ways.

One part becomes the excretory ducts (the ductus biliferi). In
the cases in which the hepatic cylinders are at first solid, they begin
to become hollow and to arrange their cells into a cubical or cylin-
drical epithelium around the lumen. In this process some of the
branches of the network must degenerate. For, whereas all hepatic
cylinders at first communicate with one another by means of anas-
tomoses, this is, as KOLLIKER remarks, no longer the case in the
adult, except at the outlet of the liver (Leberpforte), where the
well-known network of bile -ducts exists.

The remaining part of the network furnishes the secretory paren-
chyma of liver-cells. The character of a netlike tubular gland,
which becomes so evident during development, is to be recognised
even in the fully developed organ in the case of the lower Verte-
brates, the Amphibia and Reptiles. The tubules of the gland,
which were from the beginning hollow, subsequently exhibit an
exceedingly narrow lumen, which is demonstrable only by means of
artificial injection, and which in cross section is surrounded by three
to five liver-cells. Through their manifold anastomoses they produce
an extraordinarily fine network, the small meshes of which are filled
up by a network of capillary blood-vessels, together with a very small
amount of connective substance.

In the higher Vertebrates (Birds, Mammals, Man) the tubular
structure of the gland subsequently becomes very inconspicuous and
the liver acquires a complicated structure, information concerning
the details of which is given in the text-books of histology.

There are three things which, from a developmental point of view, are not to
be lost sight of : first, the capillaries of the bile-duct have arisen by canalisa-
tion of the primitive hepatic cylinders ; secondly, they are bounded by only
two liver-cells, which are very large and flake-like ; thirdly, they send out
evaginations between and even into the liver-cells themselves. In this way a
greater complication is brought about in the arrangement of the fine biliary

330

EMBRYOLOGY.

Capillaries and the hepatic cells, to which there also corresponds a greater
complication in the distribution of the capillaries of the blood-vessels. By
means of all this the original tubular structure of the gland becomes almost
•entirely obliterated in the fully developed organ. In the adult, as is well
known, the parenchyma of the liver is divided by means of connective-tissue
partitions into small lobes (acini or lobuli). At the beginning of development
nothing is seen of the lobulated structure, because all the hepatic cylinders

are united into a network. Detailed in-
formation concerning the development of
the lobules is wanting.

Now a few words concerning the
ligaments and the conditions of form
and size which the liver presents up to
the time of birth.

The ligamentous apparatus, as was
remarked in the beginning, is preformed
in a ventral mesentery (the Yorleber).
Owing to the fact that the two hepatic
sacs grow out from the duodenum
into this ventral mesentery, and by
continual branching produce the right
and the left lobes of the liver (figs. 184,
185, and 188), the ventral mesentery
becomes divided into three portions :
first, a middle part, which furnishes
the peritoneal covering for both lobes
of the liver; secondly, a ligament which
proceeds from the front convex surface
of the liver in a sagittal direction to the
ventral wall of the body, extending as

Tig. 188. — Diagram to show the
original positions of the liver,
stomach, duodenum, pancreas,
and spleen, and the ligamentous
apparatus pertaining to them.
The organs are seen in longi-
tudinal section.

<J. Liver ; m, spleen ; p, pancreas ;
dd, small intestine ; dg, vitelline
duct ; bid, coecum ; md, rectum ;
kc, lesser curvature, gc, greater
curvature of the stomach; mes,
mesentery ; kn, lesser omentum
(lig. hepato-gastricum and hepato-
duodenale); Is, ligamentum sus-
pensorium hepatis.

far as the navel and embracing in its

free margin the subsequently disappearing umbilical vein (ligamentum
suspensorium and teres hepatis, figs. 184, 188 Is)', and thirdly, a liga-
ment which proceeds from the opposite, concave or portal surface of
the liver to the duodenum and the lesser curvature of the stomach,
and which contains the ductus choledochus and the afferent hepatic
blood-vessels (omentum minus, which is divided into the ligamentum
hepato-gastricum and hepato-duodenale). (Figs. 1 84 Ihd and 1 88 kn. )
The lesser omentum or omentum minus soon loses its original
sagittal position and is stretched out into a thin membrane running
from right to left (fig. 166 kn) ; this is due to the fact that the
stomach undergoes the previously described displacement, and moves

THE ORGANS OF THE INNER GERM-LAYER. 331

into the left half of the peritoneal cavity, whereas the liver grows out
into the right half more than into the left. In consequence of the
formation of the liver and the lesser omentum, the greater omentum,
produced by the torsion of the stomach, receives an addition, which
is designated as its antechamber (atrium bursse omentalis). For there
comes to be associated with the greater omentum that part of the
body-cavity which lies behind the liver and lesser omentum, and which
in the adult possesses, as is well known, only a narrow entrance (the
foramen of WINSLOW) lying below the ligamentum hepato-duodenale.

Concerning the development of the coronary ligament, see a subsequent part
which treats of the diaphragm.

As far as regards the conditions of form and size which the liver
presents up to the time of birth, there are two points which are
worthy of attention : first, the liver early acquires a very extra-
ordinary size ; secondly, its two lobes are developed at first quite
symmetrically. In the third month it nearly fills the whole body-
cavity ; its free sharp margin — on which a deep incision between the
two lobes is observable — reaches down almost to the inguinal region,
leaving here only a small space free, in which, upon opening the body-
cavity, loops of the small intestine are to be seen. It is a very vas-
cular organ, for a great part of the blood returning from the placenta
to the heart passes through it. At this time the secretion of bile
begins, although only to a slight extent. This increases in the second
half of pregnancy. In consequence of this the intestine gradually
becomes filled with a brownish-black mass, the meconium. This is
a mixture of bile with mucus and detached epithelial cells of
intestine, to which is added amniotic water with flakes of epidermis
and hairs that have been swallowed. After birth the meconium is
accumulated in the large intestine, from which it is soon afterwards
eliminated.

In the second half of pregnancy the growth of the two lobes of
the liver becomes unequal, and the left is surpassed more and more in
size by the right. Before birth the lower margin of the liver projects
downward for some distance beyond the costal cartilages, almost to
the umbilicus. After birth it diminishes rapidly in size and weight,
in consequence of the change in the circulation produced by the pro-
cess of respiration. For the stream of blood which during embryonic
life has branched off from the umbilical vein into the liver now ceases.
During the growth of the body the liver also increases in size still
further, but less than the body taken as a whole, so that its relative
weight is constai tly undergoing reduction.

332 EMBRYOLOGY.

(2) The Pancreas. •

The pancreas is developed in all Vertebrates — with the exception
of a few in which it is wanting (Bony Fishes) — as an evagination on
the dorsal side of the duodenum, usually opposite to the origin of the-
liver (figs. 162, 163, 186 p). In the Chick (fig. 186) the first funda-
ment is distinguishable as early as the fourth day ; in Man it appears
somewhat later than the primitive hepatic tube, and has been de-
monstrated by His in embryos 8 mm. long as a small evagination
(figs. 162 and 163). The sac, usually hollow, grows into the dorsal
mesentery (figs. 184, 188 p) by giving off hollow, branching, lateral
outgrowths.

In the case of Man the pancreas is present as early as the sixth,
week in the form of an elongated gland (fig. 164 p), the free end of
which has penetrated upward [cephalad] into the mesogastrium,
and thus, midway between the greater curvature of the stomach and
the vertebral column, it can move freely. It is therefore com-
pelled to share in the alteration of position which the stomach to-
gether with its mesentery undergoes. In embryos of the sixth week
its long axis still corresponds approximately with the longitudinal
axis of the body. The free end then moves into the left half of
the body-cavity, the whole organ being turned (fig. 166) until finally
its long axis comes to lie in the transverse axis of the body, as in the
adult. In this position its head is imbedded in the horseshoe -shaped
curvature of the duodenum, whereas its tail reaches to the spleen and
left kidney.

Inasmuch as the pancreas in its development has grown into the
mesogastrium (figs. 164, 166, 188), it possesses in the first half
of embryonic life, as TOLDT has shown, a mesentery, on which it
accomplishes the turning previously described. But at the fifth,
month this disappears. (Compare the diagrams fig. 167 A and Bp.)
For as soon as the gland has taken its transverse position, it at-
taches itself firmly to the posterior wall of the trunk and soon loses its
freedom of motion, because its peritoneal covering and its mesentery
become fused with the adjacent parts of the peritoneum (fig. 167
B gn4). In this manner the pancreas of Man, which was developed,
like the liver, as an intraperitoneal organ, has become a so-called
extraperitoneal organ, owing to a process of fusion between the
serous surfaces that come in contact with each other. By means of
this also the attachment of the mesogastrium is displaced from the-
vertebral column farther to the left.

THE ORGANS OF THE INNER GERM-LAYER. 333

It still remains to be mentioned, in regard to the outlet of the
pancreas, that during development it is continually moving nearer
to the ductus choledochus, and that finally it opens in common with
the latter into the duodenum at the diverticulum of VATER.

SUMMARY.
A. Orifices of the Alimentary Canal.

1. The original orifice of the alimentary canal (resulting from the
invagination of the inner germ-layer), the primitive mouth (blasto-
pore), becomes closed later, owing to the circumcrescence of the
medullary ridges, and furnishes temporarily an open communica-
tion with the neural tube, the canalis neurentericus.
>J 2. The neurenteric canal likewise disappears subsequently by the
fusion of its walls.

3. The alimentary tube acquires new openings to the outside
(visceral clefts, mouth, anus) by the fusion of its walls with the
body-wall at certain places, and by the regions of fusion then
becoming thinner and rupturing.

4. The visceral clefts arise on both sides of the future neck-region
of the body, usually five or six pairs in the lower Vertebrates, four
pairs in Birds, Mammals, and Man. (Formation of outer and inner
throat-furrows ; breaking through of the closing plate.)

5. In water-inhabiting Vertebrates the visceral clefts serve for
branchial respiration (development of branchial lamellsa by the for-
mation of folds of the mucous membrane) ; in Reptiles, Birds, and
Mammals they become closed and disappear, with the exception of
the upper part of the first fissure, which is employed in the develop-
ment of the organ of hearing (external ear, tympanum, Eustachian
tube).

6. The mouth is developed at the head-end of the embryo by an
unpaired invagination of the epidermis, which, as oral sinus, grows
toward the blindly ending fore gut, and by the breaking through of
the primitive pharyngeal membrane. (Primitive palatal velum.)

7. The anus arises, in a manner similar to that of the mouth, on
the ventral side at some distance in front of the posterior end of the
body, so that the intestinal tube is continued for a certain distance
beyond the anus toward the tail.

8. The post- anal or caudal intestine, which at first stretches from
the anus to the posterior end of the body (tail-part of the body),
becomes rudimentary afterwards and wholly disappears, so that the

334 EMBRYOLOGY.

anus then marks the termination, as the mouth does the beginning,,
of the alimentary canal.

B. Separation of the Alimentary Tube and its Mesentery into
Distinct Regions.

1. The alimentary canal is originally a tube running straight front
mouth to anus, near the middle of which the yolk-sac (umbilical
vesicle) is attached by means of the vitelline duct (stalk of the
intestine).

2. The alimentary tube is attached throughout its whole length to-
the vertebral column by means of a narrow dorsal mesentery ; it is
also connected with the anterior wall of the trunk, as far back as the
umbilicus, by means of a ventral mesentery (mesocardium anterius
and posterius, anterior [ventral] gastric and duodenal mesentery).
(Yorleber.)

3. At some distance behind the visceral clefts, the stomach arises-
as a spindle-shaped enlargement of the alimentary tube ; its dorsal
mesentery is designated as mesogastrium.

4. The portion which follows the stomach grows more rapidly in
length than the trunk, and therefore forms in the body-cavity a
loop with an upper [anterior], descending narrower arm, which be-
comes the small intestine, and a lower [posterior], ascending more
capacious arm, which produces the large intestine.

5. The stomach takes on the form of a sac, and becomes so turned
that its long axis coincides with the transverse axis of the body, and
that the line of attachment of the mesogastrium, or its greater
curvature, which was at first dorsal, comes to lie below, cr caudad.

6. The intestinal loop undergoes such a twisting that its lower,,
ascending arm (large intestine) is laid over [ventral to] the upper,
descending arm (small intestine) from right to left, and crosses
it near its origin from the st.omach.

7. The twisting of the intestinal loop explains why in the-
adult the duodenum, as it merges into the jejunum, passes under
the transverse colon and through its mesocolon. (Crossing and
crossed parts of the intestine.)

8. The lower arm of the loop, during and after its twisting and
crossing of the upper arm, assumes the form of a horseshoe and.
permits one to distinguish the coacum, the colon ascendens, c. trans-
versum, and c. descendens.

9. Within the space bounded by the horseshoe, the upper arm.

THE ORGANS OF THE INNER GERM-LAYER. 335

of the loop becomes folded to form the convolutions of the small
intestine.

10. The mesentery, which is at first uniform and common to the-
whole alimentary tube, becomes differentiated into separate regions,
for it adapts itself to the folds and to the elongations of the ali-
mentary tube. It is elongated and here and there undergoes fusion
with the peritoneum of the body-cavity, by means of which it either
acquires new points of attachment or in certain tracts wholly
disappears ; some portions of the intestine are thus deprived of their
mesentery.

11. The mesentery of the duodenum, and in part also that of the
colon ascendens and c. descendens, fuses with the wall of the body
(extraperitoneal parts of the intestine).

12. The mesentery of the colon transversum acquires a new line of
attachment running from right to left, and becomes differentiated
from the common mesentery as mesocolon.

13. The mesogastrium of the stomach follows the torsions of the
latter and is converted into the greater omentum, which grows out
from the greater curvature of the stomach to cover over all the:
viscera lying below.

14. Fusions of the walls of the omentum with adjacent serous
membranes take place : (1) on the posterior wall of the body, in
consequence of which the line of origin from the vertebral column is
displaced to the left side of the body ; (2) with the mesocolon and
colon transversum ; (3) on the part of the sac which has overgrown
the intestines, where its anterior and posterior walls come into close
contact and fuse into an omental plate.

C. Development of /Special Organs out of the Walls of the
Alimentary Tube.

1. The surface of the alimentary tube increases in extent inward
by means of folds and villi, and by glandular evaginations outward.

2. There are developed, as organs of the oral cavity, the tongue,
the salivary glands, and the teeth.

3. The teeth, which in the higher Vertebrates are found only at
the entrance of the mouth, are distributed in the lower Vertebrates
(Selachians, etc.) over the whole of the cavity of the mouth and
throat, and indeed as dermal teeth over the whole surface of the
body.

4. The dermal teeth are dermal papillae ossified in a peculiar

336 EMBRYOLOGY.

manner, in the development of which both the superficial layer of
the corium and also the deepest cell-layer of the epidermis investing
the latter are concerned.

(a) The corium [dermis] produces the abundantly cellular dental

papilla, which secretes the dentine at its surface, where
a layer of odontoblasts is formed.

(b) The epidermis furnishes a layer of tall cylindrical cells, the

enamel-membrane, which covers the dentine-cap with a
thin layer of enamel.

(c) The base of the dentine-cap acquires a better attachment

in the dermis from the fact that the latter becomes ossi-
fied in its vicinity and furnishes the cementum.

5. At the margins of the jaws the tooth-forming tract of the
mucous membrane sinks down into the underlying tissue ; there is
first developed by a proliferation on the part of the epithelium a
dental ridge, on which the teeth of the jaws arise in the same way
that the dermal teeth do on the surface of the body.

6. The development of a tooth takes place on the ridge in the
following way : the epithelium grows more rapidly at one point, and
a papilla of the connective-tissue part of the mucous membrane
.grows into this proliferated part or enamel-organ. The dental
papilla forms the dentine, but the enamel-organ, developing an
enamel-membrane, secretes the enamel ; finally, the connective-tissue
•dental sac becomes ossified and furnishes the cementum.

7. Beneath the milk-teeth there are early formed in Mammals,
and Man, at the deep edge of the dental ridge, the fundaments of
•supplementary teeth.

8. From the throat-region of the intestine there are developed
thymus, thyroid gland, accessory thyroid gland, and lungs.

9. The thymus arises by the thickening and peculiar metamorphosis
of the epithelium of several pairs (Selachii, Teleostei, Amphibia,
Reptilia), or of only one pair, of visceral clefts.

(a) In Selachians and Teleosts there is a proliferation of

epithelium at the dorsal ends of all the visceral clefts,
which are penetrated by growths of connective tissue and
blood-vessels.

(b) In Mammals and Man there is formed from the third

pair of visceral clefts a pair of epithelial thymus-sacs,
which send out lateral buds and become peculiarly
altered histologically.

(c) In Man the two thymus-sacs are joined in the median

THE ORGANS OF THE INNER GERM-LAYER. 337

plane to an unpaired body, which begins to degenerate
in the first years after birth.

10. The thyroid gland is an unpaired organ, which arises in the
region of the body of the hyoid bone from either a hollow or a solid
outgrowth of the epithelium in the floor of the pharyngeal cavity.

(a) The epithelial rod detaches itself from its parental tissue

and forms lateral rods.

(b) At a later stage these epithelial cords become separated

into small epithelial spheres, which secrete in their
interiors colloid substance and are converted into
wholly closed glandular sacs enveloped in highly vascular
capsules of connective tissue.

11. The accessory thyroid glands are paired and arise from evagi-
nations of the epithelium of the last pair of visceral clefts, which
undergo metamorphoses similar to those of the unpaired thyroid
gland.

12. The accessory thyroid glands in most Vertebrates remain
separated from the unpaired thyroid gland by a greater (Reptiles)
or less (Birds) space, whereas in Mammals they appear to fuse with
it to form a single body.

13. The lung is developed out of the floor of the alimentary canat
in the throat-region, behind the fundament of the unpaired thyroid
gland.

(a) A groove-like evagination, which is constricted off from the

alimentary canal as far forward as its anterior end, —
the entrance to the larynx, — becomes larynx and wind-
pipe.

(b) From the posterior end of the groove there grow out two

sacs, which acquire at their ends vesicular enlargements
and constitute the fundaments of the right and left
bronchus, together with the corresponding lung.

(c) The want of symmetry between the right and left lung

is early exhibited, since the right sac provides itself
with three vesicular lateral buds, the fundaments of the
three lobes, whereas the left sac forms only two buds.

(d) The further development of the lungs allows one to dis-

tinguish two stages, of which the first exhibits a great
similarity to the development of an acinous gland. In
the first stages the primitive pulmonary sacs increase in
number by constrictions and at the same time become
differentiated into a narrower conducting part, the

338 EMBRYOLOGY.

bronchial tubes, and a broader vesicular terminal part.
In the second stage the air-cells or pulmonary alveoli
are formed.

14. From the intestinal canal proper there are formed only two
glands, which are large and developed from the duodenum — the
liver and the pancreas.

15. The liver is developed as a branched tubular gland which
becomes a network.

(a) There grow out from the duodenum into the ventral

mesentery or prehepaticus (Vorleber) two liver-tubes,
the fundaments of the left and right lobes of the liver.

(b) The tubes form hollow or solid lateral branches, the

hepatic cylinders, which are united into a network and
become in part bile-ducts, in part the secretory paren-
chyma of the liver and biliary capillaries.

(c) The ductus choledochus arises as an evagination of the

wall of the duodenum which receives the two hepatic
tubes, and it forms at one place an evagination which
becomes the gall-bladder arid the cystic duct. .

16. From the ventral mesentery, into which the hepatic tubes
grow, are derived the serous investment and a part of the ligamentous
apparatus of the liver, namely, the lesser omentum (ligamentum
hepato-gastricum and hepato-duodenale) and the ligamentum sus-
pensorium hepatis.

17. The pancreas grows from the duodenum into the dorsal
mesentery and into the mesogastrium.

18. The mesentery which the pancreas originally possesses subse-
quently disappears by becoming fused with the posterior wall of the
trunk ; at the same time, in consequence of the twisting of the
stomach, the long axis of the pancreatic gland comes to lie in
the transverse axis of the body.

LITERATURE.

Afanassiew. Weitere Untersuchungen iiber den Bau und die Entwickelung

der Thymus und der "VVinterschlaf druse der Saugethiere. Archiv f. mikr.

Anat. Bd. XIV. 1877.
TJemmelen, van. Die Visceraltaschen und Aortenbogen bei Eeptilien und

Vogeln. Zool. Anzeiger, Nr. 231, 232, 1886, pp. 528, 543.
Bemmelen, van. Ueber die Suprapericardialkb'rper. Anat. Anzeiger, Jahrg.

IV. 1889, Nr. 13.
Bemmelen, van. Die Halsgegend der Reptilien. Zool. Anzeiger, Jahrg. X.

Nr. 244, 1887, p. 88.

LITERATURE. 339

Bonnet. Ueber die Entwicklung der Allantois und die Bildung des Afters

bei den Wiederkauern und iiber die Bedeutung der Primitivrinne und des

Priraitivstreifs bei den Embryonen der Saugethiere. Anat. Anzeiger. 1 888.
Born, G. Ueber die Derivate der embryonalen Schlundbogen und Schlund-
spalten bei Saugethieren. Archiv f. mikr. Anat. Bd. XXII. 1883, p. 271.
Braun. Entwicklungsvorgange am Schwanzende bei Saugethieren. Archiv

f. Anat. u. Physiol. 1882. Anat. Abth. p. 207.
Chievitz, J. C. Beitrage zur Entwicklungsgeschichte der Speicheldriisen.

Archiv f. Anat. u. Physiol. Anat. Abth. 1885.
Dohrn. Studien zur Urgeschichte des Wirbelthierkorpers. Die Thyreoidea

bei Petromyzon, Amphioxus und Tunicaten. Mittheil. a. d. zool. Station

Neapel. Bd. VI. 1886.

Dohrn. Studien zur Urgeschichte des Wirbelthierkorpers. Nr. 12. Thyre-
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Bd. VII. 1887.
Dubois. Zur Morphologic des Larynx. Anat. Anzeiger, Jahrg. I. Nr. 7 u. 9.

1886.
Fischelis. Beitrage zur Kenntniss der Entwicklungsgeschichte der Gl.

thyreoidea u. Gl. thymus. Archiv f. mikr. Anat. Bd. XXV. 1885,

p. 405.
Pol. Ueber die Schleimdriise oder den Endostyl der Tunicaten. Morphol.

Jahrb. Bd. I. 1875.
Gasser. Die Entstehung der Cloakenoffnung bei Hiihnerembryonen. Archiv

f. Anat. u. Entwicklungsg. Jahrg. 1880.
Giacomini. Sul canale neurenterico e sul canale anale nelle vesicola blasto-

dermiche di coniglio. Torino 1888.
Gotte. Beitrage zur Entwicklungsgeschichte des Darmcanals im Hiihnchen.

Tubingen 1867.
Hannover. Ueber die Entwicklung und den Bau des Saugethierzahns. Nova

Acta Acad. Caes. Leop. Natur. curiosorum. Breslau und Bonn. 1856.

Bd. XXV. Abth. 2.
Hertwig, Oscar. Ueber Bau und Entwicklung der Placoidschuppen und

der Zahne der Selachier. Jena. Zeitschr. Bd. VIII. 1874.
Hertwig, Oscar. Ueber das Zahnsystem der Amphibien und seine Bedeu-

tung fur die Genese des Skelets der Mundhohle. Archiv f. mikr. Anat.

Bd. XI. Supplement. 1874.
His, Wilhelm. Mittheilungen zur Embryologie der Saugethiere u. des

Menschen. Archiv f. Anat. u. Physiol. Anat. Abth. 1881.
His, Wilhelm. Ueber den Sinus praecervicalis und iiber die Thymusanlage.

Archiv f. Anat. u. Physiol. Anat. Abth. 1886.
His, Wilhelm. Zur Bildungsgeschichte der Lungen beim menschlichen

Embryo. Archiv f. Anat. u. Physiol. Anat. Abth. 1887.
His, Wilhelm. Schlundspalten u. Thymusanlagen. Archiv f. Anat. u.

Physiol. Anat. Abth. 1889.
Kadyi, H. Ueber accessorische Schilddrusenlappchen in der Zungenbeinge-

gend. (Gland, praehyoides et suprahyoides.) Archiv f. Anat. u. Physiol.

Anat. Abth. 1879.

JKastschenko. Das Schicksal der embryonalen Schlundspalten bei Sauge-
thieren. Archiv f. mikr. Anat. Bd. XXX. 1887, pp. 1-26.
Kastschenko.Das Schlundspaltengebiet des Hiihnchens. Archiv f . Anat. u.

Physiol. Anat. Abth. 1887.

340 EMBRYOLOGY.

Keibel. Die Entwicklungsvorgange am hinteren Ende des Meerschweinchen*

embryos. Archiv f. Anat. u. Physiol. Anat. Abth. 1888.
K511iker. Die Entwicklung des Zahnsackchens der Wiederkauer. Zeitschr.

f. wiss. Zoologie. Bd. XII. 1863.
Kollmann, J. Entwicklung der Milch- u. Ersatzzahne beim Menschen.

Zeitschr. f . wiss. Zoologie. Bd. XX. 1870.
Kupffer, C. Ueber den Canalis neurentericus der Wirbelthiere. Sitzungsb.

d. Gesellsch. f. Morphol. u. Physiol. Munchen. 1887.
Liessner. Ein Beitrag zur Kenntniss der Kiemenspalten und ihrer Anlagen

bei amnioten Wirbelthieren. Morphol. Jahrb. Bd. XIII. 1888, p. 402.
Mall, F. The Branchial Clefts of the Dog, with Special Reference to the

Origin of the Thymus Gland. Studies Biol. Lab. Johns Hopkins Uni-
versity. Vol. IV. 1888, p. 185.
Mall, P. Entwicklung der Branchialbogen u. Spalten des Huhnchens. Archiv

f. Anat. u. Physiol. Anat. Abth. 1887.
Maurer. Schilddrtise und Thymus der Teleostier. Morphol. Jahrb. Bd. XI.

1886, p. 129.
Merten. Historisches Uber die Entdeckung der Glandula suprahyoidea.

Archiv f. Anat. u. Physiol. Anat. Abth. 1879.
Meuron, Pierre de. Kecherches sur le developpement du Thymus et de la

Glande Thyroide. Dissertation. Geneve. 1886.
Miiller, Johannes. Ueber den Ursprung der Netze und ihr Verhaltniss zum

Peritonealsacke beim Menschen, aus anatomischen Untersuchungen an

Embryonen. Archiv f. Anat. u. Physiol. 1830.
Miiller, W. Ueber die Entwicklung der Schilddriise. Jena. Zeitschr.

Bd. VI. 1871.

Miiller, W. DieHypobranchialrinnederTunicaten. Jena.Zeits. Bd.VII. 1872.
Ostroumoff. Ueber den Blastoporus u. den Schwanzdarm bei Eidechsen u.

Selachiern. Zool. Anzeiger. 1889, p. 364.
Owen, R. Odontography. London 1840-45.
Perenyi. Blastoporus bei den Froscheu. Berichte d. Akad. d. Wissensch.

zu Budapest. Bd. V. pp. 254-8.
Piersol. Ueber die Entwicklung der embryonalen Schlundspalten u. ihrer

Derivate. Zeitschr. f. wiss. Zoologie. Bd. XLVII. 1888.
Rabl, Karl. Ueber das Gebiet des Nervus facialis. Anat. Anzeiger. Jahrg

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B-abl, Karl. Zur Bildungsgeschichte des Halses. Pniger medicin. Wochen-

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THE ORGANS OF THE MIDDLE GERM-LAYER. 341

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Berlin 1880.
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HUhnchcn. Uebersetzt von Fr. Meckel. Halle 1812.

CHAPTER XV.
THE ORGANS OF THE MIDDLE GERM-LATER.

VOLUNTARY MUSCULATURE, URINARY AND SEXUAL ORGANS.

Lr >y^

THE organs which take their origin from the middle germ-layer

stand in the closest genetic relation to the morphological products of
the entoblast. For, as was stated in the first part of this work, the
middle germ-layer is developed by a process of evagination from the
inner germ-layer, and is therefore, like the latter, an epithelial mem-
brane, which serves as the boundary of a cavity. In view of its
origin, is it remarkable that the organs arising from it are of a
glandular nature, and such as produce excretions by means of genuine
epithelial glandular colls 1

In earlier times this phenomenon was the cause of a good deal

342 EMBRYOLOGY.

of difficulty, because since the time of REMAK there hac3 been an
endeavor to bring the middle germ-layer as a non-epithelial structure
into contrast with the other germ-layers. Attempts were also made
to explain this supposed contradiction by assuming that the glandular
organs in question were derived, sometimes in one way, sometimes in
another, from the outer germ-layer. With the acceptance of the
coelom- theory, however, the theoretical objections to the production
of glands by the middle germ-layer have caased to have any
foundation.

Out of the middle germ-layer, or, otherwise expressed, out of the
epithelial wall of the embryonic body-sacs, are developed — aside from
the mesenchyme, concerning the source of which an extended account
was given in the ninth chapter — three very different products : first
the whole voluntary musculature, secondly the urinary and sexual
organs, thirdly the epithelial or endothelial linings of the large
eerous cavities of the body.

I. The Development of the Voluntary Musculature.

The total, transversely striped, voluntary musculature, aside from
a part of the muscles of the head, arises from those parts of the
middle germ-layer which have been differentiated as primitive
segments, and with their appearance have effected the first primitive
and most important segmentation of the vertebrate body. As has
been previously stated, the segmentation affects the head as well as
the trunk, so that trunk-segments and head-segments must be dis-
tinguished. Since the latter are in many points distinguished in
their origin and metamorphosis from the former, a separate descrip-
tion of the two is fitting. I begin with the history of the metamor-
phosis of the primitive segments of the trunk, and treat of the same
first in Amphioxus and the Cyclostomes, which furnish the simplest
and most easily interpreted conditions, and then in the Amphibia,
and finally in the higher Vertebrates.

A. Primitive /Segments of the Trunk.

In Amphioxus the primitive segments (fig. 103 ush} are sacs, which
are provided with a large cavity, and the walls of which are composed
of a single layer of epithelial cells. The latter are further developed
in two ways, for an accurate knowledge of which we are indebted to
HATSCHEK. Only the cells (fig. 189) which abut upon the chorda (ch)
and the neural tube (n) are destined to form muscle-fibres ; they

THE ORGANS OF THE MIDDLE GERM-LAYER 343

increase considerably in size, project far into the cavity of the
primitive segment, and assume the form of plates ; these lie parallel
to one another and to the longitudinal axis of the body ; and one
margin, which I shall designate as the base, is placed perpendicularly
upon the surface of the chorda. Very early (in the stage with ten
primitive segments) the cell-plates begin at their bases to be differ-
entiated into transversely striped muscle-fibrillae, with which the
embryos are already able to execute feeble contractions. By the
continual addition of new fibrillse to those which are formed at the
surface of the chorda, and by an extension of the differentiation to
both the surfaces of the cell-plates
which are in contact with ea^h other,
there arise the transversely striped
muscle-layers (Muskelblatter) which
are characteristic of the musculature
of Amphioxus. These are attached
to the chorda on the right and left
like the leaves of a book. The more **
the fibrillse increase in number, the
more the protoplasm of the forma- Fig. i89._cross section through the
tive cells between them diminishes in middle of the body of an Am'

phioxus embryo with 11 primitive
amount and the more is the nucleus segments, after HATSCHEK.

With a remnant of protoplasm forced ak> ik . Outer.'inner germ-layer ;«*'

r r m ink", parietal, visceral lamella of

toward that edge of the Cell which the middle germ-layer ; us, primi-

faces the cavity of the primitive. £•.— •, LEX7£

Segment. intestinal cavity.

The remaining cells of the primitive

segment are converted into a low pavement-epithelium, which neither
now nor later takes part in the formation of muscles. (Cutis-layer
of HATSCHEK.)

Having arisen in the vicinity of the chorda, the muscle-layer in
older animals spreads out both dorsal ly and vent rally, and thus
furnishes the total voluminous musculature of the trunk, which, like
the cellular primitive segments from which it is derived, is separated
into successive portions (the myomeres).

In general the Cyclostomes (fig. 190) agree in the development of
their muscles with Amphioxus. Here, as there, one must distinguish
between an inner muscle-forming epithelial layer (mf), which bounds
the chorda (Cti) and the neural tube (^V), and an outer indifferent
epithelial layer (ae), which occupies the side toward the epidermis.
The latter (ae) consists of low flat cells, the former of very broad and

344

EMBRYOLOGY.

elongated plates (mfc), which as in Amphioxus are arranged perpen-
dicularly to the surface of the chorda and neural tube. Since in
Petromyzon the primitive segments are destitute of cavities, the two
epithelial layers lie immediately in contact, and are continuous with
each other, both dorsally and ventrally, by means of transitional
cells (WZ), in the same way that in the fundament of the lens its
epithelium is continuous with the lens-fibres. Muscle-fibrillse (nif)
are now differentiated on both the broad surfaces of the cell-plates.

Thus arise muscle-layers (Mus-
kelblatter) which are perpen-
dicular to the chorda. These
layers are each composed of
two sheets of the finest fibrillee,
running parallel to one an-
other. The two sheets are
separated from each other by
a delicate film of cementing
substance ; one of them owes its
existence to one formative cell,
the other to an adjacent cell.
In older larvae the primi-
tive segments spread out both
above and below ; accom-
panying this process there is
a continual formation of new
muscle-layers from the pre-
viously mentioned cells ( WZ).
The upper and lower margins
of the primitive segments
therefore constitute a zone
of proliferation, by means of
which the musculature of the
trunk is continually growing further dorsad arid ventrad.

At a later stage of development, in larvse six weeks old (fig. 191),
the muscle-layers are converted into Muskelkastchen (k), as SCHNEIDER
has named these peculiar definite structural elements of the Cyclo-
stomes. The facing fibrillae-sheets of two adjacent layers (Blatter)
unite with each other along their margins. Since these sheets have
been produced on the two sides of one cell-plate, each formative cell
is now surrounded on all sides, as though with a mantle, by the
fibrillse which it has generated.

Ch

Fig. 190. — Gross section through the trunk-muscu-
lature of a larva of Petromyzon Planeri 14
days old. Magnified 500 diameters.

N and. Ch, the part of the cross section which is
adjacent to the neural tube and the chorda ;
chs, skeletogenous sheath of the chorda; ep,
epidermis ; ae, outer epithelial layer of the
primitive segment ; mk, nuclei of muscle-cells ;
mf, muscle-fibrillse in cross section ; WZ, zone
of growth— transition from the outer cell-layer
to the muscle-forming layer of the primitive
segment.

THE ORGANS OF THE MIDDLE GERM-LAYER. 345

Finally, three alterations of the Muskelkastchen take place. The
homogeneous cementing substance, which was indicated during the
first stage by only a fine line between the two fibrillse-sheets of
a muscle-layer, increases and produces the partition by means of
which the individual Muskelkastchen are separated from each other,
and in which afterwards connective-tissue cells and blood-vessels are
also to be found. Secondly, the protoplasmic matrix of the formative
cells is almost completely consumed in the continued production of
numerous fine fibrillse, which finally fill the whole interior of the Kast-
chen. One can now distinguish two different kinds of fibrillae— those
that are centrally located, and those that are firmlyiattached to the
partitions. Thirdly, there are to be found scattered between the
fibrillse numerous small nuclei, which pro-
bably are descended from the original
single nucleus of the formative cell by
frequently repeated division.

The development of the muscle -seg-
ments takes place in the remaining Ver-
tebrates in a somewhat different manner
from that of Amphioxus and the Cyclo-
stomes. For the study of this process Fi*« w-o™* *ection

the trunk-musculature of a

the tailed Amphibia furnish the most larva of Petromyzon Pianerf

instructive objects. In Triton (figs. 106, * wee*8 old' Masnified 50°

0 \ c diameters.

105 USk) each of the primitive Segments k, Muskelkastchen; mk, nuclei

contains a considerable cavity, which is f^Z^±^ "^

bounded on all sides by large cylindrical

epithelial cells. In somewhat older embryos active cell-multiplication
takes place in the part of the epithelium which is adjacent to the
chorda and neural tube, and which, therefore, corresponds to the
previously described muscle-forming layer of Amphioxus and the
Cyclostomes. By this growth the cavity of a primitive segment
becomes entirely filled. At the same time the cells lose their original
arrangement and form ; they are converted into longitudinally ar-
ranged cylinders, which correspond in length to a primitive segment
and are located by the side of and above one another on both sides of,
and parallel to, the spinal cord and chorda dorsalis (fig. 192). ffach_
cylinder, which in the beginning exhibits only a single nucleus (mk),
becomes surrounded with a mantle of the finest transversely striped
fibrillse (mf) • it is now comparable with a Muskelkastchen of the
Cyclostomes (fig. 191). A series of further alterations also takes
place in this instance as in the former. In older larves there are

346 EMBRYOLOGY.

continually being formed more fibrillse (fig. 193), which gradually fill
the interior portion of the cylinder. Only in the axis of the latter
are there places left free, in which the small nuclei (ink) come to lie ;
these, formed by division of the single mother-nucleus, increase
considerably in number. Moreover, connective tissue with blood-
vessels now penetrates between the muscle-fibres or the primitive
bundles (pb), as the finished elements are subsequently called.

If we consider from a general point of view the facts here presented,
— which have been acquired in the study of the lower Vertebrates, —

Fig. 193.
Fig. 192.— Cross section through the musculature of the trunk of a larva of Triton tseniatus

5 days old. Magnified 500 diameters.
ink, Nuclei of muscle-cells ; mf, muscle-fibrillse cut crosswise ; dk, yolk -granules.

Fig. 193.— Cross section through the musculature of the trunk of a larva of Triton tseniatus
10 days old. Magnified 500 diameters.

pb, Primitive bundle of muscle-fibrillse (Musktlprimitivburidel) ; mf, muscle-fibrillse cut cross-
wise ; mk, nuclei of muscle cells.

we arrive at two propositions of importance concerning the origin of
the musculature : —

(1) In Vertebrates the elements of the musculature of the trunk are
developed out of epithelial cells which are derived from a circumscribed
ten*ritory of the epithelium of the body-cavity, — a territory that is con-
stricted off from the latter to form the primitive segments.

(2) The epithelial products become surrounded and enveloped on all
sides by connective tissue, just as do the glands and gland-ducts that
bud forth from an epithelium.

A comparison with the condition and development of the musculature of some
classes of Invertebrates leads to a still better comprehension of the above
propositions. In most of the Ccelenterates the muscular elements are components
of the epithelium, not only during their development, but also in the adult
animal, so that the designation epithelio-muscular cells is suitable for them.

THE ORGANS OF THE MIDDLE GERM-LAYER. 34:7

The characteristic feature of these consists in their being simple — sometimes
cubical, sometimes cylindrical, sometimes thread-like — epithelial cells, the
outer ends of which ordinarily reach the surface of the epithelium and are
here provided with cilia, whereas their basal ends lie upon the sustentative
lamella (Stutzlamelle) of the body and are there differentiated into one or
several either smooth or transversely striped muscle-fibrillae. Inasmuch as the
fibrillaB of numerous cells lie parallel and close to one another, muscle-lamella?
arise, by the activity of which the changes in the form of the body are
produced. In Ccelenterates both the outer and the inner germ-layers can
develop muscle-cells.

When one turns to the Vermes it is seen, in those groups in which a body-
cavity (an enteroccel) is formed by an infolding of the inner germ-layer, that
the parietal wall of the body-cavity, or the parietal lamella of the middle
germ-layer, has assumed the production of the entire musculature of the
trunk. Here also, for example in the Chsetognatha, etc., the epithelial cells
differentiate at their basal ends, which are directed toward the surface of
the body, a lamella of muscle-fibrillae, whereas their other ends bound the
body-cavity. Thus from tJie lower to the higher animals the capability of
2)roducing muscles is, with the progressive differentiation of the body, more and
more restricted to a limited special territory of the total epithelial investment
of the body.

This process has proceeded furthest in the Vertebrates, for in them the
musculature of the trunk is no longer furnished by the whole parietal lamella
of the middle germ-layer, but by only a small detached part of it, the primitive
segments. Consequently in Vertebrates the musculature spreads out from a
;>mall region where it originates, distributes itself first in the trunk, and then
from the latter grows out into the extremities.

In the Vertebrates we recognised two different forms of voluntary musculature,,
the muscle-layer (and the Muskelkiistchen derivable from it) and the primitive
bundle (Muskelprimitivbundel). Parallels to this are found in the Inverte-
brates, both in Coelenterates and in Worms. In Ccelenterates both forms are
derived from the primitive smoothly outspread muscle-lamella by the forma-
tion of folds, and are to be explained in the same way as the formation of those
folds which in epithelial lamella? play such an important part in the origin of
the most various organs. When certain tracts of a muscle-lamella are called
upon to execute additional labor, this can be effected only by an increase
in the number of the fibrillse lying parallel to one another. But a greater
number of fibrillas can be brought into a circumscribed territory only in one or
the other of two ways : either by their coming to lie in several layers one above
another, or — if the more simple arrangement of lying side by side is to be
retained— by the folding of the muscle-lamella. The folding exhibits two-
modifications. Sometimes there are produced parallel daughter-! amellas placed
side by side and perpendicular to the mother-lamellas ; sometimes the folded
lamella? become wholly detached from the parent-layer and converted into
muscle -cylinders, which imbed themselves in the underlying sustentative
lamella.

With the conception here presented of the origin of the transversely striped
muscle-fibres of Vertebrates, it must be assumed as very probable that
subsequently an increase in their number will take place as a result of
constriction and detachment into two parts, as was first maintained by
WEISMANN.

348

EMBRYOLOGY.

In Amphioxus, the Cyclostomes, and the Amphibia the most
important function of the primitive segments is the production of the
fundament of the transversely striped and voluntary musculature.
On the other hand it is not very evident that the primitive segments
also share, in the manner previously (p. 172) described, in the deve-
lopment of the mesenchyme;
this is correlated with the fact
that in general the connective
and sustentative substances
play a slight role in the con-
struction of the bodies of the
lower Vertebrates, and es-
pecially during larval life are
developed to only a very insig-
nificant amount.

This is altered in the Sela-
chians and the three higher
classes of Vertebrates. Not
only does the mesenchyme
in the adult bodies of these
attain a more voluminous
development and a degree of
differentiation that is in
all directions more advanced,
but it is also established
earlier and likewise in greater
abundance. Therefore the
primitive segments here ex-
hibit in their metamorphosis
somewhat modified pheno-
mena. At the same time
with the differentiation of

Pig. 194.- Cross section through the region of the
pronephros of a Selachian embryo, in which
the muscle-segments [myotomes] (mp) are in
process of being constricted off. Diagram
after WIJHE.

nr, Neural tube ; ch, chorda ; ao, aorta ; sch, sub-
notochordal rod ; mp, muscle-plate of the
primitive segment ; ic, zone of growth, where
the muscle-plate bends around into the cutis-
plate (cp) ; vb, tract connecting the primitive
segment with the body-cavity, out of which
are developed, among other things, the meso-
nephric tubules (fig. 205 uk) ; sk, skeleto-
genous tissue, which arises by a proliferation
from the median wall of the connecting tract
vb ; vn, pronephros ; mkl, mk"t parietal and
visceral middle layer, from whose walls
mesenchyme is developed ; Ih, body-cavity ;
ik. entobl-ast.

the muscular tissue, and in
part even before that event,
the development of mesen-
chyme is observable. The primitive segment (fig. 194) in this case
is differentiated from the start into two equally distinct fundaments,
of which the one is designated as sclerotome or skeletogenous layer
(sk), the other as muscle-plate (mp). While referring the reader to
the ninth chapter, I add to the presentation given there a few
further statements.

THE ORGANS OF THE MIDDLE GERM-LAYER.

349

In the Selachians the skeletogenons layer, the origin of which has
already been described, grows upward at the side of the chorda (fig.
195 Vr). Outside of this layer one finds the part of the primitive
segment which serves for the formation of muscle. This consists of
an inner layer (mp') and an outer layer (mp), which are separated
from each other by the remnant of the cavity of the primitive segment
(fig. 194 h). The inner layer (fig. 195 mp') is in contact with the
skeletogenous tissue (Vr), and is composed of numerous, superposed,
spindle-shaped cells, which are arranged longitudinally and give rise
to transversely striped muscle-fibrillse ; they correspond to the inner
wall of the primitive segment in the larvae of Amphioxus (fig. 189)
and Cyclostomes, which is in direct contact with the chorda. The
outer layer lies in contact
with the epidermis, and
remains for a long time
composed of cubical epi-
thelial cells. Dorsally and
vent rally it bends around
into the muscle - forming
layer, and here contributes
to the enlargement of the
latter, as in Amphioxus
and the Cyclostomes, by
its cells becoming longer
and being metamorphosed
into muscle-fibres (fig. 185).
The muscle - plate then
spreads out farther into

the wall of the trunk both above and below (figs. 185 and 205).
At the same time its cavity (myocoel) gradually disappears. The
muscle-forming layer (fig. 185 mp') continues to increase in thickness,
since the number of muscle-fibres becomes greater ; the outer layer
also loses, rather late it is true, its epithelial character, and is con-
cerned on the one hand in the development of the corium (fig. 205
cp), while on the other it furnishes an additional outer, thin muscle-
lamella. This observation, made by BALFOUR, has often been called
in question, but has recently been confirmed by VAN WIJHE.

In Reptiles, Birds, and Mammals the proliferation of the primitive
segments which furnishes the skeletogenous tissue is still more
extensive than in Selachians. Thereby the muscle -plate, or the
dorsal plate, as it is also called, is crowded farther away from the

Fig. 195.— Horizontal longitudinal section through the
trunk of an embryo of Scyllium, after BALFOUR.

The section is made at the height of the chorda, and
shows the separation from the muscle-plates of the
cells which form the bodies of the vertebrae.

cA, Chorda ; ep, epidermis ; Vr, fundament of the
bodies of the vertebrae ; mp, outer cell-layer of
the primitive segment ; mp', portion of the primi-
tive segment which has already been differentiated
into longitudinal muscles (muscle-plate).

350 EMBRYOLOGY.

chorda. The differentiation of muscle-fibres follows at a much later
stage of development, in comparison with Amphioxus and the Cyclo-
stomes. The inner layer of the muscle-plate is converted into
longitudinal muscle-fibres, the outer contributes to the formation of
the corium (fig. 202).

Let us now consider somewhat more in detail the original condition
of the musculature. It shows at the beginning complete uniformity
in all classes of Vertebrates. Everywhere there appears as its
foundation a very simple system of longitudinal contractile fibres,
which first appear near the chorda and neural tube and spread
themselves out thence dorsally toward the back and vent rally in the
wall of the belly. The muscle-mass is divided in a very uniform
manner into separate segments or myomeres by means of connective-
tissue partitions (ligamenta intermuscularia), which run transversely
or obliquely to the vertebral column. In the lower Vertebrates this
condition persists, in the higher ones it gives place to a more
complicated arrangement.

We cannot recount more precisely the details of the manner in
which the groups of muscles of the higher Vertebrates, so various in
form and position, are derived from the original system, especially
since this field of embryology has been as yet little cultivated ; let
attention be here called to only two points, which come in question
in the differentiation of the groups of muscles.

First, a very important factor is furnished in the development of
the skeleton, which with its processes affords points of attachment
for muscle-fibres. Some of these find in this way opportunity to
detach themselves from the remaining mass.

Secondly, the development of the limbs, which arise as protuberances
at the side of the trunk (figs. 157 and 158), operates toward a
greater differentiation of the musculature. The limbs likewise ac-
quire their musculature, which in the higher Vertebrates has a very
complicated arrangement, from the primitive segments, as has been
learned through the investigations of KLEINENBERG and BALFOUR, as
well as recently through the very convincing accounts of DOIIRN.

In the Selachians, in which the processes are' most clearly recog-
nisable, cell-buds sprout forth out of the still hollow primitive segments
and grow into the paired and median fins, in which they become meta-
morphosed into muscle-fibres. The fact that always from a large
number of primitive segments buds are given off to a fin is worthy of
attention, because it demonstrates that the extremity is a structure
that belongs to several somites.

THE ORGANS OP THE MIDDLE GERM-LAYER. 351

B. The Segments of the Head.

Important works on the development of the head have appeared
in late years by GOETTE, BALFOUR, MARSHALL, WIJHE, FRORIEP. RABL,
and others. They have led to the important conclusion that the
head is made up of a large number of segments, in the same manner
as the trunk. These conditions are most evident in the Selachians.

When in these animals the middle germ-layers have grown into
the fundament of the head, they here, as in the trunk, early separate
from each other, and thus embrace on either side a narrow, fissure-
like space, the head-cavity. This is continuous posteriorly with the
general body-cavity. It follows from this that
the two primitive body-sacs (ccelom-sacs) possess
a greater extent in the embryo than they do sub-
sequently, since they reach into the most anterior
part of the embryonic fundament, the head.

In the further course of development the walls ^SB^^P

of the head-cavity are differentiated, in the same Fig. 196.— Cross section
manner as the walls of the body-cavity, into a Sl™^ vUceraT* ^
ventral portion and a dorsal portion, the latter of an embryo of Pris-
producing primitive segments. Then there arises,
however, an important difference between head visceral pouch ;
and trunk ; in the trunk only the dorsal portion

is segmented, but in the head both ventral and visceral arch;

. , , . vessel of the visceral

dorsal portions are segmented, each in a manner arch (aortic arch)
peculiar to itself.

The ventral part of the head-cavity is divided, in consequence
of the development of the visceral clefts, into separate segments
(branchiomeres AHLBORN), the first of which is situated in front of
the first cleft, each of the remaining ones between two clefts. Each
segment (fig. 196) consists of a wall composed of cylindrical cells and
encloses a narrow cavity. With its enveloping connective tissue it
constitutes the visceral arches, which are separated from one another
by the visceral clefts ; for this reason the fissures arising from the
head-cavity have been designated by WIJHE as visceral-arch cavities.
The latter communicate for a time under the gill-pouches with the
pericardial chamber surrounding the heart. But then they begin to
be closed ; their walls come into contact ; and out of the cylindrical
epithelial cells are developed the transversely striped muscle-fibres
which produce the muscles of the jaws and gills.

Consequently there results for the head-region of Vertebrates this

352 EMBRYOLOGY.

important proposition : the head-musculature is developed not only out
of the primitive segments, but also out of a part of the epithelium
of the head-cavity which corresponds to the lateral plates of the trunk ;
whereas the latter do not contribute to the formation of muscles.

So far as regards the dorsal part of the middle germ-layer in the
head-region, it is divided, as in the trunk, into primitive segments,
which in the Selachians are nine in number and embrace each a
cavity, with the exception of the first, which is solid. They arise
first in the posterior region of the head, and increase from there
forward. The segmentation of the whole body is therefore accomplished
in the Selachians — and the same is likewise true for all the remaining
Vertebrates- — in such a manner that it begins in the neck-region, and
proceeds thence on the one hand backward to the tail, on the other
forward.

The walls of the primitive segments of the head in part furnish
muscles, in part degenerate. Out of the first three pairs arise the
eye-muscles, as MARSHALL and WIJHE have demonstrated in detail.
The first segment envelops the primitive eye-vesicle like a cup, and
is differentiated into musculus rectus superior, rectus inferior, and
obliquus inferior. The second pair gives origin to the obliquus
superior, and the third pair to the rectus externus. The segments
from the fourth to the sixth inclusive disappear, while out of the
last three are developed muscles which extend from the skull to the
pectoral girdle.

In the remaining Vertebrates the metamorphosis of the middle
germ-layer in the head has not been investigated in so exhaustive
a manner as in the case of the Selachians. There do not appear
to be any head-cavities developed, because the middle germ-layers
remain at all times pressed together. However, we know that
primitive segments are demonstrable even here. GOETTE describes
four pairs of them in Bombinator ; FRORIEP finds in Mammals in
the occipital region alone on either side four muscle-segments, of
which the two most anterior are believed subsequently to degenerate.
In individual cases there still remains much to be elucidated by
more exhaustive investigations.

RABL has recently expressed dissent in some points from the
exposition of the head-segments as given by WIJHE. He divides the
head-segments into two groups — four anterior or proximal, and five
posterior or distal. Only the latter are according to RABL to be
compared with the trunk-segments ; whereas the first, owing to their
method of origin, must take a separate position.

THE ORGANS OF THE MIDDLE GERM-LAYEE. 353

II. The Development of the Urinary and Sexual Organs.

The development of the urinary and sexual organs cannot be discussed
separately in two chapters, because these systems of organs are most in-
timately connected with each other, both anatomically and genetically.

First, both take their origin at one and the same place on the epi-
thelial investment of the body- cavity ; secondly, parts of the urinary
system subsequently enter into the service of the sexual apparatus,
for they furnish the passages or canals which are entrusted with the
evacuatiqn of the eggs and semen. In anatomy also one therefore
properly embraces" the two genetically united systems of organs under
the common name of urogenital system or apparatus.

Again in this subject we turn to one of the most interesting
portions of embryology. The urogenital system claims an interest
particularly from a morphological point of view, because a great
number of important metamorphoses are effected in it during
embryonic life. In the higher Vertebrates the pronephros and the
mesonephros are formed first; they are organs of an evanescent
nature, which in some cases disappear and are replaced by the
permanent kidney, in other cases their ducts alone are preserved.
But these transitory structures correspond to organs which are
permanently functional in the lower Vertebrates.

In late years, the attention of investigators having been directed to
a series of entirely new and unexpected phenomena, by the excellent
researches of WALDEYER_ arid SEMPER, 1 the topic " urogenital
organs" has been carefully worked out by very many different
observers through the investigation of each separate class of Verte-
brates. There has arisen a voluminous literature, and many im-
portant facts have been brought to light. Nevertheless it is not to
be denied that conceptions concerning many fundamental questions
are still very divergent.

As in several previous chapters, I shall also here give to the
discussion a broader foundation by treating somewhat more ex-
haustively of the lower Vertebrates in certain questions.

(a) The Pronephros and the Mesonephric Duct.
The first -thing that becomes noticeable in the origin of the uro-
genital apparatus is the fundament of the pronephros [head-kidney].
This is a structure which has now been demonstrated in the embryos
of all Vertebrates, but which plays in some a greater part, in others
a lesser one. In some Vertebrates (Myxine, Bdello&toma, Bony
Fishes) it is retained permanently ; in others, as .the Amphibia, it

23

354

EMBRYOLOGY.

grows during larval life to an important organ, which disappear^
after the animal's metamorphosis ; finally, in the Selachians and

Amniota its funda-
ment is from the
beginning very rudi-
mentary. In the
latter case it was
held to be the front
end of the meso-
nephric duct, until
through comparative
embryology the right
view had been at-
tained.

I select as types
of the development
of the pronephros /
the Selachians, Am-
phibia, and Birds.

In Selachians of
about twenty - seven
somites the prone-
phros begins with
the third or fourth '
trunk - segment and
is developed from
there backwards.
At the place where
the segmented por-
tion of the middle
germ - layer is con-
tinuous with the
lateral unsegmented
portion, there grow
out of its parietal
lamella a number of
cell -cords (fig. 197
£ vn) segmentally ar-
ranged one behind another, in Torpedo six, in Pristiurus four,
which bend backwards and become united into a longitudinal
cord. Soon afterwards the fundaments acquire small cavities

Fig. 197.

Fig. 198.

Figs. 197 and 198.— Two cross sections through an embryo of
Pristiurus, after RABL. Cross section fig. 193 lies a little
farther back than section fig. 197.

ch, Chorda ; spg, spinal ganglion ; mp, muscle-plate of primitive
segment ; W, skeletogenous tissue which has grown forth
from the median wall of the primitive segment ; sch, sub-
notochordal rod ; ao, aorta ; ik, inner germ-layer ; pmb,
vrah, parietal, visceral middle layer ; vn, pronephros ;
vg, pronephric duct ; x, fissure in the primitive segment,
which is still in communication with the body-cavity.

THE ORGANS OF THE MIDDLE GERM-LAYER.

355

through disassociation of the cells. In this manner there has now
arisen between epidermis and parietal middle layer a longitudinal
canal, which stretches over several segments of the trunk and com-
municates with the body-cavity by means of several successive openings,
the pronephric funnels (fig. 194 vn). At one place the pronephric
duct comes close up to the epidermis
and fuses with it (fig. 198 vg). Al-
though an actual opening is never
formed here, still, supported by this
fact, one may express the conjecture
that originally the pronephros in Ver-
tebrates opened out at a point far
forward on the body (VAN WIJHE,
KUCKERT).

A short time after its formation the
fundament undergoes in its_ anterior
half a complete degeneration ; the pos-
terior half, on the contrary, is further
developed and enlarges, but remains
in connection with the body-cavity by
means of a single funnel only (fig. 194
vn), either because, as VAN WIJHE as-
serts, the several funnels are fused into
a single one, or because, in accordance
with the account of RUCKERT, all the
funnels except a single one become
closed and degenerate.

In the Amphibia, with which the
Bony Fishes exactly agree in this point,
the pronephros is established in the
most anterior part of the trunk as
an organ that is from the beginning
hollow (fig. 199). Below the primitive
segments, which have already been
differentiated into muscle-fibres (m),
there appears a groove-like evagination (u) of the parietal layer
of the peritoneum, which stretches from in front backward over
several somites. By detaching itself from its parent-tissue at
several places, and remaining in connection with it at others, it is
converted into a longitudinal canal, which in Rana and Bombinator
communicates with the body-cavity by means of three pronephric

Fig. 198. — Cross section through a
very young Tadpole of Bombinator
in the region of the anterior end of
the yolk-sac, after GOETTE.

a, Fold of the outer germ-layer that
is continued into the dorsal fin ;
is*, spinal cord ; m, lateral muscle ;
as*, outer cell-layer of the muscle-
plate ; s, mesenchymatic cells ; 6,
transition of the parietal into the
visceral middle layer; u, pronephros;
/, intestinal cavity; «, entoblast,
which is continuous with the mass
of yolk-cells (d) ; /', ventral coacal
pouch of the intestine, which be-
comes the liver.

356

EMBRYOLOGY

funnels, in Triton and Salamander by means of two. The whole
fundament soon after, during the larval life, acquires ample propor-
tions, owing to the fact that the nephridial funnels grow out into long
and very tortuous tubes (pronephric canals). (FURBRINCER, GOETTE.)

In Birds, with which Rep-
tiles and Mammals agree, the
pronephros appears, much a&
in Selachians, in a more or less

v

v

rudimentary form (SEDGWICK,
£ £ GASSER, BENSON, SIEMERLING^
WELDON, MIHALKOVICS). It
is first observable in embryo
y Chicks having eight primitive
| segments and in the region of
S the seventh somite ; in older
embryos it is developed from
this place backward into the
region of the twelfth somite.
At the place where the primi-
tive segments (fig. 200 P.v)
are constricted off from the
lateral plate (S.o), but still
remain for some time in con-
tinuity with it by means of a
connecting region (the middle
plate), there grows out from
the parietal lamella of the
middle germ -layer (somato-
pleure) a ridge of cells (W.d),
which is directed toward the
overlying epidermis. Later,
like the corresponding furrow
in the Amphibia, it becomes
detached in places from its
parent - tissue, and when,
meanwhile, the primitive seg-
ments have likewise wholly detached themselves from the lateral
plates, it is converted into a longitudinal cord, which is united with
the epithelium of the body-cavity by means of short transverse
branches. Similar conditions exist in Reptiles and Mammals.
"*" Finally, the pronephros subsequently acquires a peculiar condition.

THE ORGANS OF THE MIDDLE GERM-LAYER.

357

from the fact that there are developed out of the wall of the body-
cavity, in the vicinity of the openings of its tubules, one or several
vascular glomeruli. In the Chick for example (fig. 201), in the region
from" the eleventh to the fifteenth somites, there is a proliferation of
connective tissue on either side of the mesentery (me), — by means of
which the right and left pronephridia are separated from each other,
—which grows into the body-cavity as a spheroidal body (gl).

A blood-vessel from the aorta penetrates into each proliferation
and is here resolved into a tuft of capillaries, which are then united
again into an efferent vessel. Only in those Vertebrates in which the
pronephros is functional, as in the larvae of the Amphibia, in the
Cyclostomes and the Teleosts,
does~tne glomerulus attain to a
considerable development, where-
as in the Selachians and Amniota
it remains rudimentary. In the
first case fluid or urine is pro-
"bably secreted by this apparatus,
and then taken up by the open-
ings of the pronephric tubules
and conducted outside the body
by means of the pronephric duct,
which is to be discussed directly.
There is one point in this con-
nection that is noteworthy and
characteristic of the structure of
the pronephros: the glomerulus
is developed, not in the wall of
the pronephric tubule itself, as
is the case in the tubules of the mesonephros, but in the wall of the
body-cavity, so that the urine can be evacuated only through the
agency of the latter.

But in what manner does the pronephros communicate with the
outside ?

This communication takes place by means of a longitudinal_canal,
which is developed in immediate continuation with the pronephros,
and, beginning in front, gradually grows backwards until it reaches
the proctodseum and opens into the cloaca. It is found in all
Vertebrates in the region where the primitive segments abut upon
the lateral plates. At the time of its origin it is always close under
the epidermis, later it is farther and farther removed from the latter s

Fig. 201. — Cross section through the external
glomerulus of a pronephric tubule of an
embryo Chick of about 100 hours, after
BALFOUR.

gl, Glomerulus ; ge, peritoneal epithelium ;
Wd, mesonephric (Wolffian) duct ; ao,
aorta ; me, mesentery. The pronephric
tubule and its connection with the glo-
merulus are not shown in this figure.

358 EMBRYOLOGY.

by the ingrowth of embryonic connective tissue, and comes to lie
very deep (fig. 202 wd and fig. 205 ug). This canal has acquired a
number of different names, and is cited in the literature as pro-
nephric, mesonephric, Wolffian, or segmental duct. The different
designations are explainable "from the fact that the canal alters its
function in the course of the development of the iiephridial system
serving at first as an outlet for the pronephros only, afterwards for
thejnesojifiphr os .

Views concerning the origin of the canal were for a time conflicting.
According to one supposition, which a few years ago almost all
investigators entertained, the longitudinal canal of the pronephros,
when it had been constricted off from the parietal wall of the body-
cavity, protruded with its posterior end as a free knob into the space
between outer and middle germ-layers, and gradually grew out inde-
pendently, by multiplication of its own cells, as far as the hind gut
(proctodseum). It was said, therefore, to be constricted ofFfrom
neither the outer nor the middle germ-layers, nor yet to derive from
them cell-material for its increase.

This interpretation has recently be6ome untenable. As is reported
in an entirely trustworthy manner concerning several different classes
of Vertebrates, — for Selachians (WiJHE, RABL, BEARD), for Amphibia
(PERENYI), for Reptiles (MrrsuKURi), and for Mammals (HENSEN,
FLEMMING, GRAF SPEE), — the posterior end of the pronephric duct in
process of growth is in these cases by no means an entirely isolated
structure, but is in close union with the outer germ-layer. Attention
has already been called to this fact apropos of the development of the
pronephros. In a Selachian embryo the condition which is repre-
sented in fig. 191-is-soon followed by a condition (fig. 198) in which,
in a series of cross sections, the pronephric duct now appears as a
ridge-like thickening of the outer germ-layer. By a study of various
older embryos it can be further established, that the ridge-like thick-
ening of the outer germ-layer is prolonged backwards by means of
cell-proliferation in that layer, while in front it is being constricted
off from the parent-tissue. The pronephric duct therefore grows at
the expense of the outer germ-layer, and moves as it were along the
latter, with its terminal opening behind, as far as to the hind gut.

When HENSEN, FLEMMING, and GRAF SPEE made their observations
on Mammals, they were thereby led to adopt the view that the
mesonephric duct, as well as the whole urinary system, was derivable
from the outer germ-layer. The union with the middle germ-layer
they regarded as one that had arisen secondarily. But their concep-

THE ORGANS OF THE MIDDLE GERM-LAYER. 359

tion cannot be brought into unison with the conditions of the pro-
nephros which have been found in the remaining and especially
in the lower Vertebrates (Selachians, Teleosts, Amphibia, Birds) ; on
the other hand allowance is made for all observations, if we sum-
marise them as follows : that the pronephros is developed from the
" middle plate," and that then its posterior end comes into union
witETthe outer germ-layer and in conjunction with the latter grows
farther backward as the pronephric duct.

If this explanation, which has also been expressed by WIJHE and
RiiCKERT, is correct, then one can designate the pronephric duct at
its first appearance as a short canal-like perforation of the wall of
the body, which begins in the body-cavity with one or several inner
ostia and opens out upon the skin by a single external ^orifice.
Originally the outer and inner openings lay near together, later they
moved so far apart that the outer opening of the canal united with
the hind gut. It may be said, in favor of the view here presented,
that in the Cyclostomes the more primitive condition, that is to say,
the union with the skin, has been preserved. For in them the
mesonephric duct opens to the outside at the abdominal pore.
" That openings should arise between the cavities of the body and its
outer surface is in no way remarkable. I call to mind the intestinal
"tube, at various places in the territory of which there are formed
openings, as mouth, anus, and branchial clefts. Still more frequent
are passages through the body-wall of Invertebrates. As such, arise
the openings at the tips of the hollow tentacles of the Actinia, on
the ring-canal of the Medusae, and the canals (segmental organs)
which in Worms lead out from the body-cavity and serve for the
elimination of the sexual products and the excretions.

(6) The Mesonephros. (Wolffian Body.)

Following upon the origin of the pronephric system there is de-
veloped in all Vertebrates, after the lapse of a longer or shorter
interval of time, a still more voluminous gland, serving for the secre-
tion of urine, the primitive kidney (mesonephros) or Wolffian body.
It is developed earlier in those cases in which the fundament of the
pronephros is from the beginning only rudimentary, as in the Sela-
chians and Amniota ; it appears relatively late, on the contrary, in
those Vertebrates in which the pronephros attains to a temporary
functional activity, as in the Amphibia and Teleosts.

The mesonephros is established on the portion of the pronephric

360

EMBRYOLOGY.

duct immediately behind the prqnephric tubules. The duct con-
sequently serves from this time forward as an outlet for the newly
formed glandular organ also, and can therefore be designated as
mesonephric or Wolffian duct.

When it is stated that a gland is developed on the mesonephrio

duct, one at first thinks that lateral buds grow out from its wall and
give forth branches, as occurs in the fundaments of £'ands formed
from the outer or the inner germ- layers. Nothing of the kind takes
place here. All observers — with the exception of a few earlier
investigators — agree rather that the glandular tubules of the meso-
nephros arise independently of the mesonephric duct. The source

THE ORGANS OF THE MIDDLE GERM-LAYER.

361

of its material is either directly or indirectly the epithelium of the
body-cavity, as it has been possible to prove in many cases — in
Cyclostomes, Selachians, Amphibia, and Amniota.

There are formed, following one another in immediate succession,
short transverse tubules (fig. 202 st), which are at one end continuous
with the epithelium of the body-cavity, and at the other end, which
remains for a long time closed, are joined to the mesonephric duct (wd)t

Pig. 203.— Embryo of a Dog of 25 days, straightened out and seen from in front, after BISCHOFF.

Magnified 5 diameters.
d, Intestinal tube ; ds, yolk-sac ; al, allantois ; un, mesonephros ; I, the two lobes of the liver,

with the lumen of the vena omphalomesenterica between them ; ve, he, anterior and posterior

extremities ; h, heart ; m, mouth ; au, eye ; g, olfactory pit.

which runs close to them, but somewhat more laterad. The mesone-
phros elongates from before backward and attains a great length on
both sides of the mesentery, for it reaches back from the region of
the liver nearly to the posterior end of the body-cavity ; it acquires
a very delicate, regular condition, as the figure of an embryo Dog
twenty-five days old shows (fig. 203 un), and can be designated as
a comb-shaped gland, composed of a lateral collecting tube, running
lengthwise of the body at a little distance from the mesentery, and,

362 EMBRYOLOGY.

attached to the median side of it, short transverse branches, which
we shall designate as mesonephric tubules.

Whereas there can no longer exist any doubt about the origin of
the mesonephric tubules from the middle germ-layer, the statements
concerning the method of their formation are still at variance with
one another. In accordance with the fundamental investigations
of SEMPER, it was generally believed that the mesonephric tubules
either were e^aginated in metameric sequence along the dorsal wall
of the body-cavity out of its epithelial lining, or grew forth as
originally solid buds, as glandular sacs do from the outer or inner
germ-layer.

This view, according to the more recent investigations of SEDGWICK,
WIJHE, and RtiCKERT for the Selachians and the three higher classes
of Vertebrates, is no longer adequate,.-. In these cases the development
'of the mesonephric tubules is intimately connected with that of the
; primitive segments. When the latter begin* to be more sharply
separated from the lateral plates, there arises at the place of con-
striction a narrow stalk, which maintains for a time a connection
between the two parts (fig. 204 vb). In the Selachians it possesses
a small cavity, which unites the cavity of the primitive segment with
the body-cavity. In the Amniota it is solid (fig. 200). Inasmuch as
the successive cords (stalks) are here closely pressed together, they
appear like a continuous cell-mass interpolated between primitive
segment and lateral plate, and have been previously mentioned under
the name of the middle plate. On account of its relation to the meso-
nephric tubules, the middle plate is also designated as mesonephric
blastema. The mesonephric duct, split off from the 'outer germ-
layer, is to be seen taking its way on the lateral side of and close
to the connecting stalks of the primitive segments. Each of the
connecting stalks, which RUCKERT names at once nephfotome, — in
contradistinction to the remaining parts of the primitive segment,
which produce the muscle-plate (myotome) and the cell-material for
the skeletogenous tissue (sclerotome), — is afterwards metamorphosed
into a mesonephric tubule. Whereas one of its ends remains con-
nected with the body-cavity, the other becomes separated from the
primitive segment (fig. 205 ukl), then applies itself closely to the
mesonephric duct, fuses with the wall of the latter, and opens into it.
In the diagram (fig. 205) the detachment of the connecting stalk
from the primitive segment is shown on the right, the fusion of the
detached end with the mesonephric duct on the left. According to
this whole process of development the mesonephros is from the very

THE ORGANS OF THE MIDDLE GERM-LAYER.

363

beginning a segmentally formed organ, as can be best followed in
the Selachians ; for each mesonephric canal is developed in a single
segment.

In Reptiles, Birds, and Mammals the connecting stalks are solid

Fig. 204.

Fig. 205.

Figs. 204 and 205.— Diagrams of cross sections through a younger and an older embryo Selachian
to show the development of the principal products of the middle germ-layer. After WIJHE,
with some alterations.

Fig. 204.— Cross section through the region of the pronephros of an embryo in which the muscle-
segments (mp) are in process of being constricted off.

Fig. 205.— Cross section through a somewhat older embryo, in which the muscle-segments have
just been constricted off.

nr, Neural tube ; ch, chorda ; ao, aorta ; sch, snbnotochordal rod ; mp, muscle-plate of the
primitive segment ; w, zone of growth where the muscle-plate bends around into the cutis-
plate (cp) ; vb, the connecting piece which unites the primitive segment to the walls of the
body-cavfty, and from which are developed, among other things, the mesonephric tubules
(fig. 205 uk) ; sk, skeletogenous tissue, which arises by a proliferation" of the median wall
of the connecting piece vb ; vn, pfonephros ; mk\ mk2, parietal and visceral middle layer,
out of which mesenchyma is developed ; Ih, body-cavity ; ik, entoblast ; h, cavity of the
primitive segment ; uk, mesonephric tubules, which have arisen from the connecting piece
vb of the diagram fig. 204 ; uk1, the place where the mesonephric tubule has been detached
from the primitive segment; ug, mesonephric duct, with which, on the left side of the
figure, the mesonephric tubule has united ; tr, union of the mesonephric tubule with the
body-cavity (nephridial funnel) ; me*1, mes', mesenchyma that has arisen from the parietal
and visceral middle layers.

cords of cells (mesonephric cords). It is only when they have de-
tached themselves from the primitive segment, and their blind ends
have united with the mesonephric duct, that they acquire a small
cavity (fig. 202 st). Now they also become more readily distin-
guishable as separate canals, since they become farther removed from

364 EMBRYOLOGY.

/ X

one another and are marked off from the surrounding tissue by
sharper contours.

Although it is often stated that in the Amniota the mesonephric tubules
" are differentiated, out of " the middle plate or the mesonephric blastema, it is
nevertheless to be observed that this is not a case of new formation out of
undifferentiated cell-material. The so-called middle plate at the time of its
origin, in the manner previously described, is at once separated into segmentally
arranged cords, which are afterwards metamorphosed into the mesonephric
tubules. The differentiation out of a blastema is therefore here, as in most
cases, to be conceived of as an increase in the distinctness of already esta-
blished structures, which constitute a cell-mass that appears undifferentiated,
but only on account of our limited means of discrimination.

In the Amphibia, Teleosts, and Ganoids the origin of the m«isonephros
deserves to be subjected to renewed investigation from the recently acquired
points of view.

Soon after their union with the mesonephric duct the individual
mesonephric tubules begin to grow somewhat in length, to take on
S-shaped curves, and to be differentiated into three regions. The
middle region undergoes a vesic^ar enlargement and is converted
into a BOWMAN'S capsule. Individual transverse branches from the
primitive aortse, which pass along close to the mesonephros, make
their w^y to the capsules, and are there resolved into a tuft of
capillaries. The knot of blood-vessels, or glomerulus, now grows
into the epithelial vesicle, the median wall of which is pushed before
it and invaginated into the interior. During this process the
epithelial cells of the invaginated part of the wall become greatly
flattened, whereas upon the opposite uninvaginated side they re-
main tall and cuboidal. Such a structure, consisting of a vascular
glomerulus and the enveloping BOWMAN'S capsule, is called a Mal-
pighian corpuscle, an organ that is exceedingly characteristic of the
primitive kidney (mesonephros) and the permanent kidney (meta-
nephros) of Vertebrates.

In addition to the enlarged middle part, there is to be distinguished
on each mesonephric tubule a narrow connecting portion, which
continues to increase in length, running to the mesonephric duct, and,
secondly, a short portion connecting with the body-cavity. The latter
is metamorphosed in different ways in the separate classes of Verte
brates. In some, as in many of the Selachians, it retains its original
connection with the body-cavity even in the adult animals ; it begins
at the peritoneum with an opening, surrounded with ciliate cells,
which was discovered by SEMPER and has been designated nephridial
funnel or nej>hro8tomet and which in many respects recalls the

THE ORGANS OF THE MIDDLE GERM-LAYER.

365

similar structures of the excretory organs of segmented Worms. In
the most of the Vertebrates, however, special nephridial funnels are
no longer developed, inasmuch as the mesonephric tubules soon after
their origin completely detach themselves from the epithelium of the
body-cavity as well as from the primitive
segments, and thereby lose all relation to
the body cavity.

A mesonephros in the simple form in
which it is at first produced develop-
mentally is retained permanently only
in Bdellostoma, a representative of the
Cyclostomes. It here consists, as JO-
HANNES MULLER has shown, of an elon-
gated canal (fig. 206 A and B a) and
short transverse tubules (6), which open
into it at short intervals. The latter are
no longer connected with the body-cavity
by means of a nephridial funnel, but they
enclose a vascular glomerulus at their
blind end (fig. 206 B c), which is some-
what set off by a constriction.

In all remaining Vertebrates the meso-
nephros is metamorphosed into a more
voluminous and more complicated organ.
For the originally short tubules, which
run transversely into the mesonephric
duct, begin to grow in length, and at the
same time to be thrown into numerous
folds (fig. 207 s.t). Moreover there are
formed mesonephric tubules of a second
and third order. These again are also
formed independently of the mesonephric
duct dorsal to the first-formed transverse
tubules; their blind ends approach the
primary urinary tubule and join its ter-
minal part, which is thereby converted
into a collecting tube. At the same time a Malpighian body is
formed on each of them also.

Still more exhaustive investigations concerning the formation of the second
ary and tertiary mesonephric tubules, especially for the higher Vertebrates,
appear to me to be desiiable. In the Selachians, according to the statements

Fig. 206.— Parts of the mesone-
phros of Myxine, after J.
MULLED.

a, Mesonephric duct; b, mesone-
phric tubules ; c, glomernlus ;
d, afferent artery ; e, efferent
artery.

B a part of A more highly mag-
nified.

366 EMBRYOLOGY.

of BALFOUB, which are also confirmed by others, the epithelium of the
already existing Malpighian glomeruli is the starting-point of a proliferation.
Cell-buds grow out from the latter and toward the urinary tubules lying in
front of them, with which their blind ends fuse. After this union has been
effected they detach their other ends from the parent-tissue.

Through the development of compound urinary tubules, each
of the branches of which is provided with a Malpighian corpuscle,
the primitive kidney (mesonephros) acquires a complicated structure.
But this is not uniform in all its parts; ordinarily the condition
realised in the most of the Vertebrates is this : the anterior part,
which afterwards enters into relation with the sexual glands,
retains simple tubules, and only the posterior part passes into a
more complicated form by the production of secondary and tertiary
fundaments.

The more the mesonephros, with its tortuous tubules and its

pd

Fig. 207.— Diagram of the original condition of the kidney in an embryo Selachian, after BALFOUB.

pd, Mesonephric duct, which opens into the body-cavity at o, and into the cloaca at the other
end ; x, line along which the Miillerian duct (lying below in the diagram) is divided off from
the mesonephric (Wolffian) duct; s.t, mesonephric (segmental) tubules, which on the one
hand open into the body-cavity, on the other into the mesonephric duct.

further differentiation, increases in volume, the more it becomes
delimited from its surroundings and emerges from the wall of
the body into the body-cavity as a distinctly differentiated organ,
where it forms a protruding band on either side of the mesentery
(fig. 210 WK).

On a cross section one can recognise in the human embryo also
(NAGEL) two distinctly separated regions on each urinary tubule — (1)
a larger one, which begins with the BOWMAN'S capsule^and is lined
with large epithelial cells containing abundant protoplasm, and (2)
a narrower region with small cubical elements. The latter is the
collecting tube, which unites with other collecting tubes before it
opens into the mesonephric duct ; on the other hand, probably the
former region alone has the secretory function, as also it is best
developed at the time of the greatest prominence of the Wolifian
body. The Malpighian glomeruli, likewise, attain at this time in
human embryos a remarkable size (NAGEL).

THE ORGANS OF THE MIDDLE GERM-LAYER. 367

The further fate of the primitive kidney is very different in the
separate classes of Vertebrates. In the Anamriia, i.e., in Fishes and
Amphibia, it becomes the permanent urinary organ, through which
the excretions of the body are eliminated ; but besides that, it also
acquires relations to the sexual apparatus, upon which, however, I
shall not enter until later. In Birds and Mammals, on the contrary,
the primitive kidney is functional only a short time during embryonic
life ; soon after its establishment it undergoes profound regressive
changes, and at last is preserved only in part, in so far as it enters
into the service of the sexual apparatus, and, as we shall likewise see
later, participates in conducting away the sexual products.

(c) The Kidney. (Metanephros.)

The secretion of urine is assumed in the higher Vertebrates by
a third gland, which is established at the posterior end of the meso-
nephric duct — the permanent kidney. The method of its formation,
which appears to differ at first from that of the mesonephros, presents
great obstacles to its investigation. It is most accurately known
from studies on the development of the Chick through the works of
SEDGWICK. At the beginning of the third day of incubation in the
Chick there grows out of the [posterior] end of the rnesonephric duct,
from its dorsal wall, an evagination — the excretory duct of the kidney
or ureter.

There are two conflicting views relative to its connection with the
development of the kidney. According to the older view, which is
still shared by many, the kidney is formed from the ureter in the
manner of an ordinary glandular growth. It is maintained that
evaginations take place which give rise to other evaginations, and
thus produce the whole parenchyma of the kidney. According to the
second view, which has been formulated especially by the more recent
•embryologists, — by SEMPER, BRAUN, FURBRINGER, SEDGWICK, and
BALFOUR, — the permanent kidney is, on the contrary, developed out
of two different fundaments, which come into relation with each other
only secondarily :|jbhe medullary substance with its collecting tubules
out of the ureter, the cortical substance with the tortuous tubules
and the loops of HENLE, on the other hand, out of a special fundament.
According to this view there would be an agreement between the
development of the kidney and primitive kidney, in as far as in the
latter the mesonephric duct and the mesonephric tubules also arise
separately, and only secondarily enter into relation with each other-

368

EMBRYOLOGY.

by means of fusion. The agreement here indicated is a not unim-
portant ground for my giving preference to the second rather than
the first view.

As far as regards the details of the conditions, they are in the
Chick — according to the investigations of SEDGWICK, which BALFOUR
has confirmed — as follows : the ureter, which has arisen by an evagi-
nation from the end of the mesoiiephric duct, grows into that part of
the middle plate which is located at the end of the Wolffian body in the
region of the thirty-first to the thirty-fourth primitive segment. The
fundament, however, is not at once and at this place converted into
a kidney, but first undergoes, after the ureter has penetrated into it, a

very considerable change in position; to-
gether with the ureter it grows forward
on the dorsal side of the mesonephric
duct farther; it meanwhile gradually
enlarges, and begins to show internal
differentiation only when it has come
into this new position. One then sees
that tortuous tubules become more and
more distinct in the small-celled mass
and that in their walls Malpighian cor-
puscles are established. One finds, in
addition, that there are evaginated
from the end of the ureter separate
sacs, which grow out into collecting
tubes, and probably later — certainty
in regard to this has not. yet been
established — join the tortuous tublues which have arisen in the
cortical portion of the kidney.

This voluminous organ, which has soon outstripped the mesonephros
in size, is originally composed of individual lobes separated by deep
furrows (fig. 208). The lobatiori is retained permanently in Reptiles,
Birds, and some of the Mammals (Cetacea). In most Mammals,
however, it disappears, in Man soon after birth. The surface of the
kidney acquires an entirely smooth condition ; the internal structure
(Malpighian pyramids) alone points to its composition out of indi-
vidual portions, originally also separated externally.

For the sake of clearness the development of the three regions,
pro-, meso-, and metanephros, has been treated as a whole up to this
point. Consequently there have been left out of consideration for
the lime being other processes which are taking place in the vicinity

Fig. 208. — Kidney and suprarenal
body of a human embryo at the
end of pregnancy.

nn, Suprarenal body ; n, kidney ;
I, lobes of the kidney ; hi, ureter.

THE ORGANS OF THE MIDDLE GERM-LAYER.

369

of the fundament of the mesonephros at the same time. These have
to do with the evolution of the Miillerian duct and the sexual organs,

(d) The Mullerian Duct.

The Miillerian duct is a canal which is found lying at first parallel
and close to the mesonephric duct in the embryos of most Vertebrates
(Selachians, Amphibia, Reptiles, Birds, Mammals). It is a canal that
is established in both sexes in the same
manner, but subsequently acquires in each
a different function. It takes its origin
in the lower Vertebrates from the mesone-
phric duct, as can be most easily followed
in the Selachians (SEMPER, BALFOUR,
HOFFMANN). In this case the mesonephric
duct becomes enlarged, acquires in cross
section (fig. 209 4) an oval form, and pre-
sents a different condition in its dorsal
(sd) and ventral (od) halves, the latter
being at the same time in immediate con-
tact with the peritoneal epithelium. The
mesonephric tubules open into the dorsal
half, while ventrally the wall is consider-
ably thickened. Then a separation of the
two parts takes place, which begins at a
little distance from the anterior end (cross
sections 3-1) and proceeds backward to
the point of opening into the hind gut.
Of the parts which result from the fission,
that which lies dorsally is the permanent
mesonephric duct (wd) ; it exhibits at first
a broad lumen and receives the urinary
tubules (fig. 207 st). Ventrally, between it and the epithelium of
the body-cavity, lies the Mullerian duct (fig. 209 od and fig. 207),
which is at first only a narrow passage, but later a much enlarged
one. In the process of fission the anterior initial part of the primary
canal (fig. 207 pd), which was described at p. 353 as pronephros and
which opens into the body-cavity by means of a cilia te funnel (o),
becomes a part of the latter duct, and the ciliate funnel becomes the
ostium abdominale tubae.

%

Also in the case of the Amphibia the Mullerian duct is developed by being
split off (FuRBEiNGEE, HOFFMANN) from the mesonephric duct, with the excep-

24

Fig. 209. —Four cross sections
through the anterior region
of the mesonephric duct of a
female embryo of Scylliua

canicula, after BALFOUR.
The figure shows how the Mul-
lerian duct (pd) is split off
from the mesonephric duct
(sd and wd).

370 EMBRYOLOGY.

tion of the anterior end, which bears the orifices leading into the body-cavity.
A small territory of the epithelium of the body-cavity immediately adjacent to
the pronephros serves for the construction of this portion. The epithelium
becomes thickened, owing to the fact that its cells take on a cylindrical shape ;
it sinks in to constitute a groove, and then becomes constricted off from the
surrounding tissue in the form of a short funnel, which in front remains in
connection with the body-cavity by means of a broad opening, but posteriorly
becomes continuous with the part of the Miillerian duct that is produced by
fission. The pronephric tubules and the glomerulus degenerate.

The fission of the single mesonephric duct into two canals lying
close together is a peculiar process, which is intelligible only upon
the assumption that the mesonephric duct has possessed a double
function. Probably it originally served as an outlet for the secre-
tions of the mesonephric tubules, and also by means of its pronephric
funnel took up out of the body-cavity the sexual products (eggs or
seminal filaments) eliminated into it at their maturity, and con-
ducted them to the outside. Similar conditions are often observed
in Invertebrates, e.g., in various divisions of the Worms, in which
also the segmental canals, which break through the body-wall,
transmit to the outside both secretions from the body and sexual
products. In Vertebrates each of the two functions is assigned to a
special canal, one of which loses its communication with the body-
cavity, but remains in connection with the transverse mesonephric
tubules, while the other retains as its part the ciliate funnel of the
pronephros, and thus is adapted to conducting away the sexual pro-
ducts (eggs).

In Reptiles, Birds, and Mammals the manner of the development
of the Miillerian duct is still a subject of scientific controversy.
Most observers (WALDEYER, BRAUN, GASSER, JANOSIK, and others)
state that at no time was a process of fission observed. According
to their representation the Miillerian duct arises in Birds and
Mammals quite independently as a new structure, at a time when the
mesonephros is already well developed and has the form of a band-
like body (the mesonephric fold) projecting into the body-cavity
(fig. 210). One then sees on the lateral face of the anterior region of
this body that the epithelium of the body-cavity over a limited area
(a1) is thickened in a remarkable manner and composed of .cylindrical
cells, whereas elsewhere the cells are flattened. The thickened
portion of the epithelium sinks down in the form of a funnel and
applies itself closely to the mesonephric duct (?/), which is near at
hand. The blind end of the funnel grows from this point backwards
independently, as is usually asserted, by means of the proliferation

THE ORGANS OF THE MIDDLE GERM-LAYER.

371

of its own cells, and gives rise to a solid cord, which lies directly
between the mesonephric duct and the peritoneal epithelium, which
is here somewhat thickened. The funnel produced by the invagina-
tion now becomes the ostium abdominale tubse, but the solid cord of
cells, which is soon hollowed out and finally opens behind into the
cloaca, becomes the
Miillerian duct.

If the representa-
tion just given is cor-
rect in all particulars,
the Miillerian ducts
in the Anamnia and
the Amniota, al-
though possessing
the same location,
form, and function,
would still be non-
homologous organs,
because their develop-
ment is different.
For the one is split
off from the meso-
nephric duct, the
other is formed in-
dependently by a
new invagination of
the epithelium.

