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=The Organs of the Outer Germ-Layer=
=The Organs of the Outer Germ-Layer=
16 [[Book_-_Text-Book of the Embryology of Man and Mammals 16|The Organs of the Outer Germ-Layer]]


[[Book_-_Text-Book of the Embryology of Man and Mammals 16-1|The Development of the Nervous System]]
*  the development of the central nervous system
**the development of the spinal cord
**the development of the brain (1) metamorphosis of the fifth brain- vesicle (2) fourth (3) third  (4) second development of the pineal gland (epiphysis cerebri)., hypophysis (pituitary body) (5) fore-brain vesicle
*  the development of the peripheral nervous system
**the development of the spinal ganglia
**the development of the peripheral nerves
**the development of the sympathetic system


THE outer germ-layer has for a long time also borne the name dermo-sensory layer. By this its two most important functions are both indicated. For in the first place it forms the epidermis together with its various products, such as hair, nails, scales, horns, and feathers ; and in addition various kinds of glands : the sebaceous, sweat- and milk-glands. Secondly, it is the matrix out of which the nervous system and the most important functional parts of the sensory organs, the optic, auditory, and olfactory cells, are derived.
[[Book_-_Text-Book of the Embryology of Man and Mammals 16-2|The Development of the Sensory Organs]]
 
*  the development of the eye
I begin with the most important function of the outer germ-layer, the development of the nervous system, then proceed to the development of the organs of sense (eye, ear, and organ of smell), and finally discuss the development of the epidermis and its products.
**the development of the lens
 
** vitreous body
 
**secondary optic cup and the coats of the eye
I. The Development of the Nervous System.
**optic nerve
 
**accessory apparatus of the eye
A. The Development of the Central Nervous System.
*  the development of the organ of hearing
 
**the development of the otocyst into the labyrinth
The central nervous system of Vertebrates is one of the organs first established after the separation of the germ into the four primary germ-layers. As has already been stated, it is developed (fig. 41 A) out of a broad band of the outer germ-layer (mp), which stretches from the anterior to the posterior end of the embryonic fundament and lies in the median plane directly above the chorda dorsalis (cli). In this region the cells of the outer germ-layer grow out into long cylindrical or spindle-shaped structures, whereas the elements occurring in the surrounding parts (ep) flatten out and under certain conditions become altogether scale-like. Consequently the outer germ-layer is now divided into two regions into the attenuated primitive epidermis (Hornblatt) (ep) and the thicker median neural or medullary plate (mp).
**membranous ear-capsule into the bony labyrinth and the perilymphatic spaces
 
**middle and external ear
Both regions are soon sharply separated from each other, since the neural plate bends in a little (fig. 41 B) and its edges rise above the surface of the germ. In this way there arise the two medullary or dorsal folds (rnf), which enclose between them the originally broad and shallow medullary or dorsal furrow. They are simply folds of : the outer germ-layer, formed at the place where the neural plate is continuous with the primitive epidermis. They are therefore composed of an outer and an inner layer, of which the inner belongs to the marginal part of the neural plate, the outer, on the contrary, to the adjacent epidermis.
*  the development of the organ of smell
 
In all the classes of Vertebrates the medullary plate is transformed into a neural tube at a very early period. This process can be accomplished in three different ways. In most of the classes of Vertebrates, namely Reptiles, Birds, and Mammals, the tube is formed by a typical process of folding. The medullary folds rise still higher above the surface of the germ, then bend together toward the median plane, and grow toward each other until their edges meet, along which they then begin to fuse. The neural tube, thus formed, still continues to remain in connection with the overlying epidermis along the line of fusion, a connection which soon disappears, since the connecting cells become loosened and separated from one another (fig. 41 C}. The closure begins in all Vertebrates at the place which corresponds approximately to the future mid-brain -in the Chick (fig. 87 hb~) on the second and in the Rabbit on the ninth day of development and from there proceeds slowly both backwards and forwards. There is retained for a long time, especially behind, a place where the neural tube is open to the exterior. A connection with the intestinal tube by means of the neurenteric canal also exists at the posterior end, as has been already mentioned (p. 126) in the discussion of the germ-layers. It is only at a later period that this connection is interrupted by the closing of the blastopore.
 
The second type in the development of the central nervous system is met with in Cyclostomes and Teleosts. In them the neural plate is transformed into a solid cord of cells instead of a tube. Instead of the folds rising up over the surface of the germ, the neural plate grows downward in the form of a wedge. In this way the right and left halves of the plate come to lie immediately in contact with each other, so that one cannot find the slightest trace of a space between them ; only after the cord of cells has been constricted off from the primitive epidermis do the halves separate and allow a small cavity, the central canal, to appear between them. Probably this modification in the Bony Fishes and Cyclostomes is connected with the fact that the egg with its abundant yolk is very closely enveloped by the vitelline membrane, as a result of which the medullary folds cannot rise toward the surface.
 
The third modification occurs only in Amphioxus lanceolatus. It has already been described briefly in another place (p. 109).
 
The neural tube retains an undifferentiated condition in Amphioxus lanceolatus only ; in all other Vertebrates, on the contrary, it is differentiated into spinal cord and brain.
 
 
 
(a) The Development of the Spinal Cord.
 
The part of the neural tube which is converted into the spinal cord is oval in cross section (fig. 200). At an early period a separation into a right and left half can be recognised (fig. 232). For the lateral walls are greatly thickened and consist of several layers of long, cylindrical cells, whereas the upper and lower walls are thin and can be distinguished respectively as posterior [dorsal] and anterior commissure (he and vc}, or as roof -plate and floor-plate.
 
 
 
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Fig. 232. Cross section of an embryo Lizard with completely closed intestinal tube, after SAOEMEHL.
 
kc, Posterior, vc, anterior commissure of the spinal cord ; vw, anterior root of nerve ; nf, nervefibrillse ; spk, spinal ganglion ; nip 1 , muscle-plate, muscle-forming layer ; mp 2 , outer layer of the muscle-plate ; w_p :! , transition of the outer into the muscle-forming layer.
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The further development, of which I shall mention only the most important points, takes place in such a manner that the lateral halves become thicker and thicker (fig. 233). The cells continue to increase in number by division, and at the same time to be differentiated into two histological groups (1) into elements which provide the sustentative framework, the epithelium, surrounding the central canal and the spongiosa (spongioblasts of His),, and (2) into elements which are transformed into ganglionic cells and nerve-fibres (neuroblasts of His). The thickening of the lateral walls depends partly upon the multiplication of cells, but mainly upon the fact that nervefibres apply themselves to the cell-mass from the outside. In time these fibres are separated into the anterior, lateral, and posterior columns of the spinal cord (fig. 233 pew, lew, aciv}. At their first appearance the nervefibres are non-medullated (fig. 232 nf), and only subsequently, sometimes earlier, sometimes later, acquire a medullary sheath. In this manner the already considerably thickened halves of the spinal cord become differentiated into the central gray substance containing the ganglionic cells, and into the white substance, which envelops the surface of the former like a mantle.
 
Since, meanwhile, the roof- and floorplates grow only a little and are not differentiated into
ganglionic cells, they coine to lie deeper and deeper at the bottom of anterior and posterior longitudinal furrows (c and af). Finally, the completely formed spinal cord is composed of large lateral halves, which are separated from each other by deep anterior and posterior longitudinal fissures, being united only deep down by a thin transverse bridge. The latter is derived from the roof- and floor-plates, which have been retarded in their growth, and encloses in its middle the central canal, which has also remained small.
 
 
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Fig. 233. Cross section through the spinal cord of an embryo Chick of seven days, after BALFOUR.
 
pew, Posterior white column ; lew, lateral white column ; acto, anterior white column ; c, dorsal tissue filling up the place where the dorsal fissure will be formed ; pc, posterior horn of the gray substance ; ac, anterior horn ; cp, epithelial cells ; age, anterior gray commissure ; pf, posterior [dorsal] part of the spinal canal ; spc, anterior [ventral] part of the spinal canal ; /, anterior fissure.
 
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At the beginning in Man np to the fourth month of embryonic development the spinal cord occupies the entire length of the body. Therefore, at the time when the axial skeleton is divided up into separate vertebral regions, it reaches from the first cervical down to the last coccygeal vertebra. The end of the spinal cord, however, does not even begin to develop ganglionic cells and nerve-fibres, but remains throughout life as a small epithelial tube. It is united to the larger anterior portion, which has developed nerve-fibres and ganglionic cells, by means of a comcally tapering region, which is spoken of in descriptive anatomy as the conus medullaris.
 
As long as the spinal cord keeps pace with the vertebral column in its growth, the pairs of nerves arising from it, in leaving the vertebral canal, pass out at right angles directly to the intervertebral foramina. In Man, beginning with the fourth month, this arrangement is changed ; from that time forward the growth of the spinal cord does not equal that of the spinal column, and therefore the cord can no longer occupy the entire length of the vertebral canal. Since it is attached above to the medulla oblongata, and this together with the brain is firmly held in the cranial capsule, it must assume a higher and higher position in the vertebral canal. In the sixth month the conus medullaris is found in the upper end of the sacral canal, at birth in the region of the third lumbar vertebra, and some years later at the lower edge of the first lumbar vertebra, where it terminates even in the adult.
 
In the ascent (ascensus medulke spinalis) the lower end of the spinal cord, the small epithelial tube which is attached to the coccyx, is drawn out into a long, fine filament, which persists even in the adult as the filwm terminate internum and externum. At first it presents a small cavity, which is lined by ciliated cylindrical cells, and which forms a continuation of the central canal of the spinal cord. Further downward it is continued in the form of a cord of connective tissue as far as the coccyx.
 
A second consequence of the ascent of the spinal cord is a change in the course of the roots of the peripheral nerve-stems. Since, together with the spinal cord, their points of origin come to lie in the spinal canal relatively nearer and nearer the head, and since the places where they pass through the intervertebral foramina do not change, they are compelled to pass from a transverse to a more and more oblique course. The obliquity, moreover, is greater the farther down the nerve leaves the vertebral canal. In the neck-region their direction is still transverse, in the thoracic region it begins to be more and
 
 
THE ORGANS OF THE OUTER GERM-LAYER. 421
more oblique, and finally, in the lumbar region, and still more so in the sacral, it is more sharply downward. On this account the nervestems arising from the last part of the spinal cord come to lie for a considerable distance in the vertebral canal before they reach the sacral foramina serving for their exit ; they therefore surround the conus medullaris and filum terminale, forming the structure known as the horse-tail or cauda equina.
 
Finally the spinal cord undergoes some changes in its form also. Even in the third and fourth months there appear differences of calibre in different regions. The places in the cervical and lumbar regions of the spinal cord at which the peripheral nerves depart to the anterior and posterior extremities, grow vigorously by the abundant formation of ganglionic cells ; they become considerably thicker than the adjoining portions of the cord, on account of which they are distinguished as cervical and lumbar enlargements (intuniescentia cervicalis et lumbalis).
 
(b) The Development of the Brain.
 
By the study of embryology knowledge of the anatomy of the brain has been greatly promoted. Justly, therefore, in all recent text books of human anatomy, the embryonic condition serves as the starting-point in the description of the intricate structure of the brain, the aim being to derive the complicated ultimate conditions from the more simple embryonic ones, and to explain them by means of the latter.
 
The initial form of the brain as well as of the spinal cord is a simple tube. At an early period, even before it is everywhere closed, it becomes metameric, on account of its growth being greater in some regions than in others. By means of two constrictions of its lateral walls it is divided into the three primary brain-vesicles (fig. 87 hb l , 7//> 2 , hb 5 ), which remain united with one another by means of wide openings, and are designated as the fore-, mid-, and hind-brain. The posterior of these divisions is the longest, gradually tapering and becoming continuous with the tubular spinal cord.
 
The first stage is quickly followed by a second, and that by a third, since the primary brain-vesicles soon separate into four, and finally five divisions.
 
During the second stage (fig. 234) the lateral walls of the primary fore- brain (pvh) begin to grow outward more vigorously and to evaginate to form the two optic vesicles (au). At the same time the lateral walls of the hind-brain, which from the beginning has been the longest portion, acquire a constriction which divides the hindbrain into two vesicles, that of the cerebellum (/,//) and the medulla (??//.), or after-brain.
 
The five-fold segmentation of the neural tube (fig. 235) soon succeeds the four-fold condition ; by means of it the fore-brain vesicle undergoes fundamental transformations. First, the primary optic vesicles (au) begin to be constricted off from the forebrain vesicle, until they remain attached by only slender, hollow stalks. Since the constriction takes place mainly from above downward, the stalks remain in connection with the base of the fore-brain vesicle. The front wall of the vesicle then begins to protrude anteriorly, and to be marked off by means of a lateral furrow, which runs from above and behind obliquely downward and forward. In this manner the primary vesicle of the fore-brain, like the hind-brain vesicle, is secondarily divided into two portions, which we can now distinguish as the vesicles of the cerebrum and the between-brain
(uh, zh). The optic nerves remain united with the base of the latter. The vesicle of the cerebrum is distinguished by a very rapid growth, and soon begins to surpass all the other parts of the brain in size. But it becomes divided before this into right and left halves. From the connective tissue enveloping the neural tube there grows down in the median plane a process, the future falx cerebri. This growth advances from above and in front against the cerebral vesicle and deeply infolds its upper wall. The halves (fig. 236 hms) that have thus arisen are united at their bases ; they present a more flat median and a convex outer surface, and are called the two vesicles of the hemispheres, since they furnish the foundation for the cerebral hemispheres. The separate regions of the brain-tube produced by constrictions and evaginations subsequently become still more sharply marked off from one another, owing to the alteration of their positions.
 
 
+++++++++++++++++++++++++++++++++++++++++
Fig. 234.- Dorsal aspect, by transmitted light, of the head of a Chick incubated 58 hours, after MIHALKOYICS. Magnified 40 diameters.
 
x, Anterior wall of the primary forebrain vesicle, which afterwards evaginates to form the cerebrum ; prh, primary fore-brain vesicle ; au, optic vesicle ; ink, mid-brain vesicle ; /<, vesicle of the cerebellum ; nil, after-brain vesicle ; //, heart; ro, omphalomesenteric vein ; -///*, spinal cord ; UK, primitive segment.
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Fig. 235. Brain of a human embryo of the third week (Ly). Profile reconstruction. After His. gh, Cerebral vesicle ; -/t, between-brain vesicle : mh. mid-brain vesicle; kh, nh, vesicles of the
cerebellum and medulla oblongata ; OH, optic vesicle ; gb, auditory vesicle ; tr, infundibiilum ;
'//, area rhomboidalis ; nb, nuchal flexure ; kb, cephalic flexure.
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At the beginning the three brain-vesicles formed by the first constrictions lie in a straight line one behind the other (fig. 87) and above the chorda dorsalis ; the latter extends only as far as to the anterior end of the midbrain vesicle, where it tapers to a point. But from the moment when the optic vesicles begin to be constricted off, the three primary vesicles shift their positions in such a way that the longitudinal axis uniting them undergoes sharp, characteristic folds, which are distinguished as the cephalic, pontal, and nuchal flexures (fig. 235 l-b, nb).
 
The cause of the formation of the curvatures, which are of fundamental importance in the anatomy of the brain, is to be sought principally in the more vigorous longitudinal growth which distinguishes the cerebral tube, and more especially its dorsal wall, from the surrounding parts. As His has established by means of measurements, the fundament of the brain more than doubles its length, while the spinal cord increases by only about one-sixth of its length.
 
The cephalic flexure (fig. 235 kb) is developed first. The floor of the fore-brain sinks downward a little around the anterior end of the chorda dorsalis (fig. 237 ch), and forms at first a right angle with the part of the base of the brain lying behind it, but afterwards an acute angle (figs. 235, 238). In consequence of this, the vesicle of the mid - brain (fig. 235 mil} comes to lie highest, and forms a prominence, which causes a great protrusion of the surface of the embryo and is known as the parietal prominence (fig. 158 s).
 
