Book - Embryology of the Pig: Difference between revisions

From Embryology
mNo edit summary
 
(12 intermediate revisions by the same user not shown)
Line 1: Line 1:
{{Header}}
{{Header}}
{{Ref-Patten1951}}
{{Ref-Patten1951}}<br>
 
{{Patten1951 TOC}}
{{Patten1951 TOC}}
{| class="wikitable mw-collapsible mw-collapsed"
{| class="wikitable mw-collapsible mw-collapsed"
Line 20: Line 19:
{{Historic Disclaimer}}
{{Historic Disclaimer}}
=Embryology of the Pig=
=Embryology of the Pig=
Frontispiece  
[[File:Bradley M. Patten.jpg|thumb|alt=Bradley M. Patten|link=Embryology History - Bradley Patten|Bradley Patten ( -1971)]]
Frontispiece


Reconstruction (X 17.5) showing the organ systems of a 9.4 mm. pig embryo. For explanation see figures 60 and 66.  
Reconstruction (X 17.5) showing the organ systems of a 9.4 mm. pig embryo. For explanation see figures 60 and 66.


By BRADLEY M. PATTEN
By Bradley M. Patten


Professor of Anatomy in the University of Michigan Medical School  
Professor of Anatomy in the University of Michigan Medical School




THIRD EDITION
Third Edition




WITH COLORED FRONTISPIECE
With Colored Frontispiece


AND 186 ILLUSTRATIONS IN THE TEXT (CONTAINING 412 FIGURES)  
And 186 Illustrations In The Text (Containing 412 Figures) Of Which 6 Are In Color
OF WHICH 6 ARE IN COLOR




Philadelphia : THE BLAKISTON COMPANY : Toronto


Philadelphia : THE BLAKISTON COMPANY : Toronto


Third Edition




Third Edition
Copyright, October 1948, by The Blakiston Company




Copyright, October 1948, by The Blakiston Company
By P. Blakiston's Son & Co.




BY P. Blakiston ’s Son & Co.  
Copyright, 1951, by P Blakiston's Son & Co , Inc.




Copyright, 1951, by P Blakiston’s Son & Co , Inc.
{{Patten1951 TOC}}


==Preface to Third Edition==


Preface to Third Edition
In making the revision for a new edition of this book it did not seem desirable essentially to change its form or scope. Effort has been concentrated on improving the presentation of the original subject matter and bringing it up to date, rather than on its expansion. The entire book has been reset to a greater page width which has permitted enlarging certain of the illustrations that, in earlier editions, had proved to be too greatly reduced. With the generous cooperation of the publishers several of the important plates on the cardiovascular system have been remade to a larger scale and with color. A number of new illustrations have been drawn for sections where experience has shown that students needed additional graphic assistance in interpreting their laboratory material. It is hoped that these changes will all contribute toward making the book as a whole more serviceable.




In making the revision for a new edition of this book it did not
Bradley M. Patten
seem desirable essentially to change its form or scope. Effort has been
concentrated on improving the presentation of the original subject
matter and bringing it up to date, rather than on its expansion. The
entire book has been reset to a greater page width which has permitted enlarging certain of the illustrations that, in earlier editions,
had proved to be too greatly reduced. With the generous cooperation
of the publishers several of the important plates on the cardiovascular
system have been remade to a larger scale and with color. A number
of new illustrations have been drawn for sections where experience
has shown that students needed additional graphic assistance in
interpreting their laboratory material. It is hoped that these changes
will all contribute toward making the book as a whole more serviceable.  


Bradley M. Patten
August 1048


August 1048


==Preface to First Edition==


Preface to First Edition
This book represents an endeavor to set forth in brief and simple form the fundamental facts of mammalian development. The thread of the story and the illustrations have been based on pig embryos because of their value and availability as laboratory material. But special stress has been laid on the embryological phenomena involved instead of on the details of specific conditions existing in the pig. Throughout the book, every efTort has been made to present developmental processes as dynamic events with emphasis on their sequence and significance, rather than as a series of still pictures of selected stages.




This book represents an endeavor to set forth in brief and simple
Obviously no book can deal fully with all phases of development, even in a single form, and still remain serviceable as a text. As this book is for the student, it has seemed expedient, for the sake of clearness and simplicity, to omit many things which I should like to have included. My primary aim has been to write an account in which the essentials stand out adequately interpreted and unobscured by a multiplicity of details — to lay a foundation which can be further built upon in accordance with special needs or individual desires.
form the fundamental facts of mammalian development. The thread
of the story and the illustrations have been based on pig embryos
because of their value and availability as laboratory material. But
special stress has been laid on the embryological phenomena involved
instead of on the details of specific conditions existing in the pig.
Throughout the book, every efTort has been made to present developmental processes as dynamic events with emphasis on their sequence
and significance, rather than as a series of still pictures of selected
stages.  


Obviously no book can deal fully with all phases of development,
even in a single form, and still remain serviceable as a text. As this
book is for the student, it has seemed expedient, for the sake of clearness and simplicity, to omit many things which I should like to have
included. My primary aim has been to write an account in which the
essentials stand out adequately interpreted and unobscured by a
multiplicity of details — to lay a foundation which can be further
built upon in accordance with special needs or individual desires.


Bradley M. Patten  
Bradley M. Patten
 
January 1927


January 1927


==Acknowledgment==
==Acknowledgment==
The pleasantest thing about working on this book has been the generous aid I have received from many sources. Throughout the preparation of the initial edition the encouragement, criticism, and suggestions of my colleagues, Dr. F. C. Waite and Dr. S. W. Chase, were of the greatest help. In the preparation of material and in making the illustrations for the first edition the beautifully accurate work of Miss Kathryn Toulmin was of inestimable value. In making the new drawings added in the third edition I was fortunate in securing the unusually able assistance of Mrs. Dorothy Van Eck.




The pleasantest thing about working on this book has been the
Dr. G. L. Streeter and Dr. C. H. Heuser of the Carnegie Institute allowed me free use of their extensive collection of young embryos and generously gave me many photographs made from their material. To Mrs. Charles S, Minot I am indebted for permission to use several figures from the late Professor Minot's works. The accrediting in the figure legends of these and other borrowed illustrations by no means covers my obligation to other writers. Practically the entire bibliography is a statement of indebtedness for information and ideas.
generous aid I have received from many sources. Throughout the
preparation of the initial edition the encouragement, criticism, and
suggestions of my colleagues, Dr. F. C. Waite and Dr. S. W. Chase,
were of the greatest help. In the preparation of material and in making
the illustrations for the first edition the beautifully accurate work of  
Miss Kathryn Toulmin was of inestimable value. In making the new
drawings added in the third edition I was fortunate in securing the
unusually able assistance of Mrs. Dorothy Van Eck.  


Dr. G. L. Streeter and Dr. C. H. Heuser of the Carnegie Institute
allowed me free use of their extensive collection of young embryos
and generously gave me many photographs made from their material.
To Mrs. Charles S, Minot I am indebted for permission to use several
figures from the late Professor Minot’s works. The accrediting in the
figure legends of these and other borrowed illustrations by no means
covers my obligation to other writers. Practically the entire bibliography is a statement of indebtedness for information and ideas.


I wish I might acknowledge individually the helpful services  
I wish I might acknowledge individually the helpful services rendered by many of my students, but they are too numerous. Several reconstructions which I have used directly or indirectly have been largely their work. Of even greater assistance have been their suggestions during the shaping of the work — suggestions of especial value because they were made from a point of view difficult for an instructor to appreciate without such aid.
rendered by many of my students, but they are too numerous. Several  
reconstructions which I have used directly or indirectly have been  
largely their work. Of even greater assistance have been their suggestions during the shaping of the work — suggestions of especial value  
because they were made from a point of view difficult for an instructor  
to appreciate without such aid.  


To The Blakiston Company, I am indebted for much helpful
cooperation and especially for their liberality with regard to the
number and quality of the illustrations.


No person other than my wife could have deciphered and put
To The Blakiston Company, I am indebted for much helpful cooperation and especially for their liberality with regard to the number and quality of the illustrations.
into usable form manuscript of the character I frequently turned over
to her for revision and typing. Without her generous help the preparation of the text would have been much more arduous and long
delayed.  


Bradley M. Patten


No person other than my wife could have deciphered and put into usable form manuscript of the character I frequently turned over to her for revision and typing. Without her generous help the preparation of the text would have been much more arduous and long delayed.




==Chapter  7==
Bradley M. Patten




Tke Structure of Emkryos from Nine to
Twelve Millimeters in Lengtk


{{Footer}}


Pig embryos of about 10 mm. crown-rump length are especially
{{Patten1951 TOC}}
valuable as material for laboratory study. They are neither so small
and delicate that procuring and preparing them involves unusually
skillful manipulation, nor so large that complete series of sections are
tedious to make and difficult to study. Developmentally they are not
so far advanced that their structure is hard to comprehend if the
student is familiar with the early stages of development in any of the
vertebrates. Yet if their morphology is thoroughly mastered it forms a
starting point from which the later developmental processes in
mammals may readily be traced. It seems advantageous, therefore, to
deal with this, the most commonly utilized stage of development,
somewhat less in narrative fashion than has been done heretofore. We
shall, as it were, pause for a while and look over carefully the conditions which thus far have been established so that we may follow the
story of the later phases of development more understandingly.
 
I. External Features
 
Flexion. ^ Like all forms which develop in the limited confines
of an egg shell or within the uterine cavity, the body of a young pig
embryo is curled up on itself. This flexion of the spinal axis is more
marked in some regions than others. The points of conspicuous bending have received special designations from the region in which
they appear. In a pig of 10 mm. (Fig. 58) the cranial flexure, cervical
flexure, dorsal flexure, and lumbosacral flexure are all well developed.
 
The Head. In the cephalic region the thin skin leaves the contours
of the brain clearly suggested (cf. Figs. 58 and 59). The nasal pits
have appeared as definitely circumscribed depressions at the rostral
end of the head and the bulging caused by the growing optic cups
clearly marks the position of the eyes. Especially in fresh specimens
the retinal pigment can be seen through the overlying skin.
 
107
 
 
 
 
108 STRUCTURE OF NINE- TO TWELVE-MILLIMETER EMBRYOS
 
 
Mesencephalon
 
 
Maxillary process'
Nasal pit
Cardiac prominence
Hepatic prominence
Belly-stalk
 
 
Posterior,
appendage bud
 
 
Metencephalon
 
Mandibular arch
 
^Hyomandibular cleft
 
Hyoid arch
 
 
 
Cervical sinus
 
 
Anterior
appendage bud
 
 
Mesonephric
 
prominence
 
 
Somite
 
 
Fig. 58. Drawing (X 7) showing external appearance of 10 min. pig embryo.
 
(Modified from Minot.)
 
 
The Gill Arches. Flanking the oral cavity and caudal to it, in the
region which will be under the chin, the gill (branchial) arches appear
as strongly marked local elevations. This entire region is at this stage
so compressed against the thorax that one gets a very incomplete view
of its structure unless an embryo is decapitated and the head viewed
in ventral aspect (Figs. 168 and 169). It is then seen that the maxillary
processes form the lateral parts of the upper jaw, and that the two
mandibular elevations meet each other in the mid-ventral line to form
the arch (mandibular arch) of the lower jaw. Posterior to the mandibular are three similar arches, the hyoid and and the unnamed
third and fourth post-oral arches. Later in development the arches
posterior to the mandible become less conspicuous and are incorporated into the neck.
 
The Gill Clefts. Between the branchial arches are deep furrows
which mark the position of ancestral gill clefts. Although in mammalian embryos these furrows do not ordinarily break through into
the pharynx they are commonly called clefts because of their phylogenetic significance. Only the most cephalic of these clefts is named
(hyomandibular cleft, Fig. 58); the others are designated by their
 
 
 
EXTERNAL FEATURES
 
 
109
 
 
post-oral numbers. The entire region about the third and fourth postoral clefts becomes especially deeply depressed and is known as the
cervical sinus.
 
The Appendage Buds. Both anterior and posterior appendage
buds in 10 mm, pigs are still paddle-shaped (Fig. 58). Not until
embryos have grown to a length of between 15 and 20 mm. do the five
digits show as terminal enlargements (Figs. 33 and 34). It is significant
that the ancestral five-digit type of appendage appears transitorily
in the pig embryo, before its characteristic highly specialized hoof is
even suggested.
 
The Trunk. At this stage the superficial bulges due to the somites
are evident all the way from the cervical to the caudal region of the
 
 
 
 
 
 
110 STRUCTURE OF NINE- TO TWELVE-MILLIMETER EMBRYOS
 
body. Well-marked prominences in the lateral and ventral portions
of the body-wall indicate the position of the heart, t^e liver, and the
mesonephros (cf. Figs. 58 and 59).
 
The band of tissue (“milk ridge”) which gives rise to the mammary
glands is not ordinarily developed in embryos of the 9 to 12 mm.
range. It usually becomes clearly marked by 15 mm. (Fig. 33), and
by 20 mm. the nipples can generallv be recognized (Fig. 34).
 
II. The Nervous System
 
The Brain. In younger embryos the brain consisted of three
regions, fore-brain (prosencephalon), mid-brain (mesencephalon),
and hind-brain (rhombencephalon) (Fig. 36, E). Now we find five
regional divisions or vesicles, as they are called. The prosencephalon
has divided to form the telencephalon and diencephalon; the mesencephalon has remained undivided; and the rhombencephalon has
become differentiated into metencephalon and myelencephalon (Figs. 59,
60, 65, and 88).
 
The telencephalon consists of the most anterior median part of the
brain and two lateral outgrowths from it called the lateral telencephalic
vesicles (Figs. 60, 67, and 69). Its posterior boundary is conventionally
established by drawing a line from a fold in the roof of the brain called
the velum transversum (see Fig. 65 where the leader to Seessel’s
pocket crosses the dorsal wall of the neural tube) to the recessus
opticus, a depression in the floor of the brain at the level of the optic
stalks (Figs, 65 and 88).
 
The diencephalon is the hinder portion of the old prosencephalon.
Its caudal boundary is conventionally established by drawing a line
from an elevation in the floor of the neural tube called the tuberculum
posterius (Fig. 88) to a depression in the roof of the neural tube which
is just appearing at this stage of development, and may (Fig. 60) or
may not (Fig. 65) be evident in the particular embryo under observation. The most conspicuous special features of the diencephalon are
the paired lateral outgrowths from it which form the optic vesicles
(Figs. 60 and 63) and the median ventral diverticulum which constitutes the infundibulum (Fig. 65). The median dorsal outgrowth of
the diencephalon known as the epiphysis, which is so conspicuous a
feature in chick embryos of the third and fourth day, appears relatively late in the pig. No suggestion of an epiphyseal evagination has
appeared in 9 to 12 mm. embryos.
 
The mesencephalon shows little change from its condition in
 
 
 
THE NERVOUS SYSTEM
 
 
111
 
 
younger embryos. Its demarcation from the metencephalon posteriorly
is indicated by a conspicuous constriction in the neural tube (Figs.
59, 60, and 65).
 
The division of the primitive hind-brain (rhombencephalon) into
metencephalon and myelencephalon is indicated at this stage,
though not conspicuous or definite. The dorsal wall of the neural tube
just caudal to the meso-rhombencephalic constriction is markedly
thick, contrasting strikingly with the very thin roof of the more
posterior part of the hind-brain (Fig. 65). The zone of the neural tube
where the dorsal thickening exists is the metencephalon ; the posterior,
thin-roofed portion of the hind-brain is the myelencephalon. Although
all external indications of individual neuromeres have by this time
disappeared, the internal face of the myelencephalic wall still shows
definite neuromeric markings (Figs. 61 and 67).
 
The Cranial Nerves. The peripheral relations of the cranial
nerves to cephalic structures and their central relations to the brain
are strikingly constant throughout the vertebrate series. In fishes we
recognize 10 pairs of cranial nerves. In the mammals we encounter
these same 10 cranial nerves with essentially similar relations both
centrally and peripherally. But the mammalian brain in its progressive
specialization has incorporated a part of the neural tube which in
primitive fishes was unmodified spinal cord. One of the clearest evidences of this process is the fact that we find in the mammals 12 pairs
of cranial nerves, the first, 10 of which are homologous with the 10
cranial nerves of fishes and the last two of which represent a modification of nerves which in fishes were the most anterior of the spinal
nerves.
 
The 12 cranial nerves of mammals are designated by numbers
almost as commonly as they are referred to by name. Beginning with
the most rostral they are: (I) olfactory, (II) optic, (III) oculomotor,
(IV) trochlear, (V) trigeminal, (VI) abducens, (VII) facial, (VIII)
acoustic, (IX) glossopharyngeal, (X) vagus, (XI) spinal accessory,
and (XII) hypoglossal. In 9 to 12 mm. pig embryos all of the cranial
nerves except the olfactory and optic are readily recognizable (Figs.
59-63, and 92). Those carrying sensory fibers show conspicuous
ganglia near their point of connection with the brain (see nerves
V, VII, VIII, IX, and X in Fig. 92). Except for the acoustic (VIII)
all these ganglionated nerves carry also some motor fibers — that is,
they are mixed nerves. The cranial nerves composed practically
entirely of motor fibers have no external ganglia (nerves III, IV, VI,
and XII, Fig. 92).
 
 
 
112 STRUCTURE OF NINE- TO TWELVE-MILLIMETER EMBRYOS
 
 
 
Fig. 60. Reconstruction (X 14) of the nervous, digestive, respiratory, and
urinary systems of a 9.4 mm. pig embryo. Compare with Frontispiece and
with figure 66. By laying a straight-edge across the numbered lines in the
margin the locations of the accompanying cross-sections may be determined.
 
Abbreviations
 
All. St., allantoic stalk, C.I., dorsal root ganglion of first
 
Br. ep., eparterial bronchus. cervical nerve.
 
 
 
EXTERNAL FEATURES
 
 
113
 
 
Fig. 60 — (Continued)
Abbreviations
 
 
Ch. t., chorda tympani branch of
facial nerve.
 
Dien., diencephalon.
 
G.acc., accessory ganglion.
 
G.acou., acoustic ganglion of eighth
nerve.
 
G.Fro., Froriep’s ganglion.
 
G.gas., Gasserian (semilunar) ganglion of fifth nerve.
 
(bgen., geniculate ganglion of
seventh nerve.
 
G.jug., jugular ganglion of tenth
nerve.
 
G.nod., nodose ganglion of tenth
nerve.
 
G.pet., petrosal ganglion of ninth
nerve.
 
G.pv., prevertebral sympathetic ganglion.
 
G.sup., superior ganglion of ninth
nerve.
 
Gen. Em. genital eminence.
 
Gl. B., gall bladder.
 
Glom.j glomerulus.
 
L. , lung.
 
Lg. Int., large intestine.
 
M. Mes.j splanchnic mesoderm cut
where reflected over mesonephros
from mesentery.
 
Mand.V., mancfibular branch of fifth
(trigeminal) nerve.
 
Max.V., maxillary branch of fifth
(trigeminal) nerve.
 
Mes., mesencephalon.
 
Mes. D., mesonephric duct.
 
Met., metencephalon.
 
Met.D., metanephric diverticulum.
 
Myel.j myelencephalon.
 
N. IIL, third cranial (oculomotor)
nerve.
 
N.IV., fourth cranial (trochlear)
nerve.
 
N.VI., sixth cranial (abducens)
nerve.
 
 
N.VI I., seventh cranial (facial)
nerve.
 
N.X., tenth cranial (vagus) nerve.
 
N.XI., eleventh cranial (accessory)
nerve.
 
N.XI I., twelfth cranial (hypoglossal)
nerve.
 
N.cerv.d., descending cervical nerve.
 
N.Ph., phrenic nerve.
 
Na., location of nasal (olfactory) pit.
 
Nch., notochord.
 
Neur. Cr., neural crest.
 
Neph., nephrogenous tissue of metanephros.
 
Oes., esophagus.
 
Op.c., optic cup.
 
Oph.V., ophthalmic branch of fifth
(trigeminal) nerve.
 
Ot., auditory vesicle (otocyst).
 
P.C.G., post-cloacal gut.
 
P.C.V., posterior cardinal vein.
 
Panc.d., dorsal pancreas.
 
Panc.v., ventral pancreas.
 
Pelvic Dil., pelvic dilation of metanephric diverticulum.
 
Ph.4., fourth pharyngeal pouch.
 
Rath, p., Rathke’s pocket.
 
Sm. Int., small intestine.
 
St., stomach.
 
Sub. Card. Sin., large venous sinus
formed by the transverse anastomosis of the subcardinal veins
(subcardinal sinus).
 
T.I., first thoracic spinal ganglion.
 
Tel., telencephalon (specifically the
label is on the right lateral telencephalic vesicle).
 
Thym., thymus.
 
Thyr., thyroid.
 
Tr., trachea.
 
V.T.M., superficial mesonephric
veins connecting post- and subcardinals (named venae transversales mediales by Sabin).
 
 
 
114 STRUCTURE OF NINE- TO TWELVE-MILLIMETER EMBRYOS
 
 
ganglion VIII ganglion VII
 
 
 
myelencephalon
 
 
Fig. 61. Transverse section of 9.4 mm. pig embryo passing through the
myelencephalic region (X 15). This and the following drawings of crosssections were taken from the same series used in making the reconstructions
which appear as figures 60 and 66. The serial number of this section is 96. Its
location on the reconstructions may be determined by laying a straight-edge
on the marginal lines numbered 96.
 
 
phanmgeal pouch I mandibular branch nerve V
 
pharyngeal pouch II \ / int ca
 
 
1st cervical
ganglion
 
 
 
 
int carotid a.
 
/ optic cup
 
diencephalon
 
 
br, am.
w ^^ard V
 
 
 
 
 
 
4 ^
 
 
 
 
 
ant cardinal v. / /
 
nerve XL /
ganglion nod.X
 
 
N. Ratbfcra
 
\ pocket
 
. ophth branch of
\ nerve V
 
nerve 111
 
 
I ^ branch of ant cardinal
 
«erve VII Imaxillary branch nerve V
 
 
Fig. 62. Transverse section of 9.4 mm. pig embryo passing through the
pharynx (X 15). (Its serial number on reconstructions appearing as figures
60 and 66 is 142.)
 
 
 
THE NERVOUS SYSTEM
 
 
115
 
 
The Spinal Ckird and Spinal Nerves. The caudal part of the
myelenccphalon merges without any definite line of demarcation
into the spinal cord. The walls of the neural tube in the cord region
have already begun to become differentiated. Dorsally and ventrally
they remain thin, but laterally rapid proliferation of primordial nerve
cells has caused them to increase greatly in thickness so that the
originally oval lumen of the tube becomes slit-like (cf. Figs. 42, B-D,
and 83).
 
The cells arising from the neural crests (Fig. 35) have become
aggregated on either side of the cord into segmentally arranged
clusters, the spinal ganglia (Fig. 59). From nerve cells in each of these
ganglia, fibers grow both toward the cord and peripherally, establishing the dorsal root (afferent root) (sensory root) of a spinal nerve
(Figs. 73, 84, and 85). The ventral root (efferent root) (motor root) of a
spinal nerve is composed of fibers which grow out from cells lying
in the wall of the neural tube (Fig. 84). Outside the cord the dorsal
and the ventral root unite to form a spinal nerve trunk.
 
Immediately distal to the union of the dorsal and the ventral root
of a spinal nerve, the nerve trunk breaks up into three main branches :
a dorsal ramus carrying the fibers associated with the dorsal part of the
body, a ventral ramus composed of fibers terminating in ventral parts
 
 
hyoid arch hyomandibular cleft
 
 
 
Fig. 63. Transverse section of 9.4 mm. pig at the level of the eyes (X 15).
(Serial number on reconstructions, 159.)
 
 
 
116 STRUCTURE OF NINE- TO TWELVE -MII.LIMETER EMBRYOS
 
of the body, and a ramus commtmicans containing the fibers which extend
by way of the prevertebral sympathetic chain to the viscera (Fig. 85).
 
Primarily the spinal nerves are strictly metameric in arrangement,
each nerve carrying the sensory fibers from, and the motor fibers to,
that segment of the body in which it arises. But the underlying
metamerism of the body in the adult is greatly modified, almost
obliterated in many regions, by such processes as the fusion of primordial tissues from several metameres to form new, highly specialized
structures, or by the migration of entire organs from their place of
origin to new positions in the body. Since the spinal nerves arise very
early in development and are at first associated with structures at
their own metameric level, their final arrangement constitutes a
valuable record of evolutionary and developmental history. The
appendages, for example, arise by the coalescence and organization
of primordial tissue from several adjacent metameres. The corresponding spinal nerves innervate these tissues. Originally entirely separate,
these nerves merge peripherally to form the nerves to the appendages.
But the story of polymetameric development is permanently recorded
by the series of nerve roots which retain their independent origin from
the spinal cord in spite of their peripheral fusion in the brachial and
sacral plexuses.
 
Furthermore, the caudal migration of the appendages during
development is clearly evidenced by the fact that their nerves arise
from the cord at a more cephalic level than that occupied by the
appendages themselves. (Note the involvement of cervical nerves
in the formation of the brachial plexus, Fig. 60.) Similarly the caudal
migration of the diaphragm from its place of first appearance at what
is destined to be the level of the neck, is indicated by the cervical
origin from the cord of the phrenic nerve to the diaphragm. In a pig
embryo of about 10 mm. the phrenic nerve (Fig. 60) can be seen
extending directly from its level of origin toward the septum transversum (Fig. 59) which is the beginning of the diaphragm. Later in
development, as the diaphragm moves caudad, the terminal portion
of the phrenic nerve will be pulled caudad with it, constituting a
permanent record of the migration of the diaphragm.
 
The Sense Organs. Although the cranial nerves associated with
the nose and the eye are not as yet well developed in 10 mm. pig
embryos, the primordia of the sense organs themselves are established.
The olfactory organs are represented by a pair of depressions situated
at the rostral end of the head (Figs. 58, 168, and 169). From special
 
 
THE NERVOUS SYSTEM
 
 
117
 
 
ized cells in the ectodermal lining of these nasal pits, nerve fibers will
later arise and grow into the telencephalon establishing the olfactory
nerves.
 
The single-walled spheroidal optic vesicle seen in younger embryos (Fig. 36, E) has been converted by invagination of its distal
portion into a double-walled cup (Figs. 41, D, and 63), The inner
layer of the optic cup is already much thickened, foreshadowing its
development into the highly specialized sensory layer of the retina.
The outer layer remains thinner and becomes the pigmented layer
of the retina. The invagination of the primary optic vesicle to form
the optic cup takers place eccentrically. As a result the lip of the cup
is not, at first, complete. It shows a ventral gap, called the choroid
fissure^ which does not ( lose until much later in development (Figs. 47
and 60, choroid fissure shown but not labeled; Fig. 41, D, section cut
somewhat on a slant so that it passes through the choroid fissure in one
eye but not in the other). The choroid fissure is continued as a groove
on the ventral surface of the optic stalk. Wh(m the fibers which constitute the optic nerve grow from cells in the sensory layer of the retina
to the brain, they pass along this groove in the optic stalk.
 
While these changes have been occurring in the optic vesicle, the
lens has been established by invagination of the superficial ectoderm
overlying the optic cup (Fig. 41, D). By the time the embryo has
attained a length of 10 mm., the lens has been completely separated
from the parent cctodcTm and appears as a spheroidal vesicle lying
in the opening of the optic cup (Figs. 60 and 63).
 
The primordium of the internal ear mechanism is as yet very
simple in form. It makes its first appearance as a loc:al thickening of
the superficial ectoderm overlying the hind-brain. This thickened
area, the olfactory placode, then sinks in to form a pit (Figs. 30 and 36,
E) which soon becomes closed over to form the auditory (otic) vesicle.
By 10 mm. the auditory vesicle has entirely lost all connection with
the ectoderm from which it was derived. The only indication of its
origin is a slender stalk, the endolymphatic duct, which extends
dorsally toward the site of the original invagination.
 
Although the nerve connections of the auditory apparatus with
the brain have not yet been definitely established, they are clearly
indicated by the nerve fibers growing from cells in the acoustic
ganglion to the brain on the one hand, and toward the otic vesicle on
the other. Of significance, also, is the close proximity of the first
pharyngeal (hyomandibular) pouch to the otic vesicle (Fig. 60).
 
 
 
118 STRUCTURE OF NINE- TO TWELVE -MILLIMETER EMBRYOS
 
 
This pouch is destined to give rise to the middle ear chamber and the
Eustachian tube.
 
III. The Digestive and Respiratory Organs
 
The Oral Region. The digestive system of 10 mm. pigs still shows
most of the primary landmarks seen in younger embryos. The stomodaeal depression has broken through into the fore-gut establishing
the oral opening, but a small diverticulum called Seessel’s pocket
persists as a vestige of the pre-oral gut (cf. Figs. 37, 40, and 65). SeessePs pocket is of no especial interest in itself for it gives rise to no adult
structure. In embryos of this age, however, it is a valuable landmark
indicating as it does precisely the point at which stomodaeal ectoderm
and fore-gut entoderm became continuous when the oral plate
ruptured.
 
The part played by the growth of nasal, maxillary, and mandibular processes in deepening the original stomodaeal depression and in
the formation of the face and jaws is discussed elsewhere (Chap. 13).
But mention should be made here of another stomodaeal structure
called Rathke’s pocket. Rathke’s pocket arises in the mid-line as a
slender diverticulum of stomodaeal ectoderm growing toward the
infundibulum (Fig. 65). Later in development it separates from the
ectoderm and its deep portion becomes fused with the infundibulum
to form an endocrine gland known as the hypophysis.
 
The Pharynx. Caudal to the oral opening, the fore-gut becomes
very broad and considerably flattened dorso-ventrally to form the
pharynx. A series of four pairs of pocket-like diverticula, the pharyngeal pouches, arise from it laterally (Fig. 60). Each pharyngeal pouch
is situated opposite one of the external gill furrows, representing, as
it were, an abortive attempt at establishing an open gill cleft. In
mammalian embryos this process ordinarily stops just short of completion, the gill clefts remaining closed by a thin membrane (Figs.
41, B, and 62).
 
The Trachea and Lung Buds. In the floor of the pharynx at the
level of the most posterior pair of pharyngeal pouches, a median
ventral groove appears which is rapidly converted into a tubular outgrowth parallel to the digestive tract. This groove is the tracheal
(Iciryngo-tracheal) groove, and the tubular outgrowth which is formed
by its prolongation caudad is the trachea. In 10 mm. embryos the
caudal end of the trachea has become enlarged and bifurcated to form
the lung buds. Thus the original evagination from the pharynx is the
 
 
 
9
 
 
 
Fig. 64. Model' of 10 mm. pig embryo dissected to the sagittal plane. (After
 
Prentiss.)
 
 
primordium of larynx, trachea, bronchi, and lungs, but for the sake
of brevity it is often referred to as “the lung bud” (Figs. 40, 60, 65,
and 69-74),
 
The Esophagus and Stomach. Posterior to the pharynx the
digestive tube is distinctly narrowed to form the esophagus (Figs. 65
and 69—74). A marked local dilation, already of suggestive shape,
indicates the beginning of the stomach (Figs, 59, 60, 64, and 67).
 
The Liver and Pancreas. Immediately caudal to the stomach
are the outgrowths of the gut which constitute the primordia of the
pancreas and of the liver and gall-bladder. The pancreas at this stage
 
 
 
 
 
 
 
120 STRUCTURE OF NINE- TO TWELVE -MIIXIMETER EMBRYOS
 
 
consists of two independent parts, a large dorsal bud and a small
ventral bud (Figs. 60, 76, and 104). The original hepatic diverticulum
(Figs. 40 and 103, A) has given rise to a very extensive mass of glandular tissue which is crowded ventrally and cephalically from its point
of origin to constitute the liver (Figs. 59, 64, and 65). The narrowed
proximal portion of the original evagination from the gut persists
as the duct draining the liver, and a diverticulum of it becomes
enlarged to form the gall-bladder (Fig. 104).
 
The Intestines. The elongation of the intestines which later
results in their characteristic coiling has just commenced in 10 mm.
embryos. The gut has become relatively thinner than in earlier stages
and protrudes into the belly-stalk in the form of a slender U-shaped
loop (cf. Figs. 37, D, 40, 64, and 65). Communicating with the gut at
the apex of the loop is the yolk-stalk. The yolk-stalk by this time has
become greatly attenuated and the yolk-sac with which it communicates is reduced to a shriveled vesicle embedded in the belly-stalk
(Figs. 64 and 65).
 
In some of the older embryos in the 9 to 12 mm. range the Ushaped bend of the gut has been twisted to form a loop and a slight
enlargement of the gut just caudal to the yolk-stalk will be found
indicating the beginning of the cecum (Fig. 64). Cephalic to this
enlargement the gut will become small intestine, and caudal to it,
large intestine.
 
The Cloaca. The dilated caudal end of the gut where the allantoic
stalk and the mesonephric ducts enter is called the cloaca (Fig. 60).
It is in this region that the proctodaeal depression ruptures into the gut
establishing its posterior opening to the outside. In 10 mm. embryor
the tissue intervening between the gut and the proctodaeum is nevet
thick and usually shows definite signs of impending disintegration if
not an actual rupture (Fig. 65). Caudal to the level of the proctodaeum a variable portion of the hind-gut persists for a time as the
so-called post-cloacal (post-anal) gut (Fig. 60).
 
IV. The Coelomic Cavity
 
When first established the coelom consisted of paired cavities
bounded by the splanchnic and somatic layers of the lateral mesoderm (Fig. 108, A). With the folding off of the body from the extraembryonic membranes and the closure of the embryonic body
ventrally, the primary right and left coelomic chambers are carried
toward each other in the mid-line (Fig. 108, B~D). In this process the
 
 
 
posterior choroid plexus^
 
 
I’HE GOKI.OMIC CAVITY
 
 
metencephalon
 
 
basilar artery .
 
 
myelencephalon
 
 
 
 
mesencephalon
 
 
tuberculum
posterious
 
 
infundibulum
 
 
aortic arch IV â– 
 
 
aortic arch VI
pericardial
 
coelom —
 
 
esophagus right atrium
 
 
lung bud
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Rathke’s pocket
 
 
Seessel’s pocket
 
 
' optic chiaama
 
 
recessus opticus
 
 
lamina terminalis
 
 
extra-embryonic
Wif V. coelom
 
 
^genital eminence
 
 
. proctodaeum
 
 
dorsal pancreas
 
omphalomesenteric
 
(sup. mesenteric) artery \
 
omphalomes. vein
( portal )
 
subcardinal anastomosis^
 
 
>oiii i
 
/ A #aripB%r **V • I
 
 
gut loop
 
 
allantoic stalk
 
 
Fig. 65. Sagittal section of 10 mm. pig embryo (X 16)
 
 
 
122 STRUCTURE OF NINE- TO TWELVE -MILLIMETER EMBRYOS
 
gut tract is caught between the layers of splanchnic mesoderm which
form the mesial boundaries of the coelomic chambers. The double
layer of splanchnic mesoderm thus formed serves as a supporting
membrane for the gut and is known as the mesentery. Shortly after its
formation the part of the mesentery ventral to the gut breaks through,
bringing the right and left coelomic chambers into confluence and
thus establishing a single body cavity within the embryo (Fig. 108, F).
 
Only in the mid-body region do these changes take place exactly
as described above. While they are essentially similar elsewhere there
are certain local modifications of the process which are of special
interest. At the level of the pancreas and liver the ventral mesentery
persists, supporting the liver (Figs. 108, E, and 111). Where the extraembryonic membranes are continuous with the embryo at the bellystalk, the body cavity remains for a long time continuous with the
extra-embryonic coelom (Figs. 108, C, and 111). In the cardiac region
the digestive tract develops in the dorsal body-wall so that no dorsal
mesentery is formed. Here the heart is formed ventral to the gut and
suspended in the coelom by a double layer of splanchnic mesoderm
in a manner quite suggestive of that in which the liver is suspended in
the ventral mesentery farther caudally in the body (cf. Figs. 43, D,
and 108, E).
 
In 10 mm. pig embryos the body cavity is not yet divided into
separate pericardial, pleural, and peritoneal chambers. Between the
liver and the heart, however, there has appeared a shelf-like structure
which partially separates the thoracic region of the coelom from the
abdominal. This incomplete partition is called the septum transversum. At this stage it is an ingrowth of ventral body-wall tissue fused
to the cephalic face of the liver (Fig. 64). The septum transversum
itself never extends all the way across the coelom. Later in development we shall see it supplemented by the pleuroperitoneal folds
which arise from the dorsal body-wall, and complete the diaphragmatic partition across the coelom.
 
V. The Urinary System
 
The Pronephros. In mammalian embryos the pronephros is a
vestigial organ appearing only transitorily in the form of a few rudimentary tubules. In 10 mm. pig embryos even these tubules have
almost completely disappeared. The paired ducts which originally
appeared in connection with the pronephric tubules persist, however,
and are appropriated by the developing mesonephric tubules. After
 
 
 
THE CIRCULATORY SYSTEM
 
 
123
 
 
forming this new association they are called the mesonephric (Wolffian) ducts.
 
The Mesonephros. In younger embryos we saw the development
of mesonephric tubules from the intermediate mesoderm and the
manner in which they attained connection with the mesonephric duct
(Figs. 38, E, F, 40, and 41, G, H). In pigs of 10 mm. mesonephric
tubules have been formed in great numbers, and each tubule has
become much elongated and exceedingly tortuous. As a result the
mesonephros becomes an organ of great bulk — in fact the most conspicuous organ in the body of an embryo of this age (Figs. 59 and 60).
 
Sections passing through the mesonephros (Figs. 74-79) convey
a very vivid impression of the interwoven mass of tubules of which it
is composed. Details as to the shape of the tubules and the relations
of the blood vessels to them can best be considered in connection with
the development of the urogenital system (Chap. 10).
 
In the more cephalic part of the mesonephros it is not always easy
to distinguish the duct from the tubules. Farther caudally the duct
can easily be identified lying along the ventral border of the mesonephros. After leaving the substance of the mesonephroi, the mesonephric ducts curve ventro-mesially to enter the cloaca together with
the allantoic stalk (Figs. 60 and 122).
 
The Metanephros. Just cephalic to the cloacal end of the mesonephric duct an outgrowth arises from it and extends antero-dorsad.
This is the metanephric diverticulum (Figs. 60 and 122). The terminal
portion of this diverticulum becomes dilated, presaging its ultimate
fate as the pelvic cavity of the kidney. Its proximal portion remains
slender as the ureter. About the enlarged pelvic end of the metanephric diverticulum a mass of mesoderm accumulates. Because it is
destined to form the excretory tubules of the permanent kidney, this
mass of mesoderm is known as the nephrogenous tissue of the metanephros (Figs. 60 and 79). Like the cell clusters which form the
mesonephric tubules it arises from intermediate mesoderm.
 
VI. The Circulatory System
 
A functionally competent circulatory system is laid down before
the developing pig has reached a length of 10 mm. Paired primordia
fuse to establish the heart as a median tubular organ receiving the
blood at its posterior end and pumping it out from its cephalic end
(Figs. 43 and 44). The aortae arise as paired vessels which lead away
from the heart, swing around to the dorsal side of the pharynx, and
 
 
 
 
 
THE CIRCULATORY SYSTEM
 
 
125
 
 
then extend caudad throughout the length of the embryo as the main
distributing channels (Fig. 45). Large collecting vessels develop in
the shape of the paired cardinal veins which receive the blood from
the anterior and posterior regions of the body and return it over the
ducts of Cuvier (common cardinal veins) to the sino-atrial part of the
heart (Fig. 45). Pigs in the 9 to 12 mm. range still retain to a large
extent this primary bilaterally symmetrical arrangement of the main
vessels which is so characteristic of young erribryos. There have been,
however, many local elaborations and modifications which are of
special interest because they initiate the series of changes which lead
toward adult conditions.
 
The Heart. The chief factor in changing the configuration of the
heart from its primitive straight tubular shape to the condition seen
in 10 mm, embryos is its own rapid elongation and consequent bending. In this process the cephalic end of the heart remains anchored
by the aortic roots and its caudal end by the omphalomesenteric veins.
Thus the receiving and discharging ends of the heart suffer no radical
change in position. The intervening portion of the heart is, however,
bent into a loop which is carried first ventrally and then caudally to
form the pumping part of the heart or ventricle (Figs. 142 and 143).
The details involved in the bending of the heart tube and the special
 
 
Fig. 66 — {Continued)
Abbreviations
 
 
A.C.V., anterior cardinal vein.
 
Ao., aorta. ^
 
Ao.A., aortic arch.
 
A.O.M., omphalomesenteric artery.
Bas.A., basilar artery.
 
Cerv. Seg. A., intersegmeiital
 
branches of aorta in cervical region.
Coel. A., celiac artery.
 
Cuv.d., common cardinal vein (duct
of Cuvier).
 
D.V., ductus venosus.
 
Ex. Car. A., external carotid artery.
Il.A., iliac artery.
 
Int. Car. A., internal carotid artery.
P.C.V., posterior cardinal vein.
Pul.A., pulmonary artery.
 
P.V.C., posterior vena cava.
 
 
S.C.V., subcardinal vein.
 
Subcl.A., subclavian artery.
 
Subcl.V., subclavian vein.
 
U.A., umbilical (allantoic) artery.
 
U. V., umbilical (allantoic) vein.
 
V. Cap., vena capitis (tributary of
anterior cardinal vein).
 
V.O.M., omphalomesenteric (portal)
vein.
 
V.T.L., lateral transverse veins of
mesonephros.
 
V.T.M., medial transverse veins of
mesonephros.
 
V. Vent., ventral vein of mesonephros.
 
Vert. A., vertebral artery.
 
 
For cardiac structures refer to figure 145.
 
 
 
126 STRUCTURE OF NINE- TO TWELVE -MILLIMETER EMBRYOS
 
features of its internal structure can best be considered in connection
with later stages of development when their significancp will be more
apparent (see Chap. 11). At present we are chiefly interested in
becoming acquainted with the more outstanding structural features
of the embryonic heart.
 
The great veins converging to enter the heart become confluent
in a thin-walled chamber called the sinus venosus (Fig. 144). The
sinus venosus opens into the atrial portion of the heart by a slit-like
orifice guarded against return flow by well-developed flaps known as
the valvulae venosae (Figs. 46, 145, 146, and 147).
 
The atrial region has undergone extensive transverse enlargement
so that it bulges out into pouch-like right and left chambers (Figs.
71, 72, 142, 144, and 147). Although the beginning of the separation
of these chambers from each other is clearly indicated by the presence
of an interatrial septum, this septum is not complete, and the atrial
chambers remain in communication through a secondary perforation
in the septum called the interatrial foramen secundum {ostium II)
(Figs. 71, 145, and 148).
 
Leaving the atrium, the blood passes through a constricted region
known as the atrio-ventricular canaL Previously a single channel (Fig.
147, A), in 10 mm. embryos this canal has, as was the case with the
atrium, become more or less completely divided into right and left
channels. The division is effected by a pair of plastic masses of mesenchymal tissue, the so-called endocardial cushions of the atrio-ventricular
canal. Located one dorsally and one ventrally (Fig. 39), these cushions
grow together and fuse to divide the atrio-ventricular canal (Figs. 147
and 148). Except for the least advanced specimens their fusion will
ordinarily have occurred in embryos of the 9-12 mm. stage.
 
In the ventricle, also, there are indications of the impending
separation of the heart into right and left sides. The interventricular
septum has appeared as a well-marked median ridge extending from
the apex of the ventricular loop toward the atrio-ventricular canal
(Figs. 71, 72, 147, and 148). Above this septum the two parts of the
ventricle are still in open communication.
 
Correlated with its activity in pumping, the ventricular wall has
become greatly thickened. Irregular branching bands of developing
muscle tissue protrude from the main part of the wall into the lumen.
These trabeculae carneae already suggest the muscular bands which
project so characteristically into the cavities of the adult ventricles.
 
From the ventricle the blood passes into the truncus arteriosus
 
 
 
 
 
 
 
 
128
 
 
STRUCTURE OF NINE- TO TWELVE-MILLIMETER EMBRYOS
 
 
^ primordium superior sagittal sinus
 
 
valvulae vcnosac ,
 
 
left duct —
 
of Cuvier
 
ductus vcnosus
 
hepatic veins
 
right umbilical v.
 
allantoic stalk
 
 
metanephric
 
duct
 
 
primordium transverse sinus
 
 
^ vein of maxillary region
(branch of int. jugular)
 
 
 
umbilical artery
 
 
vein of mandibular region
(branch of ext. jugular)
 
 
dorsal segmental v
^ ^ aorta
pulmonary artery
 
^ - right atrium
 
right duct
of Cuvier
 
subclavian v.
 
- post cardinal v.
 
- subcardinal v.
 
mesenteric
- part of
posterior
vena cava
 
- * ~ portal vein
 
transverse
' anastomosis
of subcardinals
 
mesonephric veins
 
posterior cardinal vein
mesonephric duct
 
 
Fig. 68. Reconstruction of 12 mm. pig embryo showing the relation of the
main venous channels to the viscera. (From Minot after Lewis.)
 
 
 
THE CIRCUEATORY SYSTEM
 
 
129
 
 
and thence out to the body by way of the ventral aortic roots. Aside
from the marked thickening of its walls, the truncus arteriosus shows
little change from its original condition as the anterior part of the
heart tube. Its diameter remains small and the longitudinal division
it is destined to undergo later in development is barely suggested by
the irregular shape of its lumen seen in cross-sections (Fig. 70).
 
It should not be inferred from the modifications which have occurred in the different regions of the heart that it has as yet altered
its primitive method of functioning. The heart tube has become bent
and shows local dilations and constrictions which we name because
of their future fate. Many internal conditions point toward its division
into right and left sides. But the blood enters the heart posteriorly
by way of the sinus venosus, is collected in the atria, and passes into
the ventricle whence it is pumped out by way of the truncus arteriosus
as an undivided stream, just as was the case in younger embryos
where the heart was still a straight tube.
 
The Aortic Arches. In vertebrate embryos six pairs of aortic
arches are formed extending around the pharynx from the ventral
to the dorsal aorta. Of these the most cephalic are the first to appear
and the other pairs are formed in sequence caudal to the first (Figs. 134
and 136). In pig embryos of 10 mm. the two most cephalic arches have
already degenerated. The functional arches at this stage are the third,
fourth, and vsixth (Figs. 66, 67, 134, E, and Frontispiece). The fifth
 
 
 
Fig. 69. Transverse section of 9,4 mm. pig embryo at level of posterior
part of pharynx (X 15). (The serial number of this section on the reconstructions appearing as figures 60 and 66 is 180.)
 
 
 
130 STRUCTURE OF NINE- TO TWELVE-MILLIMETER EMBRYOS
 
 
left atrium
 
 
 
Fig. 70. Transverse section of 9.4 mm. pig embryo through telencephalon
and cephalic part of pericardial chamber (X 15). (Serial No. 212.)
 
arch is always poorly developed in mammals and usually appears only
as a small collateral channel appended sometimes to the fourth, but
more commonly to the sixth arch (Fig. 66). From the sixth arches
small branches (the pulmonary arteries) extend caudad to the
developing lungs (Frontispiece).
 
Arteries of the Cephalic Region. The portions of the ventral
aortic roots which led to the two anterior aortic arches do not disappear when the arches themselves degenerate but persist as the external carotid arteries (Figs. 66 and 67). The dorsal aortae are prolonged cephalad as the internal carotid arteries (Figs. 45, 66, and 67).
 
Throughout the length of the aorta small branches appear at
regular intervals and extend dorsad on either side of the neural tube.
Since these vessels are formed between adjacent somites they are
known as the intersegmental arteries (Figs. 45, 67, and 159). In the
cervical region the intersegmental vessels form a series of connections
with each other which eventually result in the establishment of longitudinal vessels dorsal to, and parall^ with, the aortae. These are the
vertebral arteries (Fig, 67). This longitudinal anastomosing between
the cervical intersegmental arteries appears cephalically first (Fig. 66)
and then progresses caudad. As the vertebral arteries become established, the more cephalic intersegmental branches feeding them disappear. Only the most caudal of the intersegmentals concerned in the
formation of the vertebral arteries persists. Since this intersegmental
 
 
 
THE CIRCULATORY SYSTEM
 
 
131
 
 
interatrial
 
foramen secundum septiun I
 
 
interventricular septum
 
 
notochord
 
 
cervical ganglion
 
 
 
esophagus
 
 
trabeculae
 
 
duct of Cuvier
 
pulmonary artery
 
 
pericardial cavity
 
 
e^ndocardial cushion
 
 
Fig. 71. Transverse section of 9.4 mm. pij^ embryo through heart at level of
interatrial foramen secundum (X 15). (Serial No. 251.)
 
 
artery (seventh cervical) is at the same time the one situated at the
level of the anterior appendage bud and consequently the vessel
which is enlarged with the growth of the appendage to form the
subclavian artery, the vertebral artery eventually appears as a branch
of the subclavian (Figs. 67 and 133, B, C).
 
Cephalic to the cervical level the vertebral arteries bend toward
the mid-line and unite with each other to form a median vessel lying
ventral to the myelencephalon. This is the basilar artery (Figs. 65, 66,
and 67). Ventral to the cephalic flexure in the neural tube, the
internal carotid arteries send branches mesiad to unite with the basilar
(Figs. 67 and 133). This anastomosis between the internal carotid
and the basilar is the first step in the formation of the arterial circle
(circle of Willis) which is such a conspicuous landmark in the adult
anatomy of the hypophyseal region.
 
The Dorsal Aorta and Its Branches. When first formed the
dorsal aorta is a paired vessel. This paired condition is retained in
the branchial region, but posteriorly the two primitive aortae soon
fuse with each other to form a median vessel. The fusion first occurs
in the mid-body region (Fig. 51) and extends thence cephalad to
about the level of the anterior appendage buds and caudad throughout the length of the aorta (Fig. 67).
 
In young embryos the most conspicuous vessels arising from the
dorsal aorta are the omphalomesenteric trunks which are prolonged
 
 
 
132 STRUCTURE OF NINE- TO TWELVE -MILLIMETER EMBRYOS
 
 
left duct of Cuvier
 
 
dorsal aortic root
 
\
 
\
 
 
ethccrvical gan(i'lion
 
esophagus
 
 
left atrio- ventricular canal
 
 
 
sinus venosus
 
 
valvulae venosae
 
 
endocardial cushion
 
 
peiicardial cavity
 
interventricular septum
 
\
 
right atrio ventricular canal
 
 
right atrium
 
 
Fig. 72. Transverse section of 9.4 mm. pig embryo through heart at level of
atrio-ventricular canals (X 15). (Serial No. 258.)
 
 
as the vitelline arteries to the yolk-sac, and the allantoic or umbilical
arteries to the vascular plexus of the allantois (Figs. 45 and 51).
Both these vessels arise from the aorta before its fusion and are themselves paired. The umbilical arteries retain their paired condition
(Fig. 79). When the body is closed ventrally, the right and left
omphalomesenteric roots are brought together in the mid-line and
fuse with each other to form a median vessel running in the mesentery. With the early degeneration of the yolk-sac, this vessel becomes
relatively less conspicuous and is known as the anterior (superior)
mesenteric artery (Figs. 66 and 67). Its original relations are, nevertheless, apparent from its course along the intestinal loop into the
belly-stalk to the place where the small yolk-sac still retains its
attachment to the gut.
 
Somewhat cephalic to the anterior mesenteric artery, the celiac
artery arises from the aorta and extends in the mesentery toward the
gastric region of the gut tract (Fig. 67). In the adult, the celiac,
anterior mesenteric, and posterior mesenteric arteries constitute a
group of vessels which one naturally thinks of together because of
their similar ventral origin from the aorta, their course through the
mesenteries, and their termination in the gastro-intestinal tract. The
third member of this enteric group, the posterior (inferior) mesenteric
cannot ordinarily be found in pigs of 9 to 12 mm. It arises from the
 
 
 
THE CIRCULATORY SYSTEM
 
 
133
 
 
esophagus
segmental artery
7 th cervical nerve
 
notochord
 
 
septum Iransversum
 
 
ramus communicans
dorsal aortic root
 
segmental vein
 
 
left ventricle
 
 
 
interventricular
 
septum
 
 
post cardinal
 
 
pencardial cavity
 
 
ant appendage bud
 
 
posterior vena cava
 
 
bifurcation of trachea
 
 
Fig. 73. Transverse section of 9.4 mm. pig embryo at level of tracheal bifurcation (X 15). (Serial No. 293.)
 
 
aorta, caudal to the other two vessels, at a slightly more advanced
stage of development.
 
At the level of the mesonephros the aorta gives off, in addition to
the series of dorsal intersegmental branches, many small branches
which extend ventrally. These vessels feed the capillary plexuses
(glomeruli) in the dilated ends of the mesonephric tubules and the
network of capillaries which surround the tubules themselves (Fig.
117). Individually these branches are very small, but the volume of
blood they handle collectively is surprisingly large as evidenced by
the size of the veins (post- and subcardinals. Fig. 68) which drain the
mesonephroi.
 
The Anterior Cardinal Veins. In 9 to 12 mm. embryos little
alteration from primitive conditions (Fig. 47) has occurred in the veins
of the cephalo-thoracic part of the body. Numerous large tributary
vessels have appeared, especially in the cephalic region where they
converge on either side of the head as the so-called venae capitis
(Fig. 66). It is already possible to recognize in the larger of these
branches the primordial vessels from which the main venous sinuses
pf the adult cranial region are derived (Fig. 68). Fundamentally,
however, these veins are but an elaboration of the original anterior
cardinal system. From them the blood passes caudad along the less
modified portion of the anterior cardinals to enter the heart by way of
 
 
 
134 STRUCTURE OF NINE- TO TWELVE -MIL LIME TER EMBRYOS
 
 
lunc bud
 
etophagut
 
metonephros
nerve to
 
ant appendage bud
dorsal aortae
 
 
Stfacervical gangUon
 
branch of poat
 
posterior cardinal vein
 
P’lG. 74. Transverse section of 9.4 min. pig embryo through cephalic part of
liver (X 15). (Serial No. 309.)
 
the common cardinal veins (Fig. 66). Just before the anterior cardinal
vein enters the common cardinal vein a series of small tributaries (dorsal
segmental veins, Fig. 68) return to it the blood distributed by the intersegmental arteries to the cervical region. Near this point, also, a welldeveloped branch brings back the blood from the mandibular region.
The vessel which thus returns the blood distributed by the external
carotid artery is the beginning of the external jugular vein (Fig. 68).
The anterior cardinal vein itself is later known as the internal jugular.
 
The Posterior Cardinal Veins. In very young embryos (Fig. 45)
the posterior cardinal veins are the only conspicuous venous channels
in the caudal half of the body. In 9 to 12 mm. pigs these veins have
already begun to degenerate. Their relative position as vessels lying
dorsal to the mesonephroi remains unchanged, but much of the blood
formerly returned by them now reaches the heart over new channels
(cf. Figs. 45, 66, and 139, A~F). As a result the posterior cardinal
veins in the mid-mesonephric region have been interrupted. Toward
the heart from this point the old channels persist, although they are
much reduced in size. Caudal to their interruption the posterior
cardinals rapidly degenerate as main channels (Figs. 66 and 139,
D, F).
 