Such a surprising
result appears to
us, however, upon
grounds of compara-
tive anatomy, to be
very improbable, and

therefore the attempt made by some investigators to refer back
the conditions found in the Amniota to such as exist in the
Anamnia deserves every attention. This would be possible if
the statements of BALFOUR AND SEDGWICK, which have however
been called in question by others (JANOSIK), should be confirmed.
As we have previously seen, there are two different regions to
be distinguished on the Miillerian duct — an anterior, which is
the degenerated pronephros and bears the orifice of the tuba,

—I*

Fig. 210.— Cross section through the mesonephros, the funda-
ment of the Miillerian duct, and the sexual gland of a
Chick of the fourth day, after WALDEYER. Magnified 160
diameters.

m, Mesentery ; L, somatopleure ; a', the region of the germinal
epithelium from which the Miillerian duct (2) has been
invaginated ; a, thickened part of the germinal epithelium,
in which the primary sexual cells, C and o, lie ; E, modi-
fied mesenchyme out of which the stroma of the sexual
gland is formed ; WK, mesonephros ; y, mesonephric duct

372 EMBRYOLOGY.

and a posterior, which is formed by being split off from the
mesonephric duct. Such a double origin BALFOUR AND SEDGWICK
endeavor to establish for the Miillerian duct in the Chick also.
The part produced by invagination of the peritoneum (fig. 210 z)
they interpret as pronephrcs. A similarity with the latter they find
in the fact that this part does not, according to their investigations,
consist of a single invagination of the peritoneal epithelium, but of
three open invaginations lying one behind the other, which are
joined together by ridge-like epithelial thickenings which after-
wards become hollow (fig. 211 gr 2, gr 3, r 2). From this ridge is
formed a slightly curved, short duct, which communicates with the
body-cavity through three openings.

If this explanation is right, the most anterior fundament of the

Fig. 211. — Cross sections through two peritoneal invaginations out of which is formed the
anterior region of the Miillerian duct (the pronephros) of the Chick, after BALFOUR ANQ
SEDGWICK.

A is the llth, B the 15th, C the 18th section of the whole series.

g>-%, 3, Second and third furrows ; r2, second ridge ; ivd, Wolffian duct.

excretory system of the Chick, which was described on page 356 as
pronephros, must have undergone P change in position, and, with the
appearance of the Wolffian body, have slipped backward somewhat
along this organ. As long as this alteration of position is not
demonstrated by the study of intermediate stages, the interpretation,
however probable it may seem to us, still lacks actual proof,

As far as regards the posterior, longer region of the Miillerian
duct, SEDGWICK maintains that it arises by being split off from the
mesonephric duct. One always finds, according to his researches,
the pronephric part of the Miillerian duct in union at its posterior
end with the ventral wall of the mesonephric duct. He maintains
that it is enlarged at the expense of the latter in somewhat the same
manner as the mesonephric duct grows from in front backwards by
a proliferation of the outer germ-layer. The cross sections A and B

THE ORGANS OF THE MIDDLE GERM-LAYER.

373

of figure 212 exhibit this condition. Figure B shows the place

where the ventral wall of the mesonephric duct is thickened into

a ridge (md) by an increase of the epithelial cells ; upon a cross

section (A) made farther forward the thickened part has become

detached as a cord

(md), which subse-

quently becomes still

more isolated and ac-

quires a cavity of its

own. The condition

recalls very clearly

the appearances

which the cross sec-

tions through embryo

Selachians (fig. 209)

gave.

Appnvrlmir tn +>IA
Observations of SEDG-

WICK, therefore, the

anterior end of the

Mullerian duct would

be derived from the pronephros, but the posterior end by a splitting
off of cells from the mesonephric duct. Thus an agreement with
the conditions in the non-amniotic Vertebrates would be established.

Fig. 212.— Two sections to show the union of the solid terminal
P*1"* of the Mlillerian duct with the mesonephric duct in
the Chick, after BALFOUR AND SEDGWICK.

In A the terminal part of the duct is still quite distinctly

* " ha* ™™ with the waU '

, Mullerian duct ; Wd, Wolffian duct.

Fig. 213.— Cross sections through the Wolffian and Mullerian ducts of two human embryos, after

NAGEL.

A A female embryo 21 mm. long.
£, A male embryo 22 mm. long.
W.g., Wolffian duct ; M.g., end of the Mullerian duct in process of development.

It still deserves to be especially mentioned that in human embryos
also the Mullerian ducts (fig. 213 A and B M.g.) during their
development have their posterior ends fused for a short distance with
the mesonephric duct (W.g.). NAGEL, to whom we are indebted for
this fine observation, expresses himself, it is true, against a splitting

374 EMBRYOLOGY.

off ; however, the similarity with the conditions found in the Chick
and the non-amniotic Vertebrates is not to be denied, and has indeed
been emphasised by NAGEL.

(e) The Germinal Epithelium.

In Vertebrates, at the time when the Miillerian duct is established,
the first traces of the sexual glands are also to be recognised. The
parent-tissue of these is likewise the epithelium of the body-cavity.
This acquires — for example in the Chick, which is to serve as the
foundation for our description — a different appearance in the various
regions of the body-cavity (fig. 210). In most places the epithelia be-
come extraordinarily flattened and assume the condition of the perma-
nent " endothelium." Also on the mesonephros, which projects into the
body-cavity as a thick, vascular fold, the epithelium is for the most
part greatly flattened, but retains its original condition (1) on its
lateral surface along a tract (a1) from which, as we have previously
seen, the Miillerian duct is formed, and (2) along a tract (a) which
stretches from in front backward along the median side of the
mesonephros ; the signification of the latter has been correctly
estimated by BORNHAUPT and by WALDEYER, who have characterised
it as germinal epithelium. From it are derived the germ-cells : in the
female the primitive ova, in the male the primitive seminal cells. It is
only in the very earliest stages that it is impossible to distinguish
whether the germinal epithelium will be developed into testis or ovary.
Differences soon appear, which allow a positive determination. We
shall take up first the development of the ovary, then that of the
testis.

(/) The Ovary.

The development of the ovary is tolerably well known both in the
lower and the higher Vertebrates, except for a few controversial points.
I can therefore limit myself simply to the presentation of the results
which have been acquired in the case of the Chick and Mammals.

At about the fifth day of incubation the germinal epithelium in
the Chick increases a good deal in thickness, becoming two to three
layers of cells deep. Certain elements in this thickening are promi-
nent ; they are distinguishable (fig. 210 C and o) by their richness
in protoplasm and by their large round nuclei. Because they stand
in the closest relation to the development of eggs, they have been
designated as primitive eggs by WALDEYER, who was the first to
study them in detail.

THE ORGANS OF THE MIDDLE GERM-LAYER.

375

Fig. 214. — Gross sectiop. through the ovary of a
Rabbit 5 days old, after BA.LFOUR. Highly
magnified.

k.e, Germinal epithelium ; u.ei, primitive (or
primordial) ova ; ei.b, egg-nests ; bi, connec-
tive tissue.

Beneath the germinal epithelium there is to be found, even at that
time, embryonic connective tissue with stellate cells (fi), which are
in an active state of proliferation. In this way there arises on
the median side of the mesonephros the ovarian ridge, which is
separated from the urinary tubules by a small quantity of embryonic
connective substance.

Changes similar to those of the Chick occur in Mammals, with
this difference, that the ger-
minal epithelium appears to
attain a much greater thick-
ness.

In older stages of develop-
ment the boundaries between
the germinal epithelium, which
is in process of rapid prolife-
ration and therefore exhibits
numerous figures of nuclear
division, and the underlying
connective tissue become less
and less distinct. This results

from the simple fact that a
process of mutual ingrowth
now occurs between the epithe-
lium and the embryonic con-
nective tissue (fig. 214). I
purposely say a process of
mutual ingrowth, for I leave
it undetermined whether the
germinal epithelium in con-
sequence of its development
grows into the embryonic con-
nective tissue in the form of

cords and distinct groups of cells, or whether the connective tissue
penetrates with its projections into the epithelium. Probably both
tissues are actively engaged in the process.

In the phenomenon of intergrowth, which continues for a long
time during development, two chief stages can be distinguished.

At first there arise from the germinal epithelium both slender and
stout cords a'nd balls of cells (figs. 214 and 215), which have received
from the name of their discoverer the designation PFLUGER'S egg-tubes.
Occasionally these are joined to one another by means of lateral

Fig. 215. — Section through an egg-nest of a Rabbit

7 days old, after BALFOUR.
ei, Ovum, the germinative vesicle (kb) of which

exhibits a filar network ; bi, connective-tissue

stroma ; f.z, follicular cells.

376 EMBRYOLOGY.

branches. Together with the connective tissue separating them, they
form the foundation for the cortex of the ovary. Afterwards they
are covered over on the side toward the body-cavity with a thick
continuous layer of connective tissue, which becomes the albnginea
of the ovary ; they are thereby more sharply separated from the
germinal epithelium (fig. 216 k.e), which is still preserved, even after
this, as a layer of cubical cells upon the albuginea.

There are two kinds of cells to be found in the Pfliigerian egg-tubes :
jollicular cells and primitive ova (fig. 215/.2 ande^). Concerning the
source of the former opinions are still contradictory (compare p. 382) ;
according to my view both arise from the germinal epithelium.

Whereas the follicular cells become by means of an uninterrupted
process of division more numerous and smaller, the primitive ova
increase in size continually, and their nuclei become very large and
vesicular and acquire a distinctly developed filar network (kb). They
rarely lie singly in the cords and balls of follicular cells, but ordi-
narily in groups, which are designated as egg-nests. One frequently
observes in the nests, as has been announced by BALFOUR and VAN
BENEDEN, that several primitive ova become fused into a common,
multinuclear mass of protoplasm — a syncytium. From this there
is afterwards developed usually only a single egg. One of the
numerous nuclei soon outstrips the others in size and becomes the
germinative vesicle, whereas the remaining ones undergo degeneration
and are dissolved. It is not to be concluded from these processes
that the egg, as is occasionally asserted, corresponds to a multiple
of cells ; the condition is more properly to be interpreted as follows :
of the eggs contained in a nest, one outstrips the others in its growth
and thereby represses them and employs them, in a certain sense as
nutritive material, for its own growth.

This is a process that occurs very frequently in invertebrates, and in the
phylum of the Arthropods has been studied with the greatest detail by
WEISMANN. In these cases — the lower Crustacea and Insects — one can see how,
step by step, out of numerous primitive ova which are originally contained in a
germinal chamber of an ovariole, only one becomes the egg, whereas the others
from an early period lag behind in development, then undergo degeneration,
and in the form of products of degeneration are taken up as yolk-material into
the persisting egg-cell.

During the enlargement of the egg-cell the second stage of the
process of intergrowth of epithelium and connective tissue is intro-
duced : the stage of the formation of the follicle (fig. 216). At the
boundary between the medullary and cortical zones of the ovary the

THE ORGANS OF THE MIDDLE GERM-LAYER.

3T7

surrounding connective tissue, carrying with it the blood-vessels,
grows into the egg-tubes of PFLUGER (e.sch} and the nests (ei.b), and
•divides them all into spheroidal bodies, the individual follicles (/).
Each such structure contains a single ovum, that is enveloped on
all sides by a layer of f ollicular cells. The vascular connective tissue
that grows around it becomes the follicular membrane or theca
folliculi.

The resolution into follicles continually advances from the me-

e.sch

e.scJi

Tig. 216.— Part of a sagittal section of an ovary of a Child just born, after WALDEYER. Highly

magnified.
Jc.e, Germinal epithelium ; e.sch, PFLUGER'S egg-tubes ; ue, primitive ova lying in the germinal

epithelium ; e.sch', long PFLUGER'S tubes, in process of being converted into follicles ;

ei.b, egg-balls [nests], likewise in process of being resolved into follicles ; /, youngest follicle

already isolated ; gg, blood-vessels.
In the tubes and egg-nests the primordial eggs are distinguishable from the smaller epithelial

cells, the future follicular epithelium.

dullary substance toward the germinal epithelium ; however, there
are preserved under it for a long time Pfliigerian tubes, which
remain in connection with it by means of narrow epithelial cords
{e.sch) and contain eggs in process of development.

The formation of new Pfliigerian tubes and young ova is a
process which continues in the lower Vertebrates throughout life,
but in the higher appears to be limited to the period of embryonic
development, or to the first years of life. In the first case, there
being an unlimited capacity for the formation of new structures,

378 EMBRYOLOGY.

egg-germs are found, even in the adult animal, sometimes in the
most widely separated parts of the ovary, sometimes limited to
definite regions of the gland. In the second case the period of
forming primitive ova in the germinal epithelium bears a direct
ratio to the total number of ova eliminated during the life of the
individual. Thus WALDEYER states concerning Man that in the
second year after birth the formation of new ova can no longer be
shown.

Nevertheless in Man the number of ova contained in a single
ovary is very great. They have been estimated to number in a
sexually mature girl 36,000. In other Mammals the production of
new ova appears to last longer. PFLUGER'S tubes which were still
connected with the germinal epithelium and contained small pri-
mordial ova have been observed even in young animals (Dog, Rabbit,
etc.). However, it has been questioned whether we here have
really new structures or only primitive ova that in their development
have remained stationary. It is maintained by VAN BENEDEN with
certainty for a few Mammals, e.g., the Bat, that in the sexually
mature animal PFLUGER'S tubes and primitive ova still continue to>
be produced from the germinal epithelium.

In connection with the first formation of the follicle I will here
add some statements about its further metamorphosis. This is very
similar in the different Vertebrates, excepting Mammals.

In most Vertebrates the follicle (fig. 216 f) consists at first of a
small, centrally located egg-cell and a single layer of small follicular
cells enveloping it. Soon both are more sharply separated from
each other by means of a vitelline membrane. In older follicles
both parts have increased in size. The follicular cells ordinarily
grow out into long cylinders, and appear to play an important part
in the nutrition of the egg. In many animals, e.g., in Sharks and
Dipnoi, yolk-granules have been found in them, as in the egg itself,
and it has been concluded from this, as well as from other phenomena,,
that the follicular cells take up nutritive substance from the vas-
cular follicular capsule, and pass it along to the egg. Such a method
of nutrition is made easier by the fact that the vitelline membrane
(fig. 5 z.p) is traversed by tubules, through which the follicular
cells (f.z) send protoplasmic filaments to the egg. When the egg
has attained its full size, the follicular cells lose their significance a&
nutritive organs and become more and more flattened.

In the lower Vertebrates the mature ova are generally eliminated
in great numbers all at once, frequently in the course of a few days

THE ORGANS OF THE MIDDLE GERM-LAYER. 379

or even hours. The discharge takes place by the rupture of the
connective-tissue envelope, which causes the eggs to escape into the
body-cavity, as in the Fishes and most of the Amphibia. After the
elimination, the ovary, which up to tin's time was extraordinarily
large and took up most of the space in the body-cavity, shrivels into
a very small cord and now encloses only the young germs of ova,
part of which are destined to mature during the next year.

The formation of the follicle takes place in a somewhat different
way in Mammals. The follicle originally contains, as in the remaining
Vertebrates, only a single egg and a single layer of follicular cells,
which are at first flat, then cubical, then cylindrical (fig. 216 /).
For a long time these cells envelop the egg as a single layer, but

^fk

Fig. 217 A and B.— Two stages in the development of the Graafian follicle. A with the f ollicular

fluid beginning to be formed ; B with a greater accumulation of it.
ti, Egg ; fz, f ollicular cells ; fzl, follicular cells which envelop the ovum and constitute th»

discus proligerus; ff, follicular fluid (liquor folliculi); fk, follicular capsule (theca.

folliculi) ; zp, zona pelluuida.

they then grow, undergo division, and are converted into a thick
envelope of many layers. But the difference from the course of
development described above becomes still greater, owing to the fact
that a fluid, the liquor folliculi, is secreted by the proliferated
follicular cells, and collects in a small cavity at the side of the egg
(fig. 217 Aff).

In consequence of a considerable increase of the fluid, the originally
solid follicle becomes converted finally into a large or small vesicle
(fig. 217 B), which was discovered more than two hundred years aga
by the Hollander REGNIER DE GRAAF and was held to be the
human ovum. The structure has also been named after him the
trraafian follicle. Such a follicle (fig. 217 B) now consists of (1) an
outer connective-tissue, vascular envelope (fk), the theca folliculi ;

380 EMBRYOLOGY.

(2) lying on its inner surface, an epithelium composed of many layers
of small follicular cells (fz), the membrana granulosa ; (3) the liquor
folliculi (ff) ; and (4) the ovum (ei), which originally lay in the centre
of the follicle, but which has now been crowded to the periphery.
Here, enveloped in a great mass of follicular cells (fzl), it causes an
elevation of the wall, — the discus proligerus, — which protrudes into
the cavity.

When the egg has reached complete maturity its elimination
occurs by a collapse of the Graafian follicle, which has then at-
tained in Man a diameter of about 5 mm. and causes an elevation
at the surface of the ovary. The liquid of the follicle flows out
through the rupture and at the same time carries away with it
from the discus proligerus the egg, which comes first into the body-
cavity, being surrounded by a small number of follicular cells, which
still cling to the zona pellucida (fig. 5). The egg is then taken up
by the oviduct.

Into the cavity of the follicle produced by the flowing out of the
liquid an effusion of blood takes place from the ruptured blood-vessels
in the vicinity. The blood coagulates, and, accompanied by a prolifera-
tion of the adjacent tissue, is converted into the yellow body, or corpus
luteum, which is a characteristic structure of the ovary of Vertebrates.
Both the follicular cells (membrana granulosa) which are left behind
and the connective -tissue follicular capsule participate in this pro
liferation. The follicular cells continue to multiply, penetrate into
the interior of the coagulum, and after a time begin to undergo
degeneration and to be dissolved into a granular mass. Vascular
outgrowths from the capsule penetrate into the yellow body, and
at the same time there is an extensive emigration of white blood-
corpuscles or leucocytes, which likewise undergo fatty and granular
degeneration at a later period.

It is of great importance for the further development of the yellow
body whether the egg set free is fertilised or remains unfertilised.
For according as the one or the other event supervenes, the corpus
luteum is distinguished as true or false. In the first case it acquires
a, much greater size, the maximum of which is reached in the fourth
month of pregnancy. It then appears as a fleshy reddish mass.
After the fourth month a process of degeneration begins. The
products of degeneration, which have resulted from the granular
metamorphosis of the follicular cells and leucocytes, as well as from
the coagulum of blood, are absorbed by the blood-vessels. Out of the
decomposed coloring matter of the blood there have arisen hsema-

THE ORGANS OF THE MIDDLE GERM-LAYER. 381

toidin crystals, which now give to the body an orange- red color. The
connective tissue, originally with an abundance of cells, begins to
shrivel, as in the formation of a scar ; as a result of these various
processes of degeneration the yellow body, which projects beyond the
surface of the ovary, begins to become considerably smaller, and is
finally converted into a firm connective-tissue callus, which causes
a drawing in at the surface of the organ.

When fertilisation has not occurred, the same metamorphosis
and processes of growth it is true take place, but the false corpus
luteum remains very much smaller. This is probably due to
the fact that the afflux of blood to the sexual organs is very much
less when there is no fertilisation than in case pregnancy takes
place.

In addition to the tubes of PFLUGER, — which arise from the
germinal epithelium and produce the primitive ova, — in most classes
of Vertebrates epithelial cords of another kind and another origin
enter into the composition of the ovary. As has been observed by
various persons in Amphibia, Reptiles, Birds, and Mammals, there
grow out from the Wolffian body, which lies in the immediate
vicinity, epithelial shoots, the " sexual cords of the primitive kidney"
and these penetrate toward the developing ovary even as early as
the beginning of the intergrowth between germinal epithelium and
connective tissue. They arise from the epithelium of the Malpighian
corpuscles, as BRAUN has shown for Reptiles, HOFFMANN for Amphibia,
and SEMON for Birds. In Mammals, in which at present their sub-
sequent fate has been most accurately traced out, they then unite
with one another into a network at the base of the fundament of
the ovary, which protrudes as a ridge into the body-cavity, and,,
pursuing tortuous courses, grow into contact with the tubes of
PFLUGER. Whereas in Mammals the cortex of the ovary is de-
veloped out of the latter, the former share in the composition of
the future medullary substance, and are on that account designated
as medullary cords. In the vicinity of the follicle they remain solid,,
whereas the part near the primitive kidney acquires a cavity which
is surrounded by cylindrical cells.

The medullary cords exhibit in different species of Mammals
different degrees of development, as the comparative investigations of
HARZ have established. In some animals, e.g., in the Pig and Sheep,
they reach only to the base of the ovary, and therefore remain sepa-
rated from the tubes of PFLUGER by a wide space ; in others they
grow out into the vicinity of the latter, and in part apply themselves

382 EMBRYOLOGY.

closely to them (Cat, Guinea-pig, Mouse, etc.), and take a very
prominent part in the composition of the medullary substance.

There are two antagonistic views relative to the significance of the
sexual cords of the primitive kidney, or the medullary cords, in the
formation of ova. According to KOLLJKER and ROUGET the medullary
cords early fuse with the tubes of PFLUGER and furnish to them the
cells which become the follicular epithelium. The cells contained in a
follicle would, according to this, come from two sources — the follicular
cells would arise from the primitive kidney, the eggs from the ger-
minal epithelium. Most embryologists dispute this. According to
their observations the medullary cords only exceptionally extend close
up to a follicle, in many Mammals they do not reach it at all ;
consequently not only the primitive ova but also the accompanying
follicular cells must be furnished by the germinal epithelium. I also
favor the latter view, which appears to me to be best supported by
the facts. But what significance the medullary cords have will be
better understood when we have become acquainted with the develop •
ment of the testis, to which we shall now proceed.

(g) The Testis.

I will at once state that our knowledge of the development of the
testis is less complete than that of the development of the ovary.

The conditions appear to me to be the clearest in the non-amniotic
Vertebrata. We possess here the pioneer researches of SEMPER and
BALFOUR on the Selachians, and of HOFFMANN on Amphibia. All
these investigators have, with one accord, come to the conclusion
that the male sexual products, as well as the female, arise from the
germinal epithelium of the body-cavity. In males also there is to
be recognised in the region of the primitive kidney a special thickened
band of tall epithelial cells, in which are imbedded larger cells with
vesicular nuclei, the primitive spermatic cells. In the Sharks, the
conditions of which I shall make the basis of the further description,
they form irregular cords of cells, the " Yorkeimketten " of SEMPER
(fig. 218 A). Out of these are developed small, spherical, follicular-
like bodies (fig. 218 B), by the ingrowth of surrounding connective
tissue into the cords, which are thereby divided up.

Thus far, therefore, complete agreement exists in the development
of both kinds of sexual products. But whereas in the case of the
ovary one cell in each follicle increases in size and is converted into
the ovum, a like process does not take place in the male ; here the

THE ORGANS OF THE MIDDLE GERM -LAYER.

383

follicle-like structures become hollow and thus converted into seminal
ampullae, whose epithelial cells gradually grow out into long cylinders.
The greater part of these become seminal mother-cells, which by
many repeated divisions are converted into sixty seminal cells, each
of which is metamorphosed into a seminal filament. Since the
filaments derived from each
seminal mother-cell always
arrange themselves parallel
to one another, it is easily
understood .why before the
attainment of complete
maturity the seminal fila-
ments are found united in
great numbers into bundles.
Whereas the testis, like
the ovary, draws its specific
histological components di-
rectly from the germinal
epithelium, it acquires its
efferent ducts from the
primitive kidney. As in
the female, so also in the
male, epithelial shoots, the
sexual cords (genital canals
of HOFFMANN), grow from
the primitive kidney to-
ward the testis; in the
Amphibia they arise as
proliferations from the
cells of the wall of certain
Malpighian corpuscles; in
the Selachians, on the con-
trary, they sprout out in a
somewhat different manner
from the ciliate funnels.

Arrived at the base of the testicular ridge, they are joined together
into a longitudinal canal, from which fine tubules are sent still
farther into the substance of the testis, where they unite with the
structures that take their origin in the germinal epithelium. As
figure 218 B shows, the efferent tubules (sc) in Selachians at
first apply their blind ends to the ampullae, and enter into open

384 EMBRYOLOGY.

communication with them, but only after the maturation of the
seminal filaments begins.

Many differences of opinion still prevail concerning the development
of the testis in the higher Vertebrates. It is true that the presence of
a germinal epithelium upon the surface of the mesonephros has also
been established in this case by WALDEYER for the male, but its
participation in the fundament of the testis has been called in
question. According to the original account of WALDEYER, which
is still defended by many investigators, especially by KOLLIKER, the
seminal tubules are morphological products of the primitive kidney.
However, more recent researches, which it must be admitted do not
yet harmonise with one another in all points, indicate that the
development of the testis of Reptiles, Birds, and Mammals agrees
with that of non-amniotic Vertebrates in the main outlines. In
continuation of the work of BORNHAUPT and EGLI, who it is true
worked with incomplete methods of investigation, BRAUN has recently
maintained for Reptiles, SEMON for the Chick, MIHALKOVICS and
JANOSIK for the latter and for Mammals, that in the male also the
germinal epithelium begins to proliferate, penetrates into the depths
of the testis, and furnishes the primitive seminal cells. The tubules,
which according to KOLLIKER and WALDEYER grow into the funda-
ment of the testis from the primitive kidney, — the sexual cords, —
serve only for carrying away the semen. As stated by BRAUN for
Reptiles, and by SEMON for the Chick, they sprout out from the
epithelium of Malpighian corpuscles, as in the case of the Amphibia.

Although according to these accounts the double origin of the
substance of the testis, on the one hand from the germinal epithelium,
on the other from the primitive kidney, can no longer be well!
called in question, nevertheless in the details many conditions,
which are still differently described in the higher Vertebrates,
demand renewed investigation. Before all else this point should be
still further explained : In what proportion do the epithelial cells
furnished by the germinal epithelium and those by the primitive
kidney share in the formation of the testicular substance ? Are the
tubules which produce the semen formed exclusively from germinal
epithelium, or is it only the seminal mother-cells which have this
origin, while there are associated with the latter indifferent cells from
the " sexual cords of the primitive kidney " ?

I hold it to be the more probable that the tubules producing the semen,
the tubuli seminiferi, are derived from the germinal epithelium; the tubull
recti and the rete testis, on the contrary, from the primitive kidney.

THE ORGANS OF THE MIDDLE GERM-LAYER. 385

NAGEL has studied the development of the testis in human embryos. Accord-
ing to his description also, there arise from the actively proliferating germinal
epithelium numerous cords, in which large primitive seminal cells are imbedded.
The cords afterwards become the seminal tubules. In Man there prevails from
the beginning, as NAGEL remarks, such a great difference between the two
sexes, both in the form of the original germinal ridge and in the whole process
of its differentiation, that one can recognise in the anatomical structure of the
sexual glands from a very early stage whether one has before him a male
or a female.

(h) Metamorphosis of the Different Fundaments of the Urogenital
System into the Adult Condition.

We have become acquainted in the preceding pages with the first
development of the various parts which constitute the foundations of
the urogenital system. These are (fig. 219) three pairs of canals
— the mesonephric ducts (ug), the Miillerian ducts (mg), and the
ureters (hi) — and in addition a great number of glandular structures
— pronephros, mesonephros (un\ metanephros (ra), and the sexual
glands (kd), ovary and testis.

It will be my task in what follows to indicate how the ultimate
condition is derived from these embryonic fundaments. In this I
shall limit myself, in the main, to Man, because we now have to do
with more easily investigated, and in general well-known conditions.

In a human embryo eight weeks old (fig. 220) the fundaments,,
if we neglect differences which are recognisable only by the aid
of the microscope, are so similar in male and female as to be
indistinguishable.

All the glands lie at the sides of the lumbar vertebrae : farthest
forward the kidney (n), which is a small bean-shaped body ; upon
this lies the suprarenal body (nn), that at this time is dispropor-
tionately large and is to be seen only on the left half of the figure.

Somewhat lateral to the kidney one sees the primitive kidney (un)
as an elongated, narrow tract of tissue. It is attached to the wall
of the trunk by a connective-tissue lamella, a fold of the peritoneum,
the so-called mesentery of the primitive kidney. In the middle of
the gland it is rather broad, but above, toward the diaphragm, it
is elongated into a narrow band, which KOLLIKER has described as
the diaphragmatic ligament of the primitive kidney. Upon careful
examination one also observes at the lower end of the primitive
kidney a second fold of the peritoneum, which runs from it to the
inguinal region (figs. 219 and 220 gh). It encloses a firm strand
of connective tissue, a kind of ligament, that is destined to play a

25

386

EMBRYOLOGY.

part in the development of the female and male sexual organs — the
inguinal ligament of the primitive kidney. It subsequently becomes
in man the gubernaculum Hunteri, in woman the round ligament of
the uterus (ligamentum teres uteri],

On the median side of the primitive kidney is found either the

testis or the ovary (kd),
according to the sex of
the embryo, both sexual
organs still being at this
time small oval bodies.
They also possess me-
senteries of their own,
a mesorchium or meso-
varium, by means of
which they are con-
nected with the root of
the primitive kidney.
As long as the sexual
organs retain their posi-
tions on each side of
the lumbar vertebrae,
the blood-vessels that
supply them run in an
exactly transverse direc-
tion : the arteria sper-
matica from the aorta
to the ovary or the
testis, the vena sperma-
tica from the gland to

cl'

Fig. 219.— Diagram of the indifferent fundament of the
urogenital system of a Mammal at an early stage.

n, Kidney ; kd, sexual gland ; un, primitive kidney ; ug,
mesonephric duct ; mg, Miillerian duct ; nitf, its an-
terior end ; gh, gubernaculum Hunteri (mesonephric
inguinal ligament); hi, ureter; hi', its opening into
the urinary bladder ; ug", mg", openings of the mesone-
phric and Miillerian ducts into the sinus urogenitalis
(sug) ; md, rectum ; cl, cloaca ; ghS, sexual eminence ;
gw, sexual ridges ; cl', external orifice of the cloaca ;
hbl, urinary bladder ; hbl', its elongation into the
urachus (the future lig. vesico-umbilicale).

the vena cava inferior.

The various efferent
ducts lie at this time
close together at the
margin of the mesone-

phric fold (fig. 219), the
most anterior [ventral] being the Miillerian duct (mg). Farther back-
wards toward the pelvis the ducts of both sides approach the median
plane (fig. 219), whereby the Miillerian duct (mg) comes to lie for a
certain distance on the median side of and then behind [dorsal of]
the mesonephric duct (ug), so that altogether it describes around the
latter a kind of spiral course. When they reach the lesser pelvis,

THE ORGANS OF THE MIDDLE GEKM-LAYER.

387

ttae four ducts are united behind the bladder (Jibl) into a fascicle, the
genital cord ; this union is due to their becoming surrounded by the
umbilical arteries — which have at this time attained a large size, and
which run from the aorta on both
sides of the bladder up to the
umbilicus — and to their being, as
it were, tied up into a bundle by
them. In a cross section through
the genital cord (fig. 228) we find
the mesonephric ducts (ug) some-
what more anterior [ventral] and
at the same time farther apart
than the Miillerian ducts (nig),
which are a little behind them
and pressed quite close together
in the median plane.

In older embryos there arise
in the evolution of the urogenital
system differences between the
two sexes which are visible even
externally and which become
more distinct from month to

month. These result from fundamental metamorphoses, which the
whole apparatus continually undergoes in its separate parts. In
connection with this some originally quite large fundaments undergo
almost complete degeneration; of those which remain some are
serviceable only in the female, others only in the male ; when not
employed, they disappear. Moreover the conditions which were
referred to at the beginning of the description are extensively altered
by the fact that the sexual organs surrender their original position,
on either side of the lumbar vertebrae, and move farther downward
into the pelvic cavity.

I describe first the changes in the male, then those in the female.

Fig. 220. — Urinary and sexual organs of a
human embryo 8 weeks old, after KOL-
LIKER. Magnified about 3 diameters, and
seen from the ventral side.

nn, Right suprarenal body ; un, primitive
kidney ; n, kidney ; ung, mesonephric
duct ; gh, HUNTER'S directive or inguinal
ligament (gubernaculum Hunteri or liga-
mentum uteri rotundum) ; m, rectum ;
b, bladder ; Ted, sexual gland.

(A) The Metamorphosis in the Male. Descensus testiculorum.

Whereas the testis (figs. 221 and 222) by conglomeration of the
seminal tubules becomes a bulky organ (A), the mesonephros (nh+pa)
is retarded in its development more and more, and is at the same
time differently metamorphosed in its anterior and its posterior
portions. The anterior or sexual part of iJie primitive kidney (nh),

388

EMBRYOLOGY.

which has come into communication with the seminal tubules by
means of individual canals, in the manner previously described, and
has thereby furnished the rete testis and the tubuli recti, is converted
into the head of the epididymis. It exhibits in the tenth to the
twelfth week from ten to twenty short transverse canals, which are
now to be designated as vasa efferentia testis. They unite in the
mesonephric duct (fig. 222), which continues to have a straight
course, and has now become the seminal duct (si, vas deferens).
During the fourth and fifth months the individual canals begin to
grow in length and thereby to become tortuous. The vasa efferentia

in this way produce the coni vasculosir
which are at once the initial part of
the vas deferens and the tail of the
epididymis.

Incidentally let it be stated that near the
external opening of the vas deferens, as ife
passes along the posterior surface of the
bladder, there arises in the third month a
small e vagi nation, which becomes the seminal
vesicle

Pig. 221.— The internal sexual organs
of a male human embryo 9 cm.
long, after WALDEYER. Magnified
8 diameters.

h, Testis ; nh, epididymis (sexual part
of the primitive kidney) ; pa,
paradidymis (remnant of the
primitive kidney); si, vas deferens
(duct of the primitive kidney);
<7, vascular bundle of connective
tissue.

The posterior region of the primitive
kidney (pa) degenerates into very in-
significant remnants. In older embryos
one still finds for a time, between vas
deferens and testis, small, tortuous
canals, usually blind at both ends, be-
tween which degenerated Malpighian
corpuscles also occur. The whole forms
a small yellow body. In the adult these

remnants are still further reduced; they produce on the one hand?
the vasa aberrantia of the epididymis, and on the other the organ,
discovered by GIRALDES, the paradidymis. The latter consists,
according to HENLE'S description, of a small number of flat, white
bodies, lying in contact with the blood-vessels of the seminal cord,
each of which is a knotted tubule blind at both ends ; each tubule is
lined with an epithelium containing fat, and is enlarged at its blind
ends into irregularly lobed vesicles.

The Miillerian ducts (fig. 222 mg) do not acquire in the male any
function, and therefore, as useless structures, undergo degeneration ;.
the middle region in fact usually disappears without leaving a trace
although it has been for a time during embryonic life demonstrable a&

THE ORGANS OF THE MIDDLE GERM-LAYER.

389'

an epithelial cord. GASSER indeed observed a rudimentary canal of
considerable extent at the side of the vas deferens in a recently born
male child. Certain
rudiments of the ter-
minal portions, on
the contrary, are pre-
served even in the
adult individual, and
in descriptive anato-
mies are called uterus
masculinus (um) and
non-stalked hydatids
of the epididymis (hy).
The posterior ter-
minal parts of the
two Miillerian ducts,
which lie close to-
gether enclosed in
the genital cord, are
modified into the
uterus masculinus
(um). Owing to the
disappearance of the
partition separating
them, they are united
into a single small
sac, which is situated
between the openings
of the two vasa de-
ferentia at the pro-
stata and therefore
still bears the name
of sinus prostaticus.
Extraordinarily in-
conspicuous in Man,
it acquires in many
Mammals, in Carni-

hr um

Fig. 222. — Diagram to illustrate the development of the male
sexual organs of a Mammal from the indifferent funda-
ment of the urogenital system, which is diagrammatically
represented in fig. 219.

The persistent parts of the original fundament are indicated
by continuous lines, the parts which undergo degeneration
by dotted lines. Dotted lines are also employed to show
the position which the male sexual organs take after the
completion of the descensus testiculorum.

n, Kidney ; h, testis ; nh, epididymis ; pa, paradidymis ; hy,
hydatid of the epididymis ; si, vas deferens ; mg, degenerated
Miillerian duct ; um, uterus masculinus, remnant of the
Miillerian ducts ; gh, gubernaculum Hunteri ; hi, ureter ;
hi', its opening into the bladder ; sbl, vesiculae seminales ;
hbl, urinary bladder ; hbl', its upper tip, which is continuous
with the ligamentum vesico-nmbilicale medium (urachus) ;
hr, urethra ; pr, prostata ; dej, external orifice of the ductus
ejaculatorii.

The letters nk', h', si' indicate the position of the several organs
after the descent has taken place.

vores and Ruminants
(WEBER), a considerable size, and is differentiated, as in the female,
into a vaginal and a uterine part. In Man it corresponds chiefly
to the vagina (TOURNEUX).

390

EMBRYOLOGY.

The non-stalked hydatid (hy) is developed out of the other end
of the Mullerian duct. It is a small vesicle that rests upon the
epididymis, is lined with ciliate cylindrical epithelium, and is continued
into a small, likewise ciliate canal. At one place it possesses a funnel-
shaped opening, which has been compared by WALDEYEE to the-
pavilion of a Fallopian tube in miniature.

In order to complete the account of the development of the sexual
organs, there still remain to be mentioned the important changes
f position which the testis together with the attached rudiments
undergoes. Since early times, these have been embraced under the-
name of descensus testiculorum.

Originally the testes (fig. 222 h) lie, as previously stated, in the

peritoneal cavity at
the side of the lumbar
vertebrae. In the
third month we find
them already in the
greater (false) pelvis,
in the fifth and sixth
on the inner side of
the anterior wall of
the abdomen close to-
the inner abdominal
ring (fig. 223). In
consequence of these
changes the nourish-
ing blood - vessels,

at first ran transversely, have altered their direction and now
pass obliquely from below upward, because their original place of
attachment to the abdominal aorta and the inferior vena cava
remains the same. How is the migration to be explained ?

I have already mentioned the inguinal ligament, or the guberna-
culum Hunteri (fig. 222 and 223 gh), which puts the primitive
kidney, or, when this has disappeared, the testis, into connection with
the inguinal region. This ligament has in the meantime become a
.strong connective-tissue cord, in which non-striate muscles also lie.
Its upper end is attached to the head of the epididymis (nh) ; its
lower end traverses the abdominal wall to be inserted into the
corium of the inguinal region. Apparently this gubernaculum plays
a part in the migration of the sexual organs. Formerly it was be-
lieved that it exercised a traction upon the testis, in which connection

Fig. 223.— Human embryo of the fifth month, after BRAMANN.

Natural size.
Vid, Rectum ; h, testis ; nh, epididymis ; si, vas deferens ; gh,

gubernaculum Hunteri with processus vaginalis peritonei ;

bl, bladder with lig. vesico-umbilicale medium.

THE ORGANS OF THE MIDDLE GERM-LAYER.

391

attention was directed to the non-striate muscle-fibres contained in
it, or a shortening of the connective-tissue cord by gradual shrinkage
was assumed. But it is impossible for this very important change
in position to have taken place in that manner. One therefore
rightly seeks to explain the agency of the ligament in another way,
without assuming an active shortening or a traction exercised by
muscular action. We have to do here simply with processes of
unequal growth. When, out of several organs originally lying beside
one another in the same region of the body, certain ones in later
months of embryonic life increase in size less, while others, on the
contrary, grow extraordinarily in length, the natural consequence is
that the more rapidly growing parts are shoved past those that grow

Fig. 224.— Two diagrams to illustrate the descensus and the formation of the envelopes of the

testis.
A, The testis lies in the vicinity of the inner abdominal ring. B, The testis has entered the

scrotum.
1, Skin of the abdomen ; 1', scrotum with tunica dartos ; 2, superficial abdominal fascia ; 2',

COOPER'S fascia ; 3, muscle-layer and fascia transversa abdominis ; 3', tunica vaginalis

communis with cremaster ; 4, peritoneum ; 4', parietal layer of the tunica vaginalis propria ;

4", peritoneal investment of the testis or visceral layer of the tunica vaginalis propria.'
Ir, Inguinal or abdominal ring ; h, testis ; si, vas deferens.

more slowly. If, now, in the present case the skeletal parts and
their accompanying muscles in the lumbar and pelvic regions become
elongated, while the Hunterian ligament does not grow and there-
fore remains short, the latter necessarily — because one of its ends
is attached to the skin of the inguinal region and the other to the
testis — draws down the testis as the movable part; it draws the
testis at first gradually into the cavity of the false pelvis, and finally,
when the other parts have become still larger, when at the same
time the abdominal wall has become much thicker, into the vicinity
of the inner abdominal ring (fig. 223).

The testis migrates still farther in consequence of a second process,
which begins even in the second month. For there is formed at the
place where HUNTER'S ligament traverses the wall of the abdomen
an evagination of the peritoneum, the processus vaginalis peritonei

392 EMBRYOLOGY.

(fig. 224 A). This gradually penetrates the abdominal wall and
enters into a fold of the skin, which is developed in the pubic region,
as will be shown in a subsequent section (see fig. 231 gw). The
opening of the hernia-like evagination, which leads into the body-
cavity, is called the inner inguinal [abdominal] ring (Ir) ; the portion
which traverses the musculature of the abdominal wall, the inguinal
canal ; and the blind end which is expanded within the dermal fold,
the scrotum.

In its migration the testis (fig. 224 It) also sinks down into this
peritoneal fold, whereby it remains undetermined whether HUNTER'S
ligament exercises an influence on it or not. The entrance into the
inguinal canal usually takes place in the eighth month, into the
scrotum in the ninth month, so that at the end of embryonic life
the descent is, as a rule, completed. The canal then closes by
fusion of its walls, and thereby the testis comes to lie in a sac
constricted off from the abdominal cavity and enclosed on all
sides.

The various enveloping structures of the testis also become intelli-
gible from the sketch of the development just given. Since the
cavity which shelters it is simply a detached portion of the body-
cavity, it is, as a matter of course, lined by peritoneum (fig. 224 4').
This is the so-called tunica vaginalis propria, on which, as on other
regions of the peritoneum, we have to distinguish a parietal layer
(4') lining the wall of the sac and a visceral layer (4") investing the
testis. Outside of this follows the tunica vaginalis communis (/) ;
it is the evaginated, and at the same time extraordinarily attenu-
ated, layer of muscles and fasciae (3) of the abdominal wall. Con-
sequently it also contains some muscle-fibres enclosed in it, which
are derived from the musculus obliquus abdominis internus, and
constitute the suspensory muscle of the testis or cremaster.

In the descensus testiculorum, which should normally be com-
pleted in Man at the end of embryonic life, interruptions may, under
certain circumstances, occur and produce an abnormal location of the
testis, which is known under the name of cryptorchism. The descent
remains incomplete. Then the testes of the recently born child are
either found to be located in the body-cavity, or they still stick fast
in the wall of the abdomen, in the inguinal canal. In consequence
the scrotum feels small, flabby, and flaccid.

Such anomalies are designated as inhibition-malformations, because
they are explained by the fact that the processes of development
have not reached their normal termination.

THE ORGANS OF THE MIDDLE GERM-LAYER.

393

kbl'

(B) The Metamorphosis in the Female. Descensus ovariorum.

The metamorphosis of the primitive embryonic fundaments in the
female is in many particulars the opposite of that in the male, inas-
much as parts which are made use of in the latter become rudi-
mentary in the
former, and
'vice versd (com-
pare with one
another the
diagrams
shown in figs.
219, 222, and
225). Whereas
in man the
mesonephric
duct becomes
the vas defer-
ens, in woman
the Miillerian
duct (fig. 225
t, ut, sch) as-
sumes the func-
tion of conduct-
ing away the
ova, while the
mesonephric
duct (ug) and
the primitive
kidney (ep, pa)
become rudi-
mentary.

The prone-

fig. 225. — Diagram to illustrate the development of the female sexual
organs of a Mammal from the indifferent fundament of the uro-
genital system, which is diagrammatically represented in fig. 219.

The persistent parts of the original fundament are indicated by con-
tinuous lines, the parts which undergo degeneration by dotted
lines. Dotted lines are also employed to show the position which
the female sexual organs take after the completion of the descensus.

n, Kidney ; ei, ovary ; ep, epoophoron ; pa, paroophorori ; hy, hydatid ;
t, Fallopian tube (oviduct) ; ug, mesonephric duct ; ut, uterus ; sch,
vagina ; hi, ureter ; hbl, urinary bladder ; hbl', its upper tip, which
is continuous with the ligamentum vesico-umbilicale medium ; hr,
urethra ; vv, vestibulum vaginae ; rm, round ligament (inguinal
ligament of the primitive kidney) ; lo', ligamentum ovarii.

The letters t', ep', ei', lo' indicate the positions of the organs after the
descent.

phric duct in

advanced human embryos of the female sex is still demonstrable as
an inconspicuous structure in the broad ligament and at the side
of the uterus ; in the adult it has, as a rule, entirely disappeared,
except the terminal portion, which is enclosed in the substance of
the neck of the uterus, where it is distinguishable, but only by
means of cross sections, as an extraordinarily narrow tubule (BEIGEL,
H. DOHRN). In many Mammals, as in Ruminants and Swine, the

394

EMBRYOLOGY.

mesonephric ducts persist even later in a rudimentary condition, and'
are here known under the name of GARTNER'S canals.

There are to be distinguished on the degenerating primitive kidney, as
in Man, an anterior and a posterior region (WALDEYER).

The anterior region (figs. 225 ep, 226 ep), or the sexual part of the
primitive kidney, which in the male becomes the epididymis, is also
retained by the female as an organ without function and here
becomes the parovarium (ep), which was first accurately described by
KOBELT (the parovarium or epoophoron of WALDEYER). It lies in

the broad ligament (fig. 226)
between ovary (ei) and Miillerian
duct (t), and consists of a longitu-
dinal canal (ug), the remnant of
the upper end of the mesonephric
duct, and of ten to fifteen trans-
verse tubules (ep). The latter
have at first a straight course,
but afterwards become tortuous
(fig. 227 ep), in much the same
way as the canals which in the
male are converted into the coni
vasculosi. The comparison be-
tween parovarium and epididy-
mis may be carried still further.
As in the male tubules grow out
from the latter into the cortex
of the testis and are there diffe-
rentiated into the rete testis and
the tubuli recti, so there are also
canals found in the female which
proceed from the parovarium,

enter the medullary substance of the ovary itself, and form here
the previously (p. 381) described medullary cords, which are highly
developed in many Mammals.

The posterior portion of the primitive kidney, which in the male
(figs. 221 and 222 pa) furnishes the paradidymis and the vasa
aberrantia, degenerates in the female (fig. 225 pa) in a similar
manner into the paroophoron, and is still to be recognised for a long
time in the human embryo as a yellowish body (fig. 226 pa), which
lies medianwards of the epoophoron (ep) in the broad ligament, and
is composed of small, tortuous, ciliate tubules (pa) and a few

Fig. 226.— The internal sexual parts of a
female human embryo 9 cm. long, after
WALDEYER. Magnified 10 diameters.

ei, Ovary ; t, Miillerian duct or oviduct (Fallo-
pian tube) ; t', ostium abdominale tubse ;
ep, epoophoron (= epididymis of the male
— sexual part of the primitive kidney) ;
v.g, mesonephric duct (vas deferens of the
male) ; pa, paroophoron (paradidymis of
the male — rudiment of the primitive
kidney) ; mk, Malpighian corpuscles.

THE ORGANS OF THE MIDDLE GERM-LAYER.

395

degenerating vascular glomeruli (mk). Certain canals and cyst-like
structures, which are often found in the broad ligament of the adult
close to the uterus, are to be referred to it.

The two Mulkrian ducts (fig. 219 mg), which from the beginning
lie in the margin of the peritoneal fold that serves for the reception
of the ovary and subsequently becomes the broad ligament, undergo
a very profound metamorphosis. It has already been mentioned
that as they enter the lesser or true pelvis they approach the median
plane, and are joined to the genital cord. We can therefore dis-
tinguish in them two different regions, one enclosed in the genital
cord, the other lying in the margin of the broad ligament. The

Fig. 227.— Broad ligament with ovary and oviduct in the adult condition, seen from behind.
ei, Ovary ; t, oviduct ; f, ostium abdominale tubse with fimbrise ; f.o, fimbriae ovarii ; l.o, liga-

nientum ovarii ; x, a portion of the peritoneal investment is dissected away, in order to see

the epoophoron (parovarium), ep.

latter becomes the oviduct (the tuba Fallopian) with its funnel-shaped
beginning (figs. 225 t, 226, 227 t, t'). The anterior end of the
Miillerian duct, which in the embryo reaches far forward and is
here enclosed in the diaphragmatic ligament of the primitive kidney,
appears in the meantime to degenerate, whereas the permanent
opening (figs. 225 tfand 226 t'} is probably an entirely new formation.
MORGAGNI'S hydatid (fig. 225 hy) is perhaps to be referred to the
anterior rudimentary part — the conditions, here have not yet been
made entirely clear. This structure is a small vesicle, which is joined,
by means of a longer or shorter stalk, with one of the fimbrise of the
funnel-shaped end of the oviduct.

Out of the part of the Miillerian ducts enclosed in the genital
cord (fig. 219 mg) are formed the uterus and the vagina (fig. 225 ut

396 EMBRYOLOGY.

and sch), as THIERSCH and KOLLIKER have shown for Mammals, and
us DOHRN and TOURNEUX ET LEGAY afterwards showed for Man.
Their formation is accomplished by a process of fusion, which in
Man is effected in the second month. When the Miillerian ducts
(fig. 228 mg) are closely pressed together, the partition between them
becomes thin and breaks through — at first in the middle of the genital
cord. Thus there is developed out of them by an extension of this
process a single sac (the sinus genitalis), which is also established in
the male as a rudimentary organ, the previously mentioned sinus
prostaticus or uterus masculinus (fig. 222 um). In woman it begins
to be differentiated in the sixth month into uterus and vagina. The
upper portion, which receives the oviducts, acquires very thick,
muscular walls and a narrow lumen, and is limited below by a re-
entering ring-like ridge — that becomes the vaginal portion [of the
uterus] — from the lower portion, the vagina, which remains spacious
a,nd possesses a thinner wall.

Similarly to the testis, the ovaries also have to pass through a con-
siderable change in position : the descensus ovariorum (fig. 225 ei', t'),
which corresponds to the descent of the testes. In the third month
of embryonic life, at the time when the primitive kidney begins to
disappear, the ovaries move from the region of the lumbar vertebrae
•down into the false pelvis, where they are found medianwards from
the musculus psoas. Probably the above-described inguinal ligament
of the primitive kidney (fig. 225 rm), which is not wanting in the
female, participates in the change of position in this case also. As
WIEGER has recently shown, the ligament is differentiated into three
distinct regions by the fact that it acquires a firm union with the
Miillerian ducts at the place where they meet to form the sexual
cord. The uppermost region becomes a strand of non-striate muscle-
fibres, which, arising from the parovarium, is imbedded in the hilus
of the ovary. This is continuous with the second region, or the
ligamentum ovarii (lo1), and the latter with the round ligament (rm)
(ligamentum teres uteri). The round ligament, produced from the
third and most developed region of the inguinal ligament, extends
from the upper end of the genital cord to the inguinal region. Here
there is usually, as in the male, a small evagination of the peritoneum,
the processus vaginalis peritonei, which occasionally persists even in
the adult as the diverticulum Nuckii, and then may likewise be the
cause of the formation of an inguinal hernia in the female. At this
place the round ligament passes through the wall of the abdomen
and ends in the external skin of the labia majora.

THE ORGANS OF THE MIDDLE GERM-LAYER. 391

In its last stages the descent in the female is accomplished in
a manner different from that in the male. For instead of advancing
like the testes toward the inguinal region, the ovaries, when the
development is normal, sink down instead into the true pelvis. Here
they are enclosed between bladder and rectum in the broad ligament,
which is developed out of the peritoneal folds, and in which originally
the primitive kidneys, the ovaries, and the Miillerian ducts ar&
imbedded.

Naturally the round ligament cannot be of influence during this
last stage of the descent in the female, because it can exercise a
traction only in the direction of the inguinal region, where it is
attached. The descent into the true pelvis seems rather to be due to
the conversion of the lower region of the Miillerian ducts into the
uterus. At any rate, the ovaries are joined to the uterus by means
of a firm cord of connective tissue,
the ligamentum ovarii.

In rare cases in the female the
ovaries can continue to change their
position in a manner corresponding
to that in the male. They migrate
then toward the inguinal region up
to the entrance into the processus
vagirmlis (diverticulum Nuckii); oc-
casionally they here cease to advance, The cross section shows the fusion of the
but sometimes theyenter farther into J^f"1 ducte(w*); U9' m<

the abdominal wall through the in-
guinal canal ; indeed, as has been observed in several instances, they
can pass quite through the wall of the abdomen and at last imbed
themselves in the labia majora. The latter then acquire a great
similarity to the scrotum of the male.

(i) The Development of the External Sexual Organs.

The section which deals with the urinary and sexual organs is-
really the most suitable place at which to introduce the development
of the external sexual organs, notwithstanding they do not arise
from the middle germ-layer, but in part from the outer and in part
from the inner germ-layer. In order to give an exhaustive account
of them, we must go back to rather early stages of development —
to the time when in the embryo the Wolffian and Miillerian ducts
are established. Having first arisen in the most anterior part of the-

398

EMBRYOLOGY.

embryo, they grow backwards to the terminal part of the intestine,
and there implant themselves in the allantois. This is, as we have
seen in the first part of this text-book (fig. 132, 3 and 4 al), an
organ which is produced by evagination of the anterior [ventral] wall
•of the hind gut. In most Mammals (figs. 134 al and 142 ALC) it

attains during embryonic
life a quite extraordinary
development, for it grows
out of the body-cavity,
penetrates between the
other foetal membranes,
and is distended into a
large vesicle, which re-
ceives the urinary fluid
secreted by the embryo.
The part of it which lies
in the body-cavity remains,
on the contrary, narrow.

\*y\ \ /^^> ^e terminal Part of it

* ti which receives the Wolffian

and Miillerian ducts is
called sinus urogenitalis
(fig. 219 sug and 229 ug\
a structure which will often
demand our attention in
considering the develop-
ment of the external sexual
organs.

The sinus urogenitalis
and the hind gut unite
to form a short, unpaired
region, the cloaca (fig. 229
cl), a small depression
which opens out at the-
surface of the body and

in very many Vertebrates— in the Amphibia, Reptiles, Birds, and
the lowest Mammals, the Monotremes — persists throughout life.
In the remaining Mammals, however, these structures have only
an embryonic existence. In the first case all the elimination -
products of the body are conducted to the outside through the
cloaca,— out of the hind intestine the fecal masses, out of the

Tig. 229.— Diagram of the urogenital organs of a
Mammal at an early stage, after ALLEN THOMSON ;
from BALFOUR.

The parts are seen chiefly in profile, but the Mullerian
and Wolffian ducts are seen from the front.

3, Ureter ; k, urinary bladder ; 5, urachus ; ot, genital
gland (ovary or testis) ; W, left Wolffian body
(primitive kidney) ; x, its diaphragmatic ligament ;
10, Wolffian (mesonephric) duct; m, Mullerian
duct ; gc, genital cord consisting of Wolffian and
Mullerian ducts enveloped in a common sheath ;
i, rectum ; ug, urogenital sinus ; cp, genital emin-
ence, which becomes the clitoris or penis; Is, genital
ridges from which the labia majora or the scrotum
are developed.

THE ORGANS OF THE MIDDLE GERM-LAYER. 399

sinus urogenitalis the urinary fluid and the male or female sexual
products.

As far as regards the special conditions in Man, the allantois
remains in his case very small (fig. 132, 5 al) and possesses a lumen
in the region of the body-cavity only, whereas in the umbilical cord
and between the remaining fo3tal membranes only its connective -
tissue part, together with the blood-vessels, which shares largely in
the development of the placenta, grows further. In the second
month its hollow part, lying on the front wall of the abdomen,
becomes a spindle-shaped body (fig. 229 4). Its middle enlargement
becomes the urinary bladder (4), its upward prolongation, which
reaches to the navel, is called urachus (5), the other end (ug) is the
sinus urogenitalis. The urachus degenerates during embryonic life and
furnishes a connective-tissue cord, the ligamentum vesico-umbilicale
medium, which extends from the apex of the bladder (fig. 219 hbl')
to the navel, and often in the first years after birth still contains an
epithelial cord, a remnant of the original epithelial canal.

As is well known, the ureters (figs. 229 3 and 219 hi') in the adult
open close together at the posterior surface of the urinary bladder
(229 4). In very young embryos this is not the case at first, for the
two ureters arise from the posterior part of the mesonephric duct,
and this opens into the sinus urogenitalis. But this condition is
soon altered. The ureter splits off from the mesonephric duct,
and comes to open independently into the posterior wall of the sinus
urogenitalis, from which it afterwards becomes gradually removed,
since its orifice, as it were, creeps higher up on the posterior wall of the
bladder. Like the change in the position of the sexual glands, we
must also conceive of this shifting as produced by processes of growth
in such a way that especially the tract between mesonephric duct
and ureter, which is at first small, increases in size, and thereby
produces the apparent upward migration of the opening of the
ureter.

In the sixth week the cloaca in Man undergoes alterations which
are connected with the development of the external sexual organs.
The cloacal depression, which in earlier stages (fig. 230 A) appears
fissure-like, afterwards becomes (fig. 230 .Z?) surrounded by a ring-
like fold, the genital ridge (gw), and there also arises in its anterior
portion a growth of connective tissue, which produces the externally
protruding genital eminence (gti). Along the lower surface of the
latter there is formed at the same time a groove (ffr)i which extends
downward to the cloaca, of which it is, as it were, the continuation.

400 EMBRYOLOGY.

In the following weeks of development the eminence protrudes still
more, and thereby becomes converted into the genital member, which
is at first possessed by both sexes in the same condition ; meanwhile
the groove (gr) on its under surface becomes deeper, and surrounded,,
at the right and left, by projecting folds of the skin, the genital,
folds (#/*). (Compare also the diagrams fig. 219 gho, gw, cl' and
fig. 229 cp, Is, cl)

Alterations follow (fig. 231 M and W) by which the cloaca is-
differentiated into two openings, one lying behind the other, the anus
(a) and the separate urogenital opening (ug). The deep partition
(fig. 229) by which the sinus urogenitalis and the rectum are separated
from each other begins to grow outward, and at the same time folds
also arise on the lateral walls of the cloaca and unite with it. Thus
a membrane (fig. 231 d) is developed which separates a posterior
opening (a), the anus, from an anterior opening, the entrance to
the sinus urogenitalis (ug). Inasmuch as this partition continues to<
become thicker up to the end of embryonic life, it finally crowds the
two openings far apart and forms between them the perinseum (fig,
231 M* and W* d). In this way the anus (a) moves entirely out of
the territory of the previously mentioned genital ridge (fig. 230 gw).

From the fourth month onward great differences arise in the develop-
ment of the external sexual parts in male and female embryos.

In the female (fig. 231 W and W*) the metamorphoses of the
originally common embryonic foundations are on the whole only
slight ; the genital eminence grows only slowly and becomes the
female member, the clitoris (cl). Its anterior end begins to thicken,
and to be marked off from the remaining part of the body as the glans.
By a process of folding in the integument there is developed around
it (fig. 231 W* vh) a kind of foreskin (the prseputium clitoridis).
The two genital folds (W gf), which have bounded the groove on the
under surface of the genital knob, take on a more vigorous develop-
ment in the female than in the male, and are converted into the labia
minora (W* ksch). The space between them (W ug), or the sinus
urogenitalis, which receives the outlet of the urinary bladder and
the vagina developed by the fusion of the Mullerian ducts, is called
the vestibulum vagince (W* vv). In the female the genital ridges
(W gw), owing to the deposition of fatty tissue, become very volu-
minous, and are thus converted into the labia major a (W* gsch).

The corresponding fundaments pass through much more essential
metamorphoses in the male (fig. 231 M and M*). By an extra-
ordinarily vigorous growth in length the genital eminence is

THE ORGANS OF THE MIDDLE GERM-LAYER.

Fig. 230.

l

i

401

Fig. 231.

d&r

Figs. 230 and 231.— Six stages in the development of the external sexual organs in the male and

the female, after the ECKER-ZIEGLEH wax models.
Fig. 230 A and B. —Two stages in which a difference of the sexes is not yet to be recognised,

£ from an embryo 8 weeks old.
Fig. 231.— The two stages jV/and M* exhibit the metamorphosis of the original fundament in

the male in embryos 2£ and 3 months old respectively. The stages W and W* present the

metamorphosis in the female (2£ and 4£ months).
The same designations are used for all of the figures.
he, Posterior paired extremity ; do, cloaca ; gh, genital eminence ; gf, genital fold ; gr, genital

groove ; gw, genital ridges ; gp, glans penis ; cl, clitoris ; d, perinaeiim ; a, anus ; ug, entrance

to sinus urogenitalis or vestibulum vaginae ; vv, vestibulum vaginae ; vh, foreskin (prepuce) ;

ks, scrotum ; d & r, raphe perinei and scroti ; gsch, labia majora ; ksch, labia minora.

26

402 EMBRYOLOGY.

converted into the male member, or the penis, which corresponds to
the clitoris of the female. Like the latter, it possesses an anterior
knob-like enlargement, the glans (M gp), which is embraced by a
fold of the skin, the praeputium (M* vh). The sinus urogenitalis,
which in the female remains short anct broad as the vestibulum
vaginae, is in the male converted by a process of fusion into a long
narrow canal, the urinary tube or urethra. This results from the
fact that the furrow on the under surface of the genital protuberance
( M gr) becomes elongated during the development of the latter and
at the same time deeper, and that the sexual folds (gf) bordering it
protrude farther, coming into immediate contact along their edges
(M*) as early as the fourth month, and begin to fuse together.

The posterior end of the urethra early (second month) undergoes
changes by which the prostata (fig. 222 pr) is formed. The walls
become greatly thickened, acquire non-striate muscular tissue, and
constitute a ring-like ridge, into which evaginations from the epi-
thelium of the tube penetrate, and by their branchings furnish the
glandular portions of the organ. On its posterior wall are found, as
is well known, the openings (dej) of the vasa deferentia, and between
them the sinus prostaticus or uterus masculinus (urn), produced by
the fusion of the Miillerian ducts.

The genital ridges (fig. 231 M gw), which in. woman become
the labia majora, also undergo a fusion in man. They surround
the root of the penis and then fuse in the median plane, where
the place of union is indicated afterwards by the so called raphe
scroti (M* r). Into the scrotum (M* ks) thus formed the testes,
toward the end of embryonic life, migrate, as previously described.

From the fact that originally the external sexual parts are con-
stituted exactly alike in both sexes, it is evident why, with a
derangement of the normal course of development, forms come into
existence in which it is sometimes extremely difficult to determine
whether one has to do with male or female external parts. These
are cases which in earlier times were erroneously designated as
hermaphroditism. There are two ways in which they may arise.
They are either to be referred to the fact that in a female the
process of development has proceeded further than normally (i.e.,
as in the male), or that in a male the process of development has
suffered an early interruption, and thereby led to formations which
are similar to the female genital parts.

As far as regards the first kind of malformations, the genital
eminence in the female occasionally assumes such a size and form

THE ORGANS OF THE MIDDLE GERM-LATER. 403

that it resembles in every particular the male organ. The resem-
blance may become even greater, when the ovaries migrate into the
inguinal region instead of the true pelvis, pass through the wall of
the abdomen, and become imbedded in the labia majora. In con-
sequence of this the latter lie upon the root of the larga clitoris and
simulate a kind of scrotum.

The malformations which have given occasion for the assumption
of hermaphroditism are of more frequent occurrence in the male.
They are attributable to the fact that the processes of fusion which
normally take place are interrupted. We then have a genital
member, which ordinarily is rudimentary, along the under side of
which there runs only a furrow instead of the urethra, a malforma-
tion which is designated as hypospadias. With this morphological
deficiency may be united, secondly, an arrest of the normal descent
of the testes. The latter remain in the body-cavity, and the genital
ridges thus acquire a great similarity to the labia majora of the female.

III. The Development of the Suprarenal Bodies.

The discussion of the suprarenal bodies best follows that of the
urogenital system. For, aside from the fact that the suprarenal
bodies and the genito -urinary organs are in all Vertebrates very
closely connected spatially, they also appear to stand in very close
relation to each other in the history of their development. At least
the recent investigations of WELDON, JANOSIK, and MIHALKOVICS
point that way. and are perhaps also sufficient to suggest the direction
of the physiological research by which one can acquire an explanation
concerning the ever problematic function of these bodies.

As is well known, there are to be distinguished in the suprarenal
bodies two different substances, which in Mammals are described,
according to their mutual relations, as medulla and cortex. Most
investigators ascribe to them a double origin. BALFOUR, BRAUN,
KOLLIKER, and MITSUKURI make the medulla arise from the gang-
lionic fundaments of the sympathetic nerve-trunk (Grenzstrang), — it
is for this reason that in many text-books the suprarenal bodies are
treated of in connection with the sympathetic, — but GOTTSCHAU and
JANOSIK controvert this ; they maintain that only certain ganglionic
cells and nerve-fibres grow in from the sympathetic, but that the
real medullary cells arise by a metamorphosis of cortical cells. It
appears to me from the existing investigations that the question is
not ready for discussion.

404 EMBRYOLOGY.

There are also two different interpretations concerning the develop-
ment of the cortical substance. BALFOUR, BRAUN, BRUNN, and MIT-
SUKURI derive it from accumulations of connective-tissue cells, which^
are formed at the anterior portion of the primitive kidney along the
course of the inferior vena cava and the cardinal veins. According
to JANOSIK, WELDON, and MIHALKOVICS, on the contrary, the cell-
accumulations are either directly or indirectly formative products of
the epithelium of the body-cavity. I say " direct or indirect " because
in details the results of the three investigators named differ somewhat.
According to JANOSIK and MIHALKOVICS, it is the germinal epithelium
in the anterior portion of the genital ridge that furnishes by its
proliferation the material for the suprarenal body. MIHALKOVICS
therefore calls it " a detached part of the sexually undifferentiated
genital gland, which consequently remains at a primitive stage of
development." WELDON, on the contrary, brings the suprarenal
body into relation with the most anterior part of the primitive
kidney. According to his representation, which appears to me to
deserve especial consideration, and from which indeed other researches
will have to begin, the sexual cords of the primitive kidney are concerned
in the formation of the suprarenal bodies. When, at the head-end of
the kidney, they sprout out of the epithelium of the Malpighian
glomerulus in the manner previously (p. 383) described, they divide
into two branches. One of these grows ventrally into the fundament
of the sexual gland, the other turns dorsally and spreads out in the
vicinity of the vena cava.

Moreover, even MIHALKOVICS describes a connection of the sexual
cords with the fundament of the suprarenal body at certain places,
but makes both arise from proliferations of the epithelium of the
body-cavity. The connection is subsequently destroyed by the inter-
polation of blood-vessels.

For the solution of the still pending questions most is to be expected
from the investigation of non-amniotic animals.

During its development the suprarenal body is for a time of very
considerable size. In Mammals it temporarily covers the much
smaller kidney, as in the human embryo of the eighth week repre-
sented in fig. 220, in which at the left the suprarenal body (nn) is
to be seen in its normal position, whereas on the right it has been
removed to disclose the kidney (n). Afterwards its growth does not
keep pace with that of the kidney ; however at birth (fig. 208), when
it already rests upon the latter (n) as a crescentic body (nn), it still
is larger in comparison with the kidney than it is in the adult.

THE ORGANS OP THE MIDDLE GERM-LAYER. 405

During its development some small portions of the fundament of
the suprarenal cortex appear sometimes to detach themselves and to
remain in the vicinity of the sexual organs, in whose migrations they
participate. Thus, indeed, are to be explained the accessory supra-
renal bodies observed by MARCHAND at the margin of the broad
ligamentl

SUMMARY.

1. The following structures are to be interpreted as formative
products of the middle germ-layer : the epithelium of the body-cavity
(of the pericardium, of the thoracic and abdominal cavities, of the
cavity of the scrotum), the whole of the transversely striped, voluntary
musculature, the seminal cells and ova, the epithelium of the sexual
glands, of the kidneys and their outlets, and the cortical cords of the
suprarenal bodies.

The Development of the Musculature.

2. The musculature of the trunk is developed exclusively from
the cell-layer of the primitive segments that abuts upon the chorda
and neural tube, which by the formation of muscle-fibrillae is con-
verted into a muscle-plate.

3. The muscle-plate enlarges dorsally and ventrally, where it
becomes continuous (zone of growth) with the outer (lateral) epi-
thelial layer of the primitive segment, and spreads itself out over
the neural tube above and into the walls of the abdomen below.

4. The original musculature consists of segments of longitudinal
fibres (myomeres), which are separated from one another by connec-
tive-tissue partitions (ligamenta intermuscularia).

5. The musculature causes the first segmentation of the body of
Vertebrates into equivalent successive parts or metamera.

6. Buds grow out from the muscle-plates (Selachians) into the
fundaments of the limbs, and thus furnish the foundation for the
whole musculature of the extremities.

7. In the head-region of Vertebrates the musculature is developed
not only out of the primitive segments, the number of which in
Selachians amounts to nine, but also out of that part of the middle
germ-layer which corresponds to the lateral plates of the trunk, and
which is divided up by the formation of the visceral clefts into sepa-
rate visceral-arch cords, which in the Selachians are provided with
cavities.

406 EMBRYOLOGY.

8. From the primitive segments of the head are formed the muscles
of the eyes, and from the visceral-arch cords the masticatory muscles,
the muscles of the hyoid arch and also those of the small bones of the
ear (?).

The Development of the Urogenital System.

9. The first fundament of the urogenital system is the same in
both sexes: it consists of (1) three pairs of canals — the mesonephric
duct, the Miillerian duct, and the ureter; (2) four pairs of glands —
the pro-, meso-, and metanephros and the sexual gland, which at first
is indifferent.

10. The mesonephric duct arises in its most anterior part out of
a groove-like evagination or a ridge-like thickening of the parietal
middle layer ; posteriorly it detaches itself from its parental tissues,
fuses with the neighboring outer germ-layer, and thereby forms at
first a short, tubular communication between the crelom and the
surface of the body.

11. The mesonephric duct is gradually converted into a long
canal, inasmuch as it grows backward on the outer germ-layer,
which forms a thickened ridge, until it opens out into the cloaca
(terminal part of the hind intestine).

12. The pronephros (head-kidney) is developed at the anterior
part of the mesonephric duct in the following manner : the duct,
upon being constricted off from the parietal middle layer, remains in
connection with the latter at several places, and the resulting cords
of connection grow out into long pronephric tubules, at the inner
openings of which an intraperitoneal vascular glomerulus is estab-
lished out of the wall of the body-cavity.

13. Behind the pronephros the mesonephros (primitive kidney)
arises thus : when the primitive segments are constricted off from
the lateral plates, segmentally arranged cellular tubes or cords
(nephrotome) are formed, which communicate at one of their ends
with the body-cavity and at their other ends put themselves into
connection with the laterally situated mesonephric duct and become
the mesonephric tubules. (Development of Malpighian corpuscles,
of secondary and tertiary mesonephric tubules and the glomeration
of the latter.)

14. In the higher Vertebrates the development of the primitive
kidney is to a certain extent abbreviated, in so far as the separate
cords of cells which arise at the constricting off of the primitive
segments lie very close together and constitute an apparently

THE ORGANS OF THE MIDDLE GERM-LAYER. 407

undifferentiated cell-mass (the middle plate or the mesonephric
blastema), out of which the mesonephric tubules subsequently —
when they become clearly distinguishable — appear to have been
differentiated.

15. In a part of the non-amniotic Vertebrates (some Selachians,
Amphibians) the primitive kidney remains in open communication
with the body-cavity by means of numerous ciliate funne'.s (nephro-
stomes), whereas in all Amniota the mesonephric tubules early
surrender their genetically established connection with the body-
cavity through the disappearance of the ciliate funnels.

16. The permanent kidney (metanephros) is the latest to be
formed and takes its origin from two separate paits : —

(a) From an evagination of the end of the mesonephric duct,

which furnishes the ureters, the pelvis of the kidney, and
the straight urinary tubules (in other words, the efferent
apparatus) ;

(b) From a renal blastema, which represents a backward pro-

longation of the mesonephric blastema, has the same
origin as the latter, and is converted into the tortuous
urinary tubules with the Malpighian corpuscles (therefore
the secretory part of the kidney).

17. The fundaments of the kidney, which have arisen far back in
the body, rapidly increase in size and undergo a change of position
by moving farther forward by the side of the primitive kidneys,
whereby the ureter becomes wholly detached from the mesonephric
duct and moves to the posterior [dorsal] surface of the allantois, the
future urinary bladder.

18. In the non-amniotic Vertebrates the mesonephros also gives
rise by a process of fission to the Miillerian duct, which runs
parallel with it.

19. In the Amniota the relation of the Miillerian duct to the
mesonephric duct is still uncertain, because the front end of the former
is established by a groove-like depression of the epithelial invest-
ment on the lateral face of the mesonephros, while concerning the
remaining part it is still undetermined whether it grows backwards
independently or is constricted off from the mesonephric duct.

20. The sexual glands proceed from two fundaments : —

(a) From a germinal epithelium, a modified part of the epithelium
of the body-cavity, located on the median face of the
primitive kidney ;

(6) From the sexual cords, which grow out toward the germinal

408 EMBRYOLOGY.

epithelium from the adjacent part of the primitive kidney
(in Reptiles and Birds from the epithelium of Malpighian
glomeruli).

21. The specific components of the sexual glands, the eggs and
seminal cells, arise from the germinal epithelium (with its primitive
ova and primitive seminal cells).

22. In the female there arise, in consequence of a process of
mutual intergrowth on the part of the germinal epithelium and the
subjacent stroma, the tubes of PFLUGER and egg-balls (or nests), and
out of these finally egg-follicles, containing each a single ovum ; in
the male there are formed, in consequence of a similar process, seminal
ampullae (Selachians, some Amphibia) or seminal tubules (tubuli
seminiferi) with their seminal mother-cells.

23. The sexual cords of the primitive kidney participate in the
composition of the medullary substance of the ovary as medullary
cords ; in the testis they unite with the seminal ampullae or seminal
tubules and furnish the tubuli recti and the rete testis, consequently
the initial part of the outlet for the semen.

24. The ovarian follicles are composed of a centrally located ovum,
an envelope of f ollicular cells, and a vascular connective-tissue capsule
(theca folliculi).

25. In Mammals the ovarian follicle is converted into a Graafian
follicle by an increase in the number of f ollicular cells and by their
secreting between them a follicular fluid. (Discus proligerus, mem-
brana granulosa.)

26. The Graafian follicles, after the elimination of the mature ova
into the abdominal cavity, become the so-called yellow bodies in the
following manner : blood flows out of the ruptured blood-vessels
into their cavities, and both the follicular cells left behind and the
connective- tissue capsule undergo proliferation accompanied by an
emigration of white blood-corpuscles (true and false corpora lutea).

27. The yellow bodies subsequently cause by their scar -like shrivel-
ling the cicatriculae and callosities on the surface of old ovaries.

28. The canals and glands of the urogenital system, which are at
first established in the same form in both sexes, are afterwards
differently employed in the male and female and undergo a partial
degeneration.

29. In the male the mesonephric duct becomes the vas deferens,
in the female it becomes rudimentary (GARTNER'S duct, in many
Mammals).

30. The Miillerian duct assumes in the male no function, and

THE ORGANS OF THE MIDDLE GERM-LAYER. 409

only inconspicuous remnants of it are left at its ends (hydatid of
the epididymis and sinus prostaticus or uterus masculinus) ; in the
female it becomes the efferent apparatus of the ovary, — the anterior
part the oviduct, the posterior part the uterus and vagina, the latter
resulting from the fusion of the ducts of the opposite sides of the
body as far as they are enclosed in the genital cord.

31. In the male the anterior portion of the primitive kidney
(mesonephros) — having united with the seminal tubules by means
of the sexual cords — persists as the epididymis ; the remainder de-
generates into the paradidymis. In the female both parts degenerate
into epoophoron and paroophoron, which correspond respectively to
the epididymis and paradidymis of the male.

32. The sexual glands, which are originally established in the
lumbar region, gradually move with their outlets downward toward
the pelvic cavity. (Descensus testiculorum et ovariorum. Oblique
course of the spermatic arteries and veins.)

33. In the migration of the sexual glands a r61e appears to be
played by the inguinal ligament, which passes from the primitive
kidney underneath the peritoneum to the inguinal region, penetrates
through the wall of the abdomen, and ends in the skin of the genital
ridges that surround the cloaca. (Gubernaculum Hunteri in the
male ; round ligament and ligamentum ovarii of the female.)

34. The testis is received some time before birth into the scrotum,
an appendage of the body-cavity ; the scrotum owes its origin to the
fact that the peritoneum forms an evagination (processus vaginalis
peritonei) through the wall of the abdomen into the genital ridges,
and that afterwards the evagination is completely cut off from the
body-cavity by the closure of the inguinal canal.

35. The layers of the scrotum or the envelopes of the testes corre-
spond, in accordance with their development, to the separate layers of
the body-wall, as is shown in the following comparative summary : —

Envelopes of the Testes. Wall of the Abdomen.

Scrotum with tunica dartos. Skin of the abdomen.

COOPER'S fascia. Superficial abdominal fascia.

Tunica vaginalis communis with Muscle-layer and fascia trans-

cremaster. versa abdominis.

Tunica vaginalis propria (parietal Peritoneum.

and visceral layers).

36. The external sexual organs are developed in man and woman
from the same kinds of fundaments in the neighborhood of the cloaca.

410

EMBRYOLOGY.

37. The term cloaca is applied to a depression at the hinder end of
the embryo, into which opeii the hind gut and the allantois, after
the latter has received — on the posterior face of its attenuated
terminal part, the sinus urogenitalis — the closely approximated
Miillerian and meson ephric ducts.

38. The cloaca becomes divided by projecting folds, which unite
to form the perinaeum, into an anterior [ventral] and posterior
[dorsal] portion, of which the former is the prolongation of the
sinus urogenitalis, the latter the prolongation of the intestine
(anus).

39. At the anterior margin of the cloaca, or, after completed
separation, at the anterior rim of the sinus urogenitalis, there is
found in both sexes the genital eminence, which bears along its
under surface a groove flanked by the two genital folds ; the eminence,
together with the opening lying under it (cloaca or sinus urogeni-
talis), is embraced by the genital ridges.

40. In the female the genital eminence remains small and becomes
the clitoris, the genital folds become the labia minora, the genital
ridges the labia majora; the sinus urogenitalis remains short and
broad and represents the vestibulum, which receives the vagina (the
end of the Miillerian ducts) and the external orifice of the allantois
or urinary bladder, the female urethra.

41. In the male the genital eminence grows out to a great length
as the male organ ; the genital folds close on their under surface to
form a narrow canal, which appears as a prolongation of the narrow
sinus urogenitalis, together with the latter is designated as the
male urethra, and receives at its beginning the vas deferens and the
uterus masculinus ; the two genital ridges, which increase in size for
the reception of the testes, surround the roots of the male organ and
unite to form the scrotum.

42. The following table gives a brief survey (1) of the compar-
able parts of the outer and inner sexual organs of the male and
female, and (2) of their derivation from indifferent fundaments of
the urogenital system in Mammals : —

Male sexual parts.

Seminal ampullso and semi-
nal tubules.

(a) Epididymis with rete

testis and tubuli recti.
(6) Paradidytuia.

The common form from which
both arise.

Germinal epithelium.

Primitive kidney.

(a) Anterior part with the

sexual core s (sexual part).
(6) Posterior part (the real

mesonephric part).

Female sexual parts.

Ovarian follicle,
follicle.

Graafian

(a) Epoophoron with medul-
lary cords of the ovary.
(6) Paroophoron.

LITERATURE.

411

Male sexual parts.

The common form from which
both arise.

Female sexual parts.

Vas deferens with seminal

Mesonephric duct.

GARTNER'S canal, in some

vesicles.

Mammals.

Kidney and ureter.

Kidney and ureter.

Kidney and ureter.

Hydatid of epididymia.
Sinus prostaticus.
(Uterus masculinus.}

i Mullerian duct. •!

Oviduct and fimbriae.
Uterus and vagina.

Gubernaculmu HunterL

Inguinal ligament of primi-

Round ligament and lig.

tive kidney.

ovarii.

Male urethra (pars prostatica

Sinus urogenital is.

Vestibulum vaginae.

et membranacea).

Penis.

Genital eminence.

Clitoris.

Pars cavernosa urethrae.

„ folds.

lAbia roinora.

Scrotum.

„ ridges.

,, niajora.

The Development of the Suprarenal Bodies.

43. The most anterior part of the mesonephros appears to share
in the development of the suprarenal bodies, since lateral branches
sprout out from the sexual cords, become detached, and are converted
into the peculiar cellular cords of the cortical substance.

44. The suprarenal bodies in the embryo for a time exceed in size
the kidneys.

LITERATURE.

(1) Development of the Musculature.

Ahlborn. Ueber die Segmentation des Wirbelthierkorpers. Zeitschr. f.

wiss. Zoologie. Bd. XL. 1884.
Orenacher. Muskulatur der Cyclostomen und Leptocardier. Zeitschr. f.

wiss. Zoologie. Bd. XVII. 1867, p. 577.
Hertwig, Oscar. Ueber die Muskulatur der Coelenteraten. Sitzungsb. d.

Gesellsch. f. Medicin u. Naturwiss. Jena. Jahrg. 1879.
Marshall, A. Milnes. On the Head-cavities and Associated Nerves of

Elasmobranchs. Quart. Jour. Micr. Sci. Vol. XXI. 1881, p. 72.
Schneider, Anton. Beitrage zur vergleichenden Anatomic und Entwick-

lungsgeschichte der Wirbelthiere. Berlin 1879.
Sedgwick. On the Origin of Metameric Segmentation and some other

Morphological Questions. Quart. Jour. Micr. Sci. Vol. XXIV. 1884,

p. 43.
Wijhe. Ueber die Mesodermsegmente und die Entwicklung der Nerven des

Selachierkopfes. Verhandel. d. k. Akad. van Wetensch. Amsterdam

1883.
Wijhe. Ueber Somiten und Nerven im Kopfe von Vogel- und Reptilien-

embryonen. Zool. Anzeiger. Jahrg. IX. Nr. 237, 1886, p. 657.
Wijhe. Ueber die Kopfsegmente und die Phylogenie des Geruchsorgans der

Wirbelthiere. Zool. Anzeiger. Jahrg. IX. Nr. 238, 1886, p. 678.

412

EMBRYOLOGY.

(2) Development of tlie Urogenital System.
Balbiani. Lecons sur la generation des vertebras. Paris 1879.
Balfour, F. M. On the Origin and History of the Urogenital Organs of

Vertebrates. Jour. Anat. and Physiol. Vol. X. 1876.
Balfour, F. M. On the Structure and Development of the Vertebrate Ovary

Quart. Jour. Micr. Sci. Vol. XVIIL 1878.
Balfour, F. M. Ueber die Entwicklung und die Morphologic der Suprarenal -

kbrper (Nebennieren). Biol. Centralblatt. 1881. Nr. 5.
Balfour, F. M., and Adam Sedgwick. On the Existence of a Head-kidney

in the Embryo Chick and on Certain Points in the Development of the

Miillerian Duct. Quart, Jour. Micr. Sci. Vol. XIX. 1879.
Beard, J. The Origin of the Segmental Duct in Elasmobranchs. Anat.,

Anzeiger. Jahrg. II. Nr. 21. 1887.
Beneden, van. Contribution a la connaissance de 1'ovaire des mammiferes

Archives de Biologic. T. I. 1880.
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EMBRYOLOGY.

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416 EMBRYOLOGY.

CHAPTER XVI.
THE ORGANS OF THE OUTER GERM-LAYER.

THE outer germ-layer has for a long time also borne the name
dermo-sensory layer. By this its two most important functions are
both indicated. For in the first place it forms the epidermis together
with its various products, such as hair, nails, scales, horns, and
feathers ; and in addition various kinds of glands : the sebaceous,
sweat- and milk-glands. Secondly, it is the matrix out of which
the nervous system and the most important functional parts of the
•sensory organs, the optic, auditory, and olfactory cells, are derived.

I begin with the most important function of the outer germ-layer,
the development of the nervous system, then proceed to the develop-
ment of the organs of sense (eye, ear, and organ of smell), and finally
discuss the development of the epidermis and its products.

I. The Development of the Nervous System.
A. The Development of the Central Nervous System.

The central nervous system of Vertebrates is one of the organs
first established after the separation of the germ into the four
primary germ-layers. As has already been stated, it is developed
(fig. 41 A) out of a broad band of the outer germ-layer (wip), which
stretches from the anterior to the posterior end of the embryonic
fundament and lies in the median plane directly above the chorda
dorsalis (c/i). In this region the cells of the outer germ-layer grow
out into long cylindrical or spindle-shaped structures, whereas the
elements occurring in the surrounding parts (ep) flatten out and
under certain conditions become altogether scale-like. Consequently
the outer germ-layer is now divided into two regions — into the
attenuated primitive epidermis (Hornblatt) (ep) and the thicker
median neural or medullary plate (mp).

Both regions are soon sharply separated from each other, since the
neural plate bends in a little (fig. 41 B) and its edges rise above the
surface of the germ. In this way there arise the two medullary or
dorsal folds (mf), which enclose between them the originally broad
and shallow medullary or dorsal furrow. They are simply folds of
the outer germ-layer, formed at the place where the neural plate is
continuous with the primitive epidermis. They are therefore com-
posed of an outer and an inner layer, of which the inner belongs to

THE ORGANS OP THE OUTER GERM-LAYER. 417

the marginal part of the neural plate, the outer, on the contrary,
to the adjacent epidermis.

In all the classes of Vertebrates the medullary plate is transformed
into a neural tube at a very early period. This process can be
accomplished in three different ways. In most of the classes of
Vertebrates, namely Reptiles, Birds, and Mammals, the tube is
formed by a typical process of folding. The medullary folds rise
still higher above the surface of the germ, then bend together
toward the median plane, and grow toward each other until their
edges meet, along which they then begin to fuse. The neural tube,
thus formed, still continues to remain in connection with the over-
lying epidermis along the line of fusion, a connection which soon
disappears, since the connecting cells become loosened and separated
from one another (fig. 41 C). The closure begins in all Vertebrates
at the place which corresponds approximately to the future mid-brain
— in the Chick (fig. 87 hb2) on the second and in the Rabbit on the
ninth day of development — and from there proceeds slowly both
backwards and forwards. There is retained for a long time,
especially behind, a place where the neural tube is open to the
exterior. A connection with the intestinal tube by means of the
neurenteric canal also exists at the posterior end, as has been already
mentioned (p. 126) in the discussion of the germ-layers. It is only
at a later period that this connection is interrupted by the closing of
the blastopore.