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Fig. 236. Brain of a human embryo seven weeks old, parietal (Scheitel) aspect, after MIHALKOVICS.
 
msp, Longitudinal or interpallial fissure (Man telspalte), at the bottom of which is seen the embryonic lamina terminalis(Schlussplatte) hius, left hemisphere ; zh, between-brain ; mh, mid-brain ; hh, hindbrain and after-brain.
 
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The nuchal flexure, which makes its appearance at the boundary between medulla oblongata and spinal cord, is less prominent (fig. 235 nb). It produces in the embryos of the higher Vertebrates a curvature which also projects outward, the so-called
nuchal prominence
(fig. 158).
 
The third curvature, which has been designated by KOLLIKER as the pouted flexure (fig. 239 bb), because it arises in the neighborhood of the future pons
Varolii, is, on the contrary, very marked. It is further distinguished from the two other curvatures described, by the fact that its convexity is not directed toward the back of the embryo, but toward its ventral side.
 
 
 
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Fig. 237. Median section through the head of a Rabbit embryo 6 mm. long, after MIHALKOVICS.
 
rh, Pharyngeal membrane ; hp, place whence the hypophysis develops ; /(, heart ; M, cavity of the head-gut ; ch, chorda ; v, ventricle of the cerebrum ; r 3 , third ventricle, that of the betweenbrain ; v 4 , fourth ventricle, that of the hind- and after-brain ; ck, central canal of the spinal cord.
 
 
 
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Fig. 238. Median sagittal section through the head of a Chick incubated four and a-half days, after MIHALKOVICS.
 
SH, Parietal prominence; sf, lateral ventricle; r ! , third ventricle ; r 4 , fourth ventricle ; Sic, aqueduct of SYLVIUS ; yh, vesicle of the cerebrum ; r.li, between -brain ; mh, midbrain ; kh, cerebellum ; zf, pineal process (epiphysis) ; 7*2?, pocket of the hypophysis (pouch of RATHKE) ; cli, chorda ; ba, basilar artery.
 
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It is formed between the floor of the * [For terminology of the regions of the brain, see footnote, p. 282.]
 
 
vesicle of the cerebellum and that of the after-brain, and has the form of a ridge which projects ventrally for a considerable distance, where subsequently the transverse fibres of the pons Varolii are established.
 
The extent of these curvatures is very different in the various classes of Vertebrates. Thus the cephalic flexure is only slightly emphasised in the lower Vertebrates (Cyclostomes, Fishes, Amphibia) ; it is, on the contrary, much greater in Reptiles, Birds, and Mammals ; but in Man especially, whose brain is the most voluminous, all of the flexures are developed to a very high degree.
 
The five brain-vesicles furnish the foundation for a natural subdivision of the brain, whose various chief divisions can be referred back to them. As the study of the further development teaches, there are formed from the after-brain vesicle the medulla oblongata, from the vesicle of the cerebellum the vermiform process with the ^hemispheres of the cerebellum and the pons Varolii, from the niidbrain vesicle the crura cerebri and corpora quadrigemina, from the between - brain vesicle the between-brain [thalamencephalon] with the infimdibulum, the pineal gland, and the optic thalami, and finally from the vesicle of the cerebrum the cerebral hemispheres.
 
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Fig. 239. Brain of a Rabbit embryo 16 mm. long, viewed from the left side. The outer wall of the left cerebrum is removed. After MIHALKOVICS.
 
sn, Optic nerve ; ML, foramen of MONRO ; agf, fold of the choroid plexus ; amf, fold of the cornu Ammonis ; zh, between-brain ; mh, mid-brain (cephalic or parietal flexure) ; kh, cerebellum ; Dp, roof -plate of the fourth ventricle ; bb, poutal flexure ; nto, medulla oblougata.
 
 
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In this metamorphosis the cavities of the primitive cerebral tube become the so-called ventricles of the brain : from the cavities of the fourth and fifth vesicles is derived the fourth ventricle or fossa rhomboidalis ; from the cavity of the mid-brain vesicle, the aqueduct of SYLVIUS ; from the between-brain, the third ventricle ; and finally from the cavities of the hemispheres, the two lateral ventricles, which are also designated as the first and second ventricles.
 
A brief sketch will suffice to show in what manner the most important parts of the brain develop out of the five vesicular fundaments, and that at the same time histological and morphological differentiations are most intimately associated.
 
Histologically considered the wn^ls of the vesicles originally consist everywhere of closely crowded spindle-shaped cells, just ;is in the spinal cord. These cells undergo in different places unlike modifications. In some places they retain their epithelial character, and furnish (1) the epithelial covering of the choroid plexus in the roof of the between -brain and after-brain, (2) the ependyrna lining the ventricles of the brain, and (3) follicular structures such as the epiphysis (fig. 246). On the greater part of the wall of the five brain-vesicles the cells multiply to an extraordinary extent, and are transformed into more or less extensive layers of ganglionic cells and nerve-fibres. The distribution of the gray and white substances thus formed no longer presents in the brain-vesicles the same uniform condition that it does in the spinal cord. The only uniformity is found in the fact that in every part of the brain there occur gray " nuclei," which, like the anterior and posterior gray columns of the spinal cord, are enveloped with a mantle of white substance, However, there are added to the two parts of the brain that have attained the greatest development layers containing gangliouic cells, which furnish a superficial covering, the gray cortex of the cerebrum and cerebellum. By this means the white substance in certain parts of the brain becomes the core (nucleus medullaris), whereas the gray portion becomes the cortex, a condition differing in an important manner from the structure of the spinal cord.
 
The morphological differentiation of the brain depends upon the very unequal growth loth of the Jive separate vesicles and of different tracts of their walls. For example, the other four vesicles remain in their development far behind that of the cerebral vesicle, in comparison with which they constitute only a small fraction of the entire mass of the brain (figs. 240, 241). They become overgrown by the cerebral vesicle from above and on the sides, and enveloped as by a mantle, so that they remain uncovered and visible only at the base of the brain. Therefore they, together with a small part of the basal portion of the cerebrum, are grouped together as the stalk of the brain, in contradistinction to the remaining chief part of the cerebrum, which constitutes the cerebral mantle.
 
The ^mequal growth of the walls of the brain manifests itself in the appearance of thickened and attenuated places, in the development of special nerve-columns (pedunculi cerebri, cerebelli, etc.), and in the formation of more or less extensive layers of ganglionic cells (thalamus opticus, corpus striatum). By these means the principle of the formation of folds, which was fully described in the fourth chapter, is shown to be carried out in a special manner on the hemispheres of the cerebrum and cerebellum inclusive of the vermiform process, that is to say, on the two parts of the brain which are covered with a gray cortex. That the functional capacity of the cerebrum and cerebellum depends upon the extent of the gray cortex and the regularly arranged ganglionic cells in it, is to be concluded from a large number of phenomena. In this way is explained the very extensive increase of surface which is brought about in the cerebrum and cerebellum by means of somewhat different processes of folding. In the cerebrum broad ridges (gyri) arise from the medullary layer of the hemispheres (centrum semiovale), which, running in meandering convolutions, produce the characteristic relief of the surface (fig. 256). In the cerebellum the numerous ridges proceeding from the medullary nucleus are narrow, arranged parallel to one another, and provided with smaller accessory (secondary and tertiary) ridyes, so that the cross section of the cerebellum presents an arborescent figure (arbor vitre).
 
 
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Fig. 240. Lateral view of the brain of a human embryo from the first half of the fifth month,
after MIHAI.KOVICS. Natural size. st[, Frontal lobe ; schfi.l, parietal lobe ; hi, occipital lobe ; schl.l, temporal lobe ; Sy.g, fissure of
SYLVITS ; rn, olfactory nerve ; kh, cerebellum ; br, pons; mob, medulla oblongata.
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If, after these preliminary remarks, we take under consideration the metamorphoses of the five vesicles, we may distinguish on each, as MIHALKOVICS has done in his monograph of the development of the brain, four regions : floor, roof, and two lateral parts. We shall begin our description with the fifth vesicle, because in its structure it approaches most closely to the spinal cord.
 
(1) Metamorphosis of the Fifth Brain-Vesicle.
 
The ffth brain-vesicle exhibits in different Vertebrates at the beginning of development (in the Chick on the second and third days) faint, regular infoldings of its lateral walls, by means of which it becomes separated into several smaller parts, lying one behind the other. Inasmuch as these afterward disappear without leaving any trace, no great importance was ascribed to them by the earlier investigators (REMAK). Recently, however, several persons have maintained for them a real significance. RABL and BERANECK
 
 
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Fig. 241. Brain of a human embryo from the first half of the fifth month, divided in the median plane ; view of the median surface of the right half, after MIHALKOVICS. Natural size.
 
rn, Olfactory nerve ; tr, infundibulum of the between-braiu ; cma, commissura anterior ; ML, foramen of MONRO ; frx, fornix ; s^jf, septum pellucidum ; bal, corpus callosum, which below, at the genu, is continuous with the embryonic lamina terminals ; cmg, sulcus callosomarginalis ; fo, fissura occipitalis ; zw, cuneus ; fc, fissura calcarina ; z, epiphysis ; vh, corpora quatlrigemina ; kit, cerebellum.
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Fig. 242. Brain of a human embryo from the second half of the third month, seen from behind,
after MIHALKOVICS. Natural size.
 
;//x/>, Longitudinal (interpallial) fissure; vh, corpora quadrigemina ; vma, velum medullare anterius ; kh, hemispheres of the cerebellum ; v*, fourth ventricle (fossa rhomboidalis) ; mo, medulla oblongata.
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recognise in them a segmentation of the brain-tube which is related to the exit of certain cranial nerves and is of importance in regard to the question of the metamerism of the entire head-region. The circumstance that the folds are so transitory appears to me to favor the older view.
 
In the further development of the vesicle of the after-brain a distinction arises between the floor and side walls on the one hand and the roof on the other. The former (figs. 241, 242) are considerably thickened by the addition of nervous substance and become separated on either side of the body (in Man in the third to the sixth months) into columns, which are recognisable from the outside because they are separated by grooves ; these are the extensions with certain modifications of the three familiar columns of the spinal cord. The roof of the vesicle (fig. 235 rf and fig. 243 Dp), on the contrary, produces no nerve-substance, retains its epithelial structure, becomes still thinner, and in the adult consists of a single layer of flat cells. This forms the only covering to the cavity of the dorsoventrally compressed vesicle of the after-brain the fourth ventricle or fossa rhomboidalis. It is firmly applied to the under surface of the pia mater, and with it produces the posterior choroid plexus (tela choroidea inferior). The name choroid plexus has been chosen because the pia mater in this region becomes very vascular and in the form of two rows of branched villi grows into the cavity of the after-brain vesicle, always carrying before it, and thus infolding, the thin epithelial roof.
 
Laterally the roof-plate or the epithelium of the choroid plexus is continuous with the parts of the brain-vesicle that have been metamorphosed into nervous matter. The transition is effected by means of thin bands of white nervous substance, which, as obex, tsenia sinus rhomboidalis, velum medullare posterius, and pedunculus flocculi, surround the edge of the fossa rhomboidalis. If with the pia mater one strips off from the medulla oblongata the posterior medullary velum, the epithelial covering of the fourth ventricle adhering to the latter will naturally be removed with it. In this way is produced the posterior brain-fissure of the older authors, through which one can penetrate into the system of cavities in the brain and spinal cord.
 
(2) Metamorphosis of the Fourth Brain-Vesicle.
 
The wall of the fourth brain-vesicle undergoes a considerable thickening in all its parts, and surrounds its cavity in the form of a ring differentiated into several regions ; the cavity becomes the anterior part of the fossa rhomboidalis (figs. 243, 242, 241). The floor furnishes the 2 )ons (bb), the cross fibres of which become evident in the fourth month. From the lateral walls arise the pedunculi cerebelli ad pontern. But it is the roof that grows to an extraordinary extent and gives to the cerebellum its characteristic stamp. At first it appears as a thick transverse ridye (figs. 242, 243 M), which overhangs the attenuated roof of the medulla. In the third month the
middle portion of the ridge acquires four deep transverse folds by the sinking in of the pia mater (fig. 242), and in this way is distinguished as the vermiform process from the lateral parts, which still appear smooth (kJi). From this time forward the lateral parts outstrip the middle part in growth, bulge out at the sides as two hemispheres, and, acquiring transverse folds, in the fourth month become the voluminous hemispheres of the cerebellum.
 
Only a little nerve-substance is developed where the roof of the fourth brain-vesicle, which has become thickened to constitute the vermiform process and hemispheres, is continuous with the roof of the third and fifth vesicles (fig. 241). Consequently there arise here thin medullary lamellae, which serve as a transition on the one hand to the posterior choroid plexus, and on the other to the lamina quadrigemina (vJi) the 'posterior and the anterior velum medullare.
 
 
 
Fig. 243. Brain of an embryo Calf 5 cm. long, seen from the side. The lateral wall of the hemisphere is removed. After MIHALKOVICS. Magnified 3 diameters.
 
csi, Corpus striatum ; ML, foramen of MONHO ; agf, fold of the choroid plexus (plexus choroideus lateralis) ; amf, fold of the cornu Ammonis ; Teh, cerebellum ; Dp, roof -plate of the fourth ventricle ; bb, pontal flexure ; mo, medulla oblongata ; mh, mid-brain (cephalic flexure).
 
 
 
(3) Metamorphosis of the Third or Mid-brain Vesicle. (Figs. 235, 243, 242, 241.)
The mid-brain vesicle is the most conservative portion of the embryonic neural tube, the part which is changed least of all ; in Man a small portion only of the- brain is derived from it. Its walls become rather uniformly thickened on all sides of the cavity, which is narrow and becomes the aqueduct of SYLVIUS. The base and lateral walls together supply the crura cerebri and substantia perforata posterior. The roof-plate (fig. 242 vh] becomes the corpora quadrigemina, owing to the appearance, in the third month, of a median furrow, and, in the fifth month, of a transverse one crossing it at right angles.
 
 
 
THE ORGANS OF THE OUTER GERM-LAYER. 431
Whereas at the beginning of the development the mid-brain vesicle (figs. 235, 243 m/i), as a consequence of the curvature of the neural tube, occupies the highest position and produces the parietal prominence of the head (fig. 158 s), it is afterwards covered in from above by the other parts of the brain, which are becoming more voluminous, the cerebellum and cerebrum, and is crowded down to the base of the brain (compare fig. 235 mh with fig. 241 vJi).
 
 
 
(4) Metamorphosis of the Second or Between-brain Vesicle.
 
The between-brain vesicle also remains small, but undergoes a series of interesting changes, since, apart from the optic vesicles, which grow out from its walls, two other appendages, of problematical meaning, are developed from it the pineal gland and the hypophysis.
 
In the case of the between-brain vesicle, it is only in the lateral walls that a considerable amount of nerve-substance is formed. By this means the walls thicken into the optic thalami with their ganglionic layers. Between them the cavity of the vesicle is retained as a narrow vertical fissure, known as the third ventricle ; it is united with the fossa rhomboidalis by means of the aqueduct of SYLVIUS. The floor remains thin and at an early period becomes evagiiiated downwards ; it thus acquires the form (figs. 235, 241 tr) of a short funnel (infundibulum), with the apex of which is united the hypophysis, soon to be fully described.
 