The Subcardinal Veins. The diversion of the blood from the
posterior cardinals is brought about by the development of a col
 
 
 
 
THE CIRCULATORY SYSTEM
 
 
135
 
 
tubcardinal v
 
 
 
Fig. 75. Transverse section of 9.4 min. pig embryo just cephalic to attachment of belly-stalk (X 15). The belly-stalk and the tip of the tail have not
been included in the drawing. (Serial No. 388.)
 
lateral system of veins in the mesonephroi. When it first appears, this
system of vessels is but an irregular plexus tributary to the postcardinals (Fig, 139, A). The organization of longitudinal channels in
these plexuses establishes the main subcardinal veins as vessels extending cephalad in the ventro-mesial border of the mesonephroi,
parallel with and ventral to the posterior cardinal veins. In the
cephalic part of the mesonephros the newly established subcardinal
blood stream enlarges some of the small channels already entering
the posterior cardinal and discharges through them into the posterior
cardinal vein/ (Figs. 47 and 139, C). Other vessels of the primitive
plexus persist as a meshwork of small veins lying superficially in the
mesonephros. These veins afford free intercommunication between
the postcardinals dorsally and the subcardinal vessels in the ventromesial portion of the mesonephros (Figs. 117 and 139).
 
From the same primitive subcardinal plexus a minor longitudinal
channel develops along the ventral border of each mesonephros.
These vessels are called the ventral veins of the mesonephroi (Figs. 66
and 139). The fact that they are rather conspicuous in pig embryos
at this stage sometimes leads to their confusion with the main subcardinal channels. Their characteristic superficial position on the
ventral border of the mesonephros (Fig. 139, E) should preclude
such a possibility. They are to be regarded as an incidental modifica
 
 
136 STRUCTURE OF NINE- TO TWELVE -MILLIMETER EMBRYOS
 
 
 
Fig. 76. Transverse section of 9.4 inm. pijEj embryo at level of pancreatic outgrowth from gut (X 15). Tail and part of belly-stalk omitted. (Serial No. 406.)
 
 
 
Fig. 77. Transverse section of 9.4 mm. pig embryo at level of inter-subcardinal anastomosis. (Cf. Fig. 139, D, F.) (Serial No. 426.)
 
 
 
 
mesonephros elomerulus
 
 
 
velni connecting postcardinal
and subcardtnal veins
 
 
Fig. 79. Transverse section of 9.4 mm. pig embryo passing through caudal
end of mesonephros (X 15). (Serial No. 529.)
 
 
 
138 STRUCTURE OF NINE- TO TWELVE-MILLIMETER EMBRYOS
 
tion of the plexus of small vessels connecting the sub- and postcardinals
rather than as main channels of any special importarjice.
 
With the growth of the mesonephroi the rapidly enlarging subcardinal veins are brought very close to each other (cf. Fig. 139, B, E).
Where they are approximated, cross-communication is established,
first by small vessels and then by a broad anastomosis (Figs. 60, 68,
77, and 139, D-F). The large median venous sinus thus formed
probably offers less resistance to the flow of blood than surrounding
channels; in any case all the vessels connecting with it tend to drain
toward it. The diversion of blood toward this sinus by way of the
small vessels which connect the sub- and postcardinals is responsible
for the breaking down of the postcardinal veins at this level (Figs. 66
and 139, D, F).
 
The Posterior Vena Cava. One might expect that the great
volume of blood entering the subcardinal sinus would cause a corresponding enlargement of the cephalic portion of one or both subcardinal veins. Instead, a new and more direct channel toward the
heart appears. In its growth the liver is crowded very close to the
mesonephroi. The developing liver contains a maze of vascular channels, as does the mesonephros. Capillaries ramifying in the base of the
mesentery between the liver and the right mesonephros form the
connecting link between the vessels of these two organs (Fig. 140).
Once the blood begins to find its way by this route, the small irregular
channels are rapidly enlarged and straightened. The new and more
direct channel thus established leads from the subcardinal sinus
through the right subcardinal vein for a short distance and thence, by
the newly excavated channels in the mesentery, through the liver to
the heart (Fig. 139, D). This is the start of that embryologically composite^ vessel which we know in the adult as the posterior, or inferior,
vena cava (Figs. 66, 68, and 74-77).
 
The Omphalomesenteric Veins. Primarily the omphalomesenteric veins are the main channels into which the vitelline veins from
the yolk-sac converge (Fig. 45). Two factors radically change their
original relations. The early degeneration of the yolk-sac reduces their
 
^ The developmental complexity of the posterior vena cava is recognized by
designating the part of it which arises by the straightening of small channels in the
liver as its intra-^hepatic portion; the part which arises from the capillaries in the caval
fold as its mesenteric portion; the part formed by the inter-subcardinal anastomoses as
the inter-renal portion; and that part which at a later stage is added by the appropriation of the right supracardinal as the post-renal portion.
 
 
 
THE CIRCULATORY SYSTEM
 
 
139
 
 
peripheral drainage area, with a resultant decrease in their relative
size; and the growing liver envelops and breaks up their proximal
portions (Fig. 141, A-C). Thus we find them in 10 mm. pig embryos
reduced to small vessels which collect the blood delivered by the
enteric arteries to the gut. Distally the omphalomesenteric (vitelline)
veins are still paired but where they discharge into the liver they
have been reduced to a single vessel, which we can now quite properly
call by its adult name, Xht portal vein (Figs. 66, 76, and 77).
 
The Umbilical Veins. Except for a striking increase in size, the
distal portions of the umbilical veins in 9 to 12 mm. pig embryos have
undergone little change (cf. Figs. 45 and 66). Proximally, however,
they have been rerouted through the liver. The underlying factor in
this change is the extensive growth of the liver which brings it into
contact with the lateral body-walls in which the umbilical veins are
embedded in their course from the belly-stalk to the sinus venosus.
Fusion follows the contact, and small vessels develop between the
umbilicals and the network of channels in the liver (Fig. 141, B). As
these new vessels develop the portions of the umbilical veins cephalic
to them gradually drop out altogether and all the placental blood
passes through the liver (Figs. 66, 68, 74, 75, and 76).
 
With the completion of this change in the umbilical circulation,
the liver has become the common returning path for both of the
original extra-embryonic circulatory arcs and most of the intraembryonic circulation of the posterior half of the body. Only the
dwindling current of the postcardinals and the unchanged anterior
cardinal circulation now enter the sinus venosus without first passing
through the liver. When we consider all this volume of blood passing
through one organ, it leaves little room for surprise at the relatively
enormous bulk attained by the liver in mammalian embryos.
 
 
 
==Chapter  8==
 
 
Tke Development of tke Nervous System
 
 
I. The Functional Significance of the Various Parts
of the Nervous System
 
Without some knowledge of the functional significance of the
various parts of the nervous system to serve as a basis for correlation
and interpretation, its study, from either the developmental or
anatomical point of view, is barren and discouraging. Therefore, even
though it involves reviewing some familiar facts and also introducing
some material which is more neuroanatomical than embryological, it
seems advisable to summarize here certain conceptions which are
essential to an understanding of the nervous system.
 
Neurons. The nervous system is made up of cells which are
highly specialized in two of the fundamental properties of protoplasm,
irritability and conductivity. These cells develop long cytoplasmic
processes which extend from one part of the body to another, acting
in the manner of telephone lines keeping the various parts of the
organism in touch with each other and making possible prompt and
coordinated response to alterations in internal or external conditions.
In the nervous system of animals as complex as the vertebrates most
lines of communication involve chains of such cells arranged so the
ends of the processes of one cell come into close relation with the
processes or cell body of another. When a change in environmental
conditions (a stimulus) starts a wave of electro-chemical change (a
nerve impulse) in the protoplasm of one cell in the chain, the wave
traverses the processes of the cell in which it was initiated and passes
on to the next cell in the chain, and so on. Each link in the chain,
that is, each nerve cell with its processes, is called a neuron.
 
Synapses. The point at which the nerve impulse passes from the
processes of one cell to the processes of another is known as a synapse.
Synapses between neurons appear to be in the nature of ‘‘contacts”
sufficiently intimate to permit the passage of a nerve impulse, but not
ordinarily involving structural continuity of the cell processes. This
 
140
 
 
 
 
FUNCTIONAL SIGNIFICANCE OF PARIS OF NERVOUS SYSTEM 141
 
 
contact type of relation at a synapse, which apparently is “made” or
“broken” under varying physiological conditions, underlies such
phenomena as alternative responses to a given stimulus. It implies
the possibility of selective routing of the impulse over one of several
neuron chains by the occurrence of physiological contact at certain
synapses and physiological disjunction at others.
 
The arrangement of neuron chains or arcs, as they arc frequently
called, is exceedingly complex in the vertebrate nervous system.
Consideration of its details would carry us far afield, but it is quite
possible to take up enough of the basic scheme of neuron arrangement
so that the various parts of the nervous system assume some meaning
in terms of function rather than remaining as mere names, without
significance and readily confused.
 
Functional Classes of Neurons. All the myriad neurons which
go to make up the central and peripheral nervous system are alike in
that they are cells with attenuated processes specialized in conductivity. Among themselves they differ greatly as to location, relations,
length, number and distribution of processes, and type and direction
of impulses transmitted. Functionally neurons can be divided into
three main groups. Some neurons carry impulses from sensory nerve
endings and sense organs (receptors) toward the cord and brain.
'Fhesc' are said to be afferent neurons. Others conduct motor impulses
away from the cord and brain to muscles or glands (effectors) which
respond by appropriate activity. Such neurons are said to be efferent.
In the cord, and especially in the brain, are countless neurons having
many relatively short processes, which can transfer an incoming
sensory impulse to any one of a number of efferent neurons with
which their Various processes connect. These are association neurons.
These three functional categories of neurons, afferent, association,
and efferent, together with the receptors attuned to pick up various
changes in internal or external conditions, and the effectors capable
of carrying out the appropriate responses, constitute what we may
call the action system of the organism.
 
Nerves. The various anatomical parts of the nervous system can
be translated into terms of sensory, motor, and association neurons,
and their characteristic activities. Thus, what in the dissecting room
we call “nerves,” arc bundles of delicate neuron processes projected
to various peripherally located structures. The nuclei and the bulk
of the cytoplasm (cell bodies, cytons) of the neurons are either massed
at some point on the nerve to form a ganglion, or buried in the central
 
 
 
142
 
 
THE DEVELOPMENT OF THE NERVOUS SYSTEM
 
 
nervous system where they are spoken of as nuclear masses. The nerve
itself consists only of the long slender neuron processes (nerve fibers)
and the sheaths which protect them.
 
The Spinal Cord and Reflexes. The spinal cord is at once a
center for automatic local responses to local stimulation, and a conduction pathway. In its capacity as a local center it receives sensory
impulses coming to it by way of afferent neurons and sends out motor
impulses over efferent neurons which activate effectors in the region
stimulated. Such an automatic local response is known as a simple
intrasegmental reflex and represents the most primitive type of mechanism in the vertebrate action system (Fig. 80, arc 1).
 
By transmission of a sensory impulse longitudinally along the cord
through the agency of association neurons, the outgoing impulse may
be imparted to efferent neurons in several adjacent metameres. Such
a mechanism is termed an inter segmental reflex. It is a distinct step in
advance over the strictly local reflex in that it affords a concerted
response on the part of a group of effectors (Fig. 80, arc 2). The part
of the cord primarily involved in segmental and intcrsegmental
responses is the centrally located ‘‘gray matter.’^ This gray matter is
composed chiefly of association neurons and of the cell bodies of
motor neurons which send their processes into the spinal nerves.
 
Cerebrospinal Conduction Paths. The peripheral “white
matter'’ of the cord is composed of nerve fibers which run longitudinally, constituting pathways of intercommunication between the
spinal cord and nerves, and the brain. The color from which this
part of the cord takes its name and which sets it off so sharply from
the richly cellular gray matter, is due to the sheaths enclosing the
fibers. These sheaths are rich in a fatty substance (myelin) which
imparts the characteristic whitish and glistening appearance.
 
Phylogenetically these conduction paths in the peripheral part
of the cord increase in conspicuousness concomitantly with the increasing extent to which the brain assumes a coordinating control
over the basic reflexes which constitute the primary function of the
cord. The sensory (afferent) conduction paths are for the most part
grouped in the dorsal portion, whereas the motor (efferent) paths are
found in the lateral and to a less extent in the ventral portion of the
cord. (Fig. 86, E.)
 
Reflexes Involving Organs of Special Sense. Much of the control
exercised by the brain on the activities of the body as a whole depends
on afferent impulses entering from sense organs of a much more highly
 
 
 
SUP COLUCULUS
 
 
 
CEREBELU3W
 
 
SEMICIRC.
CANALS
 
 
Motor
 
Fatha
 
 
Motor fibers from
Higher Arcs to All
Segmental Levels
 
 
Long Sensory fibers
to Higher Arcs
via Sensory Paths
 
 
Sensory
Nerve Endings
in Shin
 
 
 
Motor
 
Nerve Endings
inMuacte
 
 
Arc 7
 
Voluntary and Inhibitory
Control
 
Choice of response based
on memory of past experiences. (Via pyramidal ract.)
 
Arc 6
 
Automatic Associated
Control
 
of complex muscular actions.
(Via striato-rubro-spinal
tract.)
 
Arc 5
 
a. Auditory Reflexes
e.g. Automatic response to
sudden noise.
 
b. Visual Reflexes
e.g. Automatic response
to blinding flash of light.
(Both via tecto-spinal tract.)
 
Arc 4
 
Synergic Control
Automatic coordinating
control of muscular actions.
(Via rubro-spinal tract.)
 
Arc 3
 
EquILIBRATORY CONTROL
Automatic balancing reactions. (Via vestibulo-spinal
tract.)
 
Arc 2
 
Intersegmental Reflex
Impulse carried by association neurones to neighboring segments causing
coordinated response of muscles in several segments. .
 
Arc 7
 
Intrasegmental Reflex
Response limited to segment stimulated.
 
 
Fig. 80. Schematic diagram showing the nature of the activities carried
out in various parts of the central nervous system. (Collaboration of Dr. L. J.
Karnosh.)
 
 
 
144
 
 
THE DEVELOPMENT OF THE NERVOUS SYSTEM
 
 
specialized type than the endings in the general skin surfaces. Such
organs as those of equilibrium, hearing, and sight play an exceedingly
important part in determining the appropriate reactions of the various
segmental effectors and thereby regulating the reactions of the animal
as a whole.
 
Positional changes affect special sensory end organs in the semicircular canals. Through sensory neurons the impulse passes to a
synaptic center (Deiters’ nucleus) at the boundary between myclencephalon and metencephalon (Fig. 80, arc 3). Thence conduction
fibers carry the impulse along an efl'erent path from which it may
enter the appropriate local motor neurons at any segmental level.
'J'his arc would be involved in the automatic balancing reaction to a
sudden upset in equilibrium such as slipping unexpectedly on a
patch of ice.
 
Auditory and visual stimuli are conducted to centers in the midbrain. The auditory stimuli received in the cochlea are transmitted
through a series of sensory neurons to synaptic centers in the inferior
colliculi on both sides of the mesencephalon and thence by motor
paths to the appropriate local motor fibers at any or all segmental
levels (Fig. 80, arc 5a). This arc is the one responsible for the involuntary reaction to a sudden noise.
 
Responses to sudden visual stimulation involve an arc much similar
to that described for reactions initiated by auditory stimuli. The visual
arc (Fig. 80, arc 5b) starts with sensory fibers arising in the retina of
the eye. In the superior colliculi of the mesencephalon these afferent
fibers have synapses with association and motor fibers. The motor
fibers communicate with the effector mechanism of the body over
paths paralleling those involved in the responses to auditory stimuli.
Through this arc would be brought about the automatic recoil from
a sudden blinding flash of light.
 
Coordinating Centers. So far the action mechanisms described
are purely reflex in character and relatively simple. In the complex
and more deliberate actions involving large groups of muscles in
several segments, a coordinating effect is exercised from a center in
the cerebellum. This center receives sensory impulses (position sense)
from all segmental levels in the body. These impulses pass by way
of a series of neurons in the cerebellum (metencephalon), to a synaptic
center (red nucleus) in the mid-brain. Thence (Fig. 80, arc 4) the
impulse is conducted by motor fibers through the common motor
pathways to the general body musculature. Such an arc provides for a
 
 
 
FUNCTIONAL SIGNIFICANCE OF PARTS OF NERVOUS SYSTEM 145
 
 
smooth and precise, but unconscious, coordination of muscular action,
such as that involved in slowly bringing together the tips of the forefingers of the two hands. This is the so-called synergic type of muscular
control.
 
Certain fairly complex responses are, nevertheless, largely automatic or unconscious, such as the rhythmic swaying of the trunk and
swinging of the arms in walking. These are regulated by association
neurons passing through the thalamic region of the diencephalon and
the corpus striatum of the telencephalon. Sensory fibers enter the
thalamus from all afl'erent pathways. Thence the impulses (Fig. 80,
arc 6) are transmitted to synaptic centers in the corpus striatum. From
the corpus striatum they pass over motor fibers to the red nucleus
whence they enter the common motor paths along with the motor
fibers from the cerebellar centers.
 
Voluntary and Inhibitory Control. Superimposed on the primitive types of response is a mechanism affording a wide choice of reactions in response to the stimuli entering from the various afferent
pathways. The centers for this, the highest and most plastic system,
are in the cortical areas of the telencephalon. Fibers from practically
all receptors enter this system by way of the thalamus (Fig. 80, arc 7).
From synapses in the thalamus the afferent fibers arc dispersed
according to their special functions into localized areas in the cerebral
cortex. By myriads of association neurons these various centers are in
free intercommunication. These centers are responsible for memory
and for all choices of action conditioned by previous experience. In
short, they are the centers of intelligent response, in distinction to
reflex reactions to existing conditions. Through the intercommunicating associatidn neurons of this system motor impulses may be transmitted by way of the common motor paths of the spinal cord to any
parts of the action system.
 
In becoming acquainted with the various regions of the central
nervous system, therefore, we should think of the spinal cord and the
myelencephalon as carrying out the dual role of reflex centers and
conduction pathways to and from the higher brain centers. The cerebellum acts as a coordinating center for complex muscular actions
such as those concerned with the maintenance of normal posture.
The floor of the mesencephalon is made up primeirily of great fiber
tracts passing to and from the higher brain centers. Specialized
regions in the dorsal walls of the mesencephalon are concerned with
visual and auditory reflexes. Of the two pairs of conspicuous eleva
 
 
146
 
 
THE DEVELOPMENT OF THE NERVOUS SYSTEM
 
 
tions (corpora quadrigemina) the more cephalic pair (superior colliculi) are visual reflex centers and the more caudal pair (inferior
colliculi) are auditory reflex centers. The thalamic region of the
diencephalon serves as the gateway for fibers having cerebral connections. In the deeper part of each cerebral hemisphere is the corpus
striatum which is concerned with muscle tonus and automatic associated movements. The more superficial portions of the cerebral hemispheres become specialized as the cerebral cortex. Certain cortical
areas are the highest terminal centers for the reception of incoming
impulses which keep us in touch with our environment, such as those
resulting from auditory, visual, and tactile stimulation. Other cortical
areas contain the cell bodies of neurons which are the first units in
efferent chains. The connection of afferent and efferent areas by
association neurons affords the connecting link placing the effector
mechanisms of the body under voluntary control. Thus the cerebral
hemispheres act as association centers superimposed on the lower
reflex mechanisms and affording the possibility of intelligent choice
of response based on experience.
 
II. Review of the Early Stages in the Establishment
of Nervous System
 
The initial steps in the formation of the nervous system take place
very early in development. Directly or indirectly, many points of
importance in connection with its establishment and early differentiation have already been dealt with. We have seen the origin of the
neural groove by the infolding of a thickened plate of ectoderm in the
mid-dorsal line of the embryo; the closure of the neural groove to
form the neural tube, and the coincident separation of the tube from
the parent ectoderm (Figs. 24, 25, 28, 29, and 35).
 
In the closure of the neural groove, certain cells lying near its
margins remain independent, being included neither in the walls of
the neural canal nor in the superficial ectoderm as it closes above the
newly established neural tube. These ribands of cells come to lie on
either side in the angles between the superficial ectoderm and the
neural tube and constitute the neural crests (Fig. 35). They are the
primordia of the sensory root ganglia of the spinal and cerebral nerves
and indirectly of the sympathetic ganglia.
 
Almost as soon as it is independently established the neural tube
becomes markedly enlarged cephalically. This dilated portion is the
primordium of the brain. Caudaliy the neural tube remains of relatively uniform diameter as the forerunner of the spinal cord.
 
 
 
147
 
 
THE HISTOGENESIS OF THE SPINAI. CORD
 
In its enlargement the brain at first exhibits three regional
divisions — the primary fore-brain, mid-brain, and hind-brain; or,
to use their more technical synonyms, the prosencephalon, mesencephalon, and rhombencephalon (Fig. 36). This three- vesicle stage
of the brain is short-lived. The prosencephalon is subdivided into two
regions, telencephalon and diencephalon ; the mesencephalon remains
undivided; and the rhombencephalic region becomes differentiated
into metencephalon and myelencephalon. Thus in place of three
vesicles, five are established. This stage in the development of the
brain is well shown in embryos between 9 and 12 mm. in length
(Figs. 59, 60, and 65). Starting with these familiar conditions as a
basis we are ready to trace the later differentiation of some of the
more important parts of the nervous system.
 
III. The Histogenesis of the Spinal Cord and the Formation
of the Spinal Nerves
 
The Establishment of Ependymal, Mantle, and Marginal
Layers. The ectoderm of the open neural groove is at first but a
single layer of cells in thickness (Fig. 81, A). These original cells
proliferate very rapidly and by the time the neural tube has become
closed, its wall consists of many cell layers (Fig. 81, B). The individual
cells, meanwhile, tend to lose their originally clear-cut outlines. In
the older studies it was generally stated that at this stage the cells
merged into a syncytium as suggested by the classical illustration of
Hardesty reproduced here as figure 81. More recently Sauer has
restudied such material and maintains that although the membranes
become delicate and inconspicuous, if sufficiently well-preserved
material is c;Sirefully studied the cells can be seen to retain their
membranes intact. Toward the lumen the neural tube is bounded by
an internal lim it in g ' fiiciiibi ' anc, anth peripherally ^ts extent is sharply
marked by an external limiting membrane (Fig. 8l, C).
 
Certain of the cells lying near the lumen of the neural tube can,
at this stage, be seen undergoing mitosis. They are called germinal
cells (Fig. 81, C) although they are probably merely the cells in this
region that happened to be dividing at the time the material was
fixed. Most of the new cells formed by these cell divisions are crowded
somewhat away from the internal limiting membrane into a zone in
the cord which becomes densely packed with nuclei. This zone is
called the mantle layer (Fig. 81, D). The cells which remain nearest to
the internal limiting membrane become more or less elongated and
radially arranged about the lumen of the neural tube. They constitute
 
 
 
148
 
 
THE DEVELOPMENT OF THE NERVOUS SYSTEM
 
 
 
 
 
 
mesenciiyme
 
I
 
 
 
ext. limiting nuclei of int. limiting
 
 
 
 
Fig. 81. Stages in the histogenesis of the spinal cord. (After Hardesty.)
 
A, From open neural plate of rabbit embryo.
 
B, From wall of recently closed neural tube, 5 mm. pig embryo.
 
C, From neural tube of 7 mm. pig.
 
D, From neural tube of 10 mm. pig. (All drawings X 550.)
 
 
a zone within the mantle layer known as the ependymal layer of the cord.
Outside the mantle layer is a peripheral region into which practically
no nuclei enter. This is the marginal layer (Figs. 81, D, and 83).
 
Spongioblasts and Neuroblasts. Of these three primary zones in
the developing spinal cord the mantle layer is the first to show striking
differentiation. Its cells continue to divide rapidly and undergo
divergent specialization. Some of them become spongioblasts which
are destined to form merely supporting tissue, and some of them
neuroblasts, which will become the functionally active nerve cells.
 
 
 
 
THE HISTOGENESIS OF THE SPINAL CORD
 
 
149
 
 
These two types of cells can first be differentiated from each other by
the fact that the neuroblasts develop large nuclei while the nuclei of
the spongioblasts remain small.
 
Neuroglia. The formation of supporting tissue from the spongioblasts takes place by the development of exceedingly slender and
irregular cytoplasmic processes. Some of these processes may eventually lose their association with the parent cells and appear as separate
fibers. The majority of them, however, retain some connection with
the cells from which they were derived. In this respect as well as in
its ectodermal origin, neuroglia, as this peculiar connective^ tissue of
the central nervous system is called, differs from the other connective
tissues of the body. The fibers and processes formed from the spongioblasts are so delicate that they are exceedingly difficult to demonstrate
in material stained by routine histological methods. But when they
are subjected to metallic impregnation (e.g., the Golgi silver nitrate
method) the ’glia cell processes and fibers appear as blackened strands
forming an elaborate tracery of supporting elements throughout the
substance of the cord (Fig. 82).
 
All neuroglia cells exhibit processes of one sort or another and
all of them are supporting in function, but the cells differ much
among themselves as to shape and arrangement of processes. For
convenience in description they are commonly designated as belonging
 
 
External limiting
membrane
 
 
 
Short- rayed astrocyte
(mossy ceif)
 
 
Fio. 82. Segment of the spinal cord of a 70 mm. pig showing the differentiation of the neuroglial elements. (After Hardesty.) The upper part of the
segment is drawn to show the *glia cells and fibers as demonstrated by silver
impregnation. The lower part of the segment indicates their appearance after
routine staining with hematoxylin and eosin.
 
 
 
 
CLoq
 
 
 
 
 
 
 
 
 
 
 
 
 
 
THE HISTOGENESIS OF THE SPINAL CORD
 
 
151
 
 
and are scattered along the developing myelinated nerve tracts of the
white matter of the central nervous system.
 
Neuroblasts. Preparations of the spinal cord made by the usual
methods do not show the neuroblasts to advantage (Fig. 83). If,
however, a special technique such as intra-vitam staining by methylene
blue or one of the metallic impregnation methods is used, the slender
processes of the neuroblasts can readily be seen (Fig. 84). With the
development of these characteristic nerve fibers we can think of the
neuroblasts as having become young neurons.
 
The Formation of the Spinal Nerves. The outgrowth of processes
from neuroblasts lying in the ventral and lateral portion of the mantle
layer of the cord establishes the motor fibers which compose the
ventral roots of the spinal nerves (Fig. 85). Neuroblasts in the dorsal
root ganglia send to the cord afferent processes which constitute the
dorsal roots of the spinal nerves, and send other processes peripherally
which end in connection with various types of receptors (Fig. 85).
Neuroblasts which have migrated from the cord and from the neural
crest to form the sympathetic ganglia develop processes which relay
efferent impulses thence to their destination (Fig. 85). Reference to
figure 80 will show the relations of the neurons of the spinal nerves
to the central nervous mechanism as a whole. Those interested in
working out in more detail the functional significance of the various
types of neurons encountered in the spinal nerves will find a brief
analysis appended to the legend of figure 85. For more comprehensive
information along these lines reference should be made to the discussion of ‘‘spinal nerve components” in a textbook of neurology.
 
The Development of the White and Gray Matter of the Cord.
During the period of development when the neurons are being differentiated, the appearance of the spinal cord as seen in sections undergoes very marked changes. Some of the neuroblasts in the mantle
layer of the cord, as we have seen, send out processes very early in
development. Others remain undifferentiated and continue to proliferate for a time, causing continued growth in the mantle layer. As
it grows in mass the mantle layer takes on a very characteristic configuration, becoming butterfiy-shaped in cross-section. With this
change in shape, and with the transformation of its spongioblasts
into neuroglia and its neuroblasts into characteristic nerve cells, the
mantle layer becomes the so-called ^‘gray matter” of the spinal cord
 
(Fig. 86).
 
During the growth of the mantle layer the originally extensive
 
 
 
152
 
 
THE DEVELOPMENT OF THE NERVOUS SYSTEM
 
 
Alar plate
 
 
Dorsal root
 
 
Ventral root
 
 
Ramus
 
dorsalis
 
 
Rrevertebral
sympathetic
ganglion
 
 
 
Ramus
 
communicans
 
 
â– Mesonephros
 
 
^Sensory
ending in skin
 
 
Sweat
 
gland
 
 
Fig, 85, Schematic diagram indicating the various connections made by
the neurons which develop in a typical spinal nerve. (Modified from Froriep.)
 
The neurologist classifies the fibers in a spinal nerve according to their
relations and functions. The components of a typical spinal nerve on this
basis are:
 
I. AFFERENT
 
A. General Somatic Afferent
 
(1) Exteroceptive^ i.e., fibers conducting impulses from the external
surface of the body such as touch, pain, temperature. (Represented in this figure by short broken lines.)
 
(2) Proprioceptive^ i.e., fibers carrying impulses of position sense from
joints, tendons, and muscles. (Not represented in this diagram.)
 
 
 
THE HISTOGENESIS OF THE SPINAL CORD
 
 
153
 
 
lumen of the neural tube is reduced, by obliteration of its dorsal
portion, to the small central canal characteristic of the adult cord
(Fig. 86). The cells of the ependymal layer now constitute a sort of
epithelioid lining of the central canal.
 
Meanwhile the outer or marginal layer of the cord has been
increasing extensively in mass. Its growth is due to the secondary
ingrowth of longitudinally disposed neuron processes which constitute
the conduction paths between the various levels of the spinal cord
and the brain (Fig. 80). Each of these fibers being enveloped in a
 
 
Fig. 85 — (Continued)
 
B. General Viscerai. Afferent
 
Fibers from viscera (interoceptive) by way of sympathetic chain
ganglion, white ramus communicans, and dorsal root; cell bodies in
dorsal root ganglion; no synapse before reaching cord. (Illustrated
in this figure by dotted line.)
 
II. EFFERENT
 
A. General Somatic Efferent
 
Motor neurons to skeletal muscle; cell bodies in ventral columns of
gray matter; fibers emerge by ventral roots. (Illustrated in this figure
by solid lines.)
 
B. General Viscerai. Efferent
 
Two-neuron chains from cord to glands and to smooth muscle of
viscera and blood vessels. I'he first neurons (preganglionic) have
their cells of origin in lateral column of gray matter of cord from first
thoracic to third lumbar level. Fibers leave cord by ventral root, turn
off in white ramus communicans to end in synapse with the second
neurons (postganglionic) of the two-neuron chain.
 
Note the various destinations of the visceral efferent paths, e.g.:
 
(1) fibers to smooth muscle of gut wall; impulse relayed by second order
motor neuron.^ from synapses in mesenteric ganglion.
 
(2) fibers (vaso-motor) to .smooth muscle of blood vessel wall; impulses
relayed by second order motor neurons from synapses in prevertebral
ganglia.
 
(3) fibers (pilo-motor) to muscles about hair follicles, and fibers (sudomotor) to sweat glands in skin. Impulses in both these cases relayed from
synapses in prevertebral ganglia by second order motor fibers passing back
over the ramus communicans and thence to periphery via branches of
spinal nerve.
 
Most of the fibers in the spinal nerve are medullated and therefore
whitish in appearance. The visceral second order motor (‘‘post-ganglionic”)
fibers, however, lack a myelin sheath atid are grayish in appearance. Certain
of such second order visceral motor fibers (e.g. pilo-motor and sudo-motor)
which run back along the ramus communicans after synapse in a prevertebral ganglion account for the so-called ^‘gray bundle of the ramus
communicans.”
 
 
 
154
 
 
THE DEVELOPMENT OF THE NERVOUS SYSTEM
 
 
 
columntB of
white matiter
 
 
D. loomm.
 
 
E Term
 
 
Fig. 86. Transverse sections through spinal cord of the pig at various ages.
Note especially the parts of the adult cord derived from the ependymal,
mantle, and marginal layers of the embryonic neural tube.
 
 
sheath rich in myelin, the region of the cord in which they lie has a
characteristic whitish appearance which contrasts strongly with the
gray color of the richly cellular portion of the cord derived from the
mantle layer. For this reason the fibers which develop in the marginal
layer of the cord are said to constitute its white matter. The main
groups of these fibers are more or less marked off from each other by
the dorsal and ventral horns of the gray matter. They are known as the
dorsal, lateral, and ventral columns of the white matter of the cord
(Fig. 86). The dorsal columns contain the main tactile and proprioceptive paths to the brain; the ventral columns are primarily motor;
and the lateral columns contain irnportant ascending fiber tracts to
the brain and also some of the main motor paths from brain to cord
and thence to spinal nerves (Fig. 80).
 
IV, The Regional Differentiation of the Brain
 
It will be recalled that in embryos of about 5 mm. the brain was
just beginning to progress from the three- to the five- vesicle stage.
In embryos of the 9 to 12 mm. range we saw the five-vesicle condition
 
 
 
THE REGIONAL DIFFERENTIATION OF THE BRAIN
 
 
of the brain well established. These same five basic regions of the brain
will continue to be recognized as the major divisions of the adult brain.
During their later development they become greatly altered in
appearance and certain specialized parts of them receive new names,
but their fundamental relations remain the same. The details of all
the structural features which appear in the various parts of the brain
 
 
 
 
 
 
.’v?"
 
 
L
 
 
 
 
 
 
 
 
D. ^5mm.
 
 
L. 100 mm.
 
 
Cerebnal Hemisphere
 
 
 
 
 
 
 
 
Olfocloi^ Treet
 
 
Swel
 
 
 
 
 
 
156
 
 
THE DEVEl.OPMENT OF THE NERVOUS SYSTEM
 
 
constitute too complex a story to be satisfactorily handled in brief
compass. Accordingly we shall confine ourselves to Jbecoming acquainted with the main morphological landmarks and the locations
of the principal functional centers of the brain — the bare foundation
on which subsequent work may build a fuller knowledge of this
interesting system.
 
The Myelencephalon. The myelencephalon of the embryo
becomes the medulla of the adult brain (Fig. 87). Very early in
development the lumen of this part of the neural tube becomes dilated,
foreshadowing its ultimate fate as the large cavity in the medulla
known as the fourth ventricle (Fig. 88). At the same time its roof
becomes very thin (Fig. 88, A). Small blood vessels develop against
this membranous roof and push it ahead of them into the lumen of
the fourth ventricle. The freely branching group of vessels thus
formed is known as the choroid plexus of the fourth ventricle (Figs. 65,
99, and 106).
 
The walls of the neural tube in the brain region show the same
early histological changes which occur in the walls of the spinal cord,
with the resulting establishment of ependymal, mantle, and marginal
layers. The ependymal layer of the myelencephalon becomes the
epithelioid lining of the fourth ventricle. Its mantle layer gives rise
in part to continuous columns of gray matter as in the cord, and also
forms more or less distinct cell masses (nuclei) associated with the
roots of the more posterior cranial nerves (Fig. 91). The marginal
layer receives an ingrowth of longitudinally disposed medullated
fibers constituting the conduction pathways between the spinal cord
and nerves and the more rostral parts of the brain (Fig. 80).
 
In dealing with the topography of the neural tube as it appears in
cross-sections it is customary to designate its thickened side-walls as
the lateral plates, its thin dorsal wall as the roof plate, and its thin
ventral wall as the floor plate. On this basis the membranous covering
of the fourth ventricle represents a roof plate greatly stretched out
by the divergence of the lateral plates dorsally. (Compare the configuration of the cord, as shown in figure 85, with that of the medulla
as diagramed in figure 91.) The deep ventral groove in the floor of
the ventricle overlies a very thin floor plate. The great bulk of the
myelencephalic wall consists of thickened lateral plates. Extending
along the inner surface of each lateral plate is a longitudinal sulcus
{sulcus limitans) which suggests a division of the lateral plate into a
 
 
 
THE REGIONAL DIFFERENTIATION OF THE BRAIN
 
 
157
 
 
dorsal part {alar plate) and a ventral part {basal plate^ Fig. 91). The
sulcus limitans is especially strongly marked during the early stages
of the development of the myelencephalic region. Later it becomes
masked in certain regions by the growth of underlying nuclei, but
wherever it persists it is a valuable landmark in dealing with the
location of nuclei and fiber tracts. In the brain, as in the cord, afferent
centers develop dorsal, and efferent centers ventral to the sulcus
limitans (Fig. 91).
 
The Mctencephalon. The dorso-lateral walls of the neural tube
in the metencephalic region undergo very extensive growth and give
rise to the cerebellum of the adult brain. The early smooth outline
of this region (Fig. 87, C) is broken up by the development of a complex series of folds (Fig. 87, D, E). Eventually three main lobes are
formed, each of which is subdivided into a great number of minor
folds which impart a very characteristic appearance to the cerebellum
(Fig. 87, F). In this part of the brain are developed the synaptic centers
concerned with the coordination of complex muscular movements
(Fig. 80, arc 4).
 
Relatively late in development great groups of fibers which form
the paths of intercommunication between the cerebellum and other
parts of the nervous system appear superficially in the walls of the
mctencephalon. These form the ventral prominence known as t\it pons
(Fig. 87, E, F), and the cerebellar peduncles which extend over the
lateral walls of the mctencephalon. Deep to, and partly intermingled
with, these superficial groups of fibers lie continuations of the same
longitudinal fiber tracts which, on their way to and from the brain,
traverse the iparginal layer of the medulla. Still deeper are the masses
of cells which originate from the mantle layer of this part of the
neural tube. These cells are clustered in definite centers (nuclei)
associated with the cranial nerves of the metencephalic level (see
Fig. 91).
 
The original lumen of the neural tube in the metencephalic region
remains of considerable size. Since there is no line of demarcation
between it and the lumen of the medulla, it is regarded as the anterior
part of the fourth ventricle (Fig. 88).
 
The Mesencephalon. The dorso-lateral walls of the mesencephalon give rise to two pairs of rounded elevations known as the
corpora quadrigemina (Fig. 87, E). The two more rostral prominences,
called the superior colliculi^ are the synaptic centers for visual reflexes
 
 
 
158
 
 
THE DEVELOPMENT OF THE NERVOUS SYSTEM
 
 
(Fig. 80, arc 5b); and the two more caudal prominences, called the
inferior colliculi^ are the synaptic centers for auditory reflexes (Fig. 80,
arc 5a).
 
The ventro-lateral parts of the mesencephalic walls constitute
the main pathway over which fibers pass to and from the more
anterior parts of the brain (Fig. 80, arcs 6 and 7). The fact that these
fiber tracts in the mesencephalon are continuations of the longitudinal
tracts encountered in the myelencephalon and in the floor of the
metencephalon should be especially emphasized. These tracts in the
mesencephalic floor are designated as the cerebral peduncles.
 
With the great thickening of its walls, the lumen of the mesencephalon becomes relatively reduced to form a narrow canal joining
the lumen of the metencephalon and myelencephalon (fourth ventricle) with the lumen of the diencephalon (third ventricle). This canal
is known as the cerebral aqueduct or aqueduct of Sylvius.
 
The Dicncephalon. Although the diencephalon undergoes
striking local modifications, its original name is still retained in the
terminology of adult anatomy. Its roof becomes thin and vessels
developing on its outer surface force it ahead of them in finger-like
processes which project into the third ventricle as the anterior choroid
plexus (Fig. 106).
 
In the median part of the diencephalic roof, caudal to the point
of origin of the choroid plexus, the epiphysis appears as a small local
evagination (Fig. 100). Later in development the walls of the epiphysis become thickened and its lumen is practically obliterated.
 
In the floor of the diencephalon is formed a median diverticulum
called the infundibulum. The distal portion of Rathke’s pocket loses
its original connection with the stomodaeal ectoderm and becomes
closely applied to the infundibulum (cf. Figs. 65 and 138). Somewhat
later these two structures become intimately fused to form an endocrine gland known as the hypophysis (Fig. 100).
 
Very early in development the optic vesicles arise as outgrowths
from the ventro-lateral walls of the prosencephalon (Figs. 36, E, and
41, D). When the prosencephalon is divided into telencephalon and
diencephalon the optic stalks open into the brain very near the new
boundary (Figs. 60 and 67). In fact the median depression in the
floor of the brain opposite their point of entrance is regarded as the
ventral landmark which establishes the demarcation between telencephalon arid diencephalon (recessus opticus^ Figs. 65 and 88, *A)«
Immediately caudal to the optic recess there is a marked thickening
 
 
 
THE REGIONAL DIFFERENTIATION OF THE BRAIN
 
 
159
 
 
Metacoele (ventricle TZ)
 
 
Thin roof of myelencepholon
(metotela)
 
Myelocoele (ventricle E)
 
 
Spinol cord
 
 
 
Metencepholon,
 
Ganglion 1L
 
Ganglion SUdSH
 
Auditory vesicle
 
Ganglion IZl
 
Ganglions
 
Roots of
N. 21
 
N.XI
 
 
Lateral
telocoele (ventricle I)
 
 
Meso-metencephalic fold
 
Mesocoele
[Sylvian aqueduct)
 
Location of posterior commissure
 
Tuberculum posterius
Diocoele (ventricle n)
 
Velum transversum
 
Median telocoele
(ventricle M)
 
 
Med telocoele
(ventricleM)
 
Foramen
of Monro
 
 
Lamina
 
terminolis
 
 
 
Spinal
 
cord
 
 
Infundibulum^
 
Optic stalkChoroid fissure''
 
Optic cup^
Diencephalon^
 
Lateral telencephalic
vesicle
 
 
[Lat telocoele
(ventricle n)
 
- Diocoele ^
(ventricle HI)
 
Optic cup
 
 
Mesocoele
(Sylvian aqueduct)
 
 
Metacoele
(ventricle E)
 
Myelocoele
(ventricle JZ)
 
Position of
auditory vesicle
 
Spinal cord
 
 
Fig. 88. Diagrams to show the topography of the brain shortly after the
transition from the three- to the five-vesicle stage. A, Sagittal section. The
conventional lines of demarcation between adjacent brain vesicles are
indicated by broken lines. B, Surface view of brain with position of cranial
ganglia and nerve roots indicated. C, Schematic frontal plan of brain as it
would appear if the flexures had all been straightened out before cutting.
 
 
in the floor of the diencephalon where part of the fibers of each optic
nerve cross to the other side of the mid-line. This point of crossing of
optic nerve fibers is known as the optic chiasma (Figs. 65 and 88, A).
Beyond the chiasma the crossed and uncrossed fibers on either side
run together as the optic tracts. The optic tracts pass along the lateral
walls of the diencephalon where some of their fibers end. Others pass
 
 
 
160
 
 
THE DEVELOPMENT OF THE NERVOUS 'SYSTEM
 
 
to the visual reflex centers in the superior colliculi (Fig. 80, arc 5b).
Still others concerned with the interpretation and memory of visual
impulses pass by way of the geniculate nuclei to the visual areas of the
cerebral cortex.
 
The dorsal parts of the lateral walls of the dicnccphalon become
greatly thickened by multiplication of neuroblasts in the mantle
layer. These thickened regions are known as the thalami (Fig. 100).
The dorsal portion of the thalamus is the gateway of fibers passing
from the cord and the brain-stem^ to the cerebral hemispheres
(Fig. 80, arcs 6 and 7). In it are large synaptic centers acting as relay
stations. Superficial t© these nuclear masses are fiber tracts radiating
through the lateral diencephalic walls.
 
The thickening of the lateral walls of the diencephalon greatly
reduces the width of its lumen. In its central portion the two walls
come in contact and fuse, forming across the third ventricle a conspicuous connection known as the massa intermedia.
 
The Telencephalon. The telencephalon consists of the most
rostral part of the neural tube together with paired dorso-lateral outgrowths from the primary median portion. These outgrowths first
appear as roughly hemispherical evaginations called the lateral
telencephalic vesicles (Figs. 60 and 88, C). Although the division of the
lateral walls of the neural tube into alar and basal plates is not clearly
marked this far forward in the brain, the telencephalic evaginations,
because of their general relations, are regarded as involving the alar
plates.
 
At first the cavities within the two telencephalic vesicles are
broadly continuous with the primary lumen of the neural tube (Fig.
67). Later in development these openings into the lateral vesicles
appear relatively much smaller; nevertheless they persist, even in the
adult, as the so-called joramina of Monro, Thus in spite of extensive
local modifications the original neural canal remains open throughout
the entire length of the central nervous system. Its most rostral parts,
the cavities in the telencephalic vesicles {first and second ventricles of the
adult brain), communicate with the median telencephalic lumen by
way of the foramina of Monro. Since there is no line of demarcation
between this small median telocoele and the diocoele, both are
included in the cavity of the adult brain known as the third ventricle
 
 
^ Brain-stem is a commonly used term for designating those portions of the brain
other than the telencephalon, diencephalon, and cerebellum.
 
 
 
THE REGIONAL DIFFERENTIATION OF THE BRAIN
 
 
161
 
 
Mesencephalon N. oculomotorius
 
 
Cerebellum
 
Gang, genicuti n. 7
 
Gang, acusticum n. 8
 
Gang, soperlus n. 9
Gang, accessorius
 
 
N. trochlearis
 
Gang, semilunare n. 5
 
 
Gang, jugulare n. 10,
 
Gang, petrosum n. 9
N. hypoglossus
 
 
N. accessorius
 
Gang. cerv.
5-8
 
 
Diaphragm
 
Dorsal lobe of liver.
 
Mesonephros
 
 
 
Metanephros
 
I
 
Nerve to lower limb
 
Sciatic nerve
 
 
Mandibulor ramus n. 5
 
Ophthalmic ramus n. 5
N. opticus
Cerebrum
 
Maxillary ramus n. 5
Chorda tympani n. 7
N. facialis
 
Gang, nodosum n. 10
 
Right atrium
Right ventricle
 
.Ventral lobe of liver
 
Umbilical cord


 
[[Category:Draft]]
Fig. 89. Model made from a dissection exposing the nervous system of an 18
mm. pig embryo. (After Prentiss.)
 
 
(Fig. 88, C). From the third ventricle the cerebral aqueduct leads
through the mesencephalon to the fourth ventricle^ which is the adult
term for the confluent lumina of the metencephalon and myelencephalon. The fourth ventricle becomes narrowed caudally and is
directly continuous with the central canal of the spinal cord (Fig.
88, C).
 
The lymph-like fluid which fills these cavities in the nervous system
 
 
 
162
 
 
THE DEVELOPMENT OF THE NERVOUS SYSTEM
 
 
appears to be derived primarily from plexuses of small blood vessels
which invade thin places in the dorsal wall of the brain. One such
mass of vessels we have already encountered under the name of the
posterior choroid plexus or choroid plexus of the fourth ventricle. Another
appears in the rostral part of the diencephalic roof (Fig. 106). This
anterior choroid plexus grows into the third ventricle. Closely associated
plexuses push through each foramen of Monro into the lateral ventricles of the telencephalic lobes, constituting the lateral choroid plexuses
(Fig. 100). It should perhaps be emphasized that the blood vessels of
the choroid plexuses do not break through the brain roof but push it
ahead of them so that although they appear to lie in the ventricles they
are always separated from the lumen by a thin enveloping layer
derived from the ependymal layer of the dorsal wall of the neural
tube.
 
Once established, the lateral lobes of the telencephalon undergo
exceedingly rapid growth. Their extension rostrally conceals the
median portion of the telencephalon, and their even greater expansion
dorsajiy and caudally eventually covers the entire diencephalon
and mesencephalon (Fig. 87). At first the telencephalic lobes are
smooth in contour and without striking local differentiations (Fig. 87,
B-E). Relatively late in development they become much convoluted
and certain regional divisions become clearly marked.
 
A conspicuous fissure called the sulcus rhinalis divides the ventral
part of the telencephalic lobes from the dorsal (Fig. 87, F). The region
ventral to the sulcus rhinalis is chiefly concerned with the olfactory
sense and is, therefore, often called the rhinencephalon. It includes the
olfactory bulb, the olfactory tract, and the pyriform lobe (Fig. 87, F).
The rhinencephalon reaches its maximum development in lower
forms. In higher mammals it becomes largely overshadowed by the
tremendous growth of the more dorsal portions of the cerebral cortex.
 
Dorsal to the sulcus rhinalis the outer walls (pallium) of the telencephalic vesicles constitute the non-olfactory portions of the cerebral
cortex. These cortical areas are phylogenetically the newest portions
of the brain. In them are located the suprasegmental centers concerned with memory, voluntary action, and inhibitory control (Fig.
80, arc 7).
 
In forms such as the mammals, where the cerebral hemispheres
are especially highly developed, the cortex is extensively folded. All
the principal folds (gyri) and grooves (sulci) are named and the association centers for various special functions have, with considerable
 
 
 
THE REGIONAL DIFFERENTIATION OF THE BRAIN
 
 
163
 
 
Semilunar ganglion n. 5 Ophthalmic ramus n. 5
Gang, geniculi n. 7
Mesencephalon
 
 
Cerebellum
Gang, acusticum n. 8
 
Gang, superius n. 9
Gang, jugulare n. 10
 
Froriep's ganglion
Auricular r. n. 10
Gang. n. cerv. 1
Gang, petrosum n. 9
N. accessorius
 
N. hypoglossus
 
Gang. cerv. 5—8
Gang. thor. 1
 
 
Lung
 
 
Diaphragm
 
 
Dorsal lobe of liver
 
 
Cerebral hemisphere
Hypophysis
 
N. opticus
 
Olfactory lobe
 
.Maxillary ramus n. 5
Mand. ramus n. 5
Chorda tympani n. 7
 
 
N. facialis
 
 
 
Mesonephros
 
I
 
Metanephros
 
Lumbar gang.
 
 
Gang, nodosum n. 10
 
 
Right atrium
Right ventricle
 
Ventral lobe of liver
 
Umbilical cord
 
Lower limb (cut)
 
 
Sciatic nerve
 
 
Nerve to lower limb
 
 
Fig. 90. Model made from a dissection exposing the nervous system of a 35
mm. pig embryo, (After Prentiss.)
 
 
accuracy, been located in specific areas. It would carry us beyond the
scope of this book, however, were we to attempt to do more than
become familiar with the major regional divisions of the cerebral
hemispheres known as the frontal, parietal, temporal, and occipital
lobes (Fig. 87).
 
The corpus striatum is developed in the mande layer of the ventro
 
 
164
 
 
THE DEVELOPMENT OF THE NERVOUS SYSTEM
 
 
lateral walls of the telencephalon. Its location in the tt'lencephalic
floor makes it more closely associated positionally with the rhinencephalic region than with the pallial region which gives rise to the
cerebral cortex. In its development it tends to bulge from either side
in toward the lumen of the lateral ventricles (Figs. 99 and 100),
becoming eventually one of the conspicuous internal landmarks in the
telencephalic region. It derives its name from the fact that when
sectioned it shows alternate layers of fibers and cellular substance
arranged in more or less regular bands. Two large nuclear masses,
the caudate nucleus and the lentijorm nucleus^ make up the major part
of the corpus striatum. Its connections are very complex and many
of them are not as yet entirely worked out. Whatever its other activities may be, it is clearly involved in the co5rdination of certain complex muscular activities (Fig. 80, arc 6). It also appears to exert a
steadying influence on voluntary muscular actions generally, because
interference with it is followed by the appearance of tremors during
movement.
 
V. The Cranial Nerves
 
In dealing with the spinal nerves we recognized four functional
types of neurons, somatic afferent, somatic elferent, visceral afferent,
and visceral efferent (Fig. 85). In the cranial nerves wc find these
same types of neurons and in addition other subtypes with more
restricted distribution and more specialized function. The eye and
the ear, for example, are very highly differentiated and sharply
localized somatic sense organs. Therefore their fibers are set apart
from the general somatic afferent category as special somatic afferent
fibers. The musculature in the pharyngeal region differs from other
visceral musculature in that it is striated. So the motor fibers to it are
distinguished from other visceral efferent fibers by calling them
SPECIAL visceral efferent neurons.
 
The spinal nerves are segmentally arranged and all of them are
built on the same general plan. The cranial nerves have lost their
segmental arrangement and become very highly specialized. Some
of them contain both sensory and motor fibers as is the case with the
spinal nerves. These are called mixed nerves. Some contain only motor
fibers and others only sensory fibers. No single nerve contains ail the
types of fibers which occur in the cranial nerves as a group as diagramed in figure 91.
 
In both spinal and cranial nerves, afferent fibers arise from
cell bodies outside the neural tube (cf. Figs. 85 and 91). Thus the
 
 
 
THE CRANIAL NERVES
 
 
165
 
 
cranial nerves which carry afferent fibers have ganglia composed
of clusters of their cell bodies situated just outside the brain wall
(Fig. 92). Likewise the efferent fibers in the spinal and the cranial
nerves are similar in that they arise from cell bodies inside the wall
of the neural tube. In the spinal nerves these cell bodies lie in the
ventral and lateral horns of the gray matter of the cord. In the cranial
nerves their position is homologous for they lie in clusters (nuclei) in
the basal plate of the brain wall (cf. Figs. 85 and 91).
 
If one considers these general facts it becomes apparent that,
although the cranial nerves differ from the spinal nerves in many
respects, we find the same types of neurons involved and the same
characteristic difference in the position of the cell bodies which so
clearly sets apart afferent and efferent fibers. Put in another way, the
cranial and spinal nerves contain the same types of components
differently grouped. It will be helpful to keep this in mind in considering the various cranial nerves.
 
The Olfactory Nerve (I). Unlike other sensory nerves the
olfactory nerve lacks a ganglion. It is peculiar, also, in that all its
fibers are non-medulla ted. These fibers arise from cells in the epithelial
layer lining the olfactory pits (Fig. 93). Thence they grow centripctally into the olfactory bulbs. In the olfactory bulbs the fibers
of the nerves terminate in synapses with other neurons which relay
the impulses along the olfactory tracts (Fig. 87) to centers in the
r hinencephalon .
 
The Optic Nerve (II). As is the case with the olfactory nerve,
the optic nerve fibers arise from peripherally located cells and grow
centripetally. Neuroblasts situated in the sensory layer of the retina
in close association with its photosensitive cells send out processes
which leave the optic cup through the choroid fissure. These fibers
then traverse the grooved ventral surface of the optic stalk and enter
the brain in the diencephalic floor. At their point of entrance the two
optic nerves^ intersect. At the intersection, part of the fibers from each
nerve cross over to the opposite side so that each eye has central
connections with both sides of the brain. It will be recalled that the
point of the nerve intersection and fiber crossing is known as the optic
 
^ Since both the photosensitive cells themselves and the retinal ganglion cells
sending out their associated nerve fibers arise in the walls of the optic cup, which is
in turn an evaginalion of the embryonic fore-brain, what we commonly call the optic
nerve is, strictly speaking, not a nerve but a fiber tract arising within a modified
portion of the brain wall.
 
 
 
166
 
 
THE DEVELOPMENT OF THE NERVOUS SYSTEM
 
 
Semicircular
 
Canals
 
 
 
Langleys Ganglion
 
 
Submaxillary
Gland '
 
 
Muscle Layers of
Intestinal Walls
 
 
Cells of Myenteric
Plexus Serving as
Terminal Ganglion
 
 
Fig. 91. Diagram showing the central relations of the various types of
fibers in cranial nerves. (Patten: ‘‘Human Embryology,” The Blakiston
Cpmpany.) It should be emphasized that the diagram is a schematic composite and that no one cranial nerve contains all the types of fibers shown.
 
 
 
THE CRANIAL NERVES
 
 
167
 
 
chiasma (Fig. 65). From the chiasma the fibers pass along the lateral
walls of the diencephalon to the visual reflex centers in the superior
colliculi (Fig. 80, arc 5b), and by way of relay centers (geniculate
nuclei) impulses are sent also to visual correlation centers in the cerebral cortex.
 