The second type in the development of the central nervous system
is met with in Cyclostomes and Teleosts. In them the neural plate
is transformed into a solid cord of cells instead of a tube. Instead of
the folds rising up over the surface of the germ, the neural plate
grows downward in the form of a wedge. In this way the right
and left halves of the plate come to lie immediately in contact with
each other, so that one cannot find the slightest trace of a space
between them ; only after the cord of cells has been constricted off
from the primitive epidermis do the halves separate and allow a
small cavity, the central canal, to appear between them. Probably
this modification in the Bony Fishes and Cyclostomes is connected
with the fact that the egg with its abundant yolk is very closely
enveloped by the vitelline membrane, as a result of which the
medullary folds cannot rise toward the surface.

The third modification occurs only in Amphioxus lanceolatus. It-
has already been described briefly in another place (p. 109).

The neural tube retains an undifferentiated condition in Amphioxus

27

418

EMBRYOLOGY.

lanceolatus only ; in all other Vertebrates, on the contrary, it is
differentiated into spinal cord and brain.

(a) The Development of the Spinal Cord.

The part of the neural tube which is converted into the spinal
cord is oval in cross section (fig. 200). At an early period a separa-
tion into a right and left half can be recognised (fig. 232). For

Fig. 232.— Cross section of an embryo Lizard with completely closed intestinal tube, after
SAGEMEHL.

he, Posterior, vc, anterior commissure of the spinal cord ; vw, anterior root of nerve ; nf, nerve-
fibrillae ; spk, spinal ganglion ; mpl, muscle-plate, muscle-forming layer ; mp2, outer layer of
the muscle-plate ; wzp3, transition of the outer into the muscle-forming layer.

the lateral walls are greatly thickened and consist of several layers
of long, cylindrical cells, whereas the upper and lower walls are thin
and can be distinguished respectively as posterior [dorsal] and anterior
commissure (he and vc), or as roof-plate and floor-plate.

The further development, of which I shall mention only the most
important points, takes place in such a manner that the lateral
halves become thicker and thicker (fig. 233). The cells continue to
increase in number by division, and at the same time to be differ-
entiated into two histological groups — (1) into elements which provide
the sustentative framework, the epithelium surrounding the central

THE ORGANS OF THE OUTER GERM-LAYER.

419

canal and the spongiosa (spongioblasts of His), and (2) into elements
which are transformed into ganglionic cells and nerve-fibres (neuro-
blasts of His). The thickening of the lateral walls depends partly
upon the multiplication of cells, but mainly upon the fact that nerve-
fibres apply themselves to the cell-mass from the outside. In time
these fibres are separated into the anterior, lateral, and posterior
columns of the spinal cord (fig. 233 pew, lew, acw). At their first
appearance the nerve-
fibres are non-medul-
lated (fig. 232 nf),
and only subse-
quently, sometimes
earlier, sometimes
later, acquire a me-
dullary sheath. In
this manner the al-
ready considerably
thickened halves of
the spinal cord be-
come differentiated
into the central gray
substance containing
the ganglionic cells,
and into the white
substance, which en-
velops the surface of
the former like a
mantle.

Since, meanwhile,
the roof- and floor-
plates grow only a
little and are not
differentiated into
ganglionic cells, they come to lie deeper and deeper at the bottom
of anterior and posterior longitudinal furrows (c and of). Finally,
the completely formed spinal cord is composed of large lateral halves,
which are separated from each other by deep anterior and posterior
longitudinal fissures, being united only deep down by a thin trans-
verse bridge. The latter is derived from the roof- and floor- plates,
which have been retarded in their growth, and encloses in its middle
the central canal, which has also remained small.

UC

&CW

Fig. 233.— Cross section through the spinal cord of an embryo
Chick of seven days, after BALFOUB.

pcio, Posteri.or white column ; lew, Lateral white column ;
acw, anterior yiyte column ; c, dorsal tissue filling up the
place where the dorsal fissure will be formed ; pc, posterior
horn of the gray substance ; ac, anterior horn ; ep, epithelial
cells ; age, anterior gray commissure ; pf, posterior [dorsal]
part of the spinal canal ; spc, anterior [ventral] part of the
spinal canal ; a/, anterior fissure.

420 EMBRYOLOGY.

At the beginning — in Man up to the fourth month of embryonic
development — the spinal cord occupies the entire length of the body.
Therefore, at the time when the axial skeleton is divided up into
separate vertebral regions, it reaches from the first cervical down to
the last coccygeal vertebra. The end of the spinal cord, however,
does not even begin to develop ganglionic cells and nerve-fibres, but
remains throughout life as a small epithelial tube. It is united to
the larger anterior portion, which has developed nerve-fibres and
ganglionic cells, by means of a conically tapering region, which is
spoken of in descriptive anatomy as the conus medullaris.

As long as the spinal cord keeps pace with the vertebral column
in its growth, the pairs of nerves arising from it, in leaving the
vertebral canal, pass out at right angles directly to the intervertebral
foramina. In Man, beginning with the fourth month, this arrange-
ment is changed ; from that time forward the growth of the spinal
cord does not equal that of the spinal column, and therefore the cord
can no longer occupy the entire length of the vertebral canal. Since
it is attached above to the medulla oblongata, and this together with
the brain is firmly held in the cranial capsule, it must assume a higher
and higher position in the vertebral canal. In the sixth month the
conus medullaris is found in the upper end of the sacral canal, at birth
in the region of the third lumbar vertebra, and some years later at
the lower edge of the first lumbar vertebra, where it terminates
even in the adult.

In the ascent (ascensus medullae spinalis) the lower end of the
spinal cord, the small epithelial tube which is attached to the coccyx,
is drawn out into a long, fine filament, which persists even in the
adult as the filum terminate internum and externum. At first it
presents a small cavity, which is lined by ciliated cylindrical cells,
and which forms a continuation of the central canal of the spinal
cord. Further downward it is continued in the form of a cord of
connective tissue as far as the coccyx.

A second consequence of the ascent of the spinal cord is a change
in the course of the roots of the peripheral nerve-stems. Since, together
with the spinal cord, their points of origin come to lie in the spinal
canal relatively nearer and nearer the head, and since the places where
they pass through the intervertebral foramina do not change, they
are compelled to pass from a transverse to a more and more oblique
course. The obliquity, moreover, is greater the farther down the
nerve leaves the vertebral canal. In the neck-region their direction
is still transverse, in the thoracic region it begins to be more and

THE ORGANS OF THE OUTER GERM-LAYER. 421

more oblique, and finally, in the lumbar region, and still more so in
the sacral, it is more sharply downward. On this account the nerve-
stems arising from the last part of the spinal cord come to lie for a
considerable distance in the vertebral canal before they reach the
sacral foramina serving for their exit ; they therefore surround the
conus medullaris and filum terminale, forming the structure known
as the horse-tail or cauda equina.

Finally the spinal cord undergoes some changes in its form also.
Even in the third and fourth months there appear differences of calibre
in different regions. The places in the cervical and lumbar regions
of the spinal cord at which the peripheral nerves depart to the anterior
and posterior extremities, grow vigorously by the abundant formation
of ganglionic cells ; they become considerably thicker than the adjoin-
ing portions of the cord, on account of which they are distinguished
as cervical and lumbar enlargements (intumescentia cervicalis et
lumbalis).

(b) The Development of the Brain.

By the study of embryology knowledge of the anatomy of the
brain has been greatly promoted. Justly, therefore, in all recent
text books of human anatomy, the embryonic condition serves as
the starting-point in the description of the intricate structure of the
brain, the aim being to derive the complicated ultimate conditions
from the more simple embryonic ones, and to explain them by means
of the latter.

The initial form of the brain as well as of the spinal cord is a simple
tube. At an early period, even before it is everywhere closed, it
becomes metameric, on account of its growth being greater in some
regions than in others. By means of two constrictions of its lateral
walls it is divided into the three primary brain-vesicles (fig. 87 hbl, hb2,
hb3), which remain united with one another by means of wide openings,
and are designated as the fore-, mid-, and hind-brain. The posterior
of these divisions is the longest, gradually tapering and becoming
continuous with the tubular spinal cord.

The first stage is quickly followed by a second, and that by a third,
since the primary brain-vesicles soon separate into four, and finally
five divisions.

During the second stage (fig. 234) the lateral walls of the primary
fore-brain (pvh) begin to grow outward more vigorously and to
evaginate to form the two optic vesicles (au). At the same time the

422

EMBRYOLOGY.

lateral walls of the hind-brain, which from the beginning has been
the longest portion, acquire a constriction which divides the hind-
brain into two vesicles, that of the cere-
bellum (kh) and the medulla (nJi), or
after-brain.

The five-fold segmentation of the
neural tube (fig. 235) ^oon succeeds
the four-fold condition; by means of
it the fore-brain vesicle undergoes
fundamental transformations. First,
the primary optic vesicles (au) begin
to be constricted off from the fore-
brain vesicle, until they remain at-
tached by only slender, hollow stalks.
Since the constriction takes place
mainly from above downward, the
stalks remain in connection with the
base of the fore-brain vesicle. The
front wall of the vesicle then begins
to protrude anteriorly, and to be
marked off by means of a lateral
furrow, which runs from above and
behind obliquely downward and for-
ward. In this manner the primary
vesicle of the fore-brain, like the
hind-brain vesicle, is secondarily di-
vided into two portions, which we
can now distinguish as the vesicles
of the cerebrum and the between-brain

(gh, zh). The optic nerves remain united with the base of the latter.
The vesicle of the cerebrum is distinguished by a very rapid
growth, and soon begins to surpass all the other parts of the brain
in size. But it becomes divided before this into right and left halves.
From the connective tissue enveloping the neural tube there grows
down in the median plane a process, the future falx cerebri. This
growth advances from above and in front against the cerebral vesicle
and deeply infolds its upper wall. The halves (fig. 236 hms) that have
thus arisen are united at their bases ; they present a more flat median
and a convex outer surface, and are called the two vesicles of the hemi-
spheres, since they furnish the foundation for the cerebral hemispheres.
The separate regions of the brain-tube produced by constrictions

Fig, 234.- Dorsal aspect, by trans-
mitted light, of the head of a
Chick incubated 58 hours, after
MIHALKOVICS. Magnified 40
diameters.

x, Anterior wall of the primary fore-
brain vesicle, which afterwards
evaginates to form the cerebrum ;
pvh, primary fore-brain vesicle ;
au, optic vesicle ; mh, mid-brain
vesicle ; kh, vesicle of the cere-
bellum ; nh, after-brain vesicle ;
7i, heart ; vo, omphalomesenteric
vein ; rm, spinal .cord ; us,
primitive segment.

THE ORGANS OF THE OUTER GERM-LAYER.

423

and evaginations subsequently become still more sharply marked
off from one another, owing to the alteration of their positions.

nh

Tig. 235. —Brain of a human embryo of the third week (Lg\ Profile reconstruction. After His.
gh, Cerebral vesicle ; zh, between-brain vesicle ; mh, mid-brain vesicle ; kh, nh, vesicles of the

cerebellum and medulla oblongata ; ait, optic vesicle ; gb, auditory vesicle ; tr, inf undibulum ;

rf, area rhomboidalis ; nb, nuchal flexure ; kb, cephalic flexure.

At the beginning the three brain-vesicles formed by the first
constrictions lie in a straight line one behind the other (fig. 87) and
above the chorda dorsalis ; the latter extends
only as far as to the anterior end of the mid-
brain vesicle, where it tapers to a point. But
from the moment when the optic vesicles begin
to be constricted off, the three primary vesicles
shift their positions in such a way that the
longitudinal axis uniting them undergoes sharp,
characteristic folds, which are distinguished as
the cephalic, pontal, and nuchal flexures (fig.
235 Icb, nb).

The cause of the formation of the curvatures,
which are of fundamental importance in the
anatomy of the brain, is to be sought princi-
pally in the more vigorous longitudinal growth
which distinguishes the cerebral tube, and more
especially its dorsal wall, from the surrounding
parts. As His has established by means of
measurements, the fundament of the brain more
than doubles its length, while the spinal cord
increases by only about one-sixth of its length.

The cephalic flexure (fig. 235 kb) is developed first. The floor of
the fore-brain sinks downward a little around the anterior end of the
chorda dorsalis (fig. 237 ch), and forms at first, a right angle with

Fig. 236. — Brain of a
human embryo seven
weeks old, parietal
(Scheitel) aspect, after

M.HALKOVICS.

msp, Longitudinal or in-
terpallial fissure (Man-
telspalte), at the bottom
of which is seen the
embryonic lamina ter-
minalls (Schlussplatte) ;
finis, left hemisphere ;
zh, between-brain ; mh,
mid-brain ; hh, hind-
brain and after-brain.

424

EMBRYOLOGY.

the part of the base of the brain lying behind it, but afterwards an

acute angle (figs. 235, 238).
In consequence of this, the
vesicle of the mid -brain
(fig. 235 mh) comes to lie
highest, and forms a promi-
nence, which causes a great
protrusion of the surface of
the embryo and is known
as the parietal prominence
(fig. 158 s).

The nuchal flexure, which
makes its appearance at the
boundary between medulla
oblongata and spinal cord,
is less prominent (fig. 235
Ti-6). It produces in the
embryos of the higher Ver-

ch

Fig. 237.— Median section through the head of a
Rabbit embryo 6 mm. long, after MIHALKOVICS.

rh, Pharyngeal membrane ; hp, place whence the
hypophysis develops ; h, heart ; kd, cavity of the
head-gut ; ch, chorda ; v, ventricle of the cere-
brum; v3, third ventricle, that of the between-
brain ; v*, fourth ventricle, that of the hind- and
after-brain ; ck, central canal of the spinal cord.*

tebrates a curvature which also projects outward, the so-called
nuchal prominence
(fig. 158).

The third curva-
ture, which has been
designated by KOL-
LIKER as the pontal
flexure (fig. 239 bb),
because it arises in
the neighborhood
of the future pons
Varolii, is, on the
contrary, very
marked. It is
further distinguished
from the two other
curvatures described,
by the fact that its
convexity is not di-
rected toward the
back of the embryo,
but toward its ventral side. It is formed between the rioor of the
* [For terminology of the regions of the brain, see footnote, p. 282.]

Fig. 238. Median sagittal section through the head of a Chick
incubated four and a-half days, after MIHALKOVICS.

SH, Parietal prominence ; sv, lateral ventricle ; v3, third
ventricle ; v\ fourth ventricle ; Sw, aqueduct of SYLVIUS ;
gh, vesicle of the cerebrum ; zh, between-brain ; mh, mid-
brain ; kh, cerebellum ; zf, pineal process (epiphysis) ;
hp, pocket of the hypophysis (pouch of RATHKE) ; c/i,
chorda ; ba, basilar artery.

THE ORGANS OF THE OUTER GERM-LAYER. 425

vesicle of the cerebellum and that of the after-brain, and has the
form of a ridge which projects veiitrally for a considerable distance,
where subsequently the transverse fibres of the pons Yarolii are
established.

The extent of these curvatures is very different in the various
classes of Vertebrates. Thus the cephalic flexure is only s'ightly
emphasised in the lower Vertebrates (Cyclostomes, Fishes, Amphibia) ;
it is, on the contrary, much greater in Reptiles, Birds, and Mammals ;
but in Man especially, whose brain is the most voluminous, all of the
flexures are developed to a very high degree.

The five brain-vesicles furnish the foundation for a natural sub-
division of the brain, whose various chief divisions can be referred
back to them. As the study of the further development teaches,
there are formed from

the after-brain vesicle ^^ mk

the medulla oblongata,
from the vesicle of the
cerebellum the vermi-
form process with the
hemispheres of the cere-
bellum and the pons

^ . Fig. 239.— Brain of a Rabbit embryo 16 mm. long, viewed

Varolll, trom the mid- from the left side. The outer wall of the left cerebrum

brain vesicle the crura is removed. After MIHALKOVICS.

sn, Optic nerve ; ML, foramen of MONRO ; agf, fold of the

Cerebri and Corpora choroid plexus ; amf, fold of the oornu Ammonia ;

quadrigeinina, from the **• ^tween-brain : mh, mid-brain (cephalic or parietal

1 I t flexure) ; kh, cerebellum ; Dp, roof -plate of the fourth

between - brain Vesicle ventricle ; 66, pontal flexure ; mo, medulla oblongata.

the bet wee n-b rain

[thalamencephalon] with the inf undibulum, the pineal gland, and the
optic thalami, and finally from the vesicle of the cerebrum the
cerebral hemispheres.

Tn this metamorphosis the cavities of the primitive cerebral tube
become the so-called ventricles of the brain : from the cavities of the
fourth and fifth vesicles is derived the fourth ventricle or fossa
rhomboidalis ; from the cavity of the mid-brain vesicle, the aque-
duct of SYLVIUS ; from the between-brain, the third ventricle ; and
finally from the cavities of the hemispheres, the two lateral ventricles,
which are also designated as the first and second ventricles.

A brief sketch will suffice to show in what manner the most
important parts of the brain develop out of the five vesicular
fundaments, and that at the same time histological and morphological
differentiations are most intimately associated.

426 EMBRYOLOGY.

Historically considered the wa'lls of the vesicles originally consist
everywhere of closely crowded spindle-shaped cells, just as in the
spinal cord. These cells undergo in different places unlike modifica-
tions. In some places they retain their epithelial character, and
furnish (1) the epithelial covering of the choroid plexus in the roof
of the between -brain and after-brain, (2) the ependyma lining the
ventricles of the brain, and (3) follicular structures such as the
epiphysis (fig. 246). On the greater part of the wall of the five
brain-vesicles the cells multiply to an extraordinary extent, and are
transformed into more or less extensive layers of ganglionic cells and
nerve-fibres. The distribution of the gray and white substances thus
formed no longer presents in the brain-vesicles the same uniform
condition that it does in the spinal cord. The only uniformity is
found in the fact that in every part of the brain there occur gray
" nuclei," which, like the anterior and posterior gray columns of the
spinal cord, are enveloped with a mantle of white substance. How-
ever, there are added to the two parts of the brain that have attained
the greatest development layers containing ganglionic cells, which
furnish a superficial covering, the gray cortex of the cerebrum and
cerebellum. By this means the white substance in certain parts of the
brain becomes the core (nucleus medullaris), whereas the gray portion
becomes the cortex, a condition differing in an important manner
from the structure of the spinal cord.

The morphological differentiation of the brain depends upon the very
unequal growth both of the jive separate vesicles and of different tracts
of their walls. For example, the other four vesicles remain in their
development far behind that of the cerebral vesicle, in comparison
with which they constitute only a small fraction of the entire mass of
the brain (figs. 240, 241). They become overgrown by the cerebral
vesicle from above and on the sides, and enveloped as by a mantle,
so that they remain uncovered and visible only at the base of the
brain. Therefore they, together with a small part of the basal
portion of the cerebrum, are grouped together as the stalk of the
brain, in contradistinction to the remaining chief part of the cere-
brum, which constitutes the cerebral mantle.

The unequal growth of the walls of the brain manifests itself in the
appearance of thickened and attenuated places, in the development
of special nerve-columns (pedunculi cerebri, cerebelli, etc.), and in
the formation of more or less extensive layers of ganglionic cells
(thalamus opticus, corpus striatum). By these means the principle
of the formation of folds, which was fully described in the fourth

THE ORGANS OF THE OUTER GERM-LAYER. 427

chapter, is shown to be carried out in a special manner on the
hemispheres of the cerebrum and cerebellum inclusive of the
vermiform process, — that is to say, on the two parts of the brain
which are covered with a gray cortex. That the functional capacity
of the cerebrum and cerebellum depends upon the extent of the gray
cortex and the regularly arranged ganglionic cells in it, is to be
concluded from a large number of phenomena. In this way is
explained the very extensive increase of surface which is brought
about in the cerebrum and cerebellum by means of somewhat
different processes of folding. In the cerebrum broad ridges (gyri)
arise from the medullary layer of the hemispheres (centrum semi-
ovale), which, running in meandering convolutions, produce the
characteristic relief of the surface (fig. 256). In the cerebellum the

- tchei.l

Fig. 240.— Lateral view of the brain of a human embryo from the first half of the fifth month,

after MIHALKOVICS. Natural size.
stl, Frontal lobe ; schei.l, parietal lobe ; hi, occipital lobe ; schl.l, temporal lobe ; Sy.g, fissure of

SYLVIUS ; rn, olfactory nerve ; kh, cerebellum ; br, pons; mob, medulla oblongata.

numerous ridges proceeding from the medullary nucleus are narroiv,
arranged parallel to one another, and provided with smaller accessor1)/
(secondary and tertiary) ridges, so that the cress section of the
cerebellum presents an arborescent figure (arbor vitse).

If, after these preliminary remarks, we take under consideration
the metamorphoses of the five vesicles, we may distinguish on each,
as MIHALKOVICS has done in his monograph of the development of
the brain, four regions : floor, roof, and two lateral parts. We shall
begin our description with the fifth vesicle, because in its structure
it approaches most closely to the spinal cord.

(1) Metamorphosis of the Fifth Brain-Vesicle.

The fifth brain-vesicle exhibits in different Vertebrates at the
beginning of development (in the Chick on the second and third

428

EMBRYOLOGY.

days) faint, regular infoldings of its lateral walls, by means of which
it becomes separated into several smaller parts, lying one behind the
other. Inasmuch as these afterward disappear without leaving any
trace, no great importance was ascribed to them by the earlier
investigators (EEMAK). Recently, however, several persons have
maintained for them a real significance. RABL and BERANECK

c;ng

L-h

Fig. 211. — Brain of a human embryo from the first half of the fifth month, divided in the median
plane ; view of the median surface of the right half, after M.HALKOVICS. Natural size.

rn, Olfactory nerve; tr, infundibulum of the between-brain ; cma, comtnissura anterior; ML,
foramen of MONRO ; frx, fornix ; spt, septum pellucidum ; balt corpus callosum, which
below, at the germ, is continuous with the embryonic lamina terminalis ; cmg, sulcus calloso-
marginalis ; fo, fissura occipitalis ; zw, cuneus ; fc, fissura calcaiina ; z, epiuhysia ; vht corpora
quadrigemina ; kh, cerebellum.

msp

Fig. 242.— Brain of a human embryo from the second half of the third month, seen from behind,

after MIHALKOVICS. Natural size.
msp, Longitudinal (interpallial) fissure; vh, corpora quadrigemiua ; vma, velum medullare

anterius; kh, hemispheres of the cerebellum; v*, fourth ventricle (fossa rhomboidalia) ;

mo, medulla oblongata.

recognise in them a segmentation of the brain-tube which is related
to the exit of certain cranial nerves and is of importance in regard
to the question of the metamerism of the entire head-region. The
circumstance that the folds are so transitory appears to me to favor
the older view.

In the further development of the vesicle of the after-brain a
distinction arises between the floor and side walls on the one hand

THE ORGANS OF THE OUTER GERM-LAYER. 429

and the roof on the other. The former (figs. 241, 242) are con-
siderably thickened by the addition of nervous substance and become
separated on either side of the body (in Man in the third to the
sixth months) into columns, which are recognisable from the outside
because they are separated by grooves ; these are the extensions with
certain modifications of the three familiar columns of the spinal
cord. The roof of the vesicle (fig. 235 rf and fig. 243 Dp), on the
contrary, produces no nerve -substance, retains itSy epithelial structure,
becomes still thinner, and in the adult consists of a single layer of
flat cells. This forms the only covering to the cavity of the dorso-
ventrally compressed vesicle of the after-brain — the fourth ventricle*
or fossa rhomboidalis. It is firmly applied to the under surface of
the pia mater, and with it produces the posterior choroid plexus (tela
choroidea inferior). The name choroid plexus has been chosen
because the pia mater in this region becomes very vascular and in
the form of two rows of branched villi grows into the cavity of the
after-brain vesicle, always carrying before it, and thus infolding, the
thin epithelial roof.

Laterally the roof -plate or the epithelium of the choroid plexus is
continuous with the parts of the brain-vesicle that have been meta-
morphosed into nervous matter. The transition is effected by means
of thin bands of white nervous substance, which, as obex, tsenia
sinus rhomboidalis, velum medullare posterius, and pedunculus
flocculi, surround the edge of the fossa rhomboidalis. If with the
pia mater one strips off from the medulla oblongata the posterior
medullary velum, the epithelial covering of the fourth ventricle
adhering to the latter will 'naturally be removed with7 it. In this
way is produced the posterior brain-fissure of the older authors,
through which one can penetrate into the system of cavities in the
brain and spinal cord.

(2) Metamorphosis of the Fourth Brain-Vesicle.

The wall of the fourth brain-vesicle undergoes a considerable thick-
ening in all its parts, and surrounds its cavity in the form of a ring
differentiated into several regions ; the cavity becomes the anterior
part^f the fossa rhomboidalis (tigs. 243, 242, 241). The floor
furnishes the pons (bb), the cross fibres of which become evident in
the fourth month. From the lateral walls arise the pedunculi
cere*belli ad poiitem. But it is the roof that grows to an extraordinary
extent and gives t& the cerebellum its characteristic stamp. At first

430

EMBRYOLOGY.

it appears as a thick transverse ridge (figs. 242, 243 kh), which over-
hangs the attenuated roof of the medulla. In the third month the

middle portion of the ridge
acquires four deep trans-
verse folds by the sinking
in of the pia mater (fig.
242), and in this way
is distinguished as the
vermiform process from
the lateral parts, which
still appear smooth (kh).
From this time forward
the lateral parts outstrip
the middle part in growth,
bulge out at the sides as
two hemispheres, and, ac-
quiring transverse folds,
in the fourth month be-
come the voluminous hemispheres of the cerebellum.

Only a little nerve-substance is developed where the roof of the
fourth brain-vesicle, which has become thickened to constitute the
vermiform process and hemispheres, is continuous with the roof of
the third and fifth vesicles (fig. 241). Consequently there arise here
thin medullary lamellae, which serve as a transition on the one
hand to the posterior choroid plexus, and on the other to the lamina
quadrigemina (vh) — the posterior and the anterior velum medullare.

fig. 243. —Brain of an embryo Calf 5 cm. long, seen
from the side. The lateral wall of the hemisphere
is removed. After MIHALKOVICS. Magnified 3
diameters.

cst, Corpus striatum ; ML, foramen of MONKO ; agf,
fold of the choroid plexus (plexus choroideus
lateralis) ; amf, fold of the cornu Ammonis ; kh,
cerebellum ; Dp, roof -plate of the fourth ventricle ;
66, pontal flexure; mo, medulla oblongata; mh,
mid-brain (cephalic flexure).

(3) Metamorphosis of the Third or Mid-brain Vesicle.
(Figs. 235, 243, 242, 241.)

The mid-brain vesicle is the most conservative portion of the embry-
onic neural tube, the part which is changed least of all ; in Man a
small portion only of the brain is derived from it. Its walls become
rather uniformly thickened on all sides of the cavity, which is narrow
and becomes the aqueduct of SYLVIUS. The base and lateral walls
together supply the crura cerebri and substantia perfcrata posterior,
The roof -plate (fig. 242 vh) becomes the corpora quadrigemina,
owing to the appearance, in the third month, of a median furrow,
and, in the fifth month, of a transverse one crossing it at right
angles.

THE ORGANS OF THE OUTER GERM-LAYER. 431

Whereas at the beginning of the development the mid-brain
vesicle (figs. 235, 243 mh), as a consequence of the curvature of the
neural tube, occupies the highest position and produces the parietal
prominence of the head (fig. 158 s), it is afterwards covered in from
above by the other parts of the brain, which are becoming more
voluminous, — the cerebellum and cerebrum, — and is crowded down
to the base of the brain (compare fig. 235 mh with fig. 241 vh).

(4) Metamorphosis of the Second or Betiveen-brain Vesicle.

The between-brain vesicle also remains small, but undergoes a
series of interesting changes, since, apart from the optic vesicles,
which grow out from its walls, two other appendages, of proble-
matical meaning, are developed from it — the pineal gland and the
hypophysis.

In the case of the between-brain vesicle, it is only in the lateral
walls that a considerable amount of nerve-substance is formed. By
this means the walls thicken into the optic thalami with their
ganglionic layers. Between them the cavity of the vesicle is retained
as a narrow vertical fissure, known as the third ventricle ; it is
united with the fossa rhomboidalis by means of the aqueduct of
SYLVIUS. The floor remains thin and at an early period becomes
evaginated downwards ; it thus acquires the form (figs. 235, 241 tr)
of a short funnel (infundibulum), with the apex of which is united
the hypophysis, soon to be fully described.

The roof presents' in its metamorphosis a striking similarity to the
corresponding part of the after-brain vesicle (fig. 241). It persists
as a simple, thin epithelial layer, unites with the very vascular
pia mater, — which sends out in this case also villous outgrowths
with capillary loops which pass into the third ventricle, — and together
with it constitutes the anterior choroid plexus (tela choroidea anterior
or superior). When in withdrawing the pia mater the choroid
plexus is also removed, the third ventricle is opened ; thus is produced
the anterior great fissure of the brain through which, as through
the structure of the same name in the medulla oblongata, one can
penetrate into the cavities of the brain.

The agreement with the medulla oblongata is expressed in still
another point. As in the case of the latter the edges of the roof-
plate develop into thin medullary bands, by means of which the
attachment to the sides of the fossa rhomboidalis is accomplished, so

432 EMBRYOLOGY.

here also the epithelium of the choroid plexus attaches itself to the
surface of the optic thalamus by means of thin bands consisting of
medullated nerve-fibres ftseniae thalami optici).

Finally, out of the hinderinost portion of the roof of the between-
brain vesicle a peculiar organ, the pineal gland (fig. 241 z), takes its
origin at a very early period, in Man in the course of the second
month. Since in recent years numerous interesting works have
appeared concerning it, and since many striking discoveries have
been brought to light both in the case of the Selachians and more
especially in that of the Reptiles, I will describe it at some-
what greater length.

The Development of the Pineal Gland (Epiphysis cerebri).

First it is to be mentioned that, with the exception of Amphioxus
laiiceolatus, the pineal gland (glandula pinealis s. conarium) is not
wanting in any Vertebrate. It is in all cases formed in exactly the
same way. On the roof of the between-brain, where it is continuous
with the roof of the mid-brain or the lamina quadrigemina, there
arises an evagination (figs. 238 and 241 z) which has the shape of the
finger of a glove, the pi'ocessus pinealis [epiphysis cerebri], the apex of
which is at first directed forward, but subsequently backward. In
its further metamorphosis there appear, as far as our knowledge at
present extends, differences of considerable importance.

According to the investigations of EHLERS, the pineal process
attains in adult Selachians an unusual length ; its closed end swells
into a vesicle, which penetrates the cranial capsule and extends out
to the dermal surface. In many Selachians, such as Acanthias and
Raja, the vesicular end is enclosed in a canal of the cranial capsule
itself ; in others it lies outside between the cranial capsule and the
corium. The [proximal] end of the vesicle is united to the between-
brain by means of a long slender canal.

Manifold conditions are met with in Reptiles, as the recent investi-
gations of SPENCER have taught. These conditions permit in part a
direct comparison with the Selachians, but in part they are widely
altered. Here, too, the pineal gland is a structure of considerable
length, the peripheral end of which lies far away from the between-
brain under the epidermis ; it passes out through an opening in the
roof of the skull which is situated in the parietal bone and is known
as the foramen parietale. The position of the latter can easily be
determined on the head of the living animal, because at this place

THE ORGANS OF THE OUTER GERM-LAYER.

433

the dermal scutes acquire a special condition and form, and, above all,
are transparent.

In regard to the particular form of the organ, there are essentially
three types to be distinguished.

In many Reptiles, e.g., in Platydactylus, the pineal gland has the
same structure as in Sharks : a small peripheral vesicle, which is

Fig. 244.— Diagrammatic longitudinal section through the brain of Chameleo vulgaris with the
pineal organ, which is separated into three portions, a vesicular, a cord-like, and a tube-like
portion, after BALDWIN SPENCER.

sch b, Parietal bone with the foramen parietale ; p, pigment of the integument ; st, cord-like
middle portion of the epiphysis ; bl, its vesicular terminal portion ; x, transparent region
of the integument ; grh, cerebrum ; sh, optic thalamus ; v*, third ventricle, which is
continued upwards into the tube-like initial portion (A) of the epiphysis.

enclosed in the parietal foramen, is lined with ciliated cylindrical
cells, and is connected with the roof of the between-brain by means
of a long, hollow stalk.

In other Reptiles, as in the Chameleon, the organ is differentiated
into three portions (fig. 244) : first into a small closed vesicle (bl),
which lies under a transparent scale (oc) in the foramen parietale
and is lined with ciliated epithelium ; secondly into a solid cord

28

434

EMBRYOLOGY.

(st), which consists of fibres and spindle-shaped cells, and bears a
certain resemblance to the embryonic optic nerve ; and thirdly into
a hollow, funnel-shaped projection (^4) of the roof of the between-
brain, which still exhibits here and there sac-like enlargements.

In a third
division of the
Hep tiles, in
Hatteria,
Monitor, the
Blind-w o r m s,
and Lizards,
the vesicular
distal portion
of the pineal
gland under-
goes a striking
metamo r p h o-
sis, by means
of which it ac-
quires a certain
resemblance to
the eye of many
In vertebra t e s
(fig. 245). The
portion of its

LN ~"" W wall which lies

\4V 7 next to the sur-

K^ • fjr face of the body

has been trans-
formed into a
lens-like struc-
ture (I) ; the
part of the wall
lying opposite
the latter and
continuous

with the fibrous cord (St) has, on the contrary, been converted into
a retina-like structure (r). The formation of the lens (I) is due to
the fact that the epithelial cells of the anterior wall of the vesicle
have become elongated into cylindrical cells and uninucleate fibres,
and have thereby produced an elevation, the convex surface of which

Fig. 245. — Longitudinal vertical section through the pineal eye of
Hatteria punctata and its connective-tissue capsule, after BALDWIN
SPENCER. Slightly enlarged.

The anterior part of the capsule fills up the parietal foramen.

K, Connective-tissue capsule ; I, lens ; h, cavity of the eye filled with
fluid ; r, retina-like portion of the optic vesicle ; M, molecular
layer of the retina ; g, blood-vessels ; x, cells in the stalk of the
pineal eye ; St, stalk of the pineal eye, comparable with the optic
nerve.

THE ORGANS OF THE OUTER GERM-LAYER. 435

projects into the cavity of the vesicle. In the posterior portion the
epithelial cells are separated into different layers, the innermost of
which is distinguished by the abundance of its pigment. Between
the pigmented cells there are imbedded others, which can be compared
to the rods of the visual cells in the paired eyes of Vertebrates,
and which appear to be in connection below with nerve- fibres.

Those investigators who, like RABL-RUCKHARD, AHLBORN,
SPENCER, and others, have studied the pineal gland, are of opinion
that the pineal body must be considered as an unpaired parietal eye,
which in many classes, for example in Reptiles, appears to be tolerably
well preserved, but in most Vertebrates is in process of degeneration.

That we have to do in Reptiles with an organ which reacts under
the influence of light, does not appear improbable, when one takes
into consideration that, owing to the transparency of the dermal
scutes at the place in the skull where the parietal foramen is
located, rays of light are here able to penetrate through the integu-
ment. The presence of a lens-like body and pigment is also
favorable to this view. But whether the organ serves for sight,
or only for the transmission of sensations of warmth, — whether,
consequently, it is more an organ for the perception of warmth than
an eye, — must for the present remain undecided. It is still more
an open question whether this organ of warmth is a structure
which has been developed as a special modification of the epiphysis
of Reptiles alone, — as the auditory sac, for example, has been
developed in the tail of the Crustacean Mysis, — or whether it
represents a structure originally common to all Vertebrates. In the
latter case processes of degeneration must be assumed to be wide-
spread, for up to the present time nothing like the condition in
Reptiles has been found in other Vertebrates.

In Birds and Mammals the pineal process undergoes metamor-
phoses which give rise to an organ of a glandular, follicular structure.

In Birds (fig. 246) it never attains such great length as in
Selachians and Reptiles. At a certain stage it sends out from its
surface into the surrounding vascular connective tissue cellular out-
growths, which increase in number by means of budding and finally
break up into numerous small follicles (fig. 246 f). These consist of
several layers of cells, the outermost being small, spherical elements,
the innermost cylindrical ciliated cells. The proximal portion of the
pineal process does not become involved in the follicular metamor-
phosis and persists as a funnel-shaped outfolding of the roof of the
between-brain ; the individual follicular vesicles constricted off from

436 EMBRYOLOGY.

the parental tissue are united with its upper end by means of

connective tissue.

In Mammals the development takes place in a manner similar to

that of the Chick. In the Rabbit there also arise follicles, each of

which at first encloses a small
cavity, but later becomes solid.
They are then entirely filled with
spherical cells, which possess a
certain resemblance to lymph-
corpuscles. The opinion has
therefore been expressed by many
(HENLE) that the pineal body is
a lymphoid organ, an opinion,

Fig. 246.-Section through the pineal gland however, which is refuted by the
of a Turkey, after MIHALKOVICS. Mag- study of the development, for
nified ISO diameters. * ., , „ ... ,

/.Follicle of the pineal gland with its cavities; genetically the tollicles are ex-
6, connective tissue with blood-vessels. clusively epithelial structures.

In the adult there are formed

within the individual follicles concretions, the brain-sand (acervulus
cerebri).

In Man the pineal body, which begins to appear in the sixth week
(His), exhibits a peculiarity as regards its position. Whereas the
free end of the epiphysis is at first directed forward, and in other
Vertebrates is also retained in this position, it acquires in Man an
opposite direction, inasmuch as it bends backward on to the surface of
the lamina quadrigemina. Probably this is connected with the fact
that the gland is crowded back by the excessive development of the
corpus callosum.

As the signification of the pineal gland is still doubtful, so is that
of the pituitary body or hypophysis cerebri, which, as has been
previously mentioned, is united with the floor of the between-brain
at the apex of the infundibular process.

The Development of the Hypophysis (Pituitary Body).

The hypophysis is an organ which has a double origin. This is
expressed in its entire structure, since it is composed of a larger,
anterior and a smaller, posterior lobe, which in their histological
characters are fundamentally different from each other.

In order to observe the beginning of its formation, it is necessary
to go back to a very early stage (fig. 237), in which the oral sinus

THE ORGANS OF THE OUTER GERM-LAYER.

437

has just arisen and is still separated from the cavity of the head-gut
by means of the pharyngeal membrane (rh). At this time the
cephalic flexure of the brain-vesicles has already appeared, and the
anterior end of the chorda dorsalis (ch) terminates immediately
behind the attachment of the pharyngeal membrane. In front of
this is located the important place where the hypophysis is developed,
as was first established by GOETTE and MIHALKOVICS. The hypo-
physis is therefore a product of the outer germ-layer and not a growth
from the cavity of the head- gut, as had always been maintained
previous to this time.

The first steps introductory to the formation of the hypophysis
take place soon after the rupture of the pharyngeal membrane
(figs. 238, 247), some unimportant remnants of which are retained
at the base of the skull as the .so-called primitive velum palatinum.
Anterior to these there is now developed (in the Chick on the
fourth day of incubation, in Man during the fourth week, His) a
small evagination, the pouch of RATHKE or the pocket of the hypophysis
(hy), which grows to-
ward the base of the
b e t w e e n-b rain (tr).
Then it becomes deeper,
begins to be constricted
off from its parent tissue,
and to be metamor-
phosed into a small sac,
whose wall is composed
of several layers of cylin-
drical cells (fig. 248).

The sac of the hypo-
physis (ky) remains for
a long time in connec-
tion with the oral cavity
by means of a narrow
duct (hyg). In later
stages, however, the
connection in the
higher Vertebrates is

interrupted, because the embryonic connective tissue, which supplies
the foundation for the development of the skeleton of the head,
becomes thickened and crowds the sac farther away from the oral
cavity (figs. 248, 249). When, later on, the process of chondrification

ch

nk

Fig. 247.— Median sagittal section through the hypophysis

of a Rabbit embryo 12 mm. long, after MIHALKOVICS.

Magnified 50 diameters.
tr, Floor of the between-brain with the infundibulum ;

nh,. floor of the after-brain j ch, chorda; hy, pocket

of the hypophysis.

438

EMBRYOLOGY.

_ tr

takes place in the connective tissue, by means of which the carti-
laginous base of
the skull (schb) is
established, the
sac of the hypo-
physis (hy) comes
to lie above the
latter at the under
surface of the be-
tween-brain (tr).
At this time also
the duct of the
hypophysis (hyg)t
which meanwhile
has lost its lumen,
begins to shrivel
and degenerate
(fig. 249). In
many Vertebrates,
however, as in the

schb

schb

Fig. 248.— Sagittal section through the hypophysis of a Rabbit
embryo 20 mm. long, after MIHALKOVICS. Magnified 55
diameters.

tr, Floor of the between-brain with inf undibulum ; hy, hypophysis ;
htft part of the hypophysis in which the formation of the
glandular tubules begins; hyg, duct of the hypophysis;
schb, base of the skull ; ch, chorda ; si, dorsum sellse.

Selachians, it is retained throughout life and forms a hollow canal,
which perfo-
rates the carti-
laginous base
of the skull and
is united with
the epithelium
of the mucous
membrane of
the mouth. In
extremely rare
cases there is
retained in
Man also a
canal in the
basi-sphenoid,
which leads
from the sella
turcica to the

schb

Fig. 249.— Sagittal section through the hypophysis of a Rabbit embryo
30 mm. long, after MIHALKOVICS. Magnified 40 diameters.

tr, Floor of the between-brain with infundibulum ; hy, original pouch-
like part of the hypophysis ; hy', the glandular tubules which hav«
budded out from the sac of the hypophysis; si, dorsum sellae;
ba, basilar artery; ch, chorda ; schb, cartilaginous base of the skull;
em, epithelium of oral cavity.

base of the skull and receives a prolongation of the hypophysis
(SUCHANNEK).

THE ORGANS OF THE OUTER GERM-LAYER. 439

At an early period an evagination from the between-brain
(figs. 247, 249), called the infundibuhim (tr\ has grown out toward
the sac of the hypophysis and applied itself to the posterior wall of
the latter, which it has folded in toward the anterior or opposite
wall.

This first stage is followed by a second, in which the sac and the
adjoining end of the inf undibulum are metamorphosed into the two
lobes of the complete organ already mentioned.

The sac begins (in Man in the second half of the second month,
His) to send out from its surface into the surrounding very vascular
connective tissue hollow tubules (the tubules of the hypophysis)
(figs. 248, 249 hy'). These are then detached from the walls of the
sac, by becoming enclosed on all sides by vascular connective tissue.
In this respect the process of development agrees in the main with
that of the thyroid gland, only that the spherical follicles are here
represented by tubular structures. After the entire sac has been
resolved into a large number of small, tortuous tubules provided with
narrow lumina, the lobe thus produced applies itself closely to the
lower end of the inf undibulum, with which it becomes united by
means of connective tissue.

The end of the infundibulum itself is transformed in the lower
Vertebrates into a small lobe of the brain, in which, moreover,
ganglionic cells and nerve-fibres can be identified. In the higher
Vertebrates, on the contrary, no trace of such histological elements
can be detected in the posterior lobe of the hypophysis, which in
these forms consists of closely packed spindle-cells, and thus acquiros
a close resemblance to a spindle-cell sarcoma.

(5) Development of the First or Fore-Brain Vesicle.

The most important changes, the comprehension of which is in
part attended with serious difficulties, take place in the vesicle of the
fore-brain or cerebrum. It is divided (fig. 250), even at the time of
its formation, as has already been mentioned, into a right and a left
portion, owing to the fact that its wall becomes infolded from in
front and from above by means of a vertical process of the connective-
tissue envelope of the brain, the primitive falx. The two portions,
the vesicles of the hemispheres (hms), come close together, being
separated by only the narrow longitudinal or interpallial fissure (msp),
which is filled up by the falx, so that their median surfaces become
mutually flattened, whereas their lateral and under surfaces are

440

EMBRYOLOGY.

convex. Where the plane and convex surfaces are continuous with
each other there is a sharp bend in the mantle (Mantelkante).

The vesicles of the hemispheres at first have
thin walls formed of several layers of spindle-
shaped cells (fig. 251, i) and each encloses a
large cavity, the lateral ventricle (fig. 251),
which is derived from the central canal of the
neural tube. Inasmuch as these have been
reckoned by the earlier authors as the first and
second ventricles, it is plain why the cavities
of the between-brain and medulla oblongata are
respectively designated as the third and fourth
ventricles. In Man, during the earlier months,
each lateral ventricle is in communication with
the third ventricle by means of a wide opening,
the primitive foramen of MONRO (figs. 239 ML
and 254 m).

Pig. 250.— Brain of a
human embryo seven
weeks old, parietal
(Scheitel) aspect, after

MlHALKOVICS.

msp, InterpaUial (longi-
tudinal) fissure, at the
bottom of which is seen
the embryonic lamina
tenninalis (Schluss-
platte) ; hms, left hemi-
sphere ; zh, between-
brain ; mh, mid-brain ;
hh, hind -brain and
after-brain.

Anterior to the foramen of MONEO lies the part of
the wall of the cerebrum which was infolded by the
development of the great interpallial fissure : on the
one hand it effects the anterior union of the walls of
the two hemispheres ; on the other it bounds the third

ventricle in front, and is therefore called the anterior closing plate (lamina

tenninalis). It is continuous

below with the anterior wall * 2,

of the infundibulum of the

between-brain.

In the further develop-
ment of each vesicle of the
hemispheres four processes
are intimately associated :
(1) an extraordinary growth
and an enlargement in all
directions resulting from
it ; (2) an infolding of the
wall of the vesicle, so that
externally there arise deep
clefts (the fissures), and
internally projections into

the lateral ventricles; (3) the development of a system of commissures,
by means of which the right and left hemispheres are brought into
closer union (corpus callosum and fornix) ; (4) the formation of

Fig. 251.— Brain of a human embryo of three months,
after KOLLIKER. Natural size.

1. From above with the hemispheres removed and tha
mid-brain opened. 2. The same from below.
/, Anterior part of the marginal arch (Randbogen)
of the cerebrum cut through ; /', posterior part
(hippocampus) of the marginal arch ; tho, optic
thalamus ; cst, corpus striatum ; to, tractus opticus ;
cm, corpora raammillaria ; p, pons Varolii.

THE ORGANS OF THE OUTER GERM-LAYER. 441

furrows that cut into the cortex of the cerebrum more or less deeply
from the outside, but cause no corresponding internal projections in
the wall of the ventricle.

As regards its general features, the embryonic growth of the cerebral
vesicles is especially characterised by an enlargement backward. In
the third month the posterior lobe already completely overlies the
optic thalamus (fig. 242) ; in the fifth month it begins to extend over
the corpora quaclrigemina (fig. 241), which it entirely covers up in
the sixth month. From there it spreads over the cerebellum
(fig. 256). The cerebrum is not characterised in all Mammals by
such an extraordinary growth as in Man; comparative anatomy
teaches rather that the stages of development of the human brain in
different months here described, are met with in other Mammals as
permanent conditions.

In some animals the posterior margins of the hemispheres extend as far as
the corpora quadrigemina ; in others they cover these more or less completely ;
in others, finally, they have grown over the cerebellum more or less. On the
whole, the increase in the volume of the cerebrum, which is so varied in
Mammals, goes hand in hand with an increase in intelligence.

The vesicles of the hemispheres undergo additional complication
(in Man in the course of the second and third months), owing to
infoldings of their thin walls, which still enclose a large cavity. As
a result of this there arise on the outer surface deep furrows, which
separate large areas from one another and which have been designated
as total furrows or fissures by His, who has rightly estimated their
importance in the architecture of the brain. Corresponding to the
furrows which are visible on the outer surface, there are more or less
prominent elevations on the inner surface of the lateral ventricles,
by means of which the latter become narrowed and reduced in size.
The total furrows of the cerebral hemispheres are the fissure of
SYLVIUS (fossa Sylvii), the arcuate fissure, embracing the hippo-
campal fissure (fissura hippocampi), the fissura choroidea, the fissura
calcarina, and the fissura parieto-occipitalis. The elevations produced
by them are called the corpus striatum, fornix and pes hippocampi,
tela choroidea and calcar avis. A prominence which in the embryo
corresponds to the fissura parieto-occipitalis, becomes obliterated in
the adult by a considerable thickening of the wall of the brain, so
that no permanent structure results from it.

fhef&sure of SYLVIUS (fig. 252 Sy.g) is the first one formed. It
appears as a shallow depression of the con rex outer surface at about

442 EMBRYOLOGY.

the middle of the lower margin of each hemisphere. The part of
the wall which is thus depressed becomes considerably thickened
(figs. 243, 251 cst, and 254 st), and forms an elevation on the floor of
the cerebrum projecting into its cavity, the corpus striatum, in which
several nuclei of gray matter are developed (the nucleus caudatus, the
nucleus lentiformis, and the claustrum). Inasmuch as the elevation
lies at the base of the brain and forms the direct forward and lateral
continuation of the optic thalamus, it is regarded as belonging to
the brain-stalk, and is distinguished as the stalk part of the cerebral
hemispheres in distinction from the remaining portion or mantle part.
The outer surface of the stalk part can be seen from the outside for
a time,— as long as the Sylvi an fissure is still shallow (fig. 252 Sy.g),

tchei.1

Pig. 252.— Lateral view of the brain of a human embryo during the first half of the fifth month,

after MIHALKOVICS. Natural size.
•stl, Frontal lobe ; schei.l, parietal lobe ; hi, occipital lobe ; schl.l, temporal lobe ; Sy.g, fissure

of SYLVIUS ; rn, olfactory nerve ; kh, cerebellum ; br, pons ; mob, medulla oblongata.

— but it then becomes entirely overgrown and hidden by the edges of
the gradually deepening fissure. Later this surface acquires in the
embryo several cortical furrows and becomes the island of REIL
(insula Beilii), or the central lobe (Stammlappen).

The mantle portion, as it enlarges, spreads out uniformly around
the island of REIL, as though about a fixed point, and surrounds it
in the form of a half -ring open below (fig. 252) ; on this account it
uas received the name ring-lobe. Even now the regions of the four
chief lobes into which the convex surface of each hemisphere is
subsequently divided can readily be distinguished, although they are
not yet sharply limited. The end of the half -ring which is directed
forward and lies above the fissure of SYLVIUS (Sy.g) is the frontal
lobe (stl) ; the opposite end, which embraces the fissure behind and

THE ORGANS OF THE OUTER GERM-LAYER. 443

below, is the temporal lobe (schl.l) ; the region lying above and
connecting the two is the parietal lobe (sckei.l). A prominence
which is developed from the ring-lobe backward becomes the occipital
lobe (hi).

The lateral ventricle has also become altered and corresponds to the
external form of each hemisphere (fig. 253). It also assumes the
shape of a half-ring, which lies above and surrounds the corpus
striatum (cst) — that part of the wall of the vesicle which is forced
inward by the fissure of SYLVIUS. Subsequently, when the individual
lobes of the hemispheres are more sharply differentiated from one
another, the lateral ventricle also undergoes a subdivision correspond-
ing to the lobes. It becomes slightly enlarged at both ends, in front
into the anterior cornu occupying the frontal lobe, behind and below
into the inferior cornu of the temporal lobe. Finally, from the half-
ring there is developed a small evagination, the posterior cornu,
which extends backward into the occipital lobe. The region lying
between the horns is narrowed and becomes the cella media.

All the fissures hitherto mentioned, except that of SYLVIUS, are
developed on the plane [median] surface of the vesicle of the
hemisphere.

At a very early stage — in Man in the fifth week (His) — there arise
on this wall of the hemisphere two furrows running almost parallel
with the edge or bend of the mantle, the arcuate or hippocampal fissure
and the fissure of the choroid plexus (fissura hippocampi smdjissura
choroidea) ; both conform very closely in their direction to the ring-
lobe, and, like it, with crescentic form embrace from above the stalk
part of the cerebrum, the corpus striatum. They begin at the
foramen of MONRO and extend from there to the tip of the temporal
lobe, forming the boundaries of a region known as the marginal arch
(Randbogen) ; this projects as a thickening on the median surface of
the hemisphere, and takes part in the development of the commissural
system. The in vagina tions of the median wall of the ventricle, caused
by the fissures, the hippocampal fold and the fold of the lateral choroid
plexus, are best understood by removing in an embryo the lateral
wall of the hemisphere, so that one can survey the inner surface of
the median wall of the still very spacious and ring-like lateral
ventricle (fig. 253). The cavity is then seen to be partly filled with
a reddish frilled fold (agf), which lies in the form of a crescent on the
upper surface of the corpus striatum (cst). In the region of the fold
the wall of the brain undergoes changes similar to those in the roof
of the medulla oblongata and of the vesicle of the between-brain

444

EMBRYOLOGY.

Fig. 253.— Lateral vi«w of the brain of an embryo Calf
5 cm. long. The lateral wall of the hemisphere
has been removed. After MIHALKOVICS. Magni-
fied 3 diameters.

cst, Corpus striatum ; ML, foramen of MONKO ; agf,
plexus choroideus lateralis ; amf, hippocampal
fold ; kh, cerebellum ; Dp, roof of the fourth
ventricle ; bb, pontal flexure ; mo, medulla ob-
longata ; mh, mid-brain (parietal flexure).

(figs. 254 pi and 255 aaf). Instead of thickening and developing

nerve-substance, it becomes
attenuated, and is trans-
formed into a single layer
of flat epithelial cells, which
are firmly united with the
pia mater. The latter then
becomes very vascular along
the entire fold, and grows
into the lateral ventricle in
the form of tufts, which
carry the epithelium before
them. In this way the
lateral choroid plexus arises

(fig. 254 pi), which afterwards, in the adult, fills a part of the cella

media and in-
ferior cornu.

It begins at

the foramen of

M o N R o (fi g.

253 JfZ),where

it is continuous

with the an-
terior unpaired

choroid plexus

which has

arisen in the

roof of the be-

tween-brain

vesicle. If the

delicate vas-
cular pia mater

is drawn out

from the cho-
roid fissure, the

wall of the

brain, which is

reduced to a

Fig. 254. — Transverse section through the brain of an embryo Sheep

2 -7 cm. in length, after KOLLIKER.

The section passes through the region of the foramen of MONEO.
at, Corpus striatum ; m, foramen of MONKO ; t, third ventricle ; pi,

plexus choroideus of the lateral ventricle ;/, falx cerebri ; th, deepest

anterior part of the optic thalamus; ch, chiasma ; o, optic nerve ;

c, fibres of the crus cerebri; h, hippocampal fold ; p, pharynx;

so,, presphenoid ; a, orbito-sphenoid ; s, part of the roof of the

brain at the junction of the roof of the third ventricle with the

lamina terminalis ; I, lateral ventricle.

thin epithe-
lium, is at the same time destroyed, and there is produced in the
median wall of the hemisphere a gaping fissure, which extends from

THE ORGANS OF THE OUTER GERM-LAYER.

445

the foramen of MONRO to the tip of the temporal lobe and leads from
the outside into the lateral ventricle. This is the lateral cerebral fis-
sure, or the great fissure of the hemispheres (fissura cerebri trans versa).

In a preparation made in the manner described the hippocampal
fold is to be seen at a short distance from the choroid plexus and
parallel to it (figs. 253 and 255 am/ and fig. 254 K). This increases
in size toward the apex of the inferior cornu, and in the completely
formed brain produces the cornu Ammonis or pes hippocampi.
Consequently that part of the lateral ventricle enclosed in the tem-
poral lobe becomes (as the result of two infoldings of its median
wall) restricted
by two pro-
jections, the
choroid plexus
and the cornu
Ammonis. As
in the between-
brain and me-
dulla o b 1 o n-
gata, the epi-
thelial covering
of the choroid
plexus is con-
tinuous with
the thicker
nerve-sub-
stance of the
cornu A m-
monis. The

transition is effected by means of a thin medullary plate, which in
anatomy is described as the fimbria.

Inasmuch as the occipital lobe with its cavity develops as an
evagination of the ring-lobe, the fissura calcarina belonging to it
is therefore developed somewhat later than the arcuate fissure
(fig. 241 fc). It appears at the end of the third month as a fissure
branching off from the latter, and runs in a horizontal direction until
near the apex of the occipital lobe. It invaginates the median wall
of the lobe and produces the calcar avis, which invades the posterior
cornu in the same way as the hippocampus major (cornu Ammonis)
does the inferior cornu. At the beginning of the fourth month the
fissura occipitalis (fig. 241 fo) is added to it. The latter rises from

rxf

ch

Fig. 255. — Transverse section through the brain of a Rabbit embryo

3'8 cm. in length, after MIHALKOVICS. Magnified 9 diameters.
The section passes through the foramina of MONRO.
hs, Great falx cerebri which fills up the interpallial fissure ; A1, h2, plane

inner [median] and convex outer wall of the cerebral hemisphere ;

agf, fold of the choroid plexus ; «;»/, hippocampal fold ; /, fornix ;

sv, lateral ventricle ; ML, foramen of MOXKO ; v3, third ventricle ;

ch, optic cbiasma ; frx', descending root of the fornix.

446 EMBRYOLOGY.

the anterior end of the fissura calcarina in a vertical direction to
the bent rim of the mantle (Mantelkante), and sharply separates the
occipital and parietal lobes from each other.

A third factor of great importance in the development of the
cerebrum is the formation of a system of commissures, which sup-
plements the connection of the two cerebral vesicles, at first effected
by the embryonic lamina terminalis only. Those investigators who
have occupied themselves with these difficult matters assert that in
the third embryonic month fusions take place between the facing
median walls of the hemispheres. These fusions begin in front of
the foramen of MONRO within a triangular area. The fusions in this
region occur only at the periphery, not in the middle of the area.
Three parts of the brain of the adult are thus produced : in front, the
genu of the corpus callosum, behind, the columns of the fornix, and
between them, the septum pellucidum ; the latter contains a fissure-
like cavity, in the region of which the contiguous walls of the hemi-
spheres, here very much attenuated, have remained separated from
each other. Consequently the cavity just mentioned — the ventriculus
septi pellucidi [or fifth ventricle] — ought not to be placed in the same
category with the other cavities of the brain ; for while the latter are
derived from the central canal of the embryonic neural tube, the
former is a new production, which has arisen by the enclosure of a
portion of the space lying outside the brain between the two hemi-
spheres— the narrow interpallial fissure.

A further enlargement of the commissural system is accomplished
in the fifth and sixth months. The fusion now proceeds still
farther, advancing from in front backwards, and involves that region
of the median walls of the hemispheres which, situated between the
arcuate fissure [above] and the fissure of the choroid plexus [below],
has already been described as the marginal arch (Randbogen). By
fusion of the anterior part of the marginal arch with its fellow of the
opposite side, — which process takes place as far as the posterior limit
of the between-brain, — there arise the body of the corpus callosum
and the splenium, as well as the underlying fornix. The farrow
bounding the corpus callosum above (sulcus corporis callosi) is there-
fore the anterior part of the arcuate furrow, whereas- the posterior
portion, that of the temporal lobe, is subsequently known as the
fissura hippocampi.

The structure of the cerebrum is completed by the appearance of
numerous cortical furrows. These differ in rank from the total furrows
already described, because they are confined to the outer surface of the

THE ORGANS OF THE OUTER GERM-LAYER.

447

brain and do not cause corresponding projections into the ventricles.
Their formation begins as soon as the wall of the brain becomes
greatly increased in thickness by the development of white medullary
substance, which occurs during and after the fifth month. This
is due to the fact that the gray cortex with its ganglionic cells
increases more rapidly in superficial extent than the white substance
and is therefore raised into folds, the cerebral convolutions or gyri,
into which only thin processes of white substance penetrate. At
first, therefore, the furrows are quite shallow; they become deeper
in proportion as the hemispheres become thicker and the cortical
folds project farther out-
ward.

Of the numerous fur-
rows which the completely
formed brain presents, some
appear during the develop-
ment earlier, others later.
Thus they acquire different
values in the architecture
of the cerebral surface.
For <; the earlier a furroiv
appears the deeper it be-
comes, the later it ap-
pears the shallower it is"
(PANSCH). The first are
therefore the more impor-
tant and constant ones, and
are fittingly to be distin-
guished as chief or primary
furrows from the subse-
quently formed and more variable secondary and tertiary furrows. They
begin to appear at the commencement of the sixth month. Tha
first of them to appear is the central furrow (fig. 256 cf), which is
one of the most important, since it separates the frontal and parietal
lobes from each other. " In the ninth month all of the chief sulci and
convolutions are formed, and since at this time the secondary sulci
are still wanting, the brain during the ninth month presents a
typical illustration of the sulci and convolutions " (MIHALKOVICS).

Very great differences exist between the different divisions of Mammals in
the extent to which the sulci of the cerebrum are developed. On the one hand
are the Monotremes, Insectivores, and many Rodents, whose cerebrum — also

Fig. 256. — Brain of a human embryo at the beginning
of the eighth month, after MIHALKOVICS. Three-
fourths natural size.

cf, Central furrow ; vcw, hew, anterior and posterior
central convolutions ; fo, fissura occipitalis.

448

EMBRYOLOGY.

usually less developed in other features — possesses a smooth surface, and thus,
as it were, remains permanently in the foetal condition of the human brain.
On the other hand the brains of the Carnivores and Primates, owing to the
great number of their convolutions, approach more closely to the human brain.

Finally, in treating of the development of the cerebrum there is
still to be considered an appendage to it, the olfactory nerve. This
part, as well as the optic nerve, is distinguished from the peripheral

nerves by its entire development,
and must be considered as a
specially modified portion of the
cerebral vesicle. The older de-
signation of nerve is therefore
now more frequently replaced by
the more appropriate name of
olfactory lobe (lobus olfactorius,
rhinencephalon). Even at an
early stage — in the Chick on the
seventh day of incubation, in
Man during the fifth week (His)
— there is formed on the floor of
each frontal lobe at its anterior
end a small evagination, which
is directed forward (figs. 240,
241 rn). This gradually assumes
the form of a club, the enlarged
end of which, the part ]ying
on the cribriform plate of the
ethmoid bone, is designated as
the bulbus olfactorius. The bul-
bus encloses a cavity which is in
communication with the lateral
ventricle.

During the first month of development the olfactory lobe, even in
Man, is relatively large and provided with a central cavity. Later
it begins to diminish somewhat, the sense of smell being only
slightly developed in Man ; its growth is arrested and at the
same time its cavity also disappears. In most Mammals, on the
contrary, — whose sense of smell, as is well known, is more acute
than that of Man, — the olfactory lobe attains a greater size in the
adult animal and exhibits more clearly the character of a part of
the brain, for it permanently encloses in its bulb a cavity, which

Fig. 257.— Brain of Galeus canis .in situ,
dorsal aspect, after ROHON.

Lol, Lobus olfactorius ; Tro, tractus nervi
olfactorii ; VH, fore-brain, provided at
fn with a vascular foramen (foramen
nntritium); ZH, between -br ain ; Mff,
mid-brain ; Hff, hind-brain ; NH, after-
brain ; It, spinal cord ; //, n. opticus ;
///, n. oculomotorius ; IF, 11. trochlearis ;
V, n. trigeminus ; L,Trig, lobus trigemini ;
C,rest, corpus restiforme ; IX, glosso-
pharyngeus; X, vagus; £,t, eminentise
teretes.

THE ORGANS OF THE OUTER GERM-LAYER. 44i>

frequently (Horse) is even in connection with the anterior cornu by
means of a narrow canal in the tractus olfactorius.

The olfactory lobe (Lol+Tro) attains an extraordinary develop-
ment (fig. 257) in the Selachia, in which it exceeds in size the
between-brain (ZH) and mid-brain (MH . In the Selachians two-
long hollow processes (tractus olfactorius, Tro) extend out from th&
anterior end of the little-developed cerebrum and terminate at a
considerable distance from the fore-brain in two large hollow lobes,,
that are sometimes provided with furrows (Lol).

B. The Development of the Peripheral Nervous System.

Although it is easy to follow the development of the brain and1
spinal cord, the investigation of the origin of the peripheral nervous
system is very difficult, for it requires the study of histological processes
of the most subtle nature — the first appearance of non-medullated
nerve -fibres and the method of their termination in embryos
composed of more or less undifferentiated cells. One who knows
how difficult it is even in the adult animal to follow non-medullated
nerve-fibrillse in epithelial layers or in non-striate mussle-tissue, and
to get a clear idea of their method of termination, will understand
that many, and indeed the most interesting, questions in regardi
to the development of the peripheral nerves are not yet ripe for
discussion, because the observations necessary for their settlement
are still wanting. There is only one point which is entirely clear.
That concerns the development of the spinal ganglia, which His and
BALFOUR independently of each other were the first to recognise, the
one in the Chick, the other in Selachians. Since then numerous
investigations embracing different groups of Vertebrates have been
published on this subject by HENSEN, MILNES MARSHALL, KOLLIKER,
SAGEMEHL, VAN WIJHE, BEDOT, ONODI, BERANECK, RABL, BEARD,
KASTSCHENKO, and others.

(a) The Development of the Spinal Ganglia.

The development of the spinal ganglia in the spinal cord is very
easily followed. It begins just at the time the medullary groove
closes to form a tube (fig. 258 A and B). At this time a thin
ridge of cells (spg't spy) one or two layers deep grows out of the
neural tube on either side of the line of fusion, and, passing outward

29

450

EMBRYOLOGY.

and downward, inserts itself between the tube and the closely
investing primitive epidermis. In this way it reaches the dorsal
angle of the primitive somites (us), which are by this time well

developed. Then the
neural crest, as BAL-
FOUR names it, or the
ganglionic ridge, as
SAGEMEHL calls it,
is divided up into
successive regions.
For the tracts which
alternate with the
primitive segments
lag behind in their
growth, while the
parts lying opposite
the middle of seg-
ments grow more
vigorously, become
thickened, and at
the same time ad-
vance farther ven-
trad, penetrating be-
tween primitive seg-
ment and neural
tube.

Frontal sections
furnish very instruc-
tive views of this
stage. Fig. 259 ex-
hibits such a section,
taken from SAGE-
MEHL'S work. Inas-
much as the longi-
tudinal axis of the
Lizard embryo em-
ployed for the sec-
tions was greatly curved, the five segments seen in the section are cut
at different heights, the middle one deeper than the two preceding
and the two following. In the middle segment the fundament of
the ganglion (spk) is differentiated and it is bounded by blood-vessels

Fig. 258. — A, Cross section through an embryo of Pristiurus,
after RABL.

1 he primitive segments are still connected with the remaining
portion of the middle germ-layer. At the region of tran-
sition there is to be seen an outfolding, sk, from which the
skeletogenous tissue is developed, ch, Chorda ; spg, spinal
ganglion ; mp, muscle-plate of the primitive segment ;
sch, subchordal rod ; ao, aorta ; ik, inner germ-layer ;
pmbt parietal, vmb, visceral middle layer.

£, Cross section through a Lizard embryo, after SAGEMEHL.

rm, Spinal cord ; . spg, lower thickened part of the netiral
ridge ; sptf, its upper attenuated part, which is continuous
with the roof of the neural tube ; us, primitive segment.

THE ORGANS OF THE OUTER GERM-LAYER.

451

in front and behind, whereas in the segments that are cut more
•clorsally, near the origin of the ganglia from the neural tube, the
fundaments are still connected with one
another. This connection appears to bs
most conspicuously developed arid most per-
sistent in the case of the Selachians; it
has been called the longitudinal commis-
sure by BALFOUR. Outside the ganglia are
found the primitive segments (mp, mp'\ each
of which at this time still exhibits within
it a narrow fissure.

spk

Fig. 259.— Frontal seotion of
a Lizard embryo, after
SAGEMEHL.

rm, Spinal cord ; spk, neural
ridge with thickenings that
are converted into the spinal
ganglia; mp', the part of
the primitive segment that
produces the muscle-plate ;
mp, outer layer of the
primitive segment.

In a monographic treatment of the peripheral
nervous system BEARD differs from the preceding
account, in which BALFOUR, KOLLIKER, KABL,
HENSEN, SAGEMEHL, KASTSCHENKO, and others
agree. He believes that the fundaments of the
ganglia arise, not out of the neural tube, but out
of the deeper cell-layers of the adjacent part of
the outer germ-layer. He finds that they are from
the beginning separated from each other and seg-
onentally arranged. According to him, moreover,
they make their appearance earlier than is stated
in the preceding account ; for they are already
recognisable as especially thickened places in the
outer germ-layer at the light and left of the neural
plate when the latter first begins to be bent inward.

Subsequently, upon the closure of the neural tube, the ganglionic cells come
to lie between the raphe and the primitive epidermis. From here they grow
down ventrally at the sides of the brain and spinal cord.

BEARD approximates in his results the conception first expressed and
subsequently maintained by His. For His derives the ganglionic ridge, not
from the raphe of the neural tube, but from a neighboring part of the
outer germ-layer, which he names intermediate cord (Zwischenstrang). The
.accuracy of BEARD'S description is, however, positively denied by KABL and
XASTSCHENKO.

Different views are entertained concerning the further changes
which take place in the fundaments of the spinal ganglia : —

According to His and SAGEMEHL the separate ganglionic funda-
ments are completely detached from the neural tube, and for a time
lie at the sids of it without any connection with it whatever.
•Secondarily a union is again established, through the development
of the dorsal nerve-roots, by the formation of nerve-fibrillse, which
•either grow out from the spinal cord into the ganglion, or from the
ganglion into the spinal cord, or in both directions. SAGEMEHL

452 EMBRYOLOGY.

favors the first view, His the last. All other investigators main-
tain that the fundaments of the ganglia, while they increase in size
and become spindle-shaped, are permanently united with the neural
tube by means of slender cords of cells which are metamorphosed
into the dorsal roots. If the latter view is correct, the dorsal roots
of the nerves must in time alter their place of attachment to the
neural tube by moving from the raphe laterally and ventrally.

The discrepancy of these accounts is connected with the different
interpretations which exist concerning the development of the peri-
pheral nerves in general.

(b) The Development of the Peripheral Nerves.

When one reviews the various opinions which have been expressed
concerning the development of the peripheral nerves, it is found
that there are in the literature two chief opposing views. The
greater number of investigators assume that the peripheral nervous
system is developed out of the central, — that the nerves grow forth
from the brain and spinal cord uninterruptedly until they reach the
periphery, where for the first time they effect a union with their specific
terminal organs. The outgrowth of the nerves from the spinal cord
was first asserted for the ventral roots and conjectured for the dorsal
ones by BIDDER UND KUPFFER. Their conclusions have since been
adopted by KOLLIKER, His, BALFOUR, MARSHALL, SAGEMEHL, and
others. However, views concerning the method of the formation of
the nerve-fibres are not in agreement.

According to KUPFFER, His, KOLLIKER, SAGEMEHL, and others
the outgrowing nerve-fibres are processes of ganglionic cells located in
the central organ, which must grow out to an enormous length in
order to reach their terminal apparatus. There are at first no
cells or nuclei among them. These are furnished secondarily by
the surrounding connective tissue. According to the accounts of
KOLLIKER and His, cellular elements from the mesenchyme approach
the bundles of nerve-fibrillse, surround them, and then penetrate
into the interior of the nervous stem, at first sparingly, afterwards
more abundantly, and form around the axis-cylinders the sheaths of
SCHWANN.

On the other hand, BALFOUR defends most positively the doctrine
that cells which migrate out of the spinal cord along with the nerves
share in the development. In his " Treatise on Comparative Embry-
ology " [vol. ii., p. 372] he remarks upon this subject : " The cellular-

THE ORGANS OF THE OUTER GERM-LAYER. 453

structure of embryonic nerves is a point on which I should have
anticipated that a difference of opinion was impossible, had it not
been for the fact that His and KOLLIKER, following REMAK and
other older embryologists, absolutely deny the fact. I feel quite
sure that no one studying the development of. the nerves in Elasmo-
branchii with well-preserved specimens could for a moment be doubtful
on this point." Of the more recent investigators VAN WIJHE, DOHRN,
and BEARD side with BALFOUR.

HENSEN has taken an entirely different view on the question of
the origin of the peripheral nervous system, one which differs from
that of KUPFFER, His, and KOLLIKER, as well as from that of
BALFOUR. He opposes the doctrine of the outgrowth of nerve-fibres
chiefly from physiological considerations. He can think of no
motive which is capable of conducting the nerves that grow out
from the spinal cord to their proper terminations — which shall
•cause, for example, the ventral roots always to go to muscles, the
dorsal roots to organs that are not muscular, and shall prevent
confusion taking place between the nerves of the iris and those of the
eye-muscles, between the branches of the trigeminus and the acusticus
or facialis, etc. Therefore HENSEN maintains on theoretical grounds
that it is necessary to assume that " the nerves never grow out to their
terminations, but are always in connection with them." According
to his view, which he endeavors to support by observations, the
embryonic cells are for the most part united with one another by
means of fine connecting filaments. He maintains that when a
cell divides the connecting thread also splits, and in this manner
there arises " an endless network of fibres." Out of these the nerve-
tracts are developed, while other parts of the network degenerate.

The reasons given by HENSEN are certainly worthy of great
attention. With further reflection on the subject they are easily
added to. If the nerves grow out to their terminal apparatus, why
-do they not take the most direct course to their destination, why
-are they often compelled to pursue circuitous paths, and why do they
•enter into the formation of complicated plexuses of the greatest
-variety ? whence are the ganglionic cells that are found to be
developed in considerable numbers even in the peripheral nervous
system in different organs, especially in the sympathetic nerve ? In
order to make progress in this difficult field the peripheral nervous
system of Invertebrates must be taken into account more than it is
at present, and in the investigation of embryos not only series of
sections but also other histological methods (surface-preparations of

454 EMBRYOLOGY.

suitable objects together with stainicg of the nerve-fibrillse, isolation
of the elements preceded by maceration and staining) must be
employed.

Having thus sketched out the various standpoints taken by numer-
ous investigators on the question of the source of the peripheral
nervous system, I give a number of observations that have been
made tipon the development of certain nerves. These relate to the
development of : —

(1) The ventral and dorsal roots of the nerves ;

(2) Certain large peripheral nerve-trunks, as the nervus lateralis ;

and

(3) The nerves of the head and their relation to the spinal nerves.

(I) Of the roots of the nerves the anterior [ventral] are de-
monstrable earlier. There may be distinguished three stages in
their development.

The first stage has been observed by DOHRN and VAN WIJHE in
Selachian embryos. At a time when the neural tube has not yet
developed any mantle of nervous substance, and the muscle-segment
still lies very close to it, there arises between the two a connection in
the form of a very short protoplasmic cord. The fundament of the
nerve is therefore, as VAN WIJHE remarks, ab origine near its
muscle-complex, from which it never separates. Soon after this it
is elongated by the removal of the muscle-segment farther from the
neural tube ; it increases in thickness and now encloses numerous
nuclei, and possesses therefore a cellular composition, a condition
which I shall designate as second stage.

There is a difference of opinion as to the cells which make their
appearance in the fundament of the nerve. Whereas KOLLIKER
His, and SAGEMEHL recognise in them immigrated connective-tissue
elements, which are destined to form simply the envelopes of the
nerves, BALFOUR, MARSHALL, VAN WIJHE, DOHRN, and BEARD main-
tain that they migrate out from the spinal cord and share in the
development of the nerves themselves. BEARD even derives the
motor terminal plate from them. Soon after, as is asserted,
connective-tissue cells from the surrounding mesenchyme become
associated with the nerve-cells derived from the spinal cord and
ordinarily become indistinguishable from them.

Finally, in the third stage the cellular fundament of the motor
root acquires a fibrillar condition (fig. 260 vw), and it now becomes
possible to trace the origin of the nerve-fibrillse in the spinal cord
from groups of embryonal gangl ionic cells or neuroblasts (His).

THE ORGANS OF THE OUTER GERM-LAYER.

The formation of the nerve-fibrillse is also a subject of controversy,
as has already been stated and as will be further explained in this
connection. According to the view of most observers, the nerve-
fibrillse — the future axis-cylinders — are formed as processes of gang-
1 ionic cells of the spinal cord, the free ends of which grow out from
the surface of the latter until they reach their terminal organs

(KUPFFER UND BIDDER, KoLLIKER, HlS, SAGEMEHL). Such accounts

Fig. 260.— Cross section of a Lizard embryo with completely closed intestinal canal, after

SAGEMEHL.

he, Posterior [dorsal], vc, anterior commissure of the spinal cord ; vw, ventral nerve-root j
nf, nerve-fibrillae ; spk, spinal ganglion ; mpl, muscle-plate, muscle-procUicing layer ;
»ipa, outer layer of the muscle-plate ; mp*t transition from the outer to the muscle-
forming layer.

are given especially for the development of the motor roots in the
higher Vertebrates.

According to the opinion of DOHRN and VAN WIJHE, on the
contrary, the nerve-fibrillse arise in situ, as products of differentiation,
from the protoplasm of the cords of cells by means of which muscle-
.segment and spinal cord are already united. They do not need to
seek out the terminal organ, since there exists already a protoplasmic
union with it. They arise in a manner similar to that in which
the muscle-fibrillae do from the plasma of their muscle-cells.

456 EMBRYOLOGY.

I desire to lay particular stress upon the observations of DOHEN and VAN
WIJHB, because they harmonise with the theoretical views which I have
formed as the result of investigations on Invertebrates. As I have in several
articles endeavored to establish, protoplasmic connections of the cells are the
foundation out of which the nerve-fibrillae are developed. The formation of a
specific nervous system is preceded by a protoplasmic union of cells, which is
effected at a time when the central and terminal nervous organs are still in
the immediate vicinity of each other.

The dorsal roots become visible somewhat later than the ventral
roots j there are formed fibrillse which unite the upper [dorsal] end
of the spinal ganglion with the side of the spinal cord.

(2) GO'TTE, SEMPER, WIJHE, HOFFMANN, and BEARD have made
concerning certain nerves the noteworthy statement — which has been
called in question by some observers (BALFOUR, SAGEMEHL) — that the
epidermis participates in their formation. In Amphibian larvae
and Selachian embryos the posterior end of the nervus lateralis vagi
in process of development is completely fused with the primitive
epidermis, which is thickened in the lateral line (fig. 262 nl). Some-
what farther forward the nerve is detached but still lies in close
contact with the primitive epidermis, whereas in the vicinity of the
head it is situated deeper and lies between the muscles. At the
places where the nerve has become separated from the primitive
epidermis, it remains in connection with the fundaments of the
lateral organs by means of fine accessory branches only. Similar
observations have also been made in the case of many of the branches
of other cranial nerves in Selachian embryos. WIJHE sees, for
example, a short branch of the n. facialis near its emergence from
the brain so fused with a thickened portion of the epidermis composed
of cylindrical cells, that it is impossible to say whether at the place
of transition the cell-nuclei belong to the nerve or to its terminal
organ. During a more advanced stage the older part of the nerve
is detached from the terminal organ, sinks into the depths, becoming
separated from the skin by ingrowing connective tissue, and remains
united with the terminal organ only through fine accessory branches.
The persistently growing younger end of the nerve still continues to
be connected with the epidermis.

Also in the case of the higher Vertebrates similar conditions have
oeen observed by BEARD, FRORIEP, and KASTSCHENKO. They find
the ganglionic fundaments of the facialis, glossopharyngeus, and
vagus at the dorsal margin of the corresponding visceral clefts for a
long time broadly fused with the epithelium, which is thickened and
has become depressed into a pit. In these connections they discern

THE ORGANS OF THE OUTER GERM-LAYER. 457

the fundaments of branchial sensory organs, which no longer attain
to complete development. Also FRORIEP, on the strength of his own
•observations, holds as admissible the interpretation that at those
places where fusion occurs formative material passes out of the
epidermis into deeper parts to share in the formation of nervous
tracts. BEARD expresses himself still more precisely to the effect
that the sensory nervous elements of the whole peripheral nervous
system arise as differentiations from the outer germ-layer, independ-
ently of the central nervous system.

The accounts here given concerning a connection, in early stages of develop-
ment, of certain nerve-trunks with the outer germ-layer, appear to me to afford
an indication in favor of the hypothesis expressed by my brother and me,
that the sensory nerves of the Vertebrates may have originally been formed
•out of a sub-epithelial nervous plexus, such as still exists in the epidermis of
many Invertebrates.

(3) The investigations of the last few years, which have been
carried out especially by BALFOUR, MARSHALL, KOLLIKER, WIJHE,
FRORIEP, RABL, and KASTSCHENKO, have produced important results
concerning the development of the cranial nerves, their relations to
the head-segments and their value as compared with spinal nerves.
•On the brain, as well as on the spinal cord, there arise roots, some
•of which are dorsal, some ventral. Even at the time when the
brain-plate is not yet fully closed into a tube (fig. 261), there is
formed on either side, at the place of its bending over into the
primitive epidermis, a neural ridge (vg), which begins rather far
forward and may be traced on serial sections uninterruptedly in a
posterior direction, where it is continuous with the neural ridge
• of the spinal cord. When, somewhat later, the closure and the
detachment of the brain -vesicles from the primitive epidermis has
taken place, the ridge lies on the roof of the vesicles and is fused
with them in the median plane. The most of the cranial nerves —
namely, the trigeminus with the Gasserian ganglion, the acusticus
and facialis with the ganglion acusticum and probably also the
.ganglion geniculi, and the glossopharyngeus and vagus with the
related ganglion jngulare and g. nodosum — are differentiated out of
this fundament in the same manner as the dorsal roots of the
spinal nerves. The nerves, which emerge dorsally, afterwards shift
their origin downward along the lateral walls of the brain -vesicles
toward the base of the latter.

All the remaining unenumerated cranial nerves — oculomotorius,
-trochlearis, abducens, hypoglossus, and accessorius — are developed

458 EMBRYOLOGY.

independently of the neural ridge, as individual outgrowths of the-
brain-vesicles nearer their base, and are comparable with the ventral
roots from the spinal cord.

FROEIEP finds that the hypoglossus in Mammals possesses dorsal roots,
with small ganglionic fundaments, in addition to ventral roots. The latter
subsequently undergo degeneration.

The agreement between cranial and spinal nerves which is ex-
pressed in this method of development, becomes still greater and

Fig. 261.— Cross section through the hind part of the head of a Chick embryo of 30 hours, after
BALFOUR.

hl>, Hind-brain; vg, vagus; ep, epiblast ; ch, chorda; x, thickening of hypoblasfc (pDssibly a.
rudiment of the subchordal rod) ; al, throat ; ht, heart ; pp, body-cavity ; so, somatic
mesoblast ; sf, splanchnic mesoblast (Darmseitenplatte) ; hy, hypoblast.

acquires a further significance from the fact that in the head also the
nerves can be assigned to separate segments in much the same manner
as in the trunk. In this particular the conditions are clearest in
the Selachians, where, in fact, the head-segments have been most
thoroughly investigated, so that 1 limit myself to a statement of the
results acquired in this field by WIJHE.

According to WIJHE nine* segments are distinguishable in the
head of Selachians. To the first segment belongs the ramus

* [Recent investigations indicate that the head-segments in Selachians are
much more numerous. — TRANSLATOR.]

THE ORGANS OF THE OUTER GERM-LAYER. 459

ophthalmicus of the trigeminus and, as motor root, the oculo-
motorius. The second segment is supplied by the remaining part
of the trigeminus and the trochlearis, the latter having a ventral
origin. The dorsal roots of the third (and fourth?) segments are
represented by the acustico-f acialis, the ventral roots by the
abducens. The fifth segment possesses only the exclusively sensory
glossopharyngeus, which arises from the neural ridge. The segments
from the sixth to the ninth inclusive are innervated by the vagus and
the hypoglossus, the former of which represents a series of dorsal
roots, the latter a series of ventral ones.

According to WIJHE'S account, notwithstanding the general agree-
ment, there still exists a considerable difference between the innervation
of the cephalic segments and that of the trunk-segments. For in the
head the ventral, motor roots (oculomotorius, trochlearis, abducens,
hypoglossus) supply only a part of the musculature — the eye-
muscles and certain muscles that run from the skull to the pectoral
girdle ; that is to say, muscles which, as has already been stated, are
developed out of the cephalic segments. Other groups of muscles,
which arise from the lateral plates of the head, are innervated by
the trigeminus and f acialis, which have a dorsal origin. Thus the
dorsal roots of the nerves in the head would be distinguished from
those in the trunk by the important fact that they contain motor as
well as sensory fibres. BELL'S law would consequently possess a very
limited application for the head-region of Vertebrates, and would
have to be replaced by the following law, formulated by WIJHE : —

" The dorsal roots of the head-nerves are not exclusively sensory,
but also innervate the muscles that arise from the lateral plates, not,
however, those from the primitive segments (somites)."

" The ventral roots are motor, but innervate only the muscles of
the primitive segments (somites), not those of the lateral plates."

In view of this fundamental difference, I desire to express a doubt
whether there are not after all enclosed in the facialis and trigeminus
parts which are established as ventral roots, but have hitherto been
overlooked, as in the beginning all the ventral roots in the brain
(see BALFOUR) were overlooked.

According to EABL the nerves of the posterior part of the head only—
glossopharyngeus, vagus, accessorius, and hypoglossus — can be compared with
the type of spinal nerves ; the nerves of the anterior part of the head, on the
contrary, — the olfactorius, opticus, trigeminus, together with those of the eye-
muscles and the acustico-facialis, — belong in a separate category, just as the
four most anterior head-segments do.

460 EMBRYOLOGY.

As is evident from this brief survey, there still exist many unsolved
problems in the difficult subject of the development of the peripheral
nervous system. Without permitting myself to enter upon a further
discussion of the contradictory opinions entertained on this subject,
I close this topic with a comparative-anatomical proposition, which
appears to me sufficient to furnish the morphological explanation of
BELL'S law, or the separate origin of the sensory and motor nerve-
roots.

In Amphioxus and the Cyclostomes the motor and sensory nerve-
fibres are completely separated, not only at their origin from the
spinal cord, but also throughout their whole peripheral distribution.
The former pass at once from their origin in the spinal cord to the
muscle-segments ; the latter ascend to the surface to be distributed
to all parts of the skin to supply its sensory cells and sensory organs.
The separation of the peripheral nervous system into a sensory and a
motor portion, which is rigorously carried out in Amphioxus and the
Cyclostomes, is explained by the fact that the territories to which their
ends are distributed are spatially distinct in their origin, since the
sensory cells arise from the outer germ-layer, the voluntary muscles
from a tract of the middle germ-layer. Therefore the sensory nerve-
fibres have been developed from the spinal cord in connection with the
outer germ-layer, the motor fibres in relation with the muscle-
sagments.

I regard the sub-epithelial position of the sensory nerve-fibres as
the original one, just as we find in many Invertebrates the whole
peripheral sensory nervous system developed as a plexus in the
deepest portion of the epidermis. The important conditions above
described — according to which many dermal nerves (nervus lateralis,
etc., fig. 262 nl) are fused with the epidermis at the time of their
origin, and only subsequently become detached from it and sink
•deeper into the underlying mesenchyme — appear to me to indicate
that such a position was the primitive one in the case of Vertebrates
also.

I look upon the union of the sensory and motor nerve-fibres into
mixed trunks (which occurs soon after their separate origin from
the spinal cord, in the case of all Vertebrates except Amphioxus and
the Cyclostomes) as a secondary condition, and maintain that it is
caused especially by the following embryological influences : by the
change in the position of the spinal cord and the muscular
masses, and by the great increase in the amount of the connective
substances.

THE ORGANS OF THE OUTER GERM-LAYEli.

461

Fig. 262. — Cross section through the anterior part of tie tr-ink of an embryo of Scyllium, after-
BALFOUR.