The roof presents in its metamorphosis a striking similarity to the corresponding part of the after-brain vesicle (fig. 241). It persists as a simple, thin epithelial layer, unites with the very vascular pia mater, which sends out in this case also villotis outgrowths with capillary loops which pass into the third ventricle, and together with it constitutes the anterior choroid plexus (tela choroidea anterior or superior). When in withdrawing the pia mater the choroid plexus is also removed, the third ventricle is opened ; thus is produced the anterior great fissure of the brain through which, as through the structure of the same name in the medulla oblongata, one can penetrate into the cavities of the brain.
 
The agreement with the medulla oblongata is expressed in still another point. As in the case of the latter the edges of the roofplate develop into thin medullary bands, by means of which the attachment to the sides of the fossa rhomboidalis is accomplished, so here also the epithelium of the choroid plexus attaches itself to the surface of the optic thalanius by means of thin bands consisting of medullated nerve-fibres (taenise thalaini optici).
 
Finally, out of the hindermost portion of the roof of the betweenbrain vesicle a peculiar organ, the pineal <jland (fig. 241 s), takes its origin at a very early period, in Man in the course of the second month. Since in recent years numerous interesting works have appeared concerning it, and since many striking discoveries have been brought to light both in the case of the Selachians and more especially in that of the Reptiles, I will describe it at somewhat greater length.
 
The Development of the Pineal Gland (Epiphysis cerebri).
 
First it is to be mentioned that, with the exception of Amphioxus lanceolatus, the pineal gland (glandula piiiealis s. conariuin) is not wanting in any Vertebrate. It is in all cases formed in exactly the same way. On the roof of the between-brain, where it is continuous with the roof of the mid-brain or the lamina quadrigemina, there arises an evagination (figs. 238 and 241 z) which has the shape of the finger of a glove, the processus pinealis [epip/iysis cerebri], the apex of which is at first directed forward, but subsequently backward. In its further metamorphosis there appear, as far as our knowledge at present extends, differences of considerable importance.
 
According to the investigations of EHLERS, the pineal process attains in adult /Selachians an unusual length ; its closed end swells into a vesicle, which penetrates the cranial capsule and extends out to the dermal surface. In many Selachians, such as Acanthias and Raja, the vesicular end is enclosed in a canal of the cranial capsule itself ; in others it lies outside between the cranial capsule and the corium. The [proximal] end of the vesicle is united to the betweenbrain by means of a long slender canal.
 
Manifold conditions are met with in Reptiles, as the recent investigations of SPENCER have taught. These conditions permit in part a direct comparison with the Selachians, but in part they are widely altered. Here, too, the pineal gland is a structure of considerable length, the peripheral end of which lies far away from the betweenbrain under the epidermis; it passes out through an opening in the roof of the skull which is situated in the parietal bone and is known as the foramen parietale. The position of the latter can easily be determined on the head of the living animal) because at this place the dermal scutes acquire a special condition and form, and, above all, are transparent.
 
In regard to the particular form of the organ, there are essentially three types to be distinguished.
 
In many Reptiles, e.g., in Platydactylus, the pineal gland has the same structure as in Sharks : a small peripheral vesicle, which is
schb p st bl x p
 
+++++++++++++++++++++++++++++++++++++++++
 
Fig. 244. -Diagrammatic longitudinal section through the brain of Chameleo vulgaris with the pineal organ, which is separated into three portions, a vesicular, a cord-like, and a tube-like portion, after BALDWIN SPENCER.
 
schb, Parietal bone with the foramen parietale ; p, pigment of the integument ; st, cord-like middle portion of the epiphysis ; bl, its vesicular terminal portion ; x, transparent region of the integument ; yrh, cerebrum ; sh, optic thalamus ; v 3 , third ventricle, which is continued upwards into the tube-like initial portion (A) of the epiphysis.
+++++++++++++++++++++++++++++++++++++++++
 
 
enclosed in the parietal foramen, is lined with ciliated cylindrical cells, and is connected with the roof of the between-brain by means of a long, hollow stalk.
 
In other Reptiles, as in the Chameleon, the organ is differentiated into three portions (fig. 244) : first into a small closed vesicle (bl), which lies under a transparent scale (x) in the foramen parietale and is lined with ciliated epithelium ; secondly into a solid cord, which consists of fibres and spindle-shaped cells, and bears a certain resemblance to the embryonic optic nerve j and thirdly into a hollow, funnel-shaped projection (J) of the roof of the between brain, which still exhibits here and there sac-like enlargements.
 
In a third division of the Hep tiles, in Hatteria, Monitor, the Blind-w o r m s, and Lizards,
A
the vesicular distal portion i of the pineal k gland undergoes a striking r metamo r p h osis, by means of which it acquires a certain resemblance to the eye of many Invertebra t e s (fig. 245). The portion of its wall which lies next to the surface of the body has been transformed into a lens-like structure (1} ; the part of the wall lying opposite the latter and continuous
with the fibrous cord (Si) has, on the contrary, been converted into a retina-like structure (r~). The formation of the lens (I) is clue to the fact that the epithelial cells of the anterior wall of the vesicle have become elongated into cylindrical cells and uninucleate fibres, and have thereby produced an elevation, the convex surface of which projects into the cavity of the vesicle. In the posterior portion the epithelial cells are separated into different layers, the innermost of which is distinguished by the abundance of its pigment. Between the pigmented cells there are imbedded others, which can be compared to the rods of the visual cells in the paired eyes of Vertebrates, and which appear to be in connection below with nerve-fibres.
 
 
+++++++++++++++++++++++++++++++++++++++++
 
Fig. 245. Longitudinal vertical section through the pineal eye of Hatteria punctata and its connective-tissue capsule, after BALDWIN
SPENCER. Slightly enlarged.
 
The anterior part of the capsule fills up the parietal foramen.
 
K, Connective-tissue capsule ; I, lens ; h, cavity of the eye filled with fluid ; r, retina-like portion of the optic vesicle ; M, molecular layer of the retina ; y, blood-vessels ; x, cells in the stalk of the pineal eye ; St, stalk of the pineal eye, comparable with the optic nerve.
 
+++++++++++++++++++++++++++++++++++++++++
 
 
 
Those investigators who, like RABL-RUCKHARD, AHLBORN, SPENCER, and others, have studied the pineal gland, are of opinion that the pineal body must be considered as an unpaired parietal eye, which in many classes, for example in Reptiles, appears to be tolerably well preserved, but in most Vertebrates is in process of degeneration.
 
That we have to do in Reptiles with an organ which reacts under the influence of light, does not appear improbable, when one takes into consideration that, owing to the transparency of the dermal scutes at the place in the skull where the parietal foramen is located, rays of light are here able to penetrate through the integument. The presence of a lens-like body and pigment is also favorable to this view. But whether the organ serves for sight, or only for the transmission of sensations of warmth, whether, consequently, it is more an organ for the perception of warmth than an eye, must for the present remain undecided. It is still more an open question whether this organ of warmth is a structure which has been developed as a special modification of the epiphysis of Reptiles alone, as the auditory sac, for example, has been developed in the tail of the Crustacean Mysis, or whether it represents a structure originally common to all Vertebrates. In the latter case processes of degeneration must be assumed to be widespread, for up to the present time nothing like the condition in Reptiles has been found in other Vertebrates.
 
In Birds and Mammals the pineal process undergoes metamorphoses which give rise to an organ of a glandular, follicular structure.
 
In Birds (fig. 246) it never attains such great length as in Selachians and Reptiles. At a certain stage it sends out from its surface into the surrounding vascular connective tissue cellular outgrowths, which increase in number by means of budding and finally break up into numerous small follicles (fig. 246 /). These consist of several layers of cells, the outermost being small, spherical elements, the innermost cylindrical ciliated cells. The proximal portion of the pineal process does not become involved in the follicular metamorphosis and persists as a funnel-shaped outfolding of the roof of the between-brain ; the individual follicular vesicles constricted off from the parental tissue are ' united with its upper end by means of connective tissue.
 
In Mammals the development takes place in a manner similar to that of the Chick. In the Rabbit there also arise follicles, each of
which at first encloses a small cavity, but later becomes solid. They are then entirely filled with spherical cells, which possess a certain resemblance to lymphcorpuscles. The opinion has therefore been expressed by many (HENLE) that the pineal body is a lymphoid organ, an opinion, however, which is refuted by the study of the development, for genetically the follicles are exclusively epithelial structures.
 
In the adult there are formed
within the individual follicles concretions, the brain-sand (acervulus cerebri).
 
In Man the pineal body, which begins to appear in the sixth week (His), exhibits a peculiarity as regards its position. Whereas the free end of the epiphysis is at first directed forward, and in other Vertebrates is also retained in this position, it acquires in Man an opposite direction, inasmuch as it bends backward on to the surface of the lamina quadrigemina. Probably this is connected with the fact that the gland is crowded back by the excessive development of the corpus callosum.
 
As the signification of the pineal gland is still doubtful, so is that of the pituitary body or hypophysis cerebri, which, as has been previously mentioned, is united with the floor of the bet ween -brain at the apex of the infundibular process.
 
+++++++++++++++++++++++++++++++++++++++++
 
Fig. 246. Section through the pineal gland of a Turkey, after MIHALKOVICS. Magnified ISO diameters.
 
/, Follicle of the pineal gland with its cavities ; b, connective tissue with blood-vessels.
 
+++++++++++++++++++++++++++++++++++++++++
 
The Development of the Hypophysis (Pituitary Body).
 
The hypopliysis is an organ which has a double origin. This is expressed in its entire structure, since it is composed of a larger, anterior and a smaller, posterior lobe, which in their histological characters are fundamentally different from each other.
 
In order to observe the beginning of its formation, it is necessary to go back to a very early stage (fig. 237), in which the oral sinus has just arisen and is still separated from the cavity of the head-gut by means of the pharyngeal membrane (rh). At this time the cephalic flexure of the brain-vesicles has already appeared, and the anterior end of the chorda dorsalis (ch) terminates immediately behind the attachment of the pharyngeal membrane. In front of this is located the important place where the hypophysis is developed, as was first established by GOETTE and MIHALKOVICS. The hypophysis is therefore a product of the outer germ-layer and not a growth from the cavity of the head- gut, as had always been maintained previous to this time.
 
The first steps introductory to the formation of the hypophysis take place soon after the rupture of the pharyngeal membrane (figs. 238, 247), some unimportant remnants of which are retained at the base of the skull as the so-called primitive velum palatinum. Anterior to these there is now developed (in the Chick on the fourth day of incubation, in Man during the fourth week, His) a small evagination, the pouch of RATHKE or the pocliet of the hypophysis (%), which grows toward the base of the b e t w e e n-b rain (tr). Then it becomes deeper, begins to be constricted uoff from its parent tissue, and to be metamorphosed into a small sac, whose wall is composed of several layers of cylindrical cells (fig. 248). t ./ 6
The sac of the hypophysis (hy) remains for a long time in connection with the oral cavity by means of a narrow duct (hyy). In later stages, however, the connection in the higher Vertebrates interrupted, because the embryonic connective tissue, which supplies the foundation for the development of the skeleton of the head, becomes thickened and crowds the sac farther away from the oral cavity (figs. 248, 249). When, later on, the process of chondrification takes place in the connective tissue, by means of which the cartilaginous base of the skull (sc/w) is established, the sac of the hypophysis (%) comes to lie above the latter at the under surface of the between-brain (tr). At this time also the duct of the hypophysis (hyg), which meanwhile has lost its lumen, begins to shrivel and degenerate (fig. 249). In many Vertebrates, however, as in the
 
 
+++++++++++++++++++++++++++++++++++++++++
 
Fig. 247. Median sagittal section through the hypophysis of a Rabbit embryo 12 mm. long, after MIHALKOVICS. Magnified 50 diameters.
 
Floor of the between-brain with the infundibulum ; 71/1, floor of the after-brain ; ch, chorda ; hy, pocket of the hypophysis.
 
+++++++++++++++++++++++++++++++++++++++++
 
 
 
 
+++++++++++++++++++++++++++++++++++++++++
Fig. 248. Sagittal section through the hypophysis of a Rabbit embryo 20 mm. long, after MIHALKOVICS. Magnified 55 diameters.
 
tr, Floor of the between -brain with infundibulum ; hy, hypophysis ; hy', part of the hypophysis in which the formation of the glandular tubules begins; hyg, duct of the hypophysis; schb, base of the skull ; ch, chorda ; si, dorsum sellae.
 
+++++++++++++++++++++++++++++++++++++++++
 
+++++++++++++++++++++++++++++++++++++++++
 
Fig. 249. Sagittal section through the hypophysis of a Rabbit embryo 30 mm. long, after MIHALKOVICS. Magnified 40 diameters.
 
tr, Floor of the between-brain with infundibulum ; hy, original pouch like part of the hypophysis ; Inj', the glandular tubules which have budded out from the sac of the hypophysis ; si, dorsum selhe ; ba, basilar artery; ch, chorda ; schb, cartilaginous base of the skull; cm. epithelium of oral cavity.
 
+++++++++++++++++++++++++++++++++++++++++
 
At an early period an evagination from the between-braiii (figs. 247, 249), called the infundibulum (tr), has grown out toward the sac of the hypophysis and applied itself to the posterior wall of the latter, which it has folded in toward the anterior or opposite wall.
 
This first stage is followed by a second, in which the sac and the adjoining end of the infundibulum are metamorphosed into the two lobes of the complete organ already mentioned.
 
The sac begins (in Man in the second half of the second month, His) to send out from its surface into the surrounding very vascular connective tissue hollow tubules (the tubules of the hypophysis] (figs. 248, 249 hy\ These are then detached from the walls of the sac, by becoming enclosed on all sides by vascular connective tissue. In this respect the process of development agrees in the main with that of the thyroid gland, only that the spherical follicles are here represented by tubular structures. After the entire sac has been resolved into a large number of small, tortuous tubules provided with narrow lumiiia, the lobe thus produced applies itself closely to the lower end of the infundibulum, with which it becomes united by means of connective tissue.
 
The end of the infundibulnni itself is transformed in the lower Vertebrates into a small lobe of the brain, in which, moreover, ganglionic cells and nerve-fibres can be identified. In the higher Vertebrates, on the contrary, no trace of such histological elements can be detected in the posterior lobe of the hypophysis, which in these- forms consists of closely packed spindle-cells, and thus acquires a close resemblance to a spindle-cell sarcoma.
 
(5) Development of the First or Fore-Brain Vesicle.
 
The most important changes, the comprehension of which is in part attended with serious difficulties, take place in the vesicle of the fore-brain or cerebrum. It is divided (fig. 250), even at the time of its formation, as has already been mentioned, into a right and a left portion, owing to the fact that its wall becomes infolded from in front and from above by means of a vertical process of the connectivetissue envelope of the brain, the primitive falx. The two portions, the vesicles of the hemispheres (kms), come close together, being separated by only the narrow longitudinal or interpallial fissure (msp), which is filled up by the falx, so that their median surfaces become mutually flattened, whereas their lateral and under surfaces are convex. Where the plane and convex .surfaces are continuous with each other there is a sharp bend in the mantle (Mantelkante).
 
The vesicles of the hemispheres at first have thin walls formed of several layers of spindleshaped cells (fig. 251, i) and each encloses a large cavity, the lateral ventricle (fig. 251), which is derived from the central canal of the neural tube. Inasmuch as these have been reckoned by the earlier authors as the first and second ventricles, it is plain why the cavities of the betweeii-brain and medulla oblongata are respectively designated as the third and fourth ventricles. In Man, during the earlier months, each lateral ventricle is in communication with the third ventricle by means of a wide opening, the primitive foramen of MONRO (figs. 239 ML and 254 m).
 
+++++++++++++++++++++++++++++++++++++++++
 
Fig. 250. Brain of a human embryo seven weeks old, parietal (Scheitel) aspect, after MIHALKOVICS.
 
msp, Interpallial (longitudinal) fissure, at the bottom of which is seen the embryonic lamina terminalis (Schlussplatte) ; kms, left hemisphere ; zh, betweenbrain ; mh, mid-brain ; 1th, hind - brain and after-brain.
 