The Oculomotor Nerve (III). As its name implies, the oculomotor nerve contains efferent fibers to muscles moving the eye. The
cluster of neuroblasts from which it arises is located in the basal plate
of the mesencephalon. Its fibers have internal relations in general
comparable to those indicated in figure 91 for the fibers of nerve XII
leading from the somatic efferent nucleus to the intrinsic muscles of
the tongue. Emerging from the floor of the mesencephalon (Figs. 92
and 93) they pass directly to the orbital region and innervate the
inferior oblique, and the superior, inferior, and internal rectus muscles
of the eyeball.
 
The Trochlear^ Nerve (IV). The trochlear nerve is a motor nerve
to the superior oblique muscle of the eye. Its nucleus of origin, like
that of the third nerve, is located in the basal plate of the mesencephalon. It is peculiar in that its fibers do not leave directly from the
ventro-lateral walls of the brain as usually happens in a motor nerve.
Instead they pass to the dorsal wall of the mesencephalon (Figs. 92
and 93) and cross before emerging.
 
The Trigeminal Nerve (V). The trigeminal nerve takes its
name from the fact that it has three main divisions, the ophthalmic,
the maxillary, and the mandibular (Figs. 89, 90, and 92). As is indi
 
Fig. 91 — {Continued)
 
As was the case with the spinal nerves (Fig. 85), the efferent nuclei or
clusters of efferent nerve cells are located ventro-laterally, in the basal plate
of the neural tube wall. The afferent fibers of the cranial nerves have their
cell bodies located outside the neural tube in ganglia (cf. Fig. 92). The
afferent nuclei or columns in the alar plate of the walls of the neural tube are
clusters of cell bodies belonging to neurons which relay the incoming impulses to other parts of the brain. (Cf. Fig. 80, arc 5a.) For further explanation
see text.
 
 
® Not even sufficient knowledge of Greek to recognize in the word trochlear the
root meaning pulley is of much immediate help in understanding its significance as
used in anatomy. One has to find that the nerve takes its name from an old appellation of the superior oblique musdle to which it runs. This muscle was formerly known
as the trochlear muscle because its tendon passes through a pulley-like fibrous loop
attached to the eye-socket.
 
 
 
Superior ganglion (9)
 
 
 
THE CRANIAL NERVES
 
 
169
 
 
cated by its large semilunar ganglion, the fifth nerve has great
numbers of sensory fibers. There are, nevertheless, enough motor
fibers associated with its mandibular branch so it must be regarded
as a mixed nerve (Figs. 91 and 94). The names of its branches clearly
indicate its distribution to the facial region. Its sensory fibers have
relations of the nature indicated in figure 91 by the fiber leading from
the skin of the lip to the general somatic afferent column.
 
The Abducens Nerve (VI). The abducens nerve takes its name
from the fact that it controls the external rectus muscle, contraction
of which makes the eyeball rotate outwards. Its nucleus lies in the
basal plate of the myelencephalon from which its fibers emerge
ventrally just caudal to the pons, and pass toward the orbit (Figs. 92
and 94).
 
The Facial Nerve (VII). The facial nerve is primarily motor
but the presence of the geniculate ganglion on its root shows that it
carries also some sensory fibers. A large part of its sensory fibers pass
by way of the chorda tympani branch (Figs. 91 and 92) to join the
mandibular branch of the fifth nerve. These fibers are concerned with
the sense of taste. Its motor fibers arise from a nucleus situated in the
basal plate of the myelencephalon and innervate the muscles of
facial expression.
 
The Auditory Nerve (VIII). At first the ganglionic mass from
which the fibers of the eighth nerve arise is closely associated with the
geniculate ganglion of the seventh nerve (Fig. 92). Gradually these
ganglia become entirely distinct. Still later the ganglion of the eighth
nerve divides into two parts, a vestibular ganglion and a spiral ganglion. With the division of the ganglion, the nerve fibers arising from
its cells becorhe grouped into two main bundles, one associated with
each ganglion. Meanwhile the otic vesicle has differentiated into twp
distinct parts, the cochlea, which is the organ of hearing, and the
group of semicircular canals which, together with the utriculus and
sacculus, constitute an organ of equilibration. The spiral ganglion
and the cochlear branch of the eighth nerve become associated with
the auditory part of the mechanism. The vestibular ganglion and its
branch of the eighth nerve become associated with the semicircular
canals. The auditory and equilibratory fibers have the general relations indicated in figure 91 by the sensory fibers connecting, respectively, with the cochlea and with the ampullae of the semicircular
canals.
 
 
 
170
 
 
THE DEVELOPMENT OF THE NERVOUS SYSTEM
 
 
Trochlear nerve (N.XST)
 
 
Fourth ventricle
 
 
Posterior choroid
plexus
 
 
Eye muscle
primordium
 
Nerve 21.
 
 
Auditory
 
vesicle
 
 
Pharynx
 
 
Mesocoele
 
f
 
 
Oculomotor
nerve (N.in)
 
 
 
• Diocoele
 
 
Post. ,
communicating
~ branch int.
carotid a.
 
 
Optic stalk
 
Olfactory
bulb of
telencephalon
 
Olfactory nerve
 
Nasal chamber
 
Oronasal membrane just
prior to its rupture
 
 
Fig. 93. Drawing (X 14) of parasagittal section of head of 15 mm, pig
embryo. The section is to the right of the mid-line, in a plane especially
favorable for showing the relations of the nasal pits and of the olfactory (I)
and oculomotor (III) nerves.
 
 
The Glossopharyngeal Nerve (IX). The glossopharyngeal is
a mixed nerve but by far the greater number of its fibers are sensory.
The ganglion cells from which these sensory fibers arise are grouped
in two clusters, one near the root of the nerve (superior ganglion),
and one farther peripherally on its course (petrosal ganglion) (Figs. 92
and 94). The cell bodies in the superior ganglion give rise to fibers
which innervate a small cutaneous area of the external ear. These
neurons are, therefore, general somatic afferent. The petrosal ganglion
contains cell bodies which give rise to visceral afferent fibers. Some
of these, being concerned with general sensibility in the region about
the root of the tongue, are general visceral afferent (Fig. 91). Other
fibers innervate taste buds in the back parts of the tongue and so are
classified as special visceral afferent. The efferent fibers arise from
nuclei in the basal plate of the myelencephalon. Some of these fibers
innervate the stylopharyngeus muscles. These are special visceral
 
 
 
THE CRANIAL NERVES
 
 
171
 
 
efferent neurons. Others are secretory fibers to the parotid gland by
way of the otic ganglion. These are general visceral efferent fibers.
 
The Vagus Nerve (X). The vagus is a mixed nerve carrying five
different types of fibers. General somatic afferent fibers arise from
cells in its jugular ganglion and extend peripherally to the skin in
the region of the external ear. General visceral afferent fibers arise
from cells in the nodose ganglion and extend peripherally to the
pharynx, larynx, trachea, esophagus, and the thoracic and abdominal
viscera. Special visceral afferent fibers having cells of origin in the
nodose ganglion carry gustatory impulses from scattered taste buds
in the region of the epiglottis. From nuclei of origin in the myelencephalon special visceral efferent fibers extend to striated muscles
of the pharynx and larynx. General visceral efferent fibers run to
various terminal ganglia whence the impulses are relayed to the
visceral musculature over second-order motor neurons (Fig. 91).
 
 
 
Fourth ventricle
Ganglion nerve 32111
 
Ganglion
superius
 
Auditory vesicle
 
Jugular
ganglion N.X,
 
Petrosal
ganglion
N.3X
 
Nodose
ganglion
N.X
Thymus
 
m
 
Ant.
 
cardinal
vein
 
 
Facial nerve (N.IQI)
 
Motor component
of mandibular
division N. DC
 
Trochlear
nerve
 
Gasseripn
ganglion N.!!
 
Oculomotor
nerve
 
Optic stalk
 
Abducens
nerve
 
Pharynx
Nasal pit
 
 
Hypoglossal
nerve (NXE)
 
 
Fig. 94. Drawing (X 14) of parasagittal section of head of 15 mm. pig
embryo. The plane of section is slightly farther to the right than that shown
in the preceding figure. It is particularly favorable for showing the position
of origin, and the ganglia, of the trigeminal (V), glossopharyngeal (IX), and
vagus (X) nerves.
 
 
 
172
 
 
THE DEVELOPMENT OF THE NERVOUS SYSTEM
 
 
The Accessory Nerve (XI). The commissural ganglion (Fig. 92)
which appears so closely associated with the accessory nerve is really
a continuation of the jugular ganglion of the vagus. Froriep’s ganglion
usually disappears in the adult so the accessory nerve is left without
ganglia. Its fibers, practically all efferent, originate not only from the
posterior part of the myelencephalon but also from the first five or six
segments of the spinal cord (Fig. 92). A large number of the fibers of
the accessory nerve run with the general visceral efferent fibers of the
vagus nerve to sympathetic ganglia from which the motor impulses
are relayed to the smooth muscle of the viscera. Other fibers (special
visceral efferent) from the accessory join similar vagus fibers to
striated muscles in the pharynx and larynx. Most of the fibers arising
from the cervical part of the cord turn off in the external ramus to end
in the trapezius and sterno-cleido-mastoid muscles.
 
The Hypoglossal Nerve (XII). The hypoglossal nerve is composed practically entirely of somatic motor fibers. They arise from an
elongated nucleus in the posterior part of the myelencephalon
(Fig. 91) and emerge in several separate roots which join to form a
single main trunk (Fig. 92). Peripherally they are distributed to the
muscles of the tongue.
 
 
 
==Chapter  9==
 
 
Tke Development of tke Digestive and
Respiratory Systems and tke Body Cavities
 
 
I. The Digestive System
 
In considering the structure of young embryos we traced the
walling in of the primitive gut tract by entoderm, its regional division
into fore-gut, mid-gut, and hind-gut, and the establishment of the
oral and anal openings by the breaking through of the stomodaeal
depression cephalically and the proctodaeal depression caudally
(Figs. 16, 37, and 65). In embryos of from 9 to 12 mm., local differentiations in the gut tract clearly foreshadowed the development of certain
organs and gave indications of the impending establishment of others.
Starting with these now familiar conditions as a basis we shall trace
briefly the more important steps by which the adult structure and
relations of the various organs are established.
 
Oral Cavity. The oral cavity of the adult and its various special
structures are derived from the stomodaeal region of the embryo.
The entire face and jaw complex is formed from processes which arise
about the margins of the stomodaeum. The progressive growth of
these abutting structures results in a deepening of the originally
shallow stomociaeal depression to form the oral cavity. An idea of the
extent to which this growth progresses can be gained from the fact
that the point of rupture of the stomodaeal membrane (oral plate)
comes to lie, in the adult, at about the level of the tonsils. So many
processes of special interest are involved in the changes which go on
in this region that it has seemed wise to dismiss them for the present
with this general statement and return to them later for special
consideration (Chap. 13).
 
The Pharyngeal Region. In embryos of about 4 to 6 mm. the
cephalic part of the fore-gut has become differentiated as the pharynx.
Greatly compressed dorso-ventrally, the pharynx has a wide lateral
extent with a series of pouch-Uke diverticula pushing out on either
side between the branchial arches (Figs. 41, B, and 95). This stage of
 
173
 
 
 
174 DEVELOPMENT OF THE DIGESTIVE AND RESPIRATORY SYSTEMS
 
 
 
Fig. 95. Lateral view of the pharynx of a young mammalian embryo with
its relations to important adjacent structures indicated. (Patten: “Human
Embryology,” The Blakiston Company.) The contours of the visceral arches
are suggested and the broken lines between them indicate the location of the
external gill furrows. The drawing is semischematic and equally applicable
to conditions in a 4-week human embryo or a 5 mm. pig embryo.
 
 
the pharynx is a recapitulation of conditions which had an obvious
functional significance in water-living ancestral forms. For the
pharyngeal pouches of the mammalian embryo are homologous with
the inner portion of the gill slits. The repetition of race history is here,
as so frequently happens, slurred over. Although in the mammalian
embryo the tissue closing the gill clefts becomes reduced to a thin
membrane consisting of nothing but a layer of entoderm and ectoderm with no intervening mesoderm whatever (Fig. 62), this membrane rarely disappears altogether. Occasionally the more cephalic
of the pharyngeal pouches break through to the outside, establishing
op>en gill slits, but in such cases the opening is very short-lived and the
clefts promptly close again.
 
Like many other vestigial structures which appear in the development of higher forms, the pharyngeal pouches give rise to organs
having a totally different functional significance from the ancestral
structures they represent. It is as if, to speak figuratively, nature was
too economical to discard entirely structures rendered functionally
 
 
 
THE DIGESTIVE SYSTEM
 
 
175
 
 
obsolete by the progress of evolution, but rather conserved them in
part at least and modified them to carry on new activities.
 
Discussion of the processes whereby various parts of the original
pharyngeal apparatus become converted into other structures would
involve too many details to permit of inclusion here. A bare statement
of what these pharyngeal derivatives are and where they arise must
suffice.
 
The main pharyngeal chamber of the embryo, that is, the central
portion in distinction to its various diverticula, becomes converted
directly into the pharynx of the adult. In this process its lumen is
simplified in configuration and relatively reduced in extent. An
important factor in these changes is the separation of various diverticula from the main part of the pharynx. The cell masses thus originating migrate into the surrounding tissues and there undergo divergent
differentiation.
 
The first pair of pharyngeal pouches, extending between the
mandibular and hyoid arches, come into close relation at their distal
ends with the auditory vesicles (Fig. 60). They give rise, on either side,
to the tympanic cavity of the middle ear and to the Eustachian tube.
 
The second pair of pouches become progressively shallower and
 
 
 
Fig. 96. Schematic diagrams indicating the origin and later interrelations
of some of the derivatives of the embryonic pharynx. (Modified from SwaleVincent.) In the schematic cross section of one lobe of the adult thyroid (B)
the numbers attached to parathyroids and thymus refer to their pouches of
origin as indicated in A. Note that the thymic tissue which arises from the
fourth pouch is drawn in lightly to indicate that it is not well developed in all
mammals.
 
 
 
176 DEVELOPMENT OF THE DIGESTIVE AND RESPIRATORY SYSTEMS
 
 
 
Nodose ganglion
of vagus nerve
 
Pharyng.111 ThymusIII
Larynx
 
Hypoglossal nerve
 
Lingual branch
mandibularTT
TongueMaxillary,
division nerve
Internal carotid artery
 
Oral cavity
Lateral telencephalic
vesicles
 
 
Premusc.
 
 
Esophagus
Pharynx cervical
sympathetic
ganglion '
 
Recurrent ^
Pharyng. laryngeal n,
 
. ^ Ant cardinal V.
 
ThymusIII ^
 
Int. carotid a.
 
 
Premusc.
Meckels cart
Tongue
Oral cavity
 
 
Thyroid gland
 
 
Mandible
 
 
Maxilla
 
Nasal septum Maxillary
division of r£
Olfactory n. f^Q^Q\ chamber
 
Lot.telencephotic
 
vesicles
 
 
Fig. 97. Drawings (X 11) of transverse section through the pharyngeal
region of a 15 mm. pig embryo. A, Upper laryngeal level. B, Level of third
 
 
 
 
THE DIGESTIVE SYSTEM
 
 
177
 
 
 
Fig, 98. Pharynx of 15 mm. pig embryo schematically represented in
relation to the outlines of other cephalic structures. (Adapted from several
sources.) The heavy horizontal lines indicate the levels of the correspondingly
lettered sections in the preceding figure.
 
less conspicuous. Late in fetal life the faucial tonsils are formed by the
aggregation of lymphoid tissue in their walls, and vestiges of the
pouches themselves persist as the supratonsillar fossae.
 
From the floor of the pharynx, in the mid-line at about the level
of the constriction between the first and the second pair of pharyngeal
pouches, a divf^rticulum is formed which is destined to give rise to the
thyroid gland (Figs. 95 and 96). The mass of epithelial cells making,
up the walls of this evagination push into the underlying mesenchyme,
break away from the parent pharyngeal epithelium, and migrate
down into the neck (Figs. 97, D, 98, and 138). Only after arriving in its
 
 
Fig. 97 — {Continued)
 
pharyngeal pouch. C, Level of fourth pharyngeal pouch. D, Through the
neck caudal to the level of the pharynx and larynx.
 
The level of each of the sections represented in this figure is indicated
by the correspondingly lettered line in the next figure.
 
Abbreviations: Br. gr. Ill, third branchial groove; N. XII, hypoglossal
nerve; Pharyng. Ill, third pharyngeal pouch; Pharyng. IV, fourth pharyngeal pouch; Preinusc., premuscular concentration of mesenchyme.
 
 
 
178 DEVELOPMENT OF THE DIGESTIVE AND RESPIRATORY SYSTEMS
 
 
definitive location, relatively late in development, does the thyroid
primordium undergo its final characteristic histogenetic changes.
 
The third and fourth pairs of pharyngeal pouches give rise to outgrowths which are involved in the formation of the parathyroid glands,
the thymus, and the post-branchial bodies. There are two pairs of
parathyroid glands, usually spoken of as parathyroids III and parathyroids IV because they arise from the third and the fourth pharyngeal pouches (Figs. 96, A, and 98). As was the case with the thyroid,
the parathyroid primordia soon break away from their points of
origin and migrate into the neck. Here, as their name implies, they
are positionally more or less closely associated with the thyroid.
Parathyroids IV are particularly likely to become adherent to the
thyroid capsule or even to become partially embedded in the substance of the gland (Fig. 96, B).
 
The thymus in the mammalian group is derived from outgrowths
from the more ventral portions of the third and fourth pharyngeal
pouches (Figs. 96, A, and 98). In different species there is considerable
difference in the relative conspicuousness of the two pairs of primordia.
In most of the higher mammals the primordia arising from the third
pouches are much the more important thymic contributors. This is
the situation for the pig as well as for man. In pig embryos of the
15-17 mm. range, however, it is usually possible to make out a
rudimentary thymus IV (Fig. 98). The characteristic histogenetic
changes in the thymus occur relatively late in development, and even
in 15-17 mm. embryos thymus III is but a slender pair of cell cords
growing into, the tissue at the base of the neck (Fig. 97, C, D).
 
The post-branchial bodies are structures of problematical significance. Arising as they do on the caudal face of the fourth pharyngeal pouches, many observers regard them as rudimentary fifth pharyngeal pouches. When the post-branchial bodies detach themselves from
their site of origin they lie in the loose mesenchymal tissue (Fig. 97, D)
close to the route followed by the thyroid gland in its descent. As
the thyroid expands laterally the tissue of the post-branchial bodies
becomes embedded in it on either side (Fig. 96, D). There is still
difference of opinion as to whether this post-branchial tissue contributes to the formation of true thyroid glandular tissue or remains
merely as an inconspicuous vestigial cell mass in the substance of the
thyroid gland. Those who are convinced that these buds from the
caudal face of the fourth pouches form true thyroid tissue generally
designate them as lateral thyroid primordia. The non-committal
 
 
 
 
 
 
 
 
 
 
180 DEVELOPMENT OF THE DIGESTIVE AND RESPIRATORY SYSTEMS
 
 
it p iphysis T halamus
 
Mesencephalon
 
 
Peduncidus cerebri
Cerebellum
 
ChorioidoU plexus^ ventricle 4
 
Tela of ventricle 4
M yelencephalon
Epiglottis
 
 
Esophagus !
 
 
Tela chorioldea
 
Lat. chorioid plexus
 
Corpus striatum
 
 
Ilypophys is
Lobus olf actor ius
Turbinate anlage
 
J^aiate
 
 
Spinal cord
Trachea
 
A orta .
 
R. atrium *
 
R, bronchus .
 
Dorsal aorta ^
 
Inf. vena cava ,
Stomach
Pancreas
Suprarenal gland
Genital gland
Duodenum
 
 
 
Metanephros
 
Colon
 
L. mesonephric duct
 
Uret^
 
Urogenital sinus with mesonephric duct
 
 
Gall bladder
Small intestine
 
Urethra
 
 
Bladder
 
Anus
 
 
Rectum
 
 
Fig. 100. Pig embryo of 35 mm. dissected to the mid-line to show the relations
of the alimentary tract. (After Prentiss.)
 
The region of narrowing where the trachea becomes confluent with
the gut tract may be regarded as the posterior limit of the pharynx.
From this point to the dilation which marks the beginning of the
stomach the gut remains of relatively small and uniform diameter and
becomes the Esophagus (Figs. 99 and 100). The original entodermal
lining of the primitive gut gives rise only to the epithelial lining of the
esophagus and to its glands. The connective tissue and muscle coats
 
 
 
THE DIGESTIVE SYSTEM
 
 
181
 
 
of the esophagus are derived from mesenchymal cells which gradually
become concentrated about the original epithelial tube (Fig. 97, D).
 
Stomach. The region of the primitive gut which is destined to
become the stomach is, in embryos of 10 mm., more or less clearly
marked by a dilation (Figs. 60 and 64). Its shape, even at this early
stage, is strikingly suggestive of that of the adult stomach. Its position
is, however, quite different.
 
In young embryos the stomach is mcsially placed with its cardiac
(esophageal) end somewhat more dorsal in position than its pyloric
(intestinal) end. It is slightly curved in shape, with the convexity
facing dorsally and somewhat caudally and the concavity facing
vcntrally and somewhat cephalically (Fig. 99). The positional changes
by which it reaches its adult relations involve two principal phases:
(1) the stomach is bodily shifted in position so its long axis no longer
lies in the sagittal plane of the embryo but diagonally across it, and (2)
there is a concomitant rotation of the stomach about its own long axis
so that its original dorso-ventral relations are altered as well. These
changes in position are schematically indicated in figure 101. The
shift in axis takes place in such a manner that the cardiac end of the
stomach comes to lie to the left of the mid-line and the pyloric end
to the right. Meanwhile rotation has been going on. In following the
progress of rotation the best point of orientation is the line of attachment of the primary dorsal mesentery (Fig. 101). While the stomach
occupies its original mesial position the mesentery is attached to it
mid-dorsally, along its convex curvature (Fig. 111). As the stomach
continues to grow in size and depart from the sagittal plane of the
body it rotates about its own long axis. The convex surface to which
the mesentery is attached and which was at first directed dorsally, now
swings to the left. Since the long axis itself has in the meantime been
acquiring an inclination, the greater curvature of the stomach comes
to be directed somewhat caudally as well as to the left (Fig. 101, D).
 
The Omental Bursa. The change in position of the stomach
necessarily involves changes in that part {dorsal mesogastrium) of the
primary dorsal mesentery which suspends it in the body cavity
(Figs. 101 and 111). The dorsal mesogastrium is pulled after the
stomach and forms a pouch, known as the omental bursa. The opening from the general peritoneal cavity into the bursa is known as the
epiploic foramen {foramen of Winslow). (See arrow in Fig. 101, D.)
 
The Intestines. The primitive gut is at first a fairly straight tube
extending throughout the length of the body. Near its midpoint it
 
 
 
182 DEVELOPMENT OF THE DIGESTIVE AND RESPIRATORY SYSTEMS
 
 
Esophagus
 
 
A
 
 
stomach
 
 
Attachment
dorsal
mesogastrium
* ^to body-wall
 
 
 
Duodenum
 
A. B.
 
 
 
Fig. 101. Diagrams illustrating the changes in position of the stomach,
and the formation of the omental bursa. The broken line indicates the attachment of the mesogastrium along that surface of the stomach which is primarily mid-dorsal. The arrow passes through the epiploic foramen into the
omental bursa.
 
 
opens ventrally into the yolk-sac (Figs. 37 and 40). The first conspicuous departure from this condition is the formation of a hairpin-shaped
loop in the future intestinal region. The closed end of this loop extends
into the belly-stalk (Figs. 60 and 64). The yolk-stalk connects with
the gut at the bend of the loop and forms an excellent point of orientation in following the series of foldings and kinkings by which the
definitive configuration of the intestinal tract is established. The
attachment of the yolk-stalk is just cephalic to what will be the point
of transition {ileo-cecal valve) from small to large intestine. Thus all the
gut between the yolk-stalk and the stomach becomes small intestine,
and, except for about 2 feet of the terminal part of the small intestine,
the gut caudal to the yolk-stalk goes to form the large intestine.
 
The characteristic coiling of the small intestine is the first to
become evident (Figs. 100 and 102, B). The only change of significance which has taken place meanwhile in the large intestine is the
establishment of the cecum as a definite pouch-like diverticulum
(Fig. 102, B). But the large intestine does not remain long uncoiled.
In the pig it attains a greater length and a more complicated configuration than in man, its final condition being that of a loop closely
spiraled on itself (Fig. 102^ E, F) and occupying a very conspicuous
position among the abdominal viscera (Fig. 1).
 
 
 
83
 
 
intestine
 
 
Cecum
 
 
 
intestine,
 
cut
 
 
Cecum
 
 
Duodenum
 
 
Colon
 
 
 
Cecum
 
 
Descending
 
colon
 
 
 
Ileum
 
 
Cecum
 
 
Fig. 102. Diagrams illustrating the development of the intestinal tract in
pig embryos. (After Lineback.) A, 12 mm.; B, 24 mm.; C, 35 mm.; D, 75
mm.; E, 110 mm.; F, 1 month after birth.
 
A to C show the entire gastro-intestinai tract viewed from the left side. D
to F show the large intestine only. The relations of the last three figures will
be made apparent by comparing C and D, taking for orientation the cecum
and that part of the duodenum which loops across the large intestine.
 
 
 
184 DEVELOPMENT OF THE DIGESTIVE AND RESPIRATORY SYSTEMS
 
 
Rectum and Anus. The attainment of adult conditions at the
extreme caudal end of the digestive tract is so intimately associated
with the development of the urogenital openings that changes in the
cloacal region as a whole can more profitably be taken up later in
connection with the reproductive organs.
 
The Liver. Wry early in development the diverticulum which
gives rise to the liver is budded off from the entoderm of the primitive
gut tract. In embryos as small as 4 mm. the hepatic diverticulum can
be identified extending ventrad from the duodenal portion of the gut
 
 
Pharynx —
 
LaryngO’
tracheal tvagination
 
 
Glandular
 
•cords
 
Gall-bladder
 
 
 
Yolk-sac
 
 
! Hepatic
diverticulum
 
 
A
 
 
 
Fig. 103. Reconstructions of the gut tract in the region of the hepatic and
pancreatic diverticula.
 
A, From 4 mm. pig embryo in the Carnegie Collection.
 
B, From 5.5. mm. pig embryo. (After Thyng, modified.)
 
(Fig. 103, A). This original diverticulum, in embryos of 5 to 6 mm.,
has become clearly differentiated into several parts (Figs. 40 and 103,
B). A maze of branching and anastomosing cell cords grows out from
it ventrally and cephalically. The distal portions of these cords give
rise to the secretory tubules of the liver and their proximal portions
form the hepatic ducts. Originating where the hepatic ducts become
confluent is a dilation which is the primordium of the gall-bladder.
Closer to the gut tract is a separate outgrowth of cells which constitutes the ventral primordium of the pancreas.
 
The later changes in the biliary duct region are shown in figures
104 and 105. The gall-bladder elongates very rapidly and its terminal
portion becomes distinctly saccular. The narrower proximal portion
of this limb of the diverticulum becomes the cystic duct. That portion
of the original diverticulum which lies toward the duodenum from
 
 
 
THE DIGESTIVE SYSTEM
 
 
185
 
 
the entrance of the hepatic ducts is called the common bile duct
(ductus choledochus).
 
The mass of branching and anastomosing tubules which are distal
continuations of the hepatic ducts constitute the actively secreting
portion of the liver. Their position and extent in embryos of various
ages are shown in figures 40, 65, 99, 100, and 106. The organization
of these secreting units in the liver is quite characteristic. The hepatic
tubules are not paeked so closely together in a framework of dense
connective tissue as is usually the case in massive glands. Surprisingly
 
 
 
Fig. 104. Reconstruction of gut
tract of a 9.4 mm. pig embryo showing pancreatic and hepatic diverticula
(X 33). C'ompare with figure 60.
 
little connective tissue is formed between them and the intertubular
spaces become pervaded by a maze of dilated and irregular capillaries
known as sinusoids. This tremendously extensive meshwork of small
blood vessels among the cords of liver cells is a condition which we
shall find of great importance in the development of the circulatory
system in this region.
 
The Pancreas, The pancreas makes its appearance in the same
region and at about the same time as the liver. It is derived from two
separate primordia which later become fused. One primordium arises
dorsally, directly from the duodenal entoderm; the other ^ arises
 
^ The ventral pancreatic diverticulum in a certain number of cases may be paired
instead of single. It is probable that the usual unpaired diverticulum seen in mammalian embryos represents originally paired ventro-lateral diverticula.
 
 
 
186 DEVELOPMENT OF THE DIGESTIVE AND RESPIRATORY SYSTEMS
 
 
Hepatic ducts
 
 
 
Fig. 105. Reconstruction of pancreas and hepatic duct system of 20 mm. pip^
embryo. (After Thyng, modified.)
 
ventrally, from the entoderm of the hepatic diverticulum (Fig. 103).
As they increase in size, these two buds approach each other and
eventually fuse (Figs, 104 and 105). The glandular tissue of the pancreas is formed by the budding and rebudding of cords of cells derived
from this primordial mass. The terminal parts of the cords gradually
take on the characteristic configuration of pancreatic acini while their
more proximal portions form the duct system draining the acini.
 
There is, in different forms, considerable variation in the relations
of the main pancreatic ducts which persist in the adult. In the horse
and dog, for example, there are two ducts, a dorsal one (duct of
Santorini) which opens directly into the duodenum, and a ventral
one (duct of Wirsung) which opens into the duodenum by way of the
common bile duct. These two ducts represent the two original pancreatic buds which appear in mammalian embryos generally. In
other forms the two original ducts become confluent within the
pancreas and the terminal portion of one duct only is retained. Thus
in the sheep and in man the ventral duct persists communicating with
the duodenum by way of the common bile duct, while the terminal
portion of the dorsal duct usually atrophies. In the pig and the ox the
 
 
 
THE DIGESTIVE SYSTEM
 
 
187
 
 
arachnoid space
 
 
metcncephalon
posterior choroid plexus
 
metatela
 
 
ventricle IV'
 
floor of
myelencephalon
basilar artery
 
notochord
 
cord
 
 
mesencephalon
 
 
tuberculum
 
posterius
 
 
 
aorta
 
 
ganglion
 
Ro. 106 . Sagittal section of 24 nun.
 
 
Ig. intestine
 
ellantoic artery
(umbilicaQ
 
taU
'halltts
 
 
gUantoic artery
(umbilical
 
pig embryo. (After Minot.)
 
 
 
188 DEVELOPMENT OF THE DIGESTIVE AND RESPIRATORY SYSTEMS
 
 
ventral duct ordinarily disappears and the dorsal one persists as the
definitive pancreatic duct. /
 
II. The Respiratory System
 
The Trachea. The first indication of the diflferentiation of the
respiratory system is the formation of the laryngo-tracheal groove.
This mid-ventral furrow in the primitive gut tract appears in embryos
of about 4 mm. at the posterior limit of the pharyngeal region. As it
becomes deepened it is constricted off from the gut except for a narrowed communication cephalically. Once established as a separate
diverticulum, it grows caudad as the trachea, ventral to, and roughly
parallel with, the esophagus (Figs. 40, 65, and 103).
 
The anatomical relations of the trachea in the embryo, even in
early stages, are quite similar to adult conditions. We can recognize
its communication with the posterior part of the pharynx as the future
glottis, and the slightly dilated portion of the embryonic trachea just
caudal to the glottis as foreshadowing the larynx (Fig. 106).
 
Only the epithelial lining of the adult trachea is derived from
fore-gut entoderm. The cartilage, connective tissue, and muscle of
its wall arc formed by mesenchymal cells which become massed
about the growing entodermal tube (Figs. 72, 97, D, and 161).
 
 
 
Fig. 107. Stages in the development of the trachea, bronchi, and lungs in
the pig. (After Flint.) The pulmonary arteries are shown in black; the veins
arc cross hatched. Ep, bud of eparterial bronchus.
 
 
THE BODY CAVITIES AND MESENTERIES
 
 
189
 
 
The Bronchi and Lungs. As the tracheal outgrowth lengthens,
it bifurcates at its caudal end to form the two lung buds (Fig. 107, A).
These in turn continue to grow and rebranch, giving rise to the
bronchial trees of the lungs (Fig. 107). The terminal portions of the
branches where cell proliferation is exceedingly active tend to remain
somewhat bulbous. Later in development these terminal portions of
the bronchial buds become still more dilated, their epithelium thins
markedly, and they give rise to the characteristic air sacs of the lungs.
As was the ease with the trachea, th(‘ connective-tissue framework of
the lung is derived from mesenchyme, which collects about the entodcrmal buds during their growth. The entoderm gives rise only to the
lining epithelium of the bronchi and the air sacs. The pleural covering
of the lungs is derived from splanchnic mesoderm pushed ahead of
the lung buds in their growth (Fig. 113).
 
The lungs do not at first occupy the position characteristic of
adult anatomy. In very young embryos they lie dorsal to the heart
(Figs. 40 and 110). A little later when they have extended caudad,
they are situated dorsal to the heart and liver (Figs. 99 and 138). The
changes by which they eventually come to occupy their definitive
position in the thorax can best be taken up in connection with the
partitioning of the primitive coelom to form the body cavities of the
adult.
 
Ill, The Body Cavities and Mesenteries
 
The body cavities of adult mammals are the pericardial cavity
containing the heart, the paired pleural cavities containing the lungs,
and the peritoneal cavity containing the viscera lying caudal to the
diaphragm. All three of these regional divisions of the body cavity
^re derived from the coelom of the embryo. The general location and
extent of the coelom are already familiar from the study of young
embryos, but it may be well, nevertheless, to restate some of the more
important relations here.
 
The Primitive Coelom. The coelom arises by the splitting of the
lateral mesoderm on either side of the body into splanchnic and
somatic layers (Fig. 108, A).
 
It is, therefore, primarily a paired cavity bounded proximally by
splanchnic mesoderm and distally by somatic mesoderm. In forms
such as birds and mammals which have highly developed extraembryonic membranes, the coelom extends between the mesodermal
layers of the extra-embryonic membranes beyond the confines of the
 
 
 
190 DEVELOPMENT OF THE DIGESTIVE AND RESPIRATORY SYSTEMS
 
 
 
 
c.
 
 
D.
 
 
 
Fig. 108. Diagrams illustrating the development of the coelom and
 
mesenteries.
 
developing body. In mammalia where the nutrition of the embryo depends on the uterine relations established by the extra-embryonic
membranes, they develop exceedingly precociously. It is not surprising, in view of this fact, that the splitting of the mesoderm in
mammals occurs first extra-embryonically and progresses thence
toward the embryo (Fig. 108, A, B). When the body of the embryo is
folded off from the extra-embryonic membranes the extra- and intraembryonic portions of the coelom are thereby separated from each
 
 
THE BODY CAVITIES AND MESENTERIES
 
 
191
 
 
Other, the last place of confluence to be closed off being in the region
of the belly-stalk (Fig. 108, C). It is the intra-embryonic portion of
the primitive coelom, thus delimited, which gives rise to the body
cavities.
 
It will be recalled that the typical configuration of the mesoderm
indicated diagrammatically in figure 108 does not pertain in the
cephalic part of the embryo. The mesoderm in the head region consists of mesenchymal cells which wander in from the more definitely
organized mesoderm located farther caudally in the body. Thus the
intra-embryonic coelom established by the splitting of the lateral
mesoderm extends headwards only to the level of the pharynx, and
the heart is developed in its most cephalic portion (Figs. 43, 44, 109,
and 110).
 
The Mesenteries. The same folding process that separates the
embryo from the extra-embryonic membranes completes the floor
of the gut (Figs. 37 and 108). Coincidently the splanchnic mesoderm
of either side is swept toward the mid-line enveloping the now tubular
 
 
Common
Cardinal V
 
 
Umb Post. Neural
Card V. Tube
 
 
Aortic Archil
 
 
Pericardial
Reqion of
Coelom
 
 
Splanchnic
 
mesoderm
 
(cut)
 
 
Omphalomesenteric
 
Vein Vitellu3.e
 
Vascular Plexus
 
 
Dorsal Aortae
 
^ Somite
 
 
Somatic mesoderm
Amnjon (cut)
 
 
 
Splanchnopleure
of yolK-sac
 
 
Allantoic Stalk
and Vessels
 
Coelom
 
 
Fig. 109. Schematic plan of lateral dissection of young mammalian
embryo to show the relations of the pericardial region of the coelom to the
primary paired coelomic chambers caudal to the level of the heart. (Patten;
“Human Embryology,” The Blakiston Company.) The proportions of the
illustration were based in part on Heuser’s study of human embryos about
3 weeks old, but all the essential relationships shown are equally applicable
to pig embryos of 3 to 4 mm.
 
 
 
192 DEVELOPMENT OF THE DIGESTIVE AND RESPIRATORY SYSTEMS
 
 
 
Truncus
 
Arteriosus
 
 
AJJanloic
Stalk
(cut)
 
 
Pericardial
Fa^e
 
_ Septum
I ransversu
 
 
 
Dorsal
 
Mesocardium
 
 
Pericardial
Part of
Coelom
 
 
Arrow Q
 
throuqti D
 
 
m rough
Pleural
Canal
 
Me^nephros
bulqinq
info ^
 
PafriteL
 
 
UmbV.
VOM
 
 
Pleuro-pencardial
 
Fold
 
Comm Card V
 
 
Lunq Bud
 
Pleuro
PepjtiOneal
 
Liver
 
 
Peritonea
ot Coelo
 
 
 
Left Dorsal Aorta
Esophaqus
Pleural Canal
Comm Card V
Pleurc|;^^>g'itoneal
 
Liver
 
Septum Transversum
 
 
Fig. 110. Diagrams showing the relations of the pericardial, pleural, and
peritoneal regions of the coelom while they are still confluent. (Patten:
“Human Embryology,” The Blakiston Company.)
 
A, Semischematic frontal plan with body of embryo represented as if it
had been pulled out straight. The position of the lungs is indicated by broken
lines, and arrows indicate the location of the pleural canals, on either side,
dorsal to the liver. (Cf. part C of this figure.)
 
B, Lateral dissection to show left pleural canal opened with lung bud
bulging into it. (Modified from Kollmann.)
 
C, Schematized section diagonally through body at level of line in B.
 
 
digestive tract. The two layers of splanchnic mesoderm which thus
become apposed to the gut and support it in the body cavity are
known as the primary or common mesentery. The part of the mesentery dorsal to the gut, suspending it from the dorsal body-wall, is the
dorsal mesentery. The part of the mesentery ventral to the gut, attach
 
 
THE BODY CAVITIES AND MESENTERIES
 
 
193
 
 
ing it to the ventral body- wall, is the ventral mesentery (Fig. 108, D).
The primary mesentery, while intact, keeps the original right and
left halves of the coelom separate. But the part of the mesentery ventral to the gut breaks through very early, bringing the right and left
coelom into confluence and establishing the unpaired condition of the
body cavity characteristic of the adult (Fig. 108, F).
 
 
Truncus ^r+erio«oA
 
 
Pericardial Coelom
 
 
Left Ventricle
 
 
Loft Duct of Cuvier
 
 
 
T rachea
 
Lsophaqus
 
Xeft Anterior
Carxiinal \%in
 
Spinal Ganqlicn
 
Pleuroporicandlal Fold
Phrenic Nerve
Pleuroperitoneal Feld
Pleural Openmq
Dbraal hesoc^eetrium
Spleen
 
 
Allantois
 
Codiac Artery
Rarer cae
 
Superior MeaentericArtery
Doreal Mesenlery
 
Mcaooolon
 
Interior Meaenteric Artery
 
 
Fig. 111. Semidiagrammatic drawing showing the arrangement of the
viscera, body cavities, and mesenteries in young mammalian embryos.
(Patten: ‘‘Human Embryology,’’ The Blakiston Company.) In all essentials
the conditions here represented will be found in pig embryos of 12-15 mm.
 
In the region of the developing lungs the body is cut parasagittally, well
to the left of the mid-line, in order to show the relations of pleuropericardial
and pleuroperitoneal folds. Below the developing diaphragm, dissection has
been carried to the mid-line.
 
Abbreviations: G, gall-bladder; Y, yolk-sac.
 
 
 
194 DEVELOPMENT OF THE DIGESTIVE AND RESPIRATORY SYSTEMS
 
 
In the liver region the ventral mesentery does not entirely disappear. The liver arises, as we have seen, from an outgrowth of the gut
and in its development pushes into the ventral mesentery (Fig. 108,
E). The portion of the ventral mesentery between the liver and the
stomach persists as the gastro-hepatic omentum (ventral mesogastrium), and the portion between the liver and the ventral body- wall,
although reduced, persists in part as the falciform ligament of the
liver (Fig. Ill),
 
While the ventral mesentery, except in the region of the liver,
eventually disappears, almost the entire original dorsal mesentery
persists. It serves at once as a membrane supporting the gut in the
body cavity and a path over which nerves and vessels reach the gut
from main trunks situated in the dorsal body-wall. Its different regions
are named according to the part of the digestive tube with which they
are associated, as, for example, mesogastrium^ that part of the dorsal
mesentery which supports the stomach; mesocolon^ that part of the
dorsal mesentery supporting the colon, etc. (Fig. 111).
 
The Partitioning of the Coelom. The structure which initiates
the division of the coelom into separate chambers is the septum tramversum. The septum transversum appears very early in development
(Figs. 40 and 110) and is already a conspicuous structure in embryos
of 9 to 12 mm. (Figs. 64 and 111). Extending from the ventral bodywall dorsad, it forms a sort of semicircular shelf. Fused to the caudal
face of the shelf is the liver and on its cephalic face rests the ventricular
part of the heart.
 
The septum transversum is the beginning of the diaphragm. It
should be clearly borne in mind, however, that the diaphragm is a
composite structure embryologically, and that the septum transversum gives rise only to its ventral portion. The septum transversum
itself never grows all the way to the dorsal body-wall. Dorsal to the
septum transversum, the region of the coelom occupied by the heart
and lungs is confluent with that occupied by the developing gastrointestinal tract and liver (Fig. 110). Thus, although the division of
the coelom into thoracic and abdominal regions is clearly indicated
even at this early stage, it is not as yet complete.
 
The complete isolation from one another of the pericardial,
pleural, “and peritoneal portions of the coelom is brought about by
the growth of the paired pleuroperitoneal and pleuropericardial folds.
These folds arise from the dorso-lateral body-walls where the ducts of
Cuvier bulge into the coelom as they swing around to enter the sinus
 
 
 
THE BODY CAVITIES AND MESENTERIES
 
 
195
 
 
venosus of the heart (Figs. 110 and 113, B). The folds thus established
rapidly acquire a roughly triangular shape with their bases diagonally
along the body-wall and their apices extending toward, and eventually fusing with, the dorsal part of the septum transversum. Because
of their different fate and relations the cephalic parts of these primary
triangular folds have been called the pleuropericardial folds and their
caudal parts pleuroperitoneal folds (Fig. 111).
 
In the growth processes which lead toward the separation of the
thoracic from the abdominal region, the dorsal mesentery is caught
 
 
 
Fig. 112. Diagram indicating the embryological derivation of the various
regions of the diaphragm. (Modified from Broman.)
 
between the coiiverging septum transversum and the pleuroperitoneal
folds. Fusions along the lines of contact complete the diaphragm
(Fig. 112). The last place to close is near the dorsal body- wall on
either side of the mid-line where the pleuroperitoneal folds are bent
caudad by the growing lungs (Fig. 111). The manner in which the
margins of the pleuroperitoneal folds are forced caudad by the growing lungs is one of the chief factors in establishing the characteristic
dome-shaped configuration of the adult diaphragm.
 
Later in development, the margins of the diaphragm, especially
dorso-laterally, are invaded by body-wall tissue which contributes
the main part of the diaphragmatic musculature (Fig. 112).
 
In the thoracic region of the coelom, changes have in the meantime been going on which lead toward its subdivision into a pericardial
 
 
 
 
 
Fig. 113. Schematic diagrams showing the manner in which the pleural and
pericardial regions of the coelom become separated.
 
and paired pleural chambers. The cephalic portions of the primary
triangular folds arising about the ducts of Cuvier, constitute, it will
be recalled, the pleuropericardial folds (Fig. 111). The convergent
growth and ultimate fusion of the pleuropericardial folds isolate the
heart from the lungs (Fig. 113, B, C). The pleural cavities thus
established lie very far dorsally and are greatly restricted in extent as
compared with the pleural cavities of the adult. The schematic diagrams of figure 113 indicate the manner in which, with the growth
in mass of the lungs, the pleural cavities are expanded ventralwards
on either side of the heart.
 
 
 
 
==Chapter  10==
 
 
Tke Development of tke Urogenital System
 
 
The excretory and reproductive systems are so closely related
both anatomically and embryologically that they must inevitably be
considered together. Neither system is particularly simple in organization and the two of them together present quite a formidable array
of structures. Naturally the development of such a composite group
involves much of special interest to the embryologist. We shall see
organs formed by the association of parts which arise independently
at different places. Certain organs appear and then disappear completely without ever having become functional. Other organs fall into
disuse in their original capacity and begin to degenerate only to have
some part seized upon and salvaged by a new organ for a new function. We have, as it were, in the story of the development of these
systems many characters. Each character, individually, is doing things
of interest. Sooner or later their activities cross. The method of the
novelist in dealing with such a situation would be to switch from one
character to another to keep us in confusion and suspense as to what
is going to happen next. Our method in dealing with this embryological story must be exactly the reverse. To prevent the various
threads of the story from becoming entangled we must, as far as
possible, follow one group of structures from their origin to their
completion before becoming involved with another. Because the ,
excretory system appears earlier than the reproductive system, we
shall take it up first and follow it through. Then we must return
to young embryos and pick up the story of the internal reproductive
system, watching constantly its relations to that of the excretory
system with which we have already become familiar. Yet again we
must go back and follow the differentiation of the external genitalia.
Any attempt to develop all the threads of the story synchronously
would lead only to confusion.
 
I. The Urinary System
 
The General Relationships of Pronephros, Mesonephros, and
Metanephros. As a preface to the account of the development of the
 
 
 
 
198
 
 
THE DEVELOPMENT OF THE UROGENITAL SYSTEM
 
 
excretory organs in the pig, it is desirable to review certain facts about
the structure and development of the excretory organs in the vertebrates generally. Without such information as a background the
story of the early stages of the formation of these organs in a mammal
seems utterly without logical sequence. With it, the progress of events
encountered in mammalian development seems but natural, because
it is so clearly an abbreviated recapitulation of conditions which
existed in the adult stages of ancestral forms.
 
There occur in adult vertebrates three distinct excretory organs.
The most primitive of these is the pronephros which exists as a functional excretory organ only in some of the lowest fishes. As its name
implies, the pronephros is located far cephalically in the body. In
all the higher fishes and in the Amphibia the pronephros has degenerated and its functional role has been assumed by the mesonephros, a new organ located farther caudally in the body. In birds and
mammals a third excretory organ develops caudal to the mesonephros.
This is the metanephros or permanent kidney. All three of these
organs are paired structures located retroperitoneally in the dorsolateral body-wall. Each consists essentially of a group of tubules which
discharge by way of a common excretory duct. In the different
nephroi the tubules vary in structural detail but their functional
significance is, in all cases, much the same. They are concerned in
collecting waste material from the capillary plexuses associated with
them and excreting it from the body.
 
In the development of the urinary system of birds and mammals,
pronephros, mesonephros, and metanephros appear in succession,
furnishing an excellent epitome of the same evolutionary hi^ory
which may be learned in more detail from comparative anatomy.
In embryos sufficiently young we find only the pronephros established.
It consists of a group of tubules emptying into ducts, called the pronephric ducts, which discharge into the cloaca (Fig. 114, A).
 
A little later in development there arises in close proximity to
each pronephric duct a second group of tubules more caudal in
position than the pronephros. These are the mesonephric tubules.
In their growth they extend toward the pronephric ducts and soon
open into them (Fig. 114, B). Meanwhile the pronephric tubules
begin to degenerate and the ducts which originally arose in connection
with the pronephros are appropriated by the developing mesonephros.
After the degeneration of the pronephric tubules these ducts lose their
original name and are called mesonephric ducts because of their new
associations (Fig. 114, C).
 
 
 
THE URINARY SYSTEM
 
 
. 199
 
 
At a considerably later stage outgrowths develop from the mesonephric ducts near their cloacal ends (Fig. 114, C). These outgrowths
form the ducts of the metanephroi. They grow cephalo-laterad and
eventually connect with a third group of tubules which constitute the
metanephros (Fig. 114, D). With the establishment of the metanephroi or permanent kidneys, the mesonephroi begin to degenerate.
The only parts of the mesonephric system to persist, except in vestigial
form, are some of the ducts and tubules which, in the male, are
appropriated by the testis as a duct system (Fig. 114, D, right).
 
The Pronephros. In the embryos of birds and mammals the
pronephros is an exceedingly transitory structure. Very young
embryos show rudimentary proncphric tubules arising from the
 
 
 
Fig. 114 . Schematic diagrams to show the relations of pronephros,
mesonephros, and metanephros. (Patten: ‘‘Early Embryology of the Chick,”
The Blakiston Company.)
 
 
 
200
 
 
THE DEVELOPMENT OF THE UROGENITAL SYSTEM
 
 
intermediate mesoderm opposite a few of the somites lying well
cephalically in the body. (Birds, usually 5th to 16th somites; mammals, usually 6th to 14th somites.) The significance of these vestigial
tubules can readily be understood by comparing them with a plan
of the fully developed and functional pronephric tubules of which
they are a sketchy recapitulation (Fig. 115, A, B).
 
The pronephric duct arises at the level of the pronephric tubules by
the extension caudad of the distal end of each tubule till it meets and
fuses with the tubule behind it to form a continuous channel. The
 
 
 
 
 
Fig. 115. Drawings to show structure of nephric tubules.
 
A, Pronephric tubule from section through 12th somite of a 16-somite
chick embryo. (After Lillie.)
 
B, Diagram of functional pronephric tubule. (After Wiedersheim.)
 
C, Primitive mesonephric tubule with rudimentary nephrostome, from
section through 17th somite of 30-somite chick embryo.
 
D, Schematic diagram of functional mesonephric tubule of the primitive
type which retains the nephrostome. (After Wiedersheim.)
 
 
THE URINARY SYSTEM
 
 
201
 
 
 
Dorsal
 
Laterai^< J â–º Mesial
 
Ventral
 
 
Fig. 116. Drawings showing the development of the mesonephric tubules
in the pig. (Based on figures by McCallum and Lewis.) Abbreviation: T,
mesonephric tubule.
 
 
duct thus estal^lished continues to grow caudad beyond the level of
the tubules until it eventually opens into the cloaca (Fig. 114). Since
the pronephric tubules never become functional in mammalian
embryos, we need give them no further consideration. The pronephric
duct, however, becomes of importance through its subsequent relations to the mesonephros.
 
The Mesonephros. The mesonephros in young mammalian
embryos attains a high degree of development. In the pig it is especially large, being one of the most conspicuous organs in the embryo
(Figs. 59 and 60). Its tubules become highly differentiated and, pending the development of the metanephros, are believed to play an
active part in the embryo’s elimination of nitrogenous waste.
 
As was the case with the pronephric tubules, the mesonephric
 
 
202
 
 
THE DEVELOPMENT OF THE UROGENITAL SYSTEM
 
 
tubules are derived from the intermediate mesoderm. At the time the
tubules arise from it the intermediate mesoderm shows no trace of
segmentation. When viewed in reconstructions or dissections showing its longitudinal extent, it appears as a continuous band connecting
the somites with the lateral mesoderm. For this reason it is sometimes
spoken of as the nephrogenic cord. When the mesonephric tubules are
first budded off from the intermediate mesoderm they appear as cell
clusters very close to, but not in contact with, the mesonephric (old
pronephric) duct (Fig. 116, A). Once the process of tubule formation
starts, the nephrogenic tissue is soon completely converted into young
tubules, three or four tubules being formed opposite each somite from
about the 14th to the 32nd.
 
The newly formed tubules grow rapidly, extending toward the
mesonephric duct with which they soon attain connection (Fig. 116,
B). In birds a few of the more cephalic tubules show a rudimentary
nephrostome opening to the coelom, a condition comparable to that in
some of the lower forms in which the mesonephros is the adult
functional kidney (Fig. 115, C, D). Most if not all of the tubules in
the mammalian mesonephros slur over this phase in recapitulation
 
 
somite
 
 
 
neural tube>J
 
notochord/
 
dorsal aorta
afferent vessel
glomerulus
efferent vessel
 
 
^ mesonephric
duct
 
subcardinal
 
vein
 
 
posterior
 
cardinal vein
 
 
collecting vein
connecting
sulvand post*
cardinals
 
 
capsule
 
 
 
Fig. 117. Diagrams showing the relations of the blood vessels to a mesonephric
tubule. (Based on figures by McCallum.)
 
 
 
THE URINARY SYSTEM
 
 
203
 
 
and develop without a nephrostome (Figs. 116 and 117). Having no
ciliated nephrostome capable of drawing in coelomic fluid, such
tubules obtain their liquid content from the glomerular capillaries
(Fig. 117). This fluid serves to carry off by way of the mesonephric
duct waste materials from the blood stream. The discarding of the
nephrostome by the more specialized of the mesonephric tubules is an
interesting step toward the still more highly differentiated tubule we
shall encounter in the metanephros.
 
After they have attained connection with the duct, the mesonephric tubules elongate rapidly. Starting from a simple S-shaped
configuration, their pattern is complicated by a series of secondary
bendings (Fig. 116, C, F). This growth in length greatly increases
their surface exposure, thereby enhancing their capacity for interchanging materials with the blood in the adjacent capillaries.
 
The relations of the mesonephric tubules to the vascular system
are indicated schematically in figure 117. The mesonephros is fed by
many small arteries arising ventro-laterally from the aorta. Each of
these arterial twigs pushes into the dilated free end of a developing
tubule, forming from it a double-walled cup called a glomerular
(Bowman’s) capsule (Fig. 117, B). Within the capsule the artery
breaks up into a knot of capillaries known as the glomerulus. Blood
from the glomerulus leaves the capsule over one or more vessels
(efferent with reference to the glomerulus) which again break up into
capillaries. This time the capillaries form a plexus in close relation
to the body of the tubule in its tortuous course from glomerulus to
duct. From these capillaries the blood passes to collecting veins which
are for the most part peripherally located in the mesonephros and
more or less circularly disposed about it (Fig. 1 17, A). These collecting
veins form a freely anastomosing system connecting both with the
posterior cardinals and the subcardinals through which the blood is
eventually returned to the general circulation.
 
Although it is relatively more conspicuous earlier in development,
the mesonephros does not attain its greatest actual bulk until the
embryo has reached a size of about 60 mm. When the metanephros
becomes well developed, the mesonephros undergoes rapid involution
and ceases to be of importance in its original capacity. In dealing with
the reproductive system, however, we shall see that its ducts and some
of its tubules still persist and give rise to structures of vital functional
importance.
 