Between the dorsal wall of the trunk and its ventral wall, where the attachment of the stalk
of the yolk-sac is cut, there is stretched a thick richly cellular mesentery, which completely
divides the body-cavity into right and left halves. Within the mesentery the duodenum
(du), from which the fundament of the pancreas (pan) is given off dorsally and the funda-
ment of the liver (hp.d) ventrally, is twice cut through. In addition, the place where the
vitelline duct [umbilical canal] (umc) joins the duodenum is visible.

sp.c, Spinal cord ; s.pg, ganglion of posterior root ; ar, anterior root ; dn, dorsally directad nerve
springing from the posterior root ; mp, muscle-plate ; mp', part of the muscle-plate already
converted into muscles ; mp.l, part of the muscle-plate which gives rise to the muscles of the
limbs ; nl, nervus lateralis ; ao, aorta ; ch, chorda ; sy.g, sympathetic ganglion; ca.v, cardinal
vein ; sp.n, spinal nerve ; sd, segmental (archinephric) duct ; st, segmental tube.

462 EMBRYOLOGY.

Since the spinal cord comes to lie in deeper layers of the body
far away from its place of origin, the dermal nerves must follow it,
and therefore their origins are correspondingly farther separated
from their terminations. Since also, on the other hand, the muscle-
plates grow around the neural tube, certain motor and sensory
nerve-cords are brought near to each other in .their passage to their
peripheral distribution. And this will occur especially in all cases
where the motor and sensory peripheral terminations lie at a great
distance from, the origin of the nerves out of the spinal cord, as, for
-example, in the case of the limbs. The mutual approximation of
sensory and motor nerve-tracts thus brought about will finally lead
to the formation of common tracts, according to the same principle
of simplified organisation in accordance with which the blood-vessels
also adapt themselves closely to the course of the nerves.

(c) The Development of the Sympathetic System

The development of the sympathetic nervous system, has as yet
been investigated by only a few observers. BALFOUR first announced
that it arose in connection with the cranial and spinal nerves, and
therefore was, like the latter, really derived from the outer germ-
layer, In the Selachians he found the sympathetic ganglia (fig. 262
sy.g) as small enlargements of the chief trunks of the spinal
nerves (sp.n) a little below their ganglia (sp.g). In older embryos,
according to BALFOUR'S account, they recede from the spinal
ganglia, and then at a later period unite with one another, by the
development of a longitudinal commissure, into a continuous cord
.(Grenzstrang).

The origin of the sympathetic system has been the most thoroughly
istudied by ONODI in researches covering several classes of Verte-
brates. According to him the sympathetic ganglia arise directly, as
BALFOUR suggested and as BEARD has also lately reiterated, from the
spinal ganglia. The ventral ends of the spinal ganglia undergo
•proliferation, as is best seen in Pishes. The proliferated part de-
taches itself, and, as fundament of a sympathetic ganglion, moves
ventrally. The fundaments of the individual segments are at first
separate from one another. The cord (Grenzstrang) is a secondary
product, produced by the growing out of the individual ganglia
toward each other and the union of the outgrowths. Afterwards
the sympathetic ganglia and plexuses of the body-cavity are derived
from this part.

THE ORGANS OP THE OUTER GERM-LAYER. 463

SUMMARY.

Central Nervous System.

1. The central nervous system is developed out of the thickened
region of the outer germ-layer which is designated as the medullary
plate.

2. The medullary plate is folded together to form the medullary
tube (medullary ridges, medullary groove).

3. The formation of the neural tube exhibits three principal
modifications : (a) Amphioxus, (6) Petromyzon, Teleosts^ (c) the re-
maining Vertebrates.

4. The lateral walls of the medullary tube become thickened,
whereas the dorsal and ventral walls remain thin ; the latter come
to occupy the depths of the anterior and posterior longitudinal
fissures, and constitute the commissures of the lateral halves of
the spinal cord.

5. The spinal cord at first fills the whole length of the vertebral
canal, but it grows more slowly than the latter, and finally terminates
at the second lumbar vertebra (explanation of the oblique course of
the lumbar and sacral nerves).

6. The part of the neural tube which forms the brain becomes
segmented into the three primary cerebral vesicles (primary fore-
brain vesicle, mid-brain vesicle, hind-brain vesicle).

7. The lateral walls of the fore-brain vesicle are evaginated to
form the optic vesicles, the anterior wall to form the vesicles of the
cerebrum.

8. The hind-brain vesicle is divided by constriction into the vesicles
of the cerebellum and the medulla.

9; Thus from the three primary brain- vesicles there finally arise
five secondary ones arranged in a single series one after the other
— (a) cerebral vesicle (that of the hemispheres), (b) between-brain
vesicle with the laterally attached optic vesicles, (c) mid-brain
vesicle, (d) vesicle of the cerebellum, (e) vesicle of the medulla
oblongata.

10. The originally straight axis uniting the brain-vesicles to one
another later becomes at certain places sharply bent, in consequence
of which the mutual relations of the vesicles are changed (cephalic
flexure, pontal flexure, nuchal flexure). The cephalic or parietal
protuberance at the surface of the embryo corresponds to the cephalic
flexure, the nuchal protuberance to the nuchal flexure.

464 EMBRYOLOGY.

11. The separate parts of the brain are derivable from the five-
brain-vesicles ; the accompanying table (MIHALKOVICS, SCHWALBE)
gives a survey of the subject.

12. In the metamorphoses of the vesicles the following processes
take place: (a) certain regions of the walls become more or less
thickened, whereas other regions undergo a diminution in thickness
and do not develop nervous substance (roof -plates of the third and:
fourth ventricles) ; (b) the walls of the vesicles are infolded "r
(c) some of the vesicles (first and fourth) greatly exceed in their
growth the remaining ones (bet ween- brain, mid-brain, after-brain, or
medulla oblongata).

13. The four ventricles of the brain and the aqueduct us Sylvii
are derived from the cavities of the vesicles.

14. Of the five vesicles that of the mid-brain is the most conser-
vative and undergoes the least metamorphosis.

15. The vesicles of the between-brain and after-brain exhibit,
similar alterations : their upper walls or roof -plates are reduced in
thickness to a single layer of epithelial cells, and in conjunction
with the growing pia mater produce the choroid plexuses (anterior,,
lateral, posterior choroid plexus ; anterior, posterior brain-fissure).

16. The cerebral vesicle is divided by the development of the
longitudinal (interpallial) fissure and the falx cerebri into lateral
halves, the two vesicles of the cerebral hemispheres.

17. In Man the cerebral hemispheres finally exceed in volume all
the remaining parts of the brain, and grow from above and from the
sides as cerebral mantle over the other brain-vesicles (from the second
to the fifth inclusive) or the brain-stalk.

18. In the folding of the walls of the hemispheres there are to be-
distinguished fissures and sulci.

19. The fissures (fossa Sylvii, fissura hippocampi, fissura choroidea,
fissura calcarina, fissura occipitalis) are complete folds of the wall of
the brain, by means of which there are produced deep incisions in.
the surface and corresponding projections into the lateral ventricles
(corpus striatum, cornu Ammonis, fold of the choroid plexus, calcar
avis).

20. The sulci are incisions limited to the cortical portion of the
wall of the brain, and are deeper or shallower according to the time
of their formation (primary, secondary, tertiary sulci).

21. In general the fissures appear earlier than the sulci.

22. The olfactory nerve is not equivalent to a peripheral nerve-
trunk, but, like the optic vesicle and optic nerve, a special part of

THE ORGANS OF THE OUTER GERM-LAYER.

465

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466 EMBRYOLOGY^- — «y

the brain produced by an evagination of the frontal lobe of the
cerebral hemisphere (lobus or .bulb^rS^ oitactorius with tractus olfac-
torius). (Enormous development of <;£n>/ olfactory lobes in lower
Vertebrates, — Sharks, — degeneration in Man.)

Peripheral Nervous System.

23. The spinal ganglia are developed ou^pf a neural ridge (crest),
which grows outward and downward from the raphe of the neural
tube on either side between the tube and the primitive epidermis,
and becomes thickened in the middle of each primitive segment into
a ganglion.

24. The spinal ganglia therefore arise, like the neural tube itself,
from the outer germ-layer.

25. The sympathetic ganglia of the longitudinal cord (Grenz-
strang) are probably detached parts of the spinal ganglia.

26. Concerning the development of the peripheral nerve-fibres
there are different hypotheses : —

First hypothesis. The peripheral nerve-fibres grow out from the
central nervous system and only secondarily unite with
their peripheral terminal apparatus.

Second hypothesis. The fundaments of the peripheral terminal
apparatus (muscles, sensory organs) and the central
nervous system are connected from early stages of
development by means of filaments which become nerve-
fibres (HENSEN).

27. Anterior and posterior nerve-roots are developed on the
spinal cord separately from each other, one ventrally, the other
dorsally.

28. The cranial nerves arise in part like posterior, in part like
anterior roots of spinal nerves.

29. The following cranial nerves with their ganglia, which are
comparable with spinal ganglia, are developed out of a neural ridge
which grows out from the raphe of the brain-vesicles : the trigeminus
with the ganglion Gasseri, the acusticus and facialis with the gang-
lion acusticum and g. geniculi, the glossopharyngeus and vagus with
the ganglion jngulare and g. nodosum.

30. The oculomotorius, trochlearis, abducens, hypoglossus, and
accessorius are developed like ventral roots of spinal nerves.

31. The olfactory and optic nerves are metamorphosed parts of
the brain.

THE ORGANS OF THE OUTER GERM-LAYER. 467

II. The Development of the Sensory Organs, Eye, Ear, and Organ

of Smell.

As the outer germ-layer is the parental tissue of the central
nervous system, so also does it form the substratuni for the higher
sensory organs, the eye, .the ear, and the organ of smell. For it
furnishes the sensory epithelium, a component which, in comparison
with the remaining parts, derived from the mesenchyma, is, it is
true, of very small volume, but, notwithstanding, by far the most
important both from a functional and a morphological point of
view. Whether a sensory organ is adapted for seeing, hearing,
smelling, or tasting depends primarily upon the character of its
sensory epithelium, i.e., upon whether it is composed of optic,
auditory, olfactory, or gustatory cells. But also morphologically
the epithelial part is preeminent, because it is chiefly this which
determines the fundamental form of the sensory organs and affords
the fixed centre around which the remaining accessory components
are arranged. The genetic connection with the outer germ-layer
may be most clearly recognised in many Invertebrates, inasmuch as
here the sensory organs are permanently located in the epidermis,
whereas in Vertebrates, as is well known, they are, for the sake of
-protection, embedded in deep-lying tissues. I begin with the eye, and
then proceed to the organ of hearing and that of smell.

A. The Development of the Eye.

As has already been stated in the description of the brain, the
lateral walls of the primary fore-brain (figs. 234, 263) are evaginated

kh rf gb nil

Fig. 263. — Brain of a human embryo of the third week (Lg). Profile reconstruction, after His.

yh, Cerebral vesicle ; zh, between-brain vesicle ; mh, mid-brain vesicle ; kh, nh, vesicles of cere-
bellum and medulla oblongata ; au, optic vesicle ; gb, auditory vesicle ; tr, infundibulum ;
rf, area rhomboidalis ; nb, nuchal flexure ; kb, cephalic flexure.

and produce the primary optic vesicles (au), which are constricted
•off more and more and remain in connection with the between-brain

468

EMBRYOLOGY.

by means of a slender stalk only (fig. 264 A st). They possess-
spacious cavities within, which are connected with the system of
brain-ventricles through the narrow canal of the stalk of the optic
vesicle. In many Vertebrates, in which the central nervous system
is formed as a solid structure, as in the Cyclostomes and Teleosts,
the optic vesicles are also without cavities; these do not maka
their appearance until the central nervous system becomes a
tube.

Since the brain is for a long time separated from the primitive
epidermis by only an exceedingly thin sheet of connective tissue,
the primary optic vesicles at the time of their evagination either
apply themselves directly to the epidermis, as in the case of the
Chick, or are separated from it by only a very thin intervening

layer, as in Mammals.

Upon each optic vesicle-
can be distinguished a
lateral, a median, an upper
and a lower wall. I
designate as lateral that
surface which reaches th&

Fig. 264. -Two diagrams illustrating the development epidermis at the surface

of the eye. of the body, as median

A. The primary optic vesicle (aw), joined by a hollow ., ., n • • j

stalk (st) to the between-brainC^), is invaginated the Opposite Wall joined
as a result of the development of the lens-pit (Ig). with the Stalk of the Optic

B, The lens-pit has become abstricted to form a lens- -1/211 i

vesicle (It). From the optic vesicle has arisen the vesicle, and finally as lower
optic cup with double walls, an inner (ib) and an \%\Q one which lies On
outer (ab) ; 1st, stalk of the lens ; gl, vitreous body.

a ' level with the floor 01

the between-brain. These designations will be useful in acquainting
ourselves with the changes which the form of the optic vesicle
undergoes (luring its invagination, which occurs at two places, namely,,
at its lateral and lower surfaces. One of the invaginations is connected
with the development of the lens, the other with the formation of the
vitreous fotftf.

The first fundament of the lens appears in the Chick as early as
the second day of incubation, in the Rabbit about ten days after
the fertilisation of the egg. At the place where the epidermis
passes over the surface of the primary optic vesicle (fig. 264 A Ig),
it becomes slightly thickened and invaginated into a small pit (lens-
pit). The pit, by its deepening and by the approximation of its
edges until they meet, is converted into a lens-vesicle (fig. 264 .5 Is),.
which for a time preserves its connection with its parental substra.-

THE ORGANS OF THE OUTER GERM-LAYER.

469

turn, the epidermis, by means of a solid epithelial cord (1st). Upon
being constricted off the lens-vesicle naturally pushes the adjacent
lateral wall of the optic vesicle before it and folds the latter in
against the median wall.

At the same time with the development of the lens, the primary
optic vesicle is also invaginated from below along a line which
stretches from the epidermis to the attachment of the stalk of the
optic vesicle, and is even continued along the latter for some distance
(fig. 265 aus). A loop of a blood-vessel from the enveloping
connective tissue, embedded in soft, gelatinous substance (gl), here
grows against the lower surface of the primary optic vesicle and its
stalk, and pushes up before it the
lower wall.

In consequence of the two invagina-
tions the optic vesicle acquires the
form of a beaker or cup, the foot of
which is represented by its stalk (Sn).
But the optic cup, as we can from this
time forward designate the structure?
exhibits two peculiarities. First, it
has, as it were, a defect (fig. 265 aus)
in its lower wall ; for there runs along
the latter from the margin of the
broad opening which embraces the
lens (I) to the attachment of the stalk
(Sn) a fissure (aus), which is caused by
the development of the vitreous body
(gl) and bears the name fatal optic
fissure [or choroid fissure]. At first
it is rather wide, but then becomes narrower and narrower by the
approximation of its edges and finally closed altogether. Secondly,
the optic cup, like the toy called the cup of Tantalus, is provided
with double walls, which are continuous with each other along the
edge of the front opening and also along the fissure. They will
henceforth be designated as inner (figs. 264 B and 265 ib) and outer
(ab) layers; the former is the invaginated, the latter the unin-
vaginated part of the primary optic vesicle.

At the beginning of the infolding the two layers are separated by
a broad space (h), which leads into the third ventricle through the
stalk of the vesicle (Sn) ; but afterwards the space becomes reduced
proportionally to the increase in the size of the vitreous body.

Fig. 265.— Plastic representation of
the optic cup with lens and
vitreous body.

ab, Outer wall of the cup ; ib, its
inner wall ; h, cavity between
the two walls, which later dis-
appears entirely ; Sn, fundament
of the optic nerve. (Stalk of the
optic vesicle with a furrow on
its lower surface.) aus, Optic
[choroid] fissure ; gl, vitreous
body ; I, lens.

470 EMBRYOLOGY.

Finally outer and inner layers come to lie in close contact (fig. 26(>
pi and r). The fundaments of the lens (le and If) and the vitreous
body (g) constitute the contents of the cup. The vitreous body fills
the bottom of the cup, the lens its opening.

In the process of invagination the stalk of the optic vesicle has

Ik

Fig. 26P, — Section through the optic fundament of an embryo Mouse, after KESSLER.

pi, Pigmented epithelium of the eye (outer lamella of the optic cup, or secondary optic vesicle) J
r, retina (inner lamella of the optic cup) ; rz, marginal zone of the optic cup, which forms
the pars ciliaris et iridis retinae ; g, vitreous body with blood-vessels ; tv, tunica vasculosa
lentis ; bk, blood -corpuscles ; ch, choroidea ; If, lens-fibres ; le, lens-epithelium ; V, zone of
the lens-fibre nuclei ; h, fxindament of the cornea ; he, external corneal epithelium.

also changed its form. Originally it is a small tube with an epithe-
lial wall, but afterwards it becomes an inverted trough with double
walls, inasmuch as its lower surface participates in the invagination
caused by that growth of connective tissue which toward the peri-
phery furnishes the vitreous body. Later the edges of the trough
bend together and fuse with each other. In this way the connective-

THE ORGANS OF THE OUTER GERM-LAYER. 471

tissue cord, with the arteria centralis retinae, which traverses it, is
enclosed within the stalk, which is now a quite compact structure.

Finally the tissue of the intermediate layer, apart from its
producing the vitreous body, takes a further active share in the de-
velopment of the whole eye, inasmuch as that portion of it which is
adjacent to the optic cup is differentiated into the choroid membrane
(fig. 266 ch) and the sclerotica of the eye.

After having thus delineated briefly the source of the most
important components of the eye, it will be my purpose in what
follows to pursue in detail the development of each part separately.
I shall begin with the lens and vitreous body, then pass to the optic
cup, and at that point add an account of the formation of the
choroid membrane and the sclerotica, as well as the optic nerve ;
in a final section I shall treat of the organs that are accessory to the
optic cup — the eye-lids, the lachrymal glands and their ducts.

(a) The Development of the Lens.

When the lens-vesicle has been completely constricted off from th&
primitive epidermis (fig. 264-5 Is), it possesses a thick wall, which is
composed of two or three layers of epithelial cells, and encloses a
cavity that in Birds is partially filled with fluid, but in the case of
Mammals by a mass of small cells. The mass of cells is the result
of a proliferation of the most superficial flattened sheet of the primitive
epidermis ; it is without importance in the further development — a
transient mass, that soon degenerates and is absorbed when the lens-
fibres are developed. (ARNOLD, MIHALKOVICS, GOTTSCHAU, KORAN YI.)

Externally the epithelial vesicle is sharply limited by a thin
membrane, which is afterwards thickened into the capsule of the lens
(capsula lentis). There are two opposing views in regard to its
development. According to one, the capsule is a cuticular structure,
that is to say, a structure secreted by the cells of the lens at their
bases ; according to the other view it is the product of a connective-
tissue layer, to be described more fully hereafter, enveloping the
lens-vesicle.

In later stages considerable differences arise in the development
of the anterior and posterior walls (fig. 266). In the region of the
anterior wall the epithelium (le) becomes more and more flattened ;
the cylindrical cells are converted into cubical elements, which are
preserved throughout life in a single layer and constitute the so-called
lens-epithelium in the lens of the adult (fig. 266 le). In the posterior

472

EMBRYOLOGY.

wall, on the contrary, the cells increase greatly in length (fig. 266 If)
and grow out into long fibres, which form a protuberance projecting
into the cavity of the vesicle. The fibres stand perpendicular to the
posterior wall, are longest in its middle, become shorter towards the
equator of the lens (figs. 266, 267 l)9 and finally appear as ordinary

pi r

k d h he

Tig. 267.— Part of a section through the fundament of the eye of an embryo Mouse. Somewhat
older stage than that shown in fig. 266. After KESSLER.

A part of the lens, the rim of the optic cup, the cornea, and the anterior chamber of the eye.
pi, Pigmented epithelium of the eye ; r, retina ; rz, marginal zone of the optic cup ; ff, blood-
vessels of the vitreous body in the vascular capsule of the lens ; tv, tunica vasculosa lentis ;
x, connection of the latter with the choroid membrane of the eye ; i', transition of the lens-
epithelium into the lens-fibres ; le, lens-epithelium ; Tc, anterior chamber of the eye ;
d, DESCEMET'S membrane ; h, cornea ; lie, corneal epithelium.

cylindrical cells; these in turn become still shorter and are
continuous with the cubical cells (le) of the lens-epithelium. In this
way there exists at the equator a zone of transition between the
fibrous portion and the epithelial part of the lens.

The next change consists in the elongation of the fibres until their
anterior ends have reached the epithelium (fig. 267). Consequently

THE ORGANS OF THE OUTER GERM- LAYER.

473

the vesicle has now become a solid structure, which, as the lens-core,
furnishes the foundation of the lens of the adult.

The further increase in the size of the lens is an appositional growth.
Around the core first formed arise new lens-fibres, which are arranged
parallel to the surface of the organ and are united into coats. These
lie in layers one over another, which in macerated lenses may be
detached like the coats of an onion. All fibres (fig. 268 If, If")
extend from the anterior to the posterior surface, where their ends
meet one another along regular lines, which in the embryo and the
new-born animal have the form of two three- rayed figures, the
so-called stars oft the lens (fig. 268 vst and hst}. These exhibit the
peculiarity that the rays of
the anterior face alternate
with those of the posterior
face, so that the three rays
of one star halve the spaces
between the three rays of the
other.

In the adult the figure
becomes more complicated,
because lateral rays arise on
•each of the three chief rays.

How have the newly de-
posited fibres been formed ?
Their origin is ultimately to
be referred to the lens-epi-
thelium of the front surface
of the organ. In these cells
figures of nuclear division can
frequently be observed even in late stages of development. The cells
which result from division serve to replace those which grow out
into lens-fibres, and are placed upon the already formed layers.
The new formation takes place only at the equator of the lens
(fig. 267) in the zone of transition (I') previously described, where,
in the adult as well as in the recently born animal, the cubical
epithelial cells gradually merge into cylindrical and fibrous elements,
as one can convince himself from any properly directed section.

In the adult, as is well known, there exist no special provisions for
the nutrition of the lens, which, after attaining full size, is not much
altered, and certainly undergoes only a slight metastasis. With the
•embryo it is otherwise. Here a more active growth necessitates a

Fig, 268, — Diagram of the arrangement of the
lens-fibres.

One sees the opposite positions of the anterior (vsl)
and the posterior (hst) stars of the lens.
If, Course of the lens-fibres on the anterior
surface of the lens and their termination at
the anterior star of the lens ; If", continuation
of the same fibres bo the posterior star on the
posterior surface.

474 EMBRYOLOGY.

special apparatus for nutrition. This is furnished in Mammals by
the tunica vasculosa lentis (figs. 266, 267 tv). By this is understood
a highly vascular connective -tissue membrane, which envelops the
outer surface of the capsule of the lens on all sides. In Man it is
already distinctly developed as early as the second month. Its
vessels are derived from those of the vitreous body. Consequently
on the posterior wall of the lens they are large. These, resolved
into numerous fine branches, bend around tltf; equator of the lens,
and run toward the middle of the anterior surface, where they form
terminal loops, and also unite with blood-vessels of the choroid
membrane (fig. 267 x).

Separate parts of the nourishing membrane of the lens, having
been discovered at different times by various investigators, have
received special names, as membrana pupillaris, m. capsulo-pupillaris,
m. capsularis. The first to be observed was the membrana pupillaris,
the part of the vascular membrane which is situated behind the
pupil on the anterior surface of the lens. It was the most easily
found, because occasionally it persists even after birth as a fine
membrane closing the pupil, and producing atresia pupillce congenita.
Later it was found that the membrana pupillaris is also continued
laterally from the pupil on the anterior face of the lens, and this
part was called membrana capsulo-pupillaris. Finally it was dis-
covered that the blood-vessels are spread out on the posterior wall of
the lens — the membrana capsularis. It is superfluous to retain all
these names, and most suitable to speak of a nutritive membrane of
the lens, or a membrana vasculosa lentis.

This vascular membrane attains its greatest development in the
seventh month, after which it begins to degenerate. Ordinarily it
has entirely disappeared before birth ; only in exceptional cases do
some parts of it persist. Toward the end of embryonic life, more-
over, the chief growth of the lens itself has ceased. For according
to weighings carried on by the anatomist HUSCHKE, it has a weight
of 123 milligrammes in the new-born child, and 190 milligrammes
in the adult, so that the total increase which the organ undergoes
during life amounts to only 67 milligrammes.

(b) The Development of the Vitreous Body.

The question of the development of the vascular membrane of the-
lens leads to that of the vitreous body. As was previously men-
tioned, there grows out fronPTEe"~embryonic connective tissue a

••

THE ORGANS OF THE OUTER GERM-LAYER. 475

process with a vascular loop, which makes its way into the primary
optic vesicle and its stalk (fig. 265). The vascular loop then begins
to send out new lalei:aTvbranches ; likewise the connective-tissue
matrix, which is at first scanty, increases greatly and is characterised
by its extraordinarily slight consistency and its large proportion of
water (figs. 266, 267 g). There are also to be found in it here and
there isolated stellate connective -tissue cells ; but these disappear
later, and in their place occur migratory cells (leucocytes), which are
assumed to be immigrated white blood-corpuscles.

There are two opposing views regarding the nature and develop-
ment of the vitreous body. According to KESSLER we have to do,
not with a genuine connective substance, but with a transudation, —
a fluid, — which has been secreted from the vascular loops ; the cells
are from the beginning simply immigrated white Jplood-corpuscles..
KOLLIKER, SCHWALBE, and other investigators, on the contrary,
regard the vitreous body as a genuine connective substance. Accord-
ing to SCHWALBE'S definition, to which I adhere, it consists of an
exceedingly watery connective tissue, whose fixed cells have early
disappeared, but whose interfibrillar substance infiltrated with water
is traversed by migratory cells. The vitreous body is afterwards
surrounded by a structureless membrane, the membrana hyaloidea,
which, according to some investigators, belongs to the retina, al-
though, according to the researches of SCHWA'LBE, this view is not
admissible.

The vitreous body, which in the adult is quite destitute of blood-
vessels, is bountifully supplied with them in the embryo'. They
come from the arteria centralis retince, the branch of the ophthalmic
artery that runs along the axis of the optic nerve.

TSe^arteria centralis retinae is prolonged from the papilla of the
optic nerve as a branch which is designated as the arteria hyaloidea.
This, resolved into several branches, runs forward through the
vitreous body to the posterior surface of the lens, where its numerous
terminal ramifications spread out in the tunica vasculosa, and at the
equator pass over on to the anterior face of the lens. During the
last months of embryonic life the vessels_of Jjia^yitreous body, to-
gether with the nutritive membrane of the lens, undergo degenera-
tion ; they entirely disappear, with the exception of a rudiment of
the chief stem, which runs forward from the entrance of the optic
nerve to the anterior surface of the vitreous body, and during the
degeneration is converted into a canal filled with fluid, the canalis
hyaloideus.

1

476

EMBRYOLOGY.

(c) The Development of the Secondary Optic Cup and the Coats

of the Eye.

The optic cup is further metamorphosed at the same time with

the layer of mesenchyma which en-
velops it, and which furnishes the
middle and outer tunics of the eye,
so that it seems to be desirable to
treat of both at the same time. I
begin with the stage represented in
figures 266 and 269. The optic cup
still possesses at this time a broad
opening, in which the lens (le) is em-
braced. The latter is either separated
from the epidermis by only an ex-
ceedingly thin sheet of mesenchyma,
as in the Mammals (fig. 266), or its
anterior face is in immediate contact
with the epidermis, as in the Chick
(fig. 269). In the beginning, therefore,
there is no separate fundament for
the cornea between lens and epidermis ;
moreover, both the anterior chamber
of the eye and the iris are wanting.

The fundament of the cornea is de-
rived from the surrounding mesen-
chyma, which, as a richly cellular tissue,
envelops the eyeball. In the Chick
(fig. 269), as early as the fourth clay,
it grows in between the epidermis and
the front surface of the lens as a thin
sheet (bi). At first this sheet is struc-
tureless, then numerous mesenchymatic
cells migrate into it from the margin
and become the corneal corpuscles.
These produce the corneal fibres in
the same way that embryonic con-
nective-tissue cells do the connective-
tissue fibres, while the structureless
sheet in part goes to form the cement-
ing substance between them, and in
part is preserved on the anterior and posterior walls as thin layers

Fig. 269.— Section through the an-
terior portion of the fundament
of the eye in an embryo Chick
on the fifth day of incubation,
after KESSLEB.

he, Corneal epithelium ; le, lens-epi-
thelium ; h, structureless sheet of
the corneal fundament ; bi, em-
bryonic connective substance,
which envelops the optic cup
and, penetrating between lens-
epithelium (te) and corneal epi-
thelium (he), furnishes the funda-
ment of the cornea; ab, outer,
ib, inner layer of the secondary
optic cup.

THE ORGANS OF THE OUTER GERM-LAYER. 477

destitute of cells ; these layers, undergoing chemical metamorphosis,
become respectively the membrana elastica anterior and the mem-
brane of DESCEMET.

The internal endothelium of the cornea is_ developed at an extra-
ordinarily early epoch in the Chick. For as soon as the structureless
sheet previously mentioned (fig. 269 h) has attained a certain thick-
ness, mesenchymatic cells proceeding from the margin spread them-
selves out onils inner surface as a single-layered thin cell-membrane.
With this begins also the formation of the anterior chamber of the eye.
For the thin fundament of the cornea, which at first lay in immediate
contact with the front surface of the lens, now becomes somewhat
elevated from the latter, and separated from it by a fissure-like space
filled with fluid (humor agueus). The fissure is first observable at
the margin of the secondary optic cup, and spreads out from this-
region toward the anterior pole of the lens. The anterior chamber
of the eye does not, however, acquire a greater size and its definite
form until the development of the iris.

i ij-v L^''fQ.-< •: •{.-< x. «_ -i

* Two opposing views exist concerning the origin of the structureless sheet
which has been described as constituting the first fundament of the cornea in
the Chick. According to KESSLER it is a [product of the secretion of the
epidermij^jvhereas the corneal corpuscles migrate in from the mesenchyma.
In mVbpinion, therefore, the cornea is composed of two entirely different
fundaments. According to KOLLIKER, on the contrary, all its parts are
developed out of the mesenchym^and the homogeneous matrix simply outstrips,
the cells in its growth^ancr^tension.

In Mammals (fig. 266) the conditions differ somewhat from those-
of the Chick ; for as soon as the lens-vesicle in Mammals is fully
constricted off, it is already enveloped by a thin sheet of mesenchyma
(h) with few cells, which separates it from the epidermis. The thin
layer is rapidly thickened by the immigration of cells from the-
vicinity. Then it is separated into two layers (fig. 267), the pupillar
membrane (tv) and the fundament of the cornea (h). The former is
a thin, very vascular membrane lying on the anterior surface of the
lens; its network of blood-vessels communicates on the one hand
posteriorly with the vessels of the vitreous body, together with which
it constitutes the tunica vasculosa lentis, and on the other anastomoses
at the margin of the optic cup with the vascular network of the
latter. The fundament of the cornea is first sharply delimited from
the pupillary membrane at the time when the anterior chamber of
the eye (k) is formed as a narrow fissure, which gradually increases
in extent with the appearance of the iris.

478

EMBRYOLOGY.

r pi bi

cfc 1.2.3.

Fig. 270.— Section through the
margin of the optic cup of
an embryo Turdus musicua,
after KESSLER.

r, Retina ; pi, pigmented epithe-
lium of the retina (outer
lamella of the optic cup) ;
bi, connective-tissue envelope
of the optic cup (choroidea
and sclera) ; * ora serrata
(boundary between the mar-
ginal zone and the fundus of
the optic cup) ; ck, ciliary
body; 1, 2, 3, iris; 1 and 2,
inner and outer lamellae of
the pars iridis retinse ; 3, con-
nective-tissue plate of the
iris ; lp, ligamentum pecti-
natum iridis ; sch, canal of
SCHLEMM ; D, DESCEMET'S
membrane ; h, cornea ; he,
corneal epithelium,

During these processes the condition of
the optic cup itself has also changed. Its
outer and inner lamellae continually be-
come more and more unlike. The former
(figs. 266, 267 pi) remains thin and com-
posed of a single layer of cubical epi-
thelial cells. Black pigment granules are
deposited in this in increasing abundance,
until finally the whole lamella appears
upon sections as a black streak. The
inner layer (r), on the contrary, remains
entirely free from pigment, with the ex-
ception of a part of the marginal zone ;
the cells, as in the wall of the brain-
vesicles, become elongated and spindle-
shaped, and lie in many superposed layers.

Moreover the bottom of the cup and
its rim assume different conditions, and
hasten to fulfil different destinies; the
former is converted into the retina, the
latter is principally concerned in the
production of the ciliary body and the
iris.

The edge of the cup (fig. 267 rz, fig. 270*,
and fig. 271) becomes very much reduced
in thickness by the cells of its inner layer
arranging themselves in a single sheet,
remaining for a time cylindrical, and then
assuming a cubical form. But with its
reduction in thickness there goes hand
in hand an increase in. its superficial
extent. Consequently the margin of the
optic cup now grows into the anterior
chamber of the eye between cornea and
the anterior surface of the lens, until it
has nearly reached the middle of the
latter. Then it at last bounds only a
small orifice which leads into the cavity
of the optic cup — the pupil. The pigment
layer of the iris is derived from the mar-
ginal region of the cup, as KESSLER first

THE ORGANS OP THE OUTER GERM-LAYER.

179

showed (fig. 270 l and 2). Pigment granules are now deposited in
the inner epithelial layer, just as in the outer lamella, so that at last
the two are no longer distinguishable as separate layers.

The mesenchymatic layer which envelops the two epithelial
lamellae keeps pace with them in their superficial extension. It
becomes thickened and furnishes the stroma of the iris with its
abundant non-striated muscles and blood-vessels (fig.' 270 3). In
Mammals (fig. 267 x) this is for a time continuous with the
tunica vasculosa lentis (tv), in consequence of which the pupil in
embryos is closed by a thin
vascular connective - tissue
membrane, as has already
been stated.

The part of the optic cup
which is adjacent to the pig-
ment layer of the iris and
surrounds the equator of the
lens, and which likewise be-
longs to the attenuated mar-
ginal zone of the cup (fig.
270 ck), undergoes an inter-
esting alteration. In con-
junction with the neighboring
layer of connective substance,
it is converted into the ciliary
body of the eye. This process
begins in the Chick on the

ninth or tenth day of incubation (KESSLER), in Man at the end of the
second or beginning of the third month (KoLLiKER). The attenuated
epithelial double lamella of the cup, in consequence of an especially
vigorous growth in area, is laid into numerous, [nearly] parallel
short folds, which are arranged radially around the equator of the
lens. As in the iris, so here, the adjacent mesenchymatic layer
participates in the growth and penetrates between the folds in the
form of fine processes. A cross section through the folded part of
the optic cup of a Cat embryo 10 cm. long (fig. 271) affords informa-
tion concerning the original form of these processes in Mammals.
It shows that the individual folds are very thin and enclose within
them only a very small amount of embryonic connective tissue (bi ')
with fine capillaries, and that, unlike the pigment epithelium of the
iris, only the outer of the two epithelial layers (ab) is pigmented,

Fig. 271.— Cross section through the ciliary par
of the eye of an embryo Cat 10 cm. long, after
KESSLER.

Three ciliary processes formed by the folding of
the optic cup are shown, bi, Connective-tissue
part of the ciliary body ; ib, inner layer,
ab, outer pigmented layer of the optic cup ;
bi', sheet of connective tissue that has pene-
trated into the epithelial fold.

480 EMBRYOLOGY.

whereas the inner (ib) remains unpigmented even later and is
composed of cylindrical cells.

Subsequently the ciliary processes become greatly thickened through
increase of the very vascular connective-tissue framework, and
acquire a firm union with the capsule of the lens through the
formation of the zonula Zinnii. In Man the latter is formed,
according to KOLLIKER'S account, during the fourth month, in a
manner that here, as well as in other Mammals, is still incompletely
explained.

LiEBEEKtrKN remarks that the zonula is distinctly recognisable in eyes
which have attained half their definite size. If one takes out of an eye the
vitreous body together with the lens, and then removes the latter by opening
the capsule on the front side, the margin of the capsule appears surrounded
oy blood-vessels which pass from the posterior over on to the anterior surface.

" At the places where the processus ciliares are entirely removed, tufts of
fine fibres are to be seen which correspond to, and fill up, the depressions
between the ciliary processes ; but between these tufts is also to be seen a
thin layer of the same kind of finely striate masses, which must have lain at
the same level as the ciliary processes." Furthermore LiEBERKttKN states
that " there lie within this striated tissue numerous cell-bodies of the same
appearance as those that are found elsewhere in the embryonic vitreous body
at a later period."

ANGELUCCT believes that the zonula arises from the anterior part of the
vitreous body ; at the time when iris and ciliary processes are developed he
finds the vitreous body traversed by fine fibres, which extend from the ora
serrata to the margin of the lens. He describes as lying between the fibres
sparse migratory cells, which are maintained, however, to have no share in
the formation of the fibres.

The fundus of the optic cup (figs. 266, 267, 270) furnishes the
most important part of the eye — the retina. The inner lamella of
the cup (r) becomes greatly thickened, and, in consequence of its
cells being elongated into spindles and overlapping one another in
several layers, acquires an appearance similar to that of the wall of
the embryonic brain. Subsequently it becomes marked off by an
indented line, the ora serrata (at the place indicated by a star in
fig. 270), from the adjoining attenuated part of the optic vesicle,
which furnishes the ciliary folds. It also early acquires at its two
surfaces a sharp limitation through the secretion of two delicate
membranes : on the side toward the fundament of the vitreous body
it is bounded by the membrana limitans interna; on that toward the
outer lamella, which becomes pigmented epithelium, by the membrana
limitans externa.

In the course of development its cells, all of which are at first

THE ORGANS OF THE OUTER GERM-LAYER. 481

alike, become specialised in very different ways, as a result of
which there are produced the well-known layers distinguished by
MAX SCHULTZE. I shall not go into the details of this histological
differentiation, but shall mention some further points of general
importance.

As WILHELM MULLER in his " Stammesentwicklung des Sehorgans
der Wirbelthiere " has clearly shown, the development of the
originally similar epithelial cells of the retina takes place in all
Vertebrates in two chief directions : a part of them become sensory
epithelium and the specific structures of the central nervous system —
ganglioriic cells and nerve-fibres; another part are metamorphosed into
supporting and isolating elements — into MULLER'S radial fibres and
the granular [reticular or molecular] layers, which can be grouped
together as epithelial sustentative tissue (fulcrum). Finally, with
the descendants of the epithelium are associated connective-tissue
elements, which grow from the surrounding connective tissue into
the epithelial layer for its better nutrition, in the same manner as
in the central nervous system. These ingrowths are branches of the
arteria centralis retinae with their extremely thin connective-tissue
sheaths. The Lampreys alone form an exception, their retina
remaining free from blood-vessels. In all other Vertebrates blood-
vessels are present, but they are limited to the inner layers of the
retina, leaving the outer granular (Kbrner) layer and that of the
rods and cones free ; the latter have been distinguished as sensory
epithelium from the remaining portions with their nerve-fibres and
ganglionic cells — the brain-part of the retina.

Of all the parts of the retina the layer of rods and cones is the
last to be developed. According to the investigations of KOLLIKER,
BABUCHIN, MAX SCHULTZE, and W. MULLER, it arises as a product
of the outer granular (Korner) layer, which, composed of fine
spindle-shaped elements, is held to be, as has been stated, the essential
sensory epithelium of the eye. In the Chick the development of the
rods and cones can be made out on the tenth day of incubation.
MAX SCHULTZE states concerning young Cats and Rabbits, which
are born blind, that the fundament of the rods and cones can be
distinguished for the first time in the early days after birth ; in
other Mammals and in Man, on the contrary, they are formed
before birth.

In all Vertebrates, as long as rods and cones are not present, the
inner layer of the optic cup is bounded on the side toward the outer
layer by an entirely smooth contour, due to the membrana limitans

31

482 EMBRYOLOGY.

externa. Then there appear upon the latter numerous, small,
lustrous elevations, which have been secreted by the outer granules
or visual cells. The elevations, which consist of a protoplasmic
substance and are stained red in carmine, become elongated and
acquire the form of the inner limb of the retinal element. Finally
there is formed at their outer ends the outer limb, which MAX
SCHULTZE and W. MILLER compare to a cuticular product, on
account of its lamellate structure.

Inasmuch as the rods and cones of the retinal cells grow out in
this way beyond the membrana limitans externa, they penetrate
into the closely applied outer lamella of the optic cup, which becomes
the pigmented epithelium of the retina (figs. 266, 267, 270 pi) ;
their outer limbs come to lie in minute niches of the large, hexagonal
pigment-cells, so that the individual elements are separated from
one another by pigmented partitions.

A few additional words concerning the connective tissue enveloping
the fundament of the optic cup. It acquires here, as on the ciliary
body and the iris, a special, and for this region characteristic, stamp.
It is differentiated into vascular [choroid] and fibrous [sclerotic]
membranes, which in Man are distinguishable in the sixth week
(KOLLIKER). The former is characterised by its vascularity at an
early period, and develops on the side toward the optic cup a special
layer, provided with a fine network of capillary vessels, the mem-
brana choriocapillaris, for the nourishment of the pigment-layer and
the layer of rods and cones, which have no blood-vessels of their
own. It further differs from the ciliary body in the fact that at
the fundament of the optic cup the choroid membrane is easily
separable from the adjoining membranes of the eye, whereas in the
ciliary body a firm union exists between all the membranes.

If we now glance back at the processes of development last
described, one thing will appear clear to us from this short sketch :
that the changes in the form of the secondary optic cup are of
preeminent importance for the origin of the individual regions of the
eye. Through different processes of growth, which have received a
general discussion in Chapter IV., there have been formed in the cup
three distinct portions. By means of an increase in thickness and
various differentiations of the numerous cell-layers, there is formed
the retina ; by an increase of surface, on the contrary, is produced
an anterior, thinner part, which bounds the pupil and is subdivided
into two regions by the formation of folds in the vicinity of the lens.
From the folded part, which joins the retina at the ora serrata, is

THE OEGANS OF THE OUTER GERM-LAYER. 483

formed the epithelial lining of the ciliary body ; from the thin portion
which surrounds the pupil and which remains smooth, the pigmented
epithelium (uvea) of the iris. Consequently there are now to be distin-
guished on the secondary optic cup three regions, as retinal, ciliary,
and iridal parts. To each of these territories the contiguous
connective tissue, and especially the part which becomes the middle
tunic of the eye, is adapted in a particular manner ; here it furnishes
the connective-tissue plate of the iris with its non-striated muscu-
lature, there the connective -tissue framework of the ciliary body
with the ciliary muscle, and in the third region the vascular choroidea
with the choriocapillaris and lamina fusca.

In the development of the optic cup there arose on its lower wall
a fissure (fig. 265 aus\ which marks the place at which the funda-
ment of the vitreous body grew into the interior of the cup. What
is the ultimate fate of this fissure, which is usually referred to in the
literature as choroid fissure ?

It is for a time easily recognisable, after pigment has been
deposited in the outer lamella of the optic cup. It then appears on
the lower median side of the eyeball as a clear, unpigmented streak,
which reaches forward from the entrance of the optic nerve to the
margin of the pupil.

The name choroid fissure takes its origin from this phenomenon. It was
given at a time when the formation of the optic cup was not adequately known,
when the pigmented epithelium was still referred to the choroidea. Therefore
in the absence of pigment along a clear streak on the under side of the eyeball
it was supposed that a defect of the choroidea — a choroid fissure — had been
•observed.

The clear streak afterwards disappears. The fissure of the eye is
-closed by the fusion of its edges and the deposition of pigment in the
raphe. In the Chick this takes place on the ninth day, in Man
during the sixth or seventh week.

In still another respect is the choroid fissure noteworthy.

In many Vertebrates (Fishes, Reptiles, Birds) a highly vascular
process of the choroidea grows through the fissure, before its closure,
into the vitreous body and there forms a lamellar projection, which
extends from the optic nerve to the lens. In Birds it has received
the name " pecten," because it is folded into numerous parallel ridges.
It consists almost entirely of the walls of blood-vessels, which are
held together by a small amount of a black pigmented connective
tissue.

In Mammals such a growth into the vitreous body is wanting

484

EMBRYOLOGY.

The closure of the choroid fissure takes place at an early period and
completely.

Occasionally in Man the normal course of development is inter-
rupted, so that the margins of the choroid fissure remain apart. The
usual consequence of this is a defective development of the vascular
tunic of the eye at the corresponding place — an indication of the
extent to which the development of the connective-tissue envelope is
dependent on the formative processes of the two epithelial layers, as
has already been stated. Both retinal and choroidal pigment are
therefore wanting along a streak which begins at the optic nerve, so
that the white sclera of the eye shows through to the inside and can
be recognised in examinations with the ophthalmoscope. When the
defect reaches forward to the margin of the pupil, a fissure is formed
in the iris which is easily recognised upon external observation of the
eye. The two structures resulting from this interrupted develop-
ment are distinguished from each other as choroidal and iridal fissures
(coloboma choroidese and coloboma iridis).

(d) The Development of the Optic Nerve.

The stalk of the optic vesicle (fig, 272), by which the vesicle is
united with the between-brain, is in direct connection with both

lamellae of the optic cup, the primary
optic vesicle having been infolded from
below by the fundament of the vitreous
body to form the cup. Its dorsal wall
is continuous with the outer lamella or
pigment-epithelium of the retina ; its-
ventral wall is prolonged into the inner
lamella, which becomes the retina.
Thus, aside from the formation of the
vitreous body, the development of a
choroid fissure also has a significance
in view of the persistence of the direct
connection between retina and optic
nerve. For if we conceive the optic
vesicle invaginated merely at its an-
terior face by the lens, the wall of the
optic nerve would be continued into
the outer, uninvaginated lamella only; direct connection with the*
retina itself, or the invaginated part, would be wanting.

Fig. 272.— Plastic representation of
the optic cup with lens and
vitreous tody.

ab, Outer wall of the cup ; ib, its
inner wall j 7i, space between the
two walls, which afterwards en-
tirely disappears ; Sn, fundament
of. the optic nerve (stalk of the
optic vesicle with groove-for-
mation along its lower face);
aus, choroid fissure ; gl, vitreous
body ; I, lens.

THE ORGANS OF THE OUTER GERM-LAYER. 485

Originally the optic nerve is a tube with a small lumen, which
unites the cavity of the optic vesicle with the third ventricle
(fig. 264 A). It is gradually converted into a solid cord. In the
case of most Vertebrates this is produced simply by a thickening of
the walls of the stalk, due to cell-proliferation, until the cavity is
obliterated. In Mammals only the larger portion, that which adjoins
the brain, is metamorphosed in this manner ; the smaller part, that
which is united with the optic vesicle, is, on the contrary, infolded by
the prolongation of the choroid fissure backward for some distance,
whereby the ventral wall is pressed in against the dorsal. Con-
sequently the optic nerve here assumes the form of a groove, in
which is imbedded a connective-tissue cord with a blood-vessel that
becomes the arteria centralis retinae. By the growing together of
the edges of the groove, the cord afterwards becomes completely
enclosed.

For a time the optic nerve consists exclusively of spindle-shaped,
radially arranged cells in layers, and resembles in its finer structure
the wall of the brain and the optic vesicle. Different views are held
concerning its further metamorphoses, and especially concerning the
origin of nerve-fibres in it. Differences similar to those concerning
the origin of the peripheral nerve-fibres are maintained. Upon this
point three theories have been brought forward.

According to the older view, which LIEBERKUHN shares, the optic
fibres are developed in loco by the elongation of the spindle-shaped
cells. According to His, KOLLIKER, and W. MULLER, on the con-
trary, the wall of the optic vesicle furnishes the sustentative tissue
only, whereas the nerve-fibres grow into it from outside, either from
the brain toward the retina (His, KOLLIKER), or in the reverse direction
(MULLER). The stalk of the optic vesicle would constitute, according
to this view, only a guiding structure as it were — would predeter-
mine the way for its growth. When the ingrowth has taken place,
the sustentative cells are, as KOLLIKER describes them, arranged
radially and so united with one another that they constitute a
delicate framework with longitudinally elongated spaces. In the
latter are lodged the small bundles of very fine non-nuclear nerve-
fibres and numerous cells, arranged in longitudinal rows, which
likewise belong to the epithelial sustentative tissue and help to
complete the trestie-work.

The embryonic optic nerve is enveloped in a connective-tissue
sheath, which is separated, as in the case of the brain and secondary
«optic cup, into an inner, soft, vascular and an outer compact

486 EMBRYOLOGY.

fibrous layer. The former, or the pial sheath, unites the pia mater
of the brain and the choroid membrane of the eye ; the latter, or the
dural sheath, is a continuation of the dura mater and at the eye-
ball becomes continuous with the sclerotica. Later the optic nerve
acquires a still more complicated structure, owing to the fact that
vascular processes of the pial sheath grow into it and provide the
nerve-bundles and the epithelial sustentative cells belonging to them
with connective-tissue investments.

As has been previously stated, the direction in which optic fibres grow into-
the stalk of the optic vesicle is still a subject of controversy. His, with whom
KOLLIKER is in agreement, maintains that they grow out from groups of gang-
lionic cells (thalamus opticus, corpora quadrigemina), and are only secondarily
distributed in the retina. He supports his view on the one hand by the agree-
ment in this particular which exists with the development of the remaining
peripheral nerves, and on the other by the circumstance that the nerve-fibres
are first distinctly recognisable in the vicinity of the brain.

W. MILLER, on the contrary, believes that the outgrowth takes place in the
opposite direction ; he maintains that the nerve-fibres arise as prolongations of
the ganglionic cells located in the retina, and that they enter into union with
the central nervous apparatus only secondarily. He is strengthened in his
opinion by the conditions in Petromyzon, which he declares to be one of the
most valuable objects for the solution of the controversy concerning the origin
of the optic nerve. I refer, moreover, in connection with this controversy, to
the section which treats of the development of the peripheral nervous system
(p. 452).

(e) The Development of the Accessory Apparatus of the Eye.

There are associated with the eyeball auxiliary apparatus, which
serve in different ways for the protection of the cornea : the eyelids
with the Meibomian glands and the eyelashes, the lachrymal glands
and the lachrymal ducts.

The eyelids, the upper and under, are developed at an early period
by the formation, at some distance from the margin of the cornea, of
two folds of the skin, which protrude beyond the surface. The folds
grow over the cornea from above and below until their edges meet
and thus produce in front of the eyeball the conjunctival sac, which
opens out through the fissure between the lids. The sac derives its
name from the fact that the innermost layer of the lid-fold, which is
reflected on to the anterior surface of the eyeball at the fornix con-
junctivse, is of the nature of a mucous membrane, and is designated
as the conjunctiva, or connecting membrane, of the eye.

In many Mammals and likewise in Man there is during embryonic
life a temporary closure of the conjunctival sac. The edges of the lids-

THE ORGANS OF THE OUTER GERM-LAYER. 487

become united throughout their whole extent, their epithelial invest-
ments fusing with each other. In Man the concrescence begins in
the third month, and usually undergoes retrogression a short time
before birth. But in many Reptiles (Snakes) the closure is perma-
nent. Thus a thin transparent membrane is formed in front of the
cornea.

In Man during the concrescence of the eyelids there are developed
at their margins the Meibomian glands. The cells of the rete
Malpighii begin to proliferate and to send into the middle connective-
tissue plate of the eyelid solid rods, which afterwards become covered
with lateral buds. The glands, at first entirely solid, acquire a
lumen by the fatty degeneration and dissolution of the axial cells.

At about the time of the development of the Meibomian glandsr
the formation of the eyelashes takes place ; this corresponds with the
development of the ordinary hair, and therefore will be considered
along with the latter in a subsequent section of this chapter.

In most of the Vertebrates there is associated with the upper
and under lids still a third, the nictitating membrane or membrana,
nictitans, which is formed at the inner [median] side of the eye as
a vertical fold of the conjunctiva. In Man it is present only in a
rudimentary condition as plica semilunaris. A number of small
glands which are developed in it produce a small reddish nodule,
the caruncula lacrymalis.

The lachrymal gland is an additional auxiliary organ of the eye,
which is destined to keep the sac of the conjunctiva moist and the
anterior surface of the cornea clean. In Man it is developed in the
third month through the formation of buds from the epithelium of
the conjunctival sac on the outer side of the eye, at the place where
the conjunctiva of the upper lid is continuous with that of the eye-
ball. The buds form numerous branches, and are at first solid, like
the Meibomian glands, but gradually become hollow, the cavity
beginning with the chief outlet and extending toward the finer
branches.

A special efferent lachrymal apparatus, which leads from the inner
angle of the eye into the nasal cavity, has been developed for the
removal of the secretions of the various glands collected in the
conjunctival sac, but particularly the lachrymal fluid. Such an
apparatus is present in all classes of Vertebrates from the Amphibia
upward ; its development has been especially investigated by BORN in
a series of researches.

In the Amphibia it begins to be formed at the time the process of

488 EMBRYOLOGY.

chondrification becomes observable in the membranous nasal capsule.
At that time the mucous layer of the epidermis, along a line that
extends from the median side of the eye directly to the nasal cavity,
undergoes proliferation and sinks into the underlying connective-
tissue layer as a solid ridge. Then from the nose to the eye the
ridge becomes constricted off, subsequently acquires a lumen, whereby
it is converted into a canal lined with epithelium, and opens out into
the nasal cavity. Toward the eye-end the canal is divided into two
tubules, which at the time of detachment from the epidermis remain
in connection with the conjunctival sac and suck up out of it the
lachrymal fluid.

In Birds and Mammals, including Man (fig. 273), the place where
the lachrymal duct is located is early marked externally by a furrow

which runs from the inner angle of
the eye to the nasal chamber. By
means of this furrow two ridges, which
play an important part in the for-
mation of the face, — the maxillary
process and the outer nasal process,
— are sharply marked off from each
other; these will engage our atten-
tion later. According to COSTE and
KOLLIKER the lachrymal duct arises
^ tbe simPle Approximation and con-

cesses have been removed to crescence of the edges of the lachrymal
"' 9roove. These older conclusions have
been contradicted by BORN and LEGAL,
one of whom has investigated Reptiles and Birds, the other Mammals.
According to them there arises, in nearly the same manner as in
Amphibia, through proliferation of the mucous epithelium, at the
bottom of the lachrymal groove an epithelial ridge, which becomes
detached but is not converted into a canal until a rather late period.
When we raise the question, how phylogenetically the lachrymal
duct may have first originated, we shall doubtless find that it has
been derived from a groove, by means of which the sac of the con-
junctiva and the nasal chamber are first put into connection. When,
therefore, we see the lachrymal duct established from the very begin-
ning simply as a solid ridge, as for example in the Amphibia, we
must call to mind how in other cases also originally groove-like
fundaments, such as the medullary furrow, make their appearance,
under special circumstances, as solid ridges.

THE ORGANS OF THE OUTER GERM-LAYER. 489

Finally, as far as regards the development of the lachrymal tubules in Birds
and Mammals, BORN and LEGAL refer the upper tubule to the proximal
part of the epithelial ridge, and maintain that the lower one buds out from
the upper. EWETSKY, on the contrary, declares that the proximal end of the
epithelial ridge expands at the inner angle of the eye. and becomes divided
by the ingrowth of underlying connective tissue, and metamorphosed into the
two tubules, so that both arise from a common fundament.

SUMMARY.

1. The lateral walls of the primary fore-brain vesicle are evaginated
lo form the optic vesicles.

2. The optic vesicles remain united by means of a stalk, the
future optic nerve, with that part of the primary fore-brain vesicle
which becomes the bet ween -brain.

3. The optic vesicle is converted into the optic cup through the
invagination of its lateral and lower walls by the fundaments of the
lens and vitreous body.

4. At the place where the lateral wall of the primary optic vesicle
encounters the outer germ-layer, the latter becomes thickened, then
depressed into a pit, and finally constricted off as a lens-vesicle.

5. The cells of the posterior wall of the lens- vesicle grow out into
lens-fibres, those of the anterior wall become the lens-epithelium.

6. The fundament of the lens is enveloped at the time of its
principal growth by a vascular capsule (tunica vasculosa lentis), which
afterwards entirely disappears.

7. The membrana capsulo-pupillaris is the anterior part of the
tunica vasculosa lentis and lies behind the pupil.

8. The development of the vitreous body causes the choroid
fissure.

9. The optic cup has double walls ; it consists of an inner and an
outer epithelium, which are continuous with each other at the open-
ing of the cup, which embraces the lens, and at the choroid
fissure.

10. Mesenchymatic cells from the vicinity grow in between the
lens and the somewhat closely applied epidermis to form the cornea
and DESCEMET'S membrane, the latter being separated from the
tunica vasculosa lentis by a fissure, the anterior chamber of the
eye.

1 1 . The optic cup is differentiated into a posterior portion, within
the territory of which its inner layer becomes thickened and con-
stitutes the retina, and an anterior portion, which begins at the ora

490 EMBRYOLOGY.

serrata, becomes very much reduced in thickness, and extends over
the front surface of the lens, growing into the anterior chamber of
the eye until the originally wide opening of the cup is reduced to the
size of the pupil.

12. The anterior attenuated portion of the cup is, in turn, divided
into two zones, of which the posterior becomes folded at the periphery
of the equator of the lens to form the ciliary processes, whereas in
front it remains smooth ; so that in the whole cup three part*
may now be distinguished, as retina, pars ciliaris, and pars iridia-
retinae.

13. Corresponding to the three portions of the epithelial optic cupy
the adjoining connective -tissue envelope takes on somewhat different
conditions as the choroid proper, and as the connective-tissue frame-
work of the ciliary body and that of the iris.

14. The skin surrounding the cornea becomes infolded to form the
upper and lower eyelids and the nictitating membrane, of which the
last is rudimentary in Man, persisting only as the plica semilunaris.

15. The epithelial layers of the edges of the two eyelids grow
together in the last months of development, but become separated
again before birth.

16. The lachrymal groove in Mammals passes from the inner
angle of the eye, between the maxillary and outer nasal processes,,
to the nasal chamber.

17. The lachrymal duct for carrying away the lachrymal fluid is
formed by the downgrowth and constricting off of an epithelial ridge-'
from the bottom of the lachrymal groove, the ridge becoming
hollow.

18. The two lachrymal tubules are developed by the division of t he-
epithelial ridge at the angle of the eye.

B. The Development of the Organ of Hearing.

In the case of the ear numerous parts of quite different origin
unite, in much the same manner as in the case of the eye, to form a
single very complicated apparatus ; of these, too, it is the portion,
to which the auditory nerve is distributed — the membranous labyrinth
with its auditory epithelium — that is by far the most important, out-
stripping as it does all the remaining parts in its development : ifc
must consequently be considered first.

THE ORGANS OF THE OUTER GERM-LAYER

491

(a) The Development of the Otocyst into the Labyrinth.

The membranous labyrinth is preeminently a product of the outer
germ-layer. However great its complication in the adult is, — a
complication that has given it the name labyrinth, — its earliest
fundament is exceedingly simple. It arises on the dorsal surface of
the embryo in the region of the medulla oblongata (fig. 263 gb), above
the first visceral cleft and the attachment of the second visceral arch
(fig. 274 above the numeral 3). Here over a circular territory the
outer germ-layer becomes thickened and soon sinks down into an
auditory pit. This process can be traced very easily in the embryo
Chick on and after the end of the second day of incubation, and
in the embryo Rabbit fifteen
days old. The auditory nerve
makes its way from the brain,
near at hand, to the fundus
of the pit, where it terminates
in a ganglionic enlargement.

The Bony Fishes alone ex-
hibit a deviation from these
conditions. Just as the central
nervous system was in their
case formed not as a tube, but
as a solid body, and the eye
not as a vesicle, but as an
epithelial ball, so we see here
that instead of an auditory
pit there is formed by means

of the proliferation of the outer germ-layer a solid epithelial plug.
This, like the brain-tube and the eye-vesicle, acquires an internal
chamber at a later period only — namely, after being constricted off.

The next stage shows the pit converted into an auditory vesicle.
In the Chick this takes place in the course of the third day. The
invagination of the outer germ-layer grows deeper and deeper, and
by the approximation of its margins becomes pear-shaped ; soon the
connection with the outer germ-layer becomes entirely lost, as is shown
by a section through the head of an embryo Sheep (fig. 275 Ib).

In nearly all Vertebrates the auditory vesicle is constricted off
from the ectoderm in the same manner. The Selachians are an
exception : here the auditory vesicle which is metamorphosed into the
labyrinth retains permanently its connection with the surface of the

Fig, 274. — Head of a human embryo 7'5 mm. long,
neck measurement. From His, "Menschliche
Embryonen."

The auditory vesicle lies above the first visceral
cleft. In the circumference of the visceral
cleft there are to be seen six elevations, de-
signated by numerals, from which the external
ear is developed.

492

EMBRYOLOGY.

body in the form of a long narrow tube, which traverses the cartila-
ginous primordial cranium and is in union dorsally with the epidermis
at the surface of the body, where it possesses an external opening.

In its first, fundament the organ of hearing in Vertebrates resembles
in the highest degree those structures which in the Invertebrates are
interpreted as organs of hearing. These are lymph-filled vesicles lying
under the skin, which are likewise developed out of the epidermis.
Either they are wholly constricted off from the epidermis, or
they remain connected with it by means of a long, ciliate, epithelial
canal, as in the Cephalopods, even after they have become surrounded

by connective tissue. In both
nh cases the vesicles are lined
with epithelium which con-
sists of two kinds of cell :
first of low, flat elements,
which ordinarily exhibit ciliary
movements and thereby put
in motion the fluid within the
vesicle, and secondly of longer
cylindrical, or thread-like, au-
ditory cells with stiff hairs,
which project into the endo-
lymph. The auditory cells are
either distributed individually
over the inner surface of the
auditory vesicle or arranged
in groups, or they are united
at a particular place into an
auditory epithelium, — the au-
ditory patch (macula acustica)
or the auditory ridge (crista acustica), — which may be either single
or double. To all the auditory vesicles of the Invertebrates there
is sent, moreover, a nerve which ends at the sensory cells in fine
fibrillae. Finally, there is present as a characteristic structure a
firm, crystalline body, the otolith, which is suspended in the midst
of the endolymph and is ordinarily set in vibration by the motion
of the cilia. It consists of crystals of phosphate or carbonate of
lime.

Sometimes there is only a single large, in most cases concentrically
laminated, spherical body, sometimes a number of small calcareous
crystals, which are held together by means of a soft pulpy substance.

Pig. 275. — Vertical [cross] section through the
vesicle of the labyrinth of an embryo Sheep
1'3 cm. long, after BOETTCHER. Magnified 30
diameters.

nh, Wall of the after-brain ; rl, recessus labyrinth! ;
Ib, vesicle of the labyrinth ; yc, ganglion coch-
leare, which is in contact with a part of the
labyrinth-vesicle (dc) that grows out into the
ductus cochlearis.

THE ORGANS OF THE OUTER GERM-LAYER.

493

It is difficult to follow the formation of the otoliths within the
otocyst. In one case, which FOL was able to follow, they were
developed by an epithelial cell in the wall of the vesicle. The cell
secretes small calcareous concretions in its protoplasm, becomes
enlarged in consequence, and protrudes as an elevation into the
endolymph. When it has become more heavily loaded with calcic
salts, it is connected with the wall by means of a stalk only, and
finally it becomes entirely detached from the wall and falls into the
cavity of the vesicle, in
which it is kept float-
ing and rotating by the
ciliate cells.

- In Vertebrates the
otocyst, which, as we
have seen, agrees in its
first fundament with
the organ of hearing
in Invertebrates, is con-
verted into a very com-
plicated structure, — the
membranous labyrinth,
—the evolution of which
in Mammals I shall de-
scribe in some detail.

de-

It undergoes metamor-
phoses, in which the
formation of folds and
constrictions plays the
principal part (fig. 276).
The auditory sac de-
tached from the epi-

Fig. 276.— Membranous labyrinth of the left side of a
[human] embryo, after a wax model by KRAUSE.

rl, Recessus labyrinth! ; dc, ductus cochlearis ; hb, pocket
from which the horizontal semicircular canal is formed ;.
am', enlargement of the pocket which becomes the
ampulla of the horizontal canal ; am (vb), vb', * com-
mon pocket from which the two vertical semicircular
canals are developed ; am (vb), enlargement of the
common pocket from which the ampulla of the an-
terior vertical canal arises. An opening (0) has been
formed in the pocket, through which one sees the
recessus labyrinthi. * Region of the pocket which
becomes the common arm of the two vertical canals
(sinus superior) ; W, part of the common pocket which
furnishes the posterior vertical canal.

dermis, and lying at the
side of the after-brain, soon exhibits a small, dorsally directed pro-
jection, the recessus labyrinthi or ductus endolymphaticus (fig. 275 rl).
Probably we have to do in this with the remnant of the original
stalk by means of which the auditory vesicle was connected with the
epidermis. According to some investigators, on the contrary, the
stalk disappears entirely and this evagination is a new structure.
The first assumption is favored especially by the previously mentioned
condition in the Selachians — the presence of a long tube, which
maintains a permanent connection between labyrinth and epidermis.

494

EMBRYOLOGY.

Later this appendage of the labyrinth (figs. 276-9 rl) grows out
dorsally to a great length, during which its walls come into close
contact with each other, excepting at the blind end, which is enlarged
into a small sac (fig. 279 rl *).

Meanwhile the auditory sac itself (figs. 275-7) begins to be
elongated and to be formed into a ventrally directed conical process
(cZc), the first fundament of the ductus cochlearis, which is curved inward
a little toward the brain (fig. 277 nh), and the concave side of which

Fig. 277.— Cross section through the head of a Sheep embryo 1*6 cm. long, in the region of the
labyrinth-sac. On the right side is represented a section which passes through the middle
of the sac ; on the left, one that is situated somewhat farther forward. After BOETTCHER.

,hn, Auditory nerve ; vb, vertical semicircular canal ; gc, ganglion cochleare (spirals) ; dc, ductus
cochlearis ; /, inward-projecting fold, whereby the sac of the labyrinth is divided into
utriculus and sacculus ; rl, recessua labyrinth! ; nh, after-brain.

lies in close contact with the previously mentioned ganglionic enlarge-
ment (gc) of the auditory nerve (hn).

It will be serviceable in the following description if we now
distinguish an upper and a lower division of the labyrinth. They are
not yet, it is true, distinctly delimited from each other, but in later
stages they become more sharply separated by an inward-projecting
fold (figs. 277-9/).

The upper part (pars superior) furnishes the utriculus and the
semicircular canals. Of the latter the two vertical canals arise first,
the horizontal canal being formed later. The method of their origin

THE ORGANS OF THE OUTER GERM-LAYER.

495

was early ascertained by the zoologist RATHKE in the case of Coluber.
Recently KRAUSE has still further elucidated the interesting pro-
cesses by the construction of wax models of the conditions in
mammalian embryos.

As is to be seen from the various sections (figs. 277, 278), but still
better from the model (fig. 276) produced by reconstruction, the
semicircular canals are developed by the protrusion of several evagina-
tions of the wall of the sac, which have the form of thin pockets or
discs (hb, vb) with a
semicircular outline.
The marginal part of
each such evagina-
tion now becomes
considerably en-
larged, whereas the
remaining portions
of the two epithelial
layers come into close
contact and begin to
fuse. As the result
of this simple process
— the enlargement at
the margin and the
fusion of the walls
which takes place in
the middle — there is
formed a semicircular
canal, which commu-
nicates at two places
with the original
cavity of the vesicle.
A.t one of its open-
ings the canal is early enlarged into an ampulla (fig. 276 am
and am'), The middle part, in which the fusion has taken place,
soon disappears, the epithelial membrane being broken through by a
growth of the connective tissue (fig. 276 o).

There exists an interesting difference between the development of

the horizontal and the two vertical canals, which was discovered by

KRAUSE. Whereas the horizontal canal is established as a small

pocket by itself (fig.. 276 hb), the two vertical canals arise together

from a single large pocket-like fundament (fig. 276 am (vl>\ *, vb1).

dc

Fig. 278.— Cross section through half of the head of a foetal
Sheep 2 cm. long, in the region of the labyrinth, after
BOETTCHER. Magnified 30 diameters.

rl, Recessus labyrinthi ; vb, Jib, vertical and horizontal semi-
circular canals ; U, utriculus ; f, inward-projecting fold,
by which the labyrinth-sac is divided into utriculus and
sacculus ; dc, ductus cochlearis ; gc, ganglion cochleare.

496

EMBRYOLOGY.

The walls of this large pocket come into contact with each other and
fuse at two different places. At one of them there has already
been formed, in the preparation from which this model (fig. 276) was
constructed, an opening (o) by the resorption of the fused epithelial
areas, whereas at the second place (vb') the epithelial membrane is
still preserved. Between the fused parts of the pocket there remains
open a middle region, which is indicated in the model by an asterisk,

dc

Fig. 279.— View produced by combination from two cross sections through the labyrinth of a

Sheep embryo 2-8 cm. long, after BOETTCHER.
rl, Recessus labyrinth! ; rl*, its flask-like enlargement ; vb, kb, vertical and horizontal canals;

U, utriculus ; S, sacculus ; /, fold by means of which the labyrinth is divided into sacculus

and utriculus ; cr, canalis reunions ; dc, ductus cochlearis ; kk, cartilaginous capsule of the

cochlea ; sp, sinus petrosus inferior.

and this becomes the common arm (sinus superior) of the two vertical
canals. Thus embryology furnishes for this peculiarity, too, a simple
satisfactory explanation.

That which remains of the upper portion of the auditory vesicle,
after the semicircular canals have grown forth from its wall, is
called the utriculus (figs. 278-80 U).

Meanwhile no less significant and fundamental alterations take
place in the lower part of the auditory sac and lead to the formation
of sacculus and ductus cochlearis.

THE ORGANS OF THE OUTER GERM-LAYER.

497

By a continually deepening constriction (fig. 279 /) the lower
portion (S) is delimited from the utriculus (U), and finally
remains connected with it by a very narrow tubule only (canalis
utriculo-saccularis — figs. 280 R and 282 2)« Since the constriction
affects exactly that place of the labyrinth-sac from which the
recessus labyrinthi arises, the opening of the latter subsequently
corned to lie within the territory of the canalis utriculo-saccularis, at
about its middle (figs. 280 R and 282 2). In this manner there is
produced an appearance as though the recessus labyrinthi were split
at its beginning into two narrow tubules, one of which leads into the
sacculus, the other into the utriculus.

By a second deep constriction (figs. 279, 280, 282) the sacculus
(S) is separated from the developing ductus cochlearis (dc\ Here
also a connection is
maintained by means
of an extraordinarily
fine connecting tubule
only (cr), which HENSEN
discovered and has de-
scribed as canalis re-
uniens. The ductus
cochlearis itself in-
creases greatly in
length, and at the same
time begins to be rolled
up in spiral turns in
the soft, enveloping, em-
bryonic connective tissue, until in Man it describes two and a half
turns (figs. 280 C and 282 Con). Since the first whorl is the
largest, and the others are successively narrower, it acquires a great
resemblance to a snail -shell.

The alterations in the external form of the vesicle are accompanied
by changes in the nature of its epithelium also. This is separated
into the indifferent epithelial cells, which simply serve as a lining,
and the real auditory cells. The former are flattened, becoming
cubical or scale-like, and cover the greater part of the inner surface
of the semicircular canals, the sacculus, the utriculus, the recessus
labyrinthi, and the ductus cochlearis. The auditory cells, on the
contrary, are elongated, become cylindrical or spindle-shaped, and
acquire at the free surface hairs, which project into the endolymph.
By the separation of the vesicle into its various divisions the

32

Fig. 290.— Diagram to illustrate the ultimate condition of
the membranous labyrinth [after WALDEVEE].

U, Utriculus ; S, sacculus ; Cr, canalis reunions ; R, recessus
labyrinthi ; C, cochlea ; K, blinu sac of the cupola ;
V, vestibular blind sac of the ductus cochlearis.

498 EMBRYOLOGY.

auditory epithelium is distributed into an equal number of separate
patches, to which then the auditory nerve is distributed. Ac-
cordingly the auditory epithelium is resolved into a macula acustica
in the sacculus and another in the utriculus, into a crista acustica
in each of the ampullae of the semicircular canals, and into an
especially complicated termination in the ductus cochlearis. Here
the auditory epithelium grows out into a long spiral band, which is
known under the name of CORTI'S organ.

Upon the separation of the auditory epithelium into maculae,
cristae, and organ of CORTI, the originally single auditory nerve
distributed to the auditory vesicle is likewise resolved into separate
branches. We distinguish in the case of the auditory nerve the
nervus vestibuli, which is in turn divided into numerous branches
distributed to the maculae and cristae, and the nervus cochleae.

The originally single ganglion acusticum belonging to the auditory
nerve also becomes differentiated into two separate portions. The
portion belonging to the nervus vestibuli is in the adult located in
the internal auditory meatus far from the terminal distribution,
forming here the well-known intumescentia gangliformis Scarpae ;
the portion belonging to the nervus cochleae, on the contrary,
adjoins the terminal distribution of the nerve. In the embryo it
(figs. 277, 278 gc) is closely united with the fundament of the ductus
'cochlearis, and as the latter increases in size grows out to the
same extent in the form of a thin band, which reaches to the blind
end of the ductus and is known under the name of ganglion spirals
(fig. 283 gap).

(b) Development of the Membranous Ear-Capsule into the Bony
Labyrinth and the Perilymphatic Spaces.

All of the changes which have been mentioned hitherto have
proceeded from the epithelial vesicle which was constricted off from
the outer germ-layer. It is now my purpose to direct attention to a
series of processes which take place around the epithelial cavities, in
the mesenchyme in which they are imbedded. The processes lead
to the formation of the bony labyrinth, the perilymphatic spaces
and soft connective-tissue layers, which are intimately joined to the
purely epithelial structures hitherto treated of, and with the latter
are embraced in descriptive anatomy under the name of membranous
labyrinth. Changes take place here similar to those in the develop-
ment of the neural tube and of the eye, in which cases also the connec-
tive-tissue surroundings are modified in a special manner and with

THE ORGANS OF THE OUTER GERM-LAYER. 499

reference to the epithelial parts. In the present instance there are
produced structures which are comparable with those existing in the
former cases, as has already been pointed out by Ko* LLIKER, SCHWALBE,
and others.

The comparison may be carried into details. The parts arising
from the primitive auditory vesicle are at first surrounded by a soft,
vascular connective-tissue layer, as the neural tube and the epithelial
optic cup are. To the pia mater of the brain corresponds the
vascular membrane of the eye and the soft ear-capsule, or the
•connective-tissue wall of the membranous labyrinth. Around all
three organs a firm envelope has been developed for the purpose of
protection ; around the brain the dura mater with the cranial
capsule, around the eye the sclerotica, and around the organ of
hearing the bony labyrinth with its periosteum. To these is to be
added still a third noteworthy agreement. In all three cases the
-soft and firm envelopes are separated by more or less considerable
fissure-like spaces, which belong to the lymphatic system. Around
the neural tube the subdural and the subarachnoid spaces are found,
around the eye the perichoroid fissure, around the organ of hearing
the perilyinphatic spaces, which have received in the cochlea the
special names of scalse (fig. 283 ST and SV).

The details of the formation of the enveloping structures around
the epithelial auditory vesicle are as follows : —

Soon after the auditory sac is constricted off from the epidermis it
is enveloped on all sides by a richly cellular mesenchyme, the indivi-
dual cells of which lie in an extremely scanty, soft, and homogeneous
intercellular substance, and possess each a large nucleus with a thin
protoplasmic covering having short processes. Gradually the envelope
is differentiated into two layers (figs. 279, 281). In the vicinity of
the epithelial canals the soft intercellular substance increases in
amount; the cells become either stellate or spindle-shaped, in the
former case sending out long processes in various directions. There
is formed here that modification of connective substance known as
mucous or gelatinous tissue (figs. 281 and 283 g), in which there are
also blood-vessels. Outside of this the cells remain smaller and more
closely crowded together, and are separated from one another by thin
partitions of a firm intermediate substance. With an increase of
the latter the tissue soon acquires the character of embryonic
cartilage (kk).

The further changes must be followed separately in the semi-
circular canals, the utriculus and sacculus and the ductus cochlearis.

500

EMBRYOLOGY.

The three semicircular canals do not lie exactly in the middle of the-
cavities of the embryonic cartilage containing the gelatinous tissue?
but are so situated that their convex borders are in almost immediate
contact with the cartilage, whereas their concave sides are separated,
from it by a thick layer of gelatinous tissue. The latter is differen-
tiated into three layers : into a middle portion, in which the gelatinous
intercellular substance is greatly increased in volume, and becomes at
the same time more fluid, and into two limiting layers, which are
converted into fibrous connective tissue. One of the two [the inner]
is intimately united to the epithelial tube, for the nutrition of which

dc C

dc

Cdc

x gsp

nc gs ns

U

Fig. 281.— Section through the cochlea of a Sheep embryo 7 cm. long, after BOETTCHER.
Magnified 20 diameters.

kk, Cartilaginous capsule of the cochlea ; 8, sacculus with the nerve (ns) distributed to it ;
U, utricle ; gs, ganglion connected with the cochlear nerve (nc) and sending nerve-fibres (ns)
to the sacculus ; gsp, ganglion spirale ; dc, ductus cochlearis ; C, CORTI'S organ ; g, gelatinous-
tissue in the periphery of the ductus cochlearis ; x, more compact connective-tissue layers.

it provides by means of a close network of blood-vessels distributed
through it ; the other [the outer] lies on the inner surface of the
cartilaginous envelope and becomes its perichondrium.

The gelatinous tissue of the middle layer is of only short duration.
It soon shows signs of degeneration. The stellate cells become filled
with fat granules in the vicinity of their nuclei and in their long
processes ; later they disintegrate. In the gelatinous matrix there
are formed, by a continually advancing process of softening, cavities
filled with fluid. These increase in size and then become confluent,
until finally there has arisen between the connective-tissue membrane
of the semicircular canals and the perichondrium, in place of tl\A

THE OEGANS OF THE OUTER GERM-LAYER.

501

gelatinous tissue, a large spacefilled with perilymph, which is indicated
in the diagram, Jig. 282, in black. Here and there, however,
connective-tissue cords remain running from one layer of connective
tissue to the other, and serving as bridges for the nerves and blood-
vessels which are distributed to the semicircular canals.

Finally, a last alteration takes place in the cartilaginous envelope

Pig. 282.— Diagrammatic representation of the whole organ of hearing in Man, from WIEDERSHEIM.

Outer ear: M, M, auricle; Mae, rneatus auditorius extern us ; 0, its wall; Mt, niembrana
tympani. Middle ear: Ct, Ct, cavum tympani ; 0l, its wall; SAp, sound-conducting
apparatus, which is drawn as a simple rod-like body in place of the auditory ossicles ; the
place f corresponds to the stapedial plate, which closes the fenestra ovalis ; Tb, tuba
Eustachii ; Tb\ its opening into the pharynx; 0", ita wall. Inner ear: 1he bony labyrinth
(KL, KL1) for the most part cut away ; S, sacculus ; a, b, the two vertical lutmbraious and
osseous semicircular canals; S.e, D.e, saccus and ductus endolymphaticus, of which the
latter is divided at 2 into two arms ; Cp, cavum perilymphaticum ; Cr, canalis reunions ;
Con, membranous cochlea, which produces at -4- the vestibular ccecum ; Con1, bony cochlea ;
Sv and St, scala vestibuli and scala tympani, which at * communicate with each other at the
cupula terminalis (Ct) ; D.p, ductus perilymphaticus, which arises from the scala tympani
at d and opens out at D.p1. The horizontal semicircular canal is not specially designated,
but is easily recognisable.

by its becoming converted into bone-substance by endochondral
ossification. Thus the membranous semicircular canals are enclosed
in the bony semicircular canals (fig. 282 a and b KL), which are
enlarged reproductions of the former.

Corresponding changes (fig. 282) are also accomplished in the
periphery of the utriculus and sacculus (S), and lead to the formation
of (1) a perilymphatic space (Cp), which is in communication with

502 EMBRYOLOGY.

the perilymphatic spaces of the semicircular canals, and (2) a bony
envelope (KL1) of the atrium or vestibulum, which constitutes the
middle region of the bony labyrinth.

The envelope of the epithelial cochlear duct, which becomes tho
bony cochlea with its scalse, undergoes a more complicated alteration.
It is already differentiated, at the time when the duct (fig. 279 dc)
makes only half of a spiral turn, into an inner, soft and an outer,
firm layer, the latter becoming cartilage (kk). The cartilaginous
capsule (fig. 281 kk\ which is continuous with the cartilaginous
mass of the remaining parts of the labyrinth and together with them
constitutes a part of the os petrosum, afterwards encloses a lenticular
cavity and possesses below a broad opening, through which the coch-
lear nerve (nc) enters. The resemblance to a snail-shell is not yet
observable ; it takes place gradually and is produced by two changes :
by the outgrowth of the epithelial duct and by the differentiation of
the soft tissue surrounding it into parts which are fluid and such as
become more firm.

In its outgrowth the epithelial ductus cochlearis describes within
its capsule the previously mentioned spiral turns (dc), shown in cross
section in fig. 283 ; at the same time it remains quite closely approxi-
mated to the inner surface of the capsule (kk). The cochlear nerve
(nc) ascends from its place of entrance straight up through the
centre of the turns, consequently in the axis of the capsule, and
gives off numerous lateral branches to the concave side of the
cochlear duct (dc), where they are enlarged into, the ganglion
(gsp), which has now also grown out into a spiral band. The
nutritive blood-vessels have taken the same course as the nerves.

When the development has advanced as far as this, there still
remains to be accomplished only an histological differentiation in
the soft mesenchyme which fills the cartilaginous capsule in order to
produce the parts of the finished cochlea that are still wanting — the
modiolus, the lamina spiralis ossea, the bony cochlea, and the vesti-
bular and tympanic scalse (fig. 283). Here, as in the vicinity of the
semicircular canals the utriculus and the sacculus, the mesenchyme
is differentiated into a firmer connective substance, which becomes
fibrous, and into a gelatinous tissue (g), which is continually becoming
softer. Fibrous connective substance is developed first around the
trunks of the nerves (nc) and blood-vessels that enter the cartilaginous
capsule ; furnishing the foundation of the future bony axis of the
snail-shell (M ), secondly it furnishes an envelope for nerve-fibres (N)
that run from the axis to the epithelial cochlear duct, for the gangli-

THE ORGANS OF THF, OUTER GERM-LAYER. 503

onic cells (gsp), and for the blood-vessels, and constitutes a connective-
tissue plate which is subsequently ossified to form the lamina spiralis
ossea. Thirdly, it clothes with a thin layer the epithelial ductus,
serving for the distribution of the blood-vessels on the latter, and
together with it is designated as the membranous ductus cochlearis.
Fourthly, it lines the inner surface of the cartilaginous capsule as
perichondrium (P). Finally, fifthly, there is formed a connective
tissue plate (Y) extending between the cartilaginous ridge which,
as previously described, projects inward from the capsule and the
connective-tissue axis of the cochlea (jff). It is stretched out between
and separates the successive turns of the membranous cochlear duct,
so that the latter now comes to lie in a large canal, the wall of which
is in part cartilaginous, in part membranous. This canal is the
foundation of the bony cochlea.

That portion of the mesenchyme which is not converted into
fibrous connective tissue becomes gelatinous tissue (g and g'). It
forms between the parts just mentioned two spiral tracts, one of
which is located above and the other below the membranous ductus
cochlearis and the membranous lamina spiralis. The tracts there-
fore occupy the place of the scala vestibuli (SV) and the scala
tympani (ST). The latter arise, even before the process of ossifica-
tion begins, in exactly the same way as the perilymphatic spaces
in the case of the semicircular canals and the vestibule. In the
gelatinous tissue the matrix becomes softer and more fluid, and
the cells begin to undergo fatty degeneration. Small fluid-filled
cavities make their appearance ; these become joined to one another,
and finally the whole space occupied by gelatinous tissue is filled
with perilymph. The process of softening begins at the base of the
cochlea in the region of the first spiral (ST and SV), and advances
slowly toward the cupola. Here vestibular and tympanic scalse finally
unite, after the last remnant of the gelatinous tissue has been dis-
solved. Figure 283 exhibits a stage in which, at the base of the
cochlea, the perilymphatic spaces (SV and ST) have been formed,
and only small remnants of the gelatinous tissue (g') are present,
whereas at the apex of the cochlea the process of liquefaction of
the gelatinous tissue (g) has not yet taken place.

With the development of the scalse the membranous ductus
cochlearis changes form. Whereas its cross section was formerly
oval, it now assumes the form of a triangle (dc). For those portions
of the wall which are adjacent to the vestibular and tympanic scalse,
and which have been named from them, gradually become flattened,

504

EMBRYOLOGY

Fig. 283, — Fart of a section through the cochlea of an embryo Cat 9 cm. long, after BOETTCIIER.

it, Cartilaginous capsule, in which the cochlear duct describes ascending spiral turns ; dc, ductus
cochlearis ; C, organ of COKTI ; Iv, lamina vestibularis ; x, outer wall of the membranous
ductus cochlearis with ligamentum spirale ; Slr, scala vestibuli ; ST, S7", scala tympani ;
g, gelatinous tissue, which still fills the scala vestibuli (sv') in its last turns ; g', remnant of
the gelatinous tissue, which is not yet liquefied ; M, firm connective tissue surrounding the
cochlear nerve (nc) ; gsp, ganglion spirale; N, nerve which runs to CORT.'S organ in the
future lamina spiralis ossea ; Y, compact connective-tissue layer, which becomes ossified and
shares in bounding the bony cochlear duct ; P, perichondrium.

THE ORGANS OF THE OUTER GERM-LAYER. 505

and are stretched out smoothly between the free margin of the lamina
spiralis and the inner wall of the cartilaginous capsule. In this process
the tympanic wall (C) comes to lie in the same plane as the lamina
spiralis, the vestibular wall (Iv) forms with the tympanic an acute
angle, and the third wall (x) is everywhere in close contact with the
perichondrium of the cartilaginous capsule.

The epithelial lining of the membranous ductus coohlearis assumes
very different conditions in the three corresponding regions of its
wall. Whereas the epithelial cells of the vestibular and the outer
walls become in part cubical, in part quite flat, those of the tympanic
wall become elongated, and are in connection with the terminal fila-
ments of the cochlear nerve ; they produce the complicated organ of
CORTI ((7), which; like the auditory ridges and auditory patches of
the ampullae, the sacculus and utriculus, contains the terminal ends
of the auditory nerve.

The construction of the intricate cochlea approaches completion
•with the beginning of the process of ossification. The latter is accom-
plished by two methods. First, the cartilaginous capsule ossifies in
the endochondral manner, as does the whole cartilaginous os petrosum,
of which it constitutes a small part. The osseous tissue thus formed
is for a long time spongy and provided with large medullary spaces.
Secondly, the previously mentioned fibrous connective-tissue layers —
the partitions between the cochlear canals, the connective-tissue
axis or the modiolus and the lamina spiralis — undergo direct ossifi-
cation. At the same time compact bone-lamellae are laid down from
within on the spongy bone-tissue formed from the cartilaginous capsule;
these lamellae are formed, as BOETTCHER has shown, by the original
perichondrium, which becomes the periosteum. Consequently the
bony cochlear capsule, since it is produced by periosteal secretion,
may be easily detached from the loose osseous tissue of endochondral
origin during early post-natal years.