+++++++++++++++++++++++++++++++++++++++++
 
Anterior to the foramen of MONRO lies the part of the wall of the cerebrum which was infolded by the development of the great interpallial fissure : on the one hand it effects the anterior union of the walls of the two hemispheres ; on the other it bounds the third
ventricle in front, and is therefore called the anterior closing plate (lamina
terminalis). It is continuous
below with the anterior wall
of the infundibulum of the
between-brain.
 
In the further development of each vesicle of the hemispheres four processes are intimately associated : ( 1 ) an extraordinary growth and an enlargement in all directions resulting from it ; (2) an infolding of the wall of the vesicle, so that externally there arise deep clefts (the fissures), and
 
+++++++++++++++++++++++++++++++++++++++++
 
Fig. 251. Brain of a human embryo of three months, after KOLLIKER. Natural size.
 
1. From above with the hemispheres removed and the mid-brain opened. '2. The same from below. /, Anterior part of the marginal arch (Randbogen) of the cerebrum cut through ; /', posterior part (hippocampus) of the marginal arch ; tho, optic thalamus ; cst, corpus striatum ; to, tractus options ; cm, corpora mammillaria ; p, pons Varolii.
 
+++++++++++++++++++++++++++++++++++++++++
 
internally projections into
the lateral ventricles; (3) the development of a system of commissures, by means of which the right and left hemispheres are brought into closer union (corpus callosum and fornix) ; (4) the formation of furrows that cut into the cortex of the cerebrum more or less deeply from the outside, but cause no corresponding internal projections in the wall of the ventricle.
 
As regards its general features, the embryonic growth of the cerebral vesicles is especially characterised by an enlargement backward. In the third month the posterior lobe already completely overlies the optic thalamus (fig. 242) ; in the fifth month it begins to extend over the corpora quaclrigemma (fig. 241), which it entirely covers up in the sixth month. From there it spreads over the cerebellum (fig. 256). The cerebrum is not characterised in all Mammals by such an extraordinary growth as in Man ; comparative anatomy teaches rather that the stages of development of the human brain in different months here described, are met with in other Mammals as permanent conditions.
 
In some animals the posterior margins of the hemispheres extend as far as the corpora quadrigemina ; in others they cover these more or less completely ; in others, finally, they have grown over the cerebellum more or less. On the whole, the increase in the volume of the cerebrum, which is so varied in Mammals, goes hand in hand with an increase in intelligence.
 
The vesicles of the hemispheres undergo additional complication (in Man in the course of the second and third months), owing to infoldings of their thin walls, which still enclose a large cavity. As a result of this there arise on the outer surface deep furrows, which separate large areas from one another and which have been designated as total furrows or fissures by His, who has rightly estimated their importance in the architecture of the brain. Corresponding to the f urrows which are visible on the outer surface, there are more or less prominent elevations on the inner surface of the lateral ventricles, by means of which the latter become narrowed and reduced in size. The total furrows of the cerebral hemispheres are the fissure of SYLVIUS (fossa Sylvii), the arcuate fissure, embracing the hippocampal fissure (fissura hippocampi), the fissura choroidea, the fissura calcarina, and the fissura parieto-occipitalis. The elevations produced by them are called the corpus striatum, fornix and pes hippocampi, tela choroidea and calcar avis. A prominence which in the embryo corresponds to the fissura parieto-occipitalis, becomes obliterated in the adult by a considerable thickening of the wall of the brain, so that no permanent structure results from it.
 
The fissure of SYLVIUS (fig. 252 Sy.g) is the first one formed. It appears as a shallow depression of the convex outer surface at about
 
 
442
 
 
EMBRYOLOGY.
 
 
 
the middle of the lower margin of each hemisphere. The part of the wall which is thus depressed becomes considerably thickened (figs. 243, 251 cst, and 254 st), and forms an elevation on the floor of the cerebrum projecting into its cavity, the corpus striatum, in which several nuclei of gray matter are developed (the nucleus caudatus, the nucleus lentiformis, and the claustrum). Inasmuch as the elevation lies at the base of the brain and forms the direct forward and lateral continuation of the optic thalamus, it is regarded as belonging to the brain-stalk, and is distinguished as the stalk part of the cerebral hemispheres in distinction from the remaining portion or mantle part. The outer surface of the stalk part can be seen from the outside for a time, as long as the Sylvian fissure is still shallow (fig. 252
 
 
Sy.g
rn
sclt 1. 1
 
 
schel.L
 
 
 
Fig. 252. Lateral view of the brain of a human embryo during the first half of the fifth month,
after MIHALKOVIC.S. Natural size.
 
stl, Frontal lobe ; schei.l, parietal lobe ; hi, occipital lobe ; schl.l, temporal lobe; Sy.y, fissure of SYLVIUS ; rn, olfactory nerve ; kh, cerebellum ; br, pons ; mob, medulla oblongata.
 
 
 
but it then becomes entirely overgrown and hidden by the edges of the gradually deepening fissure. Later this surface acquires in the embryo several cortical furrows and becomes the island of HELL (insula Reilii), or the central lobe (Stammlappen).
 
The mantle portion, as it enlarges, spreads out uniformly around the island of REIL, as though about a fixed point, and surrounds it in the form of a half-ring open below (fig. 252) ; on this account it has received the name ring-lobe. Even now the regions of the four chief lobes into which the convex surface of each hemisphere is subsequently divided can readily be distinguished, although they are not yet sharply limited. The end of the half -ring which is directed forward and lies above the fissure of SYLVIUS (tiy.y) is the frontal lobe (stl) ; the opposite end, which embraces the fissure behind and
 
 
THE ORGANS OF THE OUTER GERM-LAYER. 443
below, is the temporal lobe (schl.l) ; the region lying above and connecting the two is the parietal lobe (schei.l). A prominence which is developed from the ring-lobe backward becomes the occipital lobe (hi).
 
The lateral ventricle has also become altered and corresponds to the external form of each hemisphere (fig. 253). It also assumes the shape of a half -ring, which lies above and surrounds the corpus striatuin (cst) that part of the wall of the vesicle which is forced inward by the fissure of SYLVIUS. Subsequently, when the individual lobes of the hemispheres are more sharply differentiated from one another, the lateral ventricle also undergoes a subdivision corresponding to the lobes. It becomes slightly enlarged at both ends, in front into the anterior cornu occupying the frontal lobe, behind and below into the inferior cornu of the temporal lobe. Finally, from the half ring there is developed a small evagination, the posterior cornu, which extends backward into the occipital lobe. The region lying between the horns is narrowed and becomes the cella media.
 
All the fissures hitherto mentioned, except that of SYLVIUS, are developed on the plane [median] surface of the vesicle of the hemisphere.
 
At a very early stage in Man in the fifth week (His) there arise on this wall of the hemisphere two furrows running almost parallel with the edge or bend of the mantle, the arcuate or hippocampal fissure and the fissure of the choroid plexus (Jissura hippocampi andjfoswra choroidea) ; both conform very closely in their direction to the ringlobe, and, like it, with crescentic form embrace from above the stalk part of the cerebrum, the corpus striatum. They begin at the foramen of MONRO and extend from there to the tip of the temporal lobe, forming the boundaries of a region known as the ma/rginal arch (Randbogen) ; this projects as a thickening on the median surface of the hemisphere, and takes part in the development of the connnissural system. The imaginations of the median wall of the ventricle, caused by the fissures, the hippocampal fold and the fold of the lateral choroid plexus, are best understood by removing in an embryo the lateral wall of the hemisphere, so that one can survey the inner surface of the median wall of the still very spacious and ring -like lateral ventricle (fig. 253). The cavity is then seen to be partly filled with a reddish frilled fold (agf), which lies in the form of a crescent on the upper surface of the corpus striatum (cst). In the region of the fold the wall of the brain undergoes changes similar to those in the roof of the medulla oblongata and of the vesicle of the between-brairi
 
 
144
 
 
EMBRYOLOGY.
 
 
 
 
(figs. 254 2*1 and 255 agf}. Instead of thickening and developing
nerve-substance, it becomes attenuated, and is transformed into a single layer of flat epithelial cells, which are firmly united with the pia mater. The latter then becomes very vascular along
Fig. 253. Lateral view of the brain of an embryo Calf 11 , r i i i
the entire fold, and grows into the lateral ventricle in the form of tufts, which carry the epithelium before them. In this way the lateral choroid plexus arises (fig. 254 pi], which afterwards, in the adult, fills a part of the cella media and inferior cornu. It begins at the foramen of M o N R o (fi g.
 
 
 
cst
 
 
5 cm, long. The lateral wall of the hemisphere has been removed. After MIHALKOVICS. Magnified 3 diameters.
 
cst, Corpus striatum ; ML, foramen of MONJIO ; agf, plexus choroideus lateralis ; amf, hippucampal fold; lit, cerebellum; Dp, roof of the fourth ventricle; bb, pontal flexure ; mo, medulla oblongata ; mh, mid-brain (parietal flexure).
 
 
 
it is continuous with the anterior unpaired choroid plexus which has arisen in the roof of the between-brain vesicle. If the delicate vascular pia mater is drawn out from the choroid fissure, the wall of the brain, which is reduced to a thin epithelium, is at the median wall of
 
 
 
a
 
 
:;-/;*>
i ip\\ r A
.- \lf \
p *u \ c]l o
 
 
Fig. 254. Transverse section through the brain of an embryo Sheep
2 -7 cm. in length, after KOLLIKER.
 
The section passes through the region of the foramen of MONRO. st, Corpus striatum; m, foramen of MONRO; t, third ventricle; pi,
plexus choroideus of the lateral ventricle ;/, falx cevebri ; th, deepest
anterior part of the optic thalamns ; ch, chiasma ; o, optic nerve ;
c, fibres of the crus cerebri ; /<, hippocampal fold ; p, pharynx;
sa, presphenoid ; , orbito-sphenoid ; s, part of the roof of the
brain at the junction of the roof of the third ventricle with the
lamina terminalis ; I, lateral ventricle.
 
same time destroyed, and there is produced in the the hemisphere a gaping fissure, which extends from
 
 
THE ORGANS OF THE OUTER GERM -LAYER.
 
 
 
445
 
 
prothe
 
 
the foramen of MONRO to the tip of the temporal lobe and leads from the outside into the lateral ventricle. This is the lateral cerebral fissure, or the great fissure of the hemispheres (fissura cerebri transversa). In a preparation made in the manner described the hippocampal fold is to be seen at a short distance from the choroid plexus and parallel to it (figs. 253 and 255 aw/" and fig. 254 k). This increases in size toward the apex of the inferior cornu, and in the completely formed brain produces the cornu Ammonis or pes hippocampi. Consequently that part of the lateral ventricle enclosed in the temporal lobe becomes (as the result of two infoldings of its median wall) restricted by two jections, choroid plexus and the cornu Ammonis. As in the betweenbrain and medulla o b 1 o ngata, the epithelial covering of the choroid plexus is continuous with the thicker nerve-su Instance of the Am
 
 
 
c o r n u
 
 
Tig. 255. Transverse section through the brain of a Rabbit embryo
3'8 cm. in length, after MIHALKOVICS. Magnified diameters. The section passes through the foramina of MONRO. hs, Great falx cerebri which fills up the interpallial fissure ; A 1 , Jr, plane
inner [median] and convex outer wall of the cerebral hemisphere ;
agf, fold of the choroid plexus ; ;/, hippocampal fold ; /, fornix ;
sv, lateral ventricle ; ML, foramen of MONRO ; v' J , third ventricle ;
ch, optic chiasma ; frx', descending root of the fornix.
 
monis. The
transition is effected by means of a thin medullary plate, which in
anatomy is described as the fimbria.
 
Inasmuch as the occipital lobe with its cavity develops as an evagination of the ring-lobe, the fissura calcarina belonging to it is therefore developed somewhat later than the arcuate fissure (fig. 241 fc). It appears at the end of the third month as a fissure branching off from the latter, and runs in a horizontal direction until near the apex of the occipital lobe. It invaginates the median wall of the lobe and produces the calcar avis, which invades the posterior cornu in the same way as the hippocampus major (cornu Ammonis) does the inferior cornu. At the beginning of the fourth month the fissura occipitalis (fig. 241 fo] is added to it. The latter rises from
 
 
44G EMBRYOLOGY.
 
the anterior end of the fissura calcarina in a vortical direction to the bent rim of the mantle (Mantelkante), and sharply separates the occipital and parietal lobes from each other.
 
A third factor of great importance in the development of the cerebrum is the formation of a system of commissures, which supplements the connection of the two cerebral vesicles, at first effected by the embryonic lamina terminalis only. Those investigators who have occupied themselves with these difficult matters assert that in the third embryonic month fusions take place between the facing median walls of the hemispheres. These fusions begin in front of the foramen of MONRO within a triangular area. The fusions in this region occur only at the periphery, not in the middle of the area. Three parts of the brain of the adult are thus produced : in front, the genu of the corpus callosum, behind, the columns of the fornix, and between them, the septum pellucidum ; the latter contains a fissurelike cavity, in the region of which the contiguous walls of the hemispheres, here very much attenuated, have remained separated from each other. Consequently the cavity just mentioned the ventriculus septipettucidi [or fifth ventricle] ought not to be placed in the same category with the other cavities of the brain ; for while the latter are derived from the central canal of the embryonic neural tube, the former is a new production, which has arisen by the enclosure of a portion of the space I} 7 ing outside the brain between the two hemispheres the narrow interpallial fissure.
 
A further enlargement of the commissural system is accomplished in the fifth and sixth months. The fusion now proceeds still farther, advancing from in front backwards, and involves that region of the median walls of the hemispheres which, situated between the arcuate fissure [above] and the fissure of the choroid plexus [below], has already been described as the marginal arch (Randbogen). By fusion of the anterior part of the marginal arch with its fellow of the opposite side, which process takes place as far as the posterior limit of the between-brain, there arise the body of the corpus callosum and the splenium, as well as the underlying fornix. The furrow bounding the corpus callosum above (sulcus corporis callosi) is therefore the anterior part of the arcuate furrow, whereas the posterior portion, that of the temporal lobe, is subsequently known as the fissura hippocampi.
 
The structure of the cerebrum is completed by the appearance of numerous cortical furrows. These differ in rank from the total furrows already described, because they are confined to the outer surface of the
 
 
THE ORGANS OF TH^ OUTER GERM -LAYER.
 
 
 
447
 
 
vcw
 
 
cf
hew
 
 
brain and do not cause corresponding projections into the ventricles. Their formation begins as soon as the wall of the brain becomes greatly increased in thickness by the development of white medullary substance, which occurs during and after the fifth month. This is due to the fact that the gray cortex with its ganglionic cells increases more rapidly in superficial extent than the white substance and is therefore raised into folds, the cerebral convolutions or gyri, into which only thin processes of white substance penetrate. At first, therefore, the furrows are quite shallow; they become deeper in proportion as the hemispheres become thicker and the cortical folds project farther outward.
 
Of the numerous furrows which the completely formed brain presents, some appear during the development earlier, others later. Thus they acquire different values in the architecture
 
 
of the cerebral surface. For "the earlier a furrow appears the deeper it liecomes, the later it appears the shallower it is " (PANSCH). The first are therefore the more important and constant ones, and are fittingly to be distinguished as chief or primary fwrrow8 from the subsequently formed and more variable secondary and tertiary furrows. They begin to appear at the commencement of the sixth month. The first of them to appear is the central furrow (fig. 256 c/"), which is one of the most important, since it separates the frontal and parietal lobes from each other. " In the ninth month all of the chief sulci and convolutions are formed, and since at this time the secondary sulci are still wanting, the brain during the ninth month presents a typical illustration of the sulci and convolutions " (MiHALKOVlCs).
 