 
 
 
 
THE URINARY SYSTEM
 
 
205
 
 
The Metanephros. The metanephros has a dual origin. It arises
in part from the mesonephric duct, and in part from the intermediate
mesoderm. Of these separate primordia the diverticulum arising from
the mesonephric duct is the first to appear. In embryos as small as 5
or 6 mm. this metanephric diverticulum can usually be identified as a tiny
bud-like outgrowth just cephalic to the point where the mesonephric
duct opens into the cloaca (Fig. 118, A). Almost from its first appearance the blind end of the metanephric diverticulum is dilated, foreshadowing its subsequent enlargement to form the lining of the pelvis
of the kidney. The portion of the diverticulum near the mesonephric
duct remains slender, presaging its eventual fate as the duct draining
the kidney {ureter).
 
As the metanephric diverticulum pushes out, it collects about its
distal end mesoderm which has arisen from the nephrogenic cord of
intermediate mesoderm caudal to the mesonephros. The original
relations of this mass of mesoderm are soon entirely lost because it
becomes closely massed about the pelvic end of the metanephric
diverticulum and pushed farther and farther away from its point of
origin as the diverticulum continues to grow ccphalad (Figs. 118, 119,
and 120). This mesoderm gives rise to the secretory tubules of the
metanephros or permanent kidney, and is, therefore, often designated
as metanephrogenous tissue.
 
While the metanephric primordium is being pushed cephalad,
it is increasing rapidly in size and encroaching on the space occupied
by the mesonephros. Coincidently, rapid internal differentiation is
progressing. The pelvic end of the diverticulum expands within its
investing mass of mesoderm and takes on a shape suggestive of the
pelvic cavity of the adult kidney (Figs. 119 and 120). From this primitive pelvic dilation arise numerous outgrowths which push radially
into the surrounding mass of nephrogenic mesoderm (Fig. 138).
These outgrowths become hollow, forming ducts which branch and
rebranch as they extend toward the periphery. These are the collecting
ducts of the kidney {straight collecting tubules) (Fig. 119, E).
 
The first changes in the mesoderm which presage the formation
of the uriniferous tubules, occur near the distal ends of terminal
branches of the collecting ducts. The mesodermal cells become
arranged in small vesicular masses which lie in close proximity to the
blind end of the collecting duct (Fig. 121, A). Each of these vesicular
cell masses is destined to become a uriniferous tubule draining into
the duct near which it arises. (In figure 121, A, this condition is
 
 
 
206
 
 
THE DEVELOPMENT OF THE UROGENITAL SYSTEM
 
 
 
Fig. 119, Diagrams showing a series of stages in the growth and differentiation of the metanephric diverticulum. (Patten. ‘'Human Embryology,”
The Blakiston Company.)
 
 
represented schematically, only two uriniferous tubules being shown
in relation to the end of the collecting ducts whereas there are actually
several. The tubule on the right is represented as slightly further
differentiated than that on the left.) As the developing tubules extend
toward the end of the collecting duct, the bud-like tips of the duct
itself grow out to meet them (Fig. 121, B). Soon the two become
confluent (Fig. 121, C). In this stage the metanephric tubules are
very similar to young mesonephric tubules (cf. Fig. 116). In their later
development the metanephric tubules become much more elaborately
convoluted than the mesonephric but their functional significance is
the same.
 
As the kidney grows in mass additional generations of tubules are
formed in its peripheral zone. New orders of straight collecting tubules
arise from buds, called ampullae, which appear at about the point
where the excretory tubules become confluent with the straight
collecting tubules of the previous order (Fig. 121, D). At the tips of
the new straight collecting tubules a new order of excretory tubules is
formed from the metanephrogenous tissue in the same manner that
 
 
THE URINARY SYSTEM
 
 
207
 
 
 
Neural tube
 
 
Notochord _ .
 
Sacral ,
 
symp. plexus ^
 
Mesonephros
Metanephros
Metonep hric
duct
 
Mesonephric
duct
 
Allantoic art.
 
Bose of Morn of'
allontois urogenitol
sinus
Urogenital sinus
 
Urethral groove
in genital tubercle
 
 
 
 
Post.
 
cardinal vein
Allantoic art.
 
Caudal pole of metanephros
Metonephric duct (cut twice)
 
Coelom
Mesorectum
Anal orifice
 
Posterior appendage bud
 
 
Fig. 120. Drawings (X 15) of transverse sections through the pelvic
region of a 15 mm. pig embryo. The level of each section is indicated on the
inset lateral plan.
 
 
THE DEVELOPMENT OF THE UROGENITAL SYSTEM
 
 
 
 
 
Loop of Henie
 
 
Fio. 121. Diagrams showing the development of the mctanephric tubules
of mammalian embryos. (After Huber, from Kelly and Burnarn: “Diseases of
Kidneys, Ureters, and Bladder,'’ courtesy, D. Appleton-Uentury Co.)
 
 
the previous group was formed. This process is repeated many times
during the growth of the kidney, about 12 to 14 generations of tubules
usually having made their appearance by the time of birth. Some
additional generations of tubules may be formed in the period of
rapid growth immediately following birth but most of the postnatal
growth of the kidneys, by which they keep pace with increased body
mass, is due to the growth of the tubules rather than to further increase
in their number.
 
The blood supply to the metanephros, instead of coming directly
from the aorta by numerous small branches as is the case in the mesonephros, is brought in from the aorta through the renal artery and
thence distributed by a very elaborate system of smaller vessels.
Nevertheless the relations of the smaller vessels to the tubules are
essentially alike in the two organs. An arterial twig breaks up into a
glomerulus within a capsule at the distal end of each tubule. An
 
 
 
THE URINARY SYSTEM
 
 
209
 
 
efferent vessel leaves the glomerulus to break up again in a meshwork
of capillaries in close relation to the tortuous tubule. Collecting veins
return the blood to the general circulation, freed of the nitrogenous
waste matter which is a constant by-product of metabolism.
 
Formation of the Bladder and Early Changes in the Cloacal
Region. In dealing with the development of the extra-embryonic
membranes we have already taken up the formation of the allantois
as an evagination from the caudal end of the primitive gut (Fig. 37).
Shortly after this occurs, the gut caudal to the point of origin of the
allantois becomes enlarged to form the cloaca (Fig. 118, A). When the
cloacal dilation is first formed, the hind-gut still ends blindly, but
there is an ectodermal depression under the root of the tail which has
sunk in toward the gut until the tissue separating the gut from the
outside is very thin (Fig. 37, D). This ectodermal depression is known
as the proctodaeum and the thin plate of tissue still closing the hindgut is called the cloacal membrane. Eventually the cloacal membrane
ruptures, establishing a caudal outlet for the gut. This rupture is
similar to the rupture of the oral plate which has previously established communication between the stomodaeum and the cephalic
end of the primitive gut.
 
Before this occurs important changes take place internally. The
cloaca begins to be divided into two parts, a dorsal part which forms
the rectum and a ventral part, the urogenital sinus (Fig. 122). This
division is effected by the growth of the urorectal Jold., a crescentic fold
which cuts into the cephalic part of the cloaca where the allantois
and the gut meet (Fig. 122). The two limbs of the fold bulge into the
lumen of the cloaca from either side, eventually meeting and fusing
with each other! The progress of this partitioning fold toward the
proctodaeal end of the cloaca makes it difficult to keep track of the
original limits of the allantois, since as the urogenital sinus is lengthened, it is, in effect, added onto the allantois (cf. Fig. 118, A~D). The
point of entrance of the mesonephric ducts, however, affords a landmark which is sufficiently accurate for all practical purposes. Before
the urorectal fold has changed the relations, the mesonephric ducts
open from either side into the cephalic part of the cloaca. After the
urorectal fold has divided the cloaca, the mesonephric ducts appear
to empty into the allantois (Fig. 122). This gives us our bearings, for
the mesonephric ducts are actually opening into the newly established
urogenital sinus which is continuous with the allantois.
 
Before the cloacal membrane ruptures, separation of the cloaca is
 
 
 
210
 
 
THE DEVELOPMENT OF THE UROGENITAL SYSTEM
 
 
 
Fig. 122. Schematic ventro-latcral view of the urogenital organs of a
young mammalian embryo. (Redrawn from Kelly and Burnam, ‘'Diseases
of Kidneys, Ureters and Bladder,” courtesy, D. Appleton-Century Co.) The
figure as originally drawn was based on human embryos of 12 to 14 mm. In
all essentials the relations shown are applicable to 14 to 15 mm. pig embryos.
 
complete and its two parts open independently. The opening of the
rectum is the anus and that of the urogenital sinus is the ostium
urogenitale (Fig. 118, D).
 
Meanwhile the proximal part of the allantois has become greatly
dilated and may now quite properly be called the urinary bladder. We
should remember, however, that the neck of the bladder has been
formed largely from tissue which was originally part of the cloaca.
 
In the growth of the bladder the caudal portion of the mesonephric
duct is absorbed into the bladder wall. This absorption progresses
until the part of the mesonephric duct caudal to the point of origin
of the metanephric diverticulum has disappeared. The end result of
this process is that the mesonephric and metanephric ducts open
independently into the urogenital sinus. The metanephric duct,
 
 
 
THE DEVELOPMENT OF THE INTERNAL REPRODUCTIVE ORGANS 211
 
 
possibly due to traction exerted by the kidney in its migration headwards, acquires its definitive opening somewhat laterally and cephalically to that of the mesonephric duct. It then discharges into the
part of the urogenital sinus which was incorporated in the bladder.
The mesonephric ducts open into the part of the urogenital sinus
which remains narrower and gives rise to the urethra (Fig. 118, D-F).
The urethra acquires quite diflferent relations in the two sexes. It is,
therefore, desirable to defer consideration of it and take it up in
connection with the external genitalia.
 
II. The Development of the Internal Reproductive Organs
 
The Indifferent Stage. One of the striking things in the development of the reproductive system is the condition which at first exists
as to sexual differentiation. One might expect that reproductive
mechanisms as totally unlike as those of adult males and females
would be sharply differentiated from one another from their earliest
appearance. Such is not the case. Young embryos exhibit gonads
which at first give no evidence as to whether they are destined to
develop into testes or ovaries. Along with these neuter or indifferent
gonads there are present in an undeveloped state two different duct
systems. If the individual develops into a female, one of these duct
systems forms the oviducts, uterus, and vagina, and the other remains
rudimehtary. If the individual is destined to become a male, the
potentially female ducts remain rudimentary and the other set gives
rise to the duct system of the testes. In dealing with the embryology
of the reproductive organs, therefore, conditions as they exist in the
indifferent stage (Fig. 123) form a common starting point for the
consideration of the later developmental changes in either sex.
 
Origin of the Gonads. From their earliest appearance the gonads
are intimately associated with the nephric system. While the mesonephros is still the dominant excretory organ, the gonads arise as
ridge-like thickenings (gonadial ridges, germinal ridges) on its ventromesial face (Fig. 108, F, and 138). Histologically the gonadial ridge
consists essentially of a mesenchymal thickening covered by mesothelium. The mesothelial coat of the developing gonad is directly
continuous with the mesothelium covering the mesonephros — is in
fact merely a part of it stretched over the mesenchymal thickening.
It soon, however, begins to show characteristics which differentiate it
from the adjacent mesothelium. It grows markedly thicker and its
cells round out and increase in size. Some of the cells in the germinal
 
 
 
212
 
 
THE DEVELOPMENT OF IHE UROGENITAL SYSTEM
 
 
 
Fig. 123. Schematic diagram showing plan of urogenital system at an early
stage when it is still sexually undifferentiated. (Modified from Hertwig.)
 
 
epithelium, as this modified layer of mesothelium is now termed, are
conspicuously larger than their neighbors. These large cells are the
primordial germ cells of the gonad. Considerable evidence has been
adduced of late that these germ cells are not formed in situ by the
differentiation of mesothelial cells. It is maintained that they can be
identified elsewhere in the body before they appear in the germinal
epithelium, and that they migrate from their place of origin (yolk-sac
entoderm) to settle down in the germinal epithelium and there rear
their families. Whatever their previous history may be, they are
 
 
 
THE DEVELOPMENT OF THE INTERNAL REPRODUCTIVE ORGANS 213
 
clearly recognizable in the germinal epithelium and it is not difficult
to follow their differentiation from then on, through succeeding
generations, to give rise, finally, to the gametes.
 
If the gonad is to develop into a testis the cells of the germinal
epithelium grow into the underlying mesenchyme and form cord-like
masses. These cords eventually become differentiated into the seminiferous tubules in which the spermatozoa are formed. In case the
gonad develops into an ovary the primordial germ cells grow into the
mesenchyme and there become differentiated into ovarian follicles
containing the ova. (See Chap. 2.)
 
The Sexual Duct System in the Male. The ducts which in the
male convey the spermatozoa away from the testis are, with the
exception of the urethra, appropriated from the mesonephros — a
developmental opportunism facilitated by the proximity of the growing testes to the degenerating mesonephros (Fig. 128). The mesonephric structures which are taken over by the testes are shown
schematically in figure 124.
 
Epididymis. Some of the mesonephric tubules which lie especially
close to the testes arc retained as the efferent ductules (Figs. 3 and
124). They, together with that part of the mesonephric duct into
which they empty, become the epididymis. Cephalic to the tubules
which are converted into efferent ductules a few mesonephric tubules
sometimes persist in vestigial form as the appendix of the epididymis.
Caudal to the efferent ductules a cluster of mesonephric tubules almost
invariably persists in rudimentary form as the paradidymis.
 
Ductus Deferens, Seminal Vesicle, and Ejaculatory Duct.
Caudal to th^ epididymis the mesonephric duct receives a thick
investment of smooth muscle and becomes the ductus (vas) deferens.
A short distance before the vasa deferentia enter the urethral part of
the urogenital sinus, local dilations appear in them which become
elaborately sacculated and form the seminal vesicles (Fig. 3). The
short part of the mesonephric duct between the seminal vesicles and
the urethra constitutes the ejaculatory duct. From this point on, the
spermatozoa traverse the urethra which thus serves as a common
passageway to the exterior for both the sexual cells and the renal
excretion.
 
Prostate and O^wper’s Glands. From the urethral epithelium
the prostate and bulbo-urethral glands develop. The prostate sur*
rounds the urethra near the neck of the bladder; the bulbo-urethral
(Cowper’s) glands lie adjacent (Fig. 124). Their secretions, discharged
 
 
 
214
 
 
THE DEVELOPMENT OF THE UROGENITAL SYSTEM
 
 
«> 3 <<
 
c X)
o 3
<0 ^
 
2
 
 
Kidney
 
App.of epid.
Epididymis
 
Paradidymis
 
 
'
 
— Diaphragmatic ligament
 
• Appendage of testis
( hydatid)
 
 
Mullerian duct
 
Mesonephric duct
(Vos deferens)
 
 
Scrotum
 
 
 
Inguinal ligament
(gubernaculum)
 
 
Opening of
 
/V* if!
 
ejaculatory duct
 
 
(mesonephric d.) —
 
 
a :
 
 
Testis rr
 
(after descent)
 
' V .
 
N
 
 
\ â– 
 
 
 
Openings of
ureters
 
 
Prostotic sinus
 
Prostate gland
 
Bulbo -urethral
gland
 
Urethra (penile)
 
 
Fig. 124. Diagram of the male sexual duct system in mammalian embryos.
(Modified from Hertwig.)
 
 
into the urethra with that of the seminal vesicles, serve as a conveying
fluid for the spermatozoa.
 
The Female Duct System. The Mullerian ducts first appear
close beside and parallel to the mesonephric ducts. They are the
primordial structures from which the uterine tubes (oviducts), uterus,
atid vagina arise in the female. It is possible that phylogenetically
the Mullerian ducts arose directly from the mesonephric ducts.
Ontogenetically in the mammals any such process of splitting has been
slurred over and they seem to arise side by side from the same parent
tissue. The mesonephric ducts become well developed earlier than
the Mullerian ducts and it is very easy to overlook the Miillerian ducts
 
 
 
THE DEVELOI^MENT OF THE INTERNAL REPRODUCTIVE ORGANS 215
 
 
 
Fig. 125. Diagram of the female sexual duct system in mammalian embryos.
 
(Modified from Hertwig.)
 
*
 
altogether in young specimens. By the time embryos have reached
30 or 40 mm. in length, however, it should be possible to locate them
readily in sections or, with care, by dissection.
 
Vagina. When the Mullerian ducts first appear they are paired
throughout their entire length. At their cloacal ends the right and
left ducts lie close to the mid-line. In this region they soon approach
and fuse with each other in the mid-line to form the vagina (Fig. 125).
 
Uterus. In some of the primitive mammals fusion of the Mullerian
ducts does not progress cephalad beyond the vagina. Such animals
have paired uteri formed by enlargement of the Mullerian ducts
cephalic to their entrance into the vagina (Fig. 126, A). In all the
higher mammals, fusion of the Mullerian ducts involves the caudal
end of the uterus so that it opens into the vagina in the form of an
 
 
 
216
 
 
THE DEVELOPMENT OF THE UROGENITAL SYSTEM
 
 
 
 
 
Fig. 126. Four types of uteri occurring in different gioups of mammals.
(After Wiedersheim.)
 
A, Duplex, the type found in marsupials.
 
B, Bipartite, the type found in certain rodents.
 
C, Bicornate, the type found in most ungulatse, and carnivores.
 
D, Simplex, the type characteristic of the primates.
 
unpaired neck or cervix. Toward the ovary from the cervix there is
great variation in the degree of fusion encountered in the different
groups (Fig. 126, B, C, D). In the sow the fusion is carried only a
short way beyond the cervix to form a typical bicornate uterus
(Fig. 126, C).
 
Uterine Tubes. The part of the Mullerian duct between the
uterus and the ovary remains slender and forms the uterine tube
(oviduct). Near its cephalic end; but not usually at the extreme tip,
a more or less funnel-shaped opening develops {ostium tubae abdominale). In different forms the detailed configuration of the ostium and
its relation to the ovary are quite variable. Conditions range all the
way between a pouch-like dilation which almost completely invests
the ovary (sow), and an elaborately fringed, funnel-shaped ostium
which opens in the general direction of the ovary (man). Whatever
the morphological eccentricities of the ostium may be, they appar
 
 
THE DEVELOPMENT OF THE INTERNAL REPRODUCTIVE ORGANS 217
 
 
ently make less difference in its efficiency in picking up the discharged
ovum than one might suppose. Even in forms where the relation of
the ostium to the ovary is least intimate, abdominal pregnancies
resulting from the fertilization of an ovum which the ostium failed to
catch and start on its way to the uterus are comparatively uncommon.
 
Vestigial Structures in the Genital Duct System. In the conversion of the primordial duct systems to their definitive conditions,
some of the parts which are not utilized in the formation of functional
structures persist in vestigial form even in the adult. Mention has
already been made of the rudimentary mesonephric tubules which
persist in the male as the paradidymis and the appendix of the epididymis. Traces of the old Mullerian duct system also can usually be
found in the male. Attached to the connective tissue investing the
testis there is sometimes a well-marked vesicular structure called the
appendix of the testis {hydatid) which represents the cephalic end of the
Mullerian duct. These ducts also leave a vestige at their opposite ends
in the form of a minute diverticulum {prosiaiic simis^ vagina mascidina)
which persists where the fused Mullerian ducts opened into the urogenital sinus (Fig. 124).
 
In the iemale the ostium of the oviduct does not ordinarily develop
at the extreme cephalic end of the Mullerian duct. The tip of the
duct is likely to persist in rudimentary form as a stalked vesicle
(hydatid) attached to the oviduct (Fig. 125).
 
The mesonephric tubules and ducts may remain recognizable to
a variable extent. Usually there is embedded in the mesovarium a
cluster of blind tubules and traces of a duct, corresponding to the
part of the mesonephric duct and tubules which in the male form the
epididymis. Ifhese vestiges are called the epodphoron. Less frequently
the more distal portion of the mesonephric duct (the part which in
the male forms the vas deferens) leaves traces known as the canals of
Gartner in the broad ligament close to the uterus and vagina.
 
Changes in Position of the Gonads. Neither the testes nor the
ovaries remain located in the body at their place of origin. The
excursion of the testes is particularly extensive. Many factors are
involved in their descent from the mesonephric region, where they
first appear, to their definitive position in the scrotal sac. We can only
sketch very briefly the course of events.
 
The urogenital organs arise in the dorsal body-wall, covered by
the mesothelial lining of the coelom. Later when the coelomic mesothelium of the abdominal region is reinforced by connective tissue,
 
 
 
218
 
 
THE DEVELOPMENT OF THE UROGENITAL SYSTEM
 
 
Diaphragmatic ligament
of mesonephros
 
 
Mesonephros -Adrenal
 
Testis
Spermatic artery
 
 
Aorta
Ureter
 
Umbilical artery
 
Fig. 127. Dissection showing the relative position of mesonephros, metanephros, and testis in a 33 mm. pig embryo. (Modified from Hill.)
 
the two layers together constitute the peritoneum. As to position of
origin with reference to the body cavity, the urogenital organs may,
therefore, be briefly characterized as retroperitoneal. This primary
positional relationship is already familiar but it is emphasized again
here because it is involved in many phases of the change in position
and relations undergone by the reproductive organs.
 
Descent of the Testes. When the mesonephros begins to grow
rapidly in bulk, it bulges out into the coelom, pushing ahead of itself
a covering of peritoneum. At either end of the mesonephros the
peritoneum is, in this process, thrown into folds. One of them extends
cephalad to the diaphragm and is known as the diaphragmatic ligament
of the mesonephros 124 and 127). The other, which extends to the
 
extreme caudal end of the coelom, becomes fibrous and is then known
as the inguinal ligament of the mesonephros (Fig. 124). The inguinal ligament is destined to play an important part in the descent of the testes.
 
We have already seen that when the testis develops it causes a
local expansion of the peritoneal covering of the mesonephros to
accommodate its increasing mass. As the testis grows, the mesonephros decreases in size and the testis takes to itself more and more
of the peritoneal coat of the mesonephros (Figs. 127 and 128). In this
 
 
Mesonephric duct,
 
 
 
 
Renal artery
Metanephros
 
 
Diaphragm
 
 
 
 
THE DEVELOPMENT OF THE INTERNAL REPRODUCTIVE ORGANS 219
 
 
process it becomes closely related to the inguinal ligament of the
mesonephros. In effect the inguinal ligament extends its attachment
to include the growing testis as well as the shrinking mesonephros.
With this change the ligament is spoken of as the gubernaculum (Figs.
124, 129, and 131, A).
 
In the meantime a pair of coclomic evaginations are formed, one
in the inguinal region of each side of the pelvis where the caudal end
of the gubernaculum is attached. These are the scrotal pouches. Due
perhaps in part to traction exerted by the gubernaculum, the testes
and the mesonephric structures which give rise to the epididymis begin
to shift their relative position progressively farther caudad (cf. Figs.
127-130). Eventually they come to lie in the scrotal pouches. It would
be more direct and vivid to say that the gubernaculum “pulls the testis
down.” Although the end results of their association very nearly
justify such a phrase, it would not be strictly correct. We would be
overlooking the more important factor of differential growth. Failure
 
 
Kidney.
 
 
Testis,
Spermatic artery.
 
Mesonephros.
Mesonephric duct.
 
 
Renal artery
 
 
 
•Arteries to mesonephros
 
 
.Spermatic artery
 
 
.Ureter
 
 
Umbilical artery
 
 
Fig. 128. Dissection showing the relative size and position of mesonephros,
metanephros, and testis in an 87 mm. pig embryo. (Modified from Hill.)
 
 
 
220
 
 
THE DEVELOPMENT OE THE UROCiENlTAL SYSTEM
 
 
 
Fig. 129. Dissection of 128 mm. embryo showing an early stage in the
descent of the testis. (After Hill.) Abbreviations: A., aorta; B., urinary bladder; E., epididymis (the retrogressing 'mesonephros); G., gubernaculum; K.,
kidney (metanephros) ; R., rectum; Ring, ‘‘inguinal ring,” the fibrous tissue
surrounding the opening (inguinal canal) into the scrotal sac; T., testis; U.,
ureter; U. A., umbilical artery; W. M., mesonephric (Wolffian) duct and
Mullerian duct. The common investment of connective tissue largely conceals the smaller Mullerian duct. In this figure the line of demarcation
between the two is most clearly shown just to the left of the gubernaculum.
 
 
THE DEVELOPMENT OF THE INTERNAL REPRODUCTIVE ORGANS 221
 
 
 
Fig. 130. Dissection of 210 mm. pig embryo showing the testis just entering the inguinal canal. (After Hill.) Abbreviations: A., aorta; B., bladder;
E., epididymis; K., kidney; M. D.; Mullerian duct; R., rectum; Ring, inguinal ring; Sp. Art., spermatic artery; T., testis; U. A., umbilical artery;
U., left ureter; Ur., right ureter (cut); W. D., mesonephric (Wolffian) duct.
 
 
222
 
 
THE DEVELOPMENT OF THE UROGENITAL SYSTEM
 
 
of the gubernaculum to elongate in proportion to the growth of
surrounding pelvic structures is more responsible for the traction
exerted on the testis than actual shortening on its part.
 
In its entire descent, the testis moves caudad beneath the peritoneum. It does not, therefore, enter the lumen of the scrotal pouch
directly but slips down under the peritoneal lining and protrudes into
the lumen, reflecting a peritoneal layer over itself (Fig. 131). This
layer of reflected peritoneum is known anatomically as the visceral
tunica vaginalis. In most mammals when the testis has come to rest in
the scrotal sac, the canal connecting the sac with the abdominal cavity
becomes closed. In some of the rodents, however, it remains patent
and the testes descend into the scrotum only during the breeding
 
 
 
Fig. 131. Schematic diagrams illustrating the descent of the
testis as seen from the side. Abbreviations: d. def., ductus deferens;
Proc. Vag., processus vaginalis (the diverticulum of the peritoneum
pushed into the scrotal sac).
 
season, to be retracted again into the abdominal cavity until the next
period of sexual activity. Even in those forms normally exhibiting
complete closure of the inguinal canal the obliteration of the opening
is not uncommonly incomplete or structurally weak as evidenced by
the not infrequent occurrence of inguinal hernias.
 
Descent of the Ovaries. Although the ovaries move through far
less distance than the testes their change in position is quite characteristic and definite. As they increase in size, both the gonads and the
Mullerian ducts sag progressively farther into the body cavity. In so
doing they pull with them peritoneal folds comparable to the mesenteries of the intestinal tract. As these folds are stretched out they allow
the ovaries, uterine tubes, and uterus to move caudally, laterally,
and somewhat ventrally (Fig. 125). The peritoneal folds remain
attached to the dorsal and lateral body-walls, become reinforced by
fibrous tissue, and constitute the broad ligaments. The inguinal liga
 
 
THE DEVELOPMENT OF THE INTERNAL REPRODUCTIVE ORGANS 223
 
 
ment of the mesonephros which in the male forms the gubemaculum,
in the female is caught in the peritoneal folds which form the broad
ligaments. When the ovaries move caudad and laterad the inguinal
ligament is bent into angular form. Cephalic to the bend it becomes
the round ligament of the ovary, caudal to it, the round ligament of the uterus
(Fig. 125). Thus the changes in position of the female reproductive
organs are carried out in a manner quite different from those in the
male. In both sexes the organs arise retroperitoneally, but in the male
the testes slide along close to the body-wall beneath the peritoneum,
while in the female the ovaries, oviducts, and uterus stretch the
peritoneum into a mesentery-like structure which permits a certain
latitude of positional change and at the same time serves as a supporting ligament and a path of ingress for blood vessels and nerves.
 
The Adrenal Glands. The adrenal glands and the accessory
chromaffin bodies are endocrine organs which are in no way part of
the urogenital system. But the close proximity of the adrenal glands
to the kidneys (Figs. 127 and 128) makes it convenient to give them
a word of comment at this point.
 
Certain cells which migrate ventrally from the neural crest at the
time the sympathetic ganglia are formed become, not nerve cells,
but gland cells active in the production of a specific hormone. Due
presumably to the presence of this internal secretion in their cytoplasm they exhibit a characteristic reaction with chromic acid salts
which has led to their designation as chromaffin cells. Clusters of these
chromaffin cells become located in close proximity to each sympathetic ganglion. These clusters are called the paraganglionic chromaffin
bodies. Otheij masses of chromaffin tissue from the same source appear
in various places beneath the mesoderm lining the coelom. There is
usually a considerable amount of chromaffin tissue present in the
region of the abdominal sympathetic plexus. This mass constitutes the
aortic chromaffin body (organ of Zuckerkandl). The largest mass of
extra-sympathetic chromaffin tissue appears just cephalic to the
kidney and becomes converted into the medulla of the adrenal.
 
The cortical portion of the adrenal gland appears very early in
development. Even in embryos of 9~12 mm. there is accelerated
local proliferation of cells from the splanchnic mesoderm around the
notch on either side of the base of the primary dorsal mesentery
adjacent to the cephalic pole of the mesonephros. These cells push
into the underlying mesenchyme and begin to show a tendency to
become arranged in cords. By the 15-17 mm. stage the aggregation
 
 
 
 
A 1 . 115mm,
 
Fig. 132. Photographs (X 5) of the external genitalia of a series of pig
embryos. Abbreviations: A, anus; C, clitoris; F, genital fold; GC, glans
clitoridis; GP, glans penis; L, labia majora; N, labia minora (nymphae);
O, urogenital orifice; P, penis; Pr, prepuce; Proc, proctodaeum; R, raphe;
S, genital swelling; Sc, scrotum; T, genital tubercle.
 
 
THE EXTERNAL GENITALIA
 
 
225
 
 
of cell cords which constitutes the primordium of the adrenal cortex
is quite conspicuous (Fig. 138). Later in development the migrating
cells which give rise to the medulla of the adrenal invade the cortical
primordium and become encapsulated within it.
 
III. The External Genitalia
 
Indifferent Stages. Still another thread in the story which has to
be picked up separately is the development of the external genitals of
either sex by divergent differentiation from a common starting point.
 
In very young embryos there is formed in the mid-line just cephalic
to the proctodaeal depression, a vaguely outlined elevation known
as the genital eminence. This is soon differentiated into a central prominence {genital tubercle) closely flanked by a pair of folds {genital Jolds)
extending toward the proctodaeum. Somewhat farther to either side
are rounded elevations known as the genital swellings (Figs. 132, A,
B, C). Between the genital folds is a longitudinal depression which
attains communication with the urogenital sinus to establish the
urogenital orifice (ostium urogenitale). This opening is separated
from the anal opening by the urorectal fold (Figs. 118, 122, and 132
 
A-C).
 
The Male Genitalia. If the individual develops into a male the
genital tubercle becomes greatly elongated to form the penis, the
genital folds ensheath the penis as the prepuce, and the genital
swellings become enlarged to form the scrotal pouches (Fig. 132, C,
D, E, F). During the growth of the penis there develops on its caudal
face a groove extending throughout its entire length. Posteriorly the
groove is continuous with the slit-like opening of the urogenital sinus.
This groove in the penis later becomes closed over by a ventral fusion
of its margins, establishing the penile portion of the male urethra.
That portion of the urogenital sinus between the neck of the bladder
and the original opening of the urogenital sinus becomes the prostatic
urethra (Fig. 118, F). Since the margin of the slit-like urogenital orifice
closes coincidently with the closure of the urethral groove in the penis,
the prostatic urethra and the penile urethra become continuous and
the urogenital orifice is projected to the tip of the penis. The line of
fusion in the urogenital sinus region and along the caudal surface of
the penis is clearly marked by the persistence of a ridge-like thickening
known as the raphe (Fig. 132, D, E, F).
 
Female Genitalia. In the female the genital tubercle becomes
the clitoris, the genital folds become the labia minora and the genital
 
 
 
226
 
 
THE DEVELOPMENT OF THE UROGENITAL SYSTEM
 
 
swellings the labia raajora (Fig. 132, C, G, H, I). The original opening
of the urogenital sinus undergoes no such changes ds occur in the
male but persists nearly in its original position. Its orifice, enlarged
and flanked by the labia, becomes the vestibule into which open the
vagina and the urethra (Fig. 118, E). The urethra in the female is
derived entirely from the urogenital sinus, being homologous with
the prostatic portion of the male urethra.
 
 
 
==Chapter  11==
 
 
Tlie Development of tke Circulatory System
 
 
I. The Interpretation of the Embryonic Circulation
 
The embryonic circulation is difficult to understand only when
the meaning of its arrangement is overlooked. If one bears in mind
certain fundamental conceptions as to the significance of the circulatory system in organic economics, and the basic morphological
principle that any embryo must go through certain ancestral phases
of organization before it can arrive at its adult structure, the changes
in the arrangement of vascular channels during the course of development form a coherent and logical story.
 
In the embryo as in the adult the main vascular channels lead to
and from the centers of metabolic activity. The circulating blood
carries food from the organs concerned with its absorption to parts of
the body remote from the source of supplies; oxygen to all the tissues
of the body from organs which are especially adapted to facilitate the
taking of oxygen into the blood ; and waste materials from the places
of their liberation to the organs through which they are eliminated.
One of the primary reasons the arrangement of the vessels in an
embryonic mammal differs so much from that in the adult, is the fact
that the emjbryo lives under conditions totally unlike those which
surround its parents. Its centers of metabolic activity are, therefore,
different; and, since the course of its main blood vessels is determined
by these centers, the vascular plan is different. No such profound
changes occur between the embryonic and the adult stages in the
circulation of a fish where embryo and adult are both living under
similar conditions.
 
The organs which in the adult mammal carry out such functions
as digestion and absorption, respiration, and excretion are extremely
complex and highly differentiated structures. They are for this reason
slow to attain their definitive condition and are not ready to become
functional until toward the close of the embryonic period. Moreover
the conditions which surround certain of the developing organs during
 
227
 
 
 
 
228
 
 
THE DEVELOPMENT OF THE CIRCULATORY SYSTEM
 
 
intra-uterine life absolutely prevent their becoming functional even
were they suflSciently developed so to do. Suppose^ the lungs, for
example, were functionally competent at an early stage of development. The fact that the embryo is reliving ancestral conditions in its
private amniotic aquarium renders its lungs as incapable of functioning as those of a man under water. Likewise the developing digestive
organs of the embryo are inaccessible to raw food materials. Further
examples are not necessary to make it obvious that were the embryo
dependent on the same organs which carry on metabolism in the adult,
development would be at an impasse.
 
An embryo must, nevertheless, solve the problem of existence
during the protracted time in which it is building a set of organs
similar to those of its parents. In the absence of a dowry of stored
food in the form of yolk, the mammalian embryo draws upon the
uterine circulation of the mother. Utilization of this source of supplies
depends on the development of a special organ which serves through
fetal life and is then discarded. The embryo takes food not into its
slowly developing gastro-intestinal tract but into its chorion, a membrane projected outside its own body and applied to the uterine wall
to form, together with it, the placenta. The nutritive materials there
absorbed from the maternal blood must be transported to the body of
the growing embryo by its own blood stream.
 
The use of food materials to produce the energy expressed in
growth depends on the presence of oxygen. For growth there must
be a means of securing oxygen and carrying it, as well as food, to all
parts of the body. Nor can continued growth go on unless the waste
products liberated by the developing tissues are eliminated. The blood
of the embryo cannot be relieved of its carbon dioxide and acquire a
fresh supply of oxygen in the primordial cell clusters which will later
become its lungs. It cannot excrete its nitrogenous waste products
through undeveloped kidneys. Its respiration and excretion, like its
absorption of food, are carried out in the rich plexus of small blood
vessels in the chorion. Here the fetal blood is separated from the
maternal, by tissues so thin that it can readily give up its waste materials to, and receive food and oxygen from, the maternal blood stream,
just as the mother’s own tissues constantly carry on this interchange
with the circulating blood. The placenta is thus the temporary
alimentary system, lung, and kidney of the mammalian embryo. The
large size of the umbilical blood vessels to the placenta is not a surprising thing — it is the entirely logical, the inevitable, expression of
the conditions under which the embryo develops.
 
 
 
THE INTERPRETATION OF THE EMBRYONIC CIRCULATION 229
 
 
The enormous chorionic blood supply during fetal life, with the
entire disappearance of this special arc of the circulation when the
organism assumes adult methods of living, is a striking example of the
determination of vascular channels by the location of functional
centers. We must not, however, overlook the fact that there are many
other centers of activity in the growing embryo less conspicuous but
equally important for its continued existence. Each developing organ
in the embryonic body is a center of intense metabolic activity.
During fetal life it must be supplied by vascular channels adequate to
care for its growth. But that is not all. Up to the time of birth each
organ has been drawing on blood furnished with food and freed of
waste materials by the activities of the maternal organism. At birth
all this must change. Each organ essential to metabolism must be
ready to assume its own active share in the process. Their vessels must
be adequate to take care not only of the needs of these organs themselves but also of the functions these organs must now take over in
maintaining the metabolism of the organism as a whole.
 
While the functional significance of the arrangement of the blood
vessels is always of importance, especially in understanding the
progressive changes in vascular plan, there is another factor which we
cannot overlook. This factor is conservative, having to do with the
things we inherit from our forebears. The goal of the embryonic
period is the attainment of a bodily structure similar to that of the
parents. Because it is so familiar, we accept with complaisance the
remarkable fact that this goal is attained with absolute regularity.
Accidents there may be, leading to defective development or malformation — but the fertilized ovum of a pig never gives rise to a cow.
The new individual will show detailed differences from its parents,
differences which are capitalized in the slow march of evolution; but
in a single generation these differences are never radical. We say
that the offspring has inherited the structure of its parents. It does
more. It inherits the tendency to arrive at its adult condition by
passing through the same sort of changes which its ancestors underwent in the countless millions of years it took their present structure
to evolve.
 
Applied to the development of the circulatory system of mammals
this means that the earliest form in which it appears will not be a
miniature of the adult circulation. The simple tubular heart pumping
blood out over aortic arches to be distributed over the body and
returned to the posterior part of the heart by a bilaterally symmetrical
venous system, in short the vascular plan which we see in young
 
 
 
230
 
 
THE DEVELOPMENT OF THE CIRCULATORY SYSTEM
 
 
mammalian embryos (Fig. 45), is essentially the plan of the circulation
in fishes. When we realize this, we are not puzzled either by the
appearance of a full complement of aortic arches, or by their subsequent disappearance to make way for a new respiratory circulation in
the lungs. We see the march of progress from a logical beginning in
ancestral conditions toward the consummation of fetal life with an
organization like that of the parent.
 
In addition to the fundamental ground plan of the circulation of
the mammalian embryo, recapitulations account for many transitory
peculiarities. The formation of a conspicuous though empty yolk-sac
with a complement of blood vessels almost as well developed as the
vitelline vessels of animals well endowed with yolk, is clearly a recapitulation of ancestral conditions. So also is the highly developed
system of venous channels in the mesonephros. If the organ itself
appears it brings with it its quota of vessels, no matter whether or not
the organ is destined to degenerate later in development.
 
Whatever peculiarities may be impressed on the course of the
circulation by the appearance of ancestral structures or by the
development of special fetal organs such as the yolk-sac and the
placenta, the main blood currents will at any time be found concentrated at the centers of activity. Changes of these main currents as one
center retrogresses and another becomes dominant, must take place
gradually. Large vessels become smaller, what was formerly an
irregular series of small vessels becomes excavated to form a new main
channel, but the circulation of blood to all parts of the body never
ceases. Even slight curtailment of the normal blood supply to any
region would stop its growth ; any marked local decrease in the circulation would result in local atrophy or malformation ; complete interruption of any important circulatory channel, even for a short time,
would inevitably mean the death of the embryo.
 
II. The Arteries
 
The Derivatives of the Aortic Arches. In vertebrate embryos
six pairs of aortic arches are formed connecting the ventral with the
dorsal aorta. The portions of the primitive paired aortae which bend
around the anterior part of the pharynx constitute the first (i.e., the
most anterior) of these aortic arches. In its course around the pharynx
the first aortic arch is embedded in the tissues of the mandibular arch
(Fig. 136, A). The other aortic arches develop later, in sequence, one
aortic arch in each branchial (gill) arch posterior to the mandibular
 
 
 
 
 
 
 
 
 
 
 
 
 
232
 
 
THE DEVELOPMENT OF THE CIRCULATORY SYSTEM
 
 
 
Worsotremnanf,
 
^ofl^aorftcarch
 
'd^aorfic arch
fyorhc sac
S^aorhcarch
A^aorhcarch
)POhnonaryarch
 
 
Right dorsal
aorta
 
 
\Ana5t0mosiS'
 
 
External carotid! artery
External carotid artery
5^ aortic arch
 
4^ aortic arch
Pulmonary arch
Pulmonary artery
 
Left dorsal aorta
 
Putmonary
Segmental arteries
 
Subclauian artery
 
 
 
Aorta
 
 
Fig. 134. Ventral aspect of vessels in the branchial region of pig embryos
of various ages. (After Heuser.) The drawings in this and the three following
figures were made directly from injected specimens rendered transparent by
treatment with wintergreen oil. A, 24 somites; B, 4.3 mm.; C, 6 mm.; D,
8 mm.; E, 12 mm.
 
 
ftemnant of
right pu/mo'
nary arch.
 
 
Pufmanaryarch
â– PuknonatyMfery
fbsienor cervical
arhny
 
'^Bmehat artery
StMnor mtercos*
 
 
SubckMan artery
 
 
 
 
 
 
234
 
 
THE DEVELOPMENT OF THE CIRCULATORY SYSTEM
 
 
arches, leaves only the ventral and dorsal aortic roots and the third,
fourth, and sixth arches to play an important r61e in the formation
of adult vessels.
 
In dealing with embryos of 9 to 12 mm. we have already seen
how the portions of the ventral aortic roots which formerly acted as
feeders to the first two arches were retained as the external carotid
arteries. These vessels, in part through the small channels left by the
disintegration of the aortic arches with which they were originally
associated, and in part through the formation of new branches to
subsequently formed structures, nourish the oral and cervical regions
(Figs. 67, 133 and 137, A, B).
 
The internal carotid arteries also, are, familiar as vessels which
arise as prolongations of the dorsal aortic roots and extend to the brain
(Fig. 67). When the portion of the dorsal aortic root which lies between arch 3 and arch 4 dwindles and drops out, the third arch is left
constituting the curved proximal part of the internal carotid artery
(Figs. 133, B, C, and 137, A~C). The part of the ventral aortic root
which, from the first, has fed the third aortic arch becomes somewhat
elongated and persists as the common carotid artery (Figs. 133, 137).
 
The fourth aortic arch has a different fate on opposite sides of the
body. On the left it is greatly enlarged and persists as the arch of the
adult aorta (Figs. 133 and 134-137). On the right the fourth arch
forms the root of the subclavian artery. The short section of the right
ventral aortic root proximal to the fourth arch persists as the innominate (brachiocephalic) artery from which both the right subclavian and the right common carotid artery arise (Fig. 133, C).
 
The sixth aortic arch changes its original relationships somewhat
more than the others. At an early stage of development branches
extend from its right and left limbs toward the lungs (Fig. 134, D, E).
After these pulmonary vessels have been established^ the right side
 
^ The details of the formation of the pulmonary arteries differ somewhat in
different mammals. In most of the forms which have been carefully studied (man,
cat, dog, sheep, cow, opossum) the pulmonary arteries maintain their original paired
condition throughout their entire length. In these forms part of the right sixth arch
is retained as the proximal portion of the adult right pulmonary artery (Fig, 133).
The pig is unusual in having its pulmonary branches fuse with each other proximally,
forming a median vessel ventral to the trachea (cf. Figs. 134, E, and 135, A). Distal
to this short median trunk the pulmonary vessels retain their original paired condition, each running to the lung on its own side of the body. Proximally the median
trunk becomes associated with the left sixth arch and the right sixth arch drops out
altogether.
 
 
 
THE ARTERIES
 
 
235
 
 
of the sixth aortic arch loses communication with the dorsal aortic
root and disappears (Fig. 135, A, B). On the left, however, the sixth
arch retains its communication with the dorsal aortic root. The
portion of it between the point where the pulmonary trunk is given
off and the dorsal aorta is called the ductus arteriosus (Figs. 133, C, and
138). During the fetal period when the lungs are not inflated the
ductus arteriosus shunts the excess blood from the pulmonary circulation directly into the aorta. The functional importance of this channel
will be more fully appreciated when we have given it further consideration in connection with the development of the heart and the
changes which take place in the circulation at the time of birth.
 
While these changes have been taking place in the more peripheral
part of the vascular channels which lead to the lungs, a fundamental
alteration has occurred in the main ventral aortic stem. Formerly a
single channel leading away from the undivided ventricle of the
primitive tubular heart, the ventral aorta now becomes divided
lengthwise into two separate channels. This division begins in the
aortic root just where the sixth arches come off, and progresses thence
toward the heart. Meanwhile, as wc shall see when we take up the
development of the heart, the ventricle has become divided into right
and left chambers. The final result of these two synchronous partitionings is the establishment of a channel leading from the right
ventricle to the lungs by way of the sixth aortic arches, and another
separate channel leading from the left ventricle to the dorsal aorta by
way of the left fourth aortic arch.
 
The Derivatives of the Intersegmental Branches of the Aorta.
In dealing with the structure of 9-12 mm. embryos comment was
made on the importance of the small intersegmental branches from
the dorsal adrta (Figs. 67 and 136, F). At that time, too, we became
familiar with some of the vessels which are derived from these branches.
The anterior appendage bud first appears at the level of the seventh
cervical intersegmental, and it is this artery which becomes enlarged
to form the subclavian. With the enlargement of the left fourth aortic
arch to form the main channel leading from the heart to the dorsal
aorta, the dorsal aortic root on the right side becomes much reduced
(Fig. 135, A-D). Caudal to the level of the subclavian it drops out
entirely. It will be recalled that the sixth aortic arch also drops out
on this side. This leaves the right subclavian communicating with the
dorsal aorta by way of a considerable section of the old dorsal aortic
root and the fourth aortic arch. In the adult, both the distal part of
 
 
 
236
 
 
THE DEVELOPMENT OF THE CIRCULATORY SYSTEM
 
 
LeffJVaorhc arch
 
 
 
 
Lehl^Qorh'carch
 
 
Optic vesich
 
 
 
 
Left 3^ aortic arch
 
 
Segmental a rtenes
 
 
Left dorsal aorta
 
 
 
 
Lefr pulmonary
arch
 
 
Left anterior cardinal i/etrt
 
Left dorsal aorta
 
 
LeftS^aorhc arci
 
 
Fig. 136. Lateral aspect of vessels in the branchial region of pig embryos
of various ages. (After Heuser.) A, 10 somites; B, 19 somites; C, 26 somites;
D, 28 somites; E, 30 somites; F, 36 somites (6 mm.).
 
this vessel (formed by the intersegmental artery) and its proximal
portion (appropriated from the old aortic arch system) pass under the
name subclavian. This accounts for the striking dissimilarities of
origin between the right and left subclavian arteries in the adult.
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
THE ARTERIES
 
 
237
 
 
 
VtrhbmlarUry
 
 
Fig. 137. Continuation of the same series of lateral views of injected embryos.
A, 14 mm.; B, 17 mrn.; C, 19.3 mm.; D; 20.7 mm.
 
 
Cephalic to the subclavian arteries, a series of longitudinal anastomoses appear connecting the cervical intersegmentals to form the
vertebral arteries (Fig. 137). When the vertebral arteries are thus
established, all the intersegmental roots back to the subclavian drop
out, leaving the vertebral as a branch of the subclavian (Figs. 1 33, C,
 
 
 
238
 
 
THE DEVELOPMENT OF THE CIRCULATORY SYSTEM
 
 
and 137). The manner in which the vertebrals swing in to the mid-line
rostrally and become confluent with each other to form the basilar
artery, and the anastomosis between the internal carotids and the
basilar artery in the region of the hypophysis, are already familiar.
 
Caudal to the subclavian, the internal mammary artery is formed
by longitudinal anastomosing of the more cephalic of the thoracic
intersegmental arteries. Subsequent dropping out of the proximal
parts of the other intersegmentals leaves it arising from the subclavian.
Thus the steps in its origin are strikingly similar to the processes by
which the vertebral artery was established cephalic to the subclavian
(Fig. 133). Still farther caudally in the body, the intersegmental
arteries retain their original independent condition as paired branches
extending from the aorta dorsad on either side of the neural tube and
the developing spinal column (Fig. 67). Even in the adult these vessels
appear with little change in their original relations.
 
The Enteric Arteries. The first of the three enteric arteries to
appear is the anterior {superior) mesenteric. We have already followed
its origin as a pair of arteries originally called the omphalomesentcrics
which, in young embryos, extended to the surface of the yolk-sac
(Fig. 45). When the yolk-sac degenerates and the ventral part of the
body closes in, these paired channels fuse with each other to form a
median vessel situated in the mesentery and extending to the gut loop
in the belly-stalk (Fig. 66). This is now called the anterior mesenteric
artery. With the elongation and coiling of the intestine in the region
fed by it, the anterior mesenteric artery acquires many radiating
terminal branches. Its primary relations, however, remain unchanged.
 
The celiac artery arises from the aorta in a manner basically similar
to the origin of the anterior mesenteric artery, but at a slightly later
stage of development. The embryonic body has, therefore, become
more nearly closed ventrally and the primary dorsal mesentery has
been established. As a result the primary paired condition we expect
to see in the early stages of the formation of all of the main enteric
arteries is greatly abbreviated in the case of the celiac artery, and
almost from its first appearance it is a median vessel extending in the
mesentery toward the gastric region of the gut (Fig. 67). As development progresses it becomes extensively branched, being the main
artery which feeds the gastro-hepato-pancreatic region of the digestive
system and also the spleen which arises in its territory (Fig. 111).
 
The inferior mesenteric artery has an origin similar to that of the
celiac. It is established caudal to the anterior mesenteric artery slightly
 
 
 
THE ARTERIES
 
 
239
 
 
 
Choroid plexus of ventricle IZ
 
 
Basilar artery
 
Primordium of
occipital bone
 
Arytenoid process//^;
of larynx
 
Pharyngeal
bursa
Recurrent
laryngeal n
 
Aortic arch
 
Ductus
arteriosus
 
Dorsal aorta
 
Left common
cardinal vein
 
Lung bud
 
Adrenal gland
 
Stomach
 
Pancreas
 
Gonad
 
Gut loop in
mesentery
 
Mesonephros
 
Metanephros
 
Post cardinal vein
 
Dorsal root
ganglion
 
 
Mesocoele
 
 
Tuberoulum
posterius
 
Infundib
ulum
 
Rathke's
pocket
 
Foremen
of Monro
 
Tongue
Thyroid
gland
 
Pulmonary valves
 
 
Pericardial coelom
 
 
Septum transversum
 
Gastric branch
of vagus n.
 
Left umbilical
vein in liver
 
Dorsal
 
mesogastrium
(omental portion)
 
Gut loop in
^^^^belly-stolk
 
(umbilical) art
 
Genital tubercle
 
Nerves of
lumbosocral plexus
 
 
Fig. 138. Drawing (X 10) of parasagittal section of 15 mm. pig embryo.
The section is in a plane slightly to the left of the mid-line and passes through
the ductus arteriosus, lung bud, stomach, gonad, and metanephros.
 
 
 
240
 
 
THE DEVELOPMENT OF THE CIRCULATORY SYSTEM
 
 
later in development than the time at which the celiac appears and
is the main vessel to the posterior part of the intestinal tract (Fig. 111).
 
The Renal Arteries. The mesonephros is suppliea by many small
arteries which arise ventro-laterally from the aorta. While the metanephroi or permanent kidneys are still very small, they lie in close
proximity to the mesonephroi and are fed by small arteries which
arise from the aorta along with the mesonephric vessels (Fig. 127). The
local vessels associated with the kidneys are progressively enlarged
as the kidneys themselves grow in bulk and become the renal arteries
of the adult (Fig. 128).
 
The Arteries Arising from the Caudal End of the Aorta. The
 
main aortic trunk decreases abruptly in size where the large umbilical
(allantoic) arteries (Fig. 138) turn off into the belly-stalk. Beyond
this point the aorta is continued toward the tail as a slender median
vessel called the caudal artery (Fig. 67).
 
The posterior appendage buds arise some time after the placental
circulation has been established. The umbilical arteries are consequently of considerable size, and the small vessels which branch off
from them to feed the appendage buds are by comparison quite
insignificant. As the appendage buds grow, these small vessels grow
with them to become the external iliac arteries. When, at birth, the
placental circulation stops, the umbilical arteries are reduced to small
vessels nourishing the local tissues between their point of origin and
the umbilicus. We then know their proximal portions as the internal
iliac^ or hypogastric arteries^ and the fibrous cords which still mark their
course along the wall of the bladder (the old allantoic stalk) as the
obliterated branches of the hypogastric arteries. Thus the tables are
turned between fetal and adult life. In the fetus the external iliac
artery to the leg appears as a branch of the dominating umbilical
artery. After birth the reduced umbilical arteries under their new
name of internal iliacs, or hypogastrics, appear as branches of the
now larger external iliacs. The original umbilical root proximal to
the origin of the external iliac is called the common iliac (Fig. 150).
 
III. The Veins
 
There is a natural grouping of the veins according to their relationships which it is convenient to follow in discussing their development.
Under the term systemic veins we can include all the vessels which
collect the blood distributed to various parts of the body in the routine
of local metabolism. In young embryos these would be the cardinal
 
 
 
THE VEINS
 
 
241
 
 
veins and their tributaries, that is, the return channels of the primitive
intra-embryonic circulatory arc. In older embryos and adults the
systemic veins would include the anterior (superior) caval system
which is evolved from the anterior cardinals, and the posterior
(inferior) caval system which takes the place of the postcardinals and
their tributaries.
 
We can set apart from the general systemic circulation three
special venous arcs: the umbilical, returning the blood from the
})lacenta; the pulmonary, returning the blood from the lungs; and
the hepatic portal, carrying blood from the intestinal tract to the liver.
I'he specialized nature of the placental and pulmonary circulations
is obvious. The peculiarities of the hepatic portal system call, perhaps, for a word of explanation. Ordinarily veins^ collect blood from
local capillaries and pass it on directly to the heart. Their blood stream
is away from the organ with which they arc associated ; once collected
within a vein the blood is not redistributed in capillaries until it has
again jiassed through the heart. The portal vein arises in typical
fashion by collecting the blood from capillaries in the digestive tube.
But then, contrary to the usual procedure, its blood flows, not directly
to the heart, but to the liver where it enters a second capillary bed
and is returned by a second set of collecting vessels to the heart. With
reference to the plexus of capillaries in the liver this vein is aflferent.
Hence its designation as a portal (translated = carrying to) vein,
setting it apart from other veins which carry blood only away from
the organ with which they are associated.
 
There is a tendency among those who have done but little work on the circulation to regard any vessel which carries oxygenated blood as an artery, and any vessel
which carries blood poor in oxygen and high in carbon dioxide content as a vein.
This is not entirely correct even for the circulation of adult mammals on which the
( onception is based. In comparative anatomy and especially in embryology it is far
from being the .case. It is necessary, therefore, in dealing with the circulation of the
embryo, to eradicate this not uncommon misconception.
 
The differentiation between arteries and veins which holds good for all forms,
both embryonic and adult, is based on the structure of their walls, and on the direction of their blood flow with reference to the heart. An artery is a vessel carrying
blood away from the heart under a relatively high, fluctuating pressure due to the
pumping of the heart. Correlated with the pressure conditions in it, its walls are
heavily reinforced by elastic tissue and smooth muscle. A vein is a vessel carrying
blood toward the heart under relatively low and constant pressure from the blood
welling into it from capillaries. Correlated with the pressure conditions characteristic for it, the walls of a vein have much less elastic and muscle tissue than artery
walls, and more non-elastic connective-tissue fibers.
 