(c) Development of the Accessory Apparatus of the, Organ of Hearing.
(Middle and External Ear.}

With the membranous and bony labyrinth, which are together
called the inner ear, there is associated a subsidiary apparatus, in the
same way that the eye-muscles, the lids, and the lachrymal glands
and ducts are added to the eyeball. It is made up of structures
which are wanting in the lower Vertebrates (Fishes), but, beginning
to be developed in the Amphibia, become more and more complete in

506 EMBRYOLOGY.

the higher forms. Their function is to transmit vibrations to the-
labyrinth, and consequently they are together called the conducting
apparatus. From their position they are also known as middle and
outer ear. The former consists in Mammals, where it attains its
highest development (diagram, fig. 284), of the tympanic cavity (Ci},.
the Eustachian tube (Tb), and the three auditory ossicles (SAp) ; the
latter, of the tympanic membrane (Mt)y the external meatus (Mae]-,
and the external ear or auricle (M ). The statement just made, that
these parts are wanting in Fishes, is to be taken cum grano salis : it
is as a sound-conducting apparatus only that they are wanting, for
they are present even in the case of Fishes, but only as structures
of a different function and in a more simple condition. For the
various accessory apparatus of the organ of hearing are developed
out of the first visceral cleft and certain parts which are located in
its periphery.

Here also it will be well to acquaint ourselves with the original —
the initial condition, for which the Selachians may serve as an
example.

In them the greater part of the first visceral cleft, which is
situated between the mandibular and hyoid arches and between the
nervus trigeminus and n. acustico-facialis, disappears ; at the side
of the throat it becomes closed, remaining open only at the origin, or
base, of the two visceral arches. It then has the form of a short
canal, which possesses a small round opening at its inner .and
another at its outer end, and which passes in very close proximity to
the labyrinth-region of the skull, in which the organ of hearing is
located. The canal, here called the spiracle, has no longer anything
to do with respiration, since the branchial leaflets on its wall have
undergone degeneration. Owing to its position in the immediate
vicinity of the labyrinth, it presents, even in the Selachians, the best
course for the propagation of the sound-waves to the inner ear, and
this is the chief ground for its entering wholly into the service of
the organ of hearing in the remaining Vertebrates, and for its being
developed in a more serviceable manner for this particular function.

The structures in the higher Vertebrates corresponding to the
spiracle of the Selachians are (fig. 284) the tympanic cavity (Ct),
the Eustachian tube (Tb), and the external meatus (Mae). They
likewise are developed out of the upper part of the first visceral
cleft. Although it has recently been asserted by certain investi-
gators (FRBANTSCHITSCH) that they have nothing to do with the
first visceral cleft, but are established independently by the e vagina-

THE ORGANS OF THE OUTER GERM-LAYER.

507

tion of the pharynx, this view is opposed not only to comparative-
anatomical considerations, but also to statements of KOLLIKER,
MOLDENHAUER, and HOFFMANN, which relate to the development in
Keptiles, Birds, and Mammals.

In the classes of Vertebrates just mentioned the first visceral

Fig, 284. -Diagrammatic representation of the whole organ of hearing in Man, from WIEDERSHEIM.

Outer ear: M, M, auricle; Mae, meatus auditorius externus ; O, its wall; Mt, membrana
tympani. Middle ear: Ct, Ct, cavum tympani ; O1, its wall; SAp, sound-conducting
apparatus, which is drawn as a simple rod-like body in place of the auditory ossicles ; the
place t corresponds to the stapedial plate, which closes the fenestra ovalis ; Tb, tuba
Eustachii ; Tb1, its opening into the pharynx ; 0", its wall. Inner ear : the bony labyrinth
(KL, KL1) for the most part cut away ; S, sacculus ; a, b, the two vertical membranous and
osseous semicircular canals ; S.e, D.e, saccus and ductus endolymphaticus, of which the
latter is divided at 2 into two arms ; Cp, cavum perilymphaticum ; Or, canalis reunions ;
Con, membranous cochlea, which produces at + the vestibular coecum ; Con1, bony cochlea ;
Sv and St, scala vestibuli and scala tympani, which at * communicate with each other at the
cupula terminalis (Ct) ; D.p, ductus perilymphaticus, which arises from the scala tympani
at d and opens out at D.p1. The horizontal semicircular canal is not specially designated,
but is easily recognisable.

cleft is closed in its upper part also, contrary to the condition in
Selachians.*

The closure becomes more firm and complete owing to the in-
growth of a connective-tissue layer between the inner and outer
epithelial plates. Remnants of the first visceral cleft are preserved

* See the statements discussed in a previous chapter (p. 287), concerning
the mooted question whether the visceral clefts remain closed by means of
an epithelial membrane or are temporarily open.

508 EMBRYOLOGY.

on both sides of the closing membrane as depressions of greater or less
depth ; an inner one on the side toward the pharyngeal cavity, and
an outer one which is surrounded by ridges of the first and second
visceral arches.

The inner depression, which is called canalis or sulcus tubo-tym-
panicus (pharyngo-tympanicus), is located, like the spiracle, between
trigeminus and acustico-facialis. It becomes the middle ear, and is
enlarged by an evagination that is directed upward, outward, and
backward. The evagination inserts itself between the labyrinth and
the place of closure of the first visceral cleft, and takes the form of
a laterally compressed space, which is now to be distinguished as
tympanic cavity from the tubular remnant of the sulcus tympanicus,
or Eustachian tube. Its lumen is very small, especially in the case
of advanced embryos of Man and Mammals, its lateral and median
walls being almost in immediate contact. This results chiefly from
the fact that there is present beneath the epithelial lining of the
middle ear a richly developed gelatinous tissue. The latter still
encloses at this time structures, — the auditory ossicles and the
chorda tympani, — which later come to lie, as it were, free in the
tympanic cavity.

The tympanic membrane also is now in a condition very unlike
that which it afterwards acquires. The history of its formation is
by no means so simple as was formerly supposed. For it is not
derived exclusively from the narrow closing membrane of the first
visceral cleft ; the neighboring parts of the first and second mem-
branous visceral arches also participate in its production. The
embryonic tympanic membrane is therefore at first a thick con-
nective-tissue plate, and encloses at its margins the auditory ossicles,
the tensor tympani, and the chorda tympani. The reduction in the
thickness of the tympanic membrane takes place at a late period,
simultaneously with an increasing enlargement of the tympanic
cavity. Both are brought about by shrinkage of the gelatinous
tissue, and by an accompanying growth of the mucous membrane
lining the tympanic cavity. Wherever the gelatinous tissue disappears
the mucous membrane takes its place, inserting itself between the
individual ossicles and the chorda tympani, which thus come to
lie apparently free in the tympanic cavity. In reality, however,
they lie outside of it, for they continue to be clothed on all sides by
the growing mucous membrane, and are connected with the wall of
the tympanic cavity by m«ans of folds of that membrane (malleus-
iold, incus-fold, etc.), in much the same manner as the abdominal

THE ORGANS OF THE OUTER GERM-LAYER.

509

organs which grow into the body-cavity are invested by the peri-
toneum and supported from its walls by the mesenteries.

With a reduction in the thickness of the tympanic .membrane
there occurs a condensation of its connective-tissue substance,,
whereby it is enabled to fulfil its ultimate function as a vibrating
membrane.

A more extended discussion of the development of the auditory
ossicles will be deferred to a subsequent section, which deals with the
origin of the skeleton. At present, only a few words further — con-
cerning the formation of the external ear, which, as has already been
stated, is derived from a depression on the outer side of the place
of closure of the first visceral cleft. Its
development has been minutely inves-
tigated in the Chick by MOLDENHAUER
and in the human embryo by His. As
the lateral view of a very young human
embryo (fig. 274) shows, the first visceral
cleft is surrounded by ridge-like margins,
which belong to the first and second
visceral arches, and are early divided into
six elevations designated by Arabic nu-
merals. From these is derived the auricle,
which therefore involves a rather exten-
sive tract of the embryonic head (the
pars auricularis). The pocket between
the ridges, at the bottom of which the
tympanic membrane is met with, becomes
the external meatus. This is continually
growing deeper owing to the surrounding
wall of the side of the face becoming greatly thickened ; finally it
is developed into a long canal, the wall of which is in part bony,,
in part cartilaginous. The six elevations mentioned, which sur-
round the orifice of the external ineatus, together constitute a
bulky ring. The accompanying representation (fig. 285) shows
clearly its metamorphosis into the external ear. It shows that
out of the elevations 1 and 5 the tragus and antitragus are
developed, out of 2 and 3 the helix, and out of 4 the antihelix.
The lobule of the ear remains for a long time small; it is not
until the fifth month that it becomes more distinct. It is derived
from the hillock marked with the numeral 6. At the close of the
second month all the essential parts of the external ear are easily

Fig. 285, — 'Fundament of the
outer ear of a human embryo,
after His.

The elevation marked 1 produces
the tragus ; 5, the antitragus.
The elevations 2 and 3 produce-
the helix; 4, the antihelix.
From the tract 6 is formed the
lobule. K, Lower jaw.

510 EMBRYOLOGY.

recognisable ; from the third month onward the upper and posterior
part of the auricle grows out more from the surface of the head ;
and it acquires greater firmness upon the differentiation of the
auricular cartilage, which had already begun at the end of the
second month.

SUMMARY.

1. The most essential part of the organ of hearing, the mem-
branous labyrinth, is developed at the side of the after-brain above
the first visceral cleft from a pit-like depression of the outer germ-
layer.

2. By closure the auditory pit becomes the auditory vesicle ; it
sinks down and becomes imbedded in embryonic connective tissue,
from which the cranial capsule is subsequently developed.

3. The auditory vesicle acquires the complicated form of the
membranous labyrinth by various evaginatiohs of its wall, and
becomes differentiated into the utriculus, with the three semicircular
•canals, into the sacculus with the canalis reunions and the cochlea,
as well as into the recessus vestibuli, by means of which sacculus
and utriculus remain permanently connected with each other.

4. The auditory nerve and the auditory epithelium, which are
at first single, are likewise divided — as soon as the vesicle is
•differentiated into a number of regions — into several nerve- branches
(nervus vestibuli, n. cochleae) and nerve-terminations (the cristse
acusticse of the three ampullae, a macula acustica for the utriculus
and another for the sacculus, and the organ of CORTI).

5. The embryonic connective tissue, in which are enclosed the
auditory vesicle and the products of its metamorphosis, is differen-
tiated into three parts : — ,

(a) Into a thin connective-tissue layer, which is closely applied

to the epithelial wall and together with it constitutes
the membranous labyrinth ;

(b) Into a gelatinous tissue, which becomes liquefied during

embryonic life and furnishes the perilymphatic spaces
(in the cochlea the scala vestibuli and the scala tym-
pani) ;

(c) Into a cartilaginous capsule, from which there arises by a

process of ossification the bony labyrinth.

6. The middle and outer ear are derived from the upper part
of the first visceral cleft (the spiracle of Selachians) and its
periphery.

THE ORGANS OF THE OUTER GERM-LAYER. 511

7. The tympanic membrane, which at first is rather thick and
only gradually becomes reduced to a thin, tense membrane, is de-
veloped out of the closing plate of the first visceral cleft and the
adjacent parts of the visceral arches.

8. The tympanic cavity and the Eustachian tube are developed
out of a depression on the median side of the tympanic membrane, —
the sulcus tubo-tympanicus, — and out of an evagination from it
extending upward, outward, and backward.

9. The tympanic cavity is at first extremely small, the connective
tissue of the mucous membrane that surrounds it being gelatinous
[and voluminous].

10. The auditory ossicles and the chorda tympani lie at first
outside the tympanic cavity in the gelatinous tissue of its wall ; it is
only after shrivelling of the gelatinous tissue that they come to lie
in folds of the mucous membrane, which project into the now more
capacious tympanic cavity (incus-fold, malleus-fold).

11. The external meatus is developed from the periphery of the
depression that lies on the lateral side of the tympanic membrane ;
the auricle arises from six elevations, which are converted into
tragus, antitragus, helix, antihelix, and the lobule of the ear.

C. The Development of the Organ of Smell.

The organ of smell is, like the eye and ear, a product of the outer
germ-layer, from which it is developed somewhat later than the two
higher sensory organs. It first becomes noticeable, at either side
of the broad frontal process (fig. 274) previously described, as a
thickening of the outer germ-layer which His has designated in
human embryos as nasal area. Both fundaments soon become more

— -"^*- — *— ^

distinct owing to the fact that each nasal area becomes depressed
into a kind of trough, the edges of which rise up as folds (fig. 286).
An olfactory lobe, which has been formed meantime by an evagina-
tion of the cerebral vesicle, grows out on either side to the thick-
ened epithelium of this area, where its nerve- fibrillse terminate.

The two olfactory pits, which are formed in a similar manner in
all Vertebrates with the exception of the Qyciostemes, in which only
an unpaired pit arises, are separated from each other by a consider-
able distance. They therefore appear at first as distinctly paired
structures, whereas in their ultimate condition in the higher-
Vertebrates they have approached each other toward the median
plane and become an apparently unpaired organ, the nose.

512

EMBRYOLOGY.

The study of the development of the organ of smell acquires

additional interest, when
one takes into account
the comparative - ana-
tomical conditions. It
is then found that the
various stages through
which the organ of smell
passes during embryonic
life, in Mammals for
example, have been
preserved as permanent
conditions in lower
classes of Vertebrates.
Thus in the case of
many groups of Fishes
the organ of smell is
preserved, as it were, in
its initial stage in the
form of a pair of pits.
Upon closer histological
investigation, however,
this condition acquires
a special interest, be-
cause it presents points of comparison with simpler sensory organs
which are distri-
buted over the in-
tegument. As
BLAUE especially
has shown in a
meritorious work,
the olfactory
nerve does
terminate in
case in a con-
tinuous olfactory
epithelium, but in
individual, sharply
differentiated or-

Fig. 286.— Frontal reconstruction of the oro-pharyngeal
cavity of a human embryo (Rg of His) 11-5 mm. long,
neck measurement. From His, "Menschliche Em-
bryonen." Magnified 12 diameters.

The upper jaw is seen in perspective, the lower jaw in
section. The posterior visceral arches are not visible
from the outside, since they have moved into the
depths of the cervical sinus.

not
this

Fig. 287.— Longitudinal section through three olfactory buds from
the regio olfactoria of Belone, after BLAUE. Highly magnified.

rk, Olfactory bud ; fe, indifferent ciliate epithelium in several
layers; R, branch of the olfactory nerve.

gans (fig. 287 rk), which, although closely crowded in an indifferent
ciliate epithelium (fe), are nevertheless separated from each other.

THE ORGANS OP THE OUTER GERM-LAYER.

513

The organs (rk) consist of numerous fine, rod-like cells, which at
their free ends bear fine bristles and are united into bundles that
are distinctly delimited from the ordinary cells of the epidermis.
They closely resemble the sensory nerve-terminations which are abun-
dantly and widely distributed in the epidermis of Fishes and other
lower Vertebrates — the beaker-like organs or the nervous end-buds.
BLAUE has therefore named them olfactory buds. He proceeds from
the conception that, like the similarly constructed gustatory buds
of the oral cavity, they are descended from the sensory organs
distributed over the whole integument. The organ of smell is
simply a depressed patch of the skin richly provided with terminal
nerve-buds, which, undergoing a change of function, has come to sub-
serve a specific sense. The continuous
olfactory epithelium of the higher Ver-
tebrates has arisen from the originally
scattered, isolated olfactory buds (fig.
287 rk) by a process of fusion, the in-
different epithelium (fe) having gradu-
ally disappeared. In certain species of
Fishes and Amphibia such a transition
can be demonstrated.

The further development of the organ
of smell is especially characterised by
the olfactory pits coming into relation
with the oral cavity. Each of them
(fig. 286) develops a furrow which
runs downward to the upper margin
of the mouth and receives on its outer

side the previously described lachrymal groove, coming in an oblique
direction from the eye. Nasal pit and nasal furrow become deeper
in older embryos (fig. 288), owing to their margins protruding out-
ward as ridges and forming the so-called inner and outer nasal pro-
cesses. The two inner nasal processes are separated from each other
by a shallow furrow running from above downward ; they together
produce a thick partition between the two olfactory pits that in the
higher Vertebrates subsequently becomes more and more reduced in
thickness. They also furnish the middle of the roof of the mouth.
The outer nasal processes (also called the lateral frontal processes by
His) form on either side a ridge protruding between the eye and the
organ of smell, and furnish the material for the formation of the
lateral walls of the nose and the alse. Their lower margins meet

33

Fig. 288.— Fundament of the nose and
the roof of the primitive mouth-
cavity of a human embryo (C. II.
of His), seen from below after
removal of the lower jaw. From
His, "Menschliche Embryonen.'
Magnified 12 diameters.

514

EMBRYOLOGY.

the front end of the transversely located maxillary processes, from
which they are delimited externally by the lachrymal grooves.

On the median wall of the nasal pit there exists a special small
depression, which was first found by DURSY in mammalian embryos,
and which is also observable in human embryos at a very early stage
(His). It is the fundament of JACOBSON'S organ, which afterwards
makes its way into the septum of the nose. It receives from the
olfactory nerve a special branch, which is indeed of remarkable size
in embryos.

The stage with the nasal groove exists as the permanent condition in many
Selachians. In these cases the deep nasal pits, which are enclosed in a car-
tilaginous capsule, and the mucous membrane of which is raised up into

numerous parallel folds,
lie on the under surface
of the elongated snout or
rostrum. Deep grooves,
which are bounded by
folds of the skin contain-
ing muscles, and which
can be closed as> if by
valves, lead to the front
margin of the mouth at
some distance from its
angle.

Fig. 289.— Roof of the oral cavity of a human embryo with the
fundaments of the palatal processes, after His. Magnified
10 diameters.

The next stage,
which in human em-
bryos is reached in
the second half of
the second month,

exhibits the organ of smell converted into two canals, which have
been produced by the fusion of the margins of the two 'grooves,
especially that of the inner nasal process with the maxillar^ process,
which advances toward the median plane. The canals now possess
two openings, the external and the internal nasal orifice (fig. 289) or
the nares. The two external nares lie only a little above the border
of the mouth-opening ; the internal, in the roof of the primitive oral
cavity, on account of which they have been named by DURSY the
primitive palatal clefts. They are located far forward, only a little
removed from the edge of the mouth, a position which they retain
permanently in the case of the Dipnoi and Amphibia. At first
round, they afterwards become elongated and assume the form of
a fissure running from in front backwaid.

With the metamorphosis of the organ of smell into a canal leading

THE ORGANS OF THE OUTER GERM -LAYER. 515

into the oral cavity, — which has been effected in all Vertebrates that
breathe by means of lungs, — a second function has been assumed. It
is now not exclusively a sensory organ for the perception of odors,
but serves at the same time to conduct currents of air both to and
from the oral and pharyngeal cavities and the lungs. It has become
a kind of respiratory atrium for the apparatus of respiration. The
assumption of this accessory function gives a special stamp to the
later stages of the development of the organ, and is to be taken into
account in a proper estimate of it. For the course of the further
development is most of all determined by the tendency to an exten-
sive enlargement of the surface of the olfactory chamber. The
increase of surface, however, does not affect the real olfactory
mucous membrane or sensory epithelium, to which the olfactory
nerve is distributed, but rather the ordinary ciliate mucous membrane.
It is therefore less connected with an improvement of the sense of
smell than with an accessory function in the process of respiration.
By an increase of the surface of the soft, vascular mucous membrane
the air that is swept gver it becomes warmed and freed from particles
of dust, which are caught by the moist surface. From this time
forward therefore one must distinguish a regio olfactoria and a regio
respiratoria. The former, which is derived from the sensory
epithelium of the original olfactory pit, remains relatively small,
receives the terminations of the olfactory nerve, and is limited in the
case of Man to the region of the upper turbinal process and a part
of the septum nasi. It is the respiratory function that causes the
vast dimensions which the organ of smell attains in the higher
Vertebrates.

The increase in the surface of the nasal cavity is produced by three
different events : (1) by the formation of the hard and soft palate,
(2) by the development of the turbinal bones, (3) by the appearance
of the accessory cavities of the nose.

The first event begins in Man toward the end of the second month.
There is then formed on the inner surface of the maxillary process
(fig. 289) a ridge, which projects into the wide primitive oral cavity
and grows out horizontally into a plate. The right and left palatal
plates at first embrace between them a broad fissure, through which
may be seen the original roof of the oral cavity and on this the inner
nasal orifices, which become more and more slit-like and are separated
by a bridge of substance which has arisen from the median frontal
process and can now be designated as the nasal septum. In the
third month the embryonic palatal fissure becomes gradually narrower.

516

EMBRYOLOGY.

The horizontal palatal processes of the upper jaw increase in size,

and finally their
free

Kg. 290.— Cross section through the head of an embryo Pig 3 cm
long, crown-rump measurement.

The nasal cavities are seen to be in communication with the oral
cavity at the places designated by a * ; K, cartilage of the nasal
septum ; m, turbinal cartilage ; J, organ of JACOBSON ; /', the
place where it opens into the nasal cavity ; gf, palatal process ;"
of, maxillary process ; zl, dental ridge.

en-
counter in the
median plane the
still broad nasal
septum, which has
grown down yet
farther into the
oral cavity. Then
the parts men-
tioned begin to
fuse with one an-
other from before
backward.

Two stages of
this process are
illustrated by the
accompanying
figures (tigs. 290,

291), in which cross sections through the anterior end of two embryo

Pigs are repre-
sented. Figure

290 shows the

stage at which

the palatal

plate (gf) of

the maxillary

process (of)

has advanced

close to the

lower margin

of the nasal

septum. Oral

and nasal cavi-
ties are still

in communica-
tion by means

of the very

narrow palatal fissure indicated by an asterisk.

In figure 291 the fusion has taken place. In this manner the

Fig. 291. — Cross section through the head of an embryo Pig 5 cm.

long, crown-rump measurement.
k, Cartilaginous nasal septum ; m, nasal turbinal process ; J. JACOBSON'S

organ with jk, JACOBSON'S cartilage ; zl, dental ridge ; bl, covering

bone.

THE ORGANS OF THE OUTER GERM-LAYER. 517

primitive oral cavity is divided into two storeys, one above the other.
One, the upper part, becomes associated with the organ of smell, to
the enlargement of which it contributes ; it is distinguished from the
space that arose from the original olfactory pit, or the olfactory
labyrinth, as naso-pharyngeal passage. This opens behind into the
pharynx by means of the posterior nares. The lower part becomes
the secondary oral cavity. The partition that has been formed from
the maxillary process is the palate, which later, when the develop-
ment of the bones of the head can be traced, is differentiated into the
hard and the soft palate.

A small portion of the palatal fissure, which in young embryos
traverses the palate from in front backward and unites oral and
nasal cavities (fig. 290 *), is preserved in most Vertebrates and con-
stitutes the ductus nasopalatinus or STENSJON'S duct. A probe may be
passed through it from the nasal to the oral cavity. In Man the
duct of STENSON is closed during embryonic life ; there is preserved,
however, in the palatal process of the bony maxilla at the correspond-
ing place a vacuity, the canalis incisivus, occupied by connective
tissue, blood-vessels, and nerves.

Where the ducts of STENSON are present, there are found in their
vicinity the organs of JACOBSON, concerning which the statement has
already been made that they are established very early as special
depressions of the two olfactory pits. In Man this organ is converted
into a narrow tube, which lies a little above the canalis incisivus and
" pursues a straight course backward and slightly upward close to
the cartilaginous partition, ending blindly" (SCHWALBE). In Mam-
mals the organ is more highly developed (figs. 290, 291 J) ; it is
enveloped in a special cartilaginous capsule (JACOBSON'S cartilage,
jk) and receives a special branch of the olfactory nerve, which ter-
minates in a sensory epithelium, which agrees with that of the
regio olfactoria. Frequently (e.g., in Kuminantia) it opens into the
beginning of STENSON'S canal, which in this case remains open as
a communication between nasal and oral cavities.

1 cited the formation of folds as the second means of increasing the
internal surface of the organ of smell. These are developed in
Mammals (figs. 290, 291) and in Man on the lateral walls of the
nasal chambers; they run parallel to one another from in front
backward ; their free margins grow downward, and in consequence of
the forms which they assume are called the three nasal turbinated
processes, while the spaces between them are designated as upper,
middle, and lower nasal passages. From the cartilaginous cranial

318 EMBRYOLOGY.

capsule they receive in Man as early as the second month a support,
which subsequently ossifies. In many Mammals the turbinated
processes acquire a complicated form owing to the production upon
the first fold of numerous smaller secondary and tertiary folds, which
become peculiarly bent and rolled up. On account of the complicated
form resulting from the production of the turbinated processes the
olfactory sac has received the name of olfactory labyrinth.

Thirdly and lastly, the mucous membrane of the nose is increased
in extent by the formation of evaginations which grow out partly
into the ethmoid region of the cranial capsule, which consists of
cartilage during early stages of development, and partly into a number
of the covering bones (Belegknochen).

In this manner are formed the numerous small cribriform pits in
the cartilaginous cribriform plate. Somewhat later (in Man during
the sixth month) an evagination into the upper jaw is developed into
the antrum of HIGHMORE. Finally, after birth evaginations penetrate
into the body of the sphenoid bone and into the frontal bone, pro-
ducing the sinus sphenoidales and sinus frontales, which, however,
attain their full development only at the time of sexual maturity.
In many Mammals the enlargement of the nasal cavity takes
place even farther backward into the body of the occipital bone
(sinus occipitales). Inasmuch as the accessory cavities of the noss
take the place of bone-substance, they naturally contribute to the
diminution of the weight of the cranial skeleton.

In connection with the account of the organ of smell the formation
of the external nose ought now to be briefly considered. It is
developed out of the frontal process and the parts designated as
nasal processes (figs. 286, 288, and 289), these becoming elevated more
and more above the level of the surrounding parts. At first broad
and bulky, the nose later becomes thinner and longer and acquires
characteristic forms. The nostrils, which at their formation are far
apart, come together in the median plane. Whereas the distance
in an embryo five weeks old is, as His has shown by measurements,
1*7 mm., it has become reduced in an embryo seven weeks old to
1*2 mm., and in one somewhat older to 0'8 mm. The median frontal
process is correspondingly reduced in thickness and furnishes the
nasal septum.

SUMMARY.

1. The organ of smell is developed out of two pit-like depressions
of the outer germ-layer, which are formed on the frontal process at
a considerable distance from each other.

THE ORGANS OF THE OUTER GERM-LAYER. 519

2. At a later stage the pits are united with the angle of the oral
cavity by means of the nasal grooves.

3. The inner and outer margins of the olfactory pits and the nasal
grooves project out as ridges and constitute the inner and outer nasal
processes.

4. By fusion of the margins of the nasal grooves the organ of
smell is converted into two nasal passages, which open out on the
frontal process by means of the external nares and on the roof of
the primitive oral cavity a little back of the upper lip by means of
the internal nares.

5. The internal nares afterwards become fissure-like and move
nearer together, owing to the nasal septum becoming thinner and
growing downward somewhat into the primitive oral cavity.

6. The upper part of the primitive oral cavity shares in the forma-
tion of the organ of smell and serves for the increase of its re-
spiratory region, since horizontal ridges (the palatal processes) grow
inward from the maxillary processes toward the lower margin of the
nasal septum, with which they fuse, and produce the hard and soft
palate.

7. In the organ of smell a further enlargement of the spaces
serving for respiratory purposes is produced by

(a) The formation of folds of its mucous membrane, by which

the turbinated processes arise ;

(b) Evaginations of its mucous membrane into the adjacent

parts of the cartilaginous and bony cephalic skeleton
(formation of the " cells " in the cribriform plate, the
frontal and sphenoidal sinuses, and the antrum of
HIGHMORE).

8. In human embryos there is early formed in the olfactory pit
a special depression of the outer germ -layer as fundament of the
organ of JACOBSON, which receives a special branch of the olfactory
nerve.

9. JACOBSON'S organ comes to lie at the base of the nasal septum
remote from the olfactory region.

10. The ducts of STENSON in many Mammals and the cariales
incisivi in Man are preserved as remnants of the so-called palatal
fissures — the original fissure-like communications between nasal
cavities and secondary oral cavity.

520 EMBRYOLOGY.

III. The Development of the Skin and its Accessory Organs.

Having now become acquainted with the physiologically more
important functions of the outer germ-layer, — which consist in the
production of the nervous system and the sensory organs, — I give a
short survey of the changes which take place in the remaining part,
which is now designated as primitive epidermis (Hornblatt). This
furnishes the whole outer skin of the body or epidermis and the
numerous and various organs that are differentiated out of it, such
as the nails, the hair, and the sweatr, sebaceous, and milk-glands.

(a) The Skin.

The epidermis of Man is, according to the statements of KOLLIKER,
very thin during the first two months of development, and consists of
only two single layers of epithelial cells. Of these the superficial
layer exhibits flattened, transparent, hexagonal elements ; the deeper
one, on the contrary, consists of smaller cells ; so that already there
is indicated by this a differentiation into a corneous and a mucous
layer. Even now, too, a detachment of epidermal cells begins to
manifest itself. For the outer cell -layer is soon found to be in
process of decay, with obliterated cell -contours and indistinct nuclei,
while a supplementary layer arises beneath it'. In many Mammals
the dying layer of cells is detached as a continuous sheet and
then constitutes for a time a kind of envelope around the whole
embryo, to which WELCKER has given the name epitrichium, because
the outgrowing hairs are developed beneath it.

From the middle of embryonic life onward both layers of the
epidermis become thicker and the outermost of them contains
cornified scales, the nuclei of which have degenerated. From this
time onward a more extensive desquamation takes place at the
surface, while the loss is made good by cell -divisions in the mucous
layer and by the metamorphosis of these products of division into
cornified cells. In consequence of this the surface of the embryo
becomes up to the time of birth more and more covered with a
yellowish-white, greasy mass — the smegma embryonum or vernix
caseosa. This consists of a mixture of detached epidermal scales and
of sebaceous secretions, which have been produced by the dermal
glands that have arisen meantime. It forms a thick layer, especially
on the flexor-side of the joints, on the sole of the foot, the palm of
the hand, and on the head. Detached portions of it get into the

THE ORGANS OF THE OUTER GERM-LAYER.

amniotic fluid and make it turbid. Finally these, as well as some
of the detached downy hairs, may be swallowed by the embryo with
the amniotic fluid, and thus become a component of the meconium
accumulated in the intestine.

The epidermis constitutes only one component of the skin of the
adult or of the integument ; the otherand more voluminous part — •
the dey^riOfGY corium — is produced by the mesenchyme. The same thing
takes place here as in the case of the other membranes and organs
of the body. The epithelial layers derived from the primary germ-
layers enter into close relationship with the mesenchyme, since they '
acquire from *tne latter a' ebnnective^tlslsue foundation that serves for
their mechanical support and nujbrition. Just as the inner germ-
layer unites with the intermediate layer to form the mucous mem-
brane of the alimentary canal, as the epithelium of the auditory
vesicle with the adjacent connective substance to form the mem-
branous labyrinth, and as the epithelial optic vesicle with the choroid
and sclera to form the eyeball, so here also the epidermis unites with
the corium to constitute the integument.

During the first months the corium forms in Man a layer of
closely packed, spindle-shaped cells, and is delimited from the
epidermis by a delicate, structureless, smooth-surfaced, bounding
membrane (basement membrane), such as exists permanently in the
case of the lower Vertebrates. In the third month it is differ-
entiated into the corium proper and the looser subcutaneous tissue,
in which there are soon developed clusters of fat cells. From the
middle of pregnancy onward the latter so increase in number that
the subcutaneous tissue soon becomes a layer of fat covering the
whole body. At this time the smooth contour between epidermis
and corium is lost, owing to the development on the surface of the
latter of small papillae, which grow into the mucous layer and
produce the corpus papillare of the skin. The papillae serve partly
for the reception of loops of capillary blood-vessels, and thus effect
a better nutrition of the mucous layer ; in part they receive the
terminations of tactile nerves (tactile corpuscles), and thus are
divided into vascular papillae and nervous papillae.

The skin of Vertebrates attains a higher degree of development in
consequence of processes similar to those described for the intestinal
canal. The epidermis increases its surface outward by the formation
of folds, inward by imaginations. Because the evaginated and
invaginated parts at the same time alter in many ways thei;
histological peculiarities, there arises a large number of organs of

522 EMBRYOLOGY.

different kinds, which are developed in different ways in the separate
classes of Vertebrates and which preeminently determine the external
appearance of the animals.

As external processes arise the dermal teeth, and scales, the
feathers, hair, and nailsi As invaginations of the epidermis are
developed the sweat-, sebaceous, and milk-glands. We will begin
with the former, and. not to go too far into details, will limit our-
selves to the organs of the skin in Mammals.

(b) The Hair.

The most characteristic epidermoidal structures of Mammals and
Man are the hairs. One can distinguish two modifications in the
method of their development. The ordinary method of development
is that which is known in Man. In this case, at the end of the
third embryonic month, the mucous layer grows at certain places
and forms small solid plugs, the hair-germs, which sink into the
underlying corium (fig. 292 B hk). By afterwards elongating and
becoming thickened at the deep end they assume the shape of a
flask. Then there ensues a process similar to that which takes place
upon the formation of the teeth. At the bottom of the epithelial
plug the adjacent corium grows and forms a richly cellular nodule
(pa), which grows into the epithelial tissue and is the fundament of
the connective-tissue hair-papillce, which is early provided with loops
of blood-vessels. Around the whole ingrowing germ of the hair the
surrounding parts of the corium are afterwards more and more
distinctly arranged into special courses of fibres — some of which run
lengthwise, others in a circular manner — and constitute a special,
vascular, nutritive envelope, the hair-follicle (fig. 292 C, D, hb).

A somewhat different method of hair-formation has been observed
by RETSSNER, GOETTE, and FEIERTAG in certain Mammals.

In these the first impulse to the formation of the fundament of a
hair is produced by a limited cell-growth of the corium immediately
below the epidermis. It produces a small elevation (fig. 292 A),
which is simply the hair-papilla itself, projecting into the epidermis.
Then the papilla is foiced farther and farther away from the surface
of the skin by the growth of the epidermal cells that cover it, and
at last is found far removed from its place of origin and at the deep,
somewhat thickened end of a long epithelial plug.

The final result is therefore the same in both cases, only the time
of the formation of the first fundament of the papilla and of the

THE ORGANS OF THE OUTER GERM-LAYER. 523

epithelial plug is different. In the latter case the papilla arises at
the surface of the skin and is forced down by a plug-like epithelial
growth ; in the former the epithelial plug first sinks into the under-
lying tissue and then at its deep end the hair-papilla is formed by a
growth of the corium.

The question arises, Which of these two methods of development
is to be considered the more primitive ? In my opinion it is the
formation of the hair-papilla at the surface of the skin. For this is
unquestionably the simpler and less complete condition, from which
the latter is derivable and through which it is explainable. The
hairs sink into the underlying tissue for the purpose of better
nourishment and attachment. A parallel is furnished by the
development of the teeth. In the Selachians the latter arise (so
far as they are developed as protective structures in the skin) from
papillae which grow from the corium into the epidermis ; in Teleosts
and Amphibia, on the contrary, the teeth, which are found dis-
tributed over extensive areas in the oral mucous membrane, are
established deep down in that membrane, for epithelial growths in
the form of plugs first sink down into the connective tissue, and it
is only subsequently that the dental papillae are formed by a process
of growth in the connective tissue at the bottom of the epithelial
down growth.

Let us return after this comparison to the further development of
the hair ; this takes place in the same manner in both the cases
distinguished above. The epithelial cells which cover the papillae
multiply and are differentiated into two parts (fig. 292 0) ; first,
into cells that are more remote from the papillae, that become
spindle-shaped and united into a small cone, and that by cornification
produce the first point of the hair (ha), and secondly into cells which
immediately invest the papilla, remain protoplasmic, and constitute
the matrix — the hair-bulb (hz) — by means of which the further
growth of the hair takes place. The cells of the hair-bulb, which
rapidly increase by division, are added below to the first-formed part
of the hair, and by cornification contribute to its elongation.

The hair in process of development on the papilla at first lies
wholly concealed in the skin and is enveloped on all sides by cells of
the epithelial plug, at the bottom of which the first trace of it was
formed. From this investment are formed the outer and the inner
sheaths of the root (fig. 292 C and D aw and iw). Of these the
outer (aw) consists of small protoplasmic cells and is continuous
externally with the mucous layer of the epidermis (schl), internally

524

EMBRYOLOGY.

with the hair-bulb (hz). The cells in the inner sheath of the root
(iw) assume a flattened form and become cornified.

In consequence of the growth which proceeds from the bulb the
hairs are gradually shoved up toward the surface of the epidermis,
and at the end of the fifth month in the case of Man begin to break
forth to the outside (fig. 292 D ha'). They protrude more and
more above the surface of the skin, even in the embryo, and consti-
tute at many 'places of the skin, especially on the head, a rather

Fig. 292 A— J).— Four diagrams of t:ie development of the hair. A, Development of the hair-
papilla on the free surface of the skin, as it occurs, according to GOETTE, in many Mammals.
B, C, D. Three different stages of the development of the hair in human embryos.

ho, Corneous layer of the epidermis ; schl, mucous layer ; pa., hair-papilla ; M, germ of hair ;
hz, bulb of hair; ha, young hair; ha', tip of the hair protruding from the hair-follicle;
aw, iw, outer and inner sheath of the root of the hair ; A6, hair-follicle ; td, sebaceous gland

thick covering. On account of their minute size and fineness, and
because they fall out soon after birth, they are called the downy hair
or lanugo.

Each hair is a, transitory structure of short duration. After a time
it falls out and is replaced by a new one. This process begins even
during embryonic life. The hairs that fall off get into the amniotic
fluid, and since with this fluid they are swallowed by the embryo, they
form one of the components of the meconium accumulated in the
intestinal canal, A more extensive change takes place in Man soon

THE ORGANS OF THE OUTER GERM-LAYER. 525

after birth with the shedding of the downy hair, which is replaced
on many parts of the body by a more vigorous growth of hair. In
Mammals the shedding of the old and the formation of new hair
exhibits a certain periodicity, which is dependent on the warmer
and colder periods of the year. Thus they develop a summer and a
winter coat. Even in Man the shedding of the hair is influenced,
although less noticeably, by the time of year.

The falling off of the hair is initiated by changes in the part
resting on the papilla and called the bulb. The cell -multiplication,
by means of which the addition of new corneous substance takes
place, ceases ; the falling hair becomes detached from its matrix and
its deep end looks as though it were split into shreds ; but it is still
retained in the hair-follicle by its closely investing sheath, until it is
forcibly removed or is crowded out by the supplementary hair that
takes its place.

The opinions of investigators still differ concerning the manner in
which the supplementary hairs are developed. An especial subject
of controversy is the point whether the young hair is formed from
an entirely new papilla (STIEDA, FEIERTAG) or from the old one
(LANGER, v. EBNER), or whether both methods occur (KOLLIKER,
UNNA). It seems to me that the first view is the correct one, and
that the shedding of the hairs is due to the atrophy of their papillae.
During this slowly occurring process of degeneration, perhaps even
before it begins, the substitution is initiated by the occurrence of an
active cell-proliferation at a place in the outer sheath of the root —
which indeed consists of cells rich in protoplasm — and by the
formation of a new plug, which grows out deeper into the derma
from the bottom of the fundament of the old hair. At the blind
[deep] end of this secondary hair-germ there is then developed from
the derma a new papilla, upon which is formed the new hair and
its sheaths alongside of and below the old one, in the manner
previously described. When it begins to increase in length, it
presses against the old hair lying above it, crowds the latter out
of its sheaths, until it falls off, and finally itself takes the place
of it.

According to this account there would be a certain similarity
between the shedding of the hair and that of the teeth, inasmuch as
in both cases secondary epithelial processes, from which the new
tooth- or hair-papilla begins, arise from the primary fundament,
and inasmuch as the new structures by their growth displace the
old.

526

EMBRYOLOGY.

In addition to the development of hairs from old fundaments, a
second method of formation, which one might designate as direct or
primary, is maintained by many writers (GOETTE, KOLLIKER). It is
assumed that even after birth, both in the case of Man and other
Mammals, hair-germs are formed directly from the mucous mem-
brane of the epidermis, in the same manner as in the embryo. In
how far, at what regions, and up to what age such a direct forma-
tion of hair takes place, demands still more detailed and exhaustive
investigation.

(c) The Nails.

A second organ resulting from a cornification of the epidermis is
the nail, which corresponds in a comparative-anatomical way to
the claw- and hoof -like structures of other Mammals. In human
embryos only seven weeks old there appear proliferations of the
epidermis at the ends of the fingers, which are noticeably short and
thick, and likewise at the ends of the toes, which are always less
developed than the fingers. In consequence of the proliferations
there arise from the loose epidermal cells complicated claw-like
appendages, which have been described by HEKSEN as predecessors of
the nails or primitive nails.

In somewhat older embryos, from the ninth to the twelfth week,
ZANDER found the epidermal growth marked off from its surround-
ings by a ring-like depression. The growth consists of a single
layer of cylindrical cells with large nuclei lying on the side toward
the derma and corresponding to the rete Malpighii, of two or three
layers of polygonal spinous cells, and of a corneous layer.

The territory thus distinguished by a depression and by an
altered condition of the cells ZANDER calls the primary basis of the
nail (Nagelgrund), and describes it as occupying a greater part of
the dorsal, but also a smaller part of the ventral surface of the
terminal segment. He infers from this that the nails in Man
originally had, like the claws of the lower Vertebrates, a terminal
position on the toes and fingers, and that they have secondarily
migrated on to the dorsal surface. Thus he explains the fact that the
region of the nail is supplied with the ventral nerves of the fingers.

GEGENBAUR subscribes to ZANDER'S view of the terminal position
of the fundament of the nail, but, supported by the investigations
of ipoAS, opposes ZANDER'S assumption of a migration of the funda-
ment of the nail dorsally. He distinguishes in the development of
nails and claws two parts (fig. 293), the dorsally located firm nail-

THE ORGANS OF THE OUTER GERM-LAYER.

527

plate (np) and the plantar horn (Sohlenhorn, sh) connected with it,
ventrally. Of these the latter arises from the smaller ventral
surface of the primary basis of the nail. In imguiculate and
ungulate Vertebrates it (fig. 294 sh) is developed to a great extent;
in Man it atrophies, and is recognisable only in an exceedingly
reduced condition as nail-welt. By this term is meant the welt-like
thickening of the epidermis which forms the transition from the
bed of the nail to the corrugated skin of the ball of the finger. The
nail-plate, on the contrary, is from the beginning exclusively a
product of the dorsal surface of the basis of the nail. There is
therefore neither in Man nor in other Mammals a dorsal migration
of the terminal fundament of the nail, but only a degeneration of

me ak Tip

Fig. 2P3. Fig. £94.

Fig. 293. — A, Longitudinal section through the toe of a Cercopithecus B, Longitudinal section

through the second finger of Macacus ater. After GEGENBAUR.
np, Nail-plate ; sh, plantar horn (Sohlenhorn) ; me. nail-wall.

Fig 294. — Section through a Dog's toe. After GEGEXBAUR.
np, Nail-pJate ; sh, plantar horn : 6, ball of toe.

its ventral portion, which otherwise furnishes a more complete
plantar horn.

So far as regards the particular events in the development of
the nail-plate, the structure is demonstrable in human embryos four
months old as a thin flat layer of cornified, closely united cells on
the dorsal surface of the primary basis of the nail or the bed of the
nail. It is produced by the mucous layer upon which it im-
mediately lies, but continues for a time to be covered by the thin
corneous layer that is present at all points of the epidermis. This
investment — UNNA'S eponychium — is not lost until the fifth month.
However, notwithstanding their investment, the nails are easily
recognisable some weeks before this from their whiteness, in dis-
tinction from the reddish or dark red color of the surrounding skin.

528 EMBRYOLOGY.

Owing to the addition of new cells from the mucous membrane, both
from below and from the posterior margin, the nail-plate grows — it
becomes thickened and increased in surface extent. It is now
pushed forward from behind over the bed of the nail, and at the
seventh month its free margin begins to project beyond the latter.

With this the nail has acquired essentially the appearance and con-
dition which it has in the adult. In new-born infants it possesses a
margin which projects far over the ball of the finger, and which —
because it was formed at an early embryonic period — is both much
thinner and also narrower than the part formed later, which rests on
the bed of the nail. This margin is therefore detached soon after birth.

(d) The Glands of the Skin.

The glandular structures of the epidermis, which are established
by invagination, are of three kinds: sebaceous, sweat-, and milk-
glands. They all arise as proliferations of the mucous layer which
grow down as solid plugs into the derma, and then undergo further
development either according to the tubular or the alveolar type.

The sweat-glands and the ear-wax glands are developed on the
tubular plan. They begin in the fifth month to penetrate from the
mucous membrane into the corium ; in the seventh month they
acquire a small lumen, take a winding course in consequence of
increased growth in length, and become coiled especially at their
deep ends, thereby giving rise to the first fundament of the
glomerulus.

Sebaceous glands and milk-glands are alveolar structures. The former
are either developed directly from the- epidermis, as, for example, at
the edges of the lips, on the prepuce and on the glans penis, or they
are in close connection with the hairs, which is the ordinary condi-
tion. In the latter case they are formed as solid thickenings of the
outer sheath of the root of the hair near the orifice of the follicle,
even before the hairs are completely developed (fig. 292 C, D, td) • at
first they have the form of a flask, then they send out a few lateral
buds, which develop club-shaped enlargements at their ends. The
glands acquire cavities by the fatty degeneration and disintegration
of the interior cells, which are eliminated as a secretion.

The development of the milk-glands, which are more voluminous
organs entrusted with an important function and peculiar to the
class Mammalia, is of greater interest. Of the numerous works
that have appeared concerning them, the comparative-anatomical
investigations of GEGENBAUR especially have led to valuable results.

THE ORGANS OF THE OUTER GERM-LAYER.

529

I present at the very beginning of the discussion the following
proposition, which is of importance in interpreting the conditions
found : each milk-gland in Man is not a simple organ, like an ear-
gland or a submaxillary salivary gland, with a simple outlet, but
a great glandular complex. Its earliest fundament has been
observed in the human embryo at the end of the second month as a
considerable thickening of the epidermis (fig. 295) upon the right
and left sides of the breast. It has arisen as the result of a special
proliferation of the mucous layer, which has sunk into the derma
in the form of a hemispherical knob (df). But modifications arise
afterwards in the corneous layer also, by its becoming thickened and
projecting as a corneous plug into the proliferation of the mucous
layer. Ordinarily there is found
a small depression (g) at the
middle of the whole epithelial
fundament.

The proliferation of the epi-
dermis .that first appears is not
precisely, as assumed by EEIN, the
first fundament of the glandular
parenchyma ; it therefore does
not correspond to the epithelial
plugs which sink into the derma
in the development of the sweat
and sebaceous glands, because
the further course of develop-
ment and especially comparative-
anatomical studies show, that by

the thickening of the epidermis there is only an early delimitation
of a tract of the skin, which is subsequently metamorphosed into the
nipple-area and papilla, and from the floor of which the separate
milk-producing glands at length sprout forth.

The correctness of this view is shown by the following changes :
In older embryos the lens-shaped thickening produced by the
proliferation of the epidermis has increased at the periphery and
has thereby become flattened (fig. 296 df). At the same time it is
more sharply defined at the surface, owing to the derma becoming
thickened and elevated into a wall (dw) — the cutis-wall. Therefore
the whole fundament now has the form of a shallow depression (df)
of the skin, for which the name glandular area is very appropriate.
For there early grow out from its mucous layer into the derma solid

34

Fig. 295.— Section through the fundament of
the milk-gland of a female human embryo
10 cm. long, after Huss.

df, Fundament of the glandular area ; g, small
depression at its surface.

530

EMBRYOLOGY.

buds (dg), just as at other places the sebaceous glands arise from the
epidermis. In the seventh month they are already well developed,
and radiate out below and laterally from the pit-like depression.
Their number increases up to the time of birth, and the larger ones
become covered with solid lateral buds (db). Each sprout is the
fundament of a Kiilk-producing gland, which opens out on the
glandular area (df) by means of a special orifice ; each is morpho-
logically comparable with a sebaceous gland, although its function
has become different.

The name glandular area is also a happily selected one
because it presents a point of comparison with the primitive
conditions of the Monotremes. For in these animals one does

Fig. 296. — Section through the fundament of the milk-gland of a female human e/nbryo 32 cm.

long, after Huss.
df, Glandular area ; die, gland-wall ; dg, duct of gland ; db, vesicle of gland.

not find, as in the higher Mammals, a sharply differentiated
single complex of milk-glands, but instead a somewhat depressed
area of the skin, even provided with small hairs, over which are
distributed single small glands, the secretion of which is licked
up with the tongue by the young, which are born in a very
immature state.

In the remaining Mammals the glands, in the former case
opening separately upon the area, are united into a single
organ, which better serves the young in sucking, namely a papilla
[nipple] or teat, which encloses all the outlets of the glands and is
grasped by the mouth of the suckling. In Man their development
begins after birth. The glandular area, which is encircled by
the cutis-wall and which before birth was depressed into a pit,

THE ORGANS OP THE OUTER GERM-LAYER. 531

now becomes flattened until it lies in the same niveau with
the surrounding skin. It is distinguished from the latter by
its redder color, which is due to its greater vascularity and the
thinner condition of its epidermis. Then during the first years
after birth the middle of the glandular area, together with the
outlets (ductus lactiferi), which there open out close to one another,
is raised up and becomes the nipple, in the derma of which non-
striate muscle-fibres are formed in great numbers ; the remaining
part of the area as far as the cutis-wall becomes the areola mammae.
The metamorphosis takes place somewhat earlier in the female than
in the male.

Soon after birth alterations take place in the still feebly developed
glandular tissue. There occurs a transitory swelling of the pectoral
glands accompanied with increased blood-pressure, and it becomes
possible to press out of the gland a small quantity of a milky fluid,
the so-called witches' milk. According to KOLLIKER its formation is
due to the originally solid ducts of the glands acquiring at this time
a lumen by the fatty degeneration of the central cells, which are
dissolved, and, suspended in a fluid, are discharged from the ducts.
According to the investigations of BARFURTH, on the contrary, the
so-called witches' milk of infants is the product of a genuine tran-
sitory secretion, and is like the real milk of the mother both in its
morphological and chemical components.

After birth great differences arise between the two sexes in
the condition of the milk-glands. Whereas in the male the
glandular parenchyma remains stationary in its development,
in the female it begins to increase, especially at the time of
sexual maturity and still more after the beginning of pregnancy.
From the first-formed ducts of the glands there grow out
numerous lateral, hollow branches, which become covered with
hollow vesicular glands (alveoli) lined with a single layer of
cylindrical epithelium. At the same time there are developed
in the connective tissue, between the separate lobules of the
gland, numerous islands of fat-cells. In consequence the region
-at which the complex of milk-glands has been formed swells into
a more or less prominent elevation, the mamma.

SUMMARY.

1. The development of the hair is inaugurated in human embryos
by the growing down of processes of the mucous layer of the
epidermis — the hair-germs — into the underlying derma.

532 EMBRYOLOGY.

2. At the deep end of the hair-germ the vascular hair-papilla
is begun by a growth of connective tissue.

3. The epithelial hair-germ is differentiated into : —

(a) A young hair, by the cornification of a part of the cells ;

(b) An actively growing cell-layer situated between the shaft

of the hair and the papilla, — the bulb, — which fur-
nishes the material for the growth of the hair ;

(c) The outer and the inner sheaths of the root.

4. Around the epithelial part of the fundament of the hair
there is formed from the surrounding connective tissue the hair-
follicle.

5. The nails in Man and the claws in other Mammals are de-
veloped from a dorsal fundament — the nail-plate — and a ventral
fundament — the plantar horn.

6. The plantar horn in Man is reduced to the nail-welt.

7. The thin nail-plate which is formed at first is for a time
covered with a layer of cornified cells, the eponychium, which in
Man is shed in the fifth month.

8. The milk-gland is a complex of alveolar glands.

9. At first there arises a thickening of the mucous layer of the
epidermis, which is converted into the glandular area that is after-
wards marked off from the surrounding parts by a wall and becomes
somewhat depressed.

10. From the bottom of the glandular area there grow forth in
great numbers the fundaments of alveolar glands.

11. After birth the glandular area, embracing the excretory
ducts of the glands, is elevated above the surface of the skin, and
converted into the nipple and the areola mammae.

12. After birth there is a transitory secretion of a small quantity
of milk-like fluid — the witches' milk.

LITERATURE.

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Kolliker, Th. Ueber das Os intermaxillare des Menschen etc. Nova acta

L.-C. Acad. Bd. XLII. p. 325. Halle 1881.
Legal. Die Nasenhohle und der Thranennasengang der amnioten Wirbelthiere.

Morphol. Jahrb. Bd. VIII. 1883.
Legal. Zur Entwicklungsgeschichte des Thranennasengangs bei Saugethieren.

Inaug.-Diss. Breslau 1882 (?).
Marshall, Milnes. The Morphology of the Vertebrate Olfactory Organ.

Quart. Jour. Micr. Sci. Vol. XIX. 1879.

(5) Development of the Skin and its Organs.

Barfurth. Zur Entwicklung der Milchdriise. Bonn 1882.

Boas, J. E. V. Ein Beitrag zur Morphol. der Nagel, Krallen, Hufe und

Klauen d. Saugethiere. Morphol. Jahrb. Bd. IX. 1884.
Creighton, C. On the Development of the Mamma and of the Mammary

Function. Jour. Anat, and Physiol. Vol. XL 1877, pp. 1-32.
Feiertag. Ueber die Bildung der Haare. Inaug.-Diss. Dorpat 1875.
Gegenbaur, C. Zur Morphologic des Nagels. Morphol. Jahrb. Bd. X.

1885.
Gegenbaur, C. Bemerkungen Uber die Milchdriisenpapillen der Saugethiere.

Jena. Zeitschr. Bd. VII. 1873.
Gegenbaur, C. Zur genaueren Kenntniss der Zitzen der Saugethiere.

Morphol. Jahrb. Bd. I. 1875.

538 EMBRYOLOGY.

Qotte. Zur Morphologie der Haare. Archiv f. mikr. Anat. Bd. IV. 1868,

p. 273.
Hensen. Beitrag zur Morphologie der Korperform und des Gehirns des

menschl. Embryos. Archiv f. Anat. u. Entwicklungsg. Anat. Abth.

Jahrg. 1877.
HUBS, M. Beitrage zur Entwicklung der Milchdriisen bei Menschen und bei

Wiederkiiuern. Jena. Zeitschr. Bd. VII. 1873.
Klaatsch, Hermann. Zur Morphologie der Saugethier-Zitzen. Morphol.

Jahrb. Bd. IX. 1884.
Kolliker, A. Zur Entwicklnngsgeschichte der aussern Haut. Zeitschr. f .

wiss. Zoologie. Bd. II. 1850, p. 67.
Kolliker, Th. Beitrage zur Kenntniss der Brustdriise. Verhandl. Wiirzburg.

physical.-med. Gesellsch. Bd. XIV. 1879.
Langer, C. Ueber den Bau und die Entwicklung der Milchdriisen. Denkschr.

d. k. Acad. d. Wissensch. Wien. Bd. in. 1851.
Rein, Q-. Untersuchungen Uber die embryonale Entwicklungsgeschichte der

Milchdriise. Archiv f. mikr. Anat. Bde. XX. u. XXI. 1882.
Reissner. Beitrage zur Kenntniss der Haare des Menschen und der Thiere.

Sreslau 1854.
Toldt, C. Ueber die Altersbestimmung menschlicher Embryonen. Prager

med. Wochenschr. 1879.
Unna, P. Z. Beitrage zur Histologie und Entwicklungsgeschichte der

menschlichen Oberhaut und ihrer Anhangsgebilde. Archiv f . mikr. Anat.

Bd. XII. 1876.
Zander, R. Die friihesten Stadien der Nagelentwicklung und ihre Beziehungen

zu den Digitalnerven. Archiv f. Anat. u. Entwicklungsg. Jahrg. 1884.

CHAPTER, XVII.

THE ORGANS OF THE INTERMEDIATE LAYER OR
MESENCHYME.

THE grounds which made it appear necessary to distinguish in
addition to the four epithelial germ-layers a special intermediate
layer or mesenchyme have already been given in the first part of
this text- book. This distinction -is also warranted by the further
progress of development. For all the various tissues and organs
which are derived in many ways from the intermediate layer allow,
even subsequently, a recognition of their close relationship. Histo-
logically the various kinds of connective substance have been for a
long time considered as constituting a single family of tissues.

It will be my endeavor to emphasise the relationship of the
organs of the intermediate layer, and whatever is characteristic of
them from a morphological point of view, more than has been
hitherto customary in text-books, and to do the same in a formal

THE ORGANS OF THE INTERMEDIATE LAYER OR MESENCHYME. 539

way by embracing these organs in a chapter by themselves and
discussing them apart from the organs of the inner, middle, and
outer germ-layers.

It is the original province of the intermediate layer to form a
packing and sustentative substance between the epithelial layers, a
fact which stands out with the greatest distinctness particularly in
the lower groups, as for example in the Ccelenterates. It is there-
fore closely dependent upon the epithelial layers in the matter of its
distribution. When the germ-layers are raised up into folds, it
penetrates between the layers of the fold as a sustentative lamella ;
when the germ-layers are folded inwards, it receives the parts that
are being differentiated — as for example in the Vertebrates, the neural
tube, the masses of the transversely striped muscles, the secretory
parenchyma of glands, the optic cups, and the auditory vesicles —
and provides them with a special envelopment that adjusts itself
to them (the membranes of the brain, the psrimysium, and the
connective- tissue substance of the glands). In consequence of this
the intermediate layer, in the same proportion as the germ-layers
become more fully organised, becomes itself converted into an extra-
ordinarily complicated framework, and resolved into the most diver-
gent organs, by the formation of evaginations and invaginations
and the constricting off of parts.

The form of the intermediate layer thus produced is of a second-
ary nature, for it is dependent upon the metamorphosis of the germ-
layers, with which it is most intimately connected. But in addition,
the intermediate layer, owing to its own great power of metamor-
phosis, acquires in all higher organisms, particularly in the Verte-
brates, an intricate structure, especially in the ivay of histological
differentiation or metamorphosis. In this way it gives rise to a
long series of various organs — the cartilaginous and bony skeletal
parts, the fasciae, aponeuroses, and tendons, the blcod-vessels and
lymphatic glands, etc.

It is therefore fitting to enter here somewhat more particularly
upon a discussion of the principle of histological differentiation, and
especially to inquire in what manner it is concerned in the origin of
organs differentiated in the mesenchyme.

The most primitive and simplest form of mesenchyme is gelatinous [,
tissue. Not only does it predominate in the lower groups of animals,
but it is also the first to be developed in all Vertebrates, out of the em-
bryonic cells of the intermediate layer, and is here the forerunner and
the foundation of all the remaining forms of sustentative substance.

540 EMBRYOLOGY.

In a homogeneous, soft, quite transparent matrix, which chemically
considered contains mucous substance or mucin, and therefore does
not swell in warm water or acetic acid, there lie at short and regular
intervals from one another numerous cells, which send out in all
directions abundantly branched protoplasmic processes and by means
of these are joined to each other in a network.

In the lower Vertebrates the gelatinous tissue persists at many
places, even when the animals are fully grown ; in Man and other
Mammals it early disappears, being converted into two higher forms
of connective substance,' either mtofibrillar connective tissue or into
cartilaginous tissue. The first-named arises in the gelatinous matrix
by the differentiation of connective-tissue fibres on the part of the
cells; which are sometimes close together, sometimes widely scattered.
These fibres consist of collagen and upon boiling produce glue.
At first sparsely represented, these glue-producing fibres continually
increase in volume in older animals. Thus transitional forms, which
are designated as foetal or immature connective tissue, lead from
gelatinous tissue to mature connective tissue, which consists almost
exclusively of fibres and the cells which have produced them. This
is capable of a great variety of uses in the organism, according as its
fibres cross one another in various directions without order, or are
arranged parallel to one another and grouped into special cords and
strands. Thus, in connection with other parts derived from the germ-
layers, it gives rise to a great variety of organs. In some places
it forms the foundation for epithelial layers of great superficial
extent ; together with them it produces the integument, composed
of epidermis, corium, and subcutaneous connective tissue, and the
various mucous and serous membranes ; in others it unites with
masses of transversely striped muscle, and arranges itself under
the influence of their traction into parallel bundles of tense fibres,
furnishing tendons and aponeuroses. Again at other places it
takes the form of firm sheets of connective tissue, which serve for
the separation or enveloping of masses of muscle, the intermuscular
ligaments and the fascise of muscles.

The second metamorphic product of the primary mesenchyme,
cartilage, is developed in the following manner : At certain places
the embryonic gelatinous tissue acquires as a result of proliferation a
greater number of cells, and the cells secrete between them a carti-
laginous matrix, chondrin. The parts which have resulted from
the process of chondrification exceed in rigidity to a considerable
extent the remaining kinds of sustentative substance, the gelatinous

THE ORGANS OF THE INTERMEDIATE LAYER OR MESENCHYME. 54)

and the glue-producing intermediate tissue; they are sharply
differentiated from their softer surroundings, and become adapted,
in consequence of their peculiar physical properties, to the as-
sumption of special functions. Cartilage serves in part to keep
canals open (cartilage of the larynx and bronchial tree),, in part
for the protection of vital organs, around which they form a firm
envelope (cartilaginous cranium, capsule of the labyrinth, vertebral
canal, etc.), and in part for the support of structures projecting from
the surface of the body (cartilage of the limbs, branchial rays, etc.).
At the same time they afford firm points of attachment for the
masses of muscle imbedded in the mesenchyme, neighboring parts
of the muscles entering into firm union with them. In this manner
there has arisen through histological metamorphosis a differentiated
skeletal apparatus, which increases in complication in the same
proportion as it acquires more manifold relations with the muscu-
lature.

Cartilaginous and connective tissues, finally, are capable of a
further histological metamorphosis, since the last form of sustenta-
tive substance, osseous tissue, is developed from them in connection
with the secretion of salts of lime. T/tere are therefore bones that
have arisen from a cartilaginous matrix and others from one of con-
nective tissue. With the appearance of bone, the skeletal apparatus
of Vertebrates has reached its highest perfection.

Even if the mesenchyme has by these processes experienced an
extraordinarily high degree of differentiation and a great diversity
of form3 the histological processes of differentiation which take place
in it are nevertheless not yet exhausted. In the gelatinous or
connective -tissue matrix canals and spaces arise in which blood and
lymph move in accomplishing their function of intermediating in
the metastasis of the organism, not only conveying the nutritive
fluids to the individual organs, but also conducting away both the
substances which — owing to the chemical processes in the tissues
— have become useless and the superfluous fluids. Out of these
first beginnings arises a very complicated organic apparatus. The
larger cavities constitute arteries and veins, and acquire peculiarly
constructed thick walls, provided with non-striate muscle-cells
and elastic fibres, in which three different layers can be dis-
tinguished as tunica intima, media, and adventitia. A small part
of the blood-passages, especially distinguished by an abundance of
muscle-cells, is converted into a propulsive apparatus for the fluid
— the heart. The elementary corpuscles that circulate in the

542 EMBRYOLOGY.

currents of the fluid, the blood-cells and lymph-cells, demand
renewal the more frequently the more complex the metastasis
becomes. This leads to the formation of special breeding places, as
it were, for the lymph-corpuscles. In the course of the lymphatic
vessels and spaces there takes place at certain points in the con-
nective tissue an especially active proliferation of cells. The
substance of the connective-tissue framework assumes here the
special modification of reticular or adenoid tissue. The surplus of
cells produced enters into the lymphatic current as it sweeps past.
According as these lymphoid organs exhibit a simple or a complicated
structure, they are distinguished as solitary or aggregated follicles, as
lymphatic ganglia and spleen.

Finally there are formed at very many places in the intermediate
foyer, as especially in the whole course of the intestinal canal,
organic [non-striate] muscles.

After this brief survey of the processes of differentiation in the
intermediate layer, which are primarily of an histological nature, I
turn to the special history of the development of the organs which
arise from it, the blood-vessel and skeletal systems.

I. The Development of the Blood-vessel System.

The very first fundament of the blood-vessels and the blood has
already been treated of in the first part of this text-book. We will
therefore here concern ourselves with the special conditions of the
vascular system, with the origin of the heart and chief blood-vessels,
and with the special forms which the circulation presents in the
various stages of development, and which are dependent on the
formation of the foetal membranes. In this I shall treat separately,
both for the heart and for the rest of the vascular system, the first
fundamental processes of development and the succeeding altera-
tions, from which the ultimate condition is finally evolved.

A. The first Developmental Conditions of the Vascular System,
(a) Of the Heart.

The vascular system of Vertebrates can be referred back to a very
simple fundamental form — namely, to two blood-vessel trunks — of
which the one runs above and the other below the intestine in the
direction of the longitudinal axis of the body. The dorsal trunk, the

THE ORGANS OF THE INTERMEDIATE LAYER OR MESENCHYME. 543

aorta, lies in the attachment of the dorsal mesentery, by means of
which the intestine is connected to the vertebral column ; the other
trunk, on the contrary, is imbedded in the ventral mesentery, as far,
at least, as such a structure is ever established in the Vertebrates ; it
is almost completely metamorphosed into the heart. The latter is
therefore nothing else than a peculiarly developed part of a main
blood-vessel provided with especially strong muscular walls.

In the first fundament of the heart there are two different types
to be distinguished, one of which is present in Selachians, Ganoids,
Amphibia, and Cyclostomes. the other in Bony Fishes and the higher
Vertebrates — Reptiles. Birds, and Mammals.

In the description of the first type I select as an example the

Tig. 297.— Cross section through the region of the heart of an embryo of Salamandra maculosa,

in which the fourth visceral arch is indicated, after RABL.
d, Epithelium of the intestine ; vm, visceral middle layer; ep, epidermis; Ih, anterior part of

the body-cavity (pericardio-thoracic cavity) ; end, endocardium ; p, pericardium ; vhff, meso-

cardium anterius.

development of the heart in the Amphibia, concerning which a
detailed account has very recently been published by HABL.

In Amphibia the heart is established very far forward in the
embryonic body, underneath the pharynx or cavity of the head-gut
(figs. 297, 298). The embryonic body-cavity (IK) reaches into this
region, and in cross sections appears upon both sides of the median
plane as a narrow fissure. The lateral halves of the body-cavity are
separated from each other by a ventral mesentery (vhg), by means
of which the under surface of the pharynx is united with the wall
of the body. If we examine the ventral mesentery more closely, we
observe that in its middle the two mesodermic layers from which it
has been developed separate from each other and allow a small
<zavity (h) to appear, the primitive cardiac cavity. This is sur-

544

EMBRYOLOGY.

rounded by a single layer of cells, which is afterwards developed
into the endocardium (end).* Outside of the latter the adjacent
cells of the middle germ-layer are thickened; they furnish the
material out of which the cardiac musculature (the myocardium) and
the superficial membrane of the heart (pericardium viscerale) arise.
The fundament of the heart is attached above [dorsally] to the
pharynx (d) and below to the body-wall by the remnant of the
mesentery, which persists as a thin membrane. We designate these
two parts as the suspensory ligaments of the heart, as back [dorsal]
and front [ventral] cardiac mesenteries (hhg, vhg), or as mesocardium
posterius and anterius. At this time there is nothing to be seen of
a pericardial sac, unless we should designate as such the anterior

[ventral] region of the body-
cavity, from which, as the
further course of development
will show, the pericardium is
chiefly derived.

In the second type the heart
arises from distinct and widely
separated halves, as the con-
ditions in the Chick and the
Rabbit most distinctly teach.

In the Chick the first traces
of the fundament may be de-
monstrated at an early period,
in embryos with four to six
primitive segments. They
appear here at a time when
the various germ-layers are still spread out flat, at a time when the
front part of the embryonic fundament first begins to be elevated as
the small cephalic protuberance, and the cephalic portion of the intes-
tine is still in the first phases of development. As has already been
stated, the intestinal cavity in the Chick is developed by the folding
together and fusion of the intestinal plates [splanchnopleure]. If
one examines carefully the ridge of an intestinal fold in the very
process of being formed (fig. 299 A df), one observes that its visceral
middle layer is somewhat thickened, composed of large cells, and
separated from the entoblast by a space filled with a jelly-like matrix.
In the latter there lie a few isolated cells, which subsequently

* Relative to the origin of the endothelial sac of the heart, compare the>
observations given on page 186.

ep

Fig. 298. — Cross section from the same series as
that from which fig. 297 was drawn, after
BABL.

d, Epithelium of the intestine ; vm, visceral, pin,
parietal middle layer ; hhg, posterior, vhg,
anterior mesocardium ; end, endocardium ;
h, cavity of the heart ; Ih, ventral part of the
body-cavity ; ep, epidermis.

THE ORGANS OF THE INTERMEDIATE LAYER OR MESENCHYME. 545

ch

Fig. 299.— Three diagrams to
illustrate the formation of
the heart in the Chick.

n, Neural tube ; JH, mesen-
chyma of the head ; d, in-
testinal cavity; df, folds
of the intestinal plate
[splanchnopleure], in which
the endothelial sacs of the
heart are established ; h, en-
dotheliai sac of the heart ;
ch, chorda ; Ih, body-
cavity ; a*-, outer, ik, inner
germ-layer ; ink1, parietal
middle layer ; mk1, visceral
middle layer, fron\ the
thickened portion of which
the musculature of the
heart is developed ; dn, in-
testinal suture, in which
the two intestinal folds are
fused ; db, part of the ento-
blast which has become de-
tached from the epithelium
of the cephalic portion of
the intestine at the intes-
tinal, suture and lies on
the yolk ; + dorsal meso-
cardium ; * ventral nieso-
cardium.

A, The youngest stage shows
the infolding of the splanch-
nopleure, by means of which
the cephalic part of the in-
testine is formed. In the
angles of the intestinal folds
the two endothelial sacs of
the heart have been esta-
blished between the inner
germ-layer and the visceral
middle layer.

£, Somewhat older stage.
The two folds (A df) have
met in the intestinal suture
(dn), so that the two endo-
thelial sacs of the hear!
lie close together in the
median plane below the
head-gut.

C, Oldest stage. The part of
the entoblast which lines
the head-gut (d) has become
separated at the intestinal
suture (1? dn) from the re-
maining part of the ento-
blast, which (db) lies upon

the yolk, so that the two eudothelial sacs of the heart are in contact ; they subsequently fuse.
They lie in a cardiac suspensorium formed by the visceral middle layers, the mesocardium, on
which one can distinguish an upper [dorsal] and an under part— mesocardium superius(+)and
inferius (*). By means of this mesocardium the primitive body-cavity is temporarily dirided
into two portions.

mfhdn

h db h mk* Ih

35

546 EMBRYOLOGY.

surround a small cavity, the primitive cardiac cavity (h). These cells
assume more of an endothelial character. While the intestinal folds
grow toward each other, the two endothelial tubes become enlarged
and push the thickened part of the visceral middle layer before them,
so that the latter forms a low, ridge-like elevation into the primitive
body-cavity. In the embryos of higher Vertebrates also, just as in
the Amphibia, this stretches forward into the embryonic fundament
as far as the last visceral arch, and has here received the special name
of neck-cavity or parietal cavity.

In older embryos (fig. 299 B) the edges of the two folds have met
in the median plane, and consequently the two cardiac tubes have
moved close together. A process of fusion then takes place between
the corresponding parts of the two intestinal folds.

First the entoblastic layers fuse, and in this way is produced
(fig. 299 J3) beneath the chorda dorsalis (ch) the cavity of the head-gut
(d), which then detaches itself from the remaining part of the ento
blast (fig. 299 C db) ; the latter is left lying on the yolk and becomes
the yolk-sac. Under the cavity of the head-gut the two cardiac
sacs have come close together, so that their cavities are separated
from each other by their own endothelial walls only. By the break-
ing through of these there soon arises from them (h) a single cardiac
tube. On the side toward the body-cavity this is covered by the
visceral middle layer (mk2), the cells of which are distinguished in
the region of the fundament of the heart by their great length and
furnish the material for the cardiac musculature, while the inner
endothelial membrane becomes only the endocardium.

The whole fundament of the heart lies, as in the Amphibia, in a
ventral mesentery, the upper [dorsal] part of which, extending from
the heart to the head-gut (fig. 299 G + ), can here also be called the
dorsal suspensory of the heart or mesocardium posterius, and the
lower [ventral] part (*) mesocardium anterius. In the Chick, when
the cardiac tube begins to be elongated and bent into an S- shaped
form, the mesocardium anterius quickly disappears.

Similar conditions are furnished by cross sections through Rabbit
embryos 8 or 9 days old. In the latter the paired fundaments of the
heart are indeed developed still earlier and more distinctly than in the
Chick, even at a time when the entoderm is still spread out flat and
has not yet begun to be infolded. Upon cross sections one sees
(fig. 301), in a small region at some distance from the median plane,
the splanchnopleure separated from the somatopleure by a small
fissure (ph), which is the front end of the primitive body-cavity. At

THE ORGANS OP THE INTERMEDIATE LAYER OR MESEN7CHYME. 547

this place the visceral middle layer (ahli) is also raised up somewhat
from the entoderm (sw), so that it causes a projection into the body-
cavity (pti). Here there is developed between the two layers a small
cavity, which is surrounded by an endothelial membrane (ihh), the
primitive cardiac sac. At their first appearance the halves of the
heart lie very far apart. They are to be seen both in the very
slightly magnified cross section (fig. 300) and also in the surface view
of an embryo Rabbit (fig. 302) at the place indicated by h. They

Fig. 301.

Figs. 300, 301.— Cross section through the head of an embryo Raboit of the same age as that
shown in fig. 302. From KOLLIKER. Fig. 301 is a part of fig. 300 more highly magnified.

Fig. 300.— A, h', Fundaments of the heart ; sr, cesophageal groove.

Fig. 301.— rf, Dorsal groove ; mp, medullary plate ; rw, medullary ridge ; h, outer germ-layer ;

' dd, inner germ-layer; dd', its chordal thickening ; sp, undivided middle layer; hp, parietal,

dfp, visceral middle layer ; ph, pericardial part of the body-cavity ; ahh, muscular wall of

the heart ; ihh, endothelial layer of the heart ; mes, lateral undivided part of the middle

layer ; sw, intestinal fold, from which the ventral wall of the pharynx is formed.

afterwards move toward each other in the same manner as in the
Chick by the infolding of the splanchnopleure, and come to lie on
the under side of the head-gut, where they fuse and are temporarily
attached above and below by means of a dorsal and ventral mesentery.
Concerning the processes of development just sketched the question
may be raised : What relation do the paired and the unpaired funda-
ments of the heart sustain to each other 1 It is to be answered to
this, that the unpaired fundament of the heart, which is present in the
lower Vertebrates, is to be regarded as the original form. The double

548

EMBRYOLOGY.

al

heart-formation, however aberrant it at first sight appears, can be

easily referred back to this.

A single cardiac tube cannot be developed in the higher

Vertebrates, because at the
time of its formation a head-
gut does not yet exist, but
only the fundament of it is
formed in the still flat ento-
derm. The parts which will
subsequently form the ventral
wall of the head-gut, and in
which the heart is developed,
are still two separated terri-
tories; they still lie at some
distance from the median
plane at the right and at
the left. If therefore it is
necessary for the heart to be
formed at this early period,
it must arise in the separated
regions, which by the process
of infolding are joined into
a single ventral tract. The
vessel must arise as two parts,
which, like the two intestinal
folds, subsequently fuse.

Whether the heart is formed
in one way or the other, in
either case it has for a time
the form of a straight sac
lying ventral to the head -gut
and composed of two tubes one
within the other, which are
separated by a large space
assumably filled with a gela-
tinous matrix. The inner,
endothelial tube becomes the
endocardium ; the outer tube,

which is derived from the visceral middle layer, furnishes the

foundation for the myocardium and the pericardial membrane that

immediately invests the surface of the heart.

Fig. 302. — Embryo Rabbit of the ninth day, seen
from the dorsal side, after KOLLIKER. Mag-
nified 21 diameters.

The axial (stem-) zone (stz) and the parietal zone
(pz) are to be distinguished. In the former 8
pairs of primitive segments have been formed
at the side of the chorda and neural tube.

ap, Area pellucida ; rf, dorsal groove ; vh, fore
brain ; ab, optic vesicle ; mh, mid -brain ; hh,
hind-brain ; me, primitive segment ; stz, axial
zone ; pz, parietal zone ; h, heart ; ph, pericar-
dial part of the body-cavity ; vd, margin of the
anterior intestinal portal showing through the
overlying structures ; af, fold of the anmion ;
vo, tena omphalomesenterica.

THE ORGANS OF THE INTERMEDIATE LAYER OR MESENCHYME. 549

(b) The First Developmental Conditions of the Large Vessels. Vitelline
Circulation, Allantoic and Placental Circulation.

At both ends, in front and behind, the heart is continuous with
the trunks of blood-vessels, which have been established at the same
time with it. The anterior or arterial end of the cardiac tube is
elongated into an unpaired vessel, the truncus arteriosus, which con-
tinues the forward course under the head-gut, and is divided in the
region of the first visceral arch into two arms, which embrace the
head-gut on the right and left and ascend within the arch to the
dorsal surface of the embryo. Here they bend around and run back-
ward in the longitudinal axis of the body to the tail-end. These
two vessels are the primitive aortce (figs. 107, 116 ao); they take
their course on either side of the chorda dorsalis, above the entoderm
and below the primitive segments. They give off lateral branches,
among which the arterice omphalomesentericce are in the Amniota
distinguished by their great size. These betake themselves to the
yolk-sac and conduct the greatest portion of the blood from the two
primitive aortae into the area vasculosa, where it goes through the
vitelline circulation.

In the Chick, the conditions of which form the basis of the following
account (fig. 303), the two vitelline arteries (R.Of.A, L.Of.A) quit
tha aortse at some distance from their tail-ends, and pass out laterally
from the embryonic fundament between entoderm and visceral middle
layer into the area pellucida, traverse the latter, and distribute them-
selves in the vascular area. They are here resolved into a fine net-
work of vessels, which lie, as a cross section (fig. 116) shows, in the
mesenchyme between the entoderm and the visceral middle layer,
and which are sharply bounded at their outer edge (toward the
vitelline area) by a large marginal vessel (fig. 303 /S.T), the sinus ter-
minalis. The latter forms a ring which is everywhere closed, with
the exception of a small region which lies in front, at the place
where the anterior amniotic sheath has been developed.

From the vascular area the blood is collected into several large
Venous trunks, by means of which it is conducted back to the heart.
From the front part of the marginal sinus it returns in the two
vence vitellince anteriores, which run in a straight line from in
front backwards and also receive lateral branches from the vascular
network. From the hind part of the sinus terminalis the blood is
taken up by the venae vitellinse posteriores, of which the one of the
left side is larger than the one of the right ; the latter afterwards

550

EMBRYOLOGY.

degenerates more and more. From the sides likewise there come
still larger collecting vessels, the venae vitellinse laterales. All
the vitelline veins of either side now unite in the middle of the
embryonic body to form a single large trunk, the vena omphalo-

Vitelline area.

Vitelline area.

HO/.A

sx.

Fig. 303.— Diagram of the vascular system of the yolk-sac at the end of the third day of
incubation, after BALFOUR.

The whole blastoderm has been removed from the egg and is represented as seen from below.
Hence what is really at the right appears at the left, and vice versd. The part of the area
opaca in which the close vascular network has been formed is sharply terminated at its
periphery by the sinus terminalis, and forms the vascular area ; outside of the latter lies the
vitelline area. The immediate neighborhood of the embryo is free from a vascular net-
work, and now, as previously, is distinguished by the name area pellucida.

H, Heart; A A, aortic .arches ; Ao, dorsal aorta; L.Of.A, left, R.Of.A, right vitelline artery;
S.T, sinus terminalis ; L.Of, left, R.Of, right vitelline vein ; S. V, sinus venosus ; D.C, ductus
Cuvieri ; S.Ca.V, superior, V.Ca, inferior cardinal vein. The veins are left in outline;
the arteries are black.

mesenterica (R.Ofsmd L.Of), which enters the posterior end of the
heart (H).

The motion of the blood begins to be visible in the case of the
Chick as early as the second day of incubation. At this time
the blood is still a clear fluid, which contains only few formed

THE ORGANS OF THE INTERMEDIATE LAYER OR MESENCHYME. 551

components. For the most of the blood-corpuscles still continue to
lie in groups on the walls of the tubes, where they constitute the
previously described blood-islands (fig. 114), which cause the red-
besprinkled appearance of the vascular area. The contractions of
the heart, by which the blood is set in motion, are at first slow and
then become more and more rapid. On the average, according to
PREYER, the strokes then amount to 130 — 150 per minute. How-
ever, the frequency of pulsations is largely dependent upon external
influences; it increases with the elevation of the temperature of
incubation and diminishes at every depression of it, as well as when
the egg is opened for study. At the time when the heart begins to
pulsate, no muscle-fibrillse have been demonstrated in the myocar-
dium ; from this results the interesting fact that purely proto-
plasmic, still undifferentiated cells are in a condition to make strong
rhythmical contractions.

At the end of the third or fourth day the vitelline circulation
in the Chick is at its highest development ; it has undergone some
slight changes. We find instead of a single vascular network a
double one, an arterial and a venous. The arterial network, which
receives the blood from the vitelline arteries, lies deeper, nearer to the
yolk, while the venous spreads itself out above the former and is
adjacent to the visceral middle layer. The circulating blood is
distinguished by the abundance of its blood-corpuscles, the blood-
islands having entirely disappeared.

The function of the vitelline circulation is twofold. First it serves
to provide the blood with oxygen, opportunity for acquiring which
is afforded by the whole vascular network being spread out
at the surface of the egg. Secondly it serves to bring nutritive
substances to the embryo. The yolk-elements below the entoblast
are disassociated, liquefied, and taken up into the blood-vessels, by
which they are carried to the embryo, where they serve as nutrition
for the rapidly dividing cells. Thus far the embryonic body
increases in size at the expense of the yolk-material in the yolk-
sac, which becomes liquefied and absorbed.

The system of vitelline blood-vessels in Mammals agrees in general
with that of the Chick, and is distinguished from the latter only in
some unimportant points, which do not need to be discussed. How-
ever, this question certainly arises • What signification has a
vitelline circulation in Mammals (fig. 134 ds) in which the egg is
furnished with only a small amount of yolk-material ?

Two things are here to be kept in mind ; first, that the eggs of

552 EMBRYOLOGY.

Mammals were originally provided with abundant yolk-material, like
those of Reptiles (compare p. 222), and, secondly, that the blasto-
dermic vesicle, which arises after the process of cleavage, becomes
greatly distended by the accumulation within it of a fluid very rich
in albumen, furnished by the walls of the uterus. Out of this vesicle
likewise the vitelline blood-vessels undoubtedly take up nutritive
material and convey it to the embryo, until a more ample nutrition
is provided by means of the placenta.

In addition to the vitelline blood-vessels there aiises in the higher
Vertebrates a second system of vessels, which is distributed in the
foetal membranes outside the embryo and for a time is more developed
than the remaining vessels of the embryo. It serves for the
allantoic circulation of Birds and Reptiles and the placental circu-
lation of Mammals.

When in the Chick the allantois (PL I., fig. 5 al) is evaginated
from the front [ventral] wall of the hind-gut, and as an ever
increasing sac soon grows out of the body-cavity through the dermal
umbilicus into the co3lom of the blastodermic vesicle between the
serosa and the yolk-sac, there appear in its walls two blood-vessels,
which grow forth from the ends of the two primitive aortse — the
umbilical vessels, or arterice umbilicales. The blood is again collected
from the fine capillary network, into which these vessels have been
resolved, into the two umbilical veins (venae umbilicales), which,
after having arrived at the navel, pass on to the two Cuvierian
ducts (see p. 577) and pour their blood into these near the entrance
of the latter into the sinus venosus. The terminal part of the
right vein soon atrophies, whereas the left receives the lateral
branches of the right side and is correspondingly developed into a
larger trunk. This now also loses its original connection with the
ductus Cuvieri, since it effects with the left hepatic vein (vena
hepatica revehens) an anastomosis, which continually becomes larger
and finally carries the whole stream of blood. Together with the left
hepatic vein the left umbilical vein then empties directly into the
sinus venosus at the posterior margin of the liver (HOCHSTETTER).

The umbilical and vitelline veins undergo opposite changes in
calibre during development : while the vitelline circulation is well
developed, the umbilical veins are inconspicuous stems ; afterwards,
however, with the increase in the size of the allantois they enlarge,
whereas the venae omphalomesentericse undergo degeneration and in
the same proportion as the yolk-sac by the absorption of the yolk
becomes smaller and loses in significance.

THU ORGANS OF THE INTERMEDIATE LAYER OR MESENCHYME. 553

So far as regards the purpose of the umbilical circulation, it
subserves in Reptiles and Birds the function of respiration. For the
allantois, when it has become larger, in the Chick for example,
applies itself closely to the serosa and spreads itself out in the
vicinity of the air-chamber and underneath the shell, so that the
blood circulating in it can enter into an exchange of gases with the
atmospheric air. It loses its importance for respiration in the egg
only at the moment when the Chick with its beak breaks through
the surrounding embryonic membranes, and breathes directly the air
contained in the air-chamber. For the conditions of the circulation
are now altered throughout the whole body, since witli the begin-
ning of the process of respiration the lungs are in a condition to take
up a greater quantity of blood, resulting in a degeneration of the
umbilical vessels (compare also p. 584).

The umbilical or placental circulation in Mammals (fig. 139 A I)
plays a still more important role ; for here the two umbilical
arteries convey the blood to the placenta. After the blood has
been laden in this organ with oxygen and nutritive substances, it
flows back again to the heart, at first through two, afterwards
through a single umbilical vtin (p. 584).

B. The further Development of the Vascular System up to the
Mature Condition.

(a] The Metamorphosis of the Tubular Heart into a Heart
with Chambers.

As has been shown in a preceding section, the heart of a Verte-
brate originally has for a short time the form of a straight sac, which
sends off at its anterior end the two primitive aortic arches, while it
receives at its posterior end the two omphalomesenteric veins. The
sac lies far forward immediately behind the head on the ventral side
of the neck (fig. 304 h), in a prolongation of the body-cavity (the
parietal or cervical cavity). It is here attached by means of a
mesentery of only brief duration, which stretches from the alimentary
canal to the ventral wall of the throat, and which is divided by
the cardiac sac itself into an upper [dorsal] and an under part, or
mesocardium posterius and anterius.

During the first period of embryonic development the heart is
distinguished by a very considerable growth, especially in the longi-
tudinal direction ; consequently it soon ceases to find the necessary

554

EMBRYOLOGY.

room for itself as a straight sac, and is therefore compelled to bend
itself into an S-shaped loop (fig. 304). It then takes such a position
in the neck that one of the bends of the S, which receives the
vitelline veins or, let us say briefly, the venous portion, comes to lie
behind and at the left ; the other or arterial portion, which sends
off the aortic arches, in front and at the right (fig. 305).