Very great differences exist between the different divisions of Mammals in the extent to which the sulci of the cerebrum are developed. On the one hand are the Monotremes, Insectivores, and many Rodents, whose cerebrum also
 
 
 
- fo
 
 
Fig. 256. Brain of a human embryo at the beginning of the eighth month, after MIHALKOVICS. Threefourths natural size.
 
cf, Central furrow ; vcio, hew, anterior and posterior central convolutions ; fo, fissura occipitalis.
 
 
 
448
 
 
EMBRYOLOGY.
 
 
 
usually less developed in other features possesses \\, smooth surface, and thus, as it were, remains permanently in the fietal condition of the human brain. On the other hand the brains of the Carnivores and I'rimates, owing to I he great number of their convolutions, approach more closely to the human brain.
 
Finally, in treating of the development of the cerebrum there is still to be considered an appendage to it, the olfactory nerve. This part, as well as the optic nerve, is distinguished from the peripheral
nerves by its entire development, and must be considered as a specially modified portion of the cerebral vesicle. The older designation of nerve is therefore now more frequently replaced by the more appropriate name of olfactory lobe (lobus olfactorius, rhinencephalon). Even at an early stage -in the Chick on the seventh day of incubation, in Man during the fifth week (His) -there is formed on the floor of each frontal lobe at its anterior end a small evagination, which is directed forward (figs. 240, 241 rn). This gradually assumes the form of a club, the enlarged end of which, the part lying 011 the cribriform plate of the ethmoid bone, is designated as the bulbus olfactorius. The bulbus encloses a cavity which is in communication with the lateral ventricle.
 
During the first month of development the olfactory lobe, even in Man, is relatively large and provided with a central cavity. Later it begins to diminish somewhat, the sense of smell being only slightly developed in Man ; its growth is arrested and at the same time its cavity also disappears. In most Mammals, on the contrary, whose sense of smell, as is well known, is more acute than that of Man, the olfactory lobe attains a greater size in the adult animal and exhibits more clearly the character of a part of the brain, for it permanently encloses in its bulb a cavity, which
 
 
 
Fig. 257. Brain of Galeus canis in situ, dorsal aspect, after EOHON.
 
Lol, Lobus olfactorius ; Tro, tractus nervi olfactorii ; VH, fore-brain, provided at fn with a vascular foramen (foramen nutritium) ; ZH, between -brain ; ]\IH, mid-brain ; HH, hind-brain ; NH, afterbrain ; R, spinal cord ; //, n. options ; ///, n. oculomotorius ; IV, n. trochlearis ; V, n. trigeminus ; L,Trig, lobns trigemini ; C,rest, corpus restiforme ; IX, glossopharyngeus; A", vagus; E,t, enriuentire teretes.
 
 
 
THE ORGANS OF THE OUTER GERM-LAYER. 449
frequently (Horse) is even in connection with the anterior cornu by means of a narrow canal in the tractus olfactorius.
 
The olfactory lobe (Lol + Tro) attains an extraordinary development (fig. 257) in the Selachia, in which it exceeds in size the between-brain. (ZH] and mid-brain (MH . In the Selachians two long hollow processes (tractus olfactorius, Tro) extend out from the anterior end of the little-developed cerebrum and terminate at a considerable distance from the fore-brain in two large hollow lobes, that are sometimes provided with furrows (Lol).
 
 
 
B. The Development of the Peripheral Nervous System.
 
Although it is easy to follow the development of the brain andspinal cord, the investigation of the origin of the peripheral nervous system is very dimcult, for it requires the study of histological processes of the most subtle nature the first appearance of non-medullated nerve-fibres and the method of their termination in embryos composed of more or less undifferentiated cells. One who knows how dimcult it is even in the adult animal to follow non-medullated iierve-fibrillse in epithelial layers or in non-striate muscle-tissue, and to get a clear idea of their method of termination, will understand that many, and indeed the most interesting, questions in regard to the development of the peripheral nerves are not yet ripe for discussion, because the observations necessary for their settlement are still wanting. There is only one point which is entirely clear. That concerns the development of the spinal ganglia, which His and BALFOUR independently of each other were the first to recognise, the one in the Chick, the other in Selachians. Since then numerous investigations embracing different groups of Vertebrates have been published on this subject by HENSEN, MILNES MARSHALL, KOLLIKER, SAGEMEHL, VAN WIJHE, BEDOT, ONODI, BERANECK, EABL, BEARD, KASTSCHENKO, and others.
 
(a) The Development of the Spinal Ganglia.
 
The development of the spinal ganglia in the spinal cord is very easily followed. It begins just at the time the medullary groove closes to form a tube (fig. 258 A and B). At this time a thin ridge of cells (spy 1 , spy] one or two layers deep grows out of the neural tube on either side of the line of fusion, and, passing outward
29
 
 
450
 
 
EMBRYOLOGY.
 
 
 
 
and downward, inserts itself between the tube and the closely investing primitive epidermis. In this way it reaches the dorsal angle of the primitive somites (us), which are by this time well
developed. Then the neural crest, as BALFOUR names it, or the ganglionic ridge, as SAGEMEHL calls it, is divided up into successive regions. For the tracts which alternate with the primitive segments lag behind in their growth, while the parts lying opposite the middle of segments grow more vigorously, become thickened, and at the same time advance farther ventrad, penetrating between primitive segment and neural tube.
 
Frontal sections furnish very instructive views of this stage. Fig. 259 exhibits such a section, taken from SAGEMEHL'S work. Inasmuch as the longitudinal axis of the Lizard embryo employed for the sections was greatly curved, the five segments seen in the section are cut at different heights, the middle one deeper than the two preceding and the two following. In the middle segment the fundament of the ganglion (spA 1 ) is differentiated and it is bounded by blood-vessels
 
 
 
Fig. 258.- -A, Cross section through an embryo of Pristiurus, after EABL.
 
The primitive segments are still connected with the remaining portion of the middle germ-layer. At the region of transition there is to be seen an outfolding, sk, from which the skeletogenous tissue is developed, ch, Chorda ; spg, spinal ganglion ; mp, muscle-plate of the primitive segment ; nch, subchordal rod ; ao, aorta ; ik, inner germ-layer ; 2nb, parietal, rmb, visceral middle layer.
 
B, Cross section through a Lizard embryo, after SAGEMEHL.
 
rm, Spinal cord ; spy, lower thickened part of the neural ridge ; spy', its upper attenuated part, which is continuous with the roof of the neural tube ; us, primitive segment.
 
 
 
THE ORGANS OF THE OUTER GERM-LAYER.
 
 
 
451
 
 
 
r/.i
 
 
nip
 
 
 
 
 
 
 
 
 
 
 
"-L
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
J
 
 
 
 
 
 
 
'
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
spk
 
 
in front and behind, whereas in the segments that are cut more dorsally, near the origin of the ganglia from the neural tube, the fundaments are still connected with one another. This connection appears to be most conspicuously developed and most persistent in the case of the Selachians ; it has been called the longitudinal commissure by BALFOUR. Outside the ganglia are found the primitive segments (mp, nip'}, each of which at this time still exhibits within it a narrow fissure.
 
In a monographic treatment of the peripheral nervous system BEARD differs from the preceding account, in which BALFOUR, KOLLIKER, EABL, HENSEN, SAGEMEHL, KASTSCHENKO, and others agree. He believes that the fundaments of the ganglia arise, not out of the neural tube, but out of the deeper cell-layers of the adjacent part of the outer germ-layer. He finds that they are from the beginning separated from each other and segmentally arranged. According to him, moreover, they make their appearance earlier than is stated in the preceding account ; for they are already recognisable as especially thickened places in the outer germ-layer at the tight and left of .the neural plate when the latter first begins to be bent inward.
 
Subsequently, upon the closure of the neural tube, the ganglionic cells corne to lie between the raphe and the primitive epidermis. From here they grow down ventrally at the sides of the brain and spinal cord.
 
BEARD approximates in his results the conception first expressed and subsequently maintained by His. For His derives the ganglionic ridge, not from the raphe of the neural tube, but from a neighboring part of the outer germ-layer, which he names intermediate cord (Zwischenstrang). The accuracy of BEARD'S description is, however, positively denied by KABL and KASTSCHENKO.
 
Different views are entertained concerning the further changes which take place in the fundaments of the spinal ganglia :
According to His and SAGEMEHL the separate ganglionic fundaments are completely detached from the neural tube, and for a time lie at the side of it without any connection with it whatever. Secondarily a union is again established, through the development of the dorsal nerve-roots, by the formation of nerve-fibrillre, which either grow out from the spinal cord into the ganglion, or from the ganglion into the spinal cord, or in both directions. SAGEMEHL
 
 
Fig. 259. Frontal section of a Lizard embryo, after SAGEMJEHL.
 
///<, Spinal cord; *j>k, neural ridge with thickenings that are converted into the spinal ganglia ; riip', the part of the primitive segment that produces the muscle-plate ; mp, outer layer of the primitive segment.
 
 
 
452 EMBRYOLOGY.
 
favors the first view, His the last. All other investigators maintain that the fundaments of the ganglia, while they increase in size and become spindle-shaped, are permanently united with the neural tube by means of slender cords of cells which are metamorphosed into the dorsal roots. If the latter view is correct, the dorsal roots of the nerves must in time alter their place of attachment to the neural tube by moving from the raphe laterally and ventrally.
 
The discrepancy of these accounts is connected with the different interpretations which exist concerning the development of the peripheral nerves in general.
 
(b) The Development of the Peripheral Nerves.
 
When one reviews the various opinions which have been expressed concerning the development of the peripheral nerves, it is found that there are in the literature two chief opposing views. The greater number of investigators assume that the peripheral nervous system is developed out of the central, that the nerves grow forth from the brain and spinal cord uninterruptedly until they reach the periphery, where for the first time they effect a union with their specific terminal organs. The outgrowth of the nerves from the spinal cord was first asserted for the ventral roots and conjectured for the dorsal ones by BIDDER UNO KUPFFER. Their conclusions have since been adopted by KOLLIKER, His, BALFOUR, MARSHALL, SAGEMEHL, and others. However, views concerning the method of the formation of the nerve-fibres are not in agreement.
 
According to KUPFFER, His, KG'LLIKER, SAGEMEHL, and others the outgrowing nerve-Jibres are processes of ganglionic cells located in the central organ, which must grow out to an enormous length in order to reach their terminal apparatus. There are at first no cells or nuclei among them. These are furnished secondarily by the surrounding connective tissue. According to the accounts of KOLLIKER and His, cellular elements from the mesenchyme approach the bundles of nerve-fibrillse, surround them, and then penetrate into the interior of the nervous stem, at first sparingly, afterwards more abundantly, and form around the axis-cylinders the sheaths of SCHWANN.
 
On the other hand, BALFOUR defends most positively the doctrine that cells which migrate out of the spinal cord along with the nerves share in the development. In his " Treatise on Comparative Embryology " [vol. ii., p. 372] he remarks upon this subject : " The cellular
 
 
THE ORGANS OF THE OUTER GERM- LAYER. 453
structure of embryonic nerves is a point on which I should have anticipated that a difference of opinion was impossible, had it not been for the fact that His and KOLLIKER, following REMAK and other older embryologists, absolutely deny the fact. I feel quite sure that no one studying the development of the nerves in Elasmobranchii with well-preserved specimens could for a moment be doubtful on this point." Of the more recent investigators VAX WIJHE, DOHRN, and BEARD side with BALFOUR.
 
HENSEN has taken an entirely different view on the question of the origin of the peripheral nervous system, one which differs from that of KUPFFER, HTS, and KOLLIKER, as well as from that of BALFOUR. He opposes the doctrine of the outgrowth of nerve-fibres chiefly from physiological considerations. He can think of no motive which is capable of conducting the nerves that gro\v out from the spinal cord to their proper terminations which shall cause, for example, the ventral roots always to go to muscles, the dorsal roots to organs that are not muscular, and shall prevent confusion taking place between the nerves of the iris and those of the eye-muscles, between the branches of the trigeminus and the acusticus or facialis, etc. Therefore HENSEN maintains on theoretical grounds that it is necessary to assume that " the nerves never grow out to their terminations, but are always in connection with them" According to his view, which he endeavors to support by observations, the embryonic cells are for the most part united with one another by means of fine connecting filaments. He maintains that when a cell divides the connecting thread also splits, and in this manner there arises " an endless network of fibres." Out of these the nervetracts are developed, while other parts of the network degenerate.
 
The reasons given by HENSEN are certainly worthy of great attention. With further reflection on the subject they are easily added to. If the nerves grow out to their terminal apparatus, why do they not take the most direct course to their destination, why are they often compelled to pursue circuitous paths, and why do they enter into the formation of complicated plexuses of the greatest variety ? whence are the ganglionic cells that are found to be developed in considerable numbers even in the peripheral nervous system in different organs, especially in the sympathetic nerve ? In order to make progress in this difficult field the peripheral nervous system of Invertebrates mast be taken into account more than it is at present, and in the investigation of embryos not only series of sections but also other histological methods (surface-preparations of
 
 
454 EMBRYOLOGY.
 
suitable objects together with staining of the nerve-fibrillce, isolation of the elements preceded by maceration and staining) must be employed.
 
Having thus sketched out the various standpoints taken by numerous investigators on the question of the source of the peripheral nervous system, I give a number of observations that have been made upon the development of certain nerves. These relate to the development of :
(1) The ventral and dorsal roots of the nerves ;
(2) Certain large peripheral nerve-trunks, as the nervus lateralis ;
and
(3) The nerves of the head and their relation to the spinal nerves.
 
(1) Of the roots of the nerves the anterior [ventral] are demonstrable earlier. There may be distinguished three stages in their development.
 
The first stage has been observed by DOHRN and VAN WIJHE in Selachian embryos. At a time when the neural tube has not yet developed any mantle of nervous substance, and the muscle-segment still lies very close to it, there arises between the two a connection in the form of a very short protoplasmic cord. The fundament of the nerve is therefore, as VAN WIJHE remarks, ab origine near its muscle-complex, from which it never separates. Soon after this it is elongated by the removal of the muscle-segment farther from the neural tube ; it increases in thickness and now encloses numerous nuclei, and possesses therefore a cellular composition, a condition which I shall designate as second stage.
 
There is a difference of opinion as to the cells which make their appearance in the fundament of the nerve. Whereas TVOLLTKER His, and SAGEMEHL recognise in them immigrated connective-tissue elements, which are destined to form simply the envelopes of the nerves, BALFOUR, MARSHALL, VAN WIJHE, DOHRN, and BEARD maintain that they migrate out from the spinal cord and share in the development of the nerves themselves. BEARD even derives the motor terminal plate from them. Soon after, as is asserted, connective-tissue cells from the surrounding mesenchyme become associated with the nerve-cells derived from the spinal cord and ordinarily become indistinguishable from them.
 
Finally, in the third stage the cellular fundament of the motor root acquires a fibrillar condition (fig. 260 vw\ and it now becomes possible to trace the origin of the nerve-fibrillse in the spinal cord from groups of embryonal ganglionic cells or neuroblasts (His).
 
 
 
THE ORGANS OF THE OUTER GERM-LAYER.
 
 
 
455
 
 
The formation of the nerve-fibrillae is also a subject of controversy, as has already been stated and as will be farther explained in this connection. According to the view of most observers, the nervefibrillae the future axis -cylinders are formed as processes of gang1 ionic cells of the spinal cord, the free ends of which grow out from the surface of the latter until they reach their terminal organs
(KUPFFER UND BlDDER, KoLLIKER, HlS, SAGEMEHL). Sticll aCCOUllts
 
 
 
!
- ;
 
 
0>
 
 
 
 
 
Wafa v
. v ' S^ \ / A (M Vl\ v ^^
: N. V\
:\
Afo\ ' \ :
- > , \. <s ._ .
 