 
 
Heart
 
 
" Artt Cardinal
 
 
Developing
SubcordinolPlwu3 in
tleson.
 
 
 
SubcL
 
 
von
 
 
 
Fig. 139. Diagrams illustrating stages in the development of the systemic
veins of the pig. (After Butler.) The cardinal and omphalomesenteric veins
are shown in black, the subcardinal system is stippled, the supracardinals are
horizontally hatched, and vessels arising independently of these three systems
are indicated by small crosses,
 
A, Ground plan of the veins of a young mammalian embryo (cf. Fig. 45).
 
B, Cross-section (at level of arrow in A) showing dorso-ventral relations
of the various veins.
 
C, Diagrammatic plot of veins of mm. pig embryos.
 
D, Arrangement of veins in 6“-7 ram. pig embryos.
 
242
 
 
 
Juoulor;;,
 
 
 
 
 
 
E, Cross-section (at level of arrow in D) showing dorso- ventral relations of
vessels.
 
F, Veins in 12—13 mm. embryos.
 
G, Veins in 16-19 mm. embryos.
 
H, Veins in 22-24 mm. embryos.
 
I, Veins in 30-35 mm. embryos.
 
J, Cross-section of 17 mm, embryo at level of arrow in G.
 
K, Plan of veins in adult pig^
 
 
243
 
 
 
244
 
 
THE DEVELOPMENT OF THE CTRC.ULATORY SYSTEM
 
 
Changes in the Anterior Systemic Veins Resulting in the
Establishment of the Anterior (Superior) Vena <^va. The main
tributaries draining the anterior parts of the adult body are the
external and internal jugulars and the subclavians. In 12 mm. embryos we saw all these vessels laid down. The internal jugular is
merely the original anterior cardinal under a new name. The external jugular develops from the small branch draining the mandibular region, and the subclavian as an enlargement of one of the segmental tributaries at the level of the anterior appendage bud (Fig. 68).
 
When the appendage buds first appear, the heart lies far forward
in the body. As development progresses it is carried caudad. With
this change in the position of the heart, the common cardinal veins
(ducts of Cuvier) change their relative position in the body and come
to lie caudal to the anterior appendage buds. As a result of this
altered relation the subclavian veins from the anterior appendages,
which early in development drain into the posterior cardinals (Fig.
139, C) eventually empty into the anterior cardinals (Fig. 139, G).
 
The outstanding characteristic of the systemic venous plan of a
young embryo is its bilateral symmetry. Paired vessels from the
anterior and from the posterior parts of the body become confluent
to enter the sinus region of a simple tubular heart (Figs. 1 39, A and
144, A-C). The rerouting of the blood to enter the right side of the
heart is the all-important end toward which the mammalian venous
system is progressing throughout its development. In dealing with
local changes this basic trend should never for a moment be forgotten.
 
In the anterior systemic channels this shift to the right is accomplished very simply and directly. A new vessel forms between the
right and left anterior cardinals and shunts the left anterior cardinal
blood stream across to the right (Fig. 139, H). With the establishment
of this new channel, the part of the left anterior cardinal toward the
heart drops out (Fig. 139, I). We have now but to apply the familiar
adult names (Fig. 139, K): the new connecting vessel is the left
innominate; the old anterior cardinal between the union of the subclavian with the jugulars and the new transverse connection is the
right innominate ; from the confluence of the innominates to the heart
is the anterior vena cava. The anterior vena cava is thus composed of
the most proximal part of the right anterior cardinal and the right
common cardinal vein (duct of Cuvier). The small azygos (cervicothoracic) vein, which is the reduced posterior cardinal, indicates the
old point of transition from anterior cardinal to common cardinal.
 
 
 
THE VEINS
 
 
245
 
 
Changes in the Posterior Systemic Veins Resulting in the
Establishment of the Posterior (Inferior) Vena Cava. The changes
in the systemic veins of the posterior part of the body are much more
radical than they are anteriorly. The posterior cardinal veins which
are the primitive systemic drainage channels are associated primarily
with the mesonephroi. When the mesonephroi degenerate, it is but
natural that the posterior cardinals should degenerate with them.
Hie posterior vena cava which replaces the cardinals is a composite
vessel which gradually takes shape by the enlargement and straightening of small local channels which are, as it were, pressed into service
as the posterior cardinals degenerate.
 
The subcardinal veins initiate the diversion of the postcardinal
blood stream. The subcardinals arc established as vessels lying along
the ventro-mesial border of the mesonephros parallel with, and ventral
to, the postcardinals. Taking origin from an irregular plexus of small
vessels emptying from the mesonephroi into the posterior cardinals,
the subcardinals from their first appearance have many channels
connecting them with the postcardinals (Fig. 139, A-C). As the mesonephroi increase in size and bulge toward the mid -line the subcardinals are brought very close together. In the mid -mesonephric
region they anastomose with each other to form a large median vessel,
the subcardinal sinus, or intersubcardinal anastomosis (Figs. 60, 77,
and 139, D-F). When this sinus is established the small vessels connecting sub- and postcardinals drain into the capacious sinus rather than
toward the posterior cardinals. The result of this change very soon
becomes apparent in the disappearance of the posterior cardinals at
the level of this sinus. The blood from the posterior part of the body is
still collcctecl by the distal ends of the postcardinals but it returns to
the heart by way of the subcardinal sinus. Consequently the anterior
portions of the posterior cardinals, although they persist, are much
reduced in size (Fig. 139, F).
 
Meanwhile the increased volume of blood entering the subcardinal
sinus is finding a new and more direct route to the heart. The cephalic
pole of the right mesonephros lies close to the liver. A fold of dorsal
body-wall tissue, just to the right of the primary dorsal mesentery,
early makes a sort of bridge between these two organs. This fold is
known as the caval plica {caval mesentery) (Fig. 140). In it, as everywhere in the growing body, are numerous small vessels. Connection
of these small vessels with the plexus of channels in the liver cephalically (Fig. 140, A), and the mesonephros caudaliy (Fig. 140, B),
 
 
 
246
 
 
THE DEVELOPMENT OF THE CIRCULATORY SYSl’EM
 
 
 
' : Dorsal aorta
 
 
Posterior
cardinal vein^rV
 
Cava leaving ‘ :
mesonephros^''
 
Caval plica
hCava
 
entering liver
 
Stomach
 
Ductus
venosus
 
Gall-bladder
 
Rt umbilical
vein
 
 
 
Fig. 140. Drawings of transverse sections of 5 mm. pig embryos showing
the relations of the caval fold of the mesentery (caval plica). A, Section at
level where cephalic end of caval plica merges with liver. Here the small
vessel which is the primordium of the mesenteric portion of the posterior
vena cava enters the sinusoidal circulation of the liver. B, Section showing
merging of caudal end of caval plica with right mesonephros. At this level
the developing mesenteric portion of the posterior vena cava anastomoses
with the right subcardinal vein (cf. Fig. 139, D).
 
 
provides the entering wedge. Once a current of blood finds its way
from the mesonephros to the liver through these small vessels, enlargement of the channel proceeds with great rapidity. This new channel
becomes the mesenteric part of the inferior vena cava, (See relations of
posterior vena cava in figures 75 and 76, and portion of cava indicated
with small crosses in figure 139, D.)
 
Within the liver this new blood stream at first finds its way by
devious small channels eventually entering the sinus venosus along
with the omphalomesenteric circulation. As its volume of blood
increases it excavates through the liver a main channel which gradually becomes walled in. As this new vessel becomes more and more
definitely organized it gradually crowds toward the surface and
eventually appears as a great vein lying in a notch along the dorsal
side of the liver. This is the hepatic part of the inferior vena cava.
 
From the subcardinal sinus the most direct route to this new
 
 
THE VEINS
 
 
247
 
 
outlet is by way of the right subcardinal vein. Thus in embryos as
young as 9 to 12 mm., the formation of the posterior vena cava is well
started with its proximal portion consisting of subcardinal sinus, a
portion of the right subcardinal vein, and the new channels through
the mesentery and through the liver. (Follow this part of the cava
through figure 139 from D to K.)
 
Posterior to the level of the subcardinal sinus still amother set of
veins enters into the formation of the post-cava. These are the supracardinal veins which appear, relatively late in development, as paired
channels draining the dorsal body-wall (Fig. 139, G, J).
 
At the mid-mesonephric level, the supracardinals are diverted into
the subcardinal sinus just as happened with the postcardinals earlier
in development. Cephalic to the sinus, parts of the supracardinals
persist as the azygos group draining in a somewhat variable manner
into the reduced proximal part of the postcardinals. Caudal to the
anastomosis with the subcardinal sinus, the right supracardinal becomes the principal drainage channel of the region. Its appropriation
of the tributary vessels from the posterior appendages establishes it as
the postrenal portion of the inferior vena cava and is the last step in the
formation of that composite vessel (Fig. 139, G—K).
 
The Coronary Sinus. The ultimate fate of the left common
cardinal vein (duct of Cuvier) is a result of the shift in the course of
the systemic blood so that it all enters the right side of the heart.
Formerly returning a full half of the systemic blood stream to the
heart, the left common cardinal vein is finally left almost without a
tributary from the body. In the pig a small amount of blood usually
does continue to enter it over the left azygos (Fig. 139, K). Occasionally in the pig, and normally in most other mammals, even this is cut
off and the azygos drainage is by way of the right side to the superior
cava (dotted line in Fig. 139, K). Nevertheless the proximal part of
the old left cardinal channel is utilized. Pulled around the heart in
the course of the migration of the sinus venosus toward the right, the
left common cardinal vein lies close against the heart wall for a considerable distance (Fig. 144, D). As the heart muscle grows in bulk it
demands a greater blood supply for its metabolism. The small returning veins of this circulation find their way into this conveniently
located main vessel (Fig. 144, E). Thus even when its peripheral
circulation is cut off the left common cardinal vein still persists as the
coronary sinus into which the vessels of the cardiac wall drain (Fig.
144, F).
 
 
 
248
 
 
THE DEVELOPMENT OF THE CIRCULATORY SYSTEM
 
 
 
right
 
omplLv'
 
 
right
 
iimb.v,
 
 
umb. vein*
fused
in belly
stalk
 
 
coronary sinus
(left duct of
 
 
hepatic v,
(omph.)
 
 
 
left
 
umb.v«
 
 
Fig. 141. Diagrams showing the development of the hepatic portal circulation from the omphalomesenteric veins, and the relations of the umbilical
veins to the liver. (Adapted from several sources.)
 
A is based on conditions in pig embryos of 3-4 mm.; B, on embryos of
about 6 mm.; C, on embryos of 8-9 mm.; D, on embryos of 20 mm. and
older.
 
 
 
THE VEINS
 
 
249
 
 
The Pulmonary V eins. Phylogenetically the lungs are relatively
new structures. It is not surprising, therefore, that we find the pulmonary veins arising independently and not by the conversion of old
vascular channels. They originate as vessels which drain the various
branches of the lung buds and converge into a common trunk (Fig.
107), entering the left atrium dorsally. In the growth of the heart this
trunk vessel is gradually absorbed into the atrial wall and two or more
of its original branches open directly into the left atrium as the main
pulmonary veins of the adult (Fig. 144, D-F).
 
The Portal Vein. The blood supply to the intestines is first
established through the omphalomesenteric arteries which later
become modified to form the anterior mesenteric artery. Likewise
the drainage of the intestinal tract is provided for by vessels which
were originally the return channels of the primitive omphalomesenteric circulatory arc (Fig. 45). In dealing with 9 to 12 mm. embryos
we have already seen the primary changes which occur in these vessels.
The growing cords of hepatic tissue break up the proximal portion
of the omphalomesenteric veins into a maze of small channels ramifying through the substance of the liver (Fig. 141, A, B). But the stubs
of the omphalomesenterics persist and drain this plexus. Distal to the
liver, the original veins are for a time retained, bringing blood from
the yolk-sac and intestines to the liver. With the disappearance of the
yolk-sac and the growth of the intestines, the omphalic (yolk-sac)
portions of these veins necessarily disappear, but the mesenteric
branches persist and become more extensive concomitantly with the
increased length and complexity of the intestinal tract.
 
The original omphalomesenteric trunks into which these tributaries converge become the unpaired portal vein by forming transverse
anastomoses and then abandoning one of the original channels. The
curious spiral course of the portal vein is due to the dropping out of
the original left channel cephalic to the middle anastomosis and the
original right channel caudal to the anastomosis (Fig. 141, D).
 
The Umbilical Veins. When they are first established the umbilical (allantoic) veins are embedded in the lateral body-walls
throughout their course from the belly-stalk to the sinus venosus
(Fig. 45). As the liver grows in bulk, it fuses with the lateral body-wall.
Where this fusion occurs vessels develop connecting the umbilical
veins with the plexus of vessels in the liver (Fig. 141, B). Once these
connections are established the umbilical stream tends more and more
 
 
 
250
 
 
THE DEVELOPMENT OF THE CIRCULATORY SYSTEM
 
 
to pass by way of them to the liver, and the old channels to the sinus
venosus gradually degenerate (Fig. 141, C). ^
 
Meanwhile the umbilical veins distal to their entrance into the
body become fused with each other so that there comes to be but a
single vein in the umbilical cord (Fig. 141, C). Following this fusion
in the cord, the intra-embryonic part of the umbilical channel also
loses its original paired condition. The right umbilical vein is abandoned as a route to the liver and all the placental blood is returned
over the left umbilical vein. It is interesting to note that in spite of its
ceasing to be a through channel, part of the right umbilical vein
persists, draining the body-wall. The small blood stream it then carries
is reversed in direction, flowing back into the left umbilical (Fig. 141,
D).
 
When first diverted into the liver, the umbilical blood stream
passes through by way of a mesh work of small anastomosing sinusoids.
As its volume increases it excavates a main channel through the
substance of the liver which is known as the ductus venosus (Figs. 138
and 141, B~D). Leaving the liver, the ductus venosus becomes confluent with the hepatic veins (omphalomesenteric stubs) which drain
the maze of small sinusoids in the liver. At this point, also, the vena
cava joins the others. Thus the blood streams from the posterior
systemic circulation, from the portal circulation, and from the placental circulation all enter the heart together. Embryologically this
great trunk vessel represents the fused proximal parts of the old
omphalomesenteric veins enlarged by the placental blood from the
ductus venosus and by the systemic blood from the vena cava (Fig.
141). During its early developmental phases it is often called the
common revehent hepatic vein. In the adult or in older fetuses it is more
convenient to regard it as a part of the vena cava because, with the
cessation of the placental circulation at the time of birth, the caval
blood stream becomes the dominant one.
 
IV. The Lymphatic System
 
Important and interesting as the subject is, it has seemed expedient
to omit any account of the development of the lymphatic vessels.
Those interested in this field will find that an unusual amount of
careful work has been done on the development of the lymphatics in
pig embryos. References to some of the more important recent papers
have been included in the bibliography appended at the end of the
book.
 
 
 
BLOOD CORPUSCLES
 
 
251
 
 
V. Blood Corpuscles
 
The first blood corpuscles which appear in the circulation are
produced extra-embryonically in the blood islands of the yolk-sac
(Fig. 48). Later in development there are many blood-forming centers
within the embryo. Concerning the establishment of these centers we
find the same controversy that was commented on in connection with
the origin of blood vessels. It is maintained by some authorities that
these centers always arise from cells originally produced in the yolksac blood islands. According to this interpretation some of these blood
cells are believed to remain sufficiently undifferentiated to retain their
power of active proliferation. As such cells are carried by the circulation to various parts of the body they settle in favorable locations and
raise new families of blood corpuscles.
 
According to the local origin idea it is not necessary to account
for all the centers of blood corpuscle formation on the basis of bloodmother-cells wandering in from the yolk-sac and settling down in new
locations within the embryo. It is maintained that mesodermal cells
arising in the body have the same capacity of becoming differentiated
into blood-mother-cells as mesodermal cells which arise in the yolksac. On this interpretation blood-forming centers arise in various
parts of the body from blood-mother-cells differentiated in situ from
local mesoderm. The recent experimental work tends to indicate that
such “local origin” does occur. That this same evidence proves that
the origin of blood-forming centers from migrating cells never occurs
is by no means so clear.
 
Whatever the source of the original blood-mother-cells may be
we always find them establishing their centers of proliferation in
places where the current of the circulation is sluggish. In very young
embryos the centers of corpuscle formation are located in the maze of
small channels in the yolk-sac and the allantois. When the yolk-sac
degenerates and the allantois becomes highly specialized as part of
the chorion, these centers cease to be active and new ones are established in connection with such rich vascular plexuses as those in the
mesonephros and the liver. Still later other centers appear in the
lymphoid organs, and last of all in the bone marrow (Fig. 152).
 
The histological details of the processes involved in the production
of red blood corpuscles and the various types of white blood corpuscles
are exceedingly complex. Moreover there is by no means agreement
as to the exact manner in which these processes occur, nor as to the
 
 
 
252
 
 
THE DEVELOPMENT OF THE CIRCULATORY SYSTEM
 
 
genetic relations of one type of blood corpuscle to another. This whole
subject, other than the recognition of the multiplicity of blood-forming
centers and their shifting locations in the embryo at various phases of
development, is a special field of histogenesis entirely beyond the
scope of an elementary text.
 
VI. The Heart
 
To appreciate the significance of the changes which occur in
the growing heart one must have in mind the exigencies under which
it develops. Starting as a simple tube with the blood passing through
 
 
 
Fig. 142. Ventral aspect of the heart of the pig at various stages showing
the formation of the cardiac loop and the establishment of the primary
regional divisions of the heart. Drawn (A-E, X 30; F, X 20) from reconstructions made from series in the Carnegie Collection (A-D) and in the
Western Reserve University Collection (E, F).
 
A, 7 somites; B, 13 somites; C, 17 somites; D, 25 somites; E, 3.7 mm.
(after flexion); F, 6 mm.
 
Abbreviations: At., atrium (t., right; 1., left); Bui., aortic bulb (bulbus
arteriosus); Endc., endocardial tubes; Myc., cut edge of epi-myocardium;
S.V., sinus venosus; Tr. Art., truncus arteriosus; V. ao. r., ventral aortic
roots; Vent., ventricle (r., right; 1., left); V.O.M., omphalomesenteric veins.
 
 
 
THE HEART
 
 
253
 
 
it in an undivided stream, it must become converted into an elaborately valved, four-chambered organ, partitioned in the mid-line
and pumping from its right side a pulmonary stream which is returned to the left side and pumped out again as the systemic blood
stream. And the heart cannot cease work for alteration ; there can be
no interruption in the current of blood it pumps to the growing
embryo. This is but one phase of the matter. At the end of gestation
the vascular mechanism must be prepared to function under conditions radically different from those surrounding the embryo. In spite
of the impossibility of the developing lungs being effectively exercised
under air-breathing conditions, they themselves, their blood vessels,
 
 
 
Fig. 143. Sinistral aspect of reconstructions of the pig heart.
 
A, 13 somite embryo (cf. Fig. 142, B); B, 17 somite embryo (cf. Fig.
142, C); C, 25 somite embryo (cf. Fig. 142, D); D, 3.7 mm. embryo (cf.
Fig. 142, E); E, 6 mm. embryo (cf. Fig. 142, F).
 
Abbreviations: A.C.V., anterior cardinal veins; Al.V., allantoic (umbilical) vein; Ao., aorta; At., atrium; Bui., aortic bulb; Cav. P., posterior
vena cava; Cuv. d., duct of Cuvier (common cardinal vein); Myc., cut edge
of epi-myocardium; P.C.V.; posterior cardinal vein; S.V., sinus venosus;
Sin-at., sino-atrial region of heart; Tr. Art., truncus arteriosus; V. ao. r.,
ventral aortic roots; Vent., ventricle; V.O.M., omphalomesenteric veins.
 
 
254
 
 
THE DEVELOPMENT OF THE CIRCULATORY SYSTEM
 
 
and the right ventricle which pumps blood to them, must at the
moment of birth be ready to take over the entire r^esponsibility of
oxygenating the blood. And the systemic part of the circulation as
well as the pulmonary must be prepared. Throughout intra-uterine
development the left side of the heart receives less blood from the
pulmonary veins than the right side of the heart receives from the
venae cavae. Yet after birth the left ventricle is destined to carry a
greater load than the right ventricle. It must pump through the
myriad peripheral vessels of the systemic circulation,, sufficient blood
to care for the active metabolism and continued growth of the entire
body. These are some of the situations which must be faced before the
heart can arrive at its adult condition. The manner in which they are
met is doubly interesting because they seem at first sight so difficult.
 
The Formation of the Cardiac Loop and the Establishment of
the Regional Division of the Heart. In dealing with the establishment of the circulatory system in very young embryos we saw how
the tubular heart was formed by the fusion of paired primordia
(see Chap. 5 and especially Figs. 43 and 44). The primary factor
which brings about its regional differentiation is the rapid elongation
of this primitive cardiac tube. The heart increases in length so much
faster than the chamber in which it lies that it is first bent to the right
and then twisted into a loop. Since the anterior end of the heart is
anchored in the body by the aortic roots, and the posterior end by
the great veins, it is the mid-portion of the heart-tube which, in this
process, undergoes the most extensive changes in position. This is
facilitated by the early disappearance of the dorsal mesocardium
which leaves the heart entirely free in its mid-region.
 
During the period in which the cardiac loop is being formed, the
primary regional divisions of the heart become clearly differentiated.
The sinus venosus is the thin-walled chamber in which the great veins
become confluent to enter the heart at its primary posterior end
(Fig. 144). The atrial region is established by transverse dilation of
the heart-tube just cephalic to the sinus venosus (Fig. 144).
 
The ventricle is formed by the bent mid-portion of the original
cardiac tube. As this ventricular loop becomes progressively more
extensive, it at first projects ventrally beneath the attached aortic
and sinus ends of the heart (Fig. 143, A-C). Later it is bent caudally
so that the ventricle, formerly situated cephalic to the atrium, is
brought into its characteristic adult position caudal to the atrium
(Fig. 143, D, E). Between the atrium and ventricle the heart remains
 
 
 
 
Pulmonary A
from Arch 11
 
 
Left
 
Com
 
CardV
 
 
Auricular /
 
App
 
 
Left Superior
Pulmonary V
 
 
Uft Inf Pul.V
 
Oblique Vein
Hrshall) â– 
of L Atrium
 
Great Cardiac V.
 
 
Coronary Sinus ^
 
toralTOv)
 
 
Leff Ventricle
 
 
f^XCom Card V
Vena Cava)
 
-Pul
Artery
 
 
 
Rt Pul
Veins
 
 
 
Right
Ventricle
 
Superior Vena Cava
 
Sulcus Terminalis
 
Sinus Venarum
 
Small Cardiac V
 
Inferior Vena Cava
 
Middle Cardiac Vein
 
 
Fig. 144. Six stages in the development of the heart, drawn in dorsal
aspect to show the changing relations of the sinus venosus and great veins
entering heart. (Patten: ‘‘Human Embryology,” The Blakiston Company.)
 
255
 
 
 
256
 
 
THE DEVELOPMENT OF THE CIRCULATORY SYSTEM
 
 
relatively undilated. This narrow connecting portion is the atrioventricular canal.
 
The most cephalic part of the cardiac tube undergoes least change
in appearance, persisting as the truncus arteriosus connecting the ventricle with the ventral aortic roots (Fig. 142). In very young embryos
there is a conspicuous bulge where the truncus arteriosus swings
toward the mid-line to break up in the aortic arches. This sharply
bent and somewhat dilated region is called the aortic bulb (Fig. 142,
B, C). Its location is of interest as being the place at which the paired
endocardial primordia first fused with each other (Figs. 43 and 44)
and the place at which, later in development, the division of the
truncus arteriosus into separate aortic and pulmonary roots will first
become apparent. The bulge itself soon merges into the rest of the
truncus arteriosus without giving rise to any special structure.
 
Almost from their earliest appearance the atrium and the ventricle
show external indications of the impending division of the heart into
right and left sides. A distinct median furrow appears at the apex of
the ventricular loop (Figs. 142, E, F, and 144, U, E). The atrium
meanwhile has undergone rapid dilation and bulges out on either
side of the mid-line (Fig. 144). Its bilobed configuration is emphasized by the manner in which the truncus arteriosus compresses it
mid-ventrally (Fig. 142, E, F).
 
The Partitioning of the Heart. These superficial features suggest
the more important changes going on internally. As the wall of the
ventricle increases in thickness it develops on its internal face a meshwork of interlacing muscular bands, the trabeculae carneae. Opposite
the external furrow in the ventricle these muscular bands become
consolidated as a partition which appears to grow from the apex of
the ventricle toward the atrium. This is the interventricular septum
(Fig. 147).
 
Meanwhile two conspicuous masses of peculiar, loosely organized
mesenchyme (called endocardial-cushion tissue) develop in the walls
of the narrowed portion of the heart between the atrium and the
ventricle. One of these so-called endocardial cushions of the atrio-ventricular
canal is formed in its dorsal wall (Fig. 147, A) and the other is formed
opposite, on the ventral wall. These two masses nearly occlude the
central part of the canal and thus initiate its separation into right and
left channels.
 
At the same time a median partition appears in the cephalic
wall of the atrium. Because another closely related partition is destined
 
 
 
THE HEART
 
 
257
 
 
to form here later, this one is called the first interatrial septum or
septum primum. In shape it is crescentic with its concavity directed
toward the ventricle and the apices of the crescent extending, one
along the dorsal wall, and one along the ventral wall of the atrium,
all the way to the atrio-ventricular canal where they merge, respectively, with the dorsal and ventral endocardial cushions (Fig. 147).
This leaves the atria separated from each other except for an opening
called the interatrial foramen primum.
 
While these changes have been occurring, the sinus venosus has
been shifted out of the mid-line so that it opens into the atrium to
the right of the interatrial septum (Fig. 147). The heart is now in a
critical stage of development. Its simple tubular form has been
altered so that the four chambers characteristic of the adult heart
are clearly recognizable. Partitioning of the heart into right and left
sides is well under way. But there is as yet no division of the blood
stream because there are still open communications from the right to
 
 
Carotid arch (III)
Aortic arch (IV)
Pulmonary arch (VI)
 
 
Left atrium—
Anterior cardinal
 
 
Posterior cardinal vein /
Interatrial foramen Iv
 
Septum 1 1
 
 
Truncus arteriosus
 
 
Pulmonary channel
 
 
-Aortic channel
 
 
 
interventricular
 
foramen
 
Interventricular
 
septum
 
 
Trabeculae
 
 
Valvulae venosae
 
 
/ Inferior vena cava
 
Atrio-ventricular valve
 
 
Fio. 145. Reconstruction of the heart of a 9.4 mm. pig embryo cut
open somewhat to the right of the mid-line to show its internal structure
(cf. Fig. 146).
 
 
 
 
 
 
 
 
 
 
258
 
 
THE DEVELOPMENT OF THE CIRCULATORY SYSTEM
 
 
the left side in both atrium and ventricle. A little further progress in
the growth of the partitions, however, and the two si^cs of the heart
would be completely separated. Were this to occur now, the left side
 
 
 
Fig. 146. Section (X 45) through the heart of a 9.4 mm. pig
embryo, at the level of the atrio-ventricular canals. (From the
series used in making the reconstruction appearing as figure 145.
This section may be oriented as passing horizontally through Fig.
145 at the level of the most caudal portion of the interventricular foramen.)
 
 
of the heart would become almost literally dry. For the sinus venosus,
into which systemic, portal, and placental currents all enter, opens
on the right of the interatrial septum, and not until much later do
the lungs, and their vessels develop sufficiently to return any considerable volume of blood to the left atrium. The partitions in the
 
 
 
THE HEART
 
 
259
 
 
ventricle and in the atrio-ventricular canal do progress rapidly to
completion (Figs. 147, 148, and 149), but an interesting series of
events takes place at the interatrial partition which assures an adequate supply of blood reaching the left atrium and thence the left
ventricle.
 
Just when it appears that the septum primum is going to fuse with
the endocardial cushions of the atrio-ventricular canals, closing the
interatrial foramen primum and isolating the left atrium, a new
opening is established. The more cephalic part of the septum primum
ruptures to form the interatrial for amen secundum, thus keeping a route
open from the right to the left atrium (Fig. 148).
 
At about this time the second interatrial partition makes its
appearance just to the right of the first. Also crescentic in form, this
septum secundum extends its apices along the dorsal and ventral walls
of the atrium to fuse with the septum primum near the endocardial
cushion mass which now completely divides the atrio-ventricular
 
 
 
Fig. 147. Drawings showing the initial steps in the partitioning of the
heart.
 
A, Slightly schematized drawing from reconstruction of heart of 3.7 mm.
pig embryo. The heart has been opened by a diagonally frontal cut in the
plane which can be indicated by drawing a line through the labels At. and
Vent, in figure 143, D. The dorsal portion of the heart is shown viewed from
the ventral side.
 
B, Slightly schematized drawing from a reconstruction of the heart of a
6 mm. pig embryo. The heart has been opened in a plane which can be
indicated by drawing a line through the labels At, and Vent, in figure 143, E.
The dorsal portion of the heart is shown viewed from the ventral side.
 
 
260
 
 
THE DEVELOPMENT OF THE CIRCULATORY SYSTEM
 
 
septum II
 
 
septum I
 
 
septum
 
spurium"
 
 
 
trabeculae
 
cameae
 
 
^ interatrial
 
foramen II
 
 
septum I
 
 
interatrial
â– " foramen I
^almost closed}
 
 
a V canal
endocardial cushion
 
 
— intervent
septum
 
 
Fig, 148. Slightly schematized drawing from a reconstruction of the heart
of a 9.4 mm. pig embryo. Dorsal part of heart, interior view. The plane in
which the heart is opened can be indicated by drawing a line through the
center of the interatrial and the interventricular foramina in figure 145.
 
 
canals. But the septum secundum never becomes a complete partition.
An oval opening of considerable size persists in its center. This is the
foramen ovale (Fig. 149).
 
The newly established septum secundum and the flap-like remains
of the septum primum constitute an efficient valvular mechanism
between the two atria. When the atria are filling, some of the blood
discharged from the venae cavae into the right atrium can pass freely
through the foramen ovale by merely pushing aside the flap of the
septum primum. The inferior caval entrance lies adjacent to, and
is directed straight into, the orifice of the foramen ovale (Fig. 149).
Consequently it is primarily — some think exclusively — blood from
the inferior vena cava which passes through the foramen ovale into
the left atrium. When the atria start to contract, pressure of the blood
within the left atrium forces the flap of the septum primum against the
foramen ovale, effectively closing it against return flow into the right
atrium. Without some such mechanism affording a supply of blood
 
 
THE HEART
 
 
261
 
 
septum 11
 
 
^ interatrial foramen 11
 
 
septum I
 
 
anterior
vena cava
 
 
- pulmonary
veins
 
left atrium
 
 
coronary
 
 
 
right
 
ventricle
 
 
papillary muscle
interventricular
 
septum
 
 
Fig. 149. Schematic drawing based on dissected heart of pig fetus shortly
before birth. Interior aspect of dorsal part of heart to show valvular mechanism at foramen ovale.
 
 
to its left side, the developing heart could not be partitioned in the
mid-line ready to assume its adult function of pumping two separate
blood streams.^
 
While alf these changes have been going on in the main part of
the heart, the truncus arteriosus has been divided into two separate
channels. Reference has already been made to the start of this process
in the aortic root between the fourth and sixth arches (Fig. 133).
Continuing toward the ventricle, the division is effected by the formation of longitudinal ridges of plastic young connective tissue of the
same type as that making up the endocardial cushions of the atrioventricular canal. These ridges, called truncus ridges^ bulge progres
 
^ There are on record a few cases of a peculiar cardiac malformation in which
this valvular communication was prematurely closed and the left atrium thereby
shut off from the right. In all these cases the left side of the heart has not been sufficiently developed to support life for any length of time after birth.
 
 
262
 
 
THE DEVELOPMENT OF THE CIRCULATORY SYSTEM
 
 
sively farther into the lumen of the truncus arteriosus and finally meet
to separate it into aortic and pulmonary channels. ^ (Note shape of
lumen in Figs. 142, F, and 145.) The semilunar valves of the aorta,
and of the main pulmonary trunk (Fig. 138), develop as local specializations of these truncus ridges. Toward the ventricles from the site
of formation of the semilunar valves the same ridges are continued
into the conus of the ventricles. The fact that proximal to the valves
these ridges are, for descriptive purposes, called conus ridges should not
be allowed to obscure their developmental and functional continuity
with the truncus ridges. The truncus and conus ridges follow a spiral
course such that where the conus ridges extend down into the ventricles they meet and become continuous with the interventricular
septum. The right ventricle then leads into the pulmonary channel
and the left into the aorta. With this condition established the heart
is completely divided into right and left sides except for the interatrial
valve which must remain open throughout fetal life, until, after birth,
the lungs attain their full functional capacity and the full volume of
the pulmonary stream passes through them to be returned to the left
atrium.
 
This leaves but one of the exigencies of heart development still to
be accounted for. If, during early fetal life, before the lungs were well
developed, the pulmonary channel were the only exit from the right
side of the heart, the right ventricle would have an outlet inadequate
to develop its pumping power. For it is only late in fetal life that the
lungs and their vessels develop to a degree which prepares them for
assuming their postnatal activity, and the power of the heart muscle
must be built up gradually by continued functional activity. This
situation is met by the ductus arteriosus leading from the pulmonary
trunk to the aorta (Fig. 138). The right ventricle is not unprepared
for its adult function because it pumps its full share of the blood
throughout fetal life. Instead of all going to the lungs, however, part
of the blood pumped by the right ventricle passes by way of the ductus
arteriosus into the aorta (Fig. 150). As the lungs increase in size,
relatively more blood goes to them and relatively less goes through
the ductus arteriosus. By the time of birth enough blood is passing
through the lungs to support life, and within a short time after birth,
under the stimulus of functional activity, the lungs are able to take all
the blood from the right side of the heart and the ductus arteriosus is
gradually obliterated. The ductus arteriosus, therefore, serves during
intra-uterine life as what might be called a ‘‘compensated exercising
channel” for the right ventricle.
 
 
 
THE HEART
 
 
263
 
 
Changes in the Sinus Region. In following the story of the
development of the heart from the functional standpoint, many things
of less striking significance have been passed over. Some of these
should have a word of comment. Cephalic to the sinus orifice the
valvulae venosae which guard it against return flow fuse and are prolonged onto the dorsal wall of the atrium in the form of a ridge called
the septum spurium (false septum). This septum is, for a time, too
conspicuous to ignore, but it is of little importance in the partitioning
of the heart and soon undergoes retrogression.
 
As the heart grows it absorbs the sinus venosus into its walls so
that eventually the anterior and posterior venae cavae and the
coronary sinus all open separately into the right atrium (cf. Figs. 147,
148, and 149). Portions of the right valvula venosa are retained as the
valves of the caval and coronary orifices. In the adult heart a small
external sulcus can usually be found between the entrance of the
anterior and the posterior vena cava which records the old line of
demarcation between sinus venosus and atrium.
 
The Atrio-ventricular Valves and the Papillary Muscles. At
the point where the atrio-ventricular canals open into the ventricles
there are early indications of the establishment of valves. From the
partition in the atrio-ventricular canal and from the outer walls on
either side, masses of tissue in the shape of thick, blunt flaps project
toward the ventricle (Figs. 146 and 148). It is these masses of a primitive type of connective tissue, similar to that in the endocardial
cushions of the canal, which later become differentiated into the flaps
of the adult valves (Fig. 149). The papillary muscles and tendinous
cords which, in the adult, act as stays to these valves, arise by modification of soine of the related trabeculae carneae (cf. Figs. 146, 148,
and 149).
 
The Aortic and Pulmonary Valves. The valves which guard
the orifices of the aorta and of the pulmonary artery arise from
mesenchymal pads (Fig. 138) already mentioned as developing in
connection with the truncus septum. In early histological appearance
and in the manner in which this loose tissue gradually becomes
organized into the exceedingly dense fibrous tissue characteristic of
adult valves, they are similar to the atrio-ventricular valves. They
do not, however, develop any supporting strands comparable to the
papillary muscles and tendinous cords.
 
Course and Balance of Blood Flow in the Fetal Heart. All the
steps in the partitioning of the embryonic heart lead gradually toward
the final adult condition in which the heart is completely divided into
 
 
 
264
 
 
THE DEVELOPMENT OF THE CIRCULATORY SYSTEM
 
 
right and left sides. Yet from the nature of its living conditions it is
not possible for the tetus in utero fully to attain the adult type of
circulation. The plan of the completely divided circulation is predicated on lung breathing. In the adult the right side of the heart
receives the blood returning from a circuit of the body and pumps
it to the lungs where it is relieved of carbon dioxide and acquires a
fresh supply of oxygen. The left side of the heart receives the blood
that has just passed through the lungs and pumps it again through
ramifying channels to all the tissues of the body. In the fetus the
function of respiration is carried out in the placenta by interchange
with the maternal blood circulating through the uterus. The lungs,
although in the last part of fetal life they are fully formed and ready
to function, cannot actually begin their work until after birth. The
radical change which must inevitably take place immediately following birth in the manner in which the blood is oxygenated has led to a
widespread belief that there must be revolutionary changes in the
routing of blood through the heart and great vessels. However, as the
embryology of the circulatory system has been studied more closely
from a functional angle it is becoming increasingly clear that the
heart and the major vascular channels develop in such a manner that
the pumping load on the different parts of the heart remains balanced
at all times during fetal life. Moreover, the very mechanisms which
maintain this cardiac balance during intra-uterine life are perfectly
adapted to rebalance the circulatory load on the new postnatal basis
without involving any sudden overloading of previously inactive
parts of the vascular system.
 
To understand the changes in circulation which are so smoothly
accomplished at the time of birth it is necessary to have clearly in
mind the manner in which the way for them has been prepared
during intra-uterine life. In the foregoing account of the development
of the interatrial septal complex, emphasis was laid upon the fact
that at no time were the atria completely separated from each other.
This permits the left atrium, throughout prenatal life, to receive a
contribution of blood from the inferior cava and the right atrium by
a transseptal flow which compensates for the relatively small amount
of blood entering the left atrium of the young embryo by way of the
pulmonary circuit, and maintains an approximate balance of intake
into the right and left sides of the heart.
 
The precise manner in which this transseptal flow occurs, and
where, and to what extent the various blood streams of the fetal
 
 
 
THE HEART
 
 
265
 
 
circulation are mixed has long been a controversial subject. The recent
brilliant work of Barcroft and Barron and their co-workers has gone
far toward putting some of these old controversies into proper perspective. Their first approach was through the quantitative analysis
of blood samples drawn from various critical parts of the fetal circulation. The oxygen content of such samples has given important
evidence as to what mixing of the currents is actually taking place in
the living fetus. Later work involving the collaboration of Barclay
and Franklin utilized serial x-ray photography following the injection
of opaque material into the blood stream at various points. This
method has given further direct evidence as to the course followed by
some of the important blood currents. Synthesizing the most significant of the anatomical evidence with the newer experimental evidence, the course followed by the blood in passing through the fetal
heart may be summarized somewhat as follows. The inferior caval
entrance is so directed with reference to the foramen ovale that a considerable portion of its stream passes directly into the left atrium
(Figs. 149 and 150). Under fluctuating pressure conditions — say
following uterine contractions which send a surge of placental blood
through the umbilical vein — the placental flow may temporarily
hold back any blood from entering the circuit by way of either the
portal vein or the inferior caval tributaries (Fig. 150). For a time,
under these conditions, the left atrium would be charged almost
completely with fully oxygenated blood. Such conditions, however,
would be but temporary and would be counterbalanced 6y periods
when the portal and systemic veins poured enough blood into the
common channels to load the heart for a time with mixed or depleted
blood. The ipiportant thing physiologically is not the fluctuations,
but the maintenance of the average oxygen content of the blood at
adequate levels.
 
Compared with conditions in adult mammals, the mixing of
oxygenated blood freshly returned from the placenta with depleted
blood returning from a circuit of the body may seem inefficient. But
this is a one-sided comparison. The fetus is an organism in transition.
Starting with a simple ancestral plan of structure and living an aquatic
life, it attains its full heritage but slowly. It must be viewed as much
in the light of the primitive conditions from which it is emerging as in
comparison with the definitive conditions toward which it is progressing. Below the bird-mammal level circulatory mechanisms with
partially divided and undivided hearts and correspondingly un
 
 
266
 
 
THE DEVELOPMENT OF THE CIRCULATORY SYSTEM
 
 
 
birth.
 
 
 
THE HEART
 
 
267
 
 
separated blood streams meet all the needs of metabolism and
growth. Maintenance of food, oxygen, and waste products at an
average level which successfully supports life does not depend on
''pure currents,” although such separated currents undoubtedly
make for higher efficiency in the rate of interchange of materials.
From a comparative viewpoint, the fact that the mammalian fetus is
supported by a mixed circulation seems but natural.
 
Another significant fact is that careful measurements have shown
that the interatrial communication in the heart of the fetus at term
is considerably smaller than the inferior caval inlet. This would mean
that the portion of the inferior caval stream which could not pass
through this opening into the left atrium would eddy back and mix
with the rest of the blood in the right atrium.
 
One of the most important inferences as to the fetal circulation
based on vessel size is that the circulation through the lungs in a fetus
which is sufficiently mature to be viable is of considerable volume.
This too has now been supported by experimental work. From the
standpoint of smooth postnatal circulatory readjustments, the larger
the fetal pulmonary return becomes the less will be the balancing
transatrial flow, and the less will be the change entailed by the assumption of lung breathing. Very early in development, before the lungs
have been formed, the pulmonary return is negligible and the flow
from the right atrium through the interatrial ostium primum constitutes practically the entire intake of the left atrium. After the
ostium primum is closed and while the lungs are but little developed,
flow through the interatrial ostium secundum must still be the major
part of the blood entering the left atrium. During the latter part of
fetal life the foramen ovale in septum secundum becomes the transseptal route. As the lungs grow and the pulmonary circulation
increases in volume, a progressively smaller proportion of the left
atrial intake comes by way of the foramen ovale and a progressively
larger amount from the vessels of the growing lungs.
 
The balanced atrial intake thus maintained implies a balanced
ventricular intake, and this in turn implies a balanced ventricular
output. Although not in the heart itself, we have seen that there is in
the closely associated great vessels a mechanism which affords an
adequate outlet from the right ventricle during the period when the
pulmonary circuit is developing. When the pulmonary arteries are
formed from the sixth pair of aortic arches, the right sixth arch soon
loses its original connection with the dorsal aorta. On the left, how
 
 
268
 
 
THE DEVELOPMENT OF THE CIRCULATORY SYSTEM
 
 
ever, a portion of the sixth arch persists as a large vessel connecting
the pulmonary artery with the dorsal aorta (Fig^. 138 and 150).
This vessel, already familiar to us as the ductus arteriosus, remains
open throughout fetal life and acts as a .shunt, carrying over to the
aorta whatever excess of blood the pulmonary vessels at any particular
phase of their development are not prepared to receive from the right
ventricle. As has already been pointed out, the ductus arteriosus can
be called the “exercising channel” of the right ventricle because it
makes it possible for the right ventricle to carry its full share of work
throughout development and thus to be prepared for pumping all the
blood through the lungs at the time of birth.
 
VII. The Changes in the Circulation Following Birth
 
The two most obvious changes which occur in the circulation at
the time of birth are the abrupt cutting off of the placental blood
stream and the immediate assumption by the pulmonary circulation
of the function of oxygenating blood. One of the most impressive
things in embryology is the perfect preparedness for this event which
has been built into the very architecture of the circulatory system
during its development. The shunt at the ductus arteriosus, whic ii
has been one of the factors in balancing ventricular loads throughout
development, and the valvular mechanism at the foramen ovale,
which has at the same time been balancing atrial intakes, are perfectly adapted to effect the postnatal rebalancing of the circulation.
The closure of the ductus arteriosus is the primary event and the
closure of the foramen ovale follows as a logical sequel.
 
It has long been known that the lumen of the ductus arteriosus is
gradually occluded postnatally by an overgrowth of its intimal tissue.
This process in the wall of the ductus is as characteristic and regular
a feature of the development of the circulatory system as the formation of the cardiac septa. Its earliest phases begin to be recognizable
in the fetus as the time of birth approaches, and postnatally the
process continues at an accelerated rate to terminate in complete
anatomical occlusion of the lumen of the ductus about six to eight
weeks after birth,
 
Barcroft, Barclay, and Barron have conducted an extensive series
of experiments on animals delivered by Cesarean section which,
indicate that the ductus arteriosus closes functionally far sooner than
it does anatomically. Following birth there appears to be a contraction of the circularly disposed smooth muscle in the wall of the ductus
 
 
 
THE CHANGES IN THE CIRCULATION FOLLOWING BIRTH 269
 
which promptly reduces the flow of blood through it. This reduction
in the shunt from the pulmonary circuit to the aorta, acting together
with the newly assumed respiratory activity of the lungs themselves,
aids in raising the pulmonary circulation promptly to full functional
level. At the same time the functional closure of the ductus by muscular contraction paves the way for the ultimate anatomical obliteration
of its lumen by overgrowth of intimal connective tissue. This concept
of the immediate functional closure of the ductus is so appealing on
theoretical grounds that a little extra caution in evaluating the evidence is indicated. It should be borne in mind that an initial tendency
on the part of the circular smooth muscle of the ductus to contract
does not necessarily imply a contraction sufficiently strongly and
steadily maintained to shut off all blood flow during the six to eight
weeks occupied by morphological closure. The dramatic quality of an
immediate muscular response should not cause us to forget the importance of the slower but more positive structural closure.
 
The results of increased pulmonary circulation with the concomitant increase in the direct intake of the left atrium are manifested secondarily at the foramen ovale. Following birth, as the
pulmonary return increases, compensatory blood flow from the right
atrium to the left decreases correspondingly, and finally ceases
altogether. This is indicated anatomically by a progressive reduction
in the looseness of the valvula foraminis ovalis and the consequent
diminution of the interatrial communication to a progressively narrower slit between the valvula and the septum. When equalization
of atrial intakes has occurred, the compensating one-way valve at the
foramen ovale falls into disuse, and the foramen ovale may be regarded as functionally closed.
 
Anatomical obliteration of the foramen ovale follows leisurely in
the wake of its functional abandonment. There is a considerable
interval following birth before the septum primum fuses with the
septum secundum to seal the foramen ovale. This delay is, however,
of no import because as long as the pulmonary circuit is normal and
pressure in the left atrium does not fall below that in the right, the
orifice between them is functionally inoperative. It is not uncommon
to find the fusion of these two septa incomplete in the hearts of individuals who have, as far as circulatory disturbances are concerned,
lived uneventfully to maturity. Such a condition can be characterized
as ‘‘probe potency’’ of the foramen ovale. When, in such hearts, one
inserts a probe under the margin of the fossa ovalis and pushes it
 
 
 
270
 
 
THE DEVELOPMENT OF THE CIRCULATORY SYSTEM
 
 
toward the left atrium one is, so to speak, prying behind the no longer
used, but still unfastened, interatrial door. ,
 
With birth and the interruption of the placental circuit there
follows the gradual fibrous involution of the umbilical vein and the
umbilical arteries. The flow of blood in these vessels, of course, ceases
immediately with the severing of the umbilical cord, but obliteration
of the lumen is likejy to take from three to , five weeks, and isolated
portions of these vessels may retain a vestigial lumen for much longer.
Ultimately these vessels are reduced to fibrous cords. The old course
of the umbilical vein is represented in the adult by the round ligament of the liver extending from the umbilicus through the falciform
ligament, and by the ligamentum venosus within the substance of the
liver. The proximal portions of the umbilical arteries are retained in
reduced relative size as the hypogastric or internal iliac arteries. The
fibrous cords extending from these arteries on either side of the urachus
toward the umbilicus represent the remains of the more distal portions
of the old umbilical arteries. They are known in the adult as the
obliterated branches of the hypogastric arteries, or as the lateral
umbilical ligaments.
 
Much yet remains to be learned as to the more precise physiology
of the fetal circulation and as to the interaction of various factors
during the transition from intra-uterine to postnatal conditions.
Nevertheless, with our present knowledge it is quite apparent that the
changes in the circulation which occur following birth involve no
revolutionary disturbances of the load carried by different parts of
the heart. The fact that the pulmonary circulation is already so well
developed before birth means that the changes which must occur
following birth are far less profound than was formerly believed ; and
the compensatory mechanisms at the foramen ovale and the ductus
arteriosus which have been functioning all during fetal life are entirely
competent to effect the final postnatal rebalancing of the circulation
with a minimum of functional disturbance. It is still true that as
individuals we crowd into a few crucial moments the change from
water living to air living that in phylogeny must have been spread
over eons of transitional amphibious existence. But as we learn more
about this change in manner of living, it becomes apparent that we
should marvel more at the completeness and the perfection of the
preparations for its smooth accomplishment, and dwell less on the
old theme of the revolutionary character of the changes involved.
 
 
 
==Chapter  12==
 
 
Tke Histogenesis of Bone and tlie
Development of tke Skeletal System
 
 
I. Histogenesis of Bone
 
Histologically bone belongs to the group of tissues known as the
connective and supporting tissues. In spite of their widely varying
adult conditions these.tissues are all similar in that the secreted parts,
rather than the cells themselves, carry out the functional role characteristic of the tissues. It is the secreted, fibrous portion of the binding
connective tissues which ties together various other tissues and
organs ; it is the secreted matrix of cartilage and of bone which affords
rigid support and protection to soft parts and furnishes a lever system
on which the muscles may be brought into play.
 
The cellular elements of these tissues must not be overlooked,
however, in emphasizing the functional importance of the cell
products. The cells are, so to speak, the power behind, in that they
extract the appropriate raw materials from the circulation, elaborate
them within their cytoplasm, and deposit the characteristic secretion
as an end-product. Moreover after the fiber is formed or the matrix
is laid down, it is dependent on the cells for maintenance in a healthy
active conditidn.
 
Embryologically the entire connective-tissue group arises from
mesenchymal cells. It is not surprising, in view of their closely related
functions and their derivation from a common type of ancestral cell,
that one type of connective tissue may be converted into or replaced
by another. This facility for changing the type of specialization is
sometimes referred to as plasticity.
 
The plasticity of the connective-tissue series is well exemplified
in the development of bone. Bone does not form in vacant spaces.
It is always laid down in an area already occupied by some less highly
specialized member of the connective-tissue family. The formation of
some bones begins in areas already occupied by connective tissue —
such bones are said to be intramembranous in origin, or are spoken
 
271
 
 
 
272 HISTOGENESIS OF BONE AND DEVELOPMENT OF SKELETAL SYSTEM
 
 
of as membrane bones. Other bones are laid down in areas already
occupied by cartilage. In this case they are said to be pndochondral in
origin, or, are called cartilage bones. It should be clearly borne in mind
that these terms apply solely to the method by which a bone develops
and do not imply any differences in histological structure, once the
bone is fully formed.
 
Likewise we should know at the outset what histologists mean
when they speak of cancellous bone and compact bone. These terms
refer not to the method of origin of the bone but to its density when
fully formed. Developmen tally all bone goes through the spongy or
cancellous stage. Some bones later become compact, others remain
cancellous. Most bones are compact in some areas and cancellous
in others.
 
The subject of bone development can be presented more simply
if we take up first the formation of primary cancellous bone intramembranously ; then the method by which this same type of spongy
bone is formed within cartilage, and finally the changes by which
cancellous bone, formed in either of the above ways, may become
secondarily compact.
 
Intramembranous Formation of Primary Cancellous Bone. In
 
an area where intramembranous bone formation is about to begin
we find an abundance of mesenchymal cells congregated and numerous small blood vessels present. The mesenchymal cells soon exhibit a
tendency to cluster together in more or less elongated groups here
and there throughout the area. If we study a group of this type which
has been aggregated for a short time we can make out the beginning
of a definite plan of organization. Near the axis of the cord delicate
fibers appear, produced by the secretory activity of the cells. As this
fibrous strand becomes more definite, the cells tend to become ranged
against it (Fig. 151, A). In so doing they retract the cytoplasmic
processes which are so characteristic of undifferentiated mesenchymal
cells and become rounded. In this stage we have essentially a connective tissue in which the fibrous strands are for the most part rather
widely separated from one another, and in which each strand has,
lined up against it^ the cells responsible for its production.
 
The actual deposition of bone matrix begins very soon after the
establishment of these primordial strands of mesenchymal cells and
fibers. In fact one usually finds the formation of bone beginning on
the older part of a strand while the strand itself is still being extended
at one end by the aggregation of more mesenchymal cells (Fig. 151,
 
 
 
HISTOGENESIS OF BONE
 
 
273
 
 
 
I'k;. 151, Formation of trabeculae of membrane bone. Projection drawings from the mandible of a pig embryo 130 mm. in length (cf. Fig. 182).
 
Abbreviations: Matrix cal., ossein matrix impregnated with calcium
salts; Matrix oss., ossein matrix not yet impregnated with calcium salts.
 
A). When the mesenchymal cells ranged against the fibrous axis of
such a strand become active in the secretion of calcareous material
they are spoken of as osteoblasts. We should not lose sight of the fact
that they are the same cells which formed the fibrous axis of the
original strands, given a new name in deference to their further
specialization and altered internal chemistry.
 
In studying the deposition of bone matrix one must bear in mind
its dual nature. The matrix consists of an organic fibrous framework
which is impregnated by a subsequent deposit of inorganic calcium
compounds. We may liken the matrix of bone to reinforced concrete*
In the making of a road or a wall, a meshwork of steel is first placed in
the forms and concrete is then poured in. The steel gives the finished
structure tensile strength and a certain amount of elasticity, the concrete gives form and hardness. So in bone the organic fibers {ossein
fibers) impart strength and resilience, while the calcium salts whh
which the fibers are impregnated give to the completed matrix body
and rigidity.
 
 
 
274 HISTOGENESIS OF BONE AND DEVELOPMENT OF SKELETAL SYSTEM
 
 
The two steps in the deposition of bone matrix may be demonstrated readily in areas where active bone forma^tion is going on,
owing to the fact that the presence of calcium compounds- in a tissue
markedly increases its affinity for stains. Even after most of the calcium salts have been removed from the ossein framework by treatment
of the tissue with acids (decalcification) to permit the making of
sections, the staining reaction is still apparent. This indicates that
the ossein fibers in which calcium has once been deposited are more
or less permanently changed chemically even though all the calcium
possible is subsequently removed.
 
If we look at a strand on which the osteoblasts have been active
for a time (Fig. 151, B) we see, next to the osteoblasts, a zone of bone
matrix which takes very little stain. This is the newly deposited
organic portion of the matrix as yet unimpregnated with calcium salts.
It consists of a feltwork of minute fibers so delicate and so closely
matted together that it is very difficult in ordinary preparations to see
the individual fibers at all. Slightly farther from the osteoblasts the
matrix is densely stained (Fig. 151, B). This part of the matrix has
been impregnated with calcium salts, chiefly phosphates and carbonates, and has thereby been converted into true bone matrix. The
calcium utilized by the osteoblasts in this process is brought to them
by the blood stream where it is carried in soluble form, probably in
organic linkage. It is interesting to note in this connection that the
presence of calcium and of phosphates in the blood is not in itself all
that is necessary for this process. There must be present also sufficient
vitamin D, which in some way facilitates the extraction by the osteoblasts of these raw materials from the blood and their deposition in
insoluble form as part of the bone matrix. The absence of vitamin D
from the system results in the formation of bone matrix deficient in
calcium salts and therefore lacking in rigidity — a cohdition not infrequent in pigs. Stock raisers have miscalled this condition rheumatism
but it is really the same condition known medically as rickets.
 