But this initial position is soon altered (figs. 305, 313) by the two

curves of the S assuming another
relation to each other. The venous
portion moves head wards, the arterial,
on the contrary, in the opposite direc-
tion, until both lie approximately in
the same transverse plane. At the
same time they become turned around
the longitudinal axis of the embryo,
the venous loop moving dorsally, the
arterial, on the contrary, ventrally.
Seen from in front [ventral aspect]
one hides the other, so that it is only
in a side view that the S-shaped cur-
vature of the cardiac sac is distinctly
recognisable.

By the increase in the size of this
viscus the anterior part of the body-
cavity is already greatly distended, and
becomes still more so in later stages,
when there is produced a very thin-walled
elevation, that projects out to a great
distance (figs. 157 h, 314). Inasmuch
as the heart completely fills the cavity,
and is covered in by only the thin,
transparent, and closely applied wall of
the trunk, — the membrana reuniens

inferior of KATHKE, — it appears as though at this time the heart
were located entirely outside of the body of the embryo.

After the completion of the twisting, there is effected a division of
the S-shaped sac into several successive compartments (figs. 306, 308).
The venous portion, which has become broader 5 and the arterial part
are separated from each other by a deep constriction (ok) and can now
be distinguished as atrium (vh) and ventricle, while the constricted
region between the two may be indicated, by a designation introduced

Fig 304.— Head of a Chick incubated
58 hours, seen from the dorsal
face, after MIHALKOVICS. Mag-
nified 40 diameters.

The brain is divided into 4 vesicles :
pvh, primary fore-brain vesicle ;
mh, mid-brain vesicle ; kh, hind-
brain vesicle ; nh, after-brain
vesicle; au, optic vesicle ; h. heart
(seen through the Jast brain-
vesjcle) ; vo, vena omphalomesen-
terica ; us, primitive segment ;
1-wi, spinal cord ; x, anterior walj
of brain, which is evaginated to
form the cerebrum.

THE ORGANS OF THE INTERMEDIATE LAYER OR MESENCHYME. 555

by HALLER, as auricular canal (ok). The atrium thereby acquires a
striking form, since its two lateral walls develop large out-pocketings
(ho), the auricles of the heart (auriculae cordis) ; the free edges of
the latter, which in addition soon acquire notches, are turned for-
ward, and subsequently enfold more and more the arterial part of the
heart, the truncus arteriosus (Ta), and a part of the surface of the
ventricle.

The auricular canal (fig. 308 ok) is in embryos a well -distinguished
narrowed place in the cardiac tube. Owing to the great flattening
of its endothelial tube in the sagittal direction, — its walls almost

Fig. 306.

Fig. 305. — Heart of a human embryo, the body of which was 2'15 mm. long (embryo Lg), after

His. [Compare fig. 313.]
K, Ventricle ; Ta, truncus arteriosua ; V, venous end of the S-shapei cardiac sac.

Fig. 306.— Heart of a human embryo that was 43 mm. long, neck measurement (embryo SI),

after His.
£, Ventricle ; Ta, truncus arteriosus ; ok, canalis auricularis ; vh, atrium with the heart-auricles

ho (auriculae cordis).

coming into contact, — the passage between atrium and -ventricle is
reduced to a narrow transverse fissure. It is here that the atrio-
ventricular valves are afterwards developed.

The fundament of the ventricle at first presents the form of a
curved tube (figs. 305, 306 k), which however soon changes its form.
For at a very early period there is observable on its anterior [ventral]
and posterior surfaces a shallow furrow running from above down-
ward, the sulcus interventricularis (fig. 307 si), which allows a left
and a right half of the ventricle to be distinguished externally. The
latter is the narrower, and is continued upward into the truncus
arteriosus (Ta), the beginning of which is somewhat enlarged and

556

EMBRYOLOGY.

designated as bulbus. Between bulbus and ventricle lies a place
that is only slightly constricted, called the fretuni Halleri ; it was
recognised even by the older anatomists, then remained for a time
little regarded, and now has been again described as noteworthy by
His. For it marks the place at which subsequently the semilunar
valves are established.

During the externally visible changes of form, some alterations
are also progressing in the finer structure of the walls of the heart.
As previously remarked, the fundament of the heart consists in the
beginning of two sacs, one within the other — an inner endothelial
tube lined with flat cells, and an outer muscular sac consisting of cells

with abundant protoplasm
and derived from the
middle germ-layer. The
two are completely sepa-
rated from each other by
a considerable space, which
is probably filled with gela-
tinous substance.

The endothelial tube is in
general a tolerably faithful
copy of the muscular sac,
yet the narrower and wider
regions are more sharply
marked off from one an-
other in the former than
in the latter • "as regards
its form, it sustains such a
relation to the whole heart

as it would if it were a greatly shrivelled, internal cast of it " (His).
In the muscular sac distinct traces of muscle-fibres can be recog-
nised even at the time when the S-shaped curvature makes its
appearance. At later stages in the development differences appear
between atrium and ventricle. In the atrium the muscular wall is
uniformly thickened into a compact plate, with the inside of which the
endothelial tube is in immediate contact. In the ventricle, on the
contrary, there occurs a loosening, as it were, of the muscular wall.
There are formed numerous small trabeculse of muscular cells, which
project into the previously mentioned space between the two sacs and
become united to one another, forming a large-meshed network (fig.
311-4). The endothelial tube of the heart, by forming out-pocketings,

Fig. 307.— Heart of a human embryo of the fifth week,

after His.
rk, Right, Ik, left ventricle ; si, sulcus interventricu-

laris ; Ta, truncus a'rteriosus ; Iho, left, rho, right

auricle of the heart.

THE ORGANS OF THE INTERMEDIATE LAYER OR MESENCHYME. 557

soon comes into intimate contact with the trabeculae, and envelops
each one of them with a special covering (His). Thus there arise
in the spongy wall of the ventricle numerous spaces lined with
endothelium, which toward the surface of the heart end blindly, but
which communicate with the central cavity and like this receive into
them the stream of blood.

The embryonic heart of Man and Mammals resembles in its first
condition — that which has been described up to this point — the heart
of the lowest Vertebrates, the Fishes. In the former as in the
latter it consists of a region, the atrium, which receives the venous
blood from the body, and of another, the ventricle, which drives the
blood into the arterial vessels. Corresponding to this condition of
the heart, the whole circulation in embryos of this stage and in Fishes
is still a simple and a single one. This becomes changed in the
evolution of Vertebrates, as in the embryonic life of the individual,
with the development "of the lungs, upon the appearance of which a
doubling of the heart and of the blood-circulation is introduced.

The cause of such a change is clear, from the topographical relation
of the two lungs to the heart, the former arising in the immediate
vicinity of the heart by evagination of the fore-gut (fig. 314 Ig).
The lungs therefore receive their blood from an arterial stem lying
very near the heart, from the fifth [sixth] pair of aortic arches that
arise from the truncus arteriosus. Similarly they give back again the
venous pulmonary blood directly to the heart through short stems,
the pulmonary veins, which, originally united into a single collecting
trunk (BoRN, ROSE), open into the atrium at the left of the great
venous trunks. Therefore the blood that flows directly out of the heart
into the lungs also floivs directly back again to the heart. Herein is
furnished the prerequisite for a double circulation. This comes into
existence when the pulmonary and the body currents are separated from
each other l)y means of partitions throughout the short course of the
vascular system which both traverse in common (viz., atrium, ventricle,
and truncus arteriosus).

The process of separation begins in the vertebrate phylum with the
Dipnoi and Amphibia, in which pulmonary respiration appears for
the first time and supplants bronchial respiration. In the amniotic
Vertebrates it is accomplished during their embryonic development.
Therefore we now have to follow out further the manner in which,
in the case of Mammals and especially of Man, according to the
recent investigations of His, BORN, and ROSE, the partitions are
formed — how atrium and ventricle are each divided into right and

558

EMBRYOLOGY.

left compartments, and the truncus arteriosus into arteria pul-
morialis and aorta, and how in this way the heart attains its definite
form.

The partitions arise independently in each of the three divisions
of the heart mentioned.

Let us first take into consideration the atrium, which is for a
time the largest and most capacious region of the cardiac sac
(fig. 308). In Man a separation into left and right halves (Iv and rv)
is observable even in the fourth week, since there is then formed

on its hinder [dorsal] and
upper wall a perpendicular
projection inward, the first
trace of the atrial partition
(vs) or septum atriorum.

The halves are even now
distinguished by the fact
that they receive different
venous trunks. The vitel-
line and umbilical veins,
as well as the Cuvierian
ducts to be discussed later,
empty their blood into the
right compartment, not
directly, however, and by
means of separate orifices,
but after they have united
with one another in the
vicinity of the heart to
form a large venous sinus
(sr} — the sinus venosus or
s. reunions. This is imme-
diately adjacent to the atrium and communicates with it by means
of a large opening in its posterior [dorsal] wall, which is flanked on
the right and on the left by a large venous valve (*). Only one
small vessel, which traverses the musculature of the heart obliquely,
opens, near the atrial partition, into the left compartment ; it is
the previously mentioned unpaired pulmonary vein, which is formed
immediately outside the atrium by the union of four branches, two
of which come from each of the two wings of the lung now being
established.

In the further course of development the atrial partition grows

Fig. 308. — Heart of a human embryo 10 mm. long,
neck measurement ; posterior [dorsal] half of the
heart, the front walls of -which have been removed.
After H:s.

i«, Partition of the ventricle ; Ik, left, rk, right ven-
tricle ; ok, auricular canal ; Iv, left, rv, right
atrium ; sr, mouth of the sinus reunions ; vs, par-
tition of the atrium (atrial crescent, His ; septum
primuin, BORN) ; * Eustachian valve ; Ps septum
spuxium *

THE ORGANS OF THE INTERMEDIATE LAYER OR MESENCHYME. 559

from above downward until it reaches the middle of the atrial canal
(fig. 309 si). In this manner two completely separated atria would
have come into existence at a very early period, if there had not
been formed in the upper part of the partition, while it was still
growing downward, an opening, the future foramen ovale, which
maintains a connection between the two chambers (fig. 309) up to
the time of birth. The opening has arisen either from the septum
atriorum having become thin and having broken through at a
certain region, or from its having been incomplete at this place
from the very beginning, as is the case with the Chick for example,
where it is traversed
by numerous small
orifices. Afterwards
the foramen ovale,
adapting itself to
the conditions of the
circulation existing
at the time, becomes
still larger.

The downgrowth
of the atrial parti-
tion has, moreover,
the immediate result
of separating the au-
ricular canal into the
left and right atrio-
ventricular orifices
(compare fig. 308 ok
with fig. 309). The
auricular canal, even

very soon after its formation, undergoes important alterations
both from without and within. At first visible from the out-
side (fig. 308 ok), it afterwards disappears from view (fig. 309)
by being in a manner overgrown on all sides by the ventricle,
and thereby incorporated in its walls, which enlarge upward and,
in consequence of a vigorous growth of the musculature, acquire con-
siderable thickness. The opening of the atrial canal into the ven-
tricle, or the foramen atrioventriculare commune (fig. 310 A JF.av.c),
now has the form of a fissure extending from left to right, which
is bounded on either side by two ridge-like lips (o.ek and u.ek) —
the atrio ventricular lips of LIN DBS, or the endothelial cushions of

Fig. 309.— Postsrior [dorsal] half of the heart of a human
embryo of the fifth week, out open, after His.

ks, Ventricular partition ; Ik, left, rk, right ventricle ; si, lowei
[posterior] part of the atrial partition (septum intermedium,
His) ; Iv, left, rv, right atrium ; sr, mouth of the sinus
reunions ; vs, atrial partition (atrial crescent, His ; septum
secundum, BOBS) ; Ps, septum spurium ; * Eustachian
valve.

560 EMBRYOLOGY.

SCHMIDT. The ridges have arisen from a growth of the endocardium*
and consist of a gelatinous connective substance and an endothelial
investment. The atrial partition, when it has grown down to the
auricular canal, soon fuses along its free lower margin with these
lips (fig. 309 si) ; the auricular canal is thereby divided into a left
and a right atrioventricular opening, — ostium atrioventriculare
sinistrum and dextrum (fig. 310 B F.av.s and F.av.d}, — and at
the same time both the dorsal and ventral endocardial ridges, which
originally bound the opening, are divided in the middle (o.ek and u.ek).
The dorsal components soon fuse with the corresponding pieces of
the opposite [ventral] side, and thus there arise at the lower margin
of the atrial partition (fig. 309 si) two new ridges, — one of which
projects into the left, the other- into the right atrioventricular
opening, — which furnish the foundation of the median cuspidate
valves.

The development of the atrial partition and the division of the
auricular canal into the two atrioventricular openings are closely
related processes, the former being the cause of the latter. This
is clearly proved by pathological -anatomical conditions of arrested
development of the heart. In all cases in which the formation of
the atrial partition has been for any reason whatever interrupted
and the lower part of it has been altogether wanting, there has
always been only one atrioventricular opening (an ostium venosum
commune) present (ARNOLD).

Before we progress further in the history of the development of
the atrium, we must add an account, of the metamorphoses which
have taken place meanwhile in the territory of the ventricle and
truncus arteriosus.

The ventricle begins to acquire its partition not much later than
the atrium. By the end of the first month its musculature has
become considerably thickened (fig. 311 A), Muscular trabeculoe
have arisen, which project far into the interior of the chamber and
are joined to one another, so as to constitute a spongy tissue, the
numerous fissures in which are continuous with the narrowed cavity
of the heart and likewise allow the current of the blood to pas.,
through them. At one place the musculature is especially thickened
and forms a crescent-shaped fold projecting inward, the fundament
of the ventricular partition (septum ventriculorum) (figs. 308, 309,
310 ks). This takes its origin from the lower and posterior [dorsal]
wall of the ventricle, in the region which is marked externally by
the previously mentioned sulcus interventricularis (fig. 307 si). Its

THE ORGANS OF THE INTERMEDIATE LAYER OR MESENCHYME. 561

free edge is directed upwards and grows toward the bulbus arteriosus
and the atrioventricular opening. The latter originally lies more in
the left half of the ventricle (fig. 310 A F.av.c), but it gradually
moves over more to the right, and finally assumes such a position
that the ventricular partition by its growth upwards meets it exactly

Fig. 310. — Two diagrams (after BoRir) to elucidate the changes in the mutual relations of the
ostium atrioventriculare and the ostium interventriculare, as well as the division of the
ventricle and large arteries. The ventricles are imagine 1 to have been divided into halves ;
one looks h to the posterior [dorsal] halves, in which, moreover, the cardiac trabeculse, etc.,
have been ondbted for the sake of simplifying the view.

A, Heart of an embryo Rabbit, in which the head is 3'5— 5-8 mm. long. The ventricle is

divided by the ventricular partition (ks) into a left and a right half as far as the ostium
interveuiriculare (Oi). The right end of the foramen atiloventriculare commune (F.av.c)
extends into the right ventricle ; the endocardial cushions (o.ek, u.ek) are developed.

B, Heart of an embryo Rabbit, head 7'5 mm. long. The endocardial cushions (o.elc, u.ek) of the

foramen atrioventriculare commune are fused, and thereby the for atrioventr. com. is now
separated into a for. a'rioventr. dextrum (F.av.d) and sinistrum (F.av.s). The ventricular
partition (les) has likewise fused with the endocardial cushions, and has grown forward as far
as the partition (s) of the truncus arceriosus. By the closure of the remnant of the ostium
interventriculare (Oi) the septum membi-anaceum is formed.

rk, Right, Ik, left ventricle ; ks, ventricular partition ; Pu, arteria pulmonalis ; Ao, aorta ;
s, partition of the truncus arteriosus ; Oi, ostium interventriculare ; F.av.c, foramen atrio-
ventriculare commune ; F.av.d and F.av.s, foramen atrioventriculare dextrum and sinistrum ;
o.ek, u.ek, upper and lower endobhelial or endocardial cushions.

in the middle and fuses with its edges directly opposite the atrial
partition (figs. 309, 310 B).

The division of the ventricle in Man is completed as early as the
seventh week. From the atrium, the two compartments of which
are united by the foramen ovale, the blood is now conducted through
a right and a left ostium atrioventriculare into completely separated
right and left ventricles.

The two atrioventricular openings are narrow a£ the time of
their origin ; they are in part surrounded by the previously mentioned

36

562 , EMBRYOLOGY.

endocardial ridges that project from the partition, in part by corre-
sponding growths of the endocardium at their lateral circumference.
The membranous projections are comparable with primitive pocket,
valves, such as are also established in the bulbus arteriosus (GEGEN-
BAUR); they constitute the starting-point for the development of
the large atrioventricular valves, but furnish, as GEGENBAUR and
BERNAYS have shown, only a part — the membranous marginal
thickening (mkl) — which subsequently disappears almost completely,
whereas the compact main part of the valve arises from that portion
of the thickened muscular wall of the ventricle itself that surrounds
the atrioventricular opening (fig. 311 B mk\

As was previously stated, in the case of Man the wall of the
ventricle during the first months consists of a close spongy network

Fig. 311.— Diagrammatic representation of the formation of the atrioventricular valves. A , Earlier,

S, later condition. After GEGENBAUR.
mk, Membranous valve ; mkl, the primitive part of the same ; cht, chordae tendineae ; v, cavity

of the ventricle ; b, trabecular network of cardiac musculature ; pm, papillary muscles ;

tc, trabeculae carnese.

of muscular trabeculse, which are invested by the endocardium and
the interstices of which communicate with the small central cavity
(fig. 311 A). Such a spongy condition of the wall of the heart
persists permanently in Fishes and Amphibia ; in the higher Verte-
brates and Man, on the contrary, metamorphoses occur. Toward
its external surface the wall of the heart becomes more compact, in
that the muscular trabeculse become thicker and the spaces between
them narrower, in some parts even disappearing entirely (fig. 311 B
tc). The reverse of this process takes place toward the inside. In
the vicinity of the atrioventricular opening the trabeculse become
thinner and the interstices larger. In this way a part of the thick
wall of the ventricle, which looks toward the atrium and encloses the
opening, is undermined, as it were, by the blood-current. In this
part the muscle-fibres afterwards become entirely rudimentary;

THE ORGANS OF THE INTERMEDIATE LAYER OR MESENCHYME. 563

there are formed from the interstitial connective-tissue substance
tendinous plates, which with the endocardial cushions attached
to their margins become the permanent atrioventricular valves
•(tig. 311 B mk). The latter therefore arise from a part of the
spongy wall of the ventricle.

The remnants of the shrivelled muscular trabeculse (fig, 311 B cht),
which are attached to the valve from below, become still more
rudimentary in the immediate vicinity of the attachment : here also
a part of the muscular fibres disappears entirely ; the connective
tissue, on the contrary, is preserved, and is converted into the tendinous
•cords which, known under the name of chordce tendinece, serve to
hold in place the valves. At some distance from the latter the
trabeculse projecting into the ventricle preserve their fleshy con-
dition and become the papillary muscles (pm), from the apices of
which the chordae tendinese arise. "Whatever of the primitive
trabecular network still persists on the inner surface of the ventricle
forms a more or less stout mesh work of muscles, the fleshy pillars of
the heart (tc), or trabeculse carneae."

In consequence of all these alterations the originally small cavity
of the ventricle has become considerably enlarged at the expense of
a part of its spongy wall. For the whole of the space which in
fig. 311 B lies below the valves has been produced from the system
of originally narrow spaces (fig. 311 A), and has been employed for the
enlargement of the central cavity by the degeneration of the fleshy
•columns into slender tendinous cords.

It still remains for us to investigate the division of the truncus
arteriosus and the final metamorphosis of the atrium.

At about the time when the formation of the partition in the
ventricle takes place, the truncus arteriosus, which arises from it,
becomes somewhat flattened, and thus acquires a fissure-like lumen.
On the flat sides two ridge-like thickenings make their appearance
'(fig. 310-4 and B s), grow toward each other, and by their fusion
•divide the cavity into two passages which are triangular in cross
section. Now, too, the beginning of the internal separation makes
itself visible externally as two longitudinal furrows, in the same
way that the formation of a partition in the ventricle is indicated
by the sulcus interventricularis. The two canals resulting from the
division are the aorta and the pulmonary artery (Ao and Pu). For
a time they continue to be surrounded by a common adventitia, then
they become widely separated and also externally detached from each
other. The whole process of separation in the truncus arteriosus

564 EMBRYOLOGY.

takes place independently of the development of a partition in the
ventricle, beginning as it does at first above and advancing from
there downwards. Finally the aortic septum penetrates also into
the cavity of the ventricle itself (tig. 310 B s and ks\ there unites
with the independently developed ventricular partition, furnishes
the part known as pars membranacea (Oi), and thus completes the
separation of the vessels leading out from the heart, the aorta falling
to the lot of the left ventricle, the art. pulmonalis to the right.

The pars membranacea indicates therefore in the finished heart
the place at which the separation between the right and left halves
of the heart is completed (fig. 310 B Oi). "It is, as it were, the
keystone in the final separation of the primitive simple cardiac sac
into the four secondary cardiac cavities, as they are formed in Birds
and Mammals" (ROSE). From a comparative-anatomical point of

view this place presents a special interest
from the fact that in Reptiles there exists
here a permanent opening between the
two ventricles, the foramen Pannizzse.

Even before the division of the truncus
Fig. 312. -Diagram of the ar- arteriosus, the semilunar valves have become

rangement of the arterial

valves. From GEGENBAUR. established as four ridges, consisting of
A, undivided truncus arteriosus gelatinous tissue with a covering of endo-

with four fundaments of

valves. B, Division into pui- thelium, at the contracted place which is
monaiis (p) and aorta (a), designated as the /return Halleri. Two of

each of which possesses three

valves. them are halved at the time of the divi-

sion of the truncus into aorta and art*

pulmonalis. For each vessel, therefore, there are now three ridges,
which, owing to a shrivelling of the gelatinous tissue, assume the
form of pockets. Their arrangement, to which GEGENBAUR has called
attention, is intelligible from their method of development, as the
accompanying diagram (fir. 312) shows. "By the division of the
originally single bulbus arteriosus (A) into two canals (2?), the
nodule-like fundaments of the four original valves are distributed
in such a manner that the anterior [ventral] one and the anterior
halves of the two lateral ones fall to the anterior arterial trunk
(pulmonalis), the posterior and the posterior halves of the lateral
ones to the posterior arterial trunk (aorta)."

Finally, as regards the atrium, it is to be said that the sinus
venosus, mentioned at p. 558, the mouth of the pulmonary vein, and
the foramen ovale undergo important alterations.

The sinus venosus disappears as an independent structure, since it

THE ORGANS OF THE INTERMEDIATE LAYER OR MESENCHYME. 565

is gradually merged into the wall of the atrium. In consequence of
this the great venous trunks, which originally emptied their blood
into it and which have meanwhile been converted into the superior
and inferior venae cavse and into the sinus coronarius (the details of
which are given in section d), empty directly into the right half of
the atrium, and here gradually separate farther and farther from
one another. Of the two valves which surround, as was previously
stated, the mouth of the sinus venosus, the left becomes rudimentary
(figs. 308, 309) ; the right (*), on the contrary, persists at the mouth
of the inferior vena cava and of the sinus coronarius, and is divided,
corresponding to these, into a larger and a smaller portion, of which
the former becomes the valvula Eustachii, the latter the valvula
Thebesii.

The four pulmonary veins are united for a time into a common
short trunk, which empties into the left half of the atrium. Sub-
sequently the common terminal portion becomes greatly enlarged
and merged with the wall of the heart, in the same way as the sinus
venosus does. In consequence the four pulmonary veins then open
separately and directly into the atrium.

The foramen ovale, the formation of which was previously
described, maintains a broad communication between the two sides
of the atrium during the entire embryonic life. It is bounded
behind and below by the atrial partition, a connective-tissue mem-
brane that subsequently receives the name of valvula foraminis
ovalis (fig. 309 si). Also from above and in front there is formed a
sharp limitation, since a muscular ridge projects inward from the
atrial partition, the anterior atrial crescent or the limbus Vieussenii
(vs). Even in the third month all of these parts are distinctly
developed ; the valvula foraminis ovalis already reaches nearly to
the thickened margin of the anterior muscular crescent, but is
deflected obliquely into the left half of the atrium, so that a broad
fissure remains open and permits the blood of the inferior vena cava
to enter into the left part of the atrium. After birth the margins
of the anterior and posterior folds come into contact, and, with
occasional exceptions, fuse completely. The posterior fold furnishes
the membranous partition of the foramen ovale ; the anterior, with
its thickened muscular margin, produces above and in front the
limbus Vieussenii. With this the heart has attained its permanent
structure.

While the cardiac sac undergoes these complicated differentiations,
it changes its position in the body of the embryo and acquires at an

566

EMBRYOLOGY.

early period a special investment, the pericardium. In connection
with the latter the diaphragm is formed as a partition between the
thoracic and abdominal cavities. This is consequently the most
suitable place at which to acquaint ourselves better with these
important processes, a part of which are not easily understood. The
most of the discoveries in this field we owe to the investigations of
CADIAT, His, BALFOUR, USKOW, and others.

Mb

(b) The Development of the Pericardial Sac and the Diaphragm.
The Differentiation of the Primary Body-cavity into Pericardial,
Thoracic, and Abdominal Cavities.

Originally the body-cavity is widely extended in the body of the
embryo, for it can be traced in the lower Vertebrates into the fun-
dament of the head, where it
furnishes the cavities of the
visceral arches. After the
latter have become closed,
during which muscles arise
from the cells composing their
walls, the body-cavity extends
forward as far as the last
visceral arch and constitutes
a large space (fig. 313), in
which the heart is developed
within the ventral mesentery
(mesocardium anterius and
posterius). REMAK and KO'L-
LIKER named this space throat-

Fig. 313.— Human embryo (Lg of His) 2:15 mm.
long, neck measurement. Reconstruction
figure, after His(" Menschliche Enibryonen ").

cavity:, His introduced the
name parietal cavity. But it
will be most appropriate if
one designates it, after the
permanent organs which are
derived from it, as the peri-
cardio - thoracic cavity. The
more the cardiac tube is
thrown into curves, the more extensive this cavity becomes, and it
soon acquires in the embryo a comparatively enormous size. By
this its front wall is protruded ventrally like a hernia between the
head and the navel of the embryo (figs. 314, 157).

Magnified 40 diameters.

Mb, Oral sinus ; Ab, aortic bulb ; Vm, middle
part of the ventricle ; Vc, vena cava superior
or ductus Cuvieri ; Sr, simis reunions ; Vu,
vena \imbilicalis ; VI, left part of the ven-
tricle ; Ho, auricle of the heart ; D, diaphragm ;
V.om, vena omphalomesenterica ; Lb, solid
fundament of the liver ; Lbg, hepatic duct.

THE ORGANS OF THE INTERMEDIATE LAYER OR MESENCHYME. 567

The pericardio-thoracic cavity begins very early to be sharply
marked off from the future abdominal cavity by a transverse fold
(figs. 313, 314 z + l), which begins at the front [ventral] and lateral
walls of the trunk, and the free edge of which projects dorsalwards
and median wards (fig. 314 z + l) into the primitive body-cavity. It
marks the course which the terminal part of the vena omphalo-
mesenterica takes in order to reach the heart. Subsequently there
are found imbedded in the fold all of the venous trunks which empty
into the atrial sinus of the heart (figs. 313, 314), — the omphalo-
mesenteric and umbilical veins and the Cuvierian ducts (dc), which
collect the blood from the walls of the trunk. Therefore the formation
of the transverse jold is most intimately connected with the development
of the veins. It takes the name of septum transversum (massa
trans versa, TJsKow), and has the form of a transverse bridge of
substance uniting the two lateral walls of the trunk (fig. 313), which
inserts itself between the sinus venosus and the stomach, and
is united with both as well as with the ventral mesentery. Its
posterior portion (fig. 314 z + l) contains abundant embryonic con-
nective tissue and blood-vessels, and constitutes a mass described as
prehepaticus (Yorleber), since the two liver-sacs (fig. 313 Lb + Lbg)
grow out from the duodenum into it and produce the hepatic
cylinders. In proportion as this takes place, and the hepatic
cylinders spread out from the ventral mesentery laterally into the
septum transversum, the latter increases in thickness and now
embraces two different fundaments, — in front, a plate of substance
in which the Cuvierian ducts and other veins run to the heart (the
primary diaphragm) \ behind, the two lobes of the liver, which produce
ridges that project into the body cavity.

By means of the septum transversum the pericardio-thoracic and
the abdominal cavities are almost completely separated (fig. 314).
There remain only two narrow canals (brh) (thoracic prolongations
of the abdominal cavity, His), which establish a connection behind
with the abdominal cavity at either side of the intestinal tube and
its dorsal mesentery. The two canals (brh) receive the two funda-
ments of the lungs (Ig) when they grow out from the ventral wall
of the intestinal tube. They afterwards become the two thoracic or
pleural cavities (brh), whereas the larger cavity communicating with
them (kk)t in which the heart has developed, becomes the pericardial
chamber. The latter takes up the whole ventral side of the embryo ;
the thoracic cavities, on the contrary, lie quite dorsal next to the
posterior wall of the trunk.

568

EMBRYOLOGY.

How does the closure of these three originally communicating
spaces take place, and how do they attain their altered, final position
in relation to one another ?

The pericardial sac is the first to be separated off. The impulse
to separation is furnished by the Cuvierian ducts (fig. 314 dc). One
portion of the latter runs down from the dorsum, where it arises by
the confluence of the jugular and cardinal veins, along the lateral
walls of the trunk to the transverse septum (fig. 314 dc) ; it thereby

Fig. 314.— Sagittal reconstruction of a human embryo 5 mm. long, neck measurement (embryo

R, Ilia), to elucidate the development of the pericardio-thoracic cavity and the diaphragm,

after His.
ab, Bulbus arteriosus ; brh, thoracic cavity (recessns parietalis, His) ; hit, pericardial cavity ;

dc, ductus Cuvieri ; dv, vena omphalomesenterica ; nv, umbilical vein ; vca. cardinal vein ;

vj, jugular vein ; Ig, lung ; 2 + I, fundament of the diaphragm and liver ; uk, mandible.

crowds the pleura into the pericardio-thoracic cavity, and in this
manner produces the pleuro-pericardial fold. Since the latter is
carried farther and farther inward, it continues to narrow the com-
munication between the pericardial cavity (hh) and the two pleural
cavities (brh) ; finally, it cuts off the communication entirely, when
its free edge has grown [median wards] as far as, and has fused with,
the mediastinum posterius, in which the oesophagus lies. By this
migration of the Cuvierian ducts is also explained the position of the
superior vena cava, which later opens into the atrium from above,
for it is derived from the Cuvierian duct. Originally located in

THE ORGANS OF THE INTERMEDIATE LAYER OR MESENCHYME. 569

the lateral wall of the trunk, its terminal part is afterwards enclosed
in the mediastinum.

After the closure of the pericardial sac, the narrow, tubular
thoracic cavities (fig. 314 brh) continue for a time to remain in
communication behind with the abdominal cavity. The fundaments
of the lungs (Ig) meantime grow farther into them, and their tips
finally come in contact with the upper surface of the liver, which
also has now become larger. Then a closure is effected at these
places also. From the lateral and posterior walls of the trunk
project folds (the pillars of USKOW), which fuse with the septum
transversum, and thus form the dorsal part of the diaphragm. One
can therefore distinguish a ventral older part and a dorsal younger one.

As GEGENBAUR points out, this explains the course of the phrenic nerve,
which runs in front of [ventral to] the heart and lungs and approaches the
diaphragm from in front.

Occasionally the fusion of the dorsal and ventral fundaments is
interrupted on one side. The consequence of such arrested develop-
ment is a diaphragmatic hernia — i.e., a permanent connection between
abdominal and thoracic cavities by means of a hernial orifice, through
which loops of the intestine can pass into the thoracic chamber.

When the four large serous spaces of the body have been com-
pletely shut off from one another, the individual organs must still
undergo extensive alterations of position, in order to attain their
ultimate condition. The pericardial sac at first takes up the whole
ventral side of the breast, and over a large area is connected with
the anterior wall of the thorax and with the upper wall of the
diaphragm. Moreover, the latter is united with the liver along its
whole under surface. The lungs lie hidden in narrow tubes at the
dorsal side of the embryo.

There are two factors that come into the account in this con-
nection (fig. 315). With the increase in the extent of the lungs (Ig),
the thoracic cavities (pl.p) extend farther ventrally, and thereby
detach the wall of the pericardial sac (pc), or the pericardium, on
the one hand from the lateral and anterior walls of the thorax, and
on the other from the surface of the diaphragm. Thus the heart (ht),
with its pericardial sac, is displaced step by step toward the median
plane, where, together with the large blood-vessels (ao), the oaso-
phagus (al), and the bronchial tubes, it helps to form a partition —
the mediastinum — between the greatly enlarged thoracic cavities.
In front the pericardial sac then remains in contact with the wall of

570

EMBRYOLOGY.

the thorax (st) and below with the diaphragm for a little distance
only.

The second factor is the separation of the liver from the primary
diaphragm, with which it was united to form the septum transversum*
This takes place as follows : At the margin of the liver the peritoneum,
which originally covered only its under surface, grows over on to-
rts upper surface, separating it from the primary diaphragm. A
connection is retained near the wall of the trunk only. Thus is
explained the development of the ligamentum coronarium hepatisr

Fig. 315.— Cross section through an advanced embryo of a Rabbit, to show how the pericardia!

cavity becomes surrounded by the pleural cavities, from BALFOUR.
lit, Heart ; pc, pericardial cavity ; pl.p, thoracic or pleural cavity ; Ig, lung ; al, alimentary

canal ; ao, dorsal aorta ; ch, chorda ; rp, rib ; st, sternum ; sp.c, spinal cord.

which was disregarded in the section which treated of the ligamentous
supports of the liver (p. 330).

The diaphragm finally acquires its permanent condition by the
ingrowth of muscles from the wall of the trunk into the connective-
tissue lamella.

(c) The Metamorphoses of the Arterial /System.

The development of the large arterial trunks lying in the vicinity
of the heart is of great interest from a comparative-anatomical point
of view. As in all Vertebrates at least five pairs of visceral arches

THE ORGANS OP THE INTERMEDIATE LAYER OR MESENCHYME. 571

are established on the two sides of the fore-gut (permanently in
the gill-breathing Fishes, Dipnoi, and a part of' the Amphibia,
transitorily in the higher Vertebrates), so also tnere are developed
at the corresponding places on the part of the vascular system five
pairs of vascular arches* (fig. 316 1-5). They take their origin
from the truncus arteriosus (figs. 316, 317), which runs forward
under the fore-gut, then follow along the visceral arches up to the
dorsal surface of the embryo, and here unite on either side of the
vertebral column into longitudinal vessels, the two primitive aortae
(fig. 317 ad). On this account they are called aortic arches, but
they are more appropriately designated as visceral-arch vessels.

In the Vertebrates that breathe by
means of gills, the vessels of the
visceral arches become of importance
in the process of respiration, and early
lose their simple structure. From
their ventral initial portions there
arise numerous lateral branches run-
ning to the branchial lamellae, which
have arisen in large numbers from
the mucous membrane investing the
visceral arches ; here they are resolved
into fine capillary networks. From
these the blood is re-collected into
venous branches, which open into the
upper end of the visceral-arch vessels.
The larger the ventral and dorsal
lateral branches, the more incon-
spicuous does the middle part of the

vessel of the visceral arch become. At length it has separated into
an initial part, the branchial artery, which is distributed to the
branchial lamellae in numerous branches, and an upper part, the
branchial vein, into which the blood is re-collected. The two are
connected with each other by means of the close network only,
which, from its superficial position in the mucous membrane, presents
a suitable condition for the removal of the gases from the blood,

Since in the Amniota there are no branchial lamellae produced,
branchial arteries and veins also fail to be developed, the vessels of

* [The existence of six pairs of vascular arches has recently been shown to be
the typical condition, the newly discovered pair, situated between the fourth and
fifth pairs of RATHKE'S scheme (fig. 316), being of short duration in Amniota.]

Fig. 316. — Diagram of the arrange-
ment of the vessels of the visceral
arches from an embryo of an
amniotic Vertebrate.

1—5, First to fifth aortic arches ; ad,
aorta dorsalis ; ci, carotis interna ;
ce, carotis externa ; v, vertebralis ;
s, subclavia ; p, pulmonalis.

572

EMBRYOLOGY.

the viscpral arches retaining their original simple condition. But
they are in part of only short duration; they soon suffer, by the
complete degeneration of extensive portions, a profound metamor-
phosis, which is effected in a somewhat different manner in Reptiles,
Birds, and Mammals. An exposition of the changes in the case of
Man only will be given here.

In human embryos only a few millimetres long, the truncus
arteriosus, which emerges from the still single cardiac tube, is divided
in the vicinity of the first visceral arch into a left and a right
branch, which surround the pharynx, and are continuous above with
the two primitive aortse. It is the first pair of aortic arches. In

Fig. 317.— Development of the large arterial trunks, represented from embryos of a Lizard (A),

the Chick (£), and the Pig (C), after RATHKE.
The first two pairs of arterial arches have in all cases disappeared. In A and B the third,

fourth, and fifth pairs are still fully preserved ; in C only the two latter are still complete.
p, Pulmonary artery arising from the fifth arch, but still joined to the dorsal aorta by means of

a ductus Botalli ; c, external, c', internal carotid ; ad, dorsal aorta ; a, atrium ; v, ventricle J

n, nasal pit ; m, fundament of the anterior limb.

only slightly older embryos their number is rapidly increased by
the formation of new connections between the ventral truncus
arteriosus and the dorsal primitive aortse. Soon a second, a third,
a fourth, and, finally, a fifth pair make their appearance in the
same sequence in which the visceral arches are established in the
case of Man as well as the remaining Vertebrates.

The five pairs of vascular arches give off lateral branches to
the neighboring organs at a very early period; of these several
acquire a great importance and become carotis externa and interim,
vertebralis and subclavia as well as pulmonalis. The carotis externa
(fig. 316 ce and fig. 317 c) arises from the beginning of the first
vascular arch, and is distributed to tbe region of the upper and

THE ORGANS OF THE INTERMEDIATE LAYER OR MESENCHYME. 573

lower jaws. The carotis interna (figs. 316 ei, 317 c') likewise arises
from the first arch, but farther dorsally, at the point where the
arch bends around to become continuous with the root of the aorta ;
it conducts the blood to the embryonic brain and to the developing
eye-ball (arteria ophthalmica). From the dorsal region of the
fourth vascular arch (fig. 316 4) a branch is given off which is
soon divided into two branches, one of which goes headwards to the
medulla oblongata and the brain, the arteria vertebralis (v), whereas
the other (s) supplies the upper limb (arteria subclavia). In the
course of development these two arteries interchange relations in
respect to calibre. In young embryos the vertebralis is by far the
more important, while the subclavia is only a small inconspicuous
lateral branch. But the more the upper extremity increases in size,,
the more the subclavia is elevated into the position of the main
trunk, and the more the vertebralis sinks to the rank of an accessory
branch. Finally, from the fifth [sixth] arch there bud forth branches
to the developing lungs (figs. 316, 317 p).

As the simple diagram shows, the fundament of the arterial trunks
which arise from the heart is originally strictly symmetrical. But at
an early period there occur reductions of certain vascular tracts even
to their complete disappearance ; in this way the symmetrical arrange-
ment is gradually converted into an unsymmetrical one.

The accompanying diagram (fig. 318) — in which the parts of the-
vascular course that degenerate are left free, and those which
continue to be functional are marked by a heavy central line — will
serve to illustrate this metamorphosis.

First, as early as the beginning of the nuchal flexure, the first
and second vascular arches — with the exception of the connecting
portions through which the blood flows to the carotis externa (b) —
disappear.

The third arch (c) persists, but loses its connection with the dorsal
end of the fourth, and therefore now conveys all its blood toward the
head into the carotis interna (a), of which it has now become the
initial part.

The chief role in the metamorphosis is assumed by the fourth and
fifth arches (fig. 317 C). They soon exceed all other vessels in size,
and as they lie nearest to the heart, they are converted into the two
chief arteries which arise from it, the aortic arch and the arteria
pulmonalis. An important modification is effected at the place of
their origin from the truncus arteriosus when the latter is divided
lengthwise by means of the development of the partition previously

574

EMBRYOLOGY.

mentioned. The fourth arch (fig. 318 e) then remains in connection
with the trunk (d) which arises from the left ventricle and receives
blood exclusively from that source. The fifth arch (n), on the con-
trary, forms the continuation of that half (m) of the truncus arteriosus
which emerges from the right ventricle. Thus the division of the
blood into two separate currents initiated in the heart is also
continued into the nearest vessels, but for a short distance only,
since the fourth and fifth pairs of vascular arches (fig. 317) still
empty their blood together into the aorta communis (ad), with the
exception of a certain portion which runs
through their accessory branches, in part to
the head (c.c7) and upper limbs, in part to
the still diminutive lungs. Gradually, how-
ever, the process of separation thus introduced
is continued still farther into the region of
the peripheral vessels and finally leads to the
establishment of the entirely distinct major
and minor circulations. The final condition is
attained by the degeneration of certain portions
of the vessels and the enlargement of others.

A preponderance of the vascular arches of
the left side over those of the right is soon
recognisable (fig. 318). The former con-
tinually increase in size, while those of the
right side become less and less apparent and
finally in places disappear altogether. They
are retained only in so far as they conduct
the blood to the lateral branches which,
arising from them, go to the head, the upper
limbs, and the lungs. Consequently of the
right aortic arch there remains only the
tract which gives rise to the right carotis communis (c) and
the right subclavia (i + Z). We designate its initial part as the
arteria anonyma brachiocephalica. With this the permanent con-
dition is now established. The remnant of the right fourth vascular
arch appears as a side branch only of the aorta (e), which forms an
arch on the left side of the body, and here gives rise to the carotis
communis sinistra (c) and the subclavia sin. (Ji) as additional lateral
branches.

The right half of the fifth [sixth] pair of vascular arches likewise
undergoes degeneration, except for the portion that conveys blood

Fig. 318.— Diagrammatic re-
presentation of the meta-
morphosis of the blood-
vessels of the visceral
arches in a Mammal,
after RATHKE.

a, Carotis interna ; 6, carotis
externa ; c, carotis com-
munis; d, body or sys-
temic aorta ; e, fourth
arch of the left side ;
/, dorsal aorta; g, left,
k, right vertebral artery ;
h, left subclavian artery ;
i, right subcla%'ian (fourth
arch of the right side) ;
I, continuation of the
right subclavian ; m, pul-
monary artery ; n, its
ductus Botalli.

THE ORGANS OF THE INTERMEDIATE LAYER OR MESENCHYME. 575

to the right lung. On the left side of the body, on the contrary,
the pulmonary arch still persists for a long time and conducts
blood into the left lung and also through the ductus arteriosus
Botalli (n), into the aorta. After birth, in connection with
pulmonary respiration, the duct of BOTALLI also degenerates, For
the lungs, when they are expanded by the first act of inspiration,
are in a condition to receive a greater quantity of blood. The
consequence is that blood no longer flows into the ductus Botalli,
and that the latter is converted into a connective-tissue cord,
which extends between aorta and art. pul-
monalis.

In addition to the regressive changes
mentioned, there are effected meantime
alterations of position in the large vascular
trunks that arise from the heart. They
move at the same time with the heart from
the neck region into the thoracic cavity. In
this fact lies the explanation of the peculiar
course of the nervus laryngeus inf. or re-
currens. At the time when the fourth
vascular arch still lies forward in the region
of its formation in the fourth visceral arch,
the vagus sends to the larynx a small nerve
branch, which, to reach its destination,
passes below [caudad of] the vascular arch.
When the latter migrates downwards, the
nervus laryngeus must thereby be carried
down with it into the thoracic cavity, and
must form a loop, one portion of which,
arising in the thoracic cavity from the vagus,
bends around the , arch of the aorta on the

left side of the body (but around the subclavia on the right side of
the body) to become continuous with the second portion, which takes
the opposite or up\fard course to the region of its distribution.

The processes of development discussed also throw light on a series
of abnormalities which are quite frequently observed in the large
vascular trunks. I shall cite and explain two of the most important
<>f these cases.

Occasionally in the territory of the vessels of the fourth visceral
arches the original symmetrical condition is retained. The aorta is
then divided in the adult into right and left vascular arches, which

a,

Fig. 319. — Diagrammatic re-
presentation of the meta-
morphosis of the arterial
arches in Birds, after
RATHKE.

Internal, b, external,
c, common carotid ; d,
systemic aorta ; e, fourth
arch of the right side
(root of the aorta); /,
right subclavian; g, dorsal
aorta ; h, left subclavian
(fourth arch of the left
side) ; i, pulmonary ar-
tery ; k and I, right and
left ductus Botalli of the
pulmonary arteries.

576 EMBRYOLOGY.

convey the blood into the unpaired aorta. From each of them/
there arises, as in the embryo, a separate carotis communis and
subclavia.

Another abnormality is brought about by the development of
the aortic arch of the right side of the body instead of that of the
left, a condition which is met with in the class of Birds (fig. 319) as
the normal state. This malformation is always connected with an
altered position of the organs of the chest, a situs inversus viscerum.
Of the other changes in the region of the arterial system the-
metamorphosis of the primitive aorta is to be mentioned before all
others. As in the other Vertebrates (fig. 127 ao\ so in Man, them
are formed a right and a left aorta; but they subsequently move
close together and fuse. This, again, explains an abnormality, which,
it is true, has very rarely been observed in Man. The aorta is
divided into right and left halves by means of a longitudinal
partition ; the process of fusion, therefore, has not been fully
effected.

The aorta gives off at an early period as branches the unpaired
mesenterica sup. and mesenterica inf. to the intestinal canal ;
furthermore, near its posterior end, the two voluminous navel
vessels, arterise umbilicales (fig. 139 Al). These run from the dorsal
wall of the trunk along the sides of the pelvic cavity ventrally to-
that part of the allantois which is subsequently differentiated into-
urinary bladder and urachus, here bend upward and pass on either side
of the latter in the abdominal wall to the navel, enter the umbilical
cord, and are resolved in the placenta into a capillary network, from
which the blood is re-collected into the venae umbilicales. During
their passage through the pelvic cavity the umbilical arteries give
off lateral branches that are at first inconspicuous, the iliacse
internse, to the pelvic viscera, the iliacae externse to the posterior
limbs now sprouting forth from the trunk as small knobs. The
more the latter increase in size in older embryos, the larger do the
iliacse externse and their continuations, the femorales, become.

After giving off the two umbilical arteries, the aorta becomes
smaller and is continued to the end of the vertebral column as an
inconspicuous vessel, the aorta caudalis or sacralis media.

At birth an important alteration occurs in this part of the
arterial system also. With the detachment of the umbilical corcTr
the umbilical arteries can 110 longer receive blood; they therefore
waste away with the exception of the proximal portion, which has
given off as lateral branches the internal and external iliacs, and is

THE ORGANS OP THE INTERMEDIATE LAYER OR MESENCHYME. 577

now designated as the iliaca communis. However, two connective-
tissue cords result from the degenerating vessels, the ligamenta
vesico-umbilicalia lateralia, which run to the navel on the right and
left of the bladder.

(d) Metamorphoses of the Venous System.

The older excellent works of RATHKE and the more recent meri-
torious investigations of His and HOCHSTETTER constitute the
foundation of our knowledge in the difficult field with which we are
now concerned. They show us that originally all of the chief trunks
of the venous system, with the exception of the inferior vena cava, are
established in pairs and symmetrically. This holds true not only for
the vessels which collect the blood from the walls of the trunk and
from the head, but also for the veins of the intestinal tube and the
embryonic appendages which arise from it.

In the first place, so far as regards the veins of the body, the
venous blood is collected from the head into the two jugular veins
(fig. 320 vj and fig. 321 A je, ji), which run downwards along the
dorsal side of the visceral clefts and unite in the vicinity of
the heart with the cardinal veins (fig. 320 vca and fig. 321 A ca).
The latter advance in the opposite direction, from below upwards,
in the dorsal wall of the trunk, and collect the blood especially
from the mesonephros. There arise from the confluence of the
two veins the Cuvierian ducts (figs. 320, 321 A- dc), from which
are subsequently developed the two superior venae cavae. The
veins of the trunk in Fishes exhibit a symmetrical arrangement
like this throughout life.

In the earliest stages the Cuvierian ducts lie for some distance in
the lateral wall of the pericardio-pleural cavity, where they run
downwards from the dorsum to the front [ventral] wall of the trunk
(fig. 320). On arriving at this point, they enter into the septum
transversum, KOLLIKER'S mesocarclitim laterale, in order to reach the
atrium of the heart. This important embryonic structure forms a
point of collection for all the venous trunks emptying into the heart.
In it there are joined to the Cuvierian ducts the veins from the
viscera (fig. 313 V.om and Vu, fig. 320 dv and nv), — the paired yolk
veins and umbilical veins, — all of which are joined into the common
sinus venosus, which was previously (p. 558) mentioned apropos of
the development of the heart, and which is situated directly between
atrium and septum transversum.

The two vitelline veins (v. omphalomesentericse) return the blood

37

578 EMBRYOLOGY

from the yolk-sac ; they are the two oldest and largest venous trunks
of the body, but they become inconspicuous in the same ratio as the
yolk-sac shrinks to an umbilical vesicle. They run close together
along the intestinal tube, and come to lie at the sides of the duodenum
and stomach, where they are united to each other by transverse
anastomoses even at a very early period.

The navel veins (venae umbilicales) are also originally double. At
first very small, they subsequently become, in contrast with the
vitelline veins, more and more voluminous, as the placenta, from

Fig. 320. —Sagittal reconstruction of a human embryo 5 mm. long, neck measurement (embryo
R, His), to illustrate the development of the pericardio-thoracic cavity and the diaphragm,
after His.

ab, Aortic bulb ; brh, thoracic cavity (recessns parietalis, His) ; hh, pericardia! cavity ; <lc, ductus
Cuvieri ; dv, vitelline vein (v. omphalomesenterica) ; nv, umbilical vein ; vca, cardinal
vein ; vj, jugular vein ; Ig, lung ; z + 1, fundament of the diaphragm and the liver ; uk,
lower jaw.

which they convey the blood back to the body of the embryo, is
further developed. At the time of their first appearance the umbilical
veins are found to be imbedded in the lateral wall of the abdomen
(fig. 313 Vu), in which they make their way to the septum trans-
versum and the sinus venosus (sr).

The inferior vena cava (fig. 321 A ci) is established later than any
of these paired trunks. It makes its appearance as an inconspicuous,
from the beginning unpaired, vessel (in the Rabbit on the twelfth
day, HOCHSTETTER) on the right side of the aorta in the tissue
between the two primitive kidneys ; caudalwards it is connected by

THE ORGANS OF THE INTERMEDIATE LAYER OR MESENCHYME. 579

lateral anastomoses with the cardinal veins. At the heart it opens
into the sinus venosus.

From this primitive form of the venous system (fig. 321 A) is
derived the ultimate condition in Man. There are three changes
which are conspicuous in this connection. (1) The veins empty
directly into the atrium instead of a venous sinus. (2) The sym-
metrical arrangement in the region of the Cuvierian ducts and the
jugular and cardinal veins gives place to an unsymmetrical arrange-

Fig. 321.— Diagram of the development of the venous system of the body.

dc, Ductns Cuvieri; je, ji, vena jugularis externa, interna ; s, v. subclavia ; vh, v. hepatica
revehens; U, v. umbilicalis; ci (ci2), v. cava inferior; ca (cal, ca3, ca3), v. cardinalis;
ilcd, ilcs, v. iliaca communis dextra, sinistra ; ad, as, v. anonynia brachiocephalica dextra,
ainistra ; cs, v. cava superior ; csd, v. cava superior dextra ; ess, rudimentary portion of
v. cava superior sinistra ; cc, v. coronaria cordis ; az, v. azygos ; hz (hzl), v. hemiazygos ;
He, v. iliaca externa ; Hi, v. iliaca interna ; r, v. renalis.

ment accompanied by a degeneration or stunting of some of the
chief trunks. (3) With the development of the liver there is formed
a special portal system.

The alteration first mentioned is accomplished by the incorporation
of the sinus venosus in the atrium. At first enclosed in the septum
transversum, the sinus elevates itself above the upper surface of the
latter, from which it detaches itself, and comes to lie as an
appendage to the atrium in the anterior trunk-cavity. Finally it
fuses completely with the heart and furnishes the smooth region of
the atrial wall, which is destitute of the pectinate muscles (His).

580 EMBRYOLOGY.

There are in it separate openings for the two Cuvierian ducts — the
future vense cavse superiores — and an opening distinct from them for
the veins coming from the viscera below (the future cava inferior).

The metamorphoses in the region of the Cuvierian ducts begin
with a change in their position. Their course from above down-
ward becomes more direct. At the same time, like the sinus
venosus, they emerge from the niveau of the transverse septum and
lateral walls of the trunk into the body-cavity and carry before them
the serous membrane, with which they are covered, as a crescent-
shaped fold, which contributes to the formation of the pericardial
sac, and has been already described as the pleuro-pericardial fold.
By fusing with the mediastinum the Cuvierian ducts pass from the
walls of the trunk into the latter and come to lie nearer together in
the median plane. Of their affluents the jugular veins gradually
predominate over the cardinal veins (fig. 322 B). There are three
reasons for this. First, the anterior part of the body, and especially
the brain, far outstrips in growth the posterior part ; secondly, there
arises in this region a competitor of the cardinal veins, the inferior
vena cava, which assumes in place of them the function of returning
the blood. Thirdly, when the anterior limbs are established, the
vense subclavise (s) empty into the jugulares. Consequently the
lower portion of the jugular, from the entrance of the subclavia
onward, now appears as the immediate continuation of the Cuvierian
duct, and together with it is designated as superior vena cava
(fig. 322 B cud).

There exists between the right and left sides a difference in the
course of the superior venae cavse, which, as GEGENBAUR has pointed
out, is the cause of the asymmetry that is developed in Man.
While the right vena cava superior (fig. 322 B csd) descends more
directly to the heart, the left (ess) describes a somewhat longer
course. Its terminal portion is bent from the right to the left
around the posterior [dorsal] wall of the atrium, where it is imbedded
in the coronal furrow and receives the blood from the coronal vein
(cc) of the heart.

In Reptiles, Birds, and many Mammals a stage of this kind, with
two venae cavae superiores, becomes permanent; in Man it exists
only during the first months. Then there is a partial degeneration
of the left vena cava superior. The degeneration is initiated by the
formation of a transverse anastomosis (fig. 322 B as) between the
right and left trunks. This conveys the blood from the left to
the right side, where the conditions are more favorable for the

THE ORGANS OP THE INTERMEDIATE LAYER OR MESENCHYME. 581

return of the blood to the heart. In consequence of this the
proximal end of the right cava becomes much larger, the left, on
the contrary, proportionately smaller. Finally, there is a complete
wasting away of the latter blood course (fig. 322 C ess) as far as the
terminal part (cc), which is lodged in the coronal groove. This part
remains open, because the cardiac veins convey blood to it, and is
now distinguished as sinus coronarius.

A process in many respects similar to this is repeated in the case

Fig. 322.— Diagram of the development of the venous system of the body.

dc> Ductus Cuvieri ; je, ji, vena jugularis externa, interna ; s, v. subclavia ; vh, v. hepatica
revehens ; U, v. umbilicalis ; ci (cia), v. cava inferior ; ca (ca1, ca', ca*), v. cardinalis ;
Ucd, itcs, v. iliaca communis dextra, sinistra ; ad, as, v. anonyma brachiocephalica dextra,
sinistra ; cs, v. cava superior ; cad, v. cava superior dextra ; ess, rudimentary portion of
v. cava superior sinistra ; cc, v. coronaria cordis ; az, v. azygos ; hz (hz1), v. hemiazygoa ;
ile, v. iliaca externa ; ili, v. iliaca interna ; r, v. renalis.

of the cardinal veins (fig. 322 A ca). The latter collect the blood
from the primitive kidneys and the posterior wall of the trunk, from
the pelvic cavity and the posterior limbs. From the pelvic cavity
they receive the venae hypogastricse (ili), and from the limbs the
v. iliacae externse (ile) and their continuation, the v. crurales. In this
way £he cardinal veins are at first, as in Fishes, the chief collecting
trunks of the lower half of the body. Subsequently, however, they
diminish in importance, since the inferior vena cava becomes the
main collecting trunk instead of them.

It is only within the last few years that the development of the

582 EMBRYOLOGY.

inferior vena cava has been (by HOCHSTETTEE) explained. According
to his investigations there are to be distinguished two tracts which
are of different origin, a shorter anterior and a longer posterior.
The former, as previously mentioned, makes its appearance as an
inconspicuous vessel on the right side of the aorta in the tissue
between the two primitive kidneys (fig. 322 A and B ci) • the latter,
on the contrary, is developed subsequently out of the posterior region
of the right cardinal vein (fig. 322 B ci2). The anterior, inde-
pendently arising part of the inferior vena cava, soon after its
establishment, unites with the two cardinal veins by means of
transverse branches in the vicinity of the vena renalis (r). In con-
sequence of this increase of drainage territory, it. scon increases con-
siderably in calibre, and since it presents more favorable conditions
for the conveyance of blood from the lower half of the body than
the upper portion of the cardinal veins does, it finally becomes the
chief conduit.

If the stage thus far described were to become the permanent
condition (fig. 322 B), we should have an inferior vena cava, which
forks in the region of the renal veins (r) into two parallel trunks,
that descend at both sides of the aorta to the pelvis. Such cases, as
is known, are found among the varieties of the venous system ; they
are derived from the previously described stages of development as
malformations by arrested growth. However, they are only rarely
observed, for in the normal course of development there is established
at an early period an asymmetry between the lower portions of the
two cardinal veins, from the momentj indeed, when they have united
themselves to the lower part of the inferior vena cava by means of
anastomoses. The right portion acquires a preponderance, becomes
enlarged, and finally alone persists (fig. 322 J5, (7), whereas the left
lags behind in growth and withers. This results from two conditions.
First, the right cardinal vein (ci2) lies more in the direct prolongation
of the vena cava inferior than does the left, and thus occupies a
more favorable situation ; secondly, there is formed in the pelvic
region an anastomosis (ilcs) between the two cardinal veins, which
conducts the blood of the left hypogastrica and the left iliaca externa
and cruralis to the right side. Owing to this anastomosis, which
becomes the vena iliaca communis sinistra, the portion of the left
cardinal vein lying between the renal veins and the pelvis (fig. 322
C ca3) is rendered functionless, and with the degeneration of the
primitive kidney disappears. The right cardinal vein has now
become for a certain distance a direct continuation of the inferior

THE ORGANS OF THE INTERMEDIATE LAYER OR MESENCHYME. 583

vena cava; it furnishes that portion of the latter which is
situated between the renal veins and the division into the two venae
iliacse communis (fig. 322 B and 0 ci'*).

While the abdominal part of the left cardinal vein (fig. 322 G ca*)
succumbs and the corresponding region of the right cardinal vein
produces the lower part of the inferior vena cava (ci2), their
thoracic portions persist in a reduced form, since they receive the
blood from the intercostal spaces (fig. 322 B ca). In this region
occurs still another and last metamorphosis, by which likewise an
asymmetry is brought about between the halves of the body. In the
thoracic part of the body the original conditions of the circulation are
altered by the degeneration of the left cava superior (fig. 322 C ess).
The direct flow of the left cardinal vein to the atrium is thereby
rendered more difficult, and finally ceases altogether, the tract desig-
nated by ca2 undergoing complete degeneration. Meanwhile a trans-
verse anastomosis (hzl), which has been formed in front of the
vertebral column and behind the aorta between the corresponding
vessels of both sides, receives the blood of the left side of the body
and transports it to the right side. In this manner the thoracic
part of the left cardinal vein and its anastomosis become the left
hemiazygos (hz and hzl) ; the right and larger cardinal vein becomes
the azygos (az).

Thus by many indirect ways is attained the permanent condition
of the venous system of the trunk, with its asymmetry and its
preponderance of the venous trunks in the right half of the body.

A third series of metamorphoses, which we shall now take into
consideration, concerns the development of a liver circulation.

The liver receives its blood in different stages of the embryonic
development from various sources : for a time from the vitelline
veins; during a second period from the umbilical veins; after
birth, finally, from the veins of the intestines — the portal vein.
This threefold alteration finds its explanation in the conditions of
growth of the liver, the yolk-sac, and the placenta. As long as the
hVer is small, the blood coming from the yolk-sac suffices for its
nourishment. But when it increases greatly in size — the yolk-sac,
on the contrary, growing smaller — other blood-vessels at this time,
the umbilical veins, must supply the deficiency. When, finally, at
birth the placental circulation ceases, the venous trunks of the
intestinal canal, which meanwhile have become very large, can
supply the needs.

These circumstances must be kept in mind, in order to comprehend

584 EMBRYOLOGY.

the shifting conditions of circulation in the liver and the profound
alterations to which the venous trunks connected with it — the
vitelline, umbilical, and portal veins — are naturally subjected in
thiTchangmg supply of blood.

When the hepatic ducts grow out from the duodenum into the
ventral mesentery and septum transversum and send out shoots,
they enclose the two vitelline veins accompanying the intestine,
which are at this place connected with each other by ring-like
anastomoses (sinus annularis, His) which surround the duodenum
(fig. 320 dv). They are supplied with blood by lateral branches
given off from these veins. The more the liver increases in size, the
larger do the lateral branches (vense hepaticse advehentes) become.
Between the network of hepatic cylinders (fig. 187 Ic) they are
resolved into a capillary network (g), from which at the dorsal
margin of the liver large efferent vessels (vense hepaticse revehentes)
re-collect the blood and convey it back into the terminal portion of
the vitelline vein, which empties into the atrium. In consequence
of this the portion of the vitelline vein which lies between the
vense hepaticse advehentes and revehentes continually becomes smaller,
and finally atrophies altogether, since all the blood from the yolk-sac
is employed for the hepatic circulation. The same process in the
main is accomplished here as in the vessels of the visceral arches of
gill-breathing Vertebrates, which upon the formation of branchial
lamellse are converted into branchial arteries, branchial veins, and a
capillary network interpolated between the two.

The two umbilical veins participate, even at an early period, in
the hepatic circulation. Originally they run from the umbilical
cord in the front [ventral] wall of the abdomen (fig. 313 Vu), from
which they receive lateral branches, and then enter the sinus
venosus ($r) above the fundament of the liver. They pursue, there-
fore, an entirely different course from that which they do later,
when the terminal part of the umbilical vein is situated under the
liver. According to His, this change in their course takes place in
the following manner : The right umbilical vein in part atrophies
(as also in the Chick, p. 552) and becomes, as far as it persists, a
vein of the ventral wall of the abdomen. The left umbilical vein,
on the contrary, gives off anastomoses in the septum transversum to
neighboring veins, one of which makes its way under the liver to
the sinus annularis of the vitelline veins, and thereby conducts a
part of the placental blood into the hepatic circulation. Since by
its rapid growth the liver demands a large accession of blood, the

THE ORGANS OF THE INTERMEDIATE LAYER OR MESENCHYME. 585

anastomosis soon becomes the chief course, and finally with the
degeneration of the original tract receives all the blood of the
umbilical veins. This, mingled with the blood of the yolk-sac,
circulates through the liver in the vessels which took their origin
from the vitelline veins — in the venae hepaticse advehentes and
revehentes. Then it flows into the atrium through the terminal
part of the vitelline vein. The latter also receives the inferior vena
cava, which at this time is still inconspicuous, and can therefore
be designated even now, in view of the ultimate condition, as the
cardiac end of the inferior vena cava.

During a brief period all of the placental blood must first traverse
the hepatic circuit in order to reach the heart. A direct passage to
the inferior vena cava
through the ductus veno-
sus Arantii does not yet
exist. But such an out-
let becomes necessary
from the moment when,
by the growth of the
embryo and the pla-
centa, the blood of the
umbilical veins has so
increased in amount
that the hepatic circu-
lation is no longer able
to contain it. There is
then developed on the

under surface of the liver out of anastomoses a more direct
connecting branch, the ductus venosus Arantii (fig. 323 d.A),
between umbilical vein (n.v) and inferior vena cava (c.i"). Thus is
established — and it persists until birth — a condition by which the
placental blood (n.v) is divided at the porta into two currents:
one passing through the ductus venosus Arantii (d.A) into the
inferior vena cava (c.i ") ; the other pursuing a round-about way,
passing through the venae hepaticae advehentes (ha.s and ha.d)
into the liver, here mingling with the blood brought to the liver
through the vitelline vein (pf.a] from the yolk-sac and from the
intestinal canal, which has in the meantime become enlarged, and
finally passing through the venae hepaticse revehentes (h.r), also to
jeach the inferior vena cava (c.i").

There is still something to be added concerning the development of

ha. s

Fig. 323.— Liver of an 8-months human embryo, seen irom

'the under surface, from GEGENBAUE.
Ue, Left lobe of the liver ; r.le, right lobe ; n.v, umbilical

vein ; d.A, ductus venosus Arantii ; pf.a, portal vein ;

ha.s, ha.d, vena hepatica advehens siuistra and dextra ;

h.r, vena hepatica revehens ; c.i', cava inferior ; c.i",

terminal part of the cava inferior, which receives the

vense hepaticae revehentes (h.r).

586 EMBRYOLOGY.

the portal vein. It is to be seen in fig. 323 as an impaired vessel
(pf.a). It empties into the right afferent hepatic vein, derives its
roots from the region of the intestinal canal, and conveys the venous
blood from the latter into the right lobe of the liver. It takes its
origin from the two primitive vitelline veins.

According to the account of His, the two vitelline veins fuse along
the tract where they run close together on the intestinal canal ; on
the contrary, in the region where they run to the liver and are
connected with each other to form two ring-like anastomoses, each of
which encircles the duodenum, an unpaired trunk is formed by the
atrophy of the right half of the lower [posterior] ring and the left
half of the upper one. The portal vein thus formed therefore runs
first to the left and backward [dorsad] around the duodenum, and
then emerges on the right side of it ; it draws its blocd partly from
the yolk-sac and partly from the intestinal canal through the vena
mesenterica. Afterwards the first source is exhausted with the
regressive metamorphosis of the yolk-sac, but the other becomes more
and more productive with the enlargement of the intestine, the
pancreas, and the spleen, and during the last months of pregnancy
conveys a large stream of blood to the liver.

The additional changes, which occur at birth, are easily compre-
hended (fig. 323). With the detachment of the after-birth the
placental circulation ceases. The umbilical vein (n.v) conveys no
more blood to the liver. That portion of its tract which extends
from the umbilicus to the porta hepatis degenerates and becomes a
fibrous ligament (the lig. hepato-umbilicale or lig. teres hepatis),
Likewise the ductus Arantii (d.A) produces the well-known ligament
enclosed in the left sagittal fissure (lig. venosum). The right and
left vense hepaticae advehentes (ha.d, ha.s) again receive their blood,
as in the beginning of the development, from the intestinal canal
through the portal vein (pf.a).

Now that we have become acquainted with the details of the
morphological changes, I close this section on the vascular system
with a short sketch of the fatal circulation of the blood. It is cha-
racteristic of this that no division into two separate circulations, into
the major or systemic and the minor or pulmonary, has yet taken
place ; further, that in most of the vessels neither purely arterial nor
purely venous blood circulates, but a mixture of the two. Purely
arterial blood is contained only in the umbilical veins as they come
from the placenta, whence we will follow the circulation.

Having arrived at the liver, the current of the umbilical veins is

THE ORGANS OF THE INTERMEDIATE LAYER OX MESENCHYME. 587

divided into two branches. One stream goes directly through the
ductus Arantii into the inferior vena cava, and is here mingled with
the venous blood which returns to the heart from the posterior limbs
and the kidneys. The other stream passes through the liver, where
there is added to it the venous blood of the portal vein coming from
the intestine ; by this circuitous course it also reaches, through the
venae hepaticae revehentes, the inferior vena cava. From the latter
the mixed blood flows into the right atrium, but, in consequence of
the position of the Eustachian valve and because the foramen ovale
is still open, the greater part of it passes through the latter into the
left atrium. The other smaller part is again mingled with venous
blood, which has been collected by the superior vena cava from the
head, the upper limbs, and (through the azygos) from the walls of
the trunk, and is propelled into the right ventricle and from there
into the pulmonalis. The latter sends a part of its highly venous
blood to the lungs, the other part through the ductus Botalli to the
aorta, where it is added to the arterial current coming from the left
ventricle.

The blood of the left ventricle comes principally from the inferior
cava, only a small part of it from the lungs, which pour their blood,
which at this time is venous, into the left atrium. It is driven into
the aortic arch and part of it is given off through lateral branches to
the head and upper limbs (carotis communis, subclavia) ; the rest is
carried on downwards in the aorta descendens, where the venous
current of blood from the right atrium by the way of the ductus
Botalli is united with it. The mixed blood is distributed to the
intestinal canal and the lower limbs, but the most of it reaches the
placenta through the umbilical veins, where it is again made arterial.

In the distribution of the blood in the anterior and the posterior regions
of the body a noteworthy difference is easily recognised. The former receives
through the carotis and subclavia a more arterial blood, since to the stream in
the aorta descendens is added the venous blood of the right ventricle through
the ductus Botalli. Especially in the middle of pregnancy is this difference
important. There has been an endeavor to refer to this fact the more rapid
growth of the upper part of the body in comparison with the lower.

As this sketch has shown, there is everywhere a mingling of the
different kinds of blood. This, it is true, is not uniform in the different
months of embryonic life, because, indeed, the separate organs do not
alter in size uniformly, and especially because the lungs during the
later stages are in a condition to receive more blood, and finally
because the foramen ovale and the ductus Botalli become narrower

588 EMBRYOLOGY.

during the last months. On account of these facts, less blood
passes, even before birth, from the inferior vena cava into the left
atrium, and likewise less from the pulmonary artery into the
descending aorta, than was the case in earlier months. Thus there
is gradually introduced toward the end of pregnancy a separation
into a right and a left heart, with their separate blood-currents
(HASSE). But it is almost at a single stroke that this separation, in
consequence of birth, becomes complete.

Great alterations are now brought about by the beginning of
pulmonary respiration and by the cessation of the placental circulation.
Both events cooperate to increase the blood-pressure in the left
heart, and to diminish that in the right. The blood -pressure becomes
reduced because no more blood runs into the right atrium from the
umbilical vein and because the right ventricle must furnish more
blood to the expanding lungs. In consequence of this the ductus
Botalli (fig. 318 n) is closed and then converted into the ligamentum
Botalli. Since, moreover, a greater quantity of blood now flows
from the lungs into the left atrium, the pressure in the latter is
increased, and since at the same time the pressure is diminished in
the right atrium, the closure of the foramen ovale, owing to the
peculiar valvular arrangements, is now effected. For the margin of
the valvuia foraminis ovalis applies itself firmly to the limbus
Vieussenii and fuses with it.

By the closure of the oval foramen and the Botallian duct the
division of the blood-current into a major, systemic circuit and a
minor, pulmonary circuit, which was initiated before birth, is now
completed.

SUMMARY.
Development of the Heart.

1. In the first fundament of the heart two different types can be
distinguished in Vertebrates.

First Type. In Cyclostomes, Selachians, Ganoids, and Amphibia
the heart is developed from the beginning as an unpaired
structure on the under [ventral] surface of the cavity of
the head-gut, in the ventral mesentery, which is thereby
divided into a mesocardium anterius and posterius.

Second Type. In Birds and Mammals the heart is developed
out of separate halves, which afterwards fuse with each
other into a single tube, which then has the same position
as in the first type.

THE ORGANS OF THE INTERMEDIATE LAYER OR MESENCHYME. 589

2. The second type is to be derived from the first, and is explain-
able as an adaptation to the great size of the yolk, in that the heart
is established at a time when the splanchnopleure is still spread out
flat upon the yolk and is not yet folded together to form the head-
gut.

3. The cells which are united to form the endothelium of the
heart are split off from a proliferating, thickened place of the
entoderm.

4. The heart is first established in all Vertebrates in the cervico-
cephalic region behind the last visceral arch.

5. The posterior or venous end of the single cardiac tube receives
the blood from the body through the omphalomesenteric veins ; the
anterior or arterial end gives off the blood to the body through the
truncus arteriosus.

6. In the ainniotic Vertebrates the single cardiac sac is converted
by a series of metamorphoses — (1) by flexures, constrictions, and
changes of position, and (2) by the formation of partitions inside of
it — into a heart composed of two ventricles and two atria.

7. The straight sac assumes the form of a letter 8.

8. The venous portion of the S comes to lie more dorsal, the
arterial more ventral ; the two are marked off from each other by a
constriction, the auricular canal, and are now to be distinguished
as atrium and ventricle.

9. The venous portion or the atrium forms lateral evaginations,
the auricles of the heart, which surround from behind the truncus
arteriosus.

10. The formation of partitions, by which atrium, ventricle, and
truncus arteriosus are divided into right and left halves, begins at
three different places.

(a) First of all, the atrium is divided by an atrial partition into

a right and a left half ; but the separation is incomplete,
since there exists a passage in the partition, the foramen
ovale, which remains open up to the time of birth.

(b) By its downward growth the atrial partition reaches the

auricular canal (septum intermedium of His) and divides
the opening in it into a right and left ostium atrioven-
triculare.

(c) The ventricle is divided into right and left halves by a

partition (septum ventriculi) beginning at the apex of
the heart ; the division is also indicated externally by the
sulcus inter vent ricularis.

590 EMBRYOLOGY.

(d) The truncus arteriosus is divided into pulmonary artery and

aorta by the development of a special partition, which
begins above, grows downward, and joins the ventricular
partition.

(e) The complete separation of the atria first takes place after

birth by the permanent closure of the foramen ovale.

11. At the ostium atrioventriculare and at the ostium arteriosum
the first fundaments of the valves are formed as thickenings of the
endocardium (endocardial cushions) projecting inward.

Development of the Chief Arterial Trunks of Man and Mammals.

12. From the truncus arteriosus there arise five pairs of visceral -
arch vessels (aortic arches), which run along the visceral arches,
embrace the head-gut laterally, and unite dorsally to form the two
primitive aortse.

13. The two vessels fuse at an early period to form the unpaired
aorta lying under the vertebral column.

14. In Mammals, of the five pairs of visceral-arch vessels the first
and second degenerate ; the third furnishes the proximal part of the
carotis interna ; the fourth arch becomes on the left side the aortic
arch, on the right side the arteria anonyma brachiocephalica and
the proximal part of the subclavia ; [the fifth early disappears ;] the
fifth [sixth] arch gives off branches to the lungs, and becomes the
pulmonary artery, but on the left side remains until the time of
birth in open communication with the aortic arch through the
ductus Botalli, whereas the corresponding portion on the right side
atrophies.

15. After birth the ductus Botalli is closed and converted into the
ligament of the same name.

16. From the aorta two pairs of large arterial trunks go to the
foetal membranes — to the yolk-sac the vitelline arteries (arterise
omphalomesentericse), to the allantois and placenta the umbilical
arteries.

17. The vitelline arteries subserve the vitelline circulation, and
afterwards, with the reduction of the umbilical vesicle, degenerate.

18. The umbilical arteries, which continually become larger with
the increasing development of the placenta, arise from the lumbar
portion of the aorta, pass forward [ventral] in the lateral wall of the
pelvis, then at the side of the bladder and along the inner surface of
the abdominal wall to the umbilicus and umbilical cord.

THE OBGANS OF THE INTERMEDIATE LAYER OR MESENCHYME. 591

19. The umbilical arteries give off the iliaca interna to the cavity
of the pelvis, the iliaca externa to the lower limbs.

20. After birth the umbilical artery degenerates into the ligamsn-
tum vesico-umbilicale laterale, with the exception of its proximal part,
which persists as the iliaca communis.

Development of the Chief Venous Trunks.

21. With the exception of the inferior vena cava, all venous trunks
are established in pairs.

22. The two jugulars collect the blood from the head, the two
cardinals from the trunk, but especially from the primitive kidneys.

23. The jugular and cardinal veins of either side unite to form the
Cuvierian ducts, which pass transversely from the lateral wall of the
trunk to the posterior end of the heart, imbedded in a transverse fold
of the front wall of the trunk, the septum transversum.

24. The two vitelline veins collect the blood from the yolk-sac ;
from the navel onward they run in the ventral mesentery to the
septum transversum.

25. The two umbilical veins collect the blood from the placenta ;
from the attachment of the umbilical cord they run at first in the
abdominal wall to the transverse septum.

26. In the septum transversum the Cuvierian ducts and the
vitelline and umbilical veins unite to form the sinus reuniens, which
subsequently disappears as an independent structure and is in-
corporated in the atrium.

27. The cardinal veins diminish in importance (1) in consequence
of the degeneration of the primitive kidneys, and (2) from the fact
that the blood from the lower half of the body is conveyed back to
the heart by the inferior vena cava.

28. The upper part of the inferior vena cava arises as an unpaired,
independent vessel between the two cardinal veins, and then, at the
place where the renal veins empty in, unites with the right cardinal
vein. The latter is in this way converted into the lower portion of
the inferior cava.

29. The Cuvierian ducts with the beginning of the jugular veins
are designated as the vense cavse superiores.

30. An asymmetry in the embryonic venous trunks, which are
established in pairs, is brought about by the fact that the two
superior vense cavse, and also at their middle the remnants of the
two cardinal veins, are joined together by transverse trunks.

592 EMBRYOLOGY.

31. Since through these cross anastomoses more and more of the
blood, and finally the whole of it, is conveyed from the trunks of the
left half of the body into those of the right half, the proximal part
of the left superior vena cava, except a small portion, which lies in
the coronary groove of the heart, degenerates, receives the cardiac
veins, and becomes the sinus.coronarius cordis. Likewise the cardiac
end of the left cardinal vein disappears.

32. From the paired fundaments of the venous trunks are formed
the single superior vena cava, the sinus coronarius cordis, and the
vena azygos and hemiazygos.

33. The vitelline veins, which afterwards become unpaired, give
rise, when the liver is developed, to the portal circulation (the venae
hepaticse advehentes and revehentes).

34. The umbilical veins, of which the right early degenerates, origi-
nally run in the abdominal wall above the liver to the sinus reuniens ;
then the left forms an anastomosis with the vitelline vein under the
liver, whereby its current shares in the portal circulation.

35. There arises out of an anastomosis between the umbilical vein
and the cardiac end of the inferior vena cava on the under surface
of the liver the ductus venosus Arantii, which results in the division
of the blood of the umbilical vein into two currents.

36. After birth the umbilical vein degenerates into the ligamentum
teres hepatis, and the ductus venosus Arantii is obliterated ; the venae
hepaticse advehentes now receive their blood from the terminal part
of the original vitelline vein or the portal vein only, which collects
the blood from the intestinal canal.

37. The septum transversum, in which run the venous trunks on
their way to the heart, is the starting-point for the development of
the diaphragm and the pericardial sac, and forms at first an incom-
plete partition between the abdominal cavity and pleuro-pericardial
cavity, which still communicate with each other on either side of
the vertebral column.

38. The pericardial sac is separated off from the thoracic cavity
as follows : (1) the Cuvierian ducts or future superior venae cavae,
instead of running transversely, run more and more obliquely from
above downward, detach themselves from the septum transversum,
and elevate the pleura into pericardial folds, which run from above
downward and project inward ; (2) the margin of the pericardial fold
fuses with the mediastinum posterius, in which are enclosed oesophagus
and aorta, whereby the superior venae cavae are transferred to the
mediastinum.

THE ORGANS OF THE INTERMEDIATE LAYER OR MESENCHYME. 593

39. The thoracic cavities have for a time the form of tubular spaces
lying on the dorsal side of the heart and on either side of the spinal
column ; they receive the developing lungs, and still communicate
caudad with the abdominal cavity.

40. The two thoracic cavities are separated from the abdominal
cavity by the fusion of the dorsal rim of the septum transversum
with peritoneal folds of the dorsal wall of the trunk (the pillars of

USKOW).

41. The diaphragm is composed of two parts, the ventral septum
transversum, and a dorsal part, the pillars.

42. Upon its first establishment the liver grows into the septum
transversum, but subsequently detaches itself from the latter and
remains united to the diaphragm by means of its peritoneal covering
only, the coronal ligament.

II. The Development of the Skeleton,

With the exception of the chorda dorsalis, which takes its origin
from the inner germ-layer, the skeleton of Vertebrates is a product
of the intermediate layer, resulting from a series of histological
differentiations, a general survey of which has already (p. 540) been
given. There have appeared many articles treating on this very
complicated apparatus in the higher Vertebrates from a develop-
mental and also especially from a comparative-anatomical standpoint.
By an exhaustive treatment of this subject this part of the work
would attain to greater proportions than the plan of the present text-
book permits. I shall therefore limit myself to the more important
conditions of organisation and for what remains refer to the text-
books of comparative anatomy.

Two chief parts are distinguishable in the skeleton of Vertebrates :
(1) the axial skeleton, which is in turn divisible into that of the
trunk and that of the head, and (2) the skeleton of the limbs.
The former is the older and more primitive, being possessed by all
Vertebrates ; the latter has been developed later, and is entirely
wanting in the lower groups (Amphioxus, Cyclostomes).

A. The Development of the Axial Skeleton.

The original foundation of the axial skeleton of all Vertebrates
is the notochord or chorda dorsalis. By this is understood a
flexible, rod-like structure, which is situated in the axis of the body

38

594

EMBRYOLOGY.

below the neural tube and above the intestine and aorta. It reaches
from the front end of the base of the mid-brain to the end of the tail.

For a time after its establishment the front end of the chorda remains in
union at a small place with the epithelium of the fore -gut. This place is
immediately behind the upper attachment of the primitive pharyngeal
membrane (Rachenhaut). There is here found, a little behind the hypo-
physial pocket, a slight depression in the epithelial lining of the fore-gut —
SEESSEL'S pocket or the palatal pocket of SELENKA. It is only some time
after the rupture of the pharyngeal membrane that the chorda becomes
detached from the intestinal epithelium and ter-
minates free in the mesenchyma, often with a
hook-like end (KEIBEL, KANN, CARIUS).

In the case of Amphioxus the chorda is
the only skeletal structure present in the
whole of the soft body; in the lower Ver-
tebrates (Cyclostomes, Fishes, Amphibia) it
exists even in the adult animals as a more
or less important organ ; but in the Amniota
it is reduced almost to obliteration, and only
in the earliest stages of development plays
a role as the forerunner, as it were, of the
higher form of axial skeleton which finally
takes its place. While reference is made
to previous portions of the text-book for in-
formation about the first development of the
chorda, its further metamorphosis may be
treated of here more at length. This varies
according as the chorda becomes a really
functional organ or soon begins to degene-
rate.

In the first instance, when the band of chordal cells has been
constricted off from the inoer germ-layer, it becomes more sharply
limited at its periphery by the secretion of a firm, homogeneous
envelope, the sheath of the chorda (fig. 324 cs). Then the cells
increase in size by the accumulation of fluid within their protoplasm,
which finally exists in the form of a thin superficial layer only ; the
cells become enveloped in firm membranes, thus acquiring exactly
the appearance of plant cells. But directly beneath the sheath of
the chorda (fig. 324) the cells remain small and protoplasmic and
constitute a special layer, the chordal epithelium, which by proli-
feration and metamorphosis of its elements causes an increase of the
substance of the chorda.

Iff. 301 — Cross section
through the vertebral
column of a young
Salmon, after GEGEN-

BAUR.

c*, Sheath of the chorda ;
k, neural arch ; k',
haemal arch ; m, spinal
cord ; a, dorsal aorta ;
v, cardinal veins.

THE ORGANS OF THE INTERMEDIATE LAYER OR MESENCHYME. 595

Immediately after its formation the chorda is in contact above
with the neural tube, below with the entoderm. and laterally
with the primitive segments. This relation is altered as soon as
the intermediate layer makes its appearance between the first
embryonic fundaments. Then a layer of cells grows around the
chorda (fig. 262), spreads itself out from here around the neural tube
above, and furnishes the foundation from which are developed the
segmented vertebral column and in front, in the region of the five
brain- vesicles, the cranial capsule ; it has therefore received the
name of membranous vertebral column and of membranous cranial
capsule (membranous primordial cranium) ; it is also appropriately
designated as skeletogenous layer, the envelope which invests the
chorda being called the skeletogenous sheath of the chorda.
(Compare p. 172 for an account of the first formation of it.)

The mesenchyme also spreads out laterally in the embryo, pene-
trates into the spaces between primitive segments, and is converted
into thin plates of connective tissue (ligamenta intermuscularia), by
means of which the musculature of the trunk is parted into separate
muscle segments (myomeres). The muscle-fibres find attachment
and support upon both the anterior and posterior faces of these
plates.

Such a condition is permanently preserved in Amphioxus lanceo-
latus. The chorda, with its sheath, is the only firm skeletal structure.
Fibrous connective tissue (membranous vertebral column) envelops
it and the neural tube, and sends out into the musculature of the
trunk the intermuscular ligaments.

When the originally membranous tissue surrounding the chorda
and neural tube is followed in its further development in the
embryos of the higher Vertebrates, it is to be seen that it succes-
sively undergoes two metamorphoses : that at first it is partially
chondrified, and that subsequently the cartilaginous pieces are
converted into osseous tissue ; or, in other words, the first-established
membranous vertebral column is soon converted into a cartilaginous,
and this in turn is replaced by a bony one, and in the same manner
the membranous primordial cranium is transformed into a cartila-
ginous, and this in turn into a bony cranial capsule.

The three stages which succeed one another in the development
of the higher Vertebrates are also encountered in a comparative-
anatomical investigation of the axial skeleton in the series of
Vertebrates, and in such a manner that the condition, which in
many classes appears only as a transitory embryonic one, is retained

596

EMBRYOLOGY.

permanently in the lower classes. As Amphioxus possesses a
membranous axial skeleton, so the Selachians and certain of the
Ganoids are representatives of the stage with cartilaginous vertebral
column. The third stage in the evolution of the axial skeleton is
more or less completely attained by all the higher Vertebrates.

This, again, is a very instructive example — of which the embryology
of the skeleton presents many others — of the parallelism which exists
between the development of the individual and that of the race ; it
teaches how e'mbryological and comparative-ana-
tomical investigations are mutually complemental.
In the detailed description of the conditions
which are observed in the development of the
cartilaginous and bony axial skeleton, I shall limit
myself to Man and Mammals, and since great
differences exist between the posterior region,
which encloses the spinal cord, and the anterior,
which envelops the vesicles of the brain, I shall
treat of them separately.

Fig. 325. — Longitu-
dinal [frontal] sec-
tion through the
thoracic region of
the vertebral
column of a human
embryo 8 weeks
old, after KOL-
LIKER.

v, Cartilaginous
body of vertebra;
li, intervertebral
ligament; ch
chorda.

(a) Development of the Vertebral Column.

The process of chondrification commences in
Man at the beginning of the second month. At
certain places in the tissue enveloping the chorda
the cells secrete between themselves a cartilaginous
matrix, and move farther apart, whereas at other
intervening and narrower tracts the character of
the tissue is not altered (fig. 325). In this manner
the skeletogenous layer is differentiated into nu-
merous vertebral bodies (v), which in longitudinal sections are the
more translucent, and into the intervertebral discs (ligamenta
intervertebralia) which separate them (li).

The process of chondrification, as FEOKIEP has followed it in the case of the
embryo calf, proceeds as follows: there arise on both sides of the chorda
masses of cartilage which are united on the ventral side of it by a thinner
layer. Somewhat later the cartilaginous half-cylinder is closed on the dorsal
side also.