'. ^<r S? .
 
u
^ -.
 
S ^
^X
e- ^ -, ''<S> V ' ,-. &
 
 
 
 
 
re
 
 
Fig. 260. Cross section of a Lisarl embryo with completely closed intestinal canal, after SAGEMEHL.
 
he, Posterior [dorsal], re, anterior commissure of the spinal cord ; cw, ventral nerve-root ; /</, nerve-fibrillae ; spk, spinal ganglion ; mp 1 , muscle-plate, muscle-producing layer ; nip", outer layer of the muscle-plate ; inp 3 , transition from the outer to the muscleforming layer.
 
 
 
are given especially for the development of the motor roots in the higher Vertebrates.
 
According to the opinion of DOHRN and VAN WIJHE, on the contrary, the nerve-fibrillse arise in situ, as products of differentiation, from the protoplasm of the cords of cells by means of which musclesegnierit and spinal cord are already united. They do not need to seek out the terminal organ, since there exists already a protoplasmic union with it. They arise in a manner similar to that in which the nmscle-fibriJlse do from the plasma of their, muscle-cells^
 
 
45G EMBRYOLOGY.
 
I desire to lay pavticnlar .shvss upon the observations oC DOTIRN and VAN WiJHK, because they harmonise with the theoretical views which I have formed as the result of investigations on Invertebrates. As 1 have in several articles endeavored to establish, protoplasmic connections of the cells are the foundation out of which the nerve-fibrillse are developed. The formation of a specific nervous system is preceded by a protoplasmic union of cells, which is effected at a time when the central and terminal nervous organs are still in the immediate vicinity of each other.
 
The dorsal roots become visible somewhat later than the ventral roots ; there are formed fibrillce which unite the upper [dorsal] end of the spinal ganglion with the side of the spinal cord.
 
(2) GOTTE, SEMPER, WIJHE, HOFFMANN, and BEARD have made concerning certain nerves the noteworthy statement which has been called in question by some observers (BALFOUR, SAGEMEHL) that the epidermis participates in their formation. In Amphibian larvae and Selachian embryos the posterior end of the nervus lateralis vagi in process of development is completely fused with the primitive epidermis, which is thickened in the lateral line (fig. 262 nl). Somewhat farther forward the nerve is detached but still lies in close contact with the primitive epidermis, whereas in the vicinity of the head it is situated deeper and lies between the muscles. At the places where the nerve has become separated from the primitive epidermis, it remains in connection with the fundaments of the lateral organs by means of fine accessory branches only. Similar observations have also been made in the case of many of the branches of other cranial nerves in Selachian embryos. WIJHE sees, for example, a short branch of the n. facialis near its emergence from the brain so fused with a thickened portion of the epidermis composed of cylindrical cells, that it is impossible to say whether at the place of transition the cell-nuclei belong to the nerve or to its terminal organ. During a more advanced stage the older part of the nerve is detached from the terminal organ, sinks into the depths, becoming separated from the skin by ingrowing connective tissue, and remains united with the terminal organ only through fine accessory branches. The persistently growing younger end of the nerve still continues to be connected with the epidermis.
 
Also in the case of the higher Vertebrates similar conditions have been observed by BEARD, FRORIEP, and KASTSCHENKO. They find the ganglionic fundaments of the facialis, glossopharyngeus, and vagus at the dorsal margin of the corresponding visceral clefts for a long time broadly fused with the epithelium, which is thickened and has become depressed into a pit. In these connections they discern
 
 
THE ORGANS OF THE OUTER GERM-LAYER. 457
the fundaments of branchial sensory organs, which no longer attain to complete development. Also FRORIEP, on the strength of his own observations, holds as admissible the interpretation that at those places where fusion occurs formative material passes out of the epidermis into deeper parts to share in the formation of nervous tracts. BEARD expresses himself still more precisely to the effect that the sensory nervous elements of the whole peripheral nervous system arise as differentiations from the outer germ-layer, independently of the central nervous system.
 
The accounts here given concerning a connection, in early stages of development, of certain nerve-trunks with the outer germ-layer, appear to me to afford an indication in favor of the hypothesis expressed by my brother and me, that the sensory nerves of the Vertebrates may have originally been formed out of a sub-epithelial nervous plexus, such as still exists in the epidermis of many Invertebrates.
 
(3) The investigations of the last few years, which have been carried out especially by BALFOUR, MARSHALL, KOLLIKER, WIJHE, FRORIEP, RABL, and KASTSCHENKO, have produced important results concerning the development of the cranial nerves, their relations to the head-segments and their value as compared with spinal nerves. On the brain, as well as on the spinal cord, there arise roots, some of which are dorsal, some ventral. Even at the time when the brain-plate is not yet fully closed into a tube (fig. 261), there is formed on either side, at the place of its bending over into the primitive epidermis, a neural ridge (vg\ which begins rather far forward and may be traced on serial sections uninterruptedly in a posterior direction, where it is continuous with the neural ridge of the spinal cord. When, somewhat later, the closure and the detachment of the brain -vesicles from the primitive epidermis has taken place, the ridge lies on the roof of the vesicles and is fused with them in the median plane. The most of the cranial nerves namely, the trigerninus with the Gasserian ganglion, the acusticus and facialis with the ganglion acusticum. and probably also the ganglion geniculi, and the glossopharyngeus and vagus with the related ganglion jugulare and g. nodosum are differentiated out of this fundament in the same manner as the dorsal roots of the spinal nerves. The nerves, which emerge dorsally, afterwards shift their origin downward along the lateral walls of the brain -vesicles toward the base of the latter.
 
All the remaining uneiiumerated cranial nerves oculomotorius, trochlearis, abducens, hypoglossus, and accessorius are developed
 
 
458
 
 
EMBRYOLOGY.
 
 
 
independently of the neural ridge, as individual outgrowths of the brain- vesicles nearer their base, and are comparable with the ventral roots from the spinal cord.
 
FROEIEP finds that the hypoglossns in Mammals possesses dorsal roots, with small gang-Home fundaments, in addition to ventral roots. The latter subsequently undergo degeneration.
 
The agreement between cranial and spinal nerves which is expressed in this method of development, becomes still greater and
 
 
 
Fig. 261. Cross section through the hind part of the head of a Chick embryo of 30 hours, after BALFOUR.
 
lib, Hind-brain ; vg, vagus ; cp, epiblast ; cli, chorda ; x, thickening of hypoblast (possibly a rudiment of the subchordal i'od) ; al, throat ; ht, heart ; pp, body-cavity ; so, somatic mesoblast ; .s/, splanchnic mesoblast (Darmseitenplatte) ; hy, hypoblasb.
 
 
 
acquires a further significance from the fact that in the head also the nerves can be assigned to separate segments in much the same manner as in the trunk. In this particular the conditions are clearest in the Selachians, where, in fact, the head-segments have been most thoroughly investigated, so that I limit myself to a statement of the results acquired in this field by WIJHE.
 
According to WIJHE nine * segments are distinguishable in the head of Selachians. To the first segment belongs the ramus
: [Recent investigations indicate that the head-segments in Selachians are much more numerous. TRANSLATOR.]
 
 
THE ORGANS OF THE OUTER GERM-LAYER. 459
ophthalmicus of the trigeminus and, as motor root, the oculomotorius. The second segment is supplied by the remaining part of the trigeminus and the trochlearis, the latter having a ventral origin. The dorsal roots of the third (and fourth'?) segments are represented by the acustico-facialis, the ventral roots by the abduceiis. The fifth segment possesses only the exclusively sensory gloFsopharyngeus, which arises from the neural ridge. The segments from the sixth to the ninth inclusive are innervated by the vagus and the hypoglossus, the former of which represents a series of dorsal roots, the latter a series of ventral ones.
 
According to WIJHE'S account, notwithstanding the general agreement, there still exists a considerable difference between the innervation of the cephalic segments and that of the trunk-segments. For in the head the ventral, motor roots (oculomotorius, trochlearis, abducens, hypoglossus) supply only a part of the musculature the eyemuscles and certain muscles that run from the skull to the pectoral girdle ; that is to say, muscles which, as has already been stated, are developed out of the cephalic segments. Other groups of muscles, which arise from the lateral plates of the head, are innervated by the trigeminus and facialis, which have a dorsal origin. Thus the dorsal roots of the nerves in the head would be distinguished from those in the trunk by the important fact that they contain motor as well as sensory fibres. BELL'S law would consequently possess a very limited application for the head-region of Vertebrates, and would have to be replaced by the following law, formulated by WIJHE :
" The dorsal roots of the head-nerves are not exclusively sensory, but also innervate the muscles that arise from the lateral plates, not, however, those from the primitive segments (somites)."
" The ventral roots are motor, but innervate only the muscles of the primitive segments (somites), not those of the lateral plates."
In view of this fundamental difference, I desire to express a doubt whether there are not after all enclosed in the facialis and trigeminus parts which are established as ventral roots, but have hitherto been overlooked, as in the beginning all the ventral roots in the brain (see BALFOUR) were overlooked.
 
According to KABL the nerves of the posterior part of the head only o-lossopharyngeus, vagus, accessorius, and hypoglossus can be compared with the type of spinal nerves ; the nerves of the anterior part of the head, on the contrary, the olfactorius, options, trigeminus, together with those of the eyemuscles and the acustico-facialis, belong in a separate category, just as the four most anterior head-segments do.
 
 
As is evident from this brief survey, there still exist many unsolved problems in the difficult subject of the development of the peripheral nervous system. Without permitting myself to enter upon a further discussion of the contradictory opinions entertained on this subject, I close this topic with a comparative-anatomical proposition, which appears to me sufficient to furnish the morphological explanation of BELL'S law, or the separate origin of the sensory and motor nerveroots.
 
In Arnphioxus and the Gyclostomes the motor and sensory nervefibres are completely separated, not only at their origin from the spinal cord, but also throughout their whole peripheral distribution. The former pass at once from their origin in the spinal cord to the muscle-segments ; the latter ascend to the surface to be distributed to all parts of the skin to supply its sensory cells and sensory organs. The separation of the peripheral nervous system into a sensory and a motor portion, ivhich is rigorously carried out in Amphioxus and the Gyclostomes, is explained by the fact that the territories to which their ends are distributed are spatially distinct in their origin, since the sensory cells arise from the outer germ-layer, the voluntary muscles from a tract of the middle germ-layer. Therefore the sensory nervefibres have been developed from the spinal cord in connection with the outer germ-layer, the motor fibres in relation with the musclesegments.
 
I regard the sub-epithelial position of the sensory nerve-fibres as the original one, just as we find in many Invertebrates the whole peripheral sensory nervous system developed as a plexus in the deepest portion of the epidermis. The important conditions above described according to which many dermal nerves (nervus lateralis, etc., fig. 262 nl) are fused with the epidermis at the time of their origin, and only subsequently become detached from it and sink deeper into the underlying mesenchyme appear to me to indicate that such a position was the primitive one in the case of Vertebrates also.
 
I look upon the union of the sensory and motor nerve-fibres into mixed trunks (which occurs soon after their separate origin from the spinal cord, in the case of all Vertebrates except Amphioxus and the Cyclostomes) as a secondary condition, and maintain that it is caused especially by the following embryological influences : by the change in the position of the spinal cord and the muscular masses, and by the great increase in the amount of the connective substances.
+++++++++++++++++++++++++++++++++++++++++
 
Fig. 262. Cross section through the anterior part of the trunk of an embryo of Scyllium, after BALFOUR.
 
Between the dorsal wall of the trunk and its ventral wall, where the attachment of the stalk of the yolk-sac is cut, there is stretched a thick richly cellular mesentery, which completely divides the body-cavity into right and left halves. Within the mesentery the duodenum (du), from which the fundament of the pancreas (pan) is given off dorsally and the fundament of the liver (hp.d) ventrally, is twice cut through. In addition, the place where the vitelline duct [umbilical canal] (HHIC) joins the duodenum is visible.
 
sp.c, Spinal cord ; s.pg, ganglion of posterior root ; or, anterior root ; dn, dorsally directed nerve springing from the posterior root ; >np, muscle-plate ; mp', part of the muscle-plate already converted into muscles ; iiip.l, part of the muscle-plate which gives rise to the muscles of the limbs ; ill, nervus lateralis ; ao, aorta ; ch, chorda ; sy.g, sympathetic ganglion; ca.v, cardinal vein ; sp.n, spinal nerve ; sd, segniental (archiaephric) duct ; st, segmental tube.
 
+++++++++++++++++++++++++++++++++++++++++
 
Since the spinal cord comes to lie in deeper layers of the body far away from its place of origin, the dermal nerves must follow it, and therefore their origins are correspondingly farther separated from their terminations. Since also, on the other hand, the muscleplates grow around the neural tube, certain motor and sensory nerve-cords are brought near to each other in their passage to their peripheral distribution. And this will occur especially in all cases where the motor and sensory peripheral terminations lie at a great distance from the origin of the nerves out of the spinal cord, as, for example, in the case of the limbs. The mutual approximation of sensory and motor nerve-tracts thus brought about will finally lead to the formation of common tracts, according to the same principle of simplified organisation in accordance with which the blood-vessels also adapt themselves closely to the course of the nerves.
 
(c) The Development of the Sympathetic System.
 
The development of the sympathetic nervous system has as yet been investigated by only a few observers. BALFOUR first announced that it arose in connection with the cranial and spinal nerves, and therefore was, like the latter, really derived from the outer germlayer. In the Selachians he found the sympathetic ganglia (fig. 262 sy.y] as small enlargements of the chief trunks of the spinal nerves (sp.n) a little below their ganglia (s/>.#). In older embryos, according to BALFOUR'S account, they recede from the spinal ganglia, and then at a later period unite with one another, by the development of a longitudinal commissure, into a continuous cord (Grenzstrang).
 
The origin of the sympathetic system has been the most thoroughly studied by ONODI in researches covering several classes of Vertebrates. According to him the sympathetic ganglia arise directly, as BALFOUR suggested and as BEARD has also lately reiterated, from the spinal ganglia. The ventral ends of the spinal ganglia undergo proliferation, as is best seen in Fishes. The proliferated part detaches itself, and, as fundament of a sympathetic ganglion, moves ventrally. The fundaments of the individual segments are at first separate from one another. The cord (Grenzstrang) is a secondary product, produced by the growing out of the individual ganglia toward each other and the union of the outgrowths. Afterwards the sympathetic ganglia and plexuses of the body-cavity are derived from this part.
 
+++++++++++++++++++++++++++++++++++++++++
 
SUMMARY.
 
Central Nervous System.
 
1. The central nervous system is developed out of the thickened region of the outer germ- layer which is designated as the medullary plate.
 
2. The medullary plate is folded together to form the medullary tube (medullary ridges, medullary groove).
 
3. The formation of the neural tube exhibits three principal modifications : (a) Ainphioxus, (6) Petromyzon, Teleosts, (c) the remaining Vertebrates.
 
4. The lateral walls of the medullary tube become thickened, whereas the dorsal and ventral walls remain thin ; the latter come to occupy the depths of the anterior and posterior longitudinal fissures, and constitute the commissures of the lateral halves of the spinal cord.
 
5. The spinal cord at first fills the whole length of the vertebral canal, but it grows more slowly than the latter, and finally terminates at the second lumbar vertebra (explanation of the oblique course of the lumbar and sacral nerves).
 
6. The part of the neural tube which forms the brain becomes segmented into the three primary cerebral vesicles (primary forebrain vesicle, mid-brain vesicle, hind-brain vesicle).
 
7. The lateral walls of the fore-brain vesicle are evaginated to form the optic vesicles, the anterior wall to form the vesicles of the cerebrum.
 