In the deposition of the matrix, the fibrous core of the original
strand serves as a sort of axis on which the first matrix is laid down.
When such a strand is completely invested by bone matrix, it is called
a trabecula (little beam). As the osteoblasts continue to secrete and
thereby thicken the trabecula, the accumulation of their own product
forces them farther and farther away from the axial strand about
which the first of the matrix was formed. The new matrix added is
not laid down uniformly. It is possible to make out in it markings
 
 
 
HISTOGENESIS OF BONE
 
 
275
 
 
which are suggestive of the growth rings of a tree. Apparently the
osteoblasts work more or less in cycles, depositing a succession of thin
layers of matrix. Each of these layers of the matrix is called a lamella
(Fig. 152). As the row of osteoblasts is forced back with the deposit of
each succeeding lamella, not all the cells free themselves from their
secretion. Here and there a cell is left behind. As its former fellows
 
 
Erythroblast extruding nucleus
 
Reticular connective-tissue cell j Erythroblast in mitosis
Young erythroblast
 
Normoblast
Blood vessel .
 
Fat cell --tHemocytoblast —
 
Granuloblast -
Hemocytoblast
in mitosis
 
Polykaryocyte.
 
 
 
:
 
Osteoblast ^ t
 
 
I
 
Bone cell
 
 
Bone
 
lamella
 
 
Fio. 152. A small area of bone and adjacent marrow
as seen in highly magnified decalcified sections. The
drawing has been schematized somewhat to emphasize
the relations of the cytoplasmic processes of the osteoblasts* and the bone cells so important in nutrition. In
the adjacent marrow developmental stages of various
types ofiiiijioQd cells, have been
 
 
continue to pile up new matrix, it becomes completely buried (Fig,
151, B). An osteoblast so caught and buried is called a bone cell
{osteocyte)^ and the space in the matrix which it occupies is called a
lacuna. The bone cells, thus entrapped, of necessity cease to be active
bone formers, but they play a vital part in the maintenance of the
bone already formed. They have delicate cytoplasmic processes
radiating into the surrounding matrix through minute canalidhli.
The processes of one cell come into communication with the processes
of its neighbors (Fig. 152). Thus the bone cells nearer to blood vessels
 
 
 
276 HISTOGENESIS OF BONE AND DEVELOPMENT OF SKELETAL SYSTEM
 
 
 
 
Fig. 153. Diagrams showing stages in establishing of a characteristic area
of primary cancellous bone by extension and coalescence of originally
separate trabeculae.
 
absorb and hand on materials to their more remote fellows which in
turn utilize these materials in maintaining a healthy condition in the
organic part of the bone matrix. It is the senescence of these cells with
the consequent lowering of their efficiency and the resultant deterioration of the ossein component of the matrix which is in part responsible
for the decreased resiliency of the bones in advanced age.
 
As the various trabeculae in an area of developing bone grow,
they inevitably come in contact with each other and fuse. Thus
trabeculae, at first isolated, soon come to constitute a continuous
system (Fig. 153). Because of its resemblance to a latticework (Latin —
cancellus), bone in thb condition, where the trabeculae are slender
and the spaces between them extensive, is known as cancellous bone.
The spaces between the trabeculae are known as marrpw spaces.
 
Endochondral Bone Formation. As the term implies, endochondral bone formation goes on within cartilage. It cannot be stated
too strongly that cartilage does not, in this process, become converted
int# bone. Cartilage is destroyed and bone is formed where the
cartilage used to be. The actual bone formation is essentially the
same as in the case of membrane bone. The phenomena of special
 
 
 
mSTCXJENESIS OF BONE
 
 
277
 
 
interest in connection with this type of bone development are those
involved in the destruction of the cartilage preliminary to the formation of bone.
 
Cartilage Formation. To trace the process logically we must start
back with the formation of cartilage. The first indication of impending
chondrogenesis is the aggregation of an exceedingly dense mass of
mesenchymal cells. This cell mass gradually takes on the shape of the
cartilage to be formed. The histogenetic changes involved are not at
first conspicuous. During the period of preliminary massing the cells
have been migrating in from surrounding regions and also increasing
the local congestion by rapid proliferation. As they are packed in
together they lose their processes and become rounded (Fig. 154, A,
1). When it seems as if no more cells could possibly be crowded in,
the course of events changes. The cells begin to separate from one
another. This is due to the fact that they have become active in
 
 
 
Fig. 154. Photomicrographs of developing cartilage. The areas photographed were from the margins of the paranasal cartilage of pig embryos
between 25 and 30 mm. in length. For location of cartilage in head see
figure 175.
 
A, Early stage showing: at (1) the massing of mesenchymal cells which
were about to be incorporated in the growing margin of the cartilage; and at
(2) an area where matrix formation is already beginning.
 
B, Slightly more advanced stage of the same cartilage showing: at (1)
increase in the amount and density of the matrix in the center of the growing
cartilage; at (2) concentration of the surrounding mesenchyme to form tire
perichondrium; and at (3) the addition of new cartilage matrix peripherally*
 
 
 
278 HISTOGENESIS OF BONE AND DEVELOPMENT OF SKELETAL SYSTEM
 
 
secreting. It is the accumulation of the secretion of the cells which
gradually forces them farther and farther apart unti^ they come to lie
isolated from one another in the matrix they have produced (Fig. 1 54,
A, 2). Such a method of increase in m^ss, where there are many
scattered growth centers contributing independently to the increase
in bulk of the whole, is known as interstitial growth. This interstitial
growth of young cartilage stands in sharp contrast to the appositional
growth of such rigid substances as bone or dentine or enamel where
the matrix is laid down in successive layers one upon another. Obviously interstitial growth implies plasticity of the substance produced.
Were the substance produced unyielding, the very activity of a number of growth centers within it would soon crowd those growth centers
to obliteration.
 
As the cartilage matrix is increased in amount its affinity for basic
stains becomes more marked, due probably to increase in concentration of the characteristic substance in it known chemically as chondrin.
At the same time the matrix becomes more rigid with a resultant
checking of interstitial growth. The cells continue to secrete to a
certain extent, however, as evidenced by the fact that in mature
cartilage the matrix immediately surrounding the cells becomes more
dense than the rest of the matrix. This area of denser matrix around
the lacuna in which the cell lies is known as the capsule. As the cartilage
grows older the capsules become more conspicuous and many of
them come to contain more than one cell. These nests of cells in a
common capsule are the result of cell divisions, following which the
daughter cells are held imprisoned in the original capsule of the
mother cell — further evidence of the loss of plasticity in the matrix.
 
The formation of a matrix so rigid that interstitial growth is
checked, takes place first centrally in an area of developing cartilage.
When the center has become too rigid for interstitial growth to continue, appositional growth begins to take place peripherally. While
the cartilage has been increasing in mass it has been acquiring a
peripheral investment of compacted mesenchyme. This investing
layer of mesenchyme soon becomes specialized into a connectivetissue covering called the perichondrium. The layer of the perichondrium next to the cartilage is less fibrous than the outer layer and the
cells in it continue to proliferate rapidly and become active in the
secretion of cartilage matrix. For this reason it is known as the
chondrogenetic layer of the perichondrium. It is through the activity
(rf the chondrogenetic layer that the cartilage continues to grow
 
 
 
Cartilage
 
ceil
 
 
Cart. trab. 1
 
 
 
Osteoblast
 
 
— Bone
ntotrix
 
 
Bone trabecula
 
 
Periosteum
 
 
Fig. 155. Drawing showing periosteal bud and an area of endochondral
bone formation from the radius of a 125 mm. sheep embryo. The small sketch
indicates the location of the area drawn in detail.
 
Abbreviations: Cart, eros., area from which cartilage has recently been
eroded; Cart, pre-eros., area with cartilage cells enlarged and arranged in
rows presaging erosion; Cart, trab,, remnant of cartilage matrix which has
become calcified and serves as an axis or core about which bone lamellae are
deposited to form a bone trabecula; Mes., mesenchymal cell.
 
279
 
 
 
280 HISTOGENESIS OF BONE AND DEVEI.OPMENT OF SKELETAL SYSTEM
 
 
peripherally, by apposition, long after interstitial growth has ceased
in the matrix first formed. ^
 
Cartilage Erosion. When a mass of cartilage is about to be replaced by bone, very striking changes in its structure take place. The
cells which have hitherto been secreting cartilage matrix begin to
destroy the matrix. The lacunae become enlarged and a curious arrangement of the cartilage cells becomes evident. The cells erode the
cartilage in such a manner that they become lined up in rows (Fig.
155). This process of destruction continues until the cartilage is extensively honeycombed. Meanwhile the tissue of the perichondrium overlying the area of cartilage erosion becomes exceedingly active. There is
rapid cell proliferation and the new cells, carrying blood vessels with
them, begin to invade the honeycombed cartilage (Fig. 155).
 
The Deposition of Bone. It is a striking fact that during its growth
cartilage is devoid of blood vessels, the nearest vessels to it being those
in the perichondrium. The invasion of cartilage by blood vessels
definitely determines its disintegration as cartilage, and at the same
time is the initial step in the formation of bone. For this reason the
enveloping layer of connective tissue, up to this time called perichondrium because of its relation to the cartilage, is now called
periosteum because of the relations it will directly acquire to the bone
about to be formed. This change will not be confusing if we stop to
think that both these terms are merely ones of relation, which translated mean, respectively, that tissue which surrounds cartilage, and that
tissue which surrounds bone. The important fact to bear in mind is that
this enveloping layer of tissue is of mesenchymal origin and therefore
contains cells of the stock that may develop into any of the connectivetissue family to which bone as well as cartilage belongs. When,
therefore, a mass of periosteal tissue {periosteal bud, Fig. 155) grows
into an area of honeycombed cartilage it carries in potentially boneforming cells. These cells come to lie along the strand-like remnants
of cartilage, just as in membrane bone formation osteoblasts ranged
themselves along fibrous strands. The actual deposition of bone proceeds in the same manner endochondrally as it does intramembranously. The only difference is that in one case a strand-like remnant of
cartilage serves as an axis for the trabecula, whereas in the other case
deposition begins on a fibrous strand. Extensions and fusions of the
growing trabeculae soon result in the establishment of typical cancellous bone similar to that formed intramembranously.
 
 
 
HISTOGENESIS OF BONE
 
 
281
 
 
The Formation of G)mpact Bone from Primary Cancellous
Bone. The difference between cancellous bone and compact bone is
architectural rather than histological. The fundamental composition
of the bone matrix, its lamellation, and the relations of the bone cells to
the matrix, are the same in both cases. It is the way in which the
lamellae are arranged that distinguishes these two types of bone from
each other. In cancellous bone the disposition of lamellae is such that
it leaves large marrow spaces between the trabeculae. In compact
bone there has been a secondary deposit of concentrically arranged
lamellae in the marrow spaces which greatly increases the density of
the bone as a whole.
 
The essential differences between the two, and the way in which
cancellous bone may become converted into compact bone, can be
illustrated by a simple schematic diagram. Figure 156, 1, shows the
arrangement of lamellae and marrow spaces in primary cancellous
bone. The osteoblasts which have formed the trabeculae still lie along
them on the surface toward the marrow cavity. If such an area is to
IxTome compact, these osteoblasts enter on a period of renewed
activity and deposit a series of concentric lamellae in the marrow
cavity. Frequently if the marrow spaces are irregular there is a
preliminary rounding out of them by local resorption of the bone
already formed (Fig. 156, 2). This is then followed by the deposition
 
 
 
Fig. 156. Diagram showing transformation of cancellous to compact bone.
The solid lines indicate the lamellae of primary cancellous bone; the dotted
lines show the subsequently added concentric (Haversian) lamellae which
nearly obliterate the marrow spaces of cancellous bone. The sequence of
events is indicated by the numbers. Note that irregularly shaped spaces in
the cancellous bone may be rounded out by absorption before the concentric
lamellae are laid down.
 
 
 
282 HISTOGENESIS OF BONE AND DEVELOPMENT OF SKELETAL SYSTEM
 
 
of the concentrically arranged lamellae, sometimes called Haversian
lamellae after the man who first described them in detail (Fig. 156, 3 ).
In this process the original marrow spaces are reduced to small canals
{Haversian canals^ into which have been crowded the blood vessels
which formerly lay in the marrow cavities (Fig. 156, 4 ). These canals
maintain intercommunication with each other in the substance of the
bone, constituting a network of pathways over which the bone receives
its vascular supply. As compared with the marrow spaces of cancellous
bone, however, they are very small; and the gross appearance of a
bone which has undergone this secondary deposit of concentric
lamellae amply justifies characterizing it as ‘'compact.’’
 
II. The Development of the Skeletal System
 
In dealing with the development of the skeletal system we must
recognize at the outset that the subject is far too extensive to be
covered here with anything like completeness. It is not difficult, however, to become acquainted with the outstanding features in the
development of two or three characteristic bones, as, for example:
the sequence of events in the formation of a flat bone; the steps involved in the establishment and growth of a long bone; the way
separate ossification centers appear in a common primordial cartilage
mass and give rise to the various parts of a vertebra. Familiarity with
such type processes gives one an understanding of the factors operative in the development of the skeleton as a whole and a background
sufficient to permit ready and intelligent following up of developmental details in specific bones in which one may become interested.
 
Development of Flat Bones. The flat bones, such as the bones
of the cranium and face, are for the most part of intramembranous
origin. We are, therefore, already familiar with the early steps in their
development from our study of the histogenesis of membrane bone
(Figs. 151 and 153). After a mass of primary cancellous bone has
been laid down in a configuration which suggests that of the adult
bone being formed, there appears about this mass a peripheral concentration of mesenchyme (Fig. 157, A). This periosteal concentration
of mesenchymal tissue contains potentially bone-forming cells which
soon become active and lay down a dense layer of parallel lamellae
about the spongy center of the growing bone (Fig. 157, B). Anatomically this dense peripheral portion is known as the outer table of the
bone. The inner portion, which in the flat bones usually remains
cancellous, is called the diploii. The original mesenchymal tissue which
 
 
 
THE DEVELOPMENT OF THE SKELETAL SYSTEM
 
 
283
 
 
Periosteum
Marrow space
 
l^one trabeculae
 
 
A
 
Subperiosteal
bone lamellae
 
 
Bone trabeculae
Marrow space
 
 
Periosteum
 
 
Fig. 157. Diagrams showing the manner in which the dense peripheral
layer of a flat bone is formed by the deposition of subperiosteal lamellae about
an area of primary cancellous bone.
 
I
 
remains in the marrow spaces of the diploe develops into characteristic “red bone marrow” rich in blood-forming elements (Fig. 152).
 
The story of the growth of the mandible, a membrane bone which
starts after the manner of flat bones but which later takes on a very
elaborate shape and finally becomes largely compact, can be gleaned
by a comparative study of figures 178, 180, and 184.
 
Development of Long Bones. The long bones are characteristically of endochondral origin. The cartilage in which they are
performed is a tempiorary miniature of the adult bone. Ordinarily
there are several ossification centers involved in the formation of long
bones. The first one to appiear is that in the shaft or diaphysis. The
location of this center is shown schematically in figure 158, A, Such
 
 
 
B
 
 
 
 
284 HISTOGENESIS OF BONE AND DEVELOPMENT OF SKELETAL SYSTEM
 
 
b
 
A
 
 
Fig. 158, Diagrams showing liie progress of ossification in a long bone.
The stippled areas represent cartilage; the black areas indicate bone.
 
A, Primary ossification center in shaft. B, Primary center plus shell of
subperiosteal bone. C, Entire shaft ossified. D, Ossification centers have
appeared in the epiphyses. E, Entire bone ossified except for the epiphyseal
cartilage plates.
 
details as the cartilage erosion which preceded its appearance and
the manner in which the deposit of bone was initiated have already
been considered (Fig. 155). Our interest now is in the relation of such
an endochondral ossification center to other centers, and to the bone
as a whole.
 
Almost coincidently with the beginning of bone formation within
the cartilage the overlying periosteum begins to add bone externally
(Fig. 158, B). In view of the fact that the bone-forming tissue carried
into the eroded cartilage arose from the periosteum, this activity of
the periosteum itself is not surprising. Moreover we have already
encountered this same phenomenon of periosteal bone formation in
the outer table of flat bones.
 
The formation of bone which starts at about the middle of the
shaft soon extends toward either end until the entire shaft is involved
(Fig. 158, C), leaving the two ends {epiphyses) still cartilage. Toward
the end of fetal life ossification centers appear in the epiphyses. The
number and location of these epiphyseal centers vary in different long
bones. There is always at least one center in each epiphysis and there
may be two or more. Not uncommonly there are two centers in one
epiphysis and one in the other, as illustrated in figure 158, D.
 
Between the bone fojcmed in the diaphysis and that formed in the
epiphysis there persists a mass of cartilage known as the epiphyseal
plaie which is of vital importance in the growth in length of the bone.
 
 
 
 
 
THE DEVELOPMENT OF THE SKELETAL SYSTEM
 
 
285
 
 
We should expect from the rigidity of bone matrix that interstitial
growth could not account for its increase in length. This was long ago
demonstrated experimentally by exposing a developing bone and
driving into it three small silver pegs, two in the shaft and one in the
epiphysis. The distance between the pegs being recorded, the incision
was closed and development allowed to proceed until a marked
increase had occurred in the length of the bone. On again exposing
the pegs, the two in the shaft were found to be exactly the same
distance apart as when they were driven in, but the distance between
the pins in the shaft and that in the epiphysis had increased by an
amount corresponding to the increase in length of the bone. This
indicates clearly that the epiphyseal plates constitute a sort of temporary, plastic union between the parts of the growing bone. Continued
increase in the length of the shaft is accomplished by the addition of
new bone at the cartilage plate. These epiphyseal plates persist during
the entire postnatal growth period. Only when the skeleton has
acquired its adult size do they finally become eroded and replaced
by bone which joins the epiphyses permanently to the diaphysis.
 
As the bone increases in length there is a corresponding increase
in its diameter. The manner in which this takes place is also susceptible of experimental demonstration. If madder leaves, or some of the
alizarin compounds extracted from them, be fed to a growing animal,
the bone formed during the time the feeding is continued is colored
red. If the madder is discontinued, bone of normal color is again
formed ; but the color still remains in the bone laid down while madder was being added to the diet. Thus it is possible, by keeping a record
of alternate f>eriods of feeding and withholding madder and comparing these records with the resulting zones of coloration in a bone, to
obtain very accurate information on the progress of bone growth and
resorption. Applied to the development of long bones this method
shows their increase in diameter to be due to continued appositional
growth beneath the periosteum. As the bone is added to peripherally
there is a corresponding resorption centrally. This central resorption
results in the formation of a cavity in the axis of the long bone which
is called the marrow canal (Fig. 158, C). With the further increase
in the diameter of a bone, its marrow canal becomes correspondingly
enlarged. A significant mechanical fact might be cited in this connection. 'Engineers have determined that the strongest rod which can be
made from a given weight of steel is obtained by molding it into
tubular form. The development of an essentially tubular shaft by
 
 
 
286 HISTOGENESIS OF BONE AND DEVELOPMENT OF SKELETAL SYSTEM
 
 
progressive increase in the size of the marrow cavity gjivcs a long bone
maximum strength with minimum weight.
 
The Formation of the Vertebrae. The development of the vertebrae is of interest to the student primarily because it exemplifies so
excellently a fundamental embryological phenomenon — the origin
of separate parts from an undifferentiated primordial tissue mass,
and the subsequent association of these parts to form an organized
structure. In studying young embryos we traced the history of the
mesodermic somites through their early differentiation. It will be
recalled that from the ventro-mesial face of each somite there arises
a group of mesenchymal cells called collectively a sclerotome (Fig.
42). These cells migrate from either side toward the mid-line and
become aggregated about the notochord. From these masses of cells
the entire vertebral column is destined to arise.
 
The first significant change which takes place in these primordial
masses is the clustering of sclerotomal cells derived in part from each
of the two adjacent somites into groups which are located opposite
the intervals between the myotomes. In studying series of transverse
sections this arrangement is easy to overlook unless the density of the
cells about the notochord is carefully noted in passing from section
to section. It shows very clearly, however, in frontal sections (Fig. 159).
Each of these cell clusters is the primordium of the centrum of a vertebra. Once formed they rapidly become more dense and more definitely
circumscribed (Fig. 160). Soon after the centrum takes shape, paired
mesenchymal concentrations extending dorsally and laterally from
the centrum establish the primordia of the neural arches and of the
ribs (Fig. 161).
 
 
 
Fig. 159. Semi-schematic coronal sections through the dorsal
region of young embryos to show how the vertebrae became intermyotomal in position. Note that the primordium of a centrum is
formed by cells originating from the sclerotomes of both the
adjacent pairs of somites.
 
 
 
THE DEVELOPMENT OF THE SKELETAL SYSTEM
 
 
287
 
 
 
Fig. 160. Transverse section from pig cm])ryo of 17 mm. cut at the level of the
lungs to show the structures in the dorsal body-wall. (After Minot.)
 
 
mantle layer ependymal
 
 
marginal layer
of eord
 
neural arch
 
 
of cord
 
 
layer
 
 
eympathetic ganghon
anterior cardinal vein
 
 
 
left left duct
erihre fetdium vt Ctteter
 
 
Fig. 161 . Transverse section of 20 mm. pig embryo cut at the level of the lungs
to show the developing vertebra and ribs. (After Minot.)
 
 
 
288 HISTOGENESIS OF BONE AND DEVELOPMENT OF SKELETAL SYSTEM
 
 
 
Fig. 162. Transverse section from 40 mm. pig embryo cut at the level of the
lungs to show the developing vertebra and ribs.
 
 
The Stage in w^hich the various parts of the vertebrae arc sketched
in mesenchymal concentrations, is frequently spoken of as the blastemal stage. It is rapidly followed by th^ cartilage stage. Conversion to
cartilage begins in the blastemal mass first in the region of the centrum
and then chondrification centers appear in each neural and each
costal process (Fig. 161). These spread rapidly until all the centers
fuse and the entire mass is involved (Fig. 162). The cartilage miniature of the vertebra thus formed is at first a single piece showing no
lines of demarcation where the original centers of cartilage formation
became confluent, and no foreshadowing of the separate parts of
which it will be made up after the cartilage has been replaced by
bone. Shortly before ossification begins the rib cartilage becomes
separated from the vertebra, but the vertebra itself remains in one
piece throughout the cartilage stage (Fig. 162).
 
The locations of the endochondral ossification centers which
appear in a vertebral cartilage are indicated schematically in figure
163. It readily can be seen how the spreading of these centers of bone
formation will establish the conditions which exist in an adult vertebra. The median ossification center gives rise to the centrum. The
centers in the neural processes extend dorsally to complete the neural
arch. The spinous process in most of the vertebrae is formed by a
prolongation of these same centers to meet dorsal to the neural canal.
 
 
 
 
Fig. 164. Diagram of four types of vertebrae indicating the parts derived
from the different ossification centers shown in figure 163. The part formed by
the median center in centrum is cdncentrically ringed; the parts arising from
the costal centers are stippled; parts derived from the lateral centers in the
neural arches are indicated in line-shading,
 
289
 
 
 
 
 
 
 
290 HISTOGENESIS OF BONE AND DEVELOPMENT OF SKELETAL SYSTEM
 
 
In forms such as the pig the spinous processes of tl>e more anterior
thoracic vertebrae are very long. In these vertebrae additional ossification centers appear in the spinous process and fuse with those in the
 
Scapula Humerus
 
 
 
Radius Mandible
 
& ulna
 
 
Fig. 165. Photograph (X 1/^ showing the
ossification centers which have appeared in pig
embryos of 35 mm. This and the two following
figures were made by photographing in transmitted light embryos in which all the uncalcified
tissues had been rendered transparent by treatment with potassium hydroxide and glycerine.
 
neural processes. The transverse processes with which the tubercles
of the ribs articulate are formed by the lateral extension of the
primary ossification centers in the neural processes. These same centers
extend ventrally also, and meet the centrum (cf. Figs. 163 and 164).
 
 
Scapula
/ Humerus
 
 
 
Fic. 166. Photograph (X IM) showing the progress of ossification in the
skeleton of a 65 mm. pig embryo.
 
 
 
Fig. 167. Photograph {X showing the extent of ossification in the skeleton of a 90 nun. pig embryo.
 
 
 
292 HISTOGENESIS OF BONE AND DEVELOPMENT OF SKELETAL SYSTEM
 
 
The shaft of the rib is formed by extension of its primary ossification center (Fig. 163). After birth, secondary epiphyseal centers
appear in the tubercle and head of the rib. These centers are separated from the shaft by persistent cartilage plates in the manner
described in discussing the development of long bones. Fusion of the
secondary epiphyseal centers with the shaft of the rib does not take
place until the skeleton has acquired its adult dimensions.
 
The foregoing discussion has been based on a thoracic vertebra in
which the relations of the rib to the vertebra show most clearly.
All the vertebrae have the costal element represented, although it is
greatly reduced and modified in other regions than the thoracic. A
study of figure 164, in which the components of vertebrae from the
cervical, thoracic, lumbar, and sacral regions are schematically
indicated, will make the homologies apparent. With these homologies
in mind it is sufficiently evident, without going into further detail,
how all these vertebrae arise by a process similar to that described
for the thoracic vertebrae.
 
The Progress of Ossification in the Skeleton as a Whole. It
 
would carry us beyond the scope of this book to take up the development of specific bones. Each has its own story involving the formation
of the connective tissue or the cartilage mass which precedes it ; local
erosion centers if it be preformed in cartilage; number, location, and
time of appearance of ossification centers; growth in length and
diameter; development of epiphyses; time of fusion of epiphyses and
diaphysis; and finally the development of muscle ridges and articular
facets. Without entering into a discussion of details of this sort, it is
possible nevertheless to follow the general progress of ossification in
the skeletal system as a whole. Embryos which have been treated with
potassium hydroxide and then cleared in glycerine clearly show the
various ossification centers. In such preparations the areas where
calcium salts have been deposited stand out white in reflected light
and opaque in transmitted light. ^Figures 165-167, which are photographs of preparations of this type, can be used to trace the history
of the more important bones. It should perhaps be stated explicitly
that these figures arc included primarily to give a general view of the
progress of ossification and secondarily to afford a readily available
source of reference for following up points of interest that may arise.
It is not a profitable use of the student’s time to attempt to memorize
the ossification centers which have appeared in embryos of any given
age.
 
 
 
==Chapter  13==
 
 
Tke Development of tke Face and Jaws
and tke Teetk
 
 
I. The Face and Jaws
 
The Stomodaeum. In studying the early development of the
digestive tract we saw that the primitive gut first appeared as a
cavity which was blind at both its anterior and posterior ends (Fig.
37). Its opening in the future oral region is established by the meeting
of an ectodermal depression, the stomodaeum, with the cephalically
growing anterior end of the gut. The stomodaeal depression, even
as late as the time the oral plate ruptures and establishes communication between the anterior end of the gut and the outside world, is very
shallow (Fig. 40). The deep oral cavity characteristic of the adult is
formed by the forward growth of structures about the margins of the
stomodaeum. Some idea of the extent of this forward growth can
be gained from the fact that the tonsillar region of the adult is at
about the level occupied by the stomodaeal plate when it ruptures.
The growth of the structures bordering the stomodaeum, then, not
only gives rise to the superficial parts of the face and jaws, but actually
builds out the walls of the oral cavity itself.
 
The Jaws. Because the face of a young embryo is pressed against
the thorax it is difficult to study unless the entire head is cut off and
mounted separately. Preparations of this kind observed under a dissecting microscope by strong reflected light show the surface configuration of the facial region very clearly. The most conspicuous landmarks
are the stomodaeal depression, which in view of its fate we may now
call the oral cavity, and the olfactory pits. In embryos as small as
7 mm. most of the structures which take part in the formation of the
face and jaws are already clearly distinguishable (Fig. 168). In the
mid-line cephalic to the oral cavity is a rounded overhanging prominence known as the Jrontal process. On either side of the frontal process
are horseshoe-shaped elevations surrounding the olfactory pits. The
 
293
 
 
 
294
 
 
DEVELOPMENT OF FACE, JAWS AND TEETH
 
 
median limbs of these elevations are known as the nap-medial processes
and the lateral limbs are called the naso-lateral processes.
 
Growing toward the mid-line from the cephalo-lateral angles of
the oral cavity are the maxillary processes. In lateral views of the
head (Figs. 31 and 32) it will be seen that the maxillary processes
and the mandibular arch merge with each other at the angles of the
mouth. Thus the structures which border the oral cavity cephalically
are: the unpaired frontal process in the mid-line, the paired nasal
processes on either side of the frontal, and the paired maxillary
 
 
 
Fig. 168. Face of 7 mm. pig embryo photographed
X 15. Note especially the unmistakably paired character of the thickenings which later fuse in the mid-line
to complete the mandibular arch.
 
 
processes at the extreme lateral angles. From these primitive tissue
masses the upper jaw and the nose are derived.
 
The caudal boundary of the oral cavity is less complex, being
constituted by the mandibular arch alone. In very young embryos
(Fig. 168) the origin of the mandibular arch from paired primordia
is still clearly evident. Appearing first on either side of the mid-line
are marked local thickenings due to the rapid proliferation of mesenchymal tissue. Until these thickenings have extended from either side
to meet in the mid-line there remains a conspicuous mesial notch.
With their fusion, the arch of the lower jaw is completed (Figs. 1 69172).
 
 
 
THE FACE AND JAWS
 
 
295
 
 
In 10-12 mm. embryos (Fig. 169) very marked progress can be
seen in the development of the facial region. The maxillary processes
are much more prominent and have grown toward the mid-line,
crowding the nasal processes closer to each other. The nasal processes
have grown so extensively that the frontal process between them is
completely overshadowed (cf. Figs. 168 and 169). The growth of the
 
 
 
Fig. 169. Face of 11 ,5 mm. pig embryo photographed
X 12. Fusion of the right and left components of the
mandibular arch is practically complete. Both the
medial and lateral limbs of the horseshoe-shaped nasal
processes have undergone conspicuous enlargement.
Note especially the approximation of each naso-medial
process to the maxillary process of the same side.
 
 
medial limbs of the nasal processes has been especially marked and
they appear almost in contact with the maxillary processes on either
side.
 
The groundwork for the formation of the upper jaw is now well
laid down. Its arch is completed by the fusion of the two nasomedial processes with each other in the mid-line, and with the
maxillary processes laterally (Fig. 170), The premaxillary bones
carrying the incisor teeth are formed, later, in the part of the upper
jaw which is of naso-medial origin. The maxillary bones, carrying all
 
 
 
296
 
 
DEVELOPMENT OF FACE, JAWS AND TEETH
 
 
the upper teeth posterior to the incisors, are developed in the part of
the arch arising from the maxillary processes.
 
Nasal Chambers. The olfactory pits have by this time become
much deepened, not only by the growth of the nasal processes about
them, but also by extension of the original pits themselves which soon
break through into the oral cavity (Figs. 93 and 97, C). We may now
 
 
lateral
process
 
naso*‘ medial
process
 
tojngue
 
hyomandibular
 
cleft
 
hyoid arch
 
 
Fig. 170. Face of 16 mm. pig embryo photographed X 10. The
naso-medial processes have fused with the maxillary processes on
either side, and with each other in the mid-line, thus completing
the arch of the upper jaw.
 
speak of the external openings of the nasal pits as the nostrils {external
nares) and their new openings into the oral cavity as posterior nares or
nasal choanae. The septum of the nose is formed by fusion in the midline of the original naso-medial processes'; the upper part of the
bridge of the nose is derived from the frontal process; and the alae
of the nose arise from the naso-lateral processes (Fig. 172).
 
Naao-Iacrimal Duct. Where the naso-lateral process and the
maxillary process meet each other there is formed iot a time a well
 
 
 
THE FACE AND JAWS
 
 
297
 
 
 
Fir;. 171. Face of 17.5 mm. pig embryo photographed X 10. The originally separate processes have now largely lost their identity in the series of
fusions which have taken place in the formation of the face.
 
 
marked groove, which extends to the mesial angle of the eye (Fig. 169).
This is known as the naso4acrimal groove. It soon closes over superficially (Fig. 171), and it is usually stated that the deep portion of the
original groove is converted into a tube, the naso-lacrimal duct^ or
tear duct, wjhich drains the fluid from the conjunctival sac of the eye
into the nose. Recently Politzer has maintained that the nasolacrimal duct arises as an independent epithelial downgrowth from
the conjunctival sac which follows closely along the line of closure of
the old naso-optic furrow.
 
Tongue. While these changes are going on externally, the tongue
is being formed in the floor of the mouth. Anatomically the tongue is
usually described as consisting of a freely movable part called its body,
and a less freely movable portion, called its root, by which it is
attached in the oro-pharyngeal floor. The body of the tongue arises
from a small median elevation, the tuberculum impar^ and paired lateral
lingual primordia. These elevations appear very early in development
on the inner face of the first branchial (mandibular) arch (Fig. 173,
B). The tuberculum impar grows slowly and is soon crowded in on
 
 
 
298
 
 
DEVELOPMENT OF FACE, JAWS AND TEETH
 
 
by the more rapidly growing lateral lingual primordia which form
the great bulk of the body of the tongue (Fig. 173, c5.
 
 
 
Fig. 172. Face of 21.5 rum. pig embryo
photographed X 10. The characteristic features
of the adult face are even at this early stage
clearly recognizable. The regions of the upper
jaw and nose which have arisen from originally
distinct primordia are differentiated by shading.
Vertical hatching indicates origin from frontal
process; stippling, from naso-lateral processes;
small crosses, from naso-medial processes; horizontal hatching, from maxillary processes. The
entire lower jaw is derived from the mandibular
arch.
 
 
Arising in the pharyngeal floor at the bases of the second and
third branchial arches is an elevation known as the copula (i.e., yoke)
 
 
THE FACE AND JAWS
 
 
299
 
 
because of the way it joins these arches together (Fig. 173, B). The
copula, supplemented by some tissue from the adjacent basal portions of branchial arches 2, 3, and 4, gives rise to the root of the
tongue.
 
All the various elevations which thus take part in the formation
 
 
- Branchial arch i
 
-Branchial arch 2
 
'Branchial arch 3
.Branchial arch 4
-Glottis
 
 
Lateral lingual anlagt
 
Copula
 
Epiglottis
 
Glottis
 
 
Branchial arch i
Lateral lingual anlage
 
Branchial arch $
 
Branchial arch 4
 
Arytenoid ridge
 
c
 
Fio. 173. Dissections of pig embryos made to expose the floor of the
mouth and show the development of the tongue. (After Prentiss.) A, 7 mm.;
B, 9 mm.; C, 13 mm. (All figures X 12.)
 
 
B
 
 
 
Tuherculum impof
 
Branchial arch 2
 
Epiglottis
 
Glottis
 
 
Lateral lingual anlage
Tuherculum impar
 
Epiglottis
Arytenoid ridge
 
 
Branchial arch i
Tuherculum impar
 
Branchial arch 2
 
Branchial arch 3
Branchial arch 4
 
Arytenoid ridge
 
 
 
300
 
 
DEVELOPMENT OF FACE, JAWS AND TEETH
 
 
 
THE FACE AND JAWS
 
 
301
 
 
of the tongue must be thought of as composed of an outer covering
and the underlying mesodermal tissue which causes the covering to
bulge into the lumen. The covering tissue arises in situ from the lining
of the branchial arches involved. The sensory innervation of the surface of the tongue is, therefore, just what one would expect from the
basic relations of the cranial nerves to the branchial arches. The
epithelium of the body of the tongue gets its sensory supply from the
lingual branch of the mandibular division of the trigeminal (V) nerve
(Fig. 97, A, B), and from the chorda tympani branch of the seventh
nerve. The root of the longue receives its sensory fibers from the glossopharyngeal (Fig. 94) and vagus nerves.
 
The skeletal muscle that makes up the main mass of the tongue
beneath the mucosal covering is derived from mesodermal cell masses
that are believed to migrate into the pharyngeal floor from the myotomes of the occipital somites. Ontogenetically, in mammalian embryos this migration is exceedingly difficult to trace, for the cells of
myotomal origin early mingle indistinguishably with the local mesenchymal cells. Nevertheless the way the hypoglossal nerve (XII),
which is the cranial nerve arising at the level of these occipital myotonies, grows in with the developing lingual muscles (Figs. 93, 94,
and 97, A, B) and innervates them, furnishes strong circumstantial
evidence for this interpretation of tongue muscle origin and migration.
 
Palate. Coincidently also the palatal shelf is being formed in the
upper jaw and separating off the more cephalic portion of the original
stomodaeal chamber. Since it is into this cephalic portion of the cavity
that the nasal pits break through (Figs. 93 and 97, C), the formation
of the palatal shelf in effect prolongs the nasal chambers backwards
so they open eventually into the region where the oral cavity becomes
continuous with the pharynx.
 
The palate as well as the arch of the upper jaw is contributed to
by both the naso-medial processes and the maxillary processes. From
the premaxillary region a small triangular median portion of the
palate is formed (Fig. 174). The main portion of the palate is derived
from the maxillary processes. From them shelf-like outgrowths arise
 
Fig. 1 74. Photographs (X 6) of dissections of pig embryos made to expose
the roof of the mouth and show the development of the palate. A, 20.5 mm.;
B, 25 mm.; C, 26.5 mm.; D, 29.5 mm.
 
The diagrams of transverse sections are set in to show the relations before
(E) and after (F) the retraction of the tongue from between the palatine
processes.
 
 
 
 
302
 
 
DEVELOPMENT OF FACE, JAWS AND TEETH
 
 
on either side and extend toward the mid-line (Fig. 174, A— G). When
these palatal shelves first start to develop, the tongue lies between
them (Fig. 174, E). As development progresses the tongue drops down
(Fig. 174, F); the palatal shelves are extended toward the mid -line
and finally fuse with each other medially and with the premaxillary
process anteriorly to complete the palate (Fig. 174, D). At the same
time the nasal septum grows toward the palate and becomes fused
to its cephalic face (Figs. 174, F, and 178). Thus the separation of
 
 
 
 
Fig. 175. Transverse section of snout of 28 mm. pig
embryo (X 12). The area included in the rectangle is
shown in detail in the following figure.
 
 
right and left nasal chambers from each other is accomplished at the
same time that the nasal region as a whole is separated from the oral.
 
II. The Development of the Teeth
 
The Dental Ledge. Local changes leading toward tooth formation can be made out in the jaws of embryos as small as 1 5 mm. or
even less. By the time a size of 28-30 mm. has been attained, a definite
thickening of the oral epithelium can readily be seen on both the
upper and the lower jaw. This band of epithelial cells which pushes
into the underlying mesenchyme around the entire arc of each jaw
is known as the labi<Hlental ledge {labio-dental lamina) (Figs. 175 and
176). Shortly after its first appearance, cross-sections show this ledge
 
 
 
THE DEVELOPMENT OF THE TEETH
 
 
303
 
 
of epithelial cells to be differentiating into two parts, a more distal
part which by its ingrowth marks off the elevation which is to become
 
 
 
Fig. 176. Drawing (X 130) showing labio-dental ledge of
28 mm. pig embryo. For location of area represented see preceding figure.
 
 
 
Fig. 177. Drawing (X 130) showing differentiation of the
labio-dental ledge into labio-gingival lamina and dental ledge.
 
The ingrowth of the labio-gingival lamina initiates the separation of the lip from the gum (gingiva). From the dental ledge a
series of local bud-like outgrowths are formed, each of which
gives rise to the enamel cap of a tooth.
 
The region shown is the same as that in the preceding figure
but from a slightly older (37 mm.) embryo.
 
the lip from that which is to become the gum, and a more proximal
part which is destined to grow into the gum and give rise to the
enamel-forming organs of the teeth. The part of the original labio
 
 
 
304
 
 
DEVELOPMENT OF FACE, JAWS AND TEETH
 
 
dental ledge which separates the lip from the gum (gingiva) is known
as the labio-gingival lamina^ and the part of the original ledge which is
to take part in tooth formation is known as the denial ledge or dental
lamina (Fig. 177).
 
Enamel Organs. Soon after the dental ledge is established, local
buds arise from it at each point where a tooth is destined to be formed.
Since these cell masses give rise to the enamel crown of the tooth they
are termed enamel organs. As would be expected, the enamel organs
 
 
nasal bone
 
 
cartilage of
 
nasal septum
 
 
nasal
 
chamber
 
 
nasal process
 
of premaxilla
 
 
 
dental papilla
enamel organ
 
 
labiogingival
 
lamina
 
Meckel’s cartilage
 
 
tooth germ
 
mandible
 
 
Fig. 178. Drawing (X 10)tDf a transverse .section of the snout
of a 71 mm. pig embryo. The area included in the rectangle is
shown in detail in the following figure.
 
 
for the milk teeth are budded off from the dental ledge first, but the
cell clusters which later give rise to the enamel of the permanent teeth
are formed at a surprisingly early time (Fig. 180). They remain
dormant, however, during the growth period of the milk teeth and
begin to develop actively only after the jaws have enlarged sufficiently
to accommodate the permanent dentition.
 
The histogenetic processes involved in the formation of milk teeth
and permanent teeth are essentially the same. It is, therefore, sufficient
to trace them in the case of the milk teeth only, keeping in mind that
the same process is repeated later in life in the formation of the permanent teeth.
 
In a section of the developing mandible which cuts the dental ledge
 
 
THE DEVELOPMENT OF THE TEETH
 
 
305
 
 
at a point where an enamel organ is being formed, the shape of the
enamel organ suggests that of an irregularly shaped, inverted goblet,
the section of the dental ledge appearing somewhat like a distorted
stem (Fig. 178). The epithelial cells lining the inside of the goblet early
take on a columnar shape. Because they constitute the layer which
secretes the enamel cap of the tooth, they are called ameloblasts (enamel
 
 
 
formers) (Fig. 179). The outer layer of the enamel organ is made up
of closely packed cells which are at first polyhedral in shape but which
soon, with the rapid growth of the enamel organ, become flattened.
They constitute the so-called outer epithelium of the enamel organ (Fig.
179). Between the outer epithelium and the ameloblast layer is a
loosely aggregated mass of ceils called collectively, because of their
characteristic appearance, the enamel pulp or the stellate reticulum
(Fig. 179).
 
 
306
 
 
DEVELOPMENT OF FACE, JAWS AND TEETH
 
 
 
Fig. 180. Developing tooth from lower jaw of a 120 mm. pig embryo
(X 14). The small sketch including half of the tongue (left) and part of the
lip (right) gives the relations of the region drawn. The area in the rectangle
is shown in detail in the following figure.
 
 
 
Fig, 181. Projection drawing (X 350) of segment of enamel organ and
adjacent pulp from a 120 mm. pig embryo to show ameloblast and odontoblast layers. For location of area represented see preceding figure.
 
 
 
THE DEVELOPMENT OF THE TEETH
 
 
307
 
 
The Dental Papilla. Inside the goblet-shaped enamel organ
there is caught a mass of mesenchymal cells which are said to constitute the dental papilla (Fig. 179). The cells of the dental papilla
proliferate rapidly and soon form a very dense aggregation. The outer
cells of this mass are destined to secrete the dentine of the tooth and
the inner cells to give rise to the pulp of the tooth.
 
A little later in development the enamel organ begins to assume
the shape characteristic of the crown of the tooth it is to lay down
(Fig. 180). At the same time the outer cells of the dental papilla
take on a columnar form similar to that of the ameloblasts (Fig. 181).
They are now called odontoblasts (dentine formers) because they are
about to become active in secreting the dentine of the tooth.
 
In the central portion of the dental papilla vessels and nerves arc
beginning to make their appearance so that the picture is already
suggestive of the condition seen in the pulp of an adult tooth. Meanwhile the growth of the dental papilla toward the gum has crowded
the stellate reticulum of the enamel organ in the crown region so it is
nearly obliterated (Fig. 180). This brings the ameloblasts of this region
much closer to the many small blood vessels which lie in the surrounding mesenchyme. The approach of the ameloblasts to the neighboring
vascular supply would appear to be significant, since it is precisely
here at the tip of the crown where the ameloblasts first begin to secrete
enamel (Fig. 182).
 
By the time the enamel organ has been well established the dental
ledge has lost its connection with the oral epithelium, although traces
of it can still be identified in the mesenchyme at the lingual side of the
tooth germ (Fig. 180). The cluster of cells which is destined to give
rise to the enamel organ of the permanent tooth of this level can be
seen budding off from the ledge close to the point from which the
enamel organ of ffie milk tooth arose (Figi >^).
 
Formation of Dentine. With these preparatory developments
complete, the tooth-forming structures are, so to speak, ready to go
about the fabrication of dentine and enamel. As is the case with bone,
enamel and dentine are both composed of an organic basis in which
inorganic compounds are deposited. We may use the same comparison
that was used in describing bone : that of the familiar use in construction operations of a steel meshwork into which concrete is poured, the
steel giving the finished structure some degree of elasticity and increasing the tensile strength while the concrete gives body and solidity.
In the case of such hard structures in the body as bone, dentine, and
 
 
 
308
 
 
DEVELOPMENT OF FACE, JAWS AND lEETH
 
 
pr^ordiutn enamel organ
' permanent tooth
 
 
odontoblast layer
pulp of tooth
 
 
 
enamel pulp (stellate reticulum)
periosteum of alveolar socket
outer epithelium of enamel organ
 
 
Fig. 182. Developing tooth from lower jaw of a 130 mm. pig embryo
(X 30). The small sketch gives the relations of the regions drawn. The area
in the rectangle is shown in detail in the following figure.
 
 
blood vessel dentine enamel blood vessel in
 
1 i, 1 mesenchyme
 
 
 
fiber lirocess of enamel organ
 
 
Fio, 183. Projection drawing (X 350) of small segment of developing
 
 
THE DEVELOPMENT OF THE TEETH
 
 
309
 
 
enamel, these interlacing organic strands in the matrix give the tissue
its resilience and tensile strength, and the calcareous compounds
deposited in the organic framework give form and hardness.
 
Although bone, dentine, and enamel are similar in having both
organic and inorganic constituents in their matrix they are quite
different in detail, both as to composition and microscopical structure.
Bone has approximately 45 per cent of organic material while dentine
has but 30 per cent and adult enamel 5 per cent or less. There is also
considerable difference in the kind and proportion of inorganic compounds present in each. Structurally they are totally unlike. Bone
matrix is formed in lamellae and has cells scattered through it.
Dentine is formed without lam^llation and has its cellular elements
lying against one face and sending long processes into tubules in the
matrix. Enamel is prismatic in structure and the cells which form
it lie against its outer surface while it is being deposited, but are
destroyed in the eruption of the tooth.
 
The first dentine is deposited against the inner face of the enamel
organ, the odontoblasts drawing their raw materials from the small
vessels in the pulp and secreting their finished product toward the
enamel organ. It is significant in this connection that in an active
odontoblast the nucleus, which is the metabolic center of the cell, has
gravitated toward the source of supplies and come to lie in the extreme
pulpal end of the cell (Fig, 183). Also, the end of the odontoblast
toward the enamel organ, where the elaborated product of the cell
is being accumulated preparatory to its extrusion, can be seen to
take the stain especially intensely. Although our knowledge of intracellular chemistry is as yet exceedingly fragmentary and we do not
know the exact chemical nature of the product in this stage, the staining reaction is clearly indicative of the presence of calcium compounds
of some sort.
 
If attention is turned now to the recently formed dentine, two
zones distinctly different in staining reaction can be seen. The zone
nearer the cells is pale, taking but little stain (Fig. 183). This zone
consists of the recently deposited organic part of the matrix not as yet
impregnated with calcareous material. The zone nearer the enamel
organ will be found, by contrast, very intensely stained. This is the
older part of the dentine matrix which has had the organic framework
impregnated with calcareous material.
 
As the odontoblasts continue to secrete additional dentine matrix
the accumulation of their own product inevitably forces the cell
 
 
 
310
 
 
DEVELOPMENT OF FACE, JAWS AND TEETH
 
 
layer back, away from the material previously deposited. Apparently
strands of their cytoplasm become embedded in the material first laid
down and are then pulled out to form the characteristic processes of
the odontoblasts known as the dentinal fibers (Fig. 183). As the layer
of secreted material becomes thicker and the cells are forced farther
from the material first deposited, these dentinal fibers become progressively longer. Even in adult teeth where the dentine may be as much
as 2 mm. in thickness they extend from the odontoblasts which line
the pulp chamber to the very outer part of the dentine. These dentinal
fibers are believed to be concerned with maintaining the organic
portion of the dentine matrix in a healthy condition. When the pulp
is removed from a tooth, taking with it the odontoblasts, we know
that the dentine undergoes degenerative changes which involve,
among other things, increase in brittleness. This would seem to be
attributable to the degeneration of the organic framework of a matrix
no longer nourished by the odontoblasts.
 
Formation of Enamel. While the dentine is being laid down by
the cells of the odontoblast layer, the enamel cap of the tooth is being
formed by the ameloblast layer of the enamel organ. As was the case
with the odontoblasts, the active cells of the ameloblast layer are
columnar in shape and their nuclei, too, lie in the ends of the cells
toward the source of supplies, in this case the small vessels in the
adjacent mesenchyme (Fig. 183). The amount of organic material
laid down as the framework of enamel is much less than is the case
with either bone or dentine, and it is therefore more difficult to make
out its precise character and arrangement. It is, nevertheless, possible
to see in decalcified sections, delicate fibrous strands projecting from
the tips of the ameloblasts into the areas of newly formed enamel
(Fig. 183). It seems probable that these strands {Tomes'' processes) are
in some way involved in the formation of the organic matrix of
enamel. The problem of tracing the relations of Tomes’ processes to
the organic framework of enamel is greatly complicated by the fact
that where the ameloblasts have deposited calcium compounds the
calcium has rendered the organic part of the matrix so avid in its
affinity for stains that it is not possible to discern fine structural details
because of the very density of the resulting coloration (Fig. 183). This
reaction of the tissue to stains persists even after the inorganic calcium
compounds have been removed by decalcification, indicating that
the organic framework itself has been chemically altered by the
calcium deposited in it.
 
 
 
THE DEVELOPMENT OF THE TEETH
 
 
311
 
 
In spite -of these difficulties in getting at the exact nature and
arrangement of the organic matrix of enamel, it is quite possible to
see the genesis of its fundamental prismatic structure. Each amcloblasl
builds up beneath itself a minute rod or prism of calcareous material.
These prisms are placed with their long axes approximately at right
angles to the dento-enamel junction. Collectively these enamel prisms
form an exceedingly hard cap over the crown of the tooth which in
its structural arrangement suggests a paving of polygonal bricks laid
on end. There is sufficient difference in the rate at which the different
 
 
growth lines
 
in enamel
 
 
pulp chamber
 
growth lines
in dentine
 
 
root canal
 
 
cementum
 
 
oral epithelium
 
 
osteolilasts
 
of periosteum
of alveolus
 
 
connective
tissue ftbers
 
 
cementoblasts
( from
dental sac)
 
 
blood vessels
and nerves to pulp
 
 
Fig. 184. Schematic diagram showing the topography of a tooth and its
relations to the bone of the jaw. The numbered zones indicate empirically
the sequence of deposition of the dentine and enamel. The so-called growth
lines in the dentine and enamel follow the general contours indicated by
the dotted lines in the figure but arc much more numerous.
 
 
 
312
 
 
DEVELOPMENT OF FACE, JAWS AND TEETH
 
 
ameloblasts work so that in actively growing enamel the surface is
jagged and irregular due to the varying extent to ^<^hich the different
prismatic elements have been calcified (Fig. 183).
 
Both enamel formation and dentine formation begin at the tip
of the crown and progress toward the root of the tooth (Figs. 182 and
184). But the entire crown is well formed before the root is much more
than begun. The progressive increase in the length of the root is an
important factor in the eruption of the tooth, for as the root increases
in length the previously formed crown must move closer to the surface
of the gum. Even when the crown of the tooth begins to erupt the
root is still incomplete, and it does not acquire its full length until the
crown has entirely emerged.
 
The Formation of Cementum. The so-called cementum of the
tooth is virtually a bone encrustation of its root. No cementum is
formed until the tooth has acquired nearly its full growth and its
definitive position in the jaw. But the first indications of specialization
in the tissue destined to give rise to it can be seen long before the
cementum itself appears.
 
Outside the entire tooth germ, between it and the developing bone
of the jaw, there occurs a definite concentration of mesenchyme.
The concentration becomes evident first at the base of the dental
papilla and extends thence crownwards about the developing tooth,
which it eventually completely surrounds.
 
This mesenchymal investment is known as the dental sac (Fig. 182).
In the eruption of the tooth the portion of the dental sac over the
crown is destroyed, but the deeper portion of the sac persists and
becomes closely applied to the growing root. At about the time the
tooth has acquired its final position in the jaw, the cells of the dental
sac begin to form the cementum. Histologically and chemically
cementum is practically identical with subperiosteal bone. When we
consider the manner of origin of the dental sac and of the periosteum
of the bone socket (alveolar socket) in which the root of the tooth lies,
and see how they arise side by side from the same sort of tissue, this
seems biit natural. The dental sac is essentially a layer of periosteal
tissue facing the root of the tooth and back to back with the periosteal
tissue of the alveolar socket (Fig. 182).
 
The Attachment of Tooth in the Jaw. The attachment of the
tooth in its socket is brought about by the development, between the
dental sac and the periosteum of the tooth socket, of an exceedingly
tough fibrous connective tissue. As the periosteum of the alveolus
 
 
 
THE DEVELOPMENT OF THE TEETH
 
 
313
 
 
adds new lamellae of bone to the jaw on the one side, and the dental
sac adds lamellae of cementum to the root of the tooth on the other,
the fibers of this connective tissue are caught in the new lamellae.
Thus the tooth comes to be supported by fibers which are literally
calcified into the cementum of the tooth at one end and into the bone
of the jaw at the other (Fig. 184). The mechanism involved is precisely
the same as that which occurs in the burying of tendon fibers in a
growing bone, where the buried ends of the fibers are known as the
penetrating fibers of Sharpey.
 
Replacement of Deciduous Teeth by Permanent Teeth. The
 
replacement of the temporary or “milk” (deciduous) dentition by the
permanent teeth is a process which varies in detail for each tooth.
The general course of events is, however, essentially similar in all
cases. The enamel organ of the permanent tooth arises from the
dental ledge near the point of origin of the corresponding deciduous
tooth (Fig. 180). With the disappearance of the dental ledge, the
permanent tooth germ comes to lie in a depression of the alveolar
socket on the lingual side of the developing deciduous tooth (Fig. 185).
 
When the jaws approach their adult size the hitherto latent primordia of the permanent teeth b<-gin to go through the same histo
 
 
Fio. 185. Photomicrograph (X 5) of upper jaw of 160 mm. pig embryo
showing the milk cuspids just breaking through the gum.
 