Upon the appearance of a segmented vertebral column the
chorda loses its function of a supporting skeletal rod. From this
time forward it therefore suffers a gradual obliteration. The parts
enclosed in the bodies of the vertebrae are restricted in their growth,

THE ORGANS OF THE INTERMEDIATE LAYER OR MESENCHYME. 597

whereas the shorter portions lying in the soft intervertebral discs
continue to enlarge (fig. 325 ch). Thus the chorda now acquires the
appearance of a string of beads, since thickened spheroidal portions
are joined to one another by small connecting thread-like portions.
Subsequently it entirely disappears in the bodies of the vertebrae,
especially when the latter begin to ossify (fig. 326) ; the intervertebral
portion (li) alone persists, although indistinctly limited from the

Fig. 326.— longitudinal [sagittal] section through the intervertebral ligament and the adjacent
parts of two vertebrae from the thoracic region of an advanced embryo Sheep, after KULLIKER.

la, Ligament longitudinale anterius ; lp, lig. long, posterius ; li, lig. inter vertebrale ; k, k', car-
tilaginous caps (epiphyses) of the vertebrae ; w and 10', anterior and posterior vertebra? ;
c, intervertebral, c' and c", vertebral enlargements of the chorda.

surrounding tissue, and produces by the proliferation of its cells the
gelatinous core of the intervertebral disc.

Soon after the appearance of the bodies of the vertebrae the funda-
ments of the corresponding arches are observable. According to
FRORIEP'S account, there arise small, independent pieces of cartilage
in the membrane enveloping the spinal cord, in the immediate
vicinity of the bodies of the vertebrae, with which they soon fuse.
Their growth is rather slow. During the eighth week they still
appear in Man as short processes from the bodies of the vertebrae,
so that the spinal cord is still covered dorsally by the membranous
skeleton. In the third month they grow into contact with each
other at the dorsum ; however, it is only in the following month

598 EMBRYOLOGY.

that a complete fusion takes place, and that cartilaginous neural
spines are formed. The part of the membrane which lies between
the cartilaginous arches furnishes the ligamentous apparatus.

In the process of chondrification the nascent bodies of the vertebrae
have a fixed position relative to the primitive or muscle-segments ;
it is such that on either side of the body they are adjacent to two
of the latter, one half to a preceding segment, the other half to a
following one ; or, in other words, the bodies of the vertebrae and the
muscle-segments do not coincide, but in their positions alternate with
each other.

The necessity of such an arrangement follows from the very
function which vertebral column and musculature together have to
fulfil. The axial skeleton must possess two opposite properties
united : it must be firm, but also flexible, — firm, in order to serve as
a support for the trunk ; flexible, so as not to impede the motions of
the latter. Since a continuous cartilaginous rod would not have
possessed sufficient flexibility, the process of chondrification could not
take place throughout the whole extent of the skeletogenous layer,
but there must be left more elastic tracts, which allow a movement
of the cartilaginous pieces on one another. But a movement of the
cartilaginous pieces would obviously be impossible if they should lie
so that the muscle fibres had their origin and insertion on one and
the same vertebral element. In order that the fibres of a muscle-
segment may operate upon two vertebrae, the muscular and vertebral
segments must alternate in position.

This process, which is easily intelligible in the way in which it has
been outlined, has given occasion for the assumption of a " reseg-
mentation of the vertebral column" This conception originated with
REMAK, and since then has been for a long time tenaciously held to
in the literature.

REMAK, like other embryologists before him (BAER), perceived in
the primitive segments of the Chick the material for the establishment
of the vertebral column, and therefore gave them the name " proto-
vertebrae." But inasmuch as he found that the cartilaginous vertebrae
did not afterwards correspond in position with the protovertebrae, he
announced the proposition that a new " segmentation of the vertebral
column takes place, from which arise the secondary, permanent bodies
of the vertebrae."

Both the name " protovertebra " and the assumption of a reseg-
mentation of the vertebral column should be dropped, and for the
following reasons : —

THE ORGANS OF THE INTERMEDIATE LAYER OR MESENOHYME. 599

The signification of the primitive segments consists, if not exclu-
sively, at least principally, in this, that they are the fundaments of
the musculature of the body. But in the arrangement of the muscur
lature is expressed the original and oldest segmentation of the vertebrate
body. It is present even in Amphioxus and the Cyclostomes. The
segmentation of the vertebral column, on the contrary, was acquired
much later, and has resulted, as was explained above, from a necessary
dependence on the segmentation of the musculature. A primary
segmentation of the vertebral column as understood by REMAK and
his followers has never existed, for the cartilaginous vertebrae are
formed from an unsegmented mass of tissue enveloping the chorda —
from the skeletogenous layer. One cannot speak of a segmentation
of the vertebral column until the beginning of the process of chon-
drification, by reason of which alone it became necessary.

Even before the cartilaginous vertebral column has been completely
established, it enters in Mammals upon the third stage, which begins
in Man at the end of the second month.

The ossification of every cartilage takes place in the main in a
corresponding, typical manner. Blood-vessels at one or several
places grow from the surface into its interior, dissolve the matrix of
the cartilage of a limited region, so that there arises a small cavity
filled wifch vascular capillaries and marrow-cells. In the vicinity of
this salts of lime are deposited in the cartilage. By a portion of the
proliferated medullary cells, which become osteoblasts, bone substance
is then secreted (fig. 326 w). In this manner there arises in the
midst of the cartilaginous tissue a so-called bone nucleus or centre of
ossification, around which the destruction of the cartilage and its
replacement by osseous tissue advance further and further.

The places where the separate bone nuclei are formed, as well as their
number, are tolerably uniform for the different cartilages.

In general the ossification of each vertebra proceeds from three
points. At first a centre of ossification is established in the base of
each half of the vertebral arch, to which there is added somewhat
later a third centre in the middle of the body of the vertebra. In
the fifth month the ossification has advanced up to the surface of
the cartilage. Each vertebra is now distinctly composed of three
pieces of bone, which for a long time continue to be joined to one
another by bridges of cartilage at the base of each half of the arch
and at the union of the latter with the vertebral spines. The last
remnants of cartilage do not ossify until after birth. During the
first year with the development of a bony spinous process the halves

600 EMBRYOLOGY.

of the arch are fused. Each vertebra is then separable after
destruction of the soft parts into two pieces, into the body and the
arch. These are united between the third and eighth years.

In addition to the pieces of bone just described, accessory centres of ossification
appear on the vertebras in subsequent years ; it is in this way that there arise
the epiphysial plates at the end-surfaces of the body and the small bony pieces
at the ends of the vertebral processes (the spinous processes and the transverse
processes). SCHWEGEL gives detailed information concerning the time of their
appearance and their fusion.

Cartilaginous skeletal parts, which serve for the support of the
lateral and ventral walls of the body, the ribs and the breast bone,
contribute to the completion of the axial skeleton.

The ribs are developed independently of the vertebral column, in
Man during the second month, by the chondrification of strips of
tissue in the intermuscular ligaments between the successive muscle-
segments. They are at first visible as small bent rods in the imme-
diate vicinity of the body of the vertebra, and from here they rapidly
extend ventrally.

In early stages of development ribs are established from the first
to the last segment of the vertebral column (the coccyx in Man
excepted), but only in the case of the lower Vertebrates (Fishes,
many Amphibia, and Reptiles) are they developed into large bows
supporting the wall of the trunk in a uniform manner in all regions,
whereas in Mammals and in Man they exhibit in the separate regions
of the vertebral column different conditions. In the neck, lumbar
and sacral regions, they appear from the beginning in a rudimentary
condition only, and imdergo metamorphoses to be described later. It
is exclusively in the thoracic region that they attain important
dimensions, and here at the same time they give rise to a new skeletal
part — the breast bone, or sternum.

The sternum, which is wanting in Fishes and Dipnoi, but is present
in Amphibia, Reptiles, Birds, and Mammals, is a formation derived
from the thoracic ribs, and is originally established, as RATHKE was the
first to discover, as a paired structure, which early fuses into an
unpaired skeletal piece.

RUGE has followed the development of the sternum in Man in a
very thorough manner, and has found that in embryos 3 cm. long the
first five to seven thoracic ribs have become prolonged into the ventral
surface of the breast and by a broadening of their ends have united
at some distance from the median plane to form a cartilaginous band,
whereas the following ribs end free and at a greater distance from

THE ORGANS OF THE INTERMEDIATE LAYER OR MESENCHYME. 601

the median plane. The two sternal bars are separated from each
other by membranous tissue ; later they approach each other in the
median plane, and commencing in front, begin to fuse together into
an unpaired piece, from which the individual ribs which gave rise to
them are afterwards separated by the formation of joints.

The paired origin of the sternum serves to explain some of its
abnormalities. For example, in the adult there is sometimes seen
a fissure, which, although closed by connective tissue, passes quite
through the sternum (fissura sterni), or a few larger or smaller gaps
are found in the body and xyphoid process of the sternum. All
these abnormal cases are explained by the complete or partial failure
of the two sternal bars to fuse in the
usual way during embryonic life.

The ossification of ribs and sternum
is in part accomplished by the develop-
ment of special centres of ossification,
that of the ribs beginning as early as
the second month, the sternum some-
what late, in the sixth foetal month.

Each rib contains at first one centre of
ossification, through the enlargement of
which the bony part is formed, while next
to the sternum a portion remains cartila-
ginous throughout life. In the eighth to
the fourteenth year there appear in the
capitulum and tuberculum of the rib, ac-
cording to SCHWEGEL and KOLLIKEB, ac-
cessory centres, which fuse with the main
piece between the fourteenth and the twenty-
fifth year.

The sternum (fig. 327) ossifies from nu-
merous centres, of which one arises in the manubrium, and from six to twelve
in its body. Between the sixth and twelfth years the latter begin to fuse
together into the three or four large pieces of which the body of the sternum
is composed. The xyphoid process remains partly cartilaginous, but acquires
a centre of ossification during childhood.

Kegarding the episternal pieces which appear on the manubrium, the text-
books of comparative anatomy and the article by HUGE should be consulted.

Through inequalities in the development of the separate vertebral
and costal fundaments and through the fusions which take place here
and there are produced the different regions of the skeleton of the
trunk: the cervical, dorsal, and lumbar regions of the vertebral
column, the sacrum and coccyx. A correct understanding of these
skeletal parts is to be acquired only through embryology.

Fig. 327. — Cartilaginous sternum,
with portions of the ribs attached
and with several centres of ossi-
fication (frfr), from a child two
years old.

k, Cartilage ; kk, centres of ossifica-
tion ; sch, xyphoid process.

602 EMBRYOLOGY.

The rudimentary fundaments of the cervical ribs at their first
appearance fuse with the cervical vertebrce, at one end with the body of
the vertebra, at the other with an outgrowth of the neural arch,
and with the latter enclose an opening through which the vertebral
artery runs — the foramen transversarium. The so-called transverse
process of the cervical vertebra is therefore a compound structure,
and were better designated lateral process, for the bony rod that lies
dorsad of the foramen transversum is formed by an outgrowth from
the vertebra and alone corresponds to the transverse process of a
dorsal vertebra ; the ventral rod, on the contrary, is a rudimentary
rib, which possesses in fact a separate centre of ossification.

The fundament of the rib of the seventh cervical vertebra occa-
sionally attains greater size, does not fuse with the vertebra — which
consequently does not possess any foramen transversarium — and is
described under the abnormalities of the skeleton as free cervical rib.
Its presence is explained therefore as being the result of a more volu-
minous development of a part which in all cases exists as a fundament.

The transverse process of the lumbar vertebrce is also better designated
as lateral process, because it encloses the rudiment of a rib. This ex-
plains the phenomenon of a thirteenth or small lumbar rib occasion-
ally observed in Man.

The sacral region is the one that is most modified. A large number
of vertebrae in this region by becoming firmly united with the pelvic
girdle have lost the power of moving on one another, and are fused
together into a large bone : the sacrum. This consists in human
embryos of five separate cartilaginous vertebrae, the first three of
which especially are characterised by very broad, well-developed
lateral processes.

I say lateral processes because comparative-anatomical grounds
and embryological evidence both indicate that there are included in
them rudimentary sacral ribs, such as in lower Vertebrates make their
appearance as independent structures. On the embryological side,
the method of their ossification favors this view, for each sacral
vertebra undergoes ossification from five centres. To the three
typical centres, those of the body and the neural arches, are added
in the lateral processes large bone-nuclei (centres), which are com-
parable with the centres of ossification of a rib. They produce the
well-known lateral masses of the sacrum (massae laterales), which
bear the articular surfaces for union with the ilium.

The fusion of the five bony pieces of a sacral vertebra, at first
separated by strips of cartilage, takes place later than in other parts

THE ORGANS OF THE INTERMEDIATE LAYER OR MESENCHYME. 603

of the vertebral column, namely, between the second and the sixth
year after birth. For a long time the five sacral vertebrae remain
separated from one another by their intervertebral discs, which
begin to ossify in the eighteenth year ; the process has usually come
to an end by the twenty -fifth year.

Behind the sacrum there follow four or five rudimentary coccygeal
vertebrae, which represent the caudal skeleton of Mammals and do
not acquire centres of ossification until very late. In the thirtieth
year or later they may fuse with one another, and sometimes with
the sacrum.

Atlas and epistropheus (axis) now demand special mention. These
vertebrae acquire their peculiarities of form by an early fusion of the
cartilaginous body of the atlas (fig. 328a) with the epistropheus (e)
to form the odontoid process of the latter. The one therefore
contains less, the other more than a normally developed vertebra.

That the odontoid process is the real body of
the atlas is recognisable even later by means of
two facts. First, like every other vertebral a

body, it is traversed, as long as it remains t

cartilaginous, by the chorda, which at the tip Fig 328._]^ian section
of the process is continued into the ligamentum through the body and

suspensorium and from this into the base of the ^8

cranium. Secondly, it acquires in the fifth in the cartilage two cen-

month of development a separate centre of ^ afareto beam n*

ossification (fig. 328 a), which is not com-

pletely fused with the body of the epistropheus until the seventh

year.

The neural arches of the atlas, which have remained independent,
are joined together on the ventral side of the odontoid process by a
tract of tissue in which an independent piece of cartilage is formed
(hypochordal cartilage-rod of FRORIEP) — a structure which, according
to FRORIEP, is present in every vertebra in the case of Birds. This
piece of cartilage develops in the first year after birth a special centre
of ossification, fuses between the fifth and the sixth year with the
lateral halves, and constitutes the anterior [ventral] arch (KOLLIKER).

(b) Development of the Head-Skeleton.

From its position the skeleton of the head appears as the most
anterior part of the axial skeleton, but it is on the whole very unlike
the posterior part, — the vertebral column, — because it is adapted to

604 EMBRYOLOGY.

peculiar purposes. For in the morphological plan of Vertebrates the
head takes, in comparison with the trunk, a preeminent position ; it
is furnished with especially numerous and highly developed organs
concentrated into a short space.

The neural tube has here become differentiated into the volu-
minous brain, with its dissimilar regions. In its immediate vicinity
have arisen complicated sensory organs such as nose, eye, and ear.
Likewise the part of the digestive tube enclosed within the head bears
in many ways its peculiar stamp, since it contains the mouth opening
and is provided with organs for the reception and trituration of the
food, and is pierced by visceral clefts. All of these parts exercise a
determining influence on the form of the skeleton, which adapts itself
most accurately to the brain, to the sensory organs, and to the
functions of the head-gut, and thereby becomes a very complicated
apparatus, especially in the higher Vertebrates.

Embryology sheds a flood of light on the method of the origin
of the cephalic skeleton of Vertebrates; it shows the relations to
one another of widely different lower and higher forms, and also
answers the question, What relation do the vertebral column and
head-skeleton sustain to each other in the plan of organisation
of Vertebrates ? Consequently the development of the cephalic
skeleton proves to be an especially interesting subject, which has
always attracted morphologists, and which has incited to careful
investigation.

During the account some comparative-anatomical digressions will
be made, which will contribute to the better comprehension of
certain facts, especially those treated of in the final section, in
which the vertebral theory of the skull will be briefly discussed.

As in the case of the vertebral column, there are to be distin-
guished three stages of development according to the histological
character of the sustentative substance : a membranous, a carti-
laginous, and a bony.

The chorda serves as the foundation for the membranous skeleton
of the head, and extends forward to the between-brain. At its
anterior end there is formed in Amniota the cephalic flexure, by which
the axis of the first two brain-vesicles makes an acute angle with
the three following ones (fig. 153). Here also the mesenchyme
early grows around the chorda and envelops it in a skeletogenous
layer, which spreads out from this region laterad and dorsad,
enveloping the five brain-vesicles, and is subsequently differentiated
into the membranes of the brain and a layer of tissue, which

THE ORGANS OF THE INTERMEDIATE LAYER OR MESENCHYME. 605

becomes the foundation of the cranial capsule, and has received the
name of membranous primordial cranium.

Thus far there is an agreement in the development of the
vertebral column and of the cranium. With the beginning of
the process of chondrification the conditions become more peculiar.
Whereas in the region of the spinal cord the skeletogenous layer
undergoes a regular differentiation into cartilaginous and connective-
tissue parts — into vertebrae and vertebral ligaments — and is thereby
divided into successive movable segments, such a segmentation does
not take place in the head.

The layer of tissue called membranous primordial cranium undergoes
continuous chondrification into a non-articulate capsule enveloping the
brain-vesicles. If we go through the whole series of Vertebrates
down to the lowest, in no one of them is there exhibited a separation
into movable segments corresponding to vertebrae. Therefore the
anterior part and the remaining part of the axial skeleton pursue from
an early period different directions in their development.

The contrast is intelligible in view of the different duties to be
fulfilled in the two regions, and especially in consideration of the
different influences which the action of the muscles exercises upon
the form of the skeleton.

In water-inhabiting animals the trunk-musculature is the most
important organ of locomotion, for it bends the trunk now in this
direction, now in that, and thereby propels it forwards through the
water. If, however, the head region were likewise flexible and
movable, it would be disadvantageous for forward motion, inasmuch
as a rigid part operates as a cut-water. Moreover, the musculature
developed on the head assumes a different function, inasmuch as in
the grasping of food and in the process of respiration — which is
accompanied by an enlargement and reduction of the respiratory
tract of the alimentary tube — it now adducts and then abducts the
ventrally situated parts of the axial skeleton. Besides, it is advan-
tageous here to have the skeletal axis present firm points of
attachment for the muscles. Finally, the voluminous development
of the brain and the higher sensory organs is likewise a participating
influence tending to make the part of the head that serves for thoir
reception an inflexible region.

In view of these various factors working in the same direction, it
becomes intelligible that in the head a segmentation of the axial skeleton
is wanting from the beginning.

In other respects there prevails a great agreement with the

606

EMBRYOLOGY.

vertebral column, especially in the manner in which the metamor
phosis into cartilaginous tissue takes place in the membranous
primordial cranium. In both the chondrification first begins at the
surface of the chorda dorsalis (fig. 329 A).

As a foundation for the base of the skull there arise two pairs of
elongated cartilages : behind, on either side of the chorda, the two
parachordal cartilages (PE); in front, the two trdbeculce cranii (TV)
of RATHKE, which begin at the tip of the chorda and from there
run forward beneath the between- and the fore-brain.

Fig. 329 A and B.— First fundament of the cartilaginous primordial cranium, from WIEDERS-

HEIM.

A, First stage. C, Chorda ; PE, parachordal cartilage ; Tr, RATHKE'S trabeculse cranii ; PR,
passage for the hypophysis ; N, A, 0, nasal pit, optic vesicle, otocyst.

B, Second stage. C, Chorda ; B, basilar plate ; T, trabeculse cranii, which have become united

in front to constitute the nasal septum (S) and the ethmoid plate ; Ct, AF, processes of the
ethmoid plate enclosing the nasal organ ; 01, foramina olfactoria for the passage of the
olfactory nerves; PF, post-orbital process; NK nasal pit A,\ 0, optic and labyrinthine
vesicles.

The four pieces soon fuse with one another (fig. 329 B). The two
parachordal elements grow around the chorda, first below, then above,
thus enveloping it and producing the basilar plate (B). Its anterior
margin rises far up into the angle of the flexure between mid-brain
and between-brain and corresponds to the future dorsum sellae. The
trabeculce cranii (T) spread out at their anterior ends, which become
fused to constitute the ethmoid plate (&), the foundation of the
anterior portion of the cranium, which acquires its particular
stamp through its reception of the organ of smell. In the middle of
their length they remain separate a long time, and enclose an opening,

THE ORGANS OF THE INTERMEDIATE LAYER OR MESENCHYME. 607

which corresponds to the sella ttircica, and has been caused by the
formation of the hypophysial pocket from the oral sinus and by its
growing through the membranous basis of the cranium toward the
infundibulum of the brain. Rather late there is also formed, as the
floor of the sella turcica, beneath the hypophysis, a thin cartilaginous
plate, which is pierced only by the holes for the internal carotids.

After the base of the cranium has been developed, the process of
chondrification involves the side walls and at last the roof of the
membranous primordial cranium, precisely as the halves of the
neural arch grow out from the body of the vertebra and finally
terminate in the dorsal spine.

In this manner there is developed around the brain in the case of
the lower Vertebrates, in which the axial skeleton remains in the
cartilaginous condition throughout life (fig. 330), a closed, tolerably
thick- walled capsule, the cartilaginous primordial cranium.

In the higher Vertebrates, in which to a greater or less degree
processes of ossification occur later, the primordial cranium attains a
less complete development, as is shown by the fact that its walls
remain thinner, and indeed acquire at some places openings, which
are closed by connective -tissue membranes. In Mammals the latter
condition occurs very extensively in the roof of the skull, which
becomes cartilaginous only around the foramen magnum, whereas in
the region in which afterwards the frontal and parietal bones are
located the cranium remains membranous. The cartilage attains a
greater thickness only at the base of the cranium and in the regions
of the olfactory organ and the membranous labyrinth, where it gives
rise to the nasal and ear capsules.

For the sake of better orientation, it is useful to distinguish in the
primordial cranium different regions. There are two different prin-
ciples of division that may be employed in this connection.

Following GEGENBAUR, one can divide the primordial cranium, in
accordance with its relation to the chorda dorsalis, into a posterior
and an anterior portion.

The posterior region reaches up to the dorsum sillse and encloses in
its basal portion the chorda, which in Man enters into it from the
odontoid process through the ligamentum suspensorium dentis. The
anterior portion is developed in front of the pointed end of the
chorda out of RATHKE'S cranial trabeculse. GEGENBAUR designates
the two as vertebral and evertebral regions (for which KOLLIKER
employs the names chordal and prechordal) ; he shows that the
vertebra^ region must be, on account of its relation to the chorda, the

608

EMBRYOLOGY.

older part and alone comparable with the remainder of the axial
skeleton, that the non-vertebral part, on the contrary, is a later acquisi-
tion and constitutes a new structure, which has been caused by the
forward extension of the fore-brain vesicle and by the development
of the organ of smell, to the enclosing of which (nasal capsule) it
contributes.

The second method of division is based upon the different appear-
ance which the individual regions of the primordial cranium acquire
through their relations to the sense organs. The anterior end of

Ik

Fig. 330.— Diagrammatic representation of the cartilaginous cranial capsule and the cartilaginous
visceral skeleton of a Selachian and of the larger nerve trunks of the head.

2V, Nasal capsule (ethmoid region of the prin ordial cranium) ; Au, cavity for the eye (orbital
region) ; La, region of the labyrinth ; Oc, occipital region of the cranium ; O, palato-quad-
ratum ; U, lower jaw (mandibulare) ; Ik, labial cartilage ; zb, hyoid arch ; kb, first to fifth
branchial arches ; Tr, nervus trigeminus ; Fa, facialis ; 01, glosso-pharyngeus ; Va, vagus ;
rl, ramns lateralis of the vagus ; rb, rami branchiales of the vagus.

the cartilaginous capsule (fig. 330) receives the organ of smell ; a
following portion contains depressions for the eyeballs ; in a third
are imbedded the membranous auditory labyrinths ; finally, a fourth
effects a union with the vertebral column. Consequently one may
distinguish an ethmoidal, an orbital, a labyrinthine, and an occipital
region.

In addition to the cartilaginous primordial cranium, there are
developed in the head numerous cartilaginous pieces (which serve as
supports to the walls of the head-gut) in a manner similar, although
not directly comparable, to that in which the ribs (fig. 330) have

THE ORGANS OF THE INTERMEDIATE LAYER OR MESENCHYME. 609

Atf.

ci '

Xm

Bnt

J.'a

LcA

arisen in the walls of the trunk in the region of the vertebral
column. Together they constitute a skeletal apparatus which under-
goes in the series of Vertebrates very profound and interesting
metamorphoses. Whereas it attains in the lower Vertebrates a
great development, it becomes in part rudimentary in Reptiles, Birds,
and Mammals. The part, however, which remains furnishes the
foundation for the facial skeleton. I begin with a short sketch of
the original conditions in the lower Vertebrates, especially in the
Selachians.

As has been described in a previous chapter, the lateral walls of
the head-gut are traversed by the visceral clefts, of which there are
ordinarily as many as six in Sharks (fig. 331). The bands of sub-
stance intervening between
the clefts are called the
membranous throat- or
visceral arches. They con-
sist of a connective-tissue
foundation invested with
epithelium, of transversely
striped muscle -fibres, and
of the visceral-arch blood-
vessels (see p. 571). Inas-
much as they have different
functions to fulfil, and con-
sequently acquire different
forms, they are distin-
guished as jaw-, hyoidj and
branchial arches. The most
anterior of them is the jaw-arch, which serves to bound the oral
opening. Following this, and separated from it by only a rudi-
mentary visceral cleft, the spiracle, is the hyoid arch, which is
connected with the origin of the tongue. Ordinarily this is followed
by five branchial arches.

At the time when the membranous primordial cranium is con-
verted into cartilage, chonclrification also takes place in the con-
nective tissue of the membranous visceral arches, thus producing the
cartilaginous visceral arches (fig. 331). These exhibit a regular
segmentation into several pieces, placed end to end and articulated
with one another by connective tissue.

The jaw-arch is divided on either side into a cartilaginous palato-
quadratum (fig. 330 0) and a lower jaw (mandibulare). These

39

Fig. 331.— Head of a Shark embryo 11 lines long.

From PARKER AND BETTANY.
Tr, RATHKE'S trabeculae cranii ; Pl.Pt, pterygo-quail-

ratum ; Mn, mandibular cartilage ; Hy, byoid

arch ; Br.1, first branchial arch ; Sp, spiracle ;

CT, first branchial cleft ; Lch, groove tinder the

eye ; JVa, fundament of the nose ; E, eyeball ;

Au, auditory vesicle ; C.I, C.2, C.3, brain-vesicles ;

Hm, cerebral hemispheres ; f.n.p, f ronto-nasal

process.

610 EMBRYOLOGY.

carry, in the mucous membrane investing them, the teeth of the
jaws. The two mandibular elements are united to each other in
the median plane by means of a mass of tense connective tissue.
The following visceral arches, on the contrary, are alike in having
their lateral halves, which are divided into several pieces, joined
ventrally by means of an unpaired connecting piece, the copula, in
a manner similar to that in which the ribs are united by the sternum.
The pieces of the hyoid arch are designated, in sequence from the
dorsal to the ventral side, hyomandibular, hyoid, and (the copula)
os entoglossum.

In Mammals and Man (figs. 154, 157) structures similar to those
of the Selachians are formed in the membranous stage, but sub-
sequently they are only in part converted into cartilaginous pieces,
which in turn never acquire a great size, having meantime lost
their original function. They help to form the facial part of the
head-skeleton, and have already been treated of partially in
previous chapters — in the discussion of the head-gut and of the
organ of smell. I am therefore compelled for the sake of continuity
to repeat much that has already been presented concerning the
visceral skeleton.

In very young human and mammalian embryos the mouth-opening
is bounded on the sides and below by the paired maxillary and
mandibular processes (tig. 156, compare p. 284). The former are
widely separated from each other, because the unpaired frontal
process, in the form of a broad, rounded projection, is at first
inserted from above between them. Afterwards this projection
becomes divided by the development, on its rounded surface, of the
two nasal pits with the nasal grooves leading down to the upper
margin of the mouth (compare p. 513); it is then divided into the
outer and inner nasal processes. The former are separated from the
maxillary process by a groove, which runs from the eye to the nasal
furrow, and is the first fundament of the lachrymal duct.

Behind the first visceral arch comes the hyoid arch (figs. 157, 158
zb), the two being separated by a small visceral cleft, which becomes
the tympanic cavity and Eustachian tube. This is followed by three
additional visceral arches with three visceral furrows (or clefts),,
which are of only short duration.

During a later stage fusions take place between the processes that
surround the oral opening (fig. 332).

The maxillary processes, by growing farther inward, meet the
inner nasal processes, fuse with them, and produce a continuous

THE ORGANS OF THE INTERMEDIATE LAYER OR MESENCHYME. 611

Fig. 332. — Roof of the oral cavity of a human embryo with
fundaments of the palatal processes, after His. Magnified
10 diameters.

upper boundary to the mouth. In this way each olfactory pit with
its nasal groove is converted into a canal, which leads into the
oral cavity through an inner opening close behind the margin of
the upper jaw. The
membranous margins
of the upper and
lower jaws also lose
their superficial posi-
tions, because the
skin that covers them
is raised up into ex-
ternally projecting
folds, and forms the
lips, which from this
time forward consti-
tute the boundary of
the oral opening.

A third stage, with
the development of the palate, practically completes the formation of
the face. (Compare pp. 515-17.) From the membranous upper jaw
there arise two ridges projecting into the mouth-cavity (fig. 290) ;
these become enlarged into the palatal plates, which grow horizontally.

The plates meet in the median plane and fuse with each other and
with the median part of the frontal process, which has meantime
become reduced by the enlargement of the olfactory organ to the thin
nasal septum. Thus there is cut off from the primary oral cavity
an upper chamber, which contributes to the enlargement of the nasal
cavity, and which opens into the pharynx through the posterior
nares; at the same time [as the result of this growth] there has
arisen a new roof of the mouth-cavity, — the palate, — which is after-
wards differentiated into hard and soft palate.

A further differentiation of the face, which is now in the mem-
branous stage of development, is brought about by the process of
chondrification. This produces, however, in Mammals, as compared
with Selachians, only small and unimportant skeletal structures.
Some of these structures undergo degeneration (MECKEL'S cartilage),
some are utilised as auditory ossicles in the function of hearing, and
others are united to form the fundament of the hyoid bone. They
arise from the soft tissue of the first, second, and third visceral
arches ; in the case of the fourth and fifth arches there is not even
a process of chondrification in Mammals, so that with the closure of

612

EMBRYOLOGY.

the fissures they are no longer recognisable as distinct parts, unless
perhaps the thyroid cartilage is to be referred to them (DUBOIS).

I will describe the conditions in detail, first in the case of sheep
embryos of different stages of development, and then in the case of
a human embryo.

In a sheep embryo 2 cm. long there are to be found, according

to the account of

am' am ha mk zb «* SALENSKY (fig. 333),

Lf^MBH^bBte^ two long and slender

cylindrical cartila-
ginous rods, one in
front, the other be-
hind the first visceral
cleft ; their posterior
(proximal) ends abut
upon the labyrinth-
region of the primor-
dial cranium, and are
hero united to each
other by means of
embryonic connective
tissue. In older em-
bryos (fig. 334) the
first visceral arch be-
comes at its upper
[proximal] end more
and more distinctly
segmented, by means
of constrictions, into
two smaller pieces
and a larger one.
The first small piece,
the one lying next
to the wall of the

labyrinth, gradually assumes the form of the incus (am) with its
processes, the second becomes the malleus (ha) ; the two are joined
by means of a mass of connective tissue. The third piece (mk) is of
considerable length, and has the form of a cylindrical rod; it is
enclosed in the membranous lower jaw, and is designated in honor
of its discoverer as MECKEL'S cartilage. It remains for a long time
in union with the fundament of the malleus by means of a narrow

Figs. 333, 334.— The dissected-out cartilages of MECKEL and
EEICHERT with the fundament of the auditory ossicles,
from a sheep embryo 2-7 cm. long. After SALENSKY.

Fig. 333. — mk, MECKEL'S cartilage ; ha, hammer (malleus) ;
am, anvil (incus) (long process) ; am', its short process ;
zb, cartilaginous hyoid arch.

Fig. 884. — am, Anvil; am', its short process; ha, hammer;
hah, hammer-handle ; st, stirrup (stapes) ; ink, MECKEL'S
cartilage ; zb, cartilaginous hyoid arch.

THE ORGANS OF THE INTERMEDIATE LAYER OR MESENCHYME. 613

cartilaginous bridge, upon which the long process (pr. gracilis) of
the malleus is afterwards developed by periosteal ossification. The
second visceral arch (zb) becomes incorporated in the hyoid bone.

In a human embryo of the fifth month one observes structures
similar to those just described, only somewhat further developed
Figure 335 exhibits the incus (am), easily recognised by its form,
lying on the wall of the labyrinth ; with it is articulated the malleus
(ha), the long process of which is continuous with MECKEL'S cartilage
(MK). This extends ventrally as far as the median line, where it
is united with the cartilage of the opposite side by means of con-
nective tissue — a kind of symphysis.

The second visceral cartilage, called also REICHERT'S cartilage, has
become divided into three portions. The uppermost portion is fused
with the labyrinth-region — the petrous portion of the temporal bone
— and constitutes the fundament of the processus styloideus (grf) •
the middle portion has become fibrous tissue in Man, and forms
a strong ligament, the lig. stylohyoideum (Isth), whereas in many
Mammals it becomes a large cartilage ; the third and lowest portion
produces the lesser cornu (kh) of the hyoid bone. This sometimes
becomes developed to a great length by the chondrification of the
lower part of the ligamentuni stylohyoideum, and reaches up very
close to the lower end of the stylohyoid process.

In the third visceral arch chondrification takes place only in the
ventral tracts, producing upon the sides of the neck the greater cornua
of the hyoid bone (gh). Greater and lesser cornua are attached to
an unpaired median piece of cartilage, which corresponds to a copula
of the visceral skeleton of Selachians and becomes the body of the
hyoid bone.

The third auditory ossicle, the stapes (fig. 335 st), also belongs to
the visceral apparatus ; it has been left unmentioned until now,
because there is, even at present, a wide difference of opinion con-
cerning its development. According to the original view of REICHERT,
which GEGENBAUR is also inclined to adopt, the stapes arises from
the uppermost end of the hyoid arch. KOLLIKER refers it to the
first visceral arch. According to GRUBER and PARKER, on the
contrary, it arises in connection with the fenestra ovalis, as though
it were cut directly out of the outer wall of the labyrinth.

According to the recent investigations of SALENSKY, GRADENIGO,
and HABL, it appears to me that the. stapes has a double origin,
arising from two different parts.

The plate of the stapes, which is let into the fenestra ovalis, is

614

EMBRYOLOGY.

differentiated in the manner first emphasised by GRUBER and PARKER,
and now again by GRADENIGO, out of the cartilaginous capsule of the
labyrinth. Its development therefore agrees with that of the oper-
culum of the Amphibia, as described by STOHR. The ring-like part
of the stapes, on the contrary, comes from the upper end of the
second visceral [hyoid] arch, which lies in contact with the capsule
of the labyrinth (GRADENIGO, RABL). Its ring-like condition' results

MK

\x

grj istli yh

Fig. 335. — Head and neck of a human embryo 18 weeks old with the visceral skeleton exposed,

after KOLLIKER. Magnified.
The lower jaw is somewhat depressed in order to show MECKEL'S cartilage, which extends to the

malleus. The tympanic membrane is removed and the annulus tympanicus is visible.
ha, Malleus, which passes uninterruptedly into MECKEL'S cartilage, MK ; uk, bony lower jaw

(dentale), with its condyloid process articulating with the temporal bone ; a,m, incus ;

st, stapes ; pr, annulus tympanicus ; grf, processus styloideus ; Isth, ligamentum stylo-

hyoideum ; kh, lesser cornu of the hyoid bone ; gh, its greater cornu.

from the fact that the tissue from which it is formed is traversed
by a small branch of the carotis interna, the arteria mandibularis 01
perforans stapedia. In Man and certain of the Mammals this
subsequently degenerates entirely, whereas in others (Rodents, In-
sectivores, etc.) it remains as a vessel of considerable size.

Both fundaments of the stapes fuse with each other very early
and form a small cartilage, which on the one hand articulates with
the incus by means of a lenticular connecting element (os lentiforme),

THE ORGANS OF THE INTERMEDIATE LAYER OR MESENCHYME. 615

and on the other reposes with its plate -like base in the fenestra
ovalis.

The view here adopted — that the stapes belongs to the second, the
malleus and incus to the first visceral arch — is supported by the
important relation of the nerves in their distribution to the musculus
stapedius and to the tensor tympani, as has recently been rightly
pointed out by RABL. The muscle of the stapes is supplied from the
nerve of the second visceral arch, the nervus facialis ; it forms part
of a group embracing the m. stylohyoideus, and the posterior belly
of the digastric; the muscle of the malleus receives a branch of the
trigeminus, which is the nerve of the mandibular arch.

The separation of the territories of innervation prevails, moreover, with the
muscles of the palate, one of which — the tensor veli palatini — arises in front
of the Eustachian tube — the remnant of the first visceral cleft — and is
therefore supplied by the n. trigeminus, whereas the levator veli palatini and
azygos uvulae lie behind it, and, because belonging to the hyoid arch, receive
branches from the n. facialis (RABL).

At first all the auditory ossicles lie imbedded in a soft gelatinous
tissue outside the tympanic cavity, which still has the form of a
narrow fissure. These conditions are not altered until after birth.
The tympanic cavity, taking in air, then becomes enlarged, its
mucous membrane is evaginated between the auditory ossicles,
and the gelatinous tissue just mentioned undergoes a process of
shrinkage. Auditory ossicles and chorda tympani thus come to
lie apparently free in the tympanic cavity ; accurately considered,
however, they are only crowded out into it, for even in the adult
they are enclosed in folds of the mucous membrane, and by means
of these they preserve their original and genetically established
connection with the wall of the tympanic cavity.

Up to the present stage the construction of the head-skeleton is,
on the whole, simple. In the third stage of development, on the
contrary, upon the beginning of the process of ossification, it attains
in a short time a high degree of complication, which is effected
especially by the development of two entirely different kinds of
bone, one of which has been called primordial bone, the other
covering bone (Deck- oder Belegknochen).

Primordial bones are such as are developed out of the cartilaginous
skeleton. Either there arise centres of ossification within the carti-
lage after softening and dissolution of its matrix, as was described
in the ossification of the vertebral column, the ribs, and the sternum,
or the perichondrium alters its formative activity, and secretes, in

616 EMBRYOLOGY.

place of layers of cartilage, bony tissue upon the already formed
cartilage. In the first instance one can speak of an endochondral,
in the second instance of a perichoiidral ossification. The cartilaginous
primordial skeleton can be crowded out and replaced by a bony one
in both ways, remnants of cartilage of greater or less magnitude
being preserved in the several classes of Vertebrates,

The covering bones, on the contrary, arise outside the primordial
cranium in the connective tissue enveloping it, either in the skin which
covers its surface or in the mucous membrane that lines the head-gut.
They are therefore ossifications which do not occur on any other part
of the axial skeleton and which are also at first foreign to the skeleton
of the head. Consequently in early stages of development, and in
many classes of Vertebrates even in the adult animal, they can be
dissected off without in any way injuring the primordial cranium.
It is otherwise with the primary bones, the removal of which always
causes a partial destruction of the cartilaginous skeleton.

If, as just now stated, the covering bones are at first foreign to the
skeleton of the head, there arises the question of their source. To
answer this I must go back a little.

In lower Vertebrates there is developed, besides the internal carti-
laginous axial skeleton, an external or dermal skeleton, which serves
for the protection of the surface of the body, and is also continued
at the mouth for some distance into the cavity of the head-gut,
where it may be designated as mucous-membrane skeleton. In the
simplest condition it consists, like the scaly armor of the Selachians,
of small close -set denticles, the placoid scales, which have arisen from
ossifications of dermal and mucous -membrane papillae. In other
groups of the Fishes the dermal armor is composed of larger or
smaller bony plates, which bear upon their surfaces numerous
denticles or simple spines. They are described according to their
form and size as scales, scutes, plates, or dermal bones ; they are
explainable in a very simple manner as derivatives from the Sela-
chian armor of placoid scales, by the fusion at their bases of larger or
smaller groups of denticles, which thus produce larger or smaller
skeletal pieces. The larger bony pieces arise principally in the
region of the head, and especially at the places where cartilaginous
parts of the cranial capsule or of the visceral arches approach close
to the surface. Thus in many Ganoids and Teleosts the brain is
found to be enveloped by a double capsule — an inner capsule, either
purely cartilaginous or provided with centres of ossification, and a
bony armor lying directly upon it.

THE ORGANS OF THE INTERMEDIATE LAYER OR MESENCHYME. 617

In the higher Vertebrates the most of the dermal skeleton has com-
pletely degenerated, but on the head it is in large part preserved,
and furnishes the previously mentioned covering bones, which serve
to supplement and complete the internal skeleton.

An interesting insight into the original method of the development
of covering bones can still be acquired in many of the Amphibians
(fig. 336). For example, the vomer and the palatinum, which are
covering bones, arise in very young Triton
larvae by the formation of small denticles
(z') in the mucous membrane of the oral
cavity, and by the fusion of their bases to
form small tooth-bearing plates of bone
(z, z). These plates increase in size for
a time, owing to the establishment in the Fig. 336.— Vomer of an Axoioti
neighboring mucous membrane of addi- By ^^^0^^ (z, „-) a
tional dental spines, which become attached tooth-bearing plate of bone

,. . . „, 1,1 <•, ha*3 arisen in the mucous

to their margins; afterwards they often membrane. ^ Apices of

lose the equipment of denticles, which are teebh in Process of develop-

ment, which are subsequently

destroyed by being resorbed. attached to the margin of the

It may be said that the original process bony Plate and contrttnite to

J its growth.

in the development of covering bones here

described is abbreviated in most of the Amphibia. For at the places
in the mucous membrane which the vomer and the palatinum occupy,
the tips of denticles are not even begun ; but in the layer of tissue
in which otherwise the bases of the denticles would have been fused,
a process of direct ossification takes place. In the same abbreviated
way the covering bones arise in all Reptiles, Birds, and Mammals.

The skulls of many Amphibia (Frog, Axoioti) likewise afford the
best explanation of the original relation of the covering bones to the
primordial skeleton (fig. 337). The covering bones are found to be
loosely superposed upon the primordial cranium, from which they can
be easily removed. Thus upon the left side of the accompanying
figure the premaxillaria (Pmx), maxillaria (M), vomer (Vo), palati-
num (Pal), pterygoid (Pt), and parasphenoid (Ps) have been detached,
whereas upon the right side they have been retained. After their
detachment there is left the inner head-skeleton proper — a capsule
still consisting in great part of the original cartilaginous tissue
(iV, Nl, PP, Qu), into which, however, there are introduced at some
places bony pieces : the occipitalia (Olat), petrosa (Pro), sphenoidea
[sphenethmoid] (E), etc.

In the higher Vertebrates, especially in Mammals, the primordial

618

EMBRYOLOGY.

cranium, the primary ossifications, and the covering bones, which in
Fishes and Amphibia are easily distinguishable from one another
even in the adult animals, are to be recognised as separate parts only
in very early stages of development; later it becomes more difficult

to distinguish them, at
last impossible. This is
due to several things : —
First, the cartila-
ginous primordial cra-
nium is laid down from
the beginning in a rudi-
mentary condition;
then, too, a large part
of the roof is wanting,
the opening being closed
by a connective-tissue
membrane.

Secondly, the cartila-
ginous primordial cra-
nium subsequently dis-
appears almost entirely,
partly by being dissolved,
partly byconversion into
primordial bones. There
persist small remnants,
which have been retained
only in the cartilaginous
septum narium and the
cartilages of the outer
nose connected with it.
Thirdly, in the fully developed skull the primordial bones and the
covering bones are no longer distinguishable ; for the latter lose their
superficial position, become intimately united to the bones derived
from the primordial cranium, and with them, filling up the gaps,
constitute a firm, closed, bony receptacle of mixed origin.

Fourthly, in the adult animal, bones which in the embryo are
formed separately, and in lower Vertebrates always remain thus, are
often fused. There is a fusion not only between bones of like origin,
but also between primordial and covering bones, whereby it finally
becomes altogether impossible to distinguish them. Many of the
bones of the human cranium are consequently bone -complexes.

Fig. 337.— Skull of a Frog (Rana esculenta). View from
beneath. After ECKER.

The lower jaw is removed. On the left side of the figure
the covering bones have been removed from the cartila-
ginous part of the skull.

Cocc, Condyli occipitales ; Olat, occipitale laterale ; GK,
auditory capsule ; Qu, quadratum ; Qjg, quadrato-
jugale ; Pro, prooticum ; Ps, parasphenoid ; As, ali-
sphenoid; Pt, osseous pterygo id; PP, palato-quadratum;
FP, fronto-parietale ; E, ethmoid (os en ceinture) ;
Pal, palatinum ; Vo, vomer ; M, maxilla •; Pmx, pre-
maxillare ; N, N1, cartilaginous nasal framework ;
//, V, VI, places of emergence of n. opticus, n. tri-
geminus, and n. abducens.

THE ORGANS OF THE INTERMEDIATE LAYER OR MESENCHYME. 619

It may be stated as a general rule that the ossifications on the base
and sides of the cranium are primordial, but that on the roof and in
the face covering bones make their appearance.

The following parts of the human skull belong to the primordial
elements : (1) occipitale, except the upper part of the squamous
portion; (2) the sphenoidale, except the internal pterygoid plate;

(3) ethmoidale and turbinatum ; (4) petrosum and mastoid portions
of the temporale ; (5) the auditory ossicles — malleus, incus, and
stapes; (6) the body of the hyoides, with its greater and lesser
cornua.

The following are covering bones : (1) the upper part of the
squamous portion of the occipitale ; (2) the parietale; (3) the frontale;

(4) the squamous portion of the temporale ; (5) the internal pterygoid
plate of the sphenoidale ; (6) the annulus tympanicus; (7) palatinum;
(8) vomer; (9) nasale; (10) lachrymale; (11) zygomaticum; (12)
maxillae sup. ; (13) maxillae inf.

I will now, after this survey, give a somewhat more detailed account
of the development of the bones of the head enumerated above.

I. Bones of the Cranial Capsule.

(1) The occipitale is at first a cartilaginous ring surrounding the
foramen magnum ; it begins to ossify early in the third month at
four points. One centre of ossification is formed below the foramen,
another above, and two more at its sides. In this way there arise
four bones, which are joined by broader or narrower bands of carti-
lage, according to the degree of their development. In the lower
Vertebrates — Fishes, Amphibia (fig. 337 Olat) — they remain in this
condition as separate bones, and are designated as occipitale basilare,
oc. superius, and oc. laterale.

To these are added in Mammals and Man a covering bone, which
arises from two centres of ossification in the connective tissue farther
above the foramen — the interparietale. This begins, even in the third
fatal month, to fuse with the superior occipital bone to constitute
the squama ; however, up to the time of birth furrows running in
from right and from left mark the boundary of the two genetically
different parts. In the new-born child squama, occipitalia lateralia
and oc. basilare are still separated from each other by thin remnants
of cartilage. Then in the first year the squama fuses with the
lateral parts (partes condyloidese), and finally there is united with
these, in the third or fourth year, the pars basilaris. The occipitale

620 EMBEYOLOGY.

is therefore a complex that has originated from five separate
bones.

(2) The sphenoidale also arises from numerous centres of ossifica-
tion, which appear in the base of the primordial cranium, and which
in the lower classes of Vertebrates represent parts of the cranial
capsule that remain separate. In the anterior prolongation of the
pars basilaris of the occipitale there appear in the vicinity of the
sella turcica an anterior and a posterior pair of centres, which con-
stitute the fundaments of the bodies of the anterior and posterior
sphenoidea. At the sides of these there are developed special centres
of ossification for the lesser and for the greater wings.

In most Mammals the lesser wings fuse with the anterior, the
greater with the posterior body. Thus there are formed two
sphenoidea, an anterior and a posterior, which are placed in front of
the occipitale, arid are separated from each other by a thin strip of
cartilage. In Man these two bones become joined together, by the
ossification of the cartilaginous strip mentioned, to constitute the
unpaired single sphenoidale, with its many processes. The fusions
of the numerous separate ossifications take place in the following
order. In the sixth foetal month the lesser wings of the sphenoid
fuse with the anterior body ; shortly before birth the latter unites
with the posterior body, and in the first year after birth the greater
wings are united with the rest. From the latter the outer pterygoicl
plates grow downward, whereas the inner pterygoid plates are formed
as covering bones. For in the connective tissue of the lateral wall of
the oral cavity there is developed a special region of ossification;
this furnishes a thin bony lamella, which is preserved in many
Mammals as a special skeletal element (os pterygoideum) lying on
the pterygoid process of the sphenoidale. In Man it early fuses
with the sphenoidale, notwithstanding it has an entirely different
origin from the latter.

(3) The temporale is a complex of various bones, the greater part of
which are still separate in the new-born infant. The bs petrosum
with the mastoid process is developed from numerous centres of
ossification in that part of the primordial cranium which encloses the
organ of hearing, and has therefore been designated as cartilaginous
ear-capsule. With it is united after birth the styloid process, which
in the embryo is a cartilaginous rod that is derived from the upper
end of the second visceral arch and that ossifies from its own
independent centre.

To the primordial bones there are added in Man two covering

THE ORGANS OF THE INTERMEDIATE LAYER OR MESENCHYME. 621

bones, — squama and pars tympanicus, — which are as foreign to the
primordial cranium as the parietal or frontal bones. Of these the
pars tympanicus (fig. 335 pr) is at first a narrow bony ring, which
serves as a frame for the tympanic membrane. It is developed in
connective tissue outside of the auditory ossicles, and, in particular,
outside the malleus (ha) and the connected MECKEL'S cartilage (MK).
Thus is explained the position of the long process of the malleus in
the fissura petrotympanica, when, soon after birth, the primordial
and covering bones fuse with each other. For the annulus tym-
panicus gradually becomes broadened into a bony plate, which serves
as a support for the external meatus. This plate then fuses with
the petrosal bone, except along a narrow cleft, — the fissura petro-
tympanica or Glaseri,— which remains open, because here the chorda
tympani and the long process of the malleus were in the embryo
shoved in between the bones, while they were still separate.

In lower Vertebrates, and also in many Mammals, the pieces
mentioned remain separate, and are distinguished in comparative
anatomy as os petrosum, os tympanicum, and os squamosum.

(4) The ethmoidale and the turbinatum of the nose are primordial
bones, which are developed out of the posterior part of the cartila-
ginous nasal capsule, whereas the anterior part remains cartilaginous
and becomes the cartilaginous septum nasorum and the external nasal
cartilages.

"The ossification begins in the lamina papyracea in the fifth
month. Then follows the ossification of the lower and middle
turbinals. At birth these are united by means of cartilaginous
portions of the ethmoidale. After birth the vertical plate with the
crista galli is the first to ossify; then follows the ossification of the
upper turbinal and of the gradually developed labyrinth, from which
the ossification advances to the corresponding halves of the cribri-
form plate. The union of the two lateral halves with the lamina
perpendicularis does not take place until between the fifth and the
seventh year." (GEGENBAUR.)

Of the covering bones of the primordial cranium, which in general
begin to ossify at the beginning of the third month, the following
remain separate : the parietale, frontale, nasale, lachrymale, and
vomer. Of these the frontale is originally, like the others, a paired
structure, and still continues in this condition into the second year
after birth, when the closure of the frontal suture begins, Nasale
and lachrymale are covering bones of the cartilaginous nasal
capsule. The vomer arises as a paired structure at the sides of the

622 EMBRYOLOGY.

cartilaginous septum of the nose in the third month. The two
lamellae afterwards fuse, the cartilage between them disappearing.

II. Bones of the Visceral Skeleton.

The remaining bones of the head, which have not been mentioned
hitherto, belong to the visceral skeleton, some of them being
primordial, others covering bones.

The hyoid bone and the auditory ossicles (perhaps also the thyroid
cartilage) are primordial parts; they are characterised by very
diminutive size and occupy a very subordinate position in comparison
with the enormously developed covering bones. The hyoides begins
toward the end of embryonic life to ossify at several points. The
auditory cartilages acquire from the periosteum as early as the fourth
month a bony investment, within which here and there remnants of
cartilage persist even in the adult. According to recent researches
the malleus is a compound skeletal piece. The long process is de-
veloped as a covering bone on that part of MECKEL'S cartilage which
penetrates between petrosal and annulus tympanicus. While the
cartilage undergoes degeneration, the covering bone fuses with the
larger-, primordial part of the malleus. It probably corresponds
with the os angulare of lower Vertebrates.

The covering bones of the visceral skeleton, the maxillare superius,
palatinum, pterygoideum, zygomaticum, and maxillare inferius, are
developed in the vicinity of the mouth-opening in the connective
tissue of the superior and inferior maxillary processes.

The maxillaria superiores are a complex of two pairs of bones,
which indeed remain separate in most Vertebrates. One pair is
developed on the two superior maxillary processes laterad of the
cartilaginous nasal capsule. The other pair appears in the eighth or
ninth week, according to TH. KOLLIKER'S detailed investigations,
upon the part of the frontal process that lies between the nasal
orifices. It corresponds to an actual paired intermaxillary (pre-
maxillare), and subsequently encloses the fundaments of the four
incisors.

The two intermaxillaries in Man early fuse with the fundaments
of the two superior maxillaries, the two membranous superior
maxillary processes having previously united with the inner nasal
processes. The boundary between maxillary and intermaxillary is
indicated 011 the crania of young persons by a suture-like place
(sutura incisiva), running transversely outward from the foramen
incisivum, which is occasionally retained even in the adult,

THE ORGANS OF THE INTERMEDIATE LAYER OR MESENCHYME. 623

There early grow out from the two superior maxillaries into the
palatal processes horizontal lamellae which produce the two palatal
bones — the hard or bony palate.

Palatals and pterygoids are developed in the roof and side walls of
the oral cavity ; they are consequently mucous-membrane bones.
The pterygoids apply themselves, as was stated on p. 620, to the
cartilaginous downgrowths of the greater wings of the sphenoid.
In many Mammals they remain separate from the latter throughout
life, but in Man they unite with it and are now distinguished as
inner pterygoid plates from the outer plates, which arise by ossifica-
tion of cartilage.

The development of the visceral skeleton, which has been discussed
here and in previous sections (pp. 284, 515), furnishes the basis for
the interpretation of the malformations which are quite frequently
met with in the maxillary and palatal region in Man. I refer to the
labial, maxillary, and palatal fissures, which are simply malformations
due to arrested development. They result when the separate funda-
ments from which are formed the upper lip, the upper jaw, and the
palate do not come into normal union (figs. 288-91).

The malformations of arrested development can present very
different variations, according as the coalescence is wholly or only
partly omitted, and according to whether it affects one or both
sides of the face.

In the case of total arrest, in palatal, maxillary, and labial fissures-
of both sides, both nasal cavities are broadly in communication with
the oral cavity by means of a right and a left fissure running from
in front backward. From above there projects free into the oral
cavity the nasal septum, which is enlarged in front, and here bears,
the incompletely developed intermaxillary with its rudimentary
incisor teeth. In front of it lies a small dermal ridge, the fundament
of the middle part of the upper lip. At the sides of the fissures and
the nasal openings, which have not been closed in below, there lie
the two separated maxillary processes, with the bony upper jaw and
the fundaments of the canine and molar teeth. The horizontal
palatal plates project as ridges only a little distance into the oral
cavity, and have not effected a junction with the nasal septum. A
malformation of this kind is very instructive for the comprehension
of the normal processes of development previously described.

When the arrest is only partial, coalescence may fail either on the

624 EMBRYOLOGY.

superior maxillary processes only, or on the palatal plates only, and
either on one or on both sides. In the first case there is produced a
labio-maxillary fissure, or even a labial fissure (hare-lip) only, while
hard and soft palates are formed normally. In the other case the
upper jaw is well developed and no external evidence of malforma-
tion is visible, while there is a fissure on one or both sides which
passes through the soft palate, and sometimes through the hard
palate also {cleft palate).

The development of the lower jaw is coupled with fundamental
metamorphoses. As has been previously explained, in the youngest
embryos the oral cavity is limited below by the membranous inferior
maxillary processes. Within this there is developed (fig. 338)
MECKEL'S cartilage (MK\ the cranial end of which becomes (compare
p. 611) the fundament of the malleus (ha), by means of which
MECKEL'S cartilage is articulated with the incus (am). At its
ventral end in Mammals it unites in the middle line with the
corresponding part of the other side, whereas in Man a small space
remains between them.

Inasmuch as the small cartilages mentioned have arisen in the
first visceral arch, they correspond both in position, and also in their
mutual connections and many other relations, to the large carti-
laginous elements with which we have already become familiar in
the Selachians (fig. 330) as palato-quadratuin (0) and mandibulare
(U). In the Selachians the palato-quadratum and mandibulare are
functional as a genuine jaw-apparatus, for they bear on their
margins the teeth, which are attached in the mucous membrane
only, and the masticatory muscles are inserted on their surface.

In Mammals and Man the function of the skeletal parts corre-
sponding to them has become essentially different, for they have
entered into the service of the auditory apparatus ; a profound, and
in its final results wonderful and highly important metamorphosis
has taken place here. In order to explain this it is necessary to
touch briefly upon a few comparative-anatomical facts.

With the beginning of ossifications the primary lower jaw oses in
Teleosts, Amphibia, and Reptiles its simple condition, and is con-
verted into an apparatus which is often very complicated. The
ossifications are here, just as was the case in the other parts of the
head-skeleton, of two different kinds, primary and secondary. One

THE ORGANS OF THE INTERMEDIATE LAYER OR MESENCHYME. 625

bone, which makes its appearance in the articular part of the
cartilage and produces the os articulare, is a primary bone. With
this are associated several covering bones arising in the surrounding
connective tissue, two of which, the angulare and the dentale,
acquire special importance. Both are attached to the outer
surface of the cartilaginous [Meckelian] rod, the angulare near the
joint, the dentale in front of it and extending to the symphysis.

Fig. 338. — Head and neck of a human embryo 18 weeks old with the visceral skeleton exposed;
after KOLLIKER. Magnified.

The lower jaw is somewhat depressed in order to show MECKEL'S cartilage, which extends to the
malleus. The tympanic membrane is removed and the annulus tympanicus is visible.

ho., Malleus, which passes uninterruptedly into MECKEL'S cartilage, MK ; uk, bony lower jaw
(dentale), with its condyloid process articulating with the temporal bone ; am, incus
st, stapes ; pr, aunulus tympanicus ; grf, processus styloideus ; Isth, ligamentum stylo-
hyoideum ; kh, lesser cornu of the hyoid bone ; gh, its greater comu.

The latter is an important skeletal element, which attains a consider-
able size, receives into its upper margin the teeth, and grows around
the cartilage of MECKEL in such a manner that the cartilage is almost
completely enclosed in a bony cylinder. The whole complicated
apparatus, composed of several bones and the original cartilage
enclosed within them, articulates at the primary joint of the jaw
between palato-quadratum and os articulare.

The same fundaments are again met with in Mammals and Man.

40

€26 EMBRYOLOGY.

In the articular part of the cartilage of the lower jaw, which has
assumed the form of the malleus (figs. 334, 338 ha), there arises a
special centre of ossification, which corresponds to the articulare of
other Vertebrates. In its vicinity appears, as a covering bone, an
exceedingly small angulare, which subsequently fuses with it, pro-
ducing the long process of the malleus. The second covering bone,
the dentale (fig. 338 uk), attains, on the contrary, a great size and
alone becomes the subsequently functioning lower jaw, whereas the
remaining parts, which in the compound mandibular apparatus of
Teleosts, Amphibia, Reptiles, and Birds participate in the function
of chewing (palato-quadratum, — or quadratum, — articulare, angu-
lare, and MECKEL'S cartilage), lose their original function and are
employed in another manner.

The most important motive to this profound metamorphosis is
to be found in the fact that in Mammals and Man there is developed
in place of the primary articulation of the jaw a secondary one. The
primary articulation, upon which the tooth-bearing dentale is moved,
lies, as we have seen, between palato-quadratum and articulare.
Inasmuch as these elements correspond respectively to the incus
and malleus of Mammals, the primary articulation of the jaw of
lower Vertebrates is to be sought in the incus-malleus articulation of
l/ie higher Vertebrates. In Mammals and Man the dentale is no
longer moved at this joint, because the dentale itself forms a direct
articulation with the cranial capsule by means of a bony projection,
— the processus condyloideus (fig. 338), — which it sends upward, and
through which it is united to the squamous portion of the temporal
bone at some distance in front of the primary articulation. This
union constitutes the secondary articulation of the jaw, in which only
covering bones participate.

The natural result of the formation of a new articulation is, that
the primary lower-jaw apparatus has become superfluous for the
act of mastication, and that its development is restricted. Incus,
malleus, and angulare, which is united with the malleus, are con-
verted into parts of the auditory organ (see p. 613). The remaining
part of MECKEL'S cartilage (MK) begins to degenerate, in Man in
the sixth month. A portion of it, which is a prolongation of the
long process of the malleus, extending from the fissura petrotym-
panica as far as the entrance into the bony lower jaw at the
foramen alveolare, is converted into a connective-tissue cord, the
ligamentum laterale internum maxillae inferioris. A small portion
near the front end early acquires a special centre of ossification and

THE ORGANS OF THE INTERMEDIATE LAYER OR MESENCHYME. 627

fuses with the covering bone. The remainder of that portion of
MECKEL'S cartilage which is enclosed in the canal of the lower jaw,
from the foramen alveolare onward, is gradually broken down and
dissolved ; however, remnants of the cartilage are found even in the
new-born infant at the symphysis.

At first the bony lower jaw is a paired structure, consisting of
tooth-bearing halves. These remain in many Mammals as separate
bones, being united in a symphysis by means of connective tissue.
In Man they are united in the first year after birth into a single
piece by the ossification of the intervening tissue.

A special peculiarity is exhibited by the articular end of the lower
jaw, phylogenetically a covering bone. Instead of beginning to be
formed, in the manner of the anterior portion, by direct ossification
of the connective-tissue foundation, there first arises here a carti-
laginous tissue consisting of large vesicular cells and soft intercelluar
substance, which is gradually converted into bone. This presents
a certain similarity to the development of the primordial bones.
But that the resemblance is only superficial is shown by the differ-
ence in the structure of the articulation, to which I shall return in
a subsequent section.

(c) Concerning the Relation of the Head-Skeleton to the
Trunk- Skeleton.

In different sections of this text-book — in discussing the primitive
segments, the nervous system, and especially now in the discussion
of the axial skeleton — reference has been made to many points
of agreement that have been recognised between the structural
conditions of the head and those of the trunk. In a critical com-
parison of these two regions of the body there arise many important
questions which have for several decades engaged the attention of
the best morphologists. It may therefore be well here, after having
given the pertinent facts, to take up these questions more particularly,
and determine the relation ivhich head and trunk, and especially that
which head-skeleton and trunk-skeleton, sustain to each other.

Before I elucidate the present state of the question, I will give a
brief survey of the history of these researches, which have been
grouped together under the name

" The Vertebral Theory of the Skull,"
The relation which t he anterior and posterior parts of the skeleton

628 EMBRYOLOGY.

of the trunk sustain to each other in the morphology of Vertebrates-
was for the first time subjected to a thorough scientific discussion
at the beginning of the present century, when the school of the
" Natural Philosophers " began its career. An attempt to solve the
problem was made in very similar ways by two persons, by the
natural philosopher OKEN and by the poet GOETHE, without either
of them having been influenced by the other.

According to the OKEN-GOETHE vertebral theory, the skull is the
most anterior part of the vertebral column, and is composed of a
small number of modified vertebrae. OKEN distinguished three
vertebrae in his " Programme " entitled " Ueber die Bedeutung der
Schadelknochen," which appeared in 1807, when he entered upon a
professorship conferred upon him in Jena. He named them the
ear-, eye-, and jaw-vertebrae.

Each head-vertebra, like a trunk-vertebra, consisted in his opinion
of several parts — a body, two arch-pieces, and a dorsal spine. OKEX,
GOETHE, and their numerous followers believed that this composition
was most distinctly recognisable in the last cranial vertebra, the
occipitale, the base of which was compared to the body of the
vertebra, the condyloid parts to the lateral arches, and the squama
to the spine of the vertebra.

A second cranial vertebra was discerned in the body of the pos-
terior sphenoidale, which together with its greater wings and the
two parietal bones formed a second bony ring around the brain.

A third vertebra was constructed out of the body of the sphenoidale
anterius, the lesser wings and the frontale.

The ethmoidale was cited by many investigators as a fourth — the
most anterior — cranial vertebra. A number of bones, which would
not fit into this scheme, were considered to be structures sui generis,
and were in part associated with the sensory organs as sensory bones,,
in part compared with the ribs of the thorax.

In this form, which underwent numerous modifications in details,
the OKEN-GOETHE vertebral theory of the cranium dominated mor-
phology for decades and formed the foundation of many investiga-
tions. It had a stimulating and fruitful effect until, with a deeper
insight into the structure of Vertebrates, it was abandoned as defective
and erroneous, giving way before the force of numerous newly dis-
covered facts.

For neither the comparative osteology of the skull nor growing
embryo! ogical research could point out in a satisfactory way which
bones were really to be interpreted as parts of vertebrae. The most

THE ORGANS OF THE INTERMEDIATE LAYER OR MESENCHYME. 629

dissimilar, and more or less arbitrary, opinions upon this subject made
their appearance. An agreement even as to the number of vertebrae
contained in the skeleton of the head could not be reached. Some
investigators assumed six, others five or four, or even three only.

HUXLEY, in his "Elements of Comparative Anatomy," by a critique
based upon facts, was the first to prepare the way for a termina-
tion of this unpleasant state of affairs, in which the vertebral
theory was held to with tenacity, notwithstanding the contradictions
that everywhere arose. In his discussion he argued from a series of
facts which embryological investigation had brought to light. As such
the following, important for the problem of the skull, should be
cited before all others.

First, the discovery that the skeleton of the head, like the verte-
bral column, is developed out of a cartilaginous condition, and that
the brain is first enclosed by a primordial cartilaginous cranium
{BAER, DUGES, JACOBSON).

Secondly, the doctrine established mainly by KOLLIKER, that the
bones of the head- skeleton are separable into two groups according
to their development— into the primordial bones, which arise in the
primordial cranium itself, and the secondary or covering bones,
which have their origin in the enveloping connective tissue.

Thirdly, the insight which was acquired, through the important
works of RATHKE and REICHERT, into the metamorphoses of the
visceral skeleton, and thereby into the development of the palato-
maxillary apparatus and the auditory ossicles.

Through an examination of these various facts, HUXLEY was led to
the important and fully justified conclusion, that not a single cranial
bone can be recognised as a modification of a vertebra, that the skull
is no more a modified vertebral column than the vertebral column is a
modified skull ; that, rather, both are essentially distinct and different
^modifications of one and the same structure.

While HUXLEY stopped at the negative standpoint, simply denying
the vertebral theory, GEGENBAUR has made the question of the
relation of skull and vertebral column, raised by GOETHE and OKEN,
but from ignorance of the facts incorrectly answered by them, again
the object of profound comparative study. Rightly recognising
that the problem can be solved only by detailed investigation of
the primordial skeleton, he selects as the object for his studies the
cartilaginous skull of the Selachians, and endeavors in his revolu-
tionising work, " Das Kopfskelet der Selachier als Grundlage zur
Beurtheilung der Genese des Kopfskelets der Wirbelthiere," to

630 EMBRYOLOGY.

produce the evidence that the primordial cranium has arisen by fusion
from a number of segments equivalent to vertebrce. Instead of the
OKEN-GOETHE vertebral theory he propounds the segmental theory of
the skull, as I suggest the doctrine of GEGENBAUR be called.

GEGENBAUR proceeds from the correct conception that the segmen-
tation of a region of the body is recognisable not only in the meta-
merism of the vertebral column, but also in many other structures —
in the method of the arrangement of the chief nerve-trunks, and in
the ventral arch-structures attached to the axial skeleton. He
investigates, accordingly, the cranial nerves of the Selachians, and
arrives at the conclusion that, with the exception of the olfactory
and optic nerves, which are metamorphosed parts of the brain itself,
they deport themselves like spinal nerves both in their origin and
their peripheral distribution. He determines that there are nine
pairs of them ; and therefore concludes that the portion of the head-
skeleton which is traversed by the nine segmentally arranged cranial
nerves must be equivalent to nine vertebral segments, and that it
must have arisen by their very early fusion.

The visceral skeleton of Selachians is regarded by GEGENBAUR
from the same instructive point of view. He discerns in the
maxillary, hyoid, and branchial arches skeletal elements which are
represented in the vertebral column by the ribs.

Inasmuch as a vertebral segment belongs to each pair of ribs, a
similar relation is also assumed as the original arrangement for the
visceral arches. Thus this method of considering the question leads
to the same result : that the primordial cranium — since at least nine
visceral arches belong to it as ventral arch-structures — has been
produced from at least nine segments.

Such an origin GEGENBAUR accepts for the posterior chorda-
traversed region of the skull only, in which alone the emerging
nerves agree with spinal nerves. He therefore distinguishes this as
vertebral from the anterior or non-vertebral portion, which does not
allow the recognition of any segmentation, and which begins in front
of the anterior end of the chorda. He interprets the latter as a new
formation which has been established by the enlargement in front of
the vertebral part of the skull.

GEGENBAUR explains the great differences which exist between
skull and vertebral column as adaptations, partly to the enormous
development of the brain, partly to the sensory organs of the head,,
which are received into pits and cavities of the primordial cranium.

Since the time when GEGENBAUR with keen discrimination pro-

THE ORGANS OF THE INTERMEDIATE LAYER OR MESENCHYME. 631

pounded his segmental theory of the skull, the way has been
prepared in many directions, chiefly through embryological investi-
gation, for a better comprehension of the skeleton of the head.

Investigations which I undertook on the dermal skeleton of
Selachians, Ganoids, and Teleosts, as well as on the head-skeleton of
Amphibia, showed that the difference between primordial and cover-
ing bones is much greater than it was originally assumed to be.
For as their development shows, the covering bones are at first
structures quite foreign to the axial and head-skeleton, formed at the
surface of the body in the skin and mucous membrane. They are
parts of a dermal skeleton, which in lower Vertebrates protect the
surface of the body as a scaly armor, — parts which have entered
into union with the superficially located portions of the inner,
primordial cartilaginous skeleton. Therefore the covering bones of the
lower Vertebrates are often tooth -bearing bony plates, which have
originated from a fusion of isolated dental fundaments, a condition
which may be regarded for many reasons as the primitive one.

A further acquisition of broad significance is the discovery of the
primitive segments of the head, which we owe to BALFOUR, MILNES
MARSHALL, GOETTE, WIJHE, and FRORIEP.

By it an important point of agreement between head and trunk
has been made out. The two body-sacs penetrate even into the
head ; here also the two middle germ-layers are separated into a
dorsal portion, lying in contact with the chorda and neural tube,
which is divided into nine pairs of primitive segments,* and into a
ventral portion (see p. 351).

The head is therefore segmented similarly to the trunk, even at a
time when the first traces of the fundament of a vertebral column or
a head-skeleton are not yet present.

Thirdly, the insight into the development of the cranial nerves
(BALFOUR, MARSHALL, WIJHE, and others) is important. An agree-
ment with the development of the spinal nerves has been established
in so far as some cranial nerves have a dorsal origin from a neural
crest, like the sensory roots of spinal nerves, while others grow out
ventrally from, the brain-vesicles like anterior roots.

Finally, I would mention as a step in advance, which is not with-
out significance for the interpretation of the head-skeleton, the
altered conception of the meaning of the primitive segments which
embryological evidence has compelled us to form.

The primitive segments are the real fundaments of the musculature
* [See footnote p. 458.J

632 EMBRYOLOGY.

of the body. The first segmentation of the vertebrate body affects
the body-sacs and the musculature arising from them. The forma-
tion of the primitive segments is only remotely and indirectly
connected with the development and segmentation of the vertebral
column. It is only after muscle-segments have existed for a long
time that, at a comparatively late stage of development, the funda-
ments of a segmented vertebral column are established. But these
arise, by histological metamorphosis, from an unsegmented con-
nective-tissue matrix, in consequence of the appearance of a process
of chondrification.

All the conditions here only briefly touched upon are of far-
reaching significance for the question of the relation of the head- and
trunk-skeletons to each other. For, as GEGENBAUR rightly points
out, since the establishment of his segmental theory " the vertebral
theory of the skull has become more and more a problem of the
phylogenesis of the whole head."

I desire to give briefly and connectedly my own views upon this
subject : —

Theory concerning the Relation of the Head and its Skeleton
to the Skeleton of the Trunk.

The segmentation of the vertebrate body begins with the walls of
the primary body-sacs, the dorsal portion of which, abutting upon
the chorda and neural tube, is divided by the formation of folds into
successive compartments, the primitive segments.

Inasmuch as the voluntary musculature is developed from the
walls of the primitive segments, it is the first system of organs in
Vertebrates to be segmented.

The myomeric condition — " myomerism " — is the direct cause of a
segmental arrangement of the peripheral nerve-tracts, for the motor
nerves pertaining to a segment unite to form an anterior [ventral]
root as they emerge from the spinal cord, and in the same manner
the sensory nerves which come from a corresponding part of the skin
together constitute a sensory root.

At a time when the segmentation of the musculature and of the
peripheral nerve-tracts has already been effected, the skeleton is
still unsegmented ; for it is represented by the chorda dorsalis alone.
The soft mesenchyme, which envelops the chorda and the neural
tube, and which becomes the matrix of the subsequently formed
segmented axial skeleton, is still a continuous mass of cells, filling in
the spaces between these organs.

THE ORGANS OF THE INTERMEDIATE LAYER OR MESENCHYME. 633

At this time the differentiation of head and trunk has already
taken place. This is accomplished, first by the establishment of the
higher sensory organs in the anterior portion of the body, secondly
~by the enlargement of the neural tube into the voluminous brain -
vesicles, thirdly by the formation of a regular series of visceral clefts
in the walls of the head-gut, which thus also undergo a kind of
segmentation (branchiomerism).

The region of the body which is thus metamorphosed into a head is
from the beginning segmented, and is composed, as the Selachians show,
of at least nine primitive segments.

The development of visceral clefts produces still further differences
between head and trunk. By the appearance of visceral clefts, the
front part of the body-cavity is divided up into several successive head-
cavities. By the disappearance of these cavities, parts corresponding
to the thoracic and abdominal cavities have become obliterated.
Further, there are developed out of the cells composing the walls of
the head-cavities important masses of transversely striped muscles f or
moving and constricting the separate portions of the branchial region
of the alimentary canal, whereas in the trunk the voluntary
musculature arises exclusively from the primitive segments. In
the trunk these masses of muscle spread out both dorsally over the
neural tube and also ventrally into the wall of the thorax and
abdomen, whereas in the head they remain limited to a small space
and do not undergo any extensive development.

It is only after head and trunk have thus already become in a high
•degree different that the cartilaginous axial skeleton begins to be formed.

The latter is therefore a structure of comparatively recent origin,
as it also is peculiar to the phylum, Yertebrata, and even here is
•wanting in the lowest representative, Amphioxus lanceolatus.

The development of the cartilaginous axial skeleton in the two
chief regions of the body is from the beginning partly similar, partly
•dissimilar.

The development is similar in so far as the process of chondrifica-
tion begins in both head and trunk in the perichordal connective
tissue, then extends around the chorda both above and below,
ensheathing it, and finally is continued into the connective-tissue
.layer that envelops the neural tube.

The dissimilarity is expressed in the occurrence or omission of
segmentation. In the trunk under the influence of the musculature
there arises a segmentation of the cartilaginous axial skeleton into
.firm vertebral pieces, alternating with intervertebral ligaments which

634 EMBRYOLOGY.

remain in the connective-tissue state. In the head there is developed
at once a continuous cartilaginous capsule around the brain-vesicles.
The segmentation, which in this region is expressed in other systems of
organs, — in the formation of primitive segments and in the arrangement
of the cranial nerves, — does not occur in the corresponding part of the
axial skeleton. Never in the course of the development of any
Vertebrate has there been observed, as the first fundament of the
primordial cranium, a succession of cartilaginous pieces, alternating
with connective-tissue discs, and there seems to be no ground for
assuming that a condition of this kind existed in earlier times. In-
the slight development of the muscles derived from the primitive
segments of the head, and in the voluminous condition attained by
the brain and sensory organs, are to be discerned, on the contrary,
factors which have converted the head, at an early period, into a
more rigid portion than the trunk. The cause, which in the trunk
has made the segmentation of the axial skeleton necessary, has been
wanting in the head.

During the last few years the opinion has been expressed by
a number of persons (ROSENBERG, STOHR, FRORIEP) that in some
classes of Vertebrates the occipital region of the primordial cranium
is increased by fusion with vertebral fundaments of the neck-region,
and thus, as it were, " is constantly advancing caudad." I leave
undetermined to what extent this is true. GEGENBAUR combats the
interpretation of STOHR, but describes a quite frequently occurring
fusion of the cranial capsule with vertebrae in Bony Fishes. One
thing only would I point out : the conception of the first unsegmented
fundament of the primordial cranium which I have presented is
not irreconcilable with the view that subsequently new vertebral
segments may be added behind.

Besides the segmented condition of the vertebrce, a segmentation of
the axial skeleton is also expressed in the appearance of ventral arches,
which are repeated in regular order from before backwards. On
the head they are designated as visceral arches, on the trunk as ribs.

The position of these skeletal parts also is dependent upon the
first segmentation which affects the organisation of Vertebrates.
For the ribs are developed between the muscle-segments by a process
of chondrification in the connective-tissue plates separating them —
the intermuscular ligaments ; while the visceral arches are dependent
upon the visceral clefts, by which the ventral part of the head-region
is divided into a number of successive segments.

It cannot be concluded from the existence of ribs and visceral

THE ORGANS OF THE INTERMEDIATE LAYER OR MESENCHYME. 635

arches that the corresponding skeletal axis must likewise have been
segmented. They are only an indication of the segmentation of the
region of the body to which they belong.

That the segmentation of the head which is present in the embryo
is more or less obliterated in the adult Vertebrate depends upon
two causes. First the primitive segments are only slightly developed,
furnishing unimportant muscles, and in part wholly degenerate;
secondly the visceral skeleton is subjected to profound metamorphoses.
Especially in the higher Vertebrates it experiences such a degenera-
tion and metamorphosis, that finally nothing of the original segmental
arrangement of its parts (palato-maxillary apparatus, auditory
ossicles, hyoid bone) is left.

/»* 8

B. The Development of the Skeleton of the Extremities.

A description of the skeleton of the extremities should be preceded
by a few words
in regard to the
fundaments of the
limbs themselves.
These at first
appear as small
elevations [limb-
buds] at the sides
of the trunk in
front and behind
(fig. 339). That
they belong more
to the ventral than
to the dorsal sur-
face of the body is
evident from the
fact that they are
innervated by the
ventral branches
of the spinal
nerves.

Moreover, the
limbs appear to
belong to a large number of trunk-segments. This is to be inferred both
from the method of the distribution of nerves and also from the source

Fig. 339. — Very young human embryo of the fourth week 4 mm
long, neck-rump measurement ; taken from the uterus of a
suicide 8 hours after her death, after RABL.

an, Eye ; ng, nasal pit ; uk, lower jaw ; zb, hyoid arch ; s3, «*, third
and fourth visceral arches ; 7t, protrusion of the wall of the
trunk caused by the growth of the heart • us, boundary between
two primitive segments ; oe, ue, anterior and posterior limbs.

636 EMBRYOLOGY.

of their musculature. For the anterior and posterior limbs always
receive their nerves from a large number of spinal nerves. The
muscles are derived from the same source as the whole musculature
of the trunk — from the primitive segments.

It has not yet been possible to establish the derivation of the
musculature in Mammals and Man. For the limb-buds consist of a
mass of small, closely crowded cells ; it' is impossible to state which
of these belong to the mesenchyme, which to the musculature, or
which to the nerves. The conditions in lower Vertebrates, on the
contrary, are much more favorable.

In Selachians the fins, which correspond to the limbs of the higher
Vertebrates, contain, even at the time of their formation as small
plates, distinctly recognisable embryonic gelatinous tissue, which is
•covered in by the epidermis. An important discovery by DOHRN has
established that there grow into the gelatinous tissue of the fin two
buds from each of a large number of primitive segments; the buds
then become detached from their parent tissue and each is divided into
a, dorsal and a ventral half — the fundaments of extensor and flexor
musculature. Each fin therefore contains a series of muscular Junda-
ments, which have arisen seymentally and are arranged one behind
another, — a fact which has its weight in many other questions
touching the origin of the limbs.

In Man the fundaments of the limbs take on a definite form as
•early as the fifth week. The outgrowths have become enlarged and
divided into two regions, of which the distal becomes the hand, or
foot. In the case of the anterior extremity the front margin of the
hand already begins to acquire indentations, by which the first
fundaments of the fingers are indicated. In the sixth week the
three chief divisions of the limbs are recognisable, for the proximal
portion is now marked off by a transverse furrow either into arm
and fore-arm or into thigh and leg. Now, too, on the foot the toes
are indicated by constrictions, but less distinctly than are the fingers
on the hand.

In the seventh week there are to be observed at the tips of the
fingers claw-like appendages, consisting of epidermal cells— the
primitive nails. As HENSEN remarks, " The similarity of the hand
at this stage to the anterior extremity of a Carnivore viewed from
the sole is striking ; in addition to the toe-like brevity and thickness
of the fingers, the pads are well developed/'

With their enlargement the limbs apply themselves to the ventral
surface of the embryo, being directed obliquely from in front back-

THE ORGANS OF THE INTERMEDIATE LAYER OR MESENCHYME. 637

ward [and ventrad], the anterior limbs more obliquely than the
posterior. In both of them the future extensor side lies dorsal,
the flexor side ventral. Both the radial and tibial margins with the
thumb and great toe are directed cephalad, the fifth finger and the
fifth toe caudad.

By this and by the fact that the limbs belong to several trunk-
segments are explained certain conditions in the distribution of the
nerves of the upper extremity. In the case of the arm "the radial
side is supplied with nerves (axillaris, musculo-cutaneus), whose fibres
are referable to the fifth, sixth, and seventh cervical nerves. Upon
the ulnar side, on the contrary, are found nerves (n. cutaneus medialis,
n. medius, and n. ulnaris) whose origin from the lower secondary
trunk of the plexus discloses their derivation from the eighth cervical
and first dorsal nerves " (SCHWALBE).

In the further course of development both limbs alter their original
position, — the anterior to a greater extent than the posterior, — in-
asmuch as they undergo a torsion around their long axes in opposite
directions. In this way the extensor side of the upper arm becomes
directed backward [caudad]. that of the thigh forward ; radius and
thumb are now directed laterad, tibia and great toe mediad. These
alterations in position due to torsion are naturally to be taken into
account in determining the homologies of the anterior and posterior
extremities, so that radius corresponds to tibia and ulna to fibula.

In the originally homogeneous cell-mass the fundaments of the
skeleton and musculature are gradually differentiated from each
other, owing to the fact that the cells acquire a more definite
histological character. In this connection the following phenomenon
is to be observed : —

The parts of the skeleton of the extremity are not all established
at the same time, but follow a definite sequence, in somewhat the
same manner as, in the development of the axial skeleton, the process
of segmentation begins in front and progresses backward. So in
the limbs the proximal skeletal elements (i.e., those which are situated
nearer to the trunk) are formed sooner than the distal ones.

This is the most strikingly apparent in the case of the fingers and
toes. Whereas the first phalanx has been differentiated from the
surrounding tissue in embryos of the fifth and sixth week, the
second and third are not at that time distinguishable ; the ends of
the fundaments of fingers and toes still consist of a mass of small
cells in process of growth. In this mass the second phalanx is then,
differentiated, and at last the third.

638 EMBRYOLOGY.

Furthermore the formation of the anterior limbs outstrips some-
what that of the posterior.

In the development of the skeleton of the extremities there are to be
recognised, as in the vertebral column and the skull, three different
stages, — the stage of the membranous, that of the cartilaginous, and that
of the osseous fundament.

After these general remarks I turn to the detailed description of
(1) the pectoral and pelvic girdles, (2) the skeleton of the appendage,
which projects free from the surface of the trunk, and (3) the
formation of joints.

(a) Pectoral and Pelvic Girdles.

The fundaments of the girdles of the limbs consist each of a pair
of curved pieces of cartilage, which are imbedded under the skin in
the muscles of the trunk, and which bear near the middle an articular
surface for the reception of the skeleton of the free extremity. By
this each cartilage is divided into a dorsal half, near the vertebral
column, and a ventral half. The former is converted in Mammals
and Man into a broad shovel-shaped piece ; the ventral half, which
reaches to, or nearly to, the median plane, is, on the contrary,
divided into two diverging processes, an anterior and a posterior.
The cartilaginous pieces thus distinguishable ossify from special
centres, and thereby acquire a higher degree of independence.

The shoulder-blade (scapula) of Man is at first a cartilage of a
form similar to that of the adult, except that the basis scapulae is
less developed. In the third month ossification begins at the collum
scapulae. However, the margins, the spine, and the acromion
remain for a long time cartilaginous, and indeed are in part so even
at the time of birth. There arise in them here and there accessory
centres during childhood.

. From the articular part of the shoulder-blade there runs ventrally
a cartilaginous process, which is short in Man, but in other Verte-
brates is of considerable size and reaches down to the sternum. It
corresponds to the posterior of the previously mentioned diverging
processes into which the ventral part of the cartilaginous arch is
divided, and is known in comparative anatomy as pars coracoidea.
In Man it is only slightly developed. Its great independence, however,
is made evident by its acquiring in the first year after birth a sepa-
rate centre of ossification. From this there gradually arises a bony
element (os coracoideum), which is joined to the shoulder-blade until

THE ORGANS OF THE INTERMEDIATE LAYER OR MESENCHYME. 639

the seventeenth year by a strip of cartilage, and may therefore be
detached. Afterwards it is united with the scapula by bony substance
and constitutes the coracoid process. Still later the fusion of the
accessory centres previously mentioned takes place, to which, how-
ever, no great morphological importance attaches.

There are two different views concerning the place which the
clavicle takes in the shoulder-girdle.

According to GOETTE, HOFFMANN, and others, it belongs to the
primordial skeletal parts, which are preformed in cartilage, and
corresponds to the anterior ventral process, which was present in the
primitive form of the shoulder-girdle. According to GEGENBAUR it
is a covering bone which has entered into union with the cartilaginous
skeleton in the same way as the covering bones of the skull have
with the primordial cranium.

It is the peculiar method of the development of the clavicle that
has caused this divergence of opinion. This is the first bone to be
formed in Man ; it begins to be ossified as early as the seventh week.
The earliest bony piece, as GEGENBAUR was the first to ascertain, is
developed out of wholly indifferent tissue. Then there are added at
both ends masses of cartilage, which are softer and provided with
less intermediate substance than the ordinary embryonic cartilage.
They serve, as in other bones that are preformed in cartilage, for the
elongation of the clavicle at both ends. There is also developed in
the sternal end, between the fifteenth and twentieth years, a kind of
epiphysial centre, as KOLLIKER states ; this fuses sometimes as late
as the twenty-fifth year with the main piece.