8. The hind-brain vesicle is divided by constriction into the vesicles of the cerebellum and the medulla.
 
9. Thus from the three primary brain-vesicles there finally arise five secondary ones arranged in a single series one after the other (a) cerebral vesicle (that of the hemispheres), (6) between-brain vesicle with the laterally attached optic vesicles, (c) mid-brain vesicle, (cl) vesicle of the cerebellum, (e) vesicle of the medulla oblongata.
 
10. The originally straight axis uniting the brain-vesicles to one another later becomes at certain places sharply bent, in consequence of which the mutual relations of the vesicles are changed (cephalic flexure, pontal flexure, nuchal flexure). The cephalic or parietal protuberance at the surface of the embryo corresponds to the cephalic flexure, the nuchal protuberance to the nuchal flexure.
 
 
 
464 EMBRYOLOGY.
 
11. The separate parts of the brain are derivable from the live brain-vesicles ; the accompanying table (MiHALKOVlCS, SCHWALBE) gives a survey of the subject.
 
12. In the metamorphoses of the vesicles the following processes take place : (a) certain regions of the walls become more or less thickened, whereas other regions undergo a diminution in thickness and do not develop nervous substance (roof-plates of the third and fourth ventricles) ; (b) the walls of the vesicles are infolded ; (c) some of the vesicles (first and fourth) greatly exceed in their growth the remaining ones (bet ween- brain, mid-brain, after-brain, or medulla oblongata).
 
13. The four ventricles of the brain and the aqueduct us Sylvii are derived from the cavities of the vesicles.
 
14. Of the five vesicles that of the mid-brain is the most conservative and undergoes the least metamorphosis.
 
15. The vesicles of the between-brain and after-brain exhibit similar alterations : their upper walls or roof -plates are reduced in thickness to a single layer of epithelial cells, and in conjunction with the growing pia mater produce the choroid plexuses (anterior, lateral, posterior choroid plexus ; anterior, posterior brain-fissure).
 
16. The cerebral vesicle is divided by the development of the longitudinal (interpallial) fissure and the falx cerebri into lateral halves, the two vesicles of the cerebral hemispheres.
 
17. In Man the cerebral hemispheres finally exceed in volume all the remaining parts of the brain, and grow from above and from the sides as cerebral mantle over the other brain- vesicles (from the second to the fifth inclusive) or the brain-stalk.
 
18. In the folding of the walls of the hemispheres there are to be distinguished fissures and sulci.
 
19. The fissures (fossa Sylvii, fissura hippocampi, fissura choroidea, fissura calcarina, fissura occipitalis) are complete folds of the wall of the brain, by means of which there are produced deep incisions in the surface and corresponding projections into the lateral ventricles (corpus striatum, cornu Ammonis, fold of the choroid plexus, calcar avis).
 
20. The sulci are incisions limited to the cortical portion of the wall of the brain, and are deeper or shallower according to the time of their formation (primary, secondary, tertiary sulci).
 
21. In general the fissures appear earlier than the sulci.
 
22. The olfactory nerve is not equivalent to a peripheral nervetrunk, but, like the optic vesicle and optic nerve, a special part of the brain produced by an evagination of the frontal lobe of the cerebral hemisphere (lobus or bulbus olfactorius with tractus olfactorius). (Enormous development of the olfactory lobes in lower Vertebrates, Sharks, degeneration in Man. )
Peripheral Nervous System.
 
23. The spinal ganglia are developed out of a neural ridge (crest), which grows outward and downward from the raphe of the neural tube 011 either side between the tube and the primitive epidermis, and becomes thickened in the middle of each primitive segment into a ganglion.
 
24. The spinal ganglia therefore arise, like the neural tube itself, from the outer germ-layer.
 
25. The sympathetic ganglia of the longitudinal cord (Grenzstrang) are probably detached parts of the spinal ganglia.
 
26. Concerning the development of the peripheral nerve-fibres there are different hypotheses :
First hypothesis. The peripheral nerve-fibres grow out from the central nervous system and only secondarily unite with their peripheral terminal apparatus.
 
Second hypothesis. The fundaments of the peripheral terminal apparatus (muscles, sensory organs) and the central nervous system are connected from early stages of development by means of filaments which become nervefibres (HENSEN).
 
27. Anterior and posterior nerve-roots are developed on the spinal cord separately from each other, one ventrally, the other dorsally.
 
28. The cranial nerves arise in part like posterior, in part like anterior roots of spinal nerves.
 
29. The following cranial nerves with their ganglia, which are comparable with spinal ganglia, are developed out of a neural ridge which grows out from the raphe of the brain -vesicles : the trigeminus with the ganglion Gasseri, the acusticus and facialis with the ganglion acusticum and g. geniculi, the glossopharyngeus and vagus with the ganglion jugulare and g. nodosum.
 
30. The oculomotorius, trochlearis, abducens, hypoglossus, and accessorius are developed like ventral roots of spinal nerves.
 
31. The olfactory and optic nerves are metamorphosed parts of the brain.
 
 
 
+++++++++++++++++++++++++++++++++++++++++
 
II. The Development of the Sensory Organs, Eye, Ear, and Organ
of Smell.
 
As the outer germ-layer is the parental tissue of the central nervous system, so also does it form the substratum for the higher sensory organs, the eye, the ear, and the organ of smell. For it furnishes the sensory epithelium, a component which, in comparison with the remaining parts, derived from the mesenchyrna, is, it is true, of very small volume, but, notwithstanding, by far the most important both from a functional and a morphological point of view. Whether a sensory organ is adapted for seeing, hearing, smelling, or tasting depends primarily upon the character of its sensory epithelium, i.e., upon whether it is composed of optic, auditory, olfactory, or gustatory cells. But also morphologically the epithelial part is preeminent, because it is chiefly this which determines the fundamental form of the sensory organs and affords the fixed centre around which the remaining accessory components are arranged. The genetic connection with the outer germ-layer may be most clearly recognised in many Invertebrates, inasmuch as here the sensory organs are permanently located in the epidermis? whereas in Vertebrates, as is well known, they are, for the sake of protection, embedded in deep-lying tissues. I begin with the eye, and then proceed to the organ of hearing and that of smell.
 
A. The Development of the Eye.
 
As has already been stated in the description of the brain, the lateral walls of the primary fore-brain (figs. 234, 263) are evaginated
 
 
kh
 
 
Tcb
 
 
 
r.h tr
 
 
t/h
Fig. 263. Brain of a human embryo of the third week (Lg). Profile reconstruction, after His. yh, Cerebral vesicle; zh, between-brain vesicle; mh, mid-brain vesicle; kh, nh, vesicles of cere
bellum and medulla oblongata ; au, optic vesicle ; gb, auditory vesicle ; tr, inf undibulum ;
r/, area rhomboidalis ; nb, nuchal flexure ; kb, cephalic flexure.
 
and produce the primary optic vesicles (au), which are constricted off more and more and remain in connection with the between-brain
 
 
468
 
 
EMBRYOLOGY.
 
 
 
by means of a slender stalk only (fig. 204 A st). They possess spacious cavities within, which are connected with the system of brain-ventricles through the narrow canal of the stalk of the optic vesicle. In many Vertebrates, in which the central nervous system is formed as a solid structure, as in the Cyclostom.es and Teleosts, the optic vesicles are also without cavities ; these do not make their appearance until the central nervous system becomes a tube.
 
Since the brain is for a long time separated from the primitive epidermis by only an exceedingly thin sheet of connective tissue, the primary optic vesicles at the time of their evagination either apply themselves directly to the epidermis, as in the case of the Chick, or are separated from it by only a very thin intervening
layer, as in Mammals.
 
Upon each optic vesicle can be distinguished a lateral, a median, an upper and a lower wall. I designate as lateral that surface which reaches the epidermis at the surface of the body, as median the opposite wall joined with the stalk of the optic
 
 
+++++++++++++++++++++++++++++++++++++++++
 
Fig. 264. Two diagrams illustrating the development of the eye.
 
A, The primary optic vesicle (au), joined by a hollow
stalk (st) to the between-brain (zh), is invaginated as a result of the development of the lens-pit (Ig).
 
B, The lens-pit has become abstricted to form a lens
vesicle (Is). From the optic vesicle has arisen the optic cup with double walls, an inner (ib) and an outer (ab) ; 1st, stalk of the lens ; gl, vitreous body.
+++++++++++++++++++++++++++++++++++++++++
 
 
vesicle, and finally as lower the one which lies on a level with the floor of the between-brain. These designations will be useful in acquainting ourselves with the changes which the form of the optic vesicle undergoes during its imagination, which occurs at two places, namely, at its lateral and lower surfaces. One of the imaginations is connected with the development of the lens, the other with the formation of the vitreous body.
 
The first fundament of the lens appears in the Chick as early as the second day of incubation, in the Rabbit about ten days after the fertilisation of the egg. At the place where the epidermis passes over the surface of the primary optic vesicle (fig. 264 A Ig), it becomes slightly thickened and invaginated into a small pit (lenspit). The pit, by its deepening and by the approximation of its edges until they meet, is converted into a lens-vesicle (fig. 264 B Is], which for a time preserves its connection with its parental substratum, the epidermis, by means of a solid epithelial cord (1st). Upon being constricted off the lens-vesicle naturally pushes the adjacent lateral wall of the optic vesicle before it and folds the latter in against the median wall.
 
At the same time with the development of the lens, the primary optic vesicle is also invaginated from below along a line which stretches from the epidermis to the attachment of the stalk of the optic vesicle, and is even continued along the latter for some distance (tig. 265 aus). A loop of a blood-vessel from the enveloping connective tissue, embedded in soft, gelatinous substance (gl), here grows against the lower surface of the primary optic vesicle and its stalk, and pushes up before it the lower wall.
 
In consequence of the two invaginations the optic vesicle acquires the form of a beaker or cup, the foot of which is represented by its stalk (Sn). But the optic cup, as we can from this time forward designate the structure, exhibits two peculiarities. First, it has, as it were, a defect (fig. 265 aus) in its lower wall ; for there runs along the latter from the margin of the broad opening which embraces the lens (/) to the attachment of the stalk (Sn) a fissure (aus), which is caused by the development of the vitreous body (gl) and bears the name fcetal optic fissure [or choroid fissure\. At first it is rather wide, but then becomes narrower and narrower by the approximation of its edges and finally closed altogether. Secondly, the optic cup, like the toy called the cup of Tantalus, is provided with double walls, which are continuous with each other along the edge of the front opening and also along the fissure. They will henceforth be designated as inner (figs. 264 B and 265 ib) and outer (ab) layers; the former is the invaginated, the latter the uninvaginatecl part of the primary optic vesicle.
 
+++++++++++++++++++++++++++++++++++++++++
Fig. 265. Plastic representation of the optic cup with lens and vitreous body.
 
o.b, Outer wall of the cup ; lb, its inner wall ; h, cavity between the two walls, which later disappears entirely ; Sn, fundament of the optic nerve. (Stalk of the optic vesicle with a furrow on its lower surface.) aus, Optic [choroid] fissure ; yl, vitreous body ; I, lens.
+++++++++++++++++++++++++++++++++++++++++
 
 
 
 
At the beginning of the infolding the two layers are separated by a broad space (k), which leads into the third ventricle through the stalk of the vesicle (/Sn) ; but afterwards the space becomes reduced proportionally to the increase in the size of the vitreous body.
 
 
Finally outer and inner layers come to lie in close contact (fig. 2G(> pi and ?). The fundaments of the lens (le and If) and the vitreous body (g) constitute the contents of the cup. The vitreous body fills the bottom of the cup, the lens its opening.
 
In the process of itfvagination the stalk of the optic vesicle has
 
 
ch
 
 
U> !&3 "' <> ,> fijirj Q 'V..i'o>. ' J V,1;
' , f .A
 
 
r, ^
 
 
o * -. / . /
" -'
 
 
-'
.- ' - -. -"'
'-.-.-, rC~, - >{
- - , --' ^
- ;
 
 
 
 
 
5 '- - g .',u '; .>K^
> -' - ' : ' rV '; '' ' - ; '"-
% ;;: ' -V v
 
 
f& & ' ' "^--/V
 
 
 
Fig.'.266. Section through the optic fundament of an embryo Mouse, after KESSLER.
 
j>i, Pigniented epithelium of the eye (outer lamella of the optic cup, or secondary optic vesicle) ; r, retina (inner lamella of the optic cup) ; /M, marginal zone of the optic cup, which forms the pars ciliaris et iridis retinas ; y, vitreous body with blood-vessels ; tv, tunica vasculosa lentis ; bk, blood-corpuscles ; ch, choroidea ; If, lens-fibres ; le, lens-epithelium ; I' ', zone of the lens-fibre nuclei ; It, fundament of the cornea ; he, external corneal epithelium.
 
 
 
also changed its form. Originally it is a small tube with an epithelial wall, but afterwards it becomes an inverted trough with double walls, inasmuch as its lower surface participates in the invagination caused by that growth of connective tissue which toward the periphery furnishes the vitreous body. Later the edges of the trough bend together and fuse with each other. In this way the connective
 
 
THE ORGANS OF THE OUTER GERM-LAYER. 471
tissue cord, with the arteria centralis retina?, which traverses it, is enclosed within the stalk, which is now a quite compact structure.
 
Finally the tissue of the intermediate layer, apart from its producing the vitreous body, takes a further active share in the development of the whole eye, inasmuch as that portion of it which is adjacent to the optic cup is differentiated into the choroid membrane (tig. 266 ch) and the sclerotica of the eye.
 
After having thus delineated briefly the source of the most important components of the eye, it will be my purpose in what follows to pursue in detail the development of each part separately. I shall begin with the lens and vitreous body, then pass to the optic cup, and at that point add an account of the formation of the choroid membrane and the sclerotica, as well as the optic nerve ; in a final section I shall treat of the organs that are accessory to the optic cup the eye-lids, the lachrymal glands and their ducts.
 
(a) The Development of the Lens.
 
When the lens- vesicle has been completely constricted off from the primitive epidermis (fig. 264 B Is), it possesses a thick wall, which is composed of two or three layers of epithelial cells, and encloses a cavity that in Birds is partially filled with fluid, but in the case of Mammals by a mass of small cells. The mass of cells is the result of a proliferation of the most superficial flattened sheet of the primitive epidermis ; it is without importance in the further development a transient mass, that soon degenerates and is absorbed when the lensfibres are developed. (ARNOLD, MIHALKOVICS, GOTTSCHAU, KORANYI.)
Externally the epithelial vesicle is sharply limited by a thin membrane, which is afterwards thickened into the capsule of the lens (capsula lentis). There are two opposing views in regard to its development. According to one, the capsule is a cuticular structure, that is to say, a structure secreted by the cells of the lens at their bast's ; according to the other view it is the product of a connectivetissue layer, to be described more fully hereafter, enveloping the lens-vesicle.
 
In later stages considerable differences arise in the development of the anterior and posterior walls (fig. 266). In the region of the anterior wall the epithelium (le) becomes more and more flattened ; the cylindrical cells are converted into cubical elements, which are preserved throughout life in a single layer and constitute the so-called lens-epithelium in the lens of the adult (fig. 266 le). In the posterior
 
 
472
 
 
EMBRYOLOGY.
 
 
 
wall, on the contrary, the cells increase greatly in length (iig. 2G6 (/') and grow out into long fibres, which form a protuberance projecting into the cavity of the vesicle. The fibres stand perpendicular to the posterior wall, are longest in its middle, become shorter towards the equator of the lens (figs. 266, 267 Z), and finally appear as ordinary
 
 
- ...'" ". /'v.- A
>. - , ' .. * -. .
 
 
 
 
, ;_
 
 
letv k d h he
 
 
Fig. 267. Part of a section through the fundament of the eye of an embryo Mouse. Somewhat older stage than that shown in fig. 266. After KESSLER.
 