 
314
 
 
DEVELOPMENT OF FACE, JAWS AND TEETH
 
 
 
Fig. 186. Photomicrograph (X 6) of section through the jaw of a puppy
showing a deciduous tooth nearly ready to drop out and the developing
permanent tooth deeply embedded in the jaw below it. The space about the
crown of the permanent tooth was occupied in the living condition by
enamel. Fully formed enamel, being approximately 97 per cent inorganic
in composition, is almost completely destroyed by the decalcification with
acids which must be carried out before such material can be sectioned.
(From a preparation loaned by Dr* S. W. Chase.)
 
 
THE DEVELOPMENT OF THE TEETH
 
 
315
 
 
genetic changes we have already traced in the case of the temporary
teeth. As the permanent tooth increases in size, the root of the deciduous tooth is resorbed and the permanent tooth comes to lie underneath
its remaining portion (Fig. 186). Eventually nearly the entire root
of the deciduous tooth- is destroyed and its loosened crown drops out,
making way for the eruption of the corresponding permanent tooth.
 
 
 
 
BiLlio grapky
 
 
Although this docs not purport to be a complete bibliography
on the development of the pig, I have tried to make it comprehensive.
At least one reference has been included on every phase of the subject
concerning which I could find published information. Under each
of the main subject headings some of the articles referred to have
extensive bibliographies of the literature in their special field. But,
with the exception of a few outstanding contributions, no papers have
been included which are merely of historical interest. For such articles
reference should be made to the exhaustive bibliographies compiled
by Minot (1893) and by Keibel (1897). Furthermore, the list is largely
restricted to contributions based directly on pig embryos. Exception
to this rule has been made in favor of a few general articles which
are of especial assistance in acquiring a perspective on some phase of
the subject. Also, a number of articles based on other forms have been
included when no work appeared to have been done on corresponding
phases of development in the pig. It is hoped that such a list of
selected references will furnish a starting point for following up any
desired line of inquiry without involving one in a discouraging
multiplicity of titles.
 
Texts and Manuals
 
Arey^ L. i?., 19^6. Developmental Anatomy. Saunders, Philadelphia, 5th Ed., ix &
 
616 pp.
 
Baumgartner, W, J,, 1924, Laboratory Manual of the Foetal Pig, Macmillan, New
York, vii & 57 pp.
 
Boyden, E. A., 1936. A Laboratory Atlas of the 13-mm. Pig Embryo. (Prefaced by
younger stages of the chick embryo.) The Wistar Institute Press, Philadelphia,
iv & 104 pp.
 
Hamilton, W. J., Boyd, J. D., and Mossman, H. W., 1945. Human Embryology.
 
Williams and Wilkins, Baltimore, viii & 366 pp.
 
Hertwig, O., 1901-07. Handbuch der Vergleichenden und experimentellen Entwicklungslehre der Wirbeltiere. (Edited by Dr. Oskar Hertwig and written by
numerous collaborators.) Fischer, Jena.
 
Huettner, A, F., 1941. Fundamentals of Comparative Embryology of the Vertebrates.
Macmillan, New York, xiv & 416 pp,
 
Jordan, H. E,, and Kindred, J. E., 1948. A Textbook of Embryology. Appleton, New
York, 5th Ed., xiv & 613 pp.
 
 
317
 
 
 
 
318
 
 
BIBLIOGRAPHY
 
 
Keihel^ F., 1897. Normentafeln zur Entwicklungsgeschichte der Wirbelthiere. I. Des
Schweines. Fischer, Jena, 114 S.
 
Martin^ P., 1912. Lehrbuch der Anatomic der Haustiere. ^chickhard & Ebner,
Stuttgart. (Bd. 1, Allgemeine und vergleichende Anatomic mit Entwicklungsgeschichte, xii & 811 S.)
 
Minot ^ C, S., 1893. A Bibliography of Vertebrate Embryology. Memoirs, Boston
Soc. Nat. History, Vol. 4, pp. 487-614.
 
Mtnot, C, S., 1911. A Laboratory Textbook of Embryology. The Blakiston Company,
Philadelphia, 2nd Ed., xii & 402 pp.
 
Needham^ J'., 1931. Chemical Embryology. Macmillan, New York, xxii & 2021 pp.
 
Patten^ B. A/., 1929. Early Embryology of the Chick. The Blakiston Company, Philadelphia, 3rd Ed., xiii & 228 pp.
 
Patten, B. M., 1946. Human Embryology. The Blakiston Company, Philadelphia,
XV & 776 pp.
 
Stssori, S., 1921. The Anatomy of the Domestic Animals. Saunders, Philadelphia,
2nd Ed., 930 pp.
 
Wetss, P.y 1939. Principles of Development. A Text in Experimental Embryology.
Holt, New York, xix & 601 pp.
 
IVieman, H. L., 1930. An Introduction to Vertebrate Embryology. McGraw-Hill,
New York, xi & 411 pp,
 
Windle, W, F., 1940. Physiology of the Fetus. Saunders, Philadelphia, xiii & 249 pp.
 
Zeitzschmann, 0,, 1923-24. Lehrbuch dcr Entwicklungsgeschichte der Haustiere.
R. Schoetz, Berlin, 542 S,
 
General Articles and Articles of Significance for the
Interpretation of Developmental Processes
 
Alexander, J., 1944. The Gene — A Structure of Colloidal Dimensions. Chapt. 37,
pp. 808-819, in “Colloid Chemistry,” Vol. V, edited by Jerome Alexander,
Reinhold Publishing Corp., New York.
 
Allen, W. F., 1918. Advantages of sagittal sections of pig embryos for a medical
embryology course. Anat. Rec., Vol. 14, pp. 183-191.
 
Barth, L. G., 1944. Colloid Chemistry in Embryonic Development. Chapt. 39, pp.
851-859, in “Colloid Chemistry,” Vol. V, edited by Jerome Alexander, Reinhold Publishing Corp., New York.
 
Chambers, R., 1944. Some Physical Properties of Protoplasm. Chapt. 41, pp. 864-875,
in “Colloid Chemistry,” Vol. V, edited by Jerome Alexander, Reinhold
Publishing Corp., New York.
 
Conklin, E, G., 1914. The cellular basis of heredity and development. Pop. Sci.
Monthly, Vol. 85, pp. 105-133. '
 
Hartman, C. G., 1 931 . Development of the egg as seen by the physiologist. Sci. Monthly,
Vol, 33, pp, 17-28.
 
Medley, 0. F., 1926. Quantitative study of growth of certain organs in pig fetus. Bull.
Med. Coll. Va., Vol. 23, pp. 19-36.
 
Holtfreter, J., 1947. Changes of structure and the kinetics of differentiating embryonic
cells. Jour. Morph., Vol. 80, pp. 57-92.
 
Holtfreter, J., 1947. Observations on the migration, aggregation and phagocytosis of
embryonic cells. Jour. Morph., Vol. 80, pp. 93-111.
 
 
 
THE SEX ORGANS AND GAMETOGENESIS
 
 
319
 
 
Kingsbury, B. F,, 1926. On the so-called law of anteroposterior development. Anat.
Rec., Vol. 33, pp. 73-87.
 
Lewis, W, H., 1947. Mechanics of invagination. Anat. Rec., Vol. 97, pp. 139-156.
 
Spemann, H., 1927. Organizers in animal development. Proc. Roy. Soc. London,
Ser. B, Vol. 102, pp. 177-187.
 
Spemann, H., 1938. Embryonic Development and Induction. Yale Univ. Press,
New Haven, xii & 401 pp.
 
The Sex Organs and Gametogenesis
 
Allen, E., 1923. Ovogenesis during sexual maturity. Am. Jour. Anat., Vol. 31, pp.
439-481.
 
Allen, E., Kountz, IV. B., and Francis, B. F., 1925. Selective elimination of ova in the
adult ovary. Am. Jour. Anat., Vol. 34, pp. 445-468.
 
Bascom, K. F., 1925. Quantitative studies of the testis. I. Some observations on the
cryptorchid testes of sheep and swine. Anat. Rec., Vol. 30, pp. 225-241.
 
Bascom, K. F., and Ouerud, H. L., 1925. Quantitative studies of the testicle. II. Pattern
and total tubule length in the testicles of certain common mammals. Anat. Rec.,
Vol. 31, pp. 159-169.
 
Blandau, R. J., 1945. The first maturation division of the rat ovum. Anat. Rec.,
Vol. 92, pp. 449-457.
 
Corner, G. W., 1917. Maturation of the ovum in swine. Anat. Rec., Vol. 13, pp. 109
112 .
 
Comer, G. IV., 1919. On the origin of the corpus luteum of the sow from both granulosa and theca interna. Am. Jour. Anat., Vol. 26, pp. 117-183.
 
Evans, H. M., and Swezv, 0., 1929. Ovogenesis and the normal follicular cycle in adult
mammalia. Mem. LTniv. Cal., Vol. 9, pp. 119-224.
 
Everett, N. B., 1945. The present status of the germ-cell problem in vertebrates. Biol.
Rev., Vol. 20, pp. 45-55.
 
Gould, H. N., 1923. Observations on the genital organs of a sex intergrade hog. Anat.
Rec., Vol. 26, pp, 241-261.
 
Hargitt, G. T., 1925-30, The formation of the sex glands and germ cells of mammals.
Jour. Morph. & Physiol., Vols. 40, 41, 42, 49.
 
Hartman, C. G., 1926. Polynuclear ova and polyovular follicles in the opossum and
other mammals, with special reference to the problem of fecundity. Am. Jour.
Anat., Vol. 37, pp. 1-52.
 
Hill, R. T., Allen, E., and Kramer, T. C., 1935. Cinemicrographic studies of rabbit
ovulation. Anat. Rec., Vol. 63, pp. 239-245.
 
Kellicott, W. E,, 1913. A Textbook of General Embryology. Holt, New York, v &
376 pp.
 
Kiipfer, M., 1920. Beitrage zur Morphologic der weiblichen Geschlechtsorgane bei
den Saugetieren. Ueber das Auftreten gelber Korper am Ovarium des domestizierten Rindes und Schweines. Vierteljahrsschrift d. Naturf. Gesellsch., Zurich,
Bd. 65, S. 377-433.
 
Latta, J, S., and Pederson, E. S,, 1944. The origin of ova and follicle cells from the
germinal epithelium of the ovary of the albino rat as demonstrated by selective
intravital staining with India ink. Anat. Rec., Vol. 90, pp. 23-35,
 
 
 
320
 
 
BIBLIOGRAPHY
 
 
Morgan^ T. H.j 1926. The Theory of the (iene. Yale Univ. Press, New Haven, xvi &
343 pp.
 
Fainter, T. S,, 1922. Studies in mammalian spermatogenesis. J(/Ur. Exp. Zodl., Vols.
35, 37, 39. Jour. Morph. & Physiol., Vol. 43.
 
Parker, G. H., and Bullard, C., 1913. On the size of litters and the number of nipples
in swine. Proc, Am. Acad. Arts & Sciences, Vol. 49, pp. 399-426.
 
Patten, W., 1925. Life, evolution and heredity. Sci. Monthly, Vol. 21, pp. 122-134.
 
Pincus, G., and Enzrnann, K. V,, 1937. The growth, maturation and atresia of ovarian
eggs in the rabbit. Jour. Morph., Vol. 61, pp. 351-383.
 
Pltske, E. C., 1940. Studies on the influence of the zona pellucida in atresia. Jour.
Morph., Vol. 67, pp 321-349.
 
Schmaltz-, B., 1911. Die Slrucktur der Ge.schlechtsorgane der ITaussaugetiere. P. Parey,
Berlin, xii & 388 S.
 
Smith, J, T., and Kettcrmgharn, R. C., 1937-38. Rupture of the graafian follicles.
Part I. Am. Jour. Obs. & Gyn., Vol. 33, pp. 820-827. Part IT Am. Join. Obs.
& Gyn., Vol. 36, pp. 45.3-460.
 
Stein, K. F., and Allen, E., 1942. Attempts to stimulate proliferaticm of the germinal
epithelium of the ovary. Anat. Rec., Vol. 82, pp. 1 -9.
 
Thanhoffer, L. de, 1934. The structure of the graafian follicle as revealed by microdissection. Zeilschr. f. Anat. u. Entwg., Bd. 102, S. 402-408.
 
Warwick, B. L., 1925. The eflect of vasectomy on swine. Anat. Rec., Vol. 31, pp.
19-21.
 
Wihon, E. B., 1925. The Cell in Development and Heredity. Macmillan, New York,
3rd Ed., ix & 1232 pp.
 
Young, W. C , 1929. A study of the function of the epididymis. I. Is the attainment
of full spermatcjzoon maturity attributable to some specific action of the epididymal secretion? Jour. Morph. & Physiol., Vol. 47, pp. 479-495.
 
Young, W. C., 1929. A study of the function of the epididymis. II. The importance of
an aging process in sperm for the length of the period during which fertilizing
capacity is retained by sperm isolated in the epididymis of the guinea-pig. Jour.
Morph. & Physiol., Vol. 48, pp. 475-491.
 
Young, W. C., 1931. A study of the function cT the epididymis. III. Functional changes
undergone by spermatozoa during their passage through the epididvmis and
vas deferens in the guinea-pig. Jour. Exp. Biol., Vol. 8, pp. 151-162.
 
The Sexual Cycle, Fertilization, Sex Determination
 
Allen, E., 1926. The ovarian follicular hormone: a study of variation in pig, cow, and
human ovaries. Proc. Soc. Exp. Biol. & Med., Vol. 23, pp. 383-387.
 
Allen, E,, Danforth, C. H., and Daisy, ErA,, 1939. Sex and Internal Secretions. Williams
and Wilkins, Baltimore, 2nd Ed., xxxvi & 1346 pp.
 
Allen, E., and Daisy, E. A., 1927. Ovarian and placental hormones. Physiol. Reviews,
Vol. 7, pp. 600-650.
 
Ampolsky, Z)., 1928. Cyclic changes in size of muscle fibers of the fallopian tube of
the sow. Am. Jour. Anat., Vol. 40, pp. 459-469.
 
Blandau, R., and Money, W. L., 1944. Observations on the rate of transport of spermatozoa in the female genital tract of the rat. Anat. Rec., Vol. 90, pp. 25.5-260.
 
 
 
THE SEXUAI, CYCLE, FERTILIZATION, SEX DETERMINATION 321
 
 
Burns, R. K., Jr., 1938. Hormonal control of sex differentiation. Am. Nat., Vol. 72,
pp. 207-227.
 
Comstock, R. E., 1939. A study of the mammalian sperm cell. I. Variations in the
glycolytic power of spermatozoa and their relation to motility and its duration.
Jour. Exp. Zool., Vol. 81, pp. 147—164.
 
Corner, G. W., 1915. The corpus luteum of pregnancy as it is in swine. Carnegie Inst.,
Contrib. to E-mbryoL, Vol. 2, pp. 69-94.
 
Corner, G. W., 1917. Variations in the amount of phosphatids in the corpus luteum of
the sow during pregnancy. Jour. Biol. Chem., Vol. 29, pp. 141-143.
 
Corner, G. W , 1919. On the origin of the corpus luteum of the sow from both granulosa and theca interna. Am. Jour. Anal., Vol. 26, pp. 117-183.
 
Cornet, G. W., 1921. Cyclic changes in the ewaries and uterus of swine, and their
relations to the mechanism of implantaticm. Carnegie Inst., Contrib. to Embryol.,
Vol. 13, pp. 117-146.
 
Corner, G. IT., 1923. Cyclic variation in uterine and tubal contraction waves. Am.
Jour. Anat., Vol. 32, pp. 345-351.
 
Corner, G IT., 1928. Physiolcjgy of the corpus luteum. I. The efTect of \Try early
ablation of the corpus lutcnun upon embryos and uterus. Am. Jour. Physiol.,
Vol. 86, pp. 74-81.
 
Coiner, G IV., 1942. The Hormones in Human Reproduction. Princeton Univ. Press,
Princeton, xix & 265 pp.
 
Corner, G. IT., and Allen, IT, M., 1929. Physiology of the corpus luteum. II. Production
(3f a special uterine reac tion (progestational proliferation) by extracts of the
cwpus luteum. Am. Jour. Physiol., Vol. 88, pp. 326-339.
 
Coinn, G. IT., and Allen, IT. A/., 1929. Physiology of the corpus luteum. III. Normal
growth and implantation of embryos after very earlv ablation of the ovaries,
under the influence of extracts of the corpus luteum. Am. lour. Physiol., Vol. 88,
pp. 340-346.
 
Cornn, G. IT, and Amsbaugh, A. E., 1917. Oestrus and ovulation in swine. Anat. Rec.,
Vol. 12, pp. 287-291.
 
Corner, G. IT., and Snyder, F. F., 1922. Observations on the structure and function
of the uterine ciliated epithelium in the pig, with reference to certain clinical
hypothesep. Am. Jour. Obs. & Gyn., VcjI. 3, pp. 358-366.
 
Crew, F. A. E., 1925. Prenatal death in the pig and its effect upon the sex-ratio.
Proc. Roy. Soc. Edinburgh, V^ol. 46, pp. 9-14.
 
Hammond, J., 1934. The fertilisation of rabbit ova in relation to time: A method of
controlling the litter size, the duration of pregnancy and the weight of the young
at birth. Jour. Exp. Biol., Vol. 11, pp. 140-161.
 
Hartman, C. G., 1929. The homology of menstruation. J. A. M. A., Vol. 92, pp. 19921995.
 
Hartman, C. G., and Squier, R. R., 1931. The follicle-stimulating effect of pig anterior
lobe on the monkey ovary. Anat. Rec., Vol. 50, pp. 267-273.
 
Keye, J. D., 1923. Periodic variations in spontaneous contractions of uterine muscle
in relation to the oestrous cycle and early pregnancy. Bull. Johns Hopkins Hosp.,
Vol. 34, pp. 60-63.
 
Lewis, L. L., 1911. The vitality of reproductive cells. Agric. Exp. Sta. Oklahoma,
Bull. No. 96.
 
 
 
322
 
 
BIBLIOGRAPHY
 
 
Lillie^ F. /?., 1919. Problems of Fertilization. Univ. Chicago Press, xii & 278 pp.
 
Loeb^ Z.., 1923. The mechanism of the sexual cycle, with special reference to the corpus
luteum. Am. Jour. Anat., Vol. 32, pp. 305-343. ^
 
Markee, J. E., Pasqualetti^ R. A., and Hinsey, J. C., 1936. Growth of intraocular endometrial transplants in spinal rabbits. Anat. R^c., Vol. 64, pp. 247-253.
 
Marshall^ F, H. A., 1922. The Physiology of Reproduction. Longmans, Green & Co.,
London, 2nd Ed., xvi & 770 pp.
 
McKenzie^ F. F, 1926. The normal oestrous cycle in the sow. Univ. Missouri Coll.
Agric. Exp. Sta. Res. Bull., Vol. 86, pp. .S-41.
 
Papanicolaou^ G. A'"., 1923. Oestrus in mammals from a comparative point of view.
Am. Jour. Anat., Vol. 32, pp. 285-292.
 
Parker^ G. IL, 1931. Passage of sperms and of eggs through oviducts in terrestrial
vertebrates. Phil. Trans. Roy. Soc. London, Ser. B, Vol. 219, pp. 381-419.
 
Phillips, R. W., and Andrews, F, j\., 1937. The speed oi travel of ram spermatozoa.
Anat. Rec., Vol. 68, pp. 127-132.
 
Pincus, G., 1936. The Eggs of Mammals. Macmillan, New York, ix & 160 pp.
 
Schott, R. G., and Phillips, R. W., 1941. Rate of sperm travel and time of ovulation in
sheep. Anal. Rec,, Vol. 79, pp. 531-540.
 
Secktnger, D, L., 1923. Spontaneous contractions of the Fallopian tube of the domestic
pig with reference to the oestrous cycle. Bull. Johns Hopkins Hosp., Vol. 34,
pp. 236-239.
 
Snyder, F. F., 1923. Changes in the Fallopian tube during the ovulation cycle and
early pregnancy. Bull. Johns Hopkins Hosp., Vol. 34, pp. 121-125.
 
Soderwall, A, L., and Blandau, R. J., 1941. The duration of the fertilizing capacity of
spermatozoa in the female genital tract of the rat. Jour. Exp. Zool , Vol. 88,
pp. 55-64.
 
Stockard, C. /?., 1923. The general morphological and physiological importance of
the oestrous problem. Am. Jour. Anat., Vol. 32, pp. 277-283.
 
Surface, F. M., 1908, Fecundity of swine. Biometrika, Vol. 6, pp. 433-436.
 
Swingle, W, W., 1926. The determination of sex in animals. Physiol. Rev., Vol. 6,
 
pp. 28-61.
 
Toothill, M. C., and Toung, W. C.,\93\. The time consumed by spermatozoa in passing
through the ductus epididymidis of the guinea-pig as determined by means of
India-ink injections. Anat. Rec., Vol. 50, pp. 95-107.
 
Wilson, K. M., 1926. Histological changes in the vaginal mucosa of the sow in relation
to the oestrous cycle. Am. Jour. Anat., Vol. 37, pp. 417-432.
 
Witschi, E., 1932. Physiology of embryonic sex differentiation. Am. Nat., Vol. 66,
pp. 108-117.
 
Cleavage, Germ Layer Formation^ and the Structure of Young
 
Embryos
 
Assheton, R., 1899. The development of the pig during the first ten days. Quart. Jour.
Micr. Sci., Vol. 41, pp. 329-359.
 
Clark, R, T,, 1934. Studies on the physiology of reproduction in the sheep. II. The
cleavage stages of the ovum. Anat. Rec., Vol. 60, pp. 135-159.
 
Conklin, E, G., 1909. The application of expieriment to the study of the organization
and early differentiation of the egg. Anat. Rec., Vol. 3, pp. 149-154.
 
 
 
CI.EAVAGE, GERM LAYERS, YOUNG EMBRYOS
 
 
323
 
 
Defrise^ A.^ 1933. Some observations on living eggs and blastulae of the albino rat.
Anat. Rec., Vol. 57, pp. 239-250.
 
Green^ W, W., and Winters, L. Af., 1946. Cleavage and attachment stages of the pig.
Jour. Morph., Vol. 78, pp. 305-316.
 
Heuser, C\ H., and Streeter, G. L., 1 929. Early stages in the development of pig embryos,
from the period of initial cleavage to the time of the appearance of limb-buds.
Carnegie Inst., Contrib. to Embryol., Vol. 20, pp. 1-29.
 
Keibel, F., 1891. Uebcr die Entwicklungsgeschichte des Schweines. Anat. Anz.,
Bd. 6, S. 193-198.
 
Keibel, F., 1894. Studien zur Entwicklungsgeschichte des Schweines (Sus scrofa
domesticus). I. Morph. Arbeiten, Bd. 3, S. 1-139.
 
Keibel, F., 1895. Ueber einige Plattenmodelle junger Schwein-embryonen. Verhandlungen d. Anat. Ges., Erganzungsheft Bd. 10, Anat. Anz., S. 199-201.
Keibel, F., 1896. Studien zur Entwicklungsgeschichte des Schweines (Sus scrofa
domesticus). II. Morph. Arbeiten, Bd. 5, S. 17-168.
 
Kingsbury, B, F., 1920. I'he developmental origin of the notochord. Science, N. S.,
Vol. 51, pp. 190-193.
 
Kingsbury, B. F., 1924a. The developmental significance of the notochord (Chorda
dorsalis). Zeitschr. f. Morphologic u. Anthropologic, Vol. 24, pp. 59-74.
Kingsbury, B. F,, 1924b. The significance of the so-called law of cephalocaudal differential growth. Anat. Rec., Vol. 27, pp. 305-321.
 
Kingsbury, B, F., 1926. On the so-called law of antero-posterior development. Anat.
Rec., Vol. 33, pp. 73-87.
 
Lewis, F. T., 1902. The gross anatomy of a 12-mm. pig. Am. Jour. Anat., Vol. 2,
 
pp. 211-226.
 
Lewis, W, H,, and Gregory, P. W,, 1929. Cinematographs of living developing rabbiteggs. Science, Vol. 69, pp. 226-229.
 
Lewis, W. H., and Hartman, C, G., 1933. Early cleavage stages of the egg of the monkey
(Macacus rhesus). Carnegie Inst., Contrib. to Embryol., Vol. 24, pp. 187-201.
Lewis, W. PL, and Wright, E, S,, 1935. On the early development of the mouse egg.
 
Carnegie Inst., Contrib. to Embryol., Vol. 25, pp. 113-144.
 
Macdonald, E., and Long, J, A., 1934. Some features of cleavage in the living egg of
the rat.^Am. Jour. Anat., Vol. 55, pp. 343-361.
 
Nicholas, J. S., and Hall, B. V., 1942. Experiments on developing rats. II. The development of isolated blastomeres and fused eggs. Jour. Exp. Zooi., Vol. 90, pp.
441-459.
 
Patten, B. M,, and Philpott, R., 1921 . The shrinkage of embryos in the processes preparatory to sectioning. Anat. Rec., Vol. 20, pp. 393-413.
 
Pincus, G,, 1939. The comparative behavior of mammalian eggs in vivo and in vitro.
IV. The development of fertilized and artificially activated rabbit eggs. Jour.
Exp. Zodl., Vol. 82, pp. 85-131.
 
Robinson, A,, 1892. Observations upon the development of the segmentation cavity,
the archenteron, the germinal layers, and the amnion in mammals. Quart.
Jour. Micr. Sci., Vol. 33, pp. 369-455.
 
Streeter, G. L,, 1926. Development of the raesoblast and notochord in pig embryos.
 
Carnegie Inst., Contrib. to Embryol., Vol. 19, pp. 73-92.
 
'J'hyng, F, W,, 1911. The anatomy of a" 7.8-mm. pig embryo. Anat. Rec., Vol. 5,
pp. 17-45.
 
 
 
324
 
 
BIBLIOGRAPHY
 
 
Waldo, C, M., and Wimsatt, W. A., 1945. The effect of colchicine on early cleavage of
mouse ova. Anat. Rec., Vol. 93, pp. 363-375.
 
Wallin, E,, 1917. A teaching model of a 10-mm. pig embryo. Anal. Rec., Vol. 13,
pp. 295-297.
 
Weysse, A, W,, 1894. On the blastodermic vesicle of Sus scrofa domesticus. Proc. Am.
Acad. Arts & Sciences, Vol. 30, pp. 283-321,
 
Williams, L. W., 1908. The later development of the notochord in mammals. Am.
Jour. Anat., Vol. 8, pp. 251-284.
 
Fetal Membranes and the Relations of the Embryos to the Uterus
 
Abromavich, C. E., 1926. The morphology and distribution of the rosettes on the foetal
placenta of the pig. Anat. Rec., Vol. 33, pp. 69-72.
 
Assheton, R., 1906. The morphology of the ungulate placenta. Phil. Trans. Roy. Soc.
London, Ser. B, Vol. 198, pp. 143-220.
 
Brambel, C. E., Jr., 1933. Allantochorionic differentiations of the pig studied morphologically and histochemically. Am. Jour. Anat., Vol. 52, pp 397-459.
 
Corner, G. W., 1921. Internal migration of the ovum. Bull. Johns Hopkins Hosp.,
Vol. 32, pp. 78-83.
 
Fawcett, D. W., Wislocki, G. B., and Waldo, C. M., 1947. The development of mouse
ova in the anterior chamber of the eye and in the abdominal cavity. Am. Jour.
Anat., Vol. 81, pp. 413-443.
 
Gellhorn, A., Flexner, L. B., and Pohl, H. A., 1941. I’he transfer of radioactive sodium
across the placenta of the sow. Jour. Cell. & Comp. Physiol., Vol. 18, pp. 393400.
 
Goldstein, S. R., 1926. A note on the vascular relations and areolae in the placenta of
the pig. Anat. Rec., Vol. 34, pp. 25-35.
 
Grosser, 0., 1909. Vergleichende Anatomic und Entwicklungsgeschichte der Eihaute
und der Placenta, Braumiiller, Leipzig, xi & 314 S.
 
Grosser, 0., 1927. Friihentwicklung, Eihautbildung und Placentation des Mcnschen
und der Saugetiere. Verlag von J. F. Bergmann, Munchen, viii & 454 pp.
 
Heuser, C. H., 1927. A study of the implantation of the ovum of the pig from the stage
of the bilaminar blastocyst to the completion of the fetal membranes. Carnegie
Inst., Contrib. to Embr^ol., Vol. 19, pp. 229-243.
 
Hubrecht, A. A. W., 1895. Die Phylogenese des Amnions und die Bedeutung des
Trophoblastes. Verh. Koniklijke Akad. van Wetenschappen te Amsterdam, fiir
1895, S. 3-66.
 
Lell, W. A., Liber, K. E., and Snyder, F. F., 1931. Quantitative study of placental transmission and permeability of fetal membranes at various stages of pregnancy.
Am. Jour. Physiol., Vol. 100, pp. 21-31.
 
Mossman, H. W., and Noer, H. R., 1947. A study of the amnion with the electron
microscope. Anat. Rec., Vol. 97, pp. 253-257.
 
Noer, H. R., 1946. A study of the effect of flow direction on placental transmission,
using artificial placentas. Anat. Rec., Vol. 96, pp. 383-389.
 
Robinson, A., 1904. Lectures on the early stages in the development of mammalian
ova and on the formation of the placenta in different groups of mammals. Jour.
Anat. & Physiol., Vol. 38, pp. 186-204.
 
 
 
THE NERVOUS SYSTEM AND SENSE ORGANS
 
 
325
 
 
Runner, M, JV,, 1947. Development of mouse eggs in the anterior chamber of the eye.
Anat. Rec., Vol. 98, pp. 1-1 7.
 
Warwick, B. L., 1926. Intra-uterine migration of ova in the sow. Anat. Rec., Vol. 33,
pp. 29-33.
 
Wislocki, G. B.y 1929. On the placentation of primates, with a consideration of the
phylogeny of the placenta. Carnegie Inst., Contrib. to Embryol., Vol. 20, pp.
51-80.
 
Wisloch, G. B., 1935. On the volume of the fetal fluids in sow and cat. Anat. Rec.,
Vol. 63, pp. 183-192.
 
Widocki, G. B., and Dempsey, E. W,, 1946. Histochemical reactions of the placenta
of the pig. Am. Jour. Anat., Vol. 78, pp. 181-225.
 
The Nervous System and Sense Organs
 
Assheton, R., 1892. On the development of the optic nerve of vertebrates and the
choroidal fissure of embryonic life. Quart. Jour. Micr. Sci., Vol. 34, pp. 85-103.
 
Bardeen, C. R., 1903. The growth and histogenesis of the cerebrospinal nerves in
mammals. Am. Jour. Anat., Vol. 2, pp. 231-257.
 
Barnes, W,, 1883-84. On the development of the posterior fissure of the spinal cord
and the reduction of the central canal in the pig. Proc. Am. Acad. Arts. &
Sciences, Vol. 19, pp. 97-110.
 
Bedford, E. A., 1904. The early history of the olfactory nerve in swine. Jour. Comp.
Ncur., Vol. 14, pp. 390-410.
 
Bradley, 0. C., 1904. Neuromeres of the rhombencephalon of the pig. Review of
Neurology & Psychiatry, Vol. 2, pp. 625-635.
 
Coghill, G. E., 1926. The growth of functional neurones and its relation to the development of behavior. Proc. Am. Philosoph. Soc., Vol. 65, pp. 51-55.
 
Detwiler, S. R., 1936. Neuroembryology. An Experimental Study. Macmillan, New
York, X & 218 pp.
 
Dowd, L. W., 1929. The development of the dentate nucleus in the pig. Jour. Comp.
Neur., Vol. 48, pp. 471-498.
 
GrademgOy G., 1887. Die embryonale Anlage des Mittelohrs; die morphologische
BedeutiAig der Gehorknochelchen. Mitth. aus dem Embryeflog. Inst. d. Universitat. Wien, 1887, S. 85-232.
 
Hardesty, /., 1904. On the development and nature of the neuroglia. Am. Jour. Anat.,
Vol. 3, pp. 229-268.
 
Hardesty, /., 1905, On the occurrence of the sheath cells and the nature of the axone
sheaths in the central nervous system. Am. Jour. Anat., Vol. 4, pp. 329-354.
 
Held, H., 1909. Die Entwicklung des Nervengewebes bei den Wirbeltieren. J. A.
Barth, Leipzig, ix & 378 S.
 
Herrick, C. J., 1893. The development of the medullated nerve fibres. Jour. Comp.
Neur., Vol. 3, pp. 11-16.
 
Herrick, C. J., 1909. The criteria of homology in the peripheral nervous system. Jour.
Comp. Neur., Vol. 19, pp. 203-209.
 
Herrick, C. J., 1925, Morphogenetic factors in the differentiation of the nervous
system. Physiol. Reviews, Vol. 5, pp. 112-130.
 
 
 
326
 
 
BIBLIOGRAPHY
 
 
Heiiser, C. H., 1913. The development of the cerebral ventricles in the pig. Am. Jour.
Anal., Vol. 15, pp. 215-252.
 
Hoskins, E. R., 1914. On the vascularization of the spinal cord o^the pig. Anat. Rec.,
Vol. 8, pp. 371-391.
 
Johnston, J. B., 1909. The morphology of the fore-brain vesicle in vertebrates. Jour.
Comp. Neur., Vol. 19, pp. 457-539.
 
Kallius, E., 1894. Untersuchungen liber die Netzhaut die Saugethiere. Anat. Hefte,
Bd. 3, S. 527-582.
 
Kappers, C. U. A., und Fortuyn, A. B. D., 1921. Vergleichende Anatomie des Nervensystems. (Theil II. Des Kleinhirns, Des Mittlc- und Zwischenhirns und des
Vorderhirns. S. 626-1329.) Bohn, Haarlem.
 
Kaslschenko, N., 1887. Das Schicksal der embryonalen Schlundspalten bei Saugetieren. Arch. f. mikr. Anat., Bd. 30, S. 1-26.
 
Kessler, L., 1877. Zur Entwicklung des Auges der Wirbelthiere. Vogel, Leipzig 112 S.
Kingsbury, B. F., 1922. The fundamental plan of the x ertebrate brain. Jour. Comp.
Neur., Vol. 34, pp. 461-491.
 
Kingsbury, B. F., and Adelmann, H. B., 1924. The morphologual plan of the head
Quart. Jour. Micr. Sci., Vol. 68, pp. 239-285.
 
Kbllicker, A., 1904. Die Entwicklung und Bedeutung des Glaskorpers. Zeitschr. f. wiss.
Zool., Bd. 76, S. 1-25.
 
Krausse, R., 1890. Entwicklungsgeschichte der hautigen Bogengange. Arch, f mikr.
Anat., Bd. 35, S. 287-304.
 
Kuntz, A,, 1909. A contribution to the histogenesis of the sympathetic nervous system.
Anat. Rec., Vol. 3, pp. 458-465.
 
KuntZi 1922. Experimental studies on the histogenesis of the sympathetic nervous
system. Jour. Comp, Neur., Vol. 34, pp. 1-36.
 
Kupffer, K. V., 1905. Die Morphogenie des Centralncrvensystems. Hertwig’s Handbuch, Bd. 2, Teil 3, Kap. VIII, S. 1-394.
 
Locy, W, A., 1895. Contribution to the structure and development of the vertebiate
head. Jour. Morph., Vol. 11, pp, 497-594.
 
Paterson, A. M., 1891. Development of the sympathetic nervous system in mammals.
 
Phil. Trans. Roy. Soc, London, Ser. B., Vol. 181, pp. 159-186.
 
Prentiss, C. JV., 1910. The development of the hypoglossal ganglia of pig embryos.
 
Jour. Comp. Neur., Vol. 20, pp. 265-282.
 
Prentiss, C. W,, 1913. On the development of the membrana tectoria with reference
to its structure and attachments. Am. Jour. Anat., Vol. 14, pp. 425-460.
 
Rabl, C., 1899. tJber den Bau und die Entwicklung der Linse. Theil III. Die Linse
der Saugethiere. Riickblick und Schluss. Zeitschr. f. wiss. Zool., Bd. 67, S.
1-138.
 
Rabl, C., 1900. Ober den Bau und die Ehtwicklung der Linse. Wilhelm Englemann,
Leipzig, vi & 324 S.
 
Retzius, G., 1881-1884. Das Gehororgan der Wirbelthiere. Theil II. Das Gehdrorgan
der Reptilien, der Vogel und der Saugethiere. Stockholm, viii & 368 S.
 
Sauer, F. C,, 1935a. Mitosis in the neural tube. Jour. Comp. Neur., Vol. 62, pp.
377-405.
 
Sau 0 r, F. C., 1935b. The cellular structure of the neural tube. Jour. Comp. Neur.,
Vol. 63, pp. 13-23.
 
 
 
THE CIRCULATORY SYSTEM
 
 
327
 
 
Sauer, F. C., 1939. Development of beta crystallin in the pig and prenatal weight of
the lens. Growth, Vol. 3, pp. 381-386.
 
Seef elder, R., 1910. Beitrage zur Histogenese und Histologie der Netzhaut, des Pigmentepithels und des Sehnerven. Arch. f. Ophthal., Bd. 73, S. 419-537.
Shambaugh, G. E., 1907. A restudy of the minute anatomy of structures in the cochlea,
with conclusions bearing on the solution of the problem of tone perception.
Am. Jour. Anat., Vol. 7, pp. 245-257.
 
Shambaugh, G. E., 1926. The development of the membranous labyrinth. Arch.
Otolaryng., Vol. 3, pp. 233-236.
 
Shaner, R, F., 1932. The development of the nuclei and tracts of the midbrain. Jour.
Comp. Neur., Vol. 55, pp. 493-511.
 
Shaner, R. F., 1934a. The development of a medial motor nucleus and an accessory
abducens nucleus in the pig. Jour. Anat., Vol. 68, pp. 314-317.
 
Shaner, R. F., 1934b. The development of the nuclei and tracts related to the acoustic
nerve in the pig. Jour. Comp. Neur., Vol. 60, pp. 5-19.
 
Takahashi, K., 1931. Pri la genezo de la papilo de nerve optica ce Sus scrofa domeslicus. Folia Anatomic a Japonica, Bd. 9, S. 149-167.
 
Tuckerman, F., 1888. Note on the papilla foliala and other taste areas of the pig. Anat.
Anz., Bd. 3, S. 69-73.
 
Tuttle, A. H., 1884. The relation of the external meatus, tympanum and Eustachian
tube to the first visceral cleft. Pnx . Ain. Acad. Arts & Sciences, Vol. 19, pp.
111-132.
 
Van Campenhout, E., 1935. Origine du ganglion acoustique chez le pore. Arch. Biol.,
T. 46, pp. 273-286.
 
Waterman, A. J., 1938. The development of the inner ear rudiment of the rabbit
embryo in a foreign environment. Am. Jour. Anat., Vol. 63, pp. 161-219.
Weed, L, W., 1917. The development of the cerebrospinal spaces in pig and in
man. Carnegie Inst., Contrib. to Embryo!., Vol. 5, No. 14, 116 pp.
 
Windle, W. F., Fish, M. W., and O'' Donnell, J, E., 1934. Myelogeny of the cat as related to development of fiber tracts and prenatal behavior patterns. Jour. Comp.
Neur., Vol. 59, pp. 139-165.
 
^ The Circulatory System
 
Barclay, A. E., Franklin, K. J., and Prichard, M, M. L., 1944. The Foetal Circulation
and Cardiovascular System, and the Changes That Ihey Undergo at Birth.
Blackwell Scientific Publications, Ltd., Oxford, xvi & 275 pp.
 
Barcroft, J., 1946. Researches on Pre-natal Life. Blackwell Scientific Publications,
Ltd., Oxford, VoL I, xiii & 292 pp.
 
Barry, A., 1942. The intrinsic pulsation rates of fragment of the embryonic chick heart.
Jour. Exp. Zool., Vol. 91, pp. 119-130.
 
Begg, A. S., 1920. Absence of the vena cava inferior in a 12-mm. pig embryo, associated with the drainage of the portal system into the cardinal system. Am. Jour.
Anat., Vol. 27, pp. 395-403.
 
Boas, J. E. V., 1887. Ueber die Arterienbogen der Wirbelthiere. Morph. Jahrb.,
Bd. 13, S. 115-118.
 
Born, G,, 1888. t)bcr die Bildung dcr Klappan, Ostien und ScheidewSnde im SSugetierherzen. Anat. Anz., Bd. 3, S. 606-612,
 
 
 
328
 
 
BIBLIOGRAPHY
 
 
Born^ G., 1889. Beitrage zur Entwicklungsgeschichte dcs Saugcthierherzens. Archf. mikx. Anat., Bd. 33, S. 284-377.
 
Bremer, J. L., 1902. I. The origin of the pulmonary arteries in ntammals. Am. Jour.
Anat., Vol. I, pp. 137-144.
 
Bremer, J, L., 1909. II. On the origin of the pulmonary arteries in mammals. Anat.
Rec., Vol. 3, pp. 334-340.
 
Butler, E. G., 1927. The relative r61e played by the embryonic veins in the development of the mammalian vena cava posterior. Am. Jour. Anat., Vol. 39, pp.
267-353.
 
Congdon, E, D., and Wang, H. W , 1926. The mechanical processes concerned in the
formation of the differing tvpes of aortic arches of the chick and the pig and in
the divergent early development of their pulmonary arches. Am. Jour. Anat.,
Vol. 37, pp. 499-520.
 
Davh, D. M., 1910. Studies on the chief veins in early pig embryos and the origin of
the vena cava inferior. Am. Jour. Anal., Vol. 10. pp. 461-472.
 
Doan, C. A., Cunningham, R. S., and Sabin, F R., 1925. Experimental studies on the
origin and maturation of avian and mammalian red blood-cells. Carnegie Inst.,
Contrib. to EmbryoL, Vol. 16, pp. 163-226.
 
Emmel, V. E., 1914. Concerning certain cytological characteristics of the erythroblasts in the pig embryo and the origin of non-nuclcated erythrocytes by a
process of cytoplasmic constriction. Am. Joui. Anat., V^ol. 16, pp. 127-206.
 
Evans, H. M., 1909. On the development of the aortae, cardinal and umbilical veins
and other blood-vessels of vertebrate embryos from capillaries. Anat. Rec., Vol.
3, pp. 498-518
 
Flint, J. M., 1903. The angiology, angiogenesis, and organogenesis of the submaxillary gland. Am. Jour. Anat., Vol. 2, pp. 417-444.
 
Frazer, J. E., 1917. Formation of Pars Membranacea Septi. Jour. Anat. & Physiol.,
Vol. 51, pp. 19-29.
 
Goss, C. M., 1935. Double hearts produced experimentally in rat embryos. Jour.
Exp. Zool., Vol. 72, pp. 33-49.
 
Goss, C. M., 1938. The first contractions of the heart in rat embryos. Anat. Rec., Vol.
70, pp. 505-524.
 
Goss, C. M., 1942. The physiology of the embryonic mammalian heart before circulation. Am. Jour. Physiol., Vol. 137, pp. 146-152.
 
Gregg, R, E., 1946. An arterial anomaly in the fetal pig. Anal. Rec., Vol. 95, pp. 53-65.
 
Henser, C. H., 1923. The branchial vessels and their derivatives in the pig. Carnegie
Inst., Contrib. to Embryol., Vol. 15, pp. 121-139.
 
Hill, E. C., 1907. On the gross development and vascularization of the testis. Am.
Jour. Anat., Vol. 6, pp. 439-459.
 
His, W., 1900. Lecithoblast und Angioblast der Wirbeltiere. Abhandl. der Math,
phys. Klasse der Konigl. Sach. Gesellsch. d. Wissenschaften, Bd. 26, S. 173-328.
 
Hochstetter, F., 1906. Die Entwicklung dcs Blutgefasssystcms. Hertwig’s Handbuch,
Bd, 3, Teil 2, S. 21-166.
 
Hofmann, L. v., 1914. Die Entwicklung der Kopfartcricn bei Sus scrofa domesticus.
Morph. Jahrb., Bd. 48, S, 645-671.
 
Hogue, M. J., 1937. Studies of heart muscle in tissue cultures. Anat. Rec., Vol. 67,
 
pp. 521-535.
 
 
 
THE CIRCULATORY SYSTEM
 
 
329
 
 
Jordan^ H. E., 1916. The microscopic structure of the yolk-sac of the pig embryo with
especial reference to the origin of erythrocytes. Am. Jour. Anat., Vol. 19, pp.
277-303.
 
Jordan^ H. E., 1919a. The histogenesis of blood-platelets in the yolk-sac of the pig
embryo. Anat. Rec., Vol. 15, pp. 391-406.
 
Jordan^ H. 1919b. The histology of the umbilical cord of the pig, with special
reference to the vasculogenic and hemopoietic activity of its extensively vascularized connective tissue. Am. Jour. Anat., Vol. 26, pp. 1-27.
 
Kellogg. H. B,, 1928. The course of the blood flow through the fetal mammalian heart.
Am. Jour. Anat., Vol. 42, pp. 443-465.
 
Kellogg^ H. B.j 1929. Studies on the fetal circulation of mammals. Am. Jour. Physiol.,
Vol. 91, pp. 637-648.
 
Kimball^ P., 1928. A comparative study of the vas subin testinale in the vertebrates.
Am. Jour. Anat., Vol. 42, pp, 371-398.
 
Kramer y T. C., 1942. The partitioning of the truncus and conus and the formation of
the membranous portion of the interventricular septum in the human heart.
Am. Jour. Anat., Vol. 71, pp. 343-370.
 
Lehmann, H., 1905. On the embryonic history of the aortic arches in mammals. Anat.
Anz., Bd. 26, S. 406-424.
 
Lewis, F. T., 1902. The development of the vena cava inferior. Am. Jour. Anat.,
Vol. 1, pp. 229-244.
 
Lewis, F. T., 1906. The fifth and sixth aortic arches and the related pharyngeal
pouches in the rabbit and pig. Anat. Anz., Bd. 28, S. 506-513.
 
Lockwood, C. B., 1888. The early development of the pericardium, diaphragm and
great veins, Phil. Trans Roy. Soc. London, Ser. B, Vol. 179, pp. 365-384.
 
McClendon, J. F., 1913. Preparation of material for histology and embryology, with
an appendix on the arteries and veins in a thirty-millimeter pig embryo. Anat.
Rec., Vol. 7, pp. 51-61,
 
McClure, C, F, W., 1921. The endothelial problem. Anat. Rec., Vol. 22, pp. 219-237.
 
McClure, C. F. W., and Huntington, G. S., 1929. The mammalian vena cava posterior.
Am. Anat. Mem., No. 15, 56 pp. and 46 plates.
 
Minot, C. S., 1898. On the veins of the Wolffian bodies in the pig. Proc. Boston Soc.
Nat. Histi, Vol. 28, pp. 265-274.
 
Morrill, C. V., 1916. On the development of the atrial septum and the valvular apparatus in the right atrium of the pig embryo with a note on the fenestration on
the anterior cardinal veins. Am. Jour. Anat., VoL 20, pp. 351-374.
 
Odgers, P, N. B., 1938. The development of the pars membranacea septi in the human
heart. Jour. Anat., Vol. 72, pp. 247-259.
 
Paff, G, H., 1936. Transplantation of sino-atrium to conus in the embryonic heart
in vitro. Am. Jour. Physiol., Vol. 117, pp. 313-317.
 
Parker, G. H., and Togier, C. H., 1898. The thoracic derivatives of the posterior cardinal
veins of swine. Bull. Museum of Comp. Zool., Harvard, Vol. 31, pp. 133-144.
 
Patten, B, M., 1930. The changes in circulation following birth. Am. Heart Journal,
Vol. 6, pp. 192-205.
 
Patten, B. M., 1931. The closure of the foramen ovale. Am. Jour. Anat., Vol. 48,
pp. 19-44.
 
Patten, B. M., 1939. Microcinematographic and electrocardiographic studies of the
 
 
 
330
 
 
BIBLIOGRAPHY
 
 
first heart beats and the beginning of the circulation in living embryos. Proc.
Inst, of Med. of Chicago, Vol. 12, pp. 366-380,
 
Patten^ B, M., and Kramer, T, C., 1933. The initiation of contracfion in the embryonic
chick heart. Am. Jour. Anat., Vol. 53, pp. 349-375.
 
Patten, B. M., Sommerjield, W. A., and Paff, G. H., 1929. Functional limitations of the
foramen ovale in the human foetal heart. Anat. Rec., Vol. 44, pp. 165-178.
 
Pohlman, A. G., 1909. The course of the blood through the heart of the fetal mammal,
with a note on the reptilian and amphibian circulations. Anat. Rec., Vol. 3.
pp. 75-109.
 
Rathke, H., 1843. Ueber die Entwicklung der Arterien welche bei den Saugethieren
von dem Bogen der Aorta ausgehen. Arch. f. Anat, u. Physiol., Jg. 1843, S.
276-302.
 
Reagan, F., 1912. The fifth aortic arch of mammalian embryos and the nature of the
last pharyngeal evagination. Am. Jour. Anat., Vol. 12, pp. 493-514.
 
Reagan, F. P., 1917. Experimental studies on the origin of vascular endothelium and
of erythrocytes. Am. Jour. Anat., Vol. 21, pp. 39-175.
 
Reagan, F. P., 1919. On the later development of the azygos veins of swine. Anat. Rec.,
Vol. 17, pp. 111-126.
 
Reagan, F. P., 1927. The supposed homology of vena azygos and vena cava inferior
considered in the light of new facts concerning their development. Anat. Rec.,
Vol. 35, pp. 129-148.
 
Reagan, F, P., 1929. A century of study upon the development of the eutherian vena
cava inferior. The Quarterly Review of Biology, Vol. 4, pp. 179-212.
 
Reinke, E. E., 1910. Note on the presence of the fifth aortic arch in a 6-mm. pig
embryo. Anat. Rec., Vol. 4, pp. 453-459.
 
Robinson, A., 1903. The early stages of the development of the pericardium. Jour.
Anat. & Physiol., Vol. 37, pp. 1-17.
 
Sabin, F. R., 1915. On the fate of the posterior cardinal veins and their relation to the
development of the vena cava and azygos in pig embryos. Carnegie Inst.,
Contrib. to Embryol,, Vol. 3, pp. 5-32.
 
Sabin, F. R., 1917. Origin and development of the primitive vessels of the chick and
the pig. Carnegie Inst., Contrib. to Embryol., Vol. 6, pp. 61-124.
 
Schafer, 7* P-, 1914. The behavior of elastic tissue in the post-fetal occlusion and
obliteration of the ductus arteriosus (Botalli) in Sus scrofa. Jour. Exp. Med.,
Vol. 19, pp. 129-143.
 
Shaner, R. F., 1928. The development of the muscular architecture of the ventricles
of the pig’s heart, with a review of the adult heart and a note on two abnormal
mammalian hearts. Anat. Rec., Vol. 39, pp. 1-36.
 
Shaner, R. F., 1929. The development of the atrioventricular node, bundle of His,
and sino-atrial node in the calf, with a description of a third embryonic nodelike structure. Anat. Rec., Vol. 44, pp. 85-99.
 
Smith, H. W., 1909. On the development of the superficial veins of the body wall in
the pig. Am. Jour. Anat., Vol. 9, pp. 439-462.
 
Stienon, L., 1926. Recherches sur Foriginc du noeud sinusal dans le coeur dcs mammif^res. Archives de Biologic, T. 36, pp. 523-539.
 
Stockard, C, J?., 1915. An experimental analysis of the origin of blood and vascular
endothelium. Amcr. Anat. Mem., No. 7, 174 pp.
 
 
 
LYMPHATIC VESSELS AND ORGANS
 
 
331
 
 
Thienes, C. //., 1925. Venous system associated with the liver of a 6-mm. pig embryo.
Anat. Rec., Vol. 31, pp. 149-158.
 
Whitehead, W. H,, 1942. A working model of the crossing caval blood streams in the
fetal right atrium. Anat. Rec., Vol. 82, pp. 277-280.
 
Windle, W, F., 1940. Circulation of blood through the fetal heart and lungs and
changes occurring with respiration at birth. Quart. Bull., Northwestern Univ.
Med. School, Vol. 14, pp. 31-36.
 
Witte, L., 1919. Histogenesis of the heart muscle of the pig in relation to the appearance and development of the intercalated discs. Am. Jour. Anat., Vol. 25, pp.
333-347.
 
Woollard, H. L., 1922. The development of the principal arterial stems in the forelimb of the pig. Carnegie Inst., Contrib. to Embryol., Vol. 14, pp. 139-154.
 
Toshida, T., 1932. On the development of the heart primordia. II. Observations upon
the development of the interatrial septum of the pig. Okayama-Igakkai-Zasshi,
Vol. 44, pp. 438-460.
 
Young, A, H., and Robinson, A., 1898. The development and morphology of the vascular
system in mammals. The posterior end of the aortae and the iliac arteries. Jour.
Anat. & Physiol., Vol. 32, pp. 605-607.
 
Lymphatic Vessels and Organs
 
Badertscher, J. A., 1915. The development of the thymus in the pig. I. Morphogenesis.
Am. Jour. Anat., Vol. 17, pp. 317-338. II. Histogenesis. Am. Jour. Anat., Vol.
17, pp. 437-494.
 
Battjer, W. A., 1908. The origin of the mesenteric sac and thoracic duct in the embryo pig^ Am. Jour. Anat., Vol. 8, pp. 303-310.
 
Bell, E. T., 1905. The development of the thymus. Am. Jour. Anat., Vol. 5, pp. 29-61.
 
Cash, J. R., 1917. On the development of the lymphatics in the heart of the embry^o
pig. Anat. Rec., Vol. 13, pp. 451-464.
 
Cash, J, R., 1921. On the development of the lymphatics in the stomach of the
embryo pig. Carnegie Inst., Contrib. to Embryol., Vol. 13, pp. 1-15.
 
Clark, A. H., 1912. On the fate of the jugular lymph sacs and the development of the
lymph clyannels in the neck of the pig. Am. Jour. Anat., Vol. 14, pp. 47-62.
 
Cunningham, R, S., 1916. On the development of the lymphatics of the lung in the
embryo pig. Carnegie Inst., Contrib. to Embryol., Vol. 4, pp. 45-68.
 
Fischelis, P., 1885. Beitrage zur Kenntnis der Entwiqklungsgeschichte der Gl. thyreoidea und Gl. thymus. Arch, f. mikr. Anat., Bd, 25, S. 405-440.
 
Fox, H., 1908. The pharyngeal pouches and their derivatives in the mammalia. Am.
Jour. Anat., Vol. 8, pp. 187-250.
 
Heuer, G. J,, 1909. The development of the lymphatics in the small intestine of the
pig. Am, Jour, Anat., Vol. 9, pp. 93-118.
 
Holyoke, E, A., 1936. The role of the primitive mesothelium in the development of
the mammalian spleen. Anat. Rec., Vol. 65, pp. 333-349.
 
Huntington, G, S., 1910a. The phylogenetic relations of the lymphatic and blood
vascular systems in the vertebrates. Anat. Rec,, Vol, 4, pp. 1-14,
 
Huntingon, G. S,, 1910b. The genetic principles of the development of the systemic
lymphatic vessels in the mammalian embryo. Anat. Rec., Vol. 4, pp. 399-424.
 
 
 
332
 
 
BIBLIOGRAPHY
 
 
Kampmeiei, 0. F,^ 1912. The development of the thoracic duct in the pig. Am. Jour.
Anat., Vol. 13, pp. 401-476.
 