The original conditions are the most faithfully preserved in the
pelvic girdle, even in Man and Mammals. The first fundament of
the girdle consists of a right and a left pelvic cartilage, which are
united ventrally in the symphysis by means of connective tissue, and
each of which has at its middle an articular fossa. Each pelvic
cartilage is composed of an expanded part extending dorsally from
the articular depression, — the iliac cartilage, — which is joined to the
sacral region of the spinal column, and two ventral cartilaginous
rods, — pubis and ischium, — which, meeting in the symphysis, enclose
the foramen obturatorium.

It is stated by ROSENBERG that the pubic cartilage is at first
formed independently, but that it soon fuses with the other cartilages
at the acetabulum.

Ossification begins at the end of the third month in three places,
and thus are formed a bony ilium, os pubis, and ischium at the

640 EMBRYOLOGY.

expense of the cartilage, of which, however, considerable remnants-
are still present at the time of birth. For the whole crest of the
ilium, the rim and fundus of the acetabulum, and the whole tract
from the tuberosity of the ischium to the spine of the pubis is still
cartilaginous.

After birth the growth of the three bony pieces advances toward
the acetabulum, where they all meet, being however separated, up to
the time of puberty, by strips of cartilage, which together form a
three-rayed figure. At about the eighth year both the ascending
and descending rami of pubis and ischium fuse with each other, so
that at this time each hip-bone consists of two pieces joined by
cartilage at the acetabulum — the ilium and an ischio-pubic bone.
These do not become united into one piece until the time of puberty.

As in the pectoral girdle, so also in the pelvic girdle, there occur
accessory centres of ossification ; of these one, which sometimes arises
in the cartilage of the acetabulum, is the most important, and is
described as os acetabuli. Others arise in the cartilaginous crest of
the ilium, in the spines and tubercles, and in the tuberosity of the
ischium. They are not united with the chief bones until the end of
the period of growth.

(b) Skeleton of the Free Extremity.

All skeletal parts of the hand, fore-arm, and arm, as well as of the
foot, leg, and thigh, are originally solid pieces of hyaline cartilage,
which early acquire the general forms of the bones that subsequently
replace them. They are marked off from their surroundings by a
special fibrous layer of connective tissue, the perichondriuin.

From the beginning of the third month the process of ossification
takes place in the larger skeletal pieces, by means of which the
cartilaginous tissue is destroyed and replaced by osseous tissue, in the
same manner as in the vertebral column. In this process several
general phenomena regularly make their appearance ; I shall go
somewhat into the details of these, without however taking into
account the complicated histological changes, information concerning
which is given in text-books of histology.

The process of ossification takes externally a somewhat different
turn according as the cartilages are small and uniformly developed
in all directions, as in the wrist and ankle, or have become more
elongated,

In the first case the course of development is more simple. From

THE ORGANS OF THE INTERMEDIATE LAYER OR MESENCHYME. 641

the perichondrium vascular, richly cellular connective-tissue processes
grow into the cartilage, dissolve its matrix, and unite with one
another in its centre. There arises a network of medullary [marrow]
cavities, in the vicinity of which there is a deposit of salts of lime (a
provisional calcification). The medullary spaces extend farther and
farther by destruction of the cartilaginous substance. Then there
are secreted by the superficially located medullary cells bone-lamellae,
which gradually increase in thickness. The osseous nucleus thus
formed slowly increases in size, until finally the cartilage is almost
entirely replaced, only a thin layer of it remaining at the surface as
a covering to the bone.

The ossification of the wrist- and ankle- bones is therefore purely
endochondral, and proceeds ordinarily from one, sometimes from two,
centres of ossification. It does not begin until very late — in the first
year after birth. The only exception occurs in the foot, where the
os calcis and astragalus acquire a bony nucleus in the sixth and
seventh months, and the cuboid begins to ossify a short time before
birth. In the others ossification takes place after birth, and, as
K.OLLIKER states, in the following order : —

I. In the hand. (1) Os magnum and unciform (first year);
(2) cuneiform (third year) ; (3) trapezium and lunar (fifth year) ;
(4) scaphoid and trapezoid (sixth to eighth year); (5) pisiform
(twelfth year).

II. In the foot. (1) Os scaphoideum (first year) ; (2) internal and
middle cuneiform (third year) ; (3) external cuneiform (fourth year).

Concerning the cartilaginous fundaments of a special centrale carpi, which
usually is not retained as a separate carpal element (ROSENBERG), as well as
a special intermedium tarsi or trigonum (BARDELEBEN), the text-books of
comparative anatomy are to be consulted.

The process of ossification is more complicated in the long car-
tilages, in which, moreover, it begins much earlier, usually even in
the third month of embryonic life. The course of ossification is
fairly typical.

At first a perichondral ossification takes place midway between
the ends of each cartilage in the humerus and femur, tibia and
fibula, radius and ulna. From the perichondrium there is deposited
upon the already formed cartilage bony tissue instead of a car-
tilaginous matrix, so that the middle portion of the cartilage becomes
ensheathed in a bony cylinder, which is continually increasing in
thickness.

41

642 EMBRYOLOGY

The further growth of the skeletal element thus composed of two
tissues proceeds in two ways : first by growth of the cartilage, and
secondly by increase of bony substance.

The cartilaginous tissue increases at both ends of the skeletal
piece and contributes to the increase of the latter both in length and
thickness. In the middle, on the contrary, where it is enveloped in
a bony cylinder, it ceases to grow. Here there is a continual ad-
dition of new bony lamellae upon those already formed; they are
produced by the original perichondrium, or, as one may now more
properly say, by the periosteum.

In this process the successive lamellae extend farther and farther
toward the two ends of the skeletal piece ; new portions of the
cartilage are being continually ensheathed in bone and restricted in
their growth.

The periosteal bony sheath assumes in consequence the form of
two funnels united at their apices.

The cartilage which fills up the funnels early undergoes a gradual
metamorphosis and degeneration. From the osseous sheath there
grow into it connective -tissue strands with blood-vessels, which
dissolve the matrix and produce larger and smaller marrow-cavities.
Then, by the secretion of osseous tissue at the surface of the
persisting remnants of cartilage, there is developed a spongy bone-
substance, which fills up the funnel-shaped cavities of the compact
bony mantle produced by the periosteum. The spongy bone is,
however, only an evanescent structure. It in turn is gradually
dissolved, beginning at the middle of the skeletal element, and its
place is occupied by a very vascular marrow. In this way there
arises in the originally quite compact cartilaginous fundament the
large central medullary cavity of the long bones.

During these processes the two ends still remain cartilaginous, and
serve for a long time by their growth to increase the length of the
skeletal element. They are designated as the two epiphyses, in
distinction from the middle piece, which is the first to ossify, and
which has received the name diaphysis. The latter increases in size
at the expense of the epiphysial cartilages, for the endochondral
process of ossification progresses, with a very distinct line of ossifica-
tion, toward both ends.

A new complication in the development of the tubular (long)
bones arises either a short time before or in the first years after
birth. There are then developed in the middle of each epiphysis
special centres of ossification, the so-called epiphysial nuclei; there

THE ORGANS OF THE INTERMEDIATE LAYER OR MESENCHYME. 643

are first produced, in the manner previously described, vascular canals,
which arise by the dissolution of the cartilaginous substance; the
canals unite to constitute large medullary spaces, at the surfaces of
which osseous tissue is .then secreted.

By a slowly progressing enlargement of the bony nucleus, which
continues for years, the epiphysial cartilage is gradually converted
into a spongy osseous disc, being finally reduced to small remnants.
First, there is preserved, as an investment of the free surface, a layer
only a few millimetres thick, which constitutes the "articular
cartilage." Secondly, there remains for a long time a thin layer of
cartilage between the older, bony middle piece and the bony disc-like
epiphysis, and this serves to keep up the elongation of the skeletal
part. For the cartilage grows vigorously by the proliferation of its
cells, and thus is being renewed as fast as its two flat surfaces are
dissolved away by the endochondral ossification which takes place at
its expense, both by the growth of the bony epiphyses and, to a much
greater extent, by that of the more rapidly elongating diaphysis.

Thus it happens that long bones which have not yet ceased
growing can be divided into three pieces, if the organic parts are
removed by maceration. A fusion into a single osseous piece does not
take place until, at the time of maturity, the increase in the length
of the body has ceased. Then the thin plates of cartilage between
the diaphysis and its two epiphyses are broken down and converted
into bony tissue. From this time forward a further increase in the
length of the bone is impossible.

Besides the three typical and chief centres already described, from
which the ossification of the cartilaginous fundament of a tubular
bone proceeds, there are established in many cases smaller centres of
ossification of secondary importance, which are denominated accessory
bone-nuclei. They always arise in the later years, when the epiphyses
are well developed, and sometimes not until they are in process of
fusion with the diaphysis. They then appear at places where the
cartilaginous fundament possesses elevations and projections, as in
the tubercles of the humerus, in the trochanters of the femur, the
epicondyles, etc. They serve for the conversion of these elevations
into osseous masses, which are generally the last to fuse with the
chief bone.

After this general description, I add some detailed statements
about the formation and the number of the more important bony
nuclei in the fundaments of the separate tubular bones, concerning
which we have the extensive investigations of SCHWEGEL.

644 EMBRYOLOGY.

1. The diaphysis of the humerus ossifies in the eighth week. Epiphysial
nuclei are not formed until after birth, at the end of the first or beginning of
the second year. In the second year there appear accessory nuclei in the
tuberculum majus and minus ; during and after the fifth year in the epicondyles
also.

2. The diaphyses of the radius and ulna also begin to ossify in the eighth
week. Epiphysial nuclei do not appear until between the second and the fifth
years. Accessory nuclei are observed rather late in the styloid processes.

3. The metacarpals begin to ossify in the ninth week, but, with the
exception of the metacarpal of the thumb, there arises only one epiphysis,
which is at the distal end. This acquires in the third year its own centre of
ossification.

4. The ossification begins in the phalanges at the same time as in the
metacarpals.

5. The femur begins to ossify in the seventh week. A short time before
birth there is formed in the distal epiphysis a centre of ossification, which is a
part of the evidence that a child has been carried to the full time, and therefore
possesses a certain importance for forensic purposes. After birth an epiphysial
nucleus soon appears in the head of the femur. Accessory nuclei are formed
in the fifth year in the trochanter major, in the thirteenth or fourteenth in.
the trochanter minor.

6. Tibia and fibula acquire epiphysial nuclei in the first and third years after
birth, first at the proximal, then at the distal end, the ossification in the
fibula occurring about a year later than that in the tibia. GEGENBAUE
regards this as indicating a subordination of the functional importance of the
fibula in comparison with the tibia.

7. The patella begins to ossify in the third year.

8. To the metatarsals and the phalanges of the toes applies in general all
that has been said about the corresponding parts of the hand.

(c) Development of the Joints.

Inasmuch as the separate pieces of cartilage in the body are
formed by histological differentiation in the connective-tissue layers,
they are at first united to one another by remnants of the* parent
tissue. This generally acquires a more compact fibrous condition
and is converted into a special ligament.

Such a union of the separate skeletal elements is the prevailing
method in the lower Vertebrates, as, e.g., in the Sharks. In the
higher Vertebrates, including Man, it is retained in many, but not
all, places, as, e.g., in the vertebral column, where the bodies of the
vertebrae are joined to each other by intervertebral discs of con-
nective tissue. But at the places where the apposed skeletal parts
acquire greater freedom of motion upon each other, there appears,
in place of the simpler connective -tissue union, the more complicated
articular connection.

THE ORGANS OW THE INTERMEDIATE LAYER OR MESENCHYME. 645

In the development of the joints the following general phenomena
occur : —

Young cartilaginous fundaments, as, e.g., those of the thigh and
leg, are in early stages separated at the place where the articular
cavity is subsequently formed by a very cellular intermediate tissue
(the intermediate disc of HENKE UND EEYHER). This subsequently
diminishes in extent, because the ends of the cartilages grow at its
expense. In many cases it disappears entirely, so that the terminal
surfaces of the skeletal parts concerned are for some distance in
immediate contact.

The specific curvature of the articular surfaces is by this time
more or less well established. This is accomplished at a time when
there is as yet no articular cavity, and when, moreover, movements
of the skeletal parts cannot be executed, because the muscles are not
capable of functioning.

From this it follows that during embryonic life the articular
surfaces cannot acquire their specific form under the influence of
muscular activity, and that they are not formed, as it were, by
attrition and adaptation to each other in consequence of definite
recurrent movements in a simply mechanical way, as has been
assumed by many. The early appearing typical form of the joint
seems therefore to be inherited (BERN AYS). Muscular activity can be
effective only for alterations at later stages; it is, however, not
without influence in the further development and formation of the
articular surfaces.

When, after the disappearance of the intermediate tissue, the
surfaces at the ends of the developing cartilages come into immediate
contact, there arises between them a narrow fissure as the first
fundament of the articular cavity. This is bounded directly by the
hyaline articular cartilage, which does not here possess any peri-
chondrium. Then a sharper delimitation of the articular cavity
from the surrounding connective tissue gradually takes place, inas-
much as a firmer connective-tissue layer, which becomes the capsular
ligament, is developed from one cartilage to the other, and addi-
tional fibrous tracts are converted into separate tense articular
ligaments.

The process of development takes a somewhat different course
when the articular surfaces do not fit into each other. In these
cases the ends of the cartilages cannot come into immediate contact
in the manner previously described ; they now remain separated by
more or less considerable remnants of the richly cellular intermediate

646 EMBRYOLOGY.

tissue, which then assumes more and more the condition of compact
fibrous tissue.

When the intermediate tissue is preserved in its whole extent,
there arises a nbro-cartilaginous interarticular disc (intermediate
or interpolated cartilage), which is inserted as an elastic cushion
between the skeletal pieces. There is formed an articular fissure
between the ligamentous disc and the terminal surfaces of each of
the articular cartilages, or, in other words, there is developed an
articular cavity, which is divided into two by means of an interpolated
disc.

Finally, a special modification of the joint occurs when the carti-
lages are partly in contact and partly remain separated by inter-
mediate tissue. In this case there appears at the place of contact
a single articular cavity ; laterally, however, this is enlarged by
the incongruent parts of the cartilaginous surfaces becoming split oft
from the intermediate tissue separating them. Thus there arises an
articular cavity which, it is true, is single, but into which are thrust
from the articular capsule the metamorphosed products of the inter-
mediate tissue, which constitute the so-called semi-lunar fibro-carti-
lages or the menisci, as in the case of the knee-joint.

As was previously described in treating of the development of the
bones of the extremities, there is preserved, even after the termination
of the process of ossification, an exceedingly small remnant of the
cartilaginous fundament, which forms on the articular surfaces a
cartilaginous covering only a few millimetres thick. The articular
ends of all bones that are developed out of a cartilaginous fundament
possess such a covering.

It is different when bones that have been produced directly in
connective tissue (the covering bones) are united to each other by
a veritable joint. Such a case occurs in the articulation of the
lower jaw in Mammals. The glenoid process of the lower jaw, as
well as the glenoid fossa of the squamous portion of the temporal
bone, is in this case covered with a thin layer of unossified tissue. It
looks like cartilage, and usually is described as such. But microscopic
examination shows that it is composed exclusively of layers of con-
nective:tissue fibres.

As there are bones which are preformed in cartilage and others which
are preformed in connective tissue, so a distinction must be made
between joints with a covering of hyaline cartilage and joints with
a covering of fibrous connective substance.

ORGANS OF THE INTERMEDIATE LAYER OR MESENCHYME. 647

SUMMARY.
A. The Vertebral Column.

1. During development the vertebral column passes through
several (from lower to higher) morphological conditions, of which the
lower are permanently preserved in the inferior classes of Vertebrates,
whereas in the higher classes they appear only at the beginning of
development and are then replaced.

2. In the axial skeleton three different stages of development are
distinguished : —

(1) As chorda dorsalis (notochord),

(2) As cartilaginous and

(3) As osseous vertebral column.

3. The chorda is developed out of a tract of cells (chorda-entoblast,
fundament of the chorda) lying below the neural tube and belonging
to the inner germ-layer, from which it is detached by abstriction
(chordal folds).

4. The chorda is a rod composed of vesiculated cells and bounded
superficially by a firm sheath ; it begins with a pointed end beneath
the mid-brain vesicle (in the region of the future sella turcica of the
cranial floor) and reaches to the blastopore (primitive groove).

5. The chorda persists as a permanent skeletal structure in
Amphioxus and the Cyclostomes.

6. A cartilaginous vertebral column is found in the adults of the
Selachians and some of the Ganoids, while in the remaining Verte-
brates it appears more or less during development as a forerunner
of the bony vertebral column.

7. The cartilaginous vertebral column is developed by histological
metamorphosis out of embryonic connective tissue, a part of which
envelops the chorda as skeletogenous chordal sheath, and a part
forms a thin continuous envelope (membranous vertebral arches)
around the neural tube.

8. The process of chondrification begins on both sides of the
chorda, progresses around it both above and below, and thus forms
a cartilaginous ring, — the body of the vertebra, — from which the
process of chondrification advances dorsnlly into the membranous
envelppe of the neural tubes, producing the arches of the vertebrae
and ceasing with the formation of the vertebral spines.

9. It is not until the beginning of the process of chondrification
in the unsegmented, connective-tissue, skeletogenous chordal sheath

648 EMBRYOLOGY.

that the axial skeleton undergoes a segmentation into separate like
portions, which are situated one behind another ; to accomplish this,
remnants of the parental tissue do not chondrify, but become,
between the bodies of the vertebrae, the intervertebral discs, and,
between the arches, the ligamenta intercruralia, etc.

10. The segmentation of the vertebral column has been dependent
in its origin upon the segmentation of the musculature, and has
been effected in such a way that skeletal segments and muscular
segments alternate with one another, and that the longitudinal
muscle-fibres, which lie alongside the axial skeleton, are attached
by their anterior and posterior ends to two [adjacent] vertebrae and
are capable of moving them upon each other.

11. The chorda is more or less restrained in its growth by the
cartilaginous bodies of the vertebrae surrounding it, and degenerates
in different ways in the different classes of Vertebrates ; in Mammals
the part located in the body of the vertebra is completely obliterated,
whereas a remnant of it is preserved between vertebrae and becomes
the jelly-core of the intervertebral disc.

12. The cartilaginous vertebral column is converted in most
Vertebrates into a bony one, by the breaking down of the carti-
laginous tissue, which begins at different places, and its replacement
by bony tissue. (Formation of bone-nuclei or centres of ossification.)

13. The ossification of each cartilaginous vertebral fundament in
Mammals and Man proceeds from three centres, from one in the
body and one in each half of the arch, to which subsequently
certain accessory centres are added.

14. With each vertebral segment there is associated a pair of ribs,
which arise by a process of chondrification in the layers of tissue
which separate the muscle-segments (the ligamenta intermuscularis).

15. In Man the various regions of the vertebral column are
produced by metamorphosis of the vertebral and costal fundaments.

(1) The thoracic part of the vertebral column (dorsal vertebrae)

is characterised by the following peculiarities : the ribs
attain to complete development ; a part of them become
expanded at their ventral ends, and united to form the
two sternal bars, by the fusion of which the unpaired
sternum is produced. (Fissura sterni, an arrested forma-
tion.)

(2) In the cervical and lumbar regions of the column the funda-

ments of the ribs remain small, and fuse with outgrowths
from the vertebrae — the transverse processes — to form

THE ORGANS OP THE INTERMEDIATE LAYER OR MESENCHYME. 649

the lateral processes. In the neck-region there is retained,
between the transverse process and the rudiment of the
rib, the foramen transversarium for the vertebral artery.

(3) Atlas and epistropheus [axis] assume special forms, owing to

the fact that the body of the atlas remains separate from
the fundaments of its arch, and unites with the body of
the axis to form its odontoid process. (Separate centre
of ossification in the odontoid process.)

(4) The sacrum results from the fusion of five vertebrae and the

sacral ribs belonging to them. The latter by their fusion
produce the so-called massse laterales, which bear the
articular surfaces for the ilium.

B. The Head-Skeleton.

16. The skull, like the vertebral column, passes through three
morphological conditions, which are designated as membranous and
as cartilaginous primordial cranium and as bony cranial capsule.

17. The membranous primordial cranium consists of —

(1) The anterior end of the chorda, which extends to the anterior

margin of the mid-brain vesicle, and

(2) A connective-tissue layer, which surrounds the chorda as

skeletogenous layer, and also furnishes a membranous
investment around the five brain-vesicles.

18. The cartilaginous primordial cranium arises by a histological
metamorphosis of the membranous one.

(1) At the sides of the chorda there are first formed two car-

tilaginous rods, the two parachordals, which soon grow
around the chorda both above and below, and become
united into a single cartilaginous plate.

(2) In front of the parachordals RATHKE'S trabeculae cranii

make their appearance ; their posterior ends soon unite
with the parachordal cartilages, their anterior ends
become enlarged and by fusing with each other produce
the ethmoid plate ; in the middle they remain for a long
time separate and embrace the hypophysis (region of
sella turcica).

(3) From the cartilaginous base of the cranium thus produced,

the process of chondrification, as in the development of
the vertebral column, first extends into the lateral walls,
and at last into the roof of the membranous primordial
cranium, partly enclosing the higher sensory organs.

650 EMBRYOLOGY.

19. In the Selachians the cartilaginous primordial cranium is a
permanent structure, and possesses rather thick uniform walls ; in
Mammals and Man, on the contrary, it is of only short duration,
serving as foundation for the bony cranial capsule that takes its place;
it is therefore less completely developed than in Selachians, for only
the base and lateral parts are in all cases cartilaginous, whereas the
roof presents large openings closed by dermal membranes.

20. From its relation to the chorda dorsalis, there are dis-
tinguishable in the cartilaginous primordial cranium two chief
portions, — a vertebral (chordal) and a non-vertebral (prechordal), —
or, according to its relations to the sensory organs, it may be
divided into four regions — ethmoidal, orbital, labyrinthal, and
occipital.

21. As the ribs are associated with the vertebral column in the
form of ventral arched structures, so also the visceral skeleton is
united to the primordial cranium in the head-region.

22. The visceral skeleton is composed of segmented cartilaginous
rods, which have arisen by a process of chondrification in the tissue
of the membranous visceral arches between the successive visceral
clefts.

23. The cartilaginous throat- or visceral arches are well developed
only in the lower Vertebrates (permanently in the Selachians), and are
distinguished, according to differences of position and form, as jaw-
arch, hyoid arch, and branchial arches, the last being variable in
number.

24. The jaw-arch is divided into the cartilaginous upper jaw
(palato-quadratum) and the cartilaginous lower jaw (mandibulare) ;
the hyoid arch into the hyomandibulare, the hyoides, and the unpaired
copula.

25. In Mammals and Man the cartilaginous visceral skeleton
attains only a very rudimentary condition, and is converted into the
cartilaginous fundaments of the three auditory ossicles and the hyoid
bone.

26. In the membranous jaw-arch arise —

(a) The incus, which corresponds to the palato-quadratum of

lower Vertebrates ;

(b) The malleus, which is the representative of the articular

part of the cartilaginous mandibulare ; and

(c) The cartilage of MECKEL, which corresponds to the remain-

ing portion of the mandibulare, but which afterwards
completely degenerates.

THE ORGANS OP THE INTERMEDIATE LAYER OR MESENCHYME. 651

27. The membranous hyoid arch furnishes, [beginning with] its
uppermost part, —

(f,) The bow of the stapes, — whereas its plate is derived from
the cranial capsule and is, as it were, cut out to form the
fenestra ovalis, —

(b) The processus styloideus,

(c) The ligamentum stylohyoideum, and

(d) The lesser horn and body of the hyoid bone.

28. The third membranous visceral arch is chondrified only in
its lowest [ventral] part, to form the greater horn of the hyoid
bone.

29. At no stage of its development does the primordial cranium
exhibit evidence that, like the vertebral column, it is composed of
separate segments.

30. The original segmentation of the head is expressed in only
three ways — in the appearance of several primitive segments (myo-
tomes), in the arrangement of the cranial nerves, and in the funda-
ment of the visceral skeleton.

31. The primordial cranium is therefore an unsegmented skeletal
fundament in a region of the body that is segmented in another
manner.

32. The ossification of the head-skeleton is a much more com-
plicated process than that of the vertebral column.

33. Whereas in the vertebral column there are developed bones of
only one kind, — through substitution for cartilage, — there are to be
distinguished in the ossification of the head-skeleton, according to
their formation and source, two different kinds of bone — primary
and secondary.

34. The primary bones of the head arise in the cartilaginous
primordial cranium and visceral skeleton, like the separate bone-
nuclei in the cartilaginous vertebral column.

35. The secondary bones, covering or membrane-bones, arise
outside the primordial skeleton of the head in the connective-tissue
foundation of the skin and mucous membrane ; they are therefore
dermal and mucous-membrane ossifications, and constitute in lower
Vertebrates a portion of a dermal skeleton that covers the surface
of the whole body.

36. The covering bones are developed in some instances, which
can be regarded as reproductions of the original method, by fusion of
the bony bases of numerous denticles which arise in the skin and
mucous membrane.

652 EMBRYOLOGY.

37. Primary and secondary bones sometimes remain separate in
later stages, sometimes they fuse with each other to form bone-
complexes, like the temporale and sphenoidale.

38. After the conclusion of the process of ossification only unim-
portant remnants of the primordial cranium persist as the carti-
laginous partition of the nose and as the nasal cartilages.

C. The Skeleton of the Extremities.

39. The skeleton of the limbs, excepting the clavicle,, the develop-
ment of which exhibits many peculiarities, is established in the
cartilaginous stage. (Cartilaginous shoulder-girdle, cartilaginous
pelvic girdle, cartilages of arm and leg.)

40. The ossification takes place, in the same manner as in the verte-
bral column and primordial cranium, from centres of ossification by
disintegration of cartilaginous tissue and its replacement by osseous
tissue.

41. The most of the small cartilages of the wrist and ankle ossify
from a single bone-nucleus, but the larger flat cartilages of the
shoulder and pelvic girdles from several centres.

42. The cartilaginous fundaments of the tubular [long] bones
ossify at first in the middle, which region is designated as diaphysis,
whereas their two ends — the epiphyses — remain for a long time
cartilaginous, and are the means of the elongation of the skeletal
element.

43. In Man the cartilaginous epiphyses begin to ossify from centres
of their own (epiphysial nuclei), some of them in the last month
before, others not until after birth.

44. The fusion of the bony diaphysis with the bony epiphyses does
not take place until the termination of the growth of the skeleton
and body in length, and is accompanied by the removal of the
intervening cartilaginous tissue.

45. Before growth is at an end the tubular bones can be divided
into a larger middle piece (diaphysis) and two small bony epiphyses.

46. Of the cartilaginous fundament of a tubular bone there is
preserved only a small remnant as a cartilaginous covering of the
articular ends (articular cartilage).

47. The medullary cavity of the tubular bones is formed by the
resorption of the spongy bone-substance that first replaced the
cartilage.

48. Whereas the articular ends of bones preformed in cartilage
are covered over with hyaline cartilage, the articular surfaces of

LITERATURE. 653

bones of connective-tissue origin (covering bones) present an invest-
ment of fibrous connective substance (articulation of the jaw).

49. The form of the articular surfaces is determined at a time
when an influence on the part of the musculature is not to be
considered

LITERATURE.

Development of the Diaphragm and Pericardium.

Cadiat, M. Du developpement de la partie cephalothoracique de 1'embryon,

de la formation du diaphragma, des pleures, du p<§ricarde, du pharynx et

de 1'oesophage. Jour, de 1'Anat. et de la Physiol. T. XIV. 1878.
Faber. TJeber den angeborenen Mangel des Herzbeutels in anatomischer,

entwicklungsgeschichtlicher und klinischer Beziehung. Virchow's Archlv.

Bd. LXXIV. 1878, p. 173.
His, W. Mittheilungen zur Embryologie der Saugethiere und des Menschen.

Archiv f. Anat. u. Physiol. Anat. Abth. 1881.
Lockwood. The Early Development of the Pericardium, Diaphragm and

Great Veins. Philos. Trans. Roy. Soc. London, 1888. Vol. CLXXIX. B,

1889, p. 365. And Proceed. Roy. Soc. London. Vol. XLIII. 1888, p. 273.
Ravn. Bildung der Scheidewand zwischen Brust- und Bauchhohle in Sauge-

thier-Embryonen. Biol. Centralblatt. Bd. VII. 1887.
Ravn. Ueber die Bildung der Scheidewand zwischen Brust- und Bauchhohle

in Saugethier-Embryonen. Archiv f. Anat. u. Physiol. Anat. Abth. 1889.
Ravn. Untersuchungen iiber die Entwicklung des Diaphragmas und der

benachbarten Organe bei den Wirbelthieren. Archiv f. Anat. u. Physiol.

Anat, Abth. 1889. Suppl.-Band.
Uskow, K". Ueber die Entwicklung des Zvverchfells, des Pericardiums und

des Coeloms. Archiv f . mikr. Anat. Bd. XXII. 1883.
Waldeyer. Ueber die Beziehungen der Hernia diaphragmatica congenita

zur Entwicklungsweise des Zwerchfells. Deutsche medic. Wochenschrift

No. 14. 1884.

Development of the Heart and Blood-vessels.

Bernays, A. C. Entwicklungsgeschichte der Atrioventricularklappen. Mor-

phol. Jahrb. Bd. II. 1876.
Born, G. Beitrage zur Entwicklungsgeschichte des Saugethierherzens.

Archiv f. mikr. Anat. Bd. XXXIII. 1889.
Brenner, A. Ueber das Verhaltniss des N. laryngeus inf. vagi zu einigen

Aortenvarietaten des Menschen und zu dem Aortensystem der durch

Lungen athmenden Wirbelthiere iiberhaupt. Archiv f. Anat. u. PhysioL

Anat. Abth. 1883.
Gasser. Ueber die Entstehung des Herzens bei Vogelembryonen. Archiv f.

mikr. Anat. Bd. XIV. 1877.

3, C. Die Ursachen des rechtzeitigen Eintritts der Geburtsthatigkeit

beim Menschen. Zeitschr. f. Geburtshilfe u. Gynakologie. Bd. VI.

1881, pp. 1-9.

654 EMBRYOLOGY.

Hochstetter, F. Ueber die Bildung der hinteren Hohlvene bei den Sauge-

thieren. Anat. Anzeiger. Jahrg. II. No. 16, 1887, p. 517.
Hochstetter, F. Ueber den Einfluss der Entwicklung der bleibenden Nieren

auf die Lage des Urnierenabschnittes der hinteren Cardinalvenen. Anat.

Anzeiger. Jahrg. III. 1888.
Hochstetter, F. Beitrage zur vergleichenden Anatomic und Entwicklungs-

geschichte des Venensystems der Araphibien und Fische. Morphol. Jahrb.

Bd. XIII 1888.
Hochstetter, F. Ueber das Gekrose der hinteren Hohlvene. Anat. Anzeiger.

Jahrg. III. 1888.
Hochstetter, F. Beitrage zur Entwicklungsgeschichte des Venensystems

der Amnioten. Morphol. Jahrb. Bd. XIII. 1888.

Iiindes. Bin Beitrag zur Entwicklungsgeschichte des Herzens. Inaugural-
dissert. Dorpat 1865.
Marshall, J. On the Development of the Great Anterior Veins in Man and

Mammalia. Philos. Trans. Koy. Soc. London. 1850.
Masius. Quelques notes sur le developpement du coeur chez le poulet.

Archives de Biologie. T. IX. 1889.
Oellacher. Ueber die erste Entwicklung des Herzens und der Pericardial-

oder Herzhohle bei Bufo cinereus. Archiv f. mikr. Anat. Bd. VII. 1871,

p. 157.
Peremeschko. Ueber die Entwicklung der Milz. Sitzungsb. d. k. Akad. d.

Wissensch. Wien. Math.-naturw. Cl. Bd. LVI. Abth. 2. 1867, p. 31.
Rabl, Carl. Ueber die Bildung des Herzens der Amphibien. MorphoL

Jahrb. Band XII. 1887, p. 252.
Rathke, H. Ueber die Bildung der Pfortader und der Lebervenen bei Sauge-

thieren. Meckel's Archiv. 1830.
E-athke, H. Ueber den Bau und die Entwicklung des Venensystems der

Wirbelthiere. Bericht iiber das naturhist. Seminar der Universitat Konigs-

berg. 1838.
Rathke, H. Ueber die Entwicklung der Arterien, welche bei den Sauge-

thieren von dem Bogen der Aorta ausgehen. Archiv f. Anat. u. Physiol.

Jahrg. 1843.
Rose, C. Zur Entwicklungsgeschichte des Saugethierherzens. Morphol

Jahrb. Bd. XV. 1889, p. 436.
Sabatier. Observations sur les transformations du systeme aortique dans la

serie des Vertebres. Ann. d. Sci. Nat. Ser. 5. T. XIX. 1874.
Schmidt, F. J. Bidrag til Kundskaben om Hjertets Udviklingshistorie.

Nordiskt medicinskt Arkiv. Bd. II. 1870.
Sertoli. Ueber die Entwicklung der Lymphdriisen. Sitzungsb. d. k. Akad.

d. Wissensch. Wien. Math.-naturw. Cl. Bd. LIV. Abth. 2. 1866.
Strahl, H., und Carius. Beitrage zur Entwicklungsgeschichte des Herzens

und der Korperhohlen. Archiv f. Anat. u. Physiol. Anat. Abth. 1889.
Tiirstig. Mittheilung iiber die Entwicklung der primitiven Aorten nach

Untersuchungen an Hiihnerembryonen. Dissertation. Dorpat 1886.
Wertheimer, E. Kecherches sur la veine ombilicale. Jour, de 1'Anat. et de

la Physiol. T. XXII. 1886, pp. 1-17.

Development of the Skeleton.

Ahlborn, Fr. Ueber die Segmentation des Wirbelthierkorpers. Zeitschr. f
wiss. Zoologie. Bd. XL. 1884, p. 309.

LITERATURE. 655

Albrecht, P. Sur la valeur morphologique de 1'articulation mandibulaire,

du cartilage de Meckel et des osselets de 1'ouie, etc. Bruxelles 1883.
Balfour. On the Development of the Skeleton of the Paired Fins of Elasmo-

branchii considered in Relation to its Bearings on the Nature of the Limbs

of the Vertebrata. Proceed. Zool. Soc. London. 1881.
Bardeleben, K. Das Os intermedium tarsi der Saugethiere. Zool. Anzeiger

Jahrg. VI. 1883.
Bardeleben, K. Ueber neue Bestandtheile der Hand- und Fusswurzel der

Saugethiere, etc. Jena. Zeitschr. Bd. XIX. Suppl.-Heft III. 1886 (?)
Baumiiller. Ueber die letzten Veranderungen des MeckeL'schen Knorpels.

Zeitschr. f. wiss. Zoologie Bd. XXXII. 1879.
Bernays, A. Die Entwicklungsgeschichte des Kniegelenks des Menschen

mit Bemerkungen iiber die Gelenke im Allgemeinen. Morphol. Jahrb.

Bd. IV. 1878.
Brock. Ueber die Entwicklung des Unterkiefers der Saugethiere. Zeitschr.

f. wiss. Zoologie. Bd. XXVII. 1876, p. 287.
Carius. Ueber die Entwicklung der Chorda und der primitiven Rachenhaut

bei Meerschweinchen und Kaninchen. In.-Diss. Marburg 1888.
Decker. Ueber den Primordialschadel einiger Saugethiere. Zeitschr. f.

wiss. Zoologie. Bd. XXXVIII. 1883.
Dohrn, A. Studien zur Urgeschichte des Wirbelthierkorpers : —

IV. Die Entwicklung und Differenzirung der Kiemenbogen der Selachier.
V. Zur Entstehung und Differenzirung der Visceralbogen bei Petromy-

zon Planer i.
VI. Die paarigen und unpaaren Flossen der Selachier.

Mitth. a. d. Zool. Station Neapel. Bd. V. 1884, p. 102.

Dujges. Recherches sur 1'osteologie et la myologie des Batraciens & leurs
differents ages. Paris 1834.

Dursy, E. Zur Entwickluugsgeschichte des Kopfes des Menschen und der
hoheren Wirbelthiere. Tubingen 1869.

Ebner, von. Urwirbel und Neugliederung der Wirbelsiiule. Sitzungsb. d. k.
Akad. d. Wissensch. Wien. Math.-naturw. Cl. Bd. XCVII. Abth. 3.
1889, p. 194.

Fraser. On the Development of the Ossicula Auditus in the Higher Mam-
malia. Proceed. Roy. Soc. London. Vol. XXXIII. 1882, pp. 446-7.

Frenkel, F. Beitrag zur anatomischen Kenntniss des Kreuzbeines der Sauge-
thiere. Jena. Zeitschr. Bd. VIII. 1873.

Froriep, August. Zur Entwicklungsgeschichte der Wirbelsaule, insbeson-
dere des Atlas und Epistropheus und der Occipitalregion.

I. Beobachtung an Huhnerembryonen. Archiv f. Anat. u. Physiol.

Anat. Abth. 1883.

II. Beobachtung an Saugethierembryonen. Archiv f . Anat. u. Physiol.
Anat, Abth. 1886.

Froriep, August. Ueber ein Ganglion des Hypoglossus und Wirbelanlagen
in der Occipitalregion. Archiv f. Anat. u. Physiol. Anat. Abth. 1882.

Gadow. On the Modifications of the First and Second Visceral Arches, with
especial Reference to the Homologies of the Auditory Ossicles. Philos.
Trans. Roy. Soc. London. 1888. Vol. CLXXIX. B. 1889, pp. 451-87.

Gegenbaur. Ueber die Entwicklung der Clavicula. Jena. Zeitschr. Bd. I.
1864, pp. 1-16.

656 EMBRYOLOGY

Gegenbaur. Zur Morphologie der Gliedmaassen der Wirbelthiere. Morphol.

Jahrb. Bd. II. 1876.
Gegenbaur.

(1) Ueber die Kopfnerven von Hexanchus und ihr Verhaltniss zur
Wirbeltheorie des Schadels. Jena. Zeitschr. Bd. VI. 1871,
p. 497.

(2) Das Kopfskelet der Selachier, ein Beitrag zur Erkenntniss der
Genese des Kopfskelets der Wirbelthiere. Leipzig 1872.

(3) Ueber das Archipterygium. Jena. Zeitschr. Bd. VII. 1873, p. 131.

(4) Die Metamerie des Kopfes und die Wirbeltheorie des Kopfskelets.
Morphol. Jahrb. Bd. XIII. 1887.

Gotte, A. Beitrage zur vergleichenden Morphologie des Skeletsystems der

Wirbelthiere (Brustbein und Schultergiirtel). Archiv f. mikr. Anat.

Bd. XIV. 1877.
Gradenigo, G. Die embryonale Anlage des Mittelohres : die morphologische

Bedeutung der Gehbrknochelchen. Mitth. a. d. embryol. Inst. d. Univ.

Wien. Heft 1887, p. 85.
Hannover, A. Primordialbrusken og dens Forbening i det menneskelige

Kranium for fodselen. Danske Videnskabernes Selskabs Skrifter. Kjoben-

havn. Ser. 5, Bd. XI. p. 349. 1880.
Hannover, A. Primordialbrusken og dens Forbening i Truncus og Ex-

tremiteter hos Mennesket for Fodselen. (Table des matieres et Extrait

en franeais.) Kjobenliavn. Ser. 6, Bd. IV. p. 265. 1887.
Hasse, C. Die Entwicklung des Atlas und Epistropheus des Menschen und

der Saugethiere. Anatomisc.he Studien. Bd. I. Leipzig 1872.
Henke und Reyher. Studien liber die Entwickelung der Extremitaten des

Menschen, insbesondere der Gelenkflachen. Sitzungsb. d. k. Akad. d.

Wissensch. Wien. Bd. LXX. 1875.
Hertwig, Oscar. Ueber das Zahnsystem der Amphibien und seine Bedeutung

fiir die Genese des Skelets der Mundhohle. Eine vergleichend anato-

mische, entwicklungsgeschichtliche Untersuchung. Archiv f . mikr. Anat.

Bd. XI. Supplementheft. 1874.
Hoffmann, C. K. Beitrage zur vergleichenden Anatomie der Wirbelthiere.

Nieder. Archiv f. Zool. Bd. V. 1879.

Huxley. Lectures on the Elements of Comparative Anatomy. London 1864.
Jacobson. Abstract by Hannover in Jahresbericht, p. 36, Archiv f. Anat.

u. Physiol. Jahrg. 1844.
Julin, Charles. Kecherches sur I'ossification du maxillaire inferieur chez le

foetus de la balaenoptera. Archives de Biologic. T. I. 1880.
Kann. Das vordere Chordaende. Inauguraldissert. Erlangen 1888.
Keibel. Zur Entwicklungsgeschichte der Chorda bei Saugern. Archiv f

Anat. u. Physiol. Anat. Abth. 1889.
KBlliker, A. Allgemeine Betrachtungen iiber die Entstehung des knocher-

nen Schadels der Wirbelthiere. Berichte von der konigl. zoot. Anstalt.

Wiirzburg. Leipzig 1849.
Kolliker, Theodor. Ueber das Os intermaxillare des Menschen und die

Anatomie der Hasenscharte und des Wolfsrachens. Nova acta Acad.

Leop.-Carol. Bd. XLIII. 1882.
Leboucq, H. Recherches sur le mode de disparition de la corde dorsale

chez les vertebra's superieurs. Archives de Biologic. Vol. I. 1880.
Magitot et Robin. Memoire sur un organe transitoire de la vie foetale

LITERATURE. 657

design^ sous le nom de cartilage de Meckel. Ann. des. Sci. Nat. T. XVIII.

1862.
Masquelin. Eecherches sur le developpement du maxillaire inferieur de

1'homme. Bull, de 1'Acad. roy. de Belgique. 2e serie. T. XLV. 1878.
Oken. Ueber die Bedeutung der Schadelknochen. Jena 1807.
Parker, W. K., and Bettany. The Morphology of the Skull. London

1877. German translation by Vetter. 1879.
Perenyi. Entwicklung der Chorda dorsalisbei Torpedo marmorata. Math. u.

Naturw. Berichte aus Ungarn. Budapest. Bd. IV. p. 214, u. V. p. 218.

1886, 1887.
Rabl, Carl. Ueber das Gebiet des Nervus facialis. Anat. Anzeiger. Jahrg.

II. 1887.
Reichert, C. Ueber die Visceralbogen der Wirbelthiere im Allgemeinen und

deren Metamorphose bei den Vogeln und Saugethieren. Archiv f. Anat.

u. Physiol. 1837.
Rosenberg, E. Untersuchungen iiber die Occipitalregion des Cranium und

den proximalen Theil der Wirbelsaule einiger Selachier. Dorpat 1884.
Rosenberg, E. Ueber die Entwicklung der Wirbelsaule und das Centrale

carpi des Menschen. Morphol. Jahrb. Bd. I. 1875.
Ruge. Untersuchungen iiber Entwicklungsvorgange am Brustbein und an

der Sternoclavicularverbindung des Menschen. Morphol. Jahrb. Bd. VI.

1880.
Salensky, W. Beitrage zur Entwicklungsgeschichte der knorpeligen Gehor-

knb'chelchen bei Saugethieren. Morphol. Jahrb. Bd. VI. 1880.
Schwegel. Die Entwicklungsgescbichte der Knochen des Stammes und der

Extremitaten mit Kiicksicht auf Chirurgie, Geburtskunde und gerichtliche

Medicin. Sitzungsb. d. k. Akad. d. Wissensch. Wien. Math.-naturw. Cl.

Bd. XXX. 1858, p. 337.
Spondli, H. Ueber den Primordialschadel der Saugethiere und des Menschen.

Inaugural-Dissertation. Zurich 1846.

Stohr. Zur Entwicklungsgeschichte des Kopfskelets der Teleostier. Fest-
schrift d. medicin. Facultat Wurzburg. Leipzig 1882.
Stohr. Zur Entwicklungsgeschichte des Urodelenschadels. Zeitschr. f. wiss,

Zoologie. Bd. XXXIII. 1879.
Stohr. Zur Entwicklungsgeschichte des Anurenschadels. Zeitschr. f. wiss.

Zoologie. Bd. XXXVI. 1881.
Stohr. Ueber Wirbeltheorie des Schadels. Sitzungsb. d. physik.-med.

Gesellsch. Wurzburg. 1881.
Wiedersheim. Ueber die Entwicklung des Schulter- und Beckengiirtels^

Anat, Anzeiger. Jahrg. IV. 1889 u. Jahrg. V. 1890.

658 EMBRYOLOGY.

Besides the writings treating of the development of the separate
systems of organs, the following larger monographic works should be
cited : —

Embryology of Man.

Coste. Histoire generate et particuliere du developpement des corps organises.

1847—1859.

Ecker. Icones physiologicae. Leipzig 1851 — 1859.
Erdl. Die Entwicklung des Menschen und Huhnchens im Eie Leipna

1845.
His. Anatomic menschlicher Embryonen.

Heft I. Embryonen des ersten Monats. Leipzig 1880.

Heft II. Gestalt und Grbssenentwicklung bis zum Schluss des zweiten

Monats. Leipzig 1882.
Heft III. Zur Geschichte der Organe. Leipzig 1885.

Embryology of Mammals.

Baer, C. E. von. Ueber Entwicklungsgeschichte der Thiere. Beobachtung
und Reflexion. Konigsberg 1828 u. 1837.

Balfour. A Monograph on the Development of Elasmobranch Fishes. Lon-
don 1878.

Bischoff. Entwicklungsgeschichte des Kaninchens. Braunschweig 1842.

Bischoff. Entwicklungsgeschichte des Hundeeies. 1845.

Bischoff. Entwicklungsgeschichte des Meerschweinchens. 1852.

Bischoff. Entwicklungsgeschichte des Eehes. 1854.

Bonnet. Beitrage zur Embryologie der Wiederkauer, gewonnen am Schaf ei.
Archiv f. Anat. u. Physiol. Anat. Abth. 1884 u. 1889.

Duval. Atlas d'embryologie. Paris 1889.

Gotte. Entwicklungsgeschichte der Unke. Leipzig 1875.

Hatschek, B. Studien iiber Entwicklung des Amphioxus. Arbeiten a. d.
zool. Inst. d. Universitat Wien. 1882.

Hensen. Beobachtungen uber die Befruchtung und Entwicklung des Kanin-
chens und Meerschweinchens. Zeitschr. f. Anat. u. Entwicklungsg. Bd.
I. 1876.

His, W. Untersuchungen iiber die erste Anlage des Wirbelthierleibes. Die
erste Entwicklung des Huhnchens im Ei. Leipzig 1868.

Hubrecht. Studies in Mammalian Embryology. Placentation of Erinaceus,
etc. Quart. Jour. Mic. Sci. Vol. XXX. 1890, p. 283.

Rathke. Entwicklungsgeschichte der Natter. Konigsberg 1839.

Remak. Untersuchungen iiber die Entwicklung der Wirbelthiere. Scrim
1855.

Riickert. Ueber die Entstehung der Excretionsorgaue bei Selachiern.
Archiv f. Anat. u. Physiol. Anat. Abth. 1888.

Schultze, M. Die Entwicklungsgeschichte von Petromyzon Planeri. 1856.

Selenka. Studien iiber Entwicklungsgeschichte der Thiere. Wiesbaden
1886, etc.

INDEX.

A.

Accessory gerin, 189.
- nuclei (centres of ossification),
599, 640, 643.

— thyroid gland. 318, 320.
Acervulus cerebri, 436.
Acroblast, 180.
After-birth — see Placenta.
After-brain, 421.

— vesicle, 422, 427.
Air-cells of lung, 323.
Air-chamber of Hen's egg, 18, 219.
Albumen of Hen's egg, 17.
Alecithal eggs, 12.
Alimentary tube, 281.
Allantoic circulation, 552.
Allantois of Mammals, of Man, 228,

245,270,398.

— of Reptiles and Birds, 217-19.
Amnion of Mammals, 227.

- of Man, 244, 250.

- of Reptiles and Birds, 207, 219.
Amniota, 238.

Amniotic fluid of Man, 251, 271.

- folds. 207-9.

— sheath of the umbilical cord, 252.
Ampulla of semicircular canals, 495.
Anal membrane, 291.

- pit, 291.
Anamnia, 238.

Animal cells of the germ, 60.

- pole of the egg, 11.
Animalculists. 24.
Ankle-bones, 641.
Antrum of Highmore, 518.
Anus, fundament of, 290, 400.
Anvil — see Incus.

Aorta caudalis 576.

— double, 576.

— permanent, 565, 576.

— primitive, 295, 549.
Aortic arch, right-sided, 576.

- arches, 286, 571, 573.
Appendix vermiformis, 301.
Aqueductus Sylvii, 425, 431.

Arbor vitse, 427.

Archenteron, 85, 95, 170 — see also

Ccelenteron.
Archiblast, 189.
Archiblastic tissue, 189.
Arcuate fissure, 443 — see also Fissura

hippocampi.
Area embryonalis, 102.

— opaca, 99, 177.

- pellucida, 99, 178.

- vasculosa, 185.

— vitellina, 185.
Areola mammae. 531.
Arteria carotis, 572.

— centralis retina;, 475, 481.

- hyaloidea, 475.

— iliaca, 576.

— omphalomesenterica, 270, 549.

- perforans stapedia, 614.

- pulmonalis, 573.

— sacralis media, 576.

— spermatica, 386, 390.

— subclavia, 572.

- umbilicalis, 260, 270, 552, 576.

- vertebralis, 572.
Arterial system, 570.
Articular cartilage, 643.
Articulare, 625.

Articulation of jaw, primary, 624.

— secondary, 646, 626.
Atlas, 603.

Atresia pupillae congenita, 474.
Atrial partition, 558.
Atrioventricular valve, 555, 559, 561.
Atrium bursse omentalis, 300, 331.

— of heart, 554.
Auditory organ, 490.

- ossicles, 508, 619.

— pit, 491.

- ridge, 492.

- spot, 492.

- sac ^ , /Invertebrates, 492.

- vesicle / \Vertebrates, 491.
Auricle (external ear), 509.

— (of heart), 555.
Auricular canal Cof heart), 555.

660

INDEX.

13.

Basal plate of the placenta uterina,

262.

Basilar plate, 606.
Bell's law, 460.

Belly-stalk of human embryo, 245.
Between-brain, 425.

— vesicle, 422, 431.
Bile-duct, 329.
Blastoderm. 67.

Blastodermic vesicle, 224 — see Blastula.
Blastopore, 85, 96, 104, 282.
Blastosphere, 68.
Blastospheric ccelom, 204.
Blastula, 68, 100, 92, 90, 88, 224.
Blood, formation of, 170, 175.
Blood-circulation, single, 557.

— double, 557, 586.
Blood-corpuscles, embryonic, 183.
Blood-islands, 179, 183, 551.
Blood-points, 183.
Blood-vessel system, 542.
Blood-vessels, formation of, 186, 175.
Body, form of the, 194.

— of Amphioxus and Amphibia, 195.

- of Fishes, Reptiles, and Birds, 197.
Body of vertebra, 598.

Bone -nuclei — see Centres of ossifica-
tion.
Bony labyrinth, 502.

— tissue, 541.

Bowman's capsule of urinary tubules,

364.

Box-within-box theory, 23.
Brain, 421.
Brain-fissure, anterior. 431.

— posterior, 429.
Brain-plate, 457.
Brain-sand, 436.
Brain- vesicles, 421.

- first, 439.

— second, 431.

— third, 430.

— fourth, 429.

— fifth, 427.
Branchial arches, 286, 609.

— arteries, 286,571.

- clefts, 285.

— furrows, 286.

- leaflets, 287, 571.

- veins, 287, 571.
Branchiomeres, 351.
Branchiomerism, 633.
Bursa omentalis, 300, 303.

C.

Calcar avis, 441.
Canalis auricularis, 555.

Canalis hyaloideus, 475.

— incisivus, 517.

— neurentericus of Amphibia, 120.

— neurentericus of Amphioxus, 110.

— neurentericus of Birds, Reptiles.

etc., 126, 417.

— neurentericus of Mammals, 129,

282, 293.

— reuniens, 497.

— utriculo-saccularis, 497.
Cardiac endothelium, source of, 175,

544.

Cardinal veins, 577.
Carpal bones, 641.
Cartilaginous tissue, 540.
Caruncula lacrymalis, 487.
Cauda equina, 421.
Caudal fold, 200.

— gut, 292.

— sheath, 209.
Cavum tympani, 507.
Cella media, 443.
Cell-budding, 31.

Cell-patches (chorionic epithelium),

261.
Central canal of the spinal cord, 419.

— furrow of the cerebrum. 447.

— lobe of hemispheres, 442.
Centres of ossification, 643, 599.
Centrolecithal eggs, 12.
Centrosomes, 53.

Cephalic curvature, 284.

— elevation, 202.

— flexure, 423.

— process — see Head-process.

— see also Head.
Cerebellum, 430.

— vesicle of, 422.
Cerebral mantle, 426.

— vesicle, 422.

— vesicles — see Brain-vesicles.
Cervical cavity, 546, 566.

— fistula, 290.

— ribs, 602.

— sinus, 289.

— vertebras, 602.
Chalaza, 18.
Chief germ, 189.
Chorda dorsalis, 110, 593.

— fundament of, 110, 117.

— tympani, 508, 621.
Chordal canal, 132.

- groove of Amphibia, 119.

— groove of Amphioxus, 111.

— groove of Birds, Selachians, Mam-

mals, 130, 131.

— sheath, 594.

— sheath, skeletogenous, 595.
Choriocapillaris, 482.
Chorion, 9.

INDEX.

661

Chorion frondosum, 249, 259.

— Iseve, 249.

- of Mammals, 230.

- of Man, 248.
Choi-ionic epithelium, 261, 268.

— villi, 248; 260.

Choroid fissure (brain), 441, 443.

- (optic cup)3 483.
Choroidea, 483.

Chromatin of nucleus, 9, 52, 55.
Chromosomes, 42, 52.
Cicatricula, 15.
Ciliary body, 478, 483.

— processes, 479.
Circumcrescence-margin of germ-disc,

123, 139.
Claustrum, 442.
Clavicle, 639.
Cleavage, process of, 51.

- equal, 57.

- history of, 69.

- partial, discoidal, 57, 62.

- partial, superficial, 57, 66.
— scheme of, 57.

- unequal, 57, 58.
Cleavage-cavity, 67.
Cleavage-cells, secondary, 65.
Cleavage-nucleus, 40.

Cleft palate, 624.
Clitoris, 400.
Cloaca, 398.
Closing membrane, 286.

- plate, 286.

- plate of brain (lamina terminalis),

423, 440.

- plate of placenta, 263.
Coccyx, 600.

Cochlea, 494, 502.
Coecum, 301.
Coelenteric folds, 114.
Ccelenteron, 85, 107, 170.
Ccelom-theory, 153, 189.
Coloboma choroidete, 484.

— iridis, 484.
Conarium, 432.
Cone of attraction, 39.
Conjunctival sac, 486.
Connective substance, 170.

— tissue, fibrillar, 540.
Conus medullaris, 421.
Coracoid process, 638.
Corium, 521 — see also Derma.
Cornea, 476.

Cornu Ammonis, fold of, 443.
Cornua of lateral ventricles of brain,

443.

Corona radiata of the egg, 14.
Corpora quadrigemina, 430.
Corpus callosum, 446.

— luteum, 380.

Corpus papillare, 521.

— striatum, 441.
Corti's organ, 498, 505.
Cortical furrows of brain, 446.
Cotyledons of the embryonic mem-
branes of Ruminants, 234.

— of human placenta, 259, 262.
Covering bones, 616, 619.

— enumeration of, 619.
Cranium, 605.

— facial part of, 609.

Crescentic groove of germ-disc, 93, 96.

121.

Crista acustica, 492. 498.
Crown-rump measurement, 319.
Crura cerebri, 430.
Cryptorchism, 392.
Cuneus, 428.
Cutis-layer, 343.
Cutis-plate, 174, 343.
Cuvier's duct — see Ductus Cuvieri.

D.

Daughter-loops of nucleus, 53, 54.
Decidua, 235.

— of Man, 243, 252.

— reflexa, 243, 256.

- serotina, 243, 257.

- vera, 243, 253.
Decidual cells, 255.
Dental furrow, 309.

— groove, 309.

— papilla, 307.

- ridge. 308.

— sac, 310.
Dentale, 625.
Derma, 521.
Dermal navel, 205.

- skeleton, 616.

- stalk, 205.

— yolk-sac, 205.
Descemet's membrane, 477.
Descensus ovariorum. 393, 396.

— testiculorum, 387, 390.
Desmohasmoblast, 180.
Deutoplasm, 8.
Diaphragm, 567.
Diaphragmatic hernia, 569.

— ligament of the pronephros, 385.
Diaphysis (diaphysial nucleus), 642.
Differentiation, histological, 83, 150,

540.

Diphyodont, 309.
Direction bodies — see Polar cells.
Discus proligerus, 15, 380.
Diverticulum Nuckii, 397.
Division of labor, 83.
Dorsum sellae, 438, 606.

662

INDEX

Double organisms, 45.
Downy hair, 524.
Ductus Botalli, 575, 587.
-- cochlearis, bonyy 503.

— cochlearis, membranous, 494, 497.

— Cuvieri, 567.

— endolymphaticus, 493.

— lingualis, 320.

— thyroideus, 320.

- thyreoglossus, 318.

— venosus Arantii, 585.

— vitello-intestinalis, 205.
Dumb-bell figure of egg, 52.

Dural sheath of the optic nerve, 486.

E.

Ear, inner, 491.

— middle. 508.

— outer, 509.
Ear-capsule — see Auditory.
Ear-wax glands, 528.
Ectoblast, 86.
Ectoderm, 86.

Egg, 7.

— abortive, 37.

— alecithal, 12.

— animal pole of. 11.

— centrolecithal. 12, 66.

— compound, 18.

— heterolecithal, 28.

— holoblastic, 57.

— homolecithal, 28.

— meroblsstic, 57, 66, 197.

- of Amphibia, 14, 58.
— of Ascaris, 41, 55.

— of Birds, 15, 62.

— of Echinoderms, 7, 38, 51.

— of Mammals, 12.

— of Man, 13.

- telolecithai, 12.
Egg-balls— see Egg-nests.
Egg-cell— see Egg.
Egg-envelopes, t) — see also Vitelline

membrane and Foetal mem-
branes.

Egg-membranes — see Vitelline mem-
brane and Foetal membranes.

Egg-nests, 375, 376.

Egg-nucleus, 32.

Egg-sacs, 376.

Egg-tubes. 376.

Egg-yolk, 7.

Embryonic area, 198.

— spot, 102.
Enamel-germ, 309.
Enamel-membrane, 306, 310.
Enamel-organ, 310.
Enamel-pulp, 310.
Endocardium. 544.

Endochondral ossification, 599, bio.

Endolymph of the ear, 492.

Enterocoel, 108.

Entoblast, 86, 108, U9—see also Ento-
derm.

Entoderm, 86, 108, 149 — see also Ento-
blast.

Epicondyles, 644.

Epidermis, 520.

— primitive (HornUatt), 520, 450,

469.

Epididymis, 388.
Epigenesis, 24.
Epiphysis cerebri — see Pineal body.

— of bone (epiphysial nuclei), 642.
Epistropheus (Axis), 603.
Epithelio-muscular cells, 346.
Epitrichium, 520.
Eponychium, 527.

Epobphoron, 394.
Eruption of the teeth, 311.
Ethmoid bone, 619.

— region of the skull, 608.
Ethmoidal cells, 518.
Eustachian tube. 511.
Extremities, muscles of, 636.

— nerves of, 637.

— skeleton of, 635, 640.
Evolution, theory of, 23.
Eye, 467.

— chambers of, 477.
Eyelid. 486.
Eye-membranes, 476.
Eye-muscles, 352.

F.

Fallopian tube. 395.

Falx cerebri, 422, 439.

Fat glands, 528.

Femur, 644.

Fenestra ovalis of temporal bone, 613.

Fertilisation, history of, 45.

— process of, 37, 41.

— theory of, 44.

Fibrin, canalised, of the placenta, 261.

268.

Fibula, 644.
Filium terminale, 420.
Fimbria, 445.
Fissura calcarina, 441, 445.

— cerebri transversa, 445.

- choroidea (brain), 441, 443.

— choroidea (optic cup), 483.

— Glaseri, 621.

- hippocampi, 441, 443.

— parieto-occipitalis, 441.

— petrotympanica, 621, 626.
Foetal membranes, deciduous, 235, 243.

— of Mammals. 221.

INDEX.

663

Foetal membranes of Man, 241.

— of Reptiles and Birds, 206.
Folds, formation of, 77, 155.
Follicles of ovary, formation of, 376,

378.

Follicular cells, 12, 376.
Foramen incisivum, 622.

- ovale, 559, 588.
- Monroi, 440.

- Pannizzas, 564.

- parietale, 432.

— of Winslow, 331.
Fore-brain, 421.

— vesicle, 439.
Fore-gut, 203, 283.
Formative yolk, 11.
Fornix, 441.

Fossa rhomboidalis, 425, 428, 429.

- Sylvii, 441.
Fretum Halleri, 556, 564.
Frontal bone, 619.

— lobes, 442.

Fundament (= Anlage)—see Trans-
lator's Preface, v.

— of tooth, 304.

- of tooth of Man, 309.

— of tooth of Selachian, 305.

— of vertebra, 597.
Funiculus umbilicalis, 252, 268.

G.

Gall-bladder, 329.
Ganglion acusticum, 498.

— spirale, 502.
Gartner's canals, 394.
Gastrsea-theory, 84, 149.
Gastrula, 84, 149.

- of Amphibia, 87.

— of Amphioxus, 85.

— of the Chick, 93.

- of Mammals, 103.

— of meroblastic eggs, 90.

- of Reptiles, 97.

- of Selachians, 90.
Gelatin of Wharton, 270.
Gelatinous core of intervertebral disc,

597.

- tissue, 539.

- tissue of membranous ear-capsule,

500.
Genital cord, 387.

— eminence, 399.

- see also Sexual.
Germarium, 18.
Germ-cells, 374.
Germ-disc, 11.
Germinal epithelium, 374.
Germinative spot, 7, 9.

Germinative vesicle, 7.

— degeneration of, 30.
Germ-layer, inner, 86.

— inner, organs of, 281.

- middle, 106, 113.

— middle, of Chgetognatha. 108.

— middle, organs of, 341.

— outer, 86.

— outer, organs of, 416.

— theory, history of, 145.
Germ-layers, 84.

— division of the organs according

to, 188.

— history of, 145.

- of Amphibia, 88.

- of Amphioxus, 86.

- of Birds, 92.

- of Mammals, 99.

— of Selachians, 91.

- primary, 84.

Giant cells of the placenta, 263.
Gill — see Branchial.
Glandula pinealis, 432.

— prehyoidea, 320.

— suprahyoidea, 320.
Glandulae utriculares, 252.
Glandular area of milk-glands, 529.

— of Monotremes, 530.
Glomerulus of mesonephros, 357.

— of pronephros, 364, 370.
Graafian follicle of Mammals, 12, 379.

— vesicle of Mammals, 12, 379.
Great fissure of brain, 431 — see also

Interpallial fissure.
Growth, principle of unequal, 76.
Gubernaculum Hunteri, 386, 390.
Gyri, 427, 447.

H.

Hair, 522.

— bulb of, 523.
— downy, 524.
- germ of, 522.

— shedding of, 525.
Hair-follicle, 522.
Hair-papilla, 522.
Hammer (malleus), 612, 621.
Hare-lip, 624.
Head-cavities, 351.
Head-gut, 203, 283.
Head-fold, 200.
Head-musculature, 352.
Head-process of primitive streak, 124,

129.

Head-segments, 169, 351, 458.
Head-sheath. 208.
Head-skeleton, 603.
Heart, 542, 545, 553.

— auricles of, 555

664

INDEX.

Heart, contractions of, 661.
Hensen's node, 129.
Hepatic circulation, 583.

- cylinders, 327.
Hermaphroditism, 402.
Hernia, diaphragmatic, 569.
Highmorian antrum, 518.
Hind-brain, 421.

— vesicle, 422.
Hind-gut, cavity of, 203.
Hippocampal fold, 443-5.

- furrow — see Fissura hippocampi.
Holoblastic eggs, 57.
Homolecithal eggs, 28.
Howship's pits, 313.

Humerus, 641, 644.
Hydatid of oviduct, 395.

— of suprarenal, 390.
Hydramnion, 251.

Hyoid arches, 289, 609, 610.

— bone, 613, 619.
Hyomandibulare, 610.
Hypobranchial furrow of Tunicates,

317.
Hypophysial pocket, 437, 594, 607.

— sac, 437.
Hypophysis, 436.
Hypospadias, 403.

Idioplasm, 44.
Ilium, 639.
Incus, 612.

Infundibulum, 431, 425.
Inguinal canal, 392.

— ligament of pronephros, 386, 390,

396.

- ring, 392.

Insertio centralis, marginalis, vela-
mentosa of human umbilical
cord, 269.

Insula Keilii, 442.

Intermaxillary, 622.

Intermediate, 171 — see also Mesen-
chyme.

— cartilage of the joints, 645.

— cord (spinal ganglia), 451.
Intermuseular ligaments, 350.
Interpallial fissure of brain, 439.
Interparietale, 619.
Interplacentar spaces of placenta, 263,

268.
Intervillous spaces of placenta, 263,

268.
Intestinal entrance, 203.

- fold, 203.

— groove, 203.

— loop of human embryo, 297, 301.

— navel, 205.

Intestinal portal (anterior and pos-
terior), 203.

— stalk, 205.

— tube, 281.

— see also Alimentary.
Intumescentia cervicalis et lumbalis,

421.

— gangliformis Scarpa, 498.
Iridal fissure, 484.

Iris, 478, 482.
Ischium, 639.

J.

Jacobson's cartilage, 517.

— organ, 514.
Jaw-arch, 284, 609.
Jaw-muscles, 351.

Jelly-core of Echinoderm larvae, 170.

— of intervertebral disc, 597.
Joints, formation of, 644.
Jugular vein, 577.

K.

Kidney, 367.

Labia majora, 400.

— minora, 400.
Labial fissure, 623.
Labyrinth, membranous, 490.

— osseous, 502.
Labyrinth-region of skull, 608,
Lachrymal bone, 619.

— ducts, 471. 487.

— glands, 487.

— groove, 487.

— tubule, 489.
Lamina fusca, 483.

-- quadrigemina, 430.

— spiralis ossea, 503.

— terminalis, 440.
Lanugo, 524.
Larynx, 320.

Latebra of Hen's egg. 16.
Lateral folds of trunk, 200.

- plates, 165.

— process of vertebra, 602.

— ventricle, 425, 440.
Lens, growth of, 473.

— star of, 473.
Lens- vesicle, 468, 471.
Ligamentum Arantii, 585.

- Botalli, 587.

— coronarium hepatis. 570.

— hepato-duodenale, 330.

— hepato-gastricum, 330.

- hepato-umbilicale, 586.

— intermusculare, 350, 595.

INDEX.

661

Ligamentum intervertebrale, 596.

— laterale internum maxillae inf.,

626.

- ovarii, 396.

— phrenico-lienale, 303,

— stylo-hyoideum, 613.

- suspensorium, 330.

— teres hepatis, 330.

- teres uteri, 386, 396.

- vesico-umbilicale laterale, 577.

— vesico-umbilicale medium, 399.
Limbs, 635 — see also Extremities.
Limbus Vieussenii, 565.

Liquor amnii, 212, 250.

— folliculi, 380.
Liver, 324.

Liver-circulation, 583.
Liver-ridge, 326.

Lobes of the cerebrum, 442.

- olfactory, 448, 511.
Lobus olfactorius, 448, 511.
Longitudinal fissure of brain, HO— see

also Interpallial fissure.
Lumbar vertebra, 602.
Lungs, 320.

— alveoli of, 323.

— fundaments of, 321.
Lung-sac, 322.
Lung- vesicle, primitive, 322.

M.

Macula acustica, 492, 498.

— germinativa, 7, 9.

Male pronucleus, 40 —see also Sperm-
nucleus.

Malformations by arrested develop-
ment, 392, 403, 484, 560, 569,
575, 601, 623.

Mamma, 531.

Mammalia achoria, 230.

- choriata, 230.

- deciduata, 236.

- indeciduata, 236.

Mandible (Maxilla inf.), 609, 619, 622.
Mandibular arch, 284, 609.

— articulation, 645.

- process, 284, 610.
Mandibulare, 624, 609.
Marginal arch, 443, 446.

- germ, 180.

— groove, 199.

- ridge, 95.

— sinus of the placenta, 264.
Maturation, phenomena of, in the

egg, 30.
Maxilla inferior— see Mandible.

— superior, 619.
Maxillary fissure, 623.

Maxillary process, 488, 284, 610.
Meckel's cartilage, 612, 621, 622, 624.
Meconium, 331, 521, 524.
Mediastinum. 569.
Medulla oblongata, 425.
Medullary cords of ovary, 381, 394.

— folds of Amphibia, 79.

— folds of Amphioxus, 110.

— folds of the Chick, 125.

— furrow, 110, 125.

— groove, 110, 125.

- plate, 109, 416.

— ridges — sec. Medullary folds.
Meibomian glands. 487.
Membrana adamantinae, 310.

- capsularis, 474.

— capsulo-pupillaris, 474.

- chorii, 260.

- eboris, 306.

— granulosa, 380.

- hyaloidea, 475.

- limitans, 480.

— nictitans, 487.

- pupillaris, 474.

— reuniens inferior, 554.

— reuniens superior, 172.

— tympani, 509.

— vasculosa lentis, 474.

- vitellina, 7, 9.
Merocytes, 64, 178.
Mesenchymatic germ, 154.
Mesenchyme, 154, 171.

— of Birds, 174.

- of Selachians, 172.

— theory, 170, 175, 189
Mesenteries, 295.
Mesenterium, 108, 295.

— commune, 300.

— ventrale, 324.
Mesoblast, 106, 108, 118.
Mesoblastic somites, 162 -see also

Primitive segments.
Mesocardium, 324, 543.

— anterius, 543.

- posterius, 543.
Mesocolon, 302.
Mesoderm, 106, 108, 118.
Mesogastrium, 296.

— anterius, 326.
Mesonephric blastema, 362.

— canals, 363.

— cords, 363.

— duct, 353, 358, 360, 394

— tubules, 365.
Mesonephros, 359.
Mesorchium, 386.
Mesovarium, 386.
Metanephros, 367.
Micropyle, 41.
Mid-brain, 421.

666

INDEX.

Mid-brain vesicle, 430.
Middle ear, 508.

— plate, 356.

Middle germ-layer, 106, 113.

— of Amphibia, 117.

— of Amphioxus, 110.

— of Birds, 120.

— of Chastognatha, 108.

— of Mammals, 110, 129.

— organs of, 341.
Milk-glands, 528.
Milk-teeth, dentition, 309, 312.
Modiolus, 502.

Morgagni's hydatid, 395.

Morula, 56, 68.

Mouth, development of the permanent,

283.

Mulberry-sphere, 56, 68.
Miillerian duct, 369, 386, 395.
Multiple organisms, 45.
Muscle-layers of Amphioxus and Cy-

clostomes, 343.
Muscle-plate, 174, 348.
Musculature of the extremities, 350.

— of the head, 352.

— voluntary, 342, 346.
Musculus cremaster, 392.

— obliquus abdom. int., 392.
Muskelkastchen, 344, 347.
Myocoele, 349.

Myomeres, 343, 350, 598.
Myomerism, 632.
Myotome, 362.

N.

Nail-plate, £27.
Nails, 526.
Nasal area, 511.

- bone, 619.

— furrow, 513.

— orifice, inner, 514.

— orifice, outer, 514.

— processes, 488, 513.
Naso-palatal (Stenson's) duct, 517.
Naso-pharyngeal passage, 517.
Neck-measurement, 283.
Nephridial funnel, 356, 364.
Nephrostome, 364.
Nephrotome, 362.

Nerves, 452.

Nervous system, 416, 449.

Nervus acusticus, 506.

- cochleae, 602.

— hypoglossus, 457.

- laryngeus inf. (recurrens), 575.

- lateralis vagi, 456.

- phrenicus, 569.

- vagus, 299.

- vestibuli, 502.

Neural crest, 450.

— plate, 416.

— ridge, 450.

— tube, 110, 417.
Nictitating membrane, 487.
Nipple, 530.

Nose, 518.

Notochord— gee Chorda dorsalis.

Nuchal flexure, 423.

— protuberance, 424.
Nuclear liquid, 8.

— loops, fission of, 53, 55.

— network, 9.

— plate, 53.

— spindle, 52.
Nuclein, 9, 26, 52.
Nucleoli, 9.
Nucleus caudatus, 442.

— lentiformis, 442.
Nutritive yolk— see Yolk,

... • 0.

Occipital bone, 617.

— lobes, 443.

— region. 608.
Odontoblasts, 306.
(Esophagus, 297, 299, 320.
Olfactory buds, 513.

— labyrinth, 518.

- lobes, 448, 511.

— nerve, 448, 611.

— organ, 511.

— pit, 511.

Omentum, greater, 299, 303,

— lesser, 300, 330.
Ooscope, 212.
Optic cup, 469, 476.

— nerve, 484.

— vesicle, 423, 467.

— vesicle, stalk of, 468.
Orbital region, 608.

Os acetabuli, 640.

— angulare, 622, 625.

— articulare, 625.

- coccygis, 600.

— • coracoideum, 638.

— dentale, 625.

— entoglossum, 610.

— ethmoidale, 621.

- frontale, 621.

- hyoides, 613, 622.

- intermaxillare, 622.

— interparietale, 619.
- ischii, 639.

- lacrymale, 621.

— lentiforme, 614.

— maxillare, 516.

- parietale, 621.

INDEX.

667

Os pet ro sum, 621.

— premaxillare, 622.

- pterygoideum, 619,

- pubis, 639.

— • squamosum, 621.

— temporale, 620.

— tympanicum. 621.
Osseous tissue, 541.
Ossification, endochondral, 616.

— perichondral, 616.

— of vertebrae, 599.
Osteoclasts, 313.

Ostium abdominale tubse, 369.

Otolith, 492.

Outer germ-layer — see Germ-layer.

Ovarium — see Ovary.

Ovary, 374.

Oviduct of the Hen, 17.

— of Man, 395.
Ovists, 24.
Ovum— see Egg.

r.

Palatal fissure, 515, 623.

— plate, 515, 611.

- velum, primitive. 233, 437.
Palate, 515, 611, 622.
Palato-quadratum, 609, 624.
Pancreas, 324, 332.

Pander's nucleus, 16.

Papilla of milk-glands, 530, 531.

Papillary bodies of skin, 521.

— muscles, 563.
Parablast, 180, 189.
Parablast-nuclei, 64.
Parablast-theory, 189.
Parachordal cartilages, 606.
Paradidymis, 388.
Paranuclein, 26.
Parietal cavity, 566.

- elevation, 284, 424, 431.

- eye, 435.

- lamella, 174.

- lobes, 443.

- prominence, 284, 424, 431.

— zone of blastoderm, 167.
Parobphoron, 394.
Parovarium, 394.

Pars coracoidea, 638.

— membranacea of heart, 564.
Parthenogenetic eggs, 34, 36.
Patella, 644.

Pecten of Bird's eye, 483.

Pectoral girdle, 638.

Pedunculus cerebelli adpontem, 429.

— cerebri, 550.

— flocculi, 429.
Pelvic girdle, 638.
Penis, 402.

Pericardial cavity, 566.
Pericardium, 543, 566.
Perichondral ossification, 616.
Perilymphatic spaces, 501.
Perineum, 400.

Perivisceral cavity — see Body-cavity.
Pes hippocampi, 441.
Pfliiger's egg-tubes, 376.
Pharyngeal membrane, 594, 283.
Pia mater, 429.

Pial sheath of optic nerve, 486.
Pineal body, 432.

— gland, 432.

— organ, 432.

— process, 432.
Pituitary body, 436.
Placenta discoidea, 236.

— fcetalis, 234, 259.

— of Mammals, 232.

— of Man, 258.

- praevia, 259.

- uterina, 233, 258.

— zonaria, 236.

Placental circulation, 263-8, 553.
Plane of division (egg), 56.
Pleuro-pericardial cavity, 566.

— fold, 568.

Plexus choroideus ant., 431.

— lateralis, 444.

- post., 429.

Plica semilunaris, 487.
Polar cells, 32.

— corpuscles— see Polar cells and

Centrosomes.
-*• differentiation of egg, 11, 35.

— spindle, 43.

Pole of egg, animal, 11.

— vegetative, 11.
Polyphyodont, 309.
Polyspermia, 44.
Pons Varolii, 429.
Pontal flexure, 423.
Portal circulation, 583.

— vein, 584, 586.
Post-anal gut, 290, 292.
Posterior nares, 611.
Preformation-theory, 23.
Prehepaticus ( Vorleber), 326. 330, 567.
Primitive ova, 374.

— groove, 121,133, 135, 282— seealsa

Blastopore.

- mouth— see Blastopore and Primi-

tive groove.

— organs, 86, 187.

— segment plates, 165.

— segments, 112, 161.

— segments of Amphibia, Birds,

Mammals, Reptiles, 112, 165.

— segments of Amphioxus, 112, 161

— segments of the head, 351.

668

INDEX.

Primitive segments of the trunk, 342.

— spermatic cells, 374, 382.

— streak, 121, 133, 135, 282— «?* also

Blastopore.
Primordial bones, 615.

- bones, enumeration of, 619.

— cranium, 605.

— cranium, cartilaginous, 595, 607.

— cranium, chord al, 607.

— cranium, evertebral, 607.

— cranium, membranous, 595, 605.

— cranium, prechordal, 607.

— cranium, vertebral, 607.
Principles of development, 76.
Proamnion, 230.

Processus ciliares, 479.

— pinealis, 432.

— styloideus of petrosal, 613.

- styloideus of radius and ulna, 644.

— vaginalis peritonei, 391, 396.
Prochorion, 224.

Pronephric duct, 358, 359.
Pronephron, 353.
Pronucleus, 32.

— female, 32 — see also Egg -nucleus.

- male, 40 — see also Sperm-nucleus.
Prostata, 402.

Prostate gland, 402.
Protoplasmic radiation, 40, 51.
Proto vertebrae, 162, 598 — see also Pri-
mitive segments.

Pterygoid process of sphenoid, 619.
Pubic bone, 639.
Pulmonary alveoli, 323.

— artery, 564.
Pupil, 478.

K.

Radiations of protoplasm, 40, 51,

Radius, 64.

Rathke's pocket, 285, 437.

— pouch, 285, 437.

— trabeculae cranii, 606.
Rauber's layer, 102.
Receptive elevation, 39.
Recessus labyrinthi, 493.
Regio olfactoria, 515.

— respiratoria, 515.
Reichert's cartilage. 613.
Re-segmentation of vertebral column,

598.

Reserve material, 21.
Rete testis, 384.
Retina, 480.
Ribs, 6CO.
Ring-lobe, 442.
Roots of attachment of the chorion,

260.
Round ligament, ?86.

Rusconian anus, 88.

— digestive cavity, 88,

S.

Sacculus, 496.
Sacral ribs, 602.
Sacrum, 602.
Salivary glands, 305.
Scala tympani, 506.

— vestibuli, 506.
Scapula, 638.
Schizocoel, 108.
Sclerotica, 471.
Sclerotome, 172, 348, 362.
Scrotum, 392, 402.
Sebaceous glands, 528.
Seessel's pocket, 594.
Segmental theory of skull, 631.
Segmentation — see Cleavage.
Sella turcica, 438. 607.
Semicircular canals, bony, 503.

— membranous, 494.
Semilunar valves, 564.
Seminal ampullae, 383.

— mother-cells, 383.

— tubules, 384.

— see also Spermatic.
Septa placentas, 262.
Septum atriorum, 558.

— trans versum, 567, 577.

— ventriculorum, 560.

Sexual cords of the mesonephros. 381-
383, 404.

— eminence, 399.

— folds, 400.

— glands — see Sexual organs.

— groove, 400.

— organs, 374.

- organs, external, 397.

- part of mesonephros, 387, 394.

— ridge, 399.

Sheath of the root of hair, 525.
Shell of Hen's egg, 17.
Shell-membrane, 17.
Shoulder-blade, 638.
Shoulder-girdle, G38.
Sinus cervicalis (precervicalis), 289.

— coronarius., 565, 581.

— ethmoid ales, 518.

— frontales, 518.

— genitalis, 396.

— occipitales, 518.

- prostaticus, 389.

— reuniens, 558.

— sphenoidales, 518.

v- superior of vertical semicircular
canals, 496.

— terminalis, 184,549.

— urogenitalis, 398.

INDEX.

Skeletogenous tissue, 172, 348.
Skeleton, 593.

— axial, 172, 593.
Skin, 520.

Skull, 603.

— facial part of, 604.
Smegma embryonum, 520.
Sole-horn, 527.
Somatopleure, 200, 356.
Somites, 162.

Spermatic bodies of Nematodes, 42.

- cells, 19, 382.

- filaments, 19.

- mother-cells, 383.

— see also Seminal.
Spermatid, 20.
Spermatozoa, 19.
Sperm-nucleus, 40.
Sphenoid, 617, 620.
Spinal cord, 418.

— ganglia, 449.
Spindle-fibres. 52.

Spiracle of. Selachians, 506, 609.

Stalk of the brain, 430.

Stapes, 613.

Stem-part of hemispheres, 442.

Stem-zone of blastoderm, 167.

Stensou's duct, 517.

Sternal bars, 600.

Sternum, 600.

Stomach, 295.

- torsion of, 298.

Styloid process of petrosal, 613.

— of ulna and radius, 644.
Substantia perforata post., 430.
Substanzinseln, 181.

Sulcus centralis, 447.

— interventricularis, 555, 560.

- tubo-tympanicus, 508.
Superfetation, 44.

Supplementary cleavage, segmenta-
tion, 65, 99, 139.

— hair, 525.
- teeth, 308.

— teeth of Man, 312.
SiiDra-pericardial bodies of Shark, 288,

318.

Suprarenal bodies, 403.
Sustentative substance, 170 — see also

Translator's Preface.

— tissue — see Connective tissue.
Sutura incisiva, 622.
Sweat-glands, 528.
Sympathetic, 462.

T.

Taenia sinus rhomboidalis, 429.
Tseniae thalami optici, 432.
Tail-fold, 200.

Tarsus — see Ankle-bones.

Teat, 530.

Teeth, reserve, 308, 312.

— shedding of (Mammals), 309.

— shedding of (Man), 313.

— shedding of (Shark), 309.

— supplementary, 308, 312.
Tela choroidea. anterior, 431.

- fold of, 443.

— furrow of, 443.

— inferior, 429.

- lateral, 444.

- posterior, 429.

— superior, 431.
Telolecithal eggs, 12.

— yolk, 12.
Temporal bone, 619, 620.

— lobes, 443.
Tensor tympani, 508.
Testa, 18.

Testis, 382.

- envelopes of, 392.
Thalamus opticus, 426.
Theca folliculi, 377.
Theory of transmission, 44.
Thoracic cavity, 567.
Throat-clefts— see Visceral clefts.
Thymus, 314.

Thyroid gland, 317.
Tibia, 644.

Tongue, fundament of, 304.
Total furrows of brain, 441, 446.
Trabeculse cranii, 606.
Trachea, 320.
Transmission-theory, 44.
Truncus arteriosus, 549, 564.
Trunk-segments, 168, 458.
Tuba Eustachii. 506.

- Fallopise, 395.
Tubuli recti of testis, 384.

— seminiferi, 384.
Tunica propria testis, 392.

— vaginalis communis, 392.
Turbinals, 515, 619.
Tympanic cavity, 506, 508, 610.

— mala, 503.

U.

Ulna, 644.

Umbilical cord, 252, 268.

- vein, 270, 552, 578.

— vesicle of Man, 251.

— vessels, 218, 260, 270, 552, 576.
Urachus, 217, 399.

Ureter, 367.
Urethra, 402.
Urinary bladder, 399.

— organs, 353.
Urogenital system, 353.

€70

INDEX.

Uterine glands, 235, 252, 253, 271.
Uterus, 395.

— masculinus, 389, 402.
Utriculus of labyrinth, 494, 496.
Uvea of iris, 483.

V.

Vagina, 395..

Valvula Eustachii, 565.

— foraminis ovalis, 565, 587.

— Thebesii, 565.
Vas deferens, 388.
Vascular endothelium, 175.

— glomerulus of the pronephros, 357.

— glomerulus of the mesonephros,

364.
Vegetative cells, 60.

— pole of egg, 11.
Velum medullare ant,, 430.

— inf., sen., post, 429.
Vena azygos, 583.

— cardinalis, 581, 582.

— cava inf., 578, 582, 583.

- cava sup., 580, 583.

— coronaria, 581.

- hemiazygos, 583.

- hepatica, 584.

— jugularis, 580.

— omphalomesenterica, 251, 270, 550,

577.

— umbilicalis, 270, 552, 578.

— vertebralis, 602, 572.

— vitellina, 549.
Venous system, 577.
Ventricle of brain, 425, 431.

— of heart, 554.
Ventricular septum, 560.
Ventriculus septi pellucidi, 446.

— (of heart), 554.
Vermiform process (brain), 430.

— appendage (coecum), 301.
Vernix caseosa, 520.
Vertebral body, 597.

— column, cartilaginous, 596.

— column, membranous, 595.

— fundament, 596.

- theory of skull, 627, 632.

- theory of skull (Gegenbaur), 630.

— theory of skull ( Goethe- Oken),

628.

Vesicula blastodermica, 224 — see also
Blastula.

Vesicula germinativa, 7.

— umbilicalis, 251.
Vestibulum of the ear, 505.

— vaginae, 400.

Villi of the chorion, 248, 259.
Villous epithelium, 261, 268.

— membrane, 230.
Visceral arches, 286, 609.

— arches, cavities of, 351, 566.

— arches, vessels of, 571.

- clefts, 285.

— furrows, 285.

— grooves, 285.

— lamella of inesoderm, 174.

— skeleton, 609, 620.
Vitelline arteries, 270.

— area, 185.

— circulation, 549, 551.'

— duct, 205, 230, 251, 270.

— membrane, 7, 9, 40.

— nuclei, 64, 178.
- plug, 117-

- sac, 197, 218.

— sac of Man, 251.

— veins, 550, 577.

— wall, 99, 178.

Vitellus (Vitelline plates), 8, 11-17,

221, 195— see also Yolk
Vitellus, 7.

— formativus, 11.

— nutritivus, 11.
Vomer, 617.

W.

Wharton's gelatin, 270.
White yolk, 15.
Winslow's foramen, 331.
Witches' milk, 531.
Wolffian body, 359.

— duct, 358, 359.
Wrist-bones, 641.

Y.

Yellow yolk, 16.

Yolk— see Vitelline and Vitellus.

Zona pellucida, 12.
Zonula Zinnii, 480.
Zygoma, 619.

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