Kastschenko^ N., 1887. Das Schicksal der embryonalen Schlun^spalten bci Saugetieren. Arch, f. mikr. Anat., Bd. 30, S. 1-26.
 
Levin, P. M., 1930. The development of the tonsil of the domestic pig. Anat. Rec.,
Vol. 45, pp. 189-201.
 
McClure, C. F. W., 1915a. On the provisional arrangement of the embryonic lymphatic system. An arrangement by means of which a centripetal flow of lymph
toward the venous circulation is controlled and regulated in an orderly and
regular manner, from the time lymph begins to collec t in the intercellular spaces
until it is forwarded to the venous circulation. Anat. Rec., V^ol. 9, pp. 281-296.
 
McClure, C. F. 1915b. I'he development of the lymphatic system in the light of
the more recent investigations in the field of vasculogenesis. Anat. Rec., Vol. 9,
pp. 563-579.
 
Rand, R., 1917. On the relation of the head chorda to the pharyngeal epithelium in
the pig embryo: a contribution to the development c:)l the bursa pharyngea and
the tonsilla pharyngea. Anat. Rec., Vol. 13, pp. 465-491.
 
Reichert, F. L,, 1921. On the fate of the primary lymph-sacs in the abdominal region
of the pig, and the development of the lymph-channels in the abdominal and
pelvic regions. Carnegie Iirst., Contrib. to Embryol., Vol 13, pp. 17-39.
 
Sabin, F. R., 1902. On the origin of the lymphatic system from the veins and the
development of the lymph hearts and thoracic duct in the pig. Am. lour. Anat.,
Vol. l, pp. 367-389
 
Sabin, F, R,, 1904. On the development of the superficial lymphatics in the skin of
the pig. Am. Jour. Anat., Vol. 3, pp. 183-195.
 
Sabin, F. R., 1905. The development of the lymphatic nodes in the pig and their
relation to the lymph hearts. Am. Jour. Anat., Vol. 4, pp. 355-389.
 
Sabin, F. R., 1912. On the origin of the abdominal lymphatics m mammals frc:)m the
vena cava and the renal veins. Anat. Rec., Vol. 6, pp. 335-342.
 
Sabin, F. /?., 1916. The origin and development of the Ivmphatic system. Johns
Hopkins Hosp. Rep., Vol. 17, pp. 347-440.
 
Theil, G, A., and Downey, //., 1921. The development of the mammalian spleen, with
special reference to its hematopoietic activity. Am. Jour. Anat., Vol. 28, pp.
279-339.
 
Zottermann, A,, 1911. Die Schweinthymus als eine Thymus ectoentodermalis. Anat.
Anz., Bd. 38, S. 514-530.
 
The Digestive and Respiratory Systems, and the Body Cavities
 
and Mesenteries
 
Boyden, E. A., 1926. The accessory gall bladder. An embryological and comparative
study of aberrant biliary vesicles occurring in man and the domestic animals.
Am. Jour. Anat., Vol. 38, pp. 177-231.
 
Bremer, J. L,, 1932. Accessory bronchi in embryos; their occurrence and probable
fate. Anat. Rec., Vol. 54, pp. 361-374.
 
Chamberlain, R. V., 1909. On the mode of disappearance of the villi from the colon of
mammals. Anat. Rec., Vol. 3, pp. 282-283.
 
 
 
THE DIGESTIVE AND RESPIRATORY SYSTEMS
 
 
333
 
 
Clements, L. P., 1 938. Embryonic development of the respiratory portion of the pig’s
lung. Anal. Rec., Vol. 70, pp. 575-595.
 
Corner, G. W., 1914. The structural unit and growth of the pancreas of the pig. Am.
Jour. Anat., Vol. 16, pp. 207-236.
 
Felix, W., 1892. Zur Leber- und Pankreasentwicklung. Arch. f. Anat. u. Phys., Anat.
Abt., f. 1892, S. 281-323.
 
Flint, J. M., 1902. The development of the reticulated basement membranes in the
submaxillary gland. Am. Jour. Anat., Vol. 2, pp. 1-11.
 
Flint, J, M., 1903. The angiology, angiogenesis, and organogenesis of the submaxillary gland. Am. Jour. Anat., Vol. 2, pp. 417-444.
 
Flint, J. M., 1906. The development of the lungs. Am. Jour. Anat., Vol. 6, pp. 1-138.
Horn, A. IT., and Baldwin, K. W., 1941. A histological study of the development of
the lung with particular reference to the nature of alveoli. Anat. Rec., Vol. 81,
pf). 363-379.
 
Harnrnar, G. A , 1893. Einige Plattenmodelle zur Beleuchtung der friiheren embryonalen Leberentwic kelung. Arch. f. Anat. u. Phvs., Anat. Abt., f. 1893, S.
123-156.
 
Hammar, G. A., 1897a. LTber einige Hauptzuge der ersten embryonalen Leberentwickelung. Anat. Anz,, Bd. 13, S. 233 -247.
 
Hammar, G. A., 1897b. Einiges iieber die Duphcitat der vertralen Pancreasanlage.
Anat. Anz., Bd. 13, S. 247-249.
 
}ler::Jeld, P., 1889. Ueber das Jacobson'sche Organ des Menschen und der Saugethiere. Zoolog. Jahrb. (Abt. f. Anat. u. Ontogenie), Bd. 3, S. 551-574.
 
Huber, G. C., 1912. On the relation of the chorda dorsalis to the anlagc of the pharyngeal bursa or mc'.dian pharyngeal recess. Anat. Rec., Vol. 6, pp. 373-404.
Johnson, F, P., 1919. The development of the lobule of the pig’s liver. Am. Jour.
Anat., Vol. 25, pp. 299-331.
 
Lewis, F. T., 1911. 7Te bi-lobed form of the ventral pancreas in mammals. Am. Jour.
Anat., Vol. 12, pp. 389-400.
 
Lewis, F. T., and Thyng, F. IT., 1908. The regular occurrence of intestinal diverticula
in embryos of the pig, rabbit and man. Am. Jour. Anat., Vol. 7, pp. 505-519.
Linehack, P, E., 1916. The development of tlie spiral coil in the large intestine of the
pig. Am. ijour. Anat., Vol. 20, pp. 483-503.
 
Mall, F. jP., 1891. Development of the lesser peritoneal cavity in birds and mammals.
Jour, Morph,, Vol. 5, pp. 165-179.
 
Mall, F. P., 1906. A study of the structural unit of the liver. Am. Jour. Anat., Vol, 5,
pp. 227-308.
 
Max, C., 1931. Das Wachstum der Leberzellen und die Entwicklung der Leberlappchen beim Schweine. Anat. Anz., Bd. 72, S. 219-227.
 
Ravn, E., 1889. Ueber die Bildung der Scheidewand zwishen Brust- und Bauchhdhle
in Saugetier-embryonen. Arch. f. Anat. u. Phys., Anat. Abt., S. 123-154.
 
Ravn, E., 1899. Ueber die Entwicklung des Septum transversum. Anat. Anz., Bd.
15, S. 528-534.
 
Reuter, C., 1896. Ueber die Entwicklung der Kaumuscuiatur beim Schwein. Anat.
Hcfte f. 1896-97, S. 239-262.
 
Robinson, A., 1903. The early stages of the development of the pericardium. Jour.
Anat. & Physiol., Vol. 37, pp. 1-17,
 
 
 
334
 
 
BIBLIOGRAPHY
 
 
Swaen, A., 1896 and 1897. Recherches sur le developpement du foie, du tube digestive,
de rarriere cavit6, du p6ritoine et du mesentere. Jour, de TAnat. et de la Physiol.,
Part I, T. 32, pp. 1-84; Part II, 1, T. 33, pp. 32-99; Paftt II, 2, T. 33, pp.
222-258; Part II, 3, T. 33, pp. 525-585.
 
Thyng, F. W,, 1908. Models of the pancreas in embryos of the pig, rabbit, cat and
man. Am. Jour. Anat., Vol. 7, pp. 489-503.
 
Uskow, JV., 1883. Ueber die Entwickelung des Zwerchfells, des Pericardiums und des
Coeloms. Arch. f. niikr. Anat., Bd. 22, S. 143-218.
 
Whitehead, W. H., Windle, W. F , and Becker, R, F,, 1942. Changes in lung structure
during aspiration of amniotic fluid and during air-breathing at birth. Anal.
Rec., Vol. 83, pp. 255-265.
 
Windle, W. F., Becker, R. F., Barth, E. E., and Schulz, M. D., 1939. Proof of fetal swallowing, gastrointestinal peristalsis and defecation in amnio. Proc. Am. Physiol.
Soc. — Am. Jour. Physiol., Vol. 126, pp. P429-P430.
 
Wlassow, 1895. Zur Entwicklung des Pankreas beim Schwein. Morph. Arbeiten, Bd.
4, S. 67-76.
 
 
The Urogenital System
 
Allen, B. M,, 1904. The embryonic development of the ovary and testis of the mammals. Am. Jour. Anat., Vol. 3, pp. 89-154.
 
Angle, E, J,, 1918. Development of the Wolffian body in bus scrofa domesticus. Trans.
Am. Micr. Soc., Vol. 37, pp. 215-238.
 
Balfour, F. M., 1876. On the origin and history of the urogenital organs of vertebrates.
 
Jour. Anat. & Physiol., Vol. 10, pp. 17-48.
 
Bascom, K. F,, and Osterud, H. L., 1927. Quantitative studies of the testis. III. A numerical treatment of the development of the pig testis. Anat. Rec., Vol. 37, pp.
63-82.
 
Bremer, J, L., 1916. The interrelations of the mesonephros, kidney, and placenta in
different classes of animals. Am. Jour. Anat., Vol. 19, pp. 179-209.
 
Brody, H,, and Bailey, P. L., Jr,, 1939. Unilateral renal agenesia in a fetal pig. Anat.
Rec., Vol. 74, pp. 159-163.
 
Corner, G. W,, 1920. A case of true lateral hermaphroditism in a pig with functional
ovary. Carnegie Inst., Contrib. to Embryo!., Vol. 11, pp. 137-142.
 
Felix, W., und Buhler, A., 1906. Die Entwicklung der Harn- und Geschlechts organe.
 
Hertwig’s Handbuch, Bd. 3, Teil I, K. II.
 
Flexner, L. B,, and Gersh, /., 1937. The correlation of oxygen consumption, function
and structure in the developing rnetanephros of the pig. Carnegie Inst., Contrib. to Embryo!., Vol. 26, pp. 121-127.
 
Gersh, 1937. The correlation of strucmre and function in the developing mesonephros and rnetanephros. Carnegie Inst,, Contrib. to Embryo!., Vol. 26, pp. 33-58.
Gruenwald, P,, 1942. The development of the sex cords in the gonads of man and
mammals. Am. Jour. Anat., Vol. 70, pp. 359-397.
 
Hamburger, 0., 1890. Ueber die Entwicklung der Saugethierniere. Arch. f. Anat. u.
 
Phys., Anat. Abt., f. 1890, SuppL, S. 15-51.
 
Henneberg, B,, 1922, Anatomic und Entwicklung der Ausseren Genitalorganc dcs
Schwcines und vergleichcnd-anatomische Bemerkungen. I. Weibliches Schwein.
Zeitschr. f. Anat. u. Entwg., Bd. 63, S. 431-494.
 
 
 
THE DUCTLESS GI.ANDS
 
 
335
 
 
Henneberg, 1925. Anatomic und Entwicklung der Ausseren Genital organe des
Schweines und vergleichend-anatomische Bemerkungen. II. Mannliches
Schwein. Zeitschr. f. Anat. u. Entwg., Bd. 75, S. 265-318.
 
Hennebergj B.y 1926. Beitrag zur ontogcnetischen Entwicklung des Scrotums und der
Labia maiora. Zeitschr. f. Anat. u. Entwg., Bd. 81, S. 198-219.
 
Hilly E. C.y 1905. On the first appearance of the renal artery and the relative development of kidneys and Wolffian bodies in pig embryos. Bull. Johns Hopkins Hosp.,
Vol. 16, pp. 60-64.
 
Hilly E. C,y 1906. On the gross development and vascularization of the testis. Am.
Jour. Anat., Vol. 6, pp. 439-459.
 
Huber y G. C., 1905. On the development and shape of uriniferous tubules of certain
of the higher mammals. Am. Jour. Anat., Supplement to Vol. 4, pp. 1-98.
Kambmeiery O, F.y 1926. The rnetanephros or so-called permanent kidney in part
provisional and vestigial. Anat. Rec., Vol. 33, pp. 115-120.
 
King^burjiy B. F.y 1913. The morphogenesis of the mammalian ovary: Felis domestica.
Am. Jour. Anat., Vol. 15, pp. 345-387.
 
Kitaharay T., 19-23. Uber die Entstehung der Zwischenzellen der Keimdru.sen des
Menschen und der Saugetiere und fiber deren physiologische Bedeutung. Arch,
f. Entwcklngsmechn. d. Organ., Bd. 52, S. 550-615. *
 
Klaafsch, //., 1890. Ueber den Descensus testiculorum. Morph Jahrb., Bd. 16, S.
587-646.
 
Lewisy F. T.y 1920. The course of the Wolffian tubules in mammalian embryos. Am.
Jour Anat., Vol. 26, pp. 423-435.
 
Lockwoody C. B.y 1888. Development and transition of the testis, normal and abnormal.
Jour. Anat. & Physiol., Part I, Vol. 21, pp. 635-664. Part II, Vol. 22, pp. 38-77.
Part III, Vol. 22, pp. 461-478. Part IV, Vol. 22, pp. 505-541.
 
MacCalluniy J. B.y 1902. Notes on the Wolffian body of higher mammals. Am. Jour.
Anat., Vol. 1, pp. 245-260.
 
Pricfy D.y 1947. An analysis of the factors influencing growth and development of the
mammalian reproductive tract. Physiol. ZooL, Vol. 20, pp. 213-247.
 
Schreiner, K. E., 1902. Ueber die Entwicklung der Amniotenniere. Zeitschr. f. wiss.
ZooL, Bd. 71, S. 1-188.
 
Selye, H., 1943. Factors influencing development of scrotum. Anat. Rec., Vol. 85,
pp. 377-385.
 
Weinberg, E., 1929. A note on the origin and histogenesis of the mesonephric duct in
mammals. Anat. Rec., Vol. 41, pp. 373-386.
 
Whitehead, R. H., 1904, The embryonic development of the interstitial cells of Leydig.
Am. Jour. Anat., Vol. 3, pp. 167-182.
 
The Ductless Glands
 
Bader tscher, J. A., 1918, The fate of the ultimobranchial bodies in the pig (Sus
scrofa). Am. Jour. Anat., Vol. 23, pp. 89-131.
 
Born, G.y 1883. Ueber die Derivate der embryonalen Schlundbogcn und Schlundspalten bei SSugethieren. Arch. f. mikr. Anat., Bd. 22, S. 271-318.
 
Emmariy E. W., 1936. A study of the histogenesis of the thymus in vitro. Anat. Rec.,
Vol. 66, pp. 59-73.
 
 
 
336
 
 
BIBIJOGRAPHY
 
 
FischeltSy P.y 1885. Beitr%e zur Kennlnis der Entwicklungsgeschichte der Gl. thyreoidea und Gl. thymus. Arch. f. mikr. Anat., Bd. 25, S. 405--440.
 
Flinty J. M,y 1900. The bloodvessels, angiogenesis, reticulum and histology of the
adrenal. Johns Hopkins Hosp. Rep., Vol. 9, pp. 153-229.
 
FoXy H,y 1908. The pharyngeal pouches and their derivatives in the mammalia. Am.
Jour. Anat., Vol. 8, pp. 187-250.
 
Gilberty M. S,, 1935. Some factors influencing the early development of the mammalian hypophysis. Anat. Rec., Vol. 62, pp. 337-359.
 
Godwin, M. C., 1939. The mammalian thymus. IV. The development in the dog. Am.
Jour. Anat., Vol. 64, pp. 165-201.
 
Holt, E.y 1921. Absence of the pars buccalis of the hypophysis in a 40-mm. pig. Anat.
Rec., Vol. 22, pp. 207-215.
 
Jacoby, Af., 1895. Studien zur Entwicklungsgeschichte der Halsorgane der Saugethiere und des Menschen. Histor. Krit. Beobachtungen iiber die Entwicklung
der Kiemendarm-derivate. Gustav Schade, Berlin, 70 S.
 
KastschenkOyN.y 1887. Das Schicksal der embryonalen Schlundspalten bci Saugelhieren
(zur Entwicklungsgeschichte des mittleren und ausseren Ohres, der Thyreoidea
und des Thymus. Carotidenanlage). Arch. f. mikr Anat., Bd. 30, S. 1-26.
 
Minervini, R., 1904. Des ^Capsules surrenalcs. Developpement, structure, fonctions.
Jour, de TAnat. et de la Phys., T. 40, pp. 449-492 and pp. 634-667.
 
Mitsukuriy K., 1882. On the development of the suprarenal in mammalia. Quart.
Jour. Micr. Sci., Vol. 22, pp. 17-29.
 
Moody, R, 0., 1910. Some features of the histogenesis of the thyreoid gland in the
pig. Anat. Rec., Vol. 4, pp. 429-452.
 
Nelson, W. 0., 1933. Studies on the anterior hypophysis. I. The development of the
hypophysis in the pig (Sus scrofa). II. The cytological differentiation in the
anterior hypophysis of the foetal pig. Am. Jour. Anat., Vol. 52, pp. 307-332.
 
Poll, H., 1906. Die vergleichende Entwicklungsgeschichte der Nebennierensystemc
der Wirbeltiere. Hertwig’s Handbuch, Bd. 3, Teil 1, K. II, 2.
 
Rumph, P., and Smith, P, E,, 1926. The first occurrence of secretory products and of a
specific structural differentiation in the thyroid and anterior pituitary during the
development of the pig foetus. Anat. Rec., Vol. 33, pp. 289-298.
 
Shanklin, W. M., 1944. Histogenesis of the pig neurohypophysis. Am. Jour. Anat.,
Vol. 74, pp. 327-353.
 
Smith, P. E., and Dortzbach, C., 1929. The first appearance in the anterior pituitary
of the developing pig foetus of detectable amounts of the hormones stimulating ovarian maturity and general body growth. Anat. Rec., Vol. 43, pp. 277297.
 
Snyder, F, F,, 1928. The presence of melanophore-expanding and uterus-stimulating
substance in the pituitary body of early pig embryos. Am. Jour. Anat,, Vol. 41,
pp. 399-409.
 
Soulii, A. H., 1903. Recherches sur le developpement des capsules surr6nales chez les
vert6bres sup6rieurs. Jour, de I’Anat. et de la Physiol., T. 39, pp. 197-293.
 
Stieda, L., 1881. Untersuchungen uber die Entwicklung der Glandula thymus,
Glandula thyreoidea und Glandula carotica. Engelmann, Leipzig, 38 S.
 
Warren^ 1917. The development of the pineal region in mammalia. Jour. Comp,
Neur., Vol. 28, pp. 75-135.
 
 
 
CONNECTIVE TISSUES, SKELETAL, AND MUSCULAR SYSTEMS 337
 
 
Weyrnann, M. F.^ 1922. I’he beginning and development of function in the suprarenal
medulla of pig embryos. Anat. Rec., Vol. 24, pp. 299-313.
 
Whitehead, R. H., 1903. The histogenesis of the adrenal in the pig. Jour. Am. Anat.,
Vol. 2, pp. 349-360.
 
Connective Tissues, Skeletal, and Muscular Systems
 
Asai, T., 1914. Beitrage zur Histologic und Histogenese der quergestreiften Muskulatur der Saugetierc. Arch, f mikr. Anat., Bd. 86, S. 8-68.
 
Augier, M. A., 1923. Notocorde et epithelium pharyngien chez sus scrofa dornesticus.
Comptes Rendus de L’Assoc des Anal., T. 18, pp. 57-65.
 
Bardeen, C. R., 1900. The development of the musculature of the body wall in the
pig, including its histogenesis and its relation to the myotomes and to the skeletal
and nervous apparatus. Johns Hopkins Hosp. Rep., Vol. 9, pp. 367-399.
 
de Beer, G. R., 1937. The Development of the Vertebrate Skull. Clarendon Press,
Oxford, xxiii & 552 pp.
 
Butcher, E. O., 1933. The development of striated muscle and tendon from the caudal
myotomes in the albino rat, and the significance of rnyotomic-cell arrangement.
Am. Jour. Anat., Vol. 53, pp. 177-189.
 
Carey, E. J., 1921. Studies in the dynamics of histogenesis. VT. Resistances to skeletal
growth as stimuli to chondrogenesis and osteogenesis. Am. Jour. Anat., Vol. 29,
pp. 93-115.
 
Carey, E. J., 1922d. Studies in the dynamics of histogenesis. Intermittent traction and
contraction of differential growth, as a stimulus to myogenesis. XI. The dynamics of the pectoralis major muscle tendon. Anat. Rec., Vol. 24, pp. 89-96.
 
Carey, E. J., 1922b. Direct observations on the transformation of the mesenchyme in
the thigh of the pig embryo (Sus scrofa), with especial reference to the genesis
of the thigh muscles, of the knee- and hip-joints, and of the primary bone of the
femur. Jour. Morph., Vol. 37, pp. 1-77.
 
Glucksmann, A., 1939. Studies on bone mechanics in vitro. II. The r61e of tension and
pressure in chondrogenesis. Anat. Rec., Vol. 73, pp. 39-55.
 
Godlewskt, E., 1902. Die Entwicklung des Skelet- und Herzmuskelgewebes der Saugethiere. Arch. f. rnikr. Anat. u. Entwg., Bd. 60, S. 111-156.
 
Hanson, F. B., 1*91 9a. The ontogeny and phylogeny of the sternum. Am. Jour. Anat.,
Vol. 26, pp. 41-115.
 
Hanson, F. B., 1919b. The development of the sternum in Sus scrofa. Anat. Rec.,
Vol. 17, pp. 1-23.
 
Hanson, F. B., 1920. The development of the shoulder-girdle of Sus scrofa. Anat. Rec.,
Vol. 18. pp. 1-21.
 
Huber, E., 1931. Evolution of Facial Musculature and Facial Expression. The Johns
Hopkins Press, Baltimore, xii & 184 pp.
 
Ingalls, T, H,, 1941. Epiphyseal growth: Normal sequence of events at the epiphyseal
plate. Endocrinology, Vol. 29, pp. 710-719.
 
Isaacs, R., 1919. The structure and mechanics of developing connective tissue. Anat.
Rec., Vol. 17, pp. 243-270.
 
Kibrick, E, A., Becks, H, Marx, W., and Evans, H, M., 1941. The effect of different
dose levels of growth hormone on the tibia of young hypophysectomized female
rats. Growth, Vol. 4, pp. 437-447.
 
 
 
338
 
 
BIBLIOGRAPHY
 
 
Kingsbury^ B. F., 1920, The developmental origin of the notochord. Science, Vol. 51,
pp. 190-193.
 
Lacroix, F., 1945. On the origin of the diaphysis. Anat. Rec., Vol. 92, pp. 433-439.
 
McGill, C., 1907-08. The histogenesis of smooth muscle in the alimentary canal and
respiratory tract of the pig. Internat. Monatschr. f. Anat. u. Physiol., Bd. 24,
S. 209-245.
 
McGill, C., 1910. The early histogenesis of striated muscle in the oesophagus of the
pig and the dogfish. Anat. Rec., Vol. 4, pp. 23-47.
 
Mead, C. S,, 1909. The chondrocranium of an embryo pig, Sus scrofa. A contribution
to the morphology of the mammalian skull. Am. Jour. Anat., Vol. 9, pp. 167-210.
 
Murray, P. D. F., 1936. Bones. A Study of the Development and Structure of the
Vertebrate Skeleton. Cambridge Univ. Press, London, x & 203 pp.
 
JVauck, E. T., 1926. Entwicklung des Schultergelenkes beim Schwein; Wachsplattenmodelle (als Ergazung zum Vortrag fiber das Coracoideum der Sauger).
Verhandl. Anat. Ges., Bd. 35, S. 260-261.
 
Parker, W. K., 1874. On the structure and development of the skull of the pig. Phil.
Trans. Roy. Soc. London, Ser. B, Vol. 164, pp. 289-336.
 
Ruth, E. B., 1932. A study of the development of the mammalian pelvis. Anat. Rec.,
Vol. 53, pp. 201-225.
 
Sawin, P. B., 1945. Morphogenetic studies of the rabbit. 1. Regional specificity of
hereditary factors affecting homoeotic variations in the axial skeleton. Jour,
Exp. Zool., Vol. 100, pp. 301-329.
 
Sawtn, P. B., 1946. Morphogenetic studies of the rabbit. III. Skeletal variations resulting from the interaction of gene determined growth forces. Anat. Rec., Vol.
96, pp. 183-200.
 
Shields, R. T., 1923. On the development of tendon sheaths. Carnegie Inst., Contrib.
to Embryo!., Vol. 15, pp. 53-61.
 
Silberberg, M., and Silberberg, R., 1946. Fufther investigations on the effect of the male
sex hormone on endochondral ossification. Anat. Rec., Vol. 95, pp. 97-117.
 
Stearns, M. L., 1940. Studies on the development of connective tissue in transparent
chambers in the rabbit’s ear. Part I, Am. Jour. Anat., Vol. 66, pp. 133-176;
Part II, Am. Jour. Anat., Vol. 67, pp. 55-97.
 
Warkany, J., and Nelson, R. C., 1942. Skeletal abnormalities induced in rats by maternal nutritional deficiency. Arch. Path., Vol. 34, pp. 375-384.
 
Weed, I. G., 1936. Cytological studies of developing muscle with special reference to
myofibrils, mitochondria, Golgi material and nuclei. Zeitschr. f. Zellforsch. u.
mikr. Anat., Bd. 25, S. 516-540.
 
Williams, L. W., 1908. The later development of the notochord in mammals. Am.
Jour. Anat., Vol. 8, pp. 251-284.,
 
Teeth, Hair, and Hoofs
 
Adlof, P., 1901. Zur Entwickelungsgeschichtc des Zahnsystems von Sus scrofa domest.
Anat. Anz., Bd, 19, S. 481-490.
 
Beams, H. W., and King, R. L., 1933. The Golgi apparatus in the developing tooth,
with special reference to polarity. Anat. Rec., Vol. 57, pp. 29-39.
 
Bevelander, G., 1941. The development and structure of the fiber system of dentin.
Anat. Rec., Vol, 81, pp. 79-97.
 
 
 
TWINS, DOUBLE MONSTERS, ANOMALIES
 
 
339
 
 
Bevelander, G., and Johnson^ P. L., 1945. The histochemical localization of alkaline
phosphatase in the developing tooth. Jour. Cell. & Comp. Physiol., Vol. 26,
pp. 25-33.
 
Bevel andei ^ G.^ and Johnson^ P. T., 1946. The histochemical localization of glycogen in
the developing tooth. Jour. Cell. & Comp. Physiol,, Vol. 28, pp, 129-137.
 
Bild^ T., 1902. Die Entwickelungsgeschithte des Zahnsystems bei Sus domesticus und
das Verhaltnis der Lippenfurchenanlage zur Zahnleiste. Anat. Anz., Bd, 20, S.
401-410.
 
Chase, S, W., 1932. Histogenesis of the enamel. Jour. Am. Dental Assn., Vol. 19, pp.
1275-1289.
 
Glasstone, S., 1935. The development of tooth germs in vitro. Jour. Anat., Vol. 70,
 
pp. 260-266.
 
Ilampp, E. G., 1940. Mineral distribution in the developing tooth. Anat. Rec., Vol.
77, pp. 273-291.
 
Held, //., 1926. Uber die Bildung des Schmelzgewebes. Zeitschr. f. mikr. Anat. P'orsch.,
Bd. 5, S. 668-687.
 
Ihrsch, M., 1921. Der Liickzahn von Sus domesticus, ein Beitrag zur Entwicklungsgeschichte des Gebisses von Sus domesticus und zur Kenntnis des Wesens der
Dentitionen. Anat. Anz., Bd. 54, S. 321-330.
 
Jasswom, G., 1924. Uber die Histogencse der Dentingrundsubstanz der Saugetiere.
Arch. f. mikr. Anat., Bd. 102, S. 291-310.
 
Morse, A , and Creep, R. 0 , 1947. Alkaline glycerophosphatase in the developing
teeth of the rat. Its localization and activity characteristics as influenced by pH
of the substiate and length of incubation time. Anat. Rec., Vol. 99, pp. 379-395.
 
Rein, G , 1882. Untersuchungen iiber embryonale Entwicklungsge.schichte der Milchdriise. Arch. f. mikr. Anat., Bd. 20, S. 431-501 und Bd. 21, S. 678-694
 
Saundeis, J, B, de C, M., Nuckolls, J., and Ftisbie, H. F., 1942. Amelogenesis. A histologic study of the development, formation and calcification of the enamel in the
molar tooth of the rat. Jour. Am, Coll. Dentists, Vol. 9, pp. 107-136.
 
Schmidt, V,, 1925. Studien fiber die Histogencse der Haut und ihrer Anhangsgebilde
bei Saugetieren und beim Menschen. I. Die Histogencse des Hufes bei Schweineembryonen. Zeitschr, f. mikr. Anat. Forsch., Bd. 3, S. 500-557.
 
Schour, /., and Steadman, S. R., 1935. The growth pattern and daily rhythm of the
incisor of the rat. Anat. Rec., Vol. 63, pp. 325-333.
 
Schultze, O., 1892. Ueber die erste Anlagc des Milchdrfisenapparates. Anat. Anz.,
Bd. 7, S. 265-270.
 
Thoms, H., 1896. Untersuchungen fiber Bau, Wachsthum und Entwicklung des Hufes
der Artiodactylen, insbesondere des Sus scrofa. Deutsche Thieraerzliche Wochenschr., Jahrgang. 4, S. 379-383.
 
Z^itzschmann, 0., 1924. Die Entwicklung des Systems der ausseren Haut. (b) Die
Haare. (Schwein.) Lehrbuch der Entwicklungsgcschichte der Haustierc, S.
186-194.
 
Twins, Double Monsters, Anomalies
 
Baumgartner, W, J,, 1928. A double monster pig — Cephalothoracopagus monosymmetros. Anat. Rec., Vol. 37, pp. 303-316.
 
Berge, S,, 1941. The inheritance of paralysed hind legs, scrotal hernia and atresia ani
in pigs. Jour. Heredity, Vol. 32, pp. 271-274.
 
 
 
340
 
 
BIBLIOGRAPHY
 
 
Bishopy Af., 1921. The nervous system of a two-headed pig embryo. Jour. Comp.
Neur., Vol. 32, pp. 379-428.
 
Bishops M., 1923. The arterial system of a two-headed pig embfyo. Anat. Rec., Vol.
26, pp. 205-222.
 
Carey, E,, 1917. The anatomy of a double pig, Syncephalus thoracopagus, with
especial consideration of the genetic significance of the circulatory apparatus.
Anat. Rec., Vol. 12, pp. 177-192.
 
Chidester, F. /?., 1914. Cyclopia in mammals. Anal. Rec., Vol. 8, pp. 355-366.
 
Cornel, G, W., 1921. Abnormalities of the mammalian embryo occurring before implantation. Carnegie Inst., Contrib. to Embryol., Vol. 13, pp. 61-66.
 
Corner, G. W., 1922. The morphological theory of monochorionic twins as illustrated
by a series of supposed early twin embryos of the pig. Bull. Johns Hopkins Hosp.,
Vol. 33, pp. 389-392.
 
Corner, G. W., 1923. The problem of embryonic pathology of mammals with observations upon intra-uterine mortality in the pig. Am. Jour. Anat., Vol. 31, pp.
523-545.
 
Denison, H., 1908. Notes on pathological changes found in the embryo pig and its
membranes. Anat. Rec., Vol. 2, pp. 253-256.
 
Dutta, S. K., 1930. Notes on the cyclopian eye and other deformities of the head in a
pig. (Sus cristatus Wagn.) Allahabad Univ. Studies, Sci. Sec., Vol. 7, pp. 53-103.
 
Fitzpatrick, F, L,, 1928. The dissection of an abnormally developed foetal pig, with
notes on the possible origins of such “freaks.” Proc. Iowa Acad. Sci., Vol. 35,
pp. 319-325.
 
Hughes, W., 1927. Sex-intergrades in foetal pigs. Biol. Bull., Vol. 52, pp. 121-136.
 
Jordan, H. E., Davis, J. S., and Blackford, S. D., 1923. The operation of a factor of
spatial relationship in mammalian development, as illustrated by a case of
quadruplex larynx and triplicate mandible in a duplicate pig monster. Anat.
Rec., Vol. 26, pp. 311-318.
 
Kingsbury, B, F., 1909. Report of a case of hermaphroditism (H. Verus lateralis) in
Sus scrofa. Anat. Rec., pp. 278-281.
 
Nordby, J. E., 1929. Congenitad skin, ear, and skull defects in a pig. Anat. Rec., Vol.
42, pp. 267-280.
 
Poklman, A, G., 1919. Double ureters in human and pig embryos. Anat. Rec., Vol.
15, pp. 369-373.
 
Schwalbe, E., 1906-1913. Die Morphologic dcr Missbildungen des Menschen und der
Tiere. Fischer, Jena, Vol. 1, xvi & 230 pp., Vol. 2, xx & 410 pp., Vol. 3, Abt. 1,
270 pp., Abt. 2, 858 pp., Anhang, 266 pp.
 
Streeter, G. L., 1924. Single-ovum twins in the pig. Am. Jour. Anat., Vol. 34, pp.
183-194.
 
Thuringer, J, M,, 1919. The anatomy of a diccphalic pig (Monosomus diprosopus).
Anat. Rec., Vol. 15, pp. 359-367.
 
JVarkany, J., and Roth, C, B., 1948. Congenital malformations induced in rats by
maternal vitamin A deficiency. II. Effect of varying the preparatory diet upon
the yield of abnormal young. Jour. Nutrition, Vol. 35, pp* 1-11.
 
Williams, S. R., and Rauch, R. W., 1917. The anatomy of a double pig (Syncephalus
thoracopagus). Anat. Rec., Vol. 13, pp. 273-280.
 
 
 
Index
 
 
To facilitate the use of this book in connection with otheis in which the terminology
may differ somewhat, many synonyms which were not used in the text have been put into
the index and cross-referenced to the alternative terms used in this book; for example,
Wolffian body, a teim not used in this text, is frequently applied to the mesonephros. It
appears m the index thus: Wolffian body (= mesonephros, q.v.).
 
Both figure and page references are given in the index. The figure references arc preceded by the letter /.
 
 
Abdominal pregnancy, 217
Abducens nerve, 169
Accessory nerve, 172
Acoustic ganglion, /92, 117, 169
Acoustico-facialis ganglion ( = early undifferentiated condition of ganglia of
7th and 8th cranial nerves), 169
Action system, 141
 
Adrenal, /1 00, /106, /1 27, /1 28, /1 38, 223
After-birth, 105
Alae of nose, 296
Alar plate of neural tube, 1 57
Allantois, circulation of, /45,/51, 99
formation of,/30,/37, 99
function of, 106
relations of,/49,/55, 103
Alveolar periosteum, 312
Ameloblasts,/179-183, 305, 310
Amnion, formation of,/25,/37,/50, 97
function ofi 96
relations of,/49, 97
Amniotes, 96
Amniotic folds, 97
Ampulla of ductus deferens, /3, 8
Anal plate ( = cloacal plate, q.v.)
Anamniotes, 96
Angioblast, 87 footnote
Animad pole, 37
 
Anterior intestinal portal, /37, 74
Anterior neuropore, /29, 71
Anus,/118,/132, 210, 225
Aorta, see arteries
Aortic arches, sec arteries
Aortic bulb, 256
Aortic chromaffin body, 223
Appendage buds, /3 1-34, 65, 109
 
 
Appendix, of epididymis, /1 24, 213
of testis, /1 24, 217
Appositional growth, 278
Aqueduct of Sylvius, 158
Archenteron, 43
Areola, 105
 
Arterial circle (of Willis), 131
Arteries, allantoic, /45,/51, 89, 132, 240
aorta, dorsal, /67, /1 33-1 37, 88, 131,
235, 240
 
aoita, ventral, /45, /1 33, 88, 235
aortic arches, /45, /1 33-1 37, 88, 129,
 
233
 
basilar, /66, /67, /133, /137, 131, 238
brarhio-cephalic,/133, 234
carotid, common, /1 33, /1 37, 234
carotid, external, /67, /1 33, /1 37, 130,
 
234
 
carotid, internal, /66, /133, /137, 130,
234, 238
caudal, 240
 
cervical, intersegmental,/66,/133,/l37,
130, 235
 
coeIiac,/67,/lll, 132, 240
ductus arteriosus /1 33, /ISO, 235, 262,
268
 
hypogastric, 240, 270
iliacs,/66, /150, 240
innominate, 234
internal mammary, 238
interscgmcntal,/67,/133, 130, 235
mesenteric, ant., /67, /1 11, 132, 238
mesenteric, post»,/lll, 238
omphalomesenteric, /45, 89, 131, 238
pulmonary, /67, /1 33-1 37, 130, 234,
267
 
 
341
 
 
 
342
 
 
INDEX
 
 
Arteries — {Continued)
 
renal, /1 27, /1 28, 240
speimatic, /1 27-1 30
 
subclavian, /67, /133-135, 131, 234,
235
 
umbilical (allantoic), /66, /1 50, 89, 132,
240
 
vertebral,/66,/67,/137, 131, 237
vitelline, /45, 89, 132
Arytenoid process of larynx, /1 38
Astrocytes, 150
Atresia of ovarian follicles, 20
Atrio-ventricular canal, 126, 256
Atrium, 126, 254
 
Auditory, ganglion, see acoustic nerve, 1 69
vesicle, /36,/61, 117, 169
 
Basal plate of neural tube,/91, 157
Belly-stalk, /49, 97
Bicornate uterus, 216
Bile duct, common, 185
Bladder (urinary), /118, /124, /125, /130,
209
 
Blastocoele, j\S, 41
Blastocyst, /1 7, 41
 
elongation of, /1 8, 45
riastodermic vesicle ( == blastocyst, q.v.)
Blastodisc ( — embryonic disc, q.v.)
Blastorneie, 38
Blastula, 41
 
Blood cells, formation of,/48,/152, 90, 251
Blood islands, /48, 89, 251
Blood vessels, formation of, /48, 87
see also arteries and veins
Body axis, 60
Body cavity, see coelom
Body folds, /38, 72
Body-stalk, sec belly-stalk
Bone, cancellous, 272
cells, /1 51, /1 52, 275
compact, 272
endochondral, 272
histogenesis of, 271
intramembranous, 272
lacuna, 275
lamellae, /1 51, 275
marrow, /1 52, 251
matrix, /1 51, 273
trabeculae, /1 51, /1 53, 274
Bone, formation of,
 
compact from cancellous, 281
 
 
Bone — '{Continued)
 
endochondral, /1 55, 276
flat, /1 57, 282 '
 
intramem branous, /1 5 1 , /1 53, 272
long, /1 58, 283
 
primary cancellous, /1 51, /153, 272,
281
 
Bowman’s capsule, /1 16, 203
Brachial plexus, 116
Brain, formation of, /36, 69
neuromeric structure of, 69
regional differentiation of,/87, 1 S4
ventricles of, /88, 156, 160
3-vesicle stage, /36, 70
5-vesicle stage, /60, 110
Branchial arches (= gill arches, q.v.)
 
Bridge of nose, 296
 
Broad ligaments of uterus, 222
 
Bronchi, 189
 
Bulbo-urethral gland, /3, /1 24, 9, 213
 
Clalcification
 
of bone, 274
of teeth, 309
 
Calyces of renal pelvis, /1 19
Canal, atrio-ventncular, 126
Haversian, /1 56, 282
inguinal, /1 29, 222
of Gartner, 217
pleural,/! 10
pleuro- peritoneal, 195
semicircular, 169
Canalicuii, /152
Cancellous bone, /1 53, 276
Capsule, glomerular, /1 21, 203
of Bowman, /1 21 , 203
of cartilage cells, 278
Cardiac loop, /1 42, 125, 254
Cardinal vessels, see veins
“Cartilage bone,” 272
Cartilage, erosion, /1 55, 280
formation, /1 54, 277
matrix, 278
Caval plica, /1 40, 245
Cecum, /102, 122, 182
Cementoblasts, /1 84
Cemcntum,/184, 312
Central canal of spinal cord,/86, 151
Centrum, see vertebrae
Cephalic region, differentiation of, 61
mesoderm of, 1 91
 
 
 
INDEX
 
 
343
 
 
Cephalic region — (Continued)
precocity of, 54
Cerebellar peduncles, 157
Cerebellum, /80,/87, 157
Cerebral aqueduct, 158
Cerebral cortex, 145, 162
Cerebral ganglia, see ganglia, cranial
Cerebral hemispheres, /87, 162
Cerebral peduncles, /1 00, 158
Cerebro-spinal paths, 142
Cervical flexure, 66
Cervical sinus, /32, /1 69, 109
Cervix of uterus, 216
Choanae, of nose, 296
Chondrin, 278
Chondrogenesis, 276
Chondrogenctic layer, 278
Chorda dorsalis ( = notochord, q.v.)
 
Chorion, /55-57, 103
Chorionic vesicle, /54, 103
Chorionic villi, /57
Choroid fissure, of eye,/39, 117
Choroid plexus, anterior (of 3rd ventricle),
/106, 158, 162
 
lateral (of 1st and 2nd ventricles), /1 00.
 
162
 
posterior (of 4th ventricle), /65, /99,
/1 38, 156
 
Chromaffin tissue, 223
Chromosomes, sex, 23
species number of, 21
Circle of Willis, /1 33, 131
Circulation, changes in at birth, 268
early embryonic, /45,/51, 92
hepatic portal, 241
interpreta^tion of embryonic, 227
placental,/45,/51,/55, 93, 263
pulmonary, 262, 267
vitelline, /45, /1 41, 93, 249
Circulatory arcs, 92
Cleavage, /1 2, /1 3, /1 4, 37
Cleavage cavity, see blastococle
aitoris,/132, 225
Cloaca, /65, /1 18, 120, 209
Cloacal plate (membrane), /37, 209
Cochlea, 169
Coelom, /1 09
 
abdominal, /1 11, 194
diflferentiation of, /1 08, 193
formation of,y20, f22,/108, 51, 120, 189
intra- and extra-embryonic, 52, 190
 
 
Coelom — (Continued)
 
partitioning of, /1 11-1 13, 194
pericardial, /26, /44, /1 09, /1 10, /111,
53, 87, 195
peritoneal, /1 10, 189
pleural,/! 11, /1 13, 194
thoracic, 194
 
Colliculi, inferior, suptTior (lobes of corpora
quadngemma), /80, /87, 157, 167
Colon (large intestine), /1 02, 182
Columns of spinal cord, /8 6, 154
Commissural ganglion, /92, 172
Components of spinal nerve, 151
Concrescence, /20, 46
Coordinating centers, 145
Copula, /41
Cord, spinal, 71, 115
 
and reflexes, /80, 142
histogenesis of, /8 1-8 3, 147
white and grey matter of,/86, 151
Cord, umbilical, 250
Corona radiata, 18
Coronary sinus, sec veins
Corpora quadrigemma, /87, 157
Corpus albicans, 27
Corpus hacmorrhagicurn, 26
Corpus luteum, formation of,/6, 24
in pregnancy, /1 0, 26
significance of, 33
Corpus striatum, 1 63
 
Cowper’s gland (= bulbo-urethral gland,
q.v.)
 
Cranial flexure, 66
 
Cranial ganglia, see ganglia
 
Cranial nerves, see nerves
 
Crura cerebri (= cerebral peduncles, q.v.)
 
Cumulus oophorus, 19
 
Cutis plate, see dermatome
 
Cystic duct,/104,/105, 184
 
Decalcification, 274
Deciduous placenta, 103
Deitcr’s nucleus, /80, 144
Dental ledge, /1 75-1 80, 302
Dental papilla, 307
Dental sac, /1 82, 312
Dentinal fiber /1 83, 310
Dentine, /1 83, 307
Dermatome, /42, 81
 
Deutoplasm, effect of on cleavage, /1 2, 37
in pig ovum, 39
 
 
 
344
 
 
INDEX
 
 
Diaphragm, /1 00, /1 12, 194
Diaphragmatic ligament of mesonephros,
/1 23, 218
 
Diaphysis, of long bone, 283
Dicnccphalon, /60, 110, 158
Diestrum, 29
 
Diocoele ( =« lumen of diencephalon)
Dio-mesencephalic boundary, 110
Dio-telcncephalic boundary, 110
Diploe, of bone, 282
Diploid number of chromosomes, 22
Dorsal, aorta, see arteries
flexure, 66
 
mesentery, /1 08, /1 11, 192
mesocardium,/43,/144, 87, 254
nerve roots, see nerves, spinal
root ganglia, see ganglia, spinal
Duct of, Cuvier ( = common cardinal
vein, q.v.)
 
Santorini, 186
Wirsung, 186
 
Ductus, arteriosus, /1 33, /1 38, /1 50, 235,
262, 268
 
choledochus ( = common bile duct, q.v.)
deferens, /3, /1 18, /1 24, 9, 213
endolymphaticus, 117
venosus, see veins
Duodenum, /1 00, /1 02, 184
 
Ear, external, /33,/34, 62
internal, 62, 117, 169
middle, 118, 170
Ectoderm, 59, 98
 
derivatives of,/27
Efferent ductules, 213
Egg nests, 1 5
 
Ejaculatory duct, /3, /1 24, 9, 213
Embryonic disk, /1 6, /1 9, 45, 60
Enamel, /183, 310
Enamel organ, /1 79-1 82, 303
Enamel prisms, 311
 
Endocardial cushion of A-V. canal, /39,
/147,/148, 126, 256
Endocardial cushion tissue, 256
Endocardial primordia,/43,/44, 85
Endocardium, 85
Endolymphatic duct, 117
Endothelium, origin of vascular, /48, 87
Entoderm, 59
 
derivatives of, /27
formation of, /1 6, 43
 
 
Eparterial bronchus, /1 07
Ep>endymal cells, 150
Ependymal layer of c^d,/81, 147
Epicardium, 85
 
Epididymis, /3, /1 24, /1 29, 213
 
Epi-myocardium,/43,/44, 85
 
Epiphyseal cartilage plates, 284
 
Epiphyseal ossification centers, 284
 
Epiphyses of long bones, /1 58, 284
 
Epiphysis, of diencephalon, /1 06, 110, 158
 
Epiploic foramen, 181
 
Epo6phoron,/125, 217
 
Equation division, 22
 
Erythroblasts, /1 52
 
Esophagus, /64,/72, 80, 119, 179
 
Estrus, 29
 
Estrus cycle, /9, 29
 
Eustachian tube, 118, 175
 
Evolution, 198, 229
 
Exocoelom, 52
 
Extra-embryonic coelom, see coelom
Extra-embryonic membranes, /49, 94
Eye, 63, 116, 167
 
Face, development of, /1 68-1 72, 293
Facial nerve, /92, 169
Falciform ligament, /1 1 1 , 193
Fallopian tube (= uterine tube, q.v.)
Fasciculi, see columns of spinal cord
Fertilization, /1 1, 34
Flexion, 65, 107
Floor plate of neural tube, 156
Fetal membranes, see extra-embryonic
membranes
 
Follicle, ovarian, /6,/7, 17
Foramen, ovale, 260, 267, 268 see also
interatrial
 
Foramen of Monro, /88, /1 38, 160
Foramen of Winslow, 181
Fore-brain, see prosencephalon
Fore-gut, /26,/37, 74
Fossa ovalis, 269
 
Fovea cardiaca (= ant. intestinal portal,
q.v.)
 
Frontal lobe, 163
 
Frontal process, /1 68-1 72, 293
 
Froriep’s ganglion, /92, 172
 
Gall-bladder, /46, /103-105, /1 40, 80, 119,
184
 
Gametes, /8, 9, 12, 15
 
 
 
{{Footer}}

Latest revision as of 11:51, 13 August 2017

Embryology - 15 Oct 2026    Facebook link Pinterest link Twitter link  Expand to Translate  
Google Translate - select your language from the list shown below (this will open a new external page)

العربية | català | 中文 | 中國傳統的 | français | Deutsche | עִברִית | हिंदी | bahasa Indonesia | italiano | 日本語 | 한국어 | မြန်မာ | Pilipino | Polskie | português | ਪੰਜਾਬੀ ਦੇ | Română | русский | Español | Swahili | Svensk | ไทย | Türkçe | اردو | ייִדיש | Tiếng Việt    These external translations are automated and may not be accurate. (More? About Translations)

Patten BM. Embryology of the Pig. (1951) The Blakiston Company, Toronto.

Patten 1951: 1 Foreword to the Student | 2 Reproductive Organs - Gametogenesis | 3 Sexual Cycle | 4 Cleavage and Germ Layers | 5 Body Form and Organs | 6 Extra-Embryonic Membranes | 7 Embryos 9-12 mm | 8 Nervous System | 9 Digestive - Respiratory and Body Cavities | 10 Urogenital | 11 Circulatory System | 12 Bone and Skeletal System | 13 Face and Jaws | Bibliography
Online Editor 
Mark Hill.jpg
This historic 1951 embryology of the pig textbook by Patten was designed as an introduction to the topic. Currently only the text has been made available online, figures will be added at a later date. My thanks to the Internet Archive for making the original scanned book available.


By the same author: Patten BM. The Early Embryology of the Chick. (1920) Philadelphia: P. Blakiston's Son and Co.

Patten BM. Developmental defects at the foramen ovale. (1938) Am J Pathol. 14(2):135-162. PMID 19970381


Modern Notes

pig

Historic Disclaimer - information about historic embryology pages 
Mark Hill.jpg
Pages where the terms "Historic" (textbooks, papers, people, recommendations) appear on this site, and sections within pages where this disclaimer appears, indicate that the content and scientific understanding are specific to the time of publication. This means that while some scientific descriptions are still accurate, the terminology and interpretation of the developmental mechanisms reflect the understanding at the time of original publication and those of the preceding periods, these terms, interpretations and recommendations may not reflect our current scientific understanding.     (More? Embryology History | Historic Embryology Papers)

Embryology of the Pig

Bradley M. Patten
Bradley Patten ( -1971)

Frontispiece

Reconstruction (X 17.5) showing the organ systems of a 9.4 mm. pig embryo. For explanation see figures 60 and 66.

By Bradley M. Patten

Professor of Anatomy in the University of Michigan Medical School


Third Edition


With Colored Frontispiece

And 186 Illustrations In The Text (Containing 412 Figures) Of Which 6 Are In Color


Philadelphia : THE BLAKISTON COMPANY : Toronto


Third Edition


Copyright, October 1948, by The Blakiston Company


By P. Blakiston's Son & Co.


Copyright, 1951, by P Blakiston's Son & Co , Inc.


Patten 1951: 1 Foreword to the Student | 2 Reproductive Organs - Gametogenesis | 3 Sexual Cycle | 4 Cleavage and Germ Layers | 5 Body Form and Organs | 6 Extra-Embryonic Membranes | 7 Embryos 9-12 mm | 8 Nervous System | 9 Digestive - Respiratory and Body Cavities | 10 Urogenital | 11 Circulatory System | 12 Bone and Skeletal System | 13 Face and Jaws | Bibliography

Preface to Third Edition

In making the revision for a new edition of this book it did not seem desirable essentially to change its form or scope. Effort has been concentrated on improving the presentation of the original subject matter and bringing it up to date, rather than on its expansion. The entire book has been reset to a greater page width which has permitted enlarging certain of the illustrations that, in earlier editions, had proved to be too greatly reduced. With the generous cooperation of the publishers several of the important plates on the cardiovascular system have been remade to a larger scale and with color. A number of new illustrations have been drawn for sections where experience has shown that students needed additional graphic assistance in interpreting their laboratory material. It is hoped that these changes will all contribute toward making the book as a whole more serviceable.


Bradley M. Patten

August 1048


Preface to First Edition

This book represents an endeavor to set forth in brief and simple form the fundamental facts of mammalian development. The thread of the story and the illustrations have been based on pig embryos because of their value and availability as laboratory material. But special stress has been laid on the embryological phenomena involved instead of on the details of specific conditions existing in the pig. Throughout the book, every efTort has been made to present developmental processes as dynamic events with emphasis on their sequence and significance, rather than as a series of still pictures of selected stages.


Obviously no book can deal fully with all phases of development, even in a single form, and still remain serviceable as a text. As this book is for the student, it has seemed expedient, for the sake of clearness and simplicity, to omit many things which I should like to have included. My primary aim has been to write an account in which the essentials stand out adequately interpreted and unobscured by a multiplicity of details — to lay a foundation which can be further built upon in accordance with special needs or individual desires.


Bradley M. Patten

January 1927

Acknowledgment

The pleasantest thing about working on this book has been the generous aid I have received from many sources. Throughout the preparation of the initial edition the encouragement, criticism, and suggestions of my colleagues, Dr. F. C. Waite and Dr. S. W. Chase, were of the greatest help. In the preparation of material and in making the illustrations for the first edition the beautifully accurate work of Miss Kathryn Toulmin was of inestimable value. In making the new drawings added in the third edition I was fortunate in securing the unusually able assistance of Mrs. Dorothy Van Eck.


Dr. G. L. Streeter and Dr. C. H. Heuser of the Carnegie Institute allowed me free use of their extensive collection of young embryos and generously gave me many photographs made from their material. To Mrs. Charles S, Minot I am indebted for permission to use several figures from the late Professor Minot's works. The accrediting in the figure legends of these and other borrowed illustrations by no means covers my obligation to other writers. Practically the entire bibliography is a statement of indebtedness for information and ideas.


I wish I might acknowledge individually the helpful services rendered by many of my students, but they are too numerous. Several reconstructions which I have used directly or indirectly have been largely their work. Of even greater assistance have been their suggestions during the shaping of the work — suggestions of especial value because they were made from a point of view difficult for an instructor to appreciate without such aid.


To The Blakiston Company, I am indebted for much helpful cooperation and especially for their liberality with regard to the number and quality of the illustrations.


No person other than my wife could have deciphered and put into usable form manuscript of the character I frequently turned over to her for revision and typing. Without her generous help the preparation of the text would have been much more arduous and long delayed.


Bradley M. Patten


Cite this page: Hill, M.A. (2026, October 15) Embryology Book - Embryology of the Pig. Retrieved from https://embryology.med.unsw.edu.au/embryology/index.php/Book_-_Embryology_of_the_Pig

What Links Here?
© Dr Mark Hill 2026, UNSW Embryology ISBN: 978 0 7334 2609 4 - UNSW CRICOS Provider Code No. 00098G


Patten 1951: 1 Foreword to the Student | 2 Reproductive Organs - Gametogenesis | 3 Sexual Cycle | 4 Cleavage and Germ Layers | 5 Body Form and Organs | 6 Extra-Embryonic Membranes | 7 Embryos 9-12 mm | 8 Nervous System | 9 Digestive - Respiratory and Body Cavities | 10 Urogenital | 11 Circulatory System | 12 Bone and Skeletal System | 13 Face and Jaws | Bibliography
Retrieved from ‘https://embryology.med.unsw.edu.au/embryology/index.php?title=Book_-_Embryology_of_the_Pig&oldid=299731’
Powered by MediaWiki