A part of the lens, the rim of the optic cup, the cornea, and the anterior chamber of the eye. pi, 1'igmented epithelium of the eye ; r, retina ; rz, marginal zone of the optic cup; y, bloodvessels of the vitreous body in the vascular capsule of the lens ; tv, tunica vasculosa lentis ; x, connection of the latter with the choroid membrane of the eye ; I', transition of the lensepithelium into the lens-fibres ; Ic, lens-epithelium ; k, anterior chamber of the eye ; d, DJESCEMET'S membrane ; //, cornea ; he, corneal epithelium.
 
cylindrical cells; these in turn become still shorter and are continuous with the cubical cells (le) of the lens-epithelium. In this way there exists at the equator a zone of transition between the fibrous portion and the epithelial part of the lens.
 
The next change consists in the elongation of the fibres until their anterior ends have reached the epithelium (fig. 267). Consequently
 
 
THE ORGANS OF THE OUTER GERM-LAYER.
 
 
 
473
 
 
the vesicle has now become a solid structure, which, as the lens-core, furnishes the foundation of the lens of the adult.
 
The further increase in the size of the lens is an appositional growth. Around the core first formed arise new lens-fibres, which are arranged parallel to the surface of the organ and are united into coats. These lie in layers one over another, which in macerated lenses may be detached like the coats of an onion. All fibres (fig. 268 If, If") extend from the anterior to the posterior surface, where their ends meet one another along regular lines, which in the embryo and the new-born animal have the form of two three-rayed figures, the so-called stars of the lens (fig. 268 vst and list). These exhibit the peculiarity that the rays of the anterior face alternate with those of the posterior face, so that the three rays of one star halve the spaces between the three rays of the other.
 
In the adult the figure becomes more complicated, because lateral rays arise on
 
 
each of the three chief rays.
 
How have the newly deposited fibres been formed ? Their origin is ultimately to be referred to the lens-epithelium of the front surface of the organ. In these cells figures of nuclear division can
frequently be observed even in late stages of development. The cells which result from division serve to replace those which grow out into lens-fibres, and are placed upon the already formed layers. The new formation takes place only at the equator of the lens (fig. 267) in the zone of transition (I'} previously described, where, in the adult as well as in the recently born animal, the cubical epithelial cells gradually merge into cylindrical and fibrous elements, as one can convince himself from any properly directed section.
 
In the adult, as is well known, there exist no special provisions for the nutrition of the lens, which, after attaining full size, is not much altered, and certainly undergoes only a slight metastasis. With the embryo it is otherwise. Here a more active growth necessitates a
 
 
 
Fig. 268. Diagram of the arrangement of the lens-fibres.
 
One sees the opposite positions of the anterior (vsl) and the posterior (/<*<) stars of the lens. if, Course of the lens-fibres on the anterior surface of the lens and their termination at the anterior star of the lens ; If", continuation of the same fibres Co the posterior star on the posterior surface.
 
 
 
474 EMBRYOLOGY.
 
special apparatus for nutrition. This is furnished in Mammals by the tunica vasculosa lentis (figs. 266, 267 tv}. By this is understood a highly vascular connective -tissue membrane, which envelops the outer surface of the capsule of the lens on all sides. In Man it is already distinctly developed as early as the second month. Its vessels are derived from those of the vitreous body. Consequently on the posterior wall of the lens they are large. These, resolved into numerous fine branches, bend around the equator of the lens, and run toward the middle of the anterior surface, where they form terminal loops, and also unite with blood-vessels of the choroid membrane (fig. 267 x).
 
Separate parts of the nourishing membrane of the lens, having been discovered at different times by various investigators, have received special names, as membrana pupillaris, m. capsulo-pupillaris, m. capsularis. The first to be observed was the membrana pupillaris, the part of the vascular membrane which is situated behind the pupil on the anterior surface of the lens. It was the most easily found, because occasionally it persists even after birth as a fine membrane closing the pupil, and producing atresia pupillw congenita. Later it was found that the membrana pupillaris is also continued laterally from the pupil on the anterior face of the lens, and this part was called membrana capsulo-pupillaris. Finally it was discovered that the blood-vessels are spread out on the posterior wall of the lens the membrana capsularis. It is superfluous to retain all these names, and most suitable to speak of a nutritive membrane of tlie lens, or a membrana vasculosa lentis.
 
This vascular membrane attains its greatest development in the seventh month, after which it begins to degenerate. Ordinarily it has entirely disappeared before birth ; only in exceptional cases do some parts of it persist. Toward the end of embryonic life, moreover, the chief growth of the lens itself has ceased. For according to weighings carried on by the anatomist HUSCHKE, it has a weight of 123 milligrammes in the new-born child, and 190 milligrammes in the adult, so that the total increase which the organ undergoes during life amounts to only 67 milligrammes.
 
(b) The Development of the Vitreous Body.
 
The question of the development of the vascular membrane of the lens leads to that of the vitreous body. As was previously mentioned, there grows out from the embryonic connective tissue a process with a vascular loop, which makes its way into the primary optic vesicle and its stalk (fig. 265). The vascular loop then begins to send out new lateral branches ; likewise the connective-tissue matrix, which is at first scanty, increases greatly and is characterised by its extraordinarily slight consistency and its large proportion of water (figs. 266, 267 g). There are also to be found in it here and there isolated stellate connective -tissue cells ; but these disappear later, and in their place occur migratory cells (leucocytes), which are assumed to be immigrated white blood-corpuscles.
 
There are two opposing views regarding the nature and development of the vitreous body. According to KESSLER we have to do, not with a genuine connective substance, but with a transudation,a fluid, which has been secreted from the vascular loops ; the cells are from, the beginning simply immigrated white blood -corpuscles KOLLIKER, SCHWALBE, and other investigators, on the contrary, regard the vitreous body as a genuine connective substance. According to SCHWALBE'S definition, to which I adhere, it consists of an exceedingly watery connective tissue, whose fixed cells have early disappeared, but whose interfibrillar substance infiltrated with water is traversed by migratory cells. The vitreous body is afterwards surrounded by a structureless membrane, the membrana hyaloidea, which, according to some investigators, belongs to the retina, although, according to the researches of SCHWALBE, this view is not admissible.
 
The vitreous body, which in the adult is quite destitute of bloodvessels, is bountifully supplied with them in the embryo. They come from the arteria centralis retince, the branch of the ophthalmic artery that runs along the axis of the optic nerve.
 
The arteria centralis retinae is prolonged from the papilla of the optic nerve as a branch which is designated as the arteria hyaloidea. This, resolved into several branches, runs forward through the vitreous body to the posterior surface of the lens, where its numerous terminal ramifications spread out in the tunica vasculosa, and at the equator pass over on to the anterior face of the lens. During the last months of embryonic life the vessels of the vitreous body, together with the nutritive membrane of the lens, undergo degeneration ; they entirely disappear, with the exception of a rudiment of the chief stem, which runs forward from the entrance of the optic nerve to the anterior surface of the vitreous body, and during the degeneration is converted into a canal filled with fluid, the canalis liyaloideus.
 
 
 
476
 
 
KM BRYOLOGY.
 
 
 
(c) The Development of the Secondary Optic Cup and the, Goats
of the Eye.
 
The optic cup is further metamorphosed at the same time with
the layer of mesenchyma which envelops it, and which furnishes the middle and outer tunics of the eye, so that it seems to be desirable to treat of both at the same time. I begin with the stage represented in figures 266 and 269. The optic cup still possesses at this time a broad opening, in which the lens (le) is embraced. The latter is either separated from the epidermis by only an exceedingly thin sheet of mesenchyma, as in the Mammals (fig. 266), or its anterior face is in immediate contact with the epidermis, as in the Chick (fig. 269). In the beginning, therefore, there is no separate fundament for the cornea between lens and epidermis ; moreover, both the anterior chamber of the eye and the iris are wanting.
 
The fundament of the cornea is derived from the surrounding mesenchyma, which, as a richly cellular tissue, envelops the eyeball. In the Chick (fig. 269), as early as the fourth day, it grows in between the epidermis and the front surface of the lens as a thin sheet (bi}. At first this sheet is structureless, then numerous mesenchymatic cells migrate into it from, the margin and become the corneal corpuscles. These produce the cornea! fibres in the same way that embryonic connective-tissue cells do the connectivetissue fibres, while the structureless sheet in part goes to form the cementing substance between them, and in part is preserved on the anterior and posterior walls as thin layers
 
 
 
Fig. 269. Section through the anterior portion of the fundament of the eye in an embryo Chick on the fifth day of incubation,
after KESSLEE.
 
he, Corneal epithelium ; h, lens-epithelium ; h, structureless sheet of the corneal fundament ; li, embryonic connective stibstance, which envelops the optic cup and, penetrating between lensepithelium (/c) and corneal epithelium (Ac), furnishes the fundament of the cornea ; ah, outer, ib, inner layer of the secondary optic cup.
 
 
 
THE ORGANS OF THE OUTER GERM-LAYER. 477
destitute of cells ; these layers, undergoing chemical metamorphosis, become respectively the membrana elastica anterior and the membrane of DESCEMET.
 
The internal endothelium of the cornea is developed at an extraordinarily early epoch in the Chick. For as soon as the structureless sheet previously mentioned (fig. 269 A) has attained a certain thickness, mesenchymatic cells proceeding from the margin spread themselves out on its inner surface as a single-layered thin cell-membrane. With this begins also the formation of the anterior chamber of the eye. For the thin fundament of the cornea, which at first lay in immediate contact with the front surface of the lens, now becomes somewhat elevated from the latter, and separated from it by a fissure-like space filled with fluid (humor aqueus). The fissure is first observable at the margin of the secondary optic cup, and spreads out from this region toward the anterior pole of the lens. The anterior chamber of the eye does not, however, acquire a greater size and its definite form until the development of the iris.
 
Two opposing views exist concerning the origin of the structureless sheet which has been described as constituting the first fundament of the cornea in the Chick. According to KESSLER it is a product of the secretion of the epidermis, whereas the corneal corpuscles migrate in from the mesenchyma. In his opinion, therefore, the cornea is composed of two entirely different fundaments. According to KOLLIKER, on the contrary, all its parts are developed out of the mesenchyma, and the homogeneous matrix simply outstrips the cells in its growth and extension.
 
In Mammals (fig. 266) the conditions differ somewhat from those of the Chick ; for as soon as the lens-vesicle in Mammals is fully constricted off, it is already enveloped by a thin sheet of mesenchyma (fi) with few cells, which separates it from the epidermis. The thin layer is rapidly thickened by the immigration of cells from the vicinity. Then it is separated into two layers (fig. 267), the pupillar membrane (tv) and the fundament of the cornea (A). The former is a thin, very vascular membrane lying on the anterior surface of the lens ; its network of blood-vessels communicates on the one hand posteriorly with the vessels of the vitreous body, together with which it constitutes the tunica vasculosa lentis, and on the other anastomoses at the margin of the optic cup with the vascular network of the latter. The fundament of the cornea is first sharply delimited from the pupillary membrane at the time when the anterior chamber of the eye (&) is formed as a narrow fissure, which gradually increases in extent with the appearance of the iris.
 
 
 
478
 
 
EMBRYOLOGY.
 
 
 
pi I',
 
 
 
1. 2. 3. 1 L> sch D
 
 
Fig. 270. Section through the margin of the optic cup of an embryo Turdus musicus,
after KESSLER.
 
/, Retina ; pi, pigmented epithelium of the retina (outer lamella of the optic cup) ; It, connective-tissue envelope of the optic cup (choroidea and sclera) ; * ora serrata (boundary between the marginal zone and the fundus of the optic cup) ; ck, ciliary body ; 1, 2, 3, iris ; 1 and 2, inner and outer lamellae of the pars iridLs i*etin?e ; 3, connective-tissue plate of the iris ; Ip, ligamentum pectinatum iridis ; sch, canal of SCHLEMM ; D, DESCEMET'S membrane ; h, cornea ; he, corneal epithelium.
 
 
 
During those processes the condition of the optic cup itself has also changed. Its outer and inner lamellae continually become more and more unlike. The former (figs. 2G6, 2G7 pi) remains thin and composed of a single layer of cubical epithelial cells. Black pigment granules are deposited in this in increasing abundance, until finally the whole lamella appears upon sections as a black streak. The inner layer (?), on the contrary, remains entirely free from pigment, with the exception of a part of the marginal zone ; the cells, as in the wall of the brain vesicles, become elongated and spindleshaped, and lie in many superposed layers.
 
Moreover the bottom of the cup and its rim assume different conditions, and hasten to fulfil different destinies; the former is converted into the retina, the latter is principally concerned in the production of the ciliary body and the iris.
 
The edge of the cup (fig. 267 rz, fig. 270*, and fig. 271) becomes very much reduced in thickness by the cells of its inner layer arranging themselves in a single sheet, remaining for a time cylindrical, and then assuming a cubical form. But with its reduction in thickness there goes hand in hand an increase in its superficial extent. Consequently the margin of the optic cup now grows into the anterior chamber of the eye between cornea and tbe anterior surface of the lens, until it has nearly reached the middle of the latter. Then it at last bounds only a small orifice which leads into the cavity of the optic cup the pupil. The pigment layer of the iris is derived from the marginal region of the cup, as KESSLER first
 
 
THE ORGANS OF THE OUTER GERM-LAYER.
 
 
 
479
 
 
 
 
 
,7,
 
 
 
showed (fig. 270 l and 2 ). Pigment granules are now deposited in the inner epithelial layer, just as in the outer lamella, so that at last the two are no longer distinguishable as separate layers.
 
The mesenchymatic layer which envelops the two epithelial lamella keeps pace with them in their superficial extension. It becomes thickened and furnishes the stroma of the iris with its abundant non-striated muscles and blood-vessels (fig. 270 s ). In Mammals (fig. 267 x) this is for a time continuous with the tunica vasculosa lentis (tv), in consequence of which the pupil in embryos is closed by a thin vascular connective - tissue membrane, as has already been stated.
 
The part of the optic cup which is adjacent to the pigment layer of the iris and surrounds the equator of the lens, and which likewise belongs to the attenuated marginal zone of the cup (fig. 270 c&), undergoes an interesting alteration. In conjunction with the neighboring layer of connective substance, it is converted into the ciliary body of the eye. This process begins in the Chick on the
ninth or tenth day of incubation (KESSLER), in Man at the end of the second or beginning of the third month (KOLLIKER). The attenuated epithelial double lamella of the cup, in consequence of an especially vigorous growth in area, is laid into numerous, [nearly] parallel short folds, which are arranged radially around the equator of the lens. As in the iris, so here, the adjacent mesenchymatic layer participates in the growth and penetrates between the folds in the form of fine processes. A cross section through the foldeel part of the optic cup of a Cat embryo 10 cm. long (fig. 271) affords information concerning the original form of these processes in Mammals. It shows that the individual folds are very thin and enclose within them only a very small amount of embryonic connective tissue (bi ') with fine capillaries, and that, unlike the pigment epithelium of the iris, only the outer of the two epithelial layers (ab) is pigmented,
 
 
Fig. 271. Cross section through the ciliary par of the eye of an embryo Cat 10 cm. long, after KESSLEB.
 
Three ciliary processes formed by the folding of the optic cup are shown, li, Connective-tissue part of the ciliary body ; ib, inner layer, a I. outer pigmented layer of the optic cup li', sheet of connective tissue that has penetrated into the epithelial fold.
 
 
 
480 EMBRYOLOGY.
 
whereas the inner (ib) remains unpigmented even later and is composed of cylindrical cells.
 
Subsequently tho ciliary processes become greatly thickened through increase of the very vascular connective-tissue framework, and acquire a firm union with the capsule of the lens through the formation of the zonula Zinnii. In Man the latter is formed, according to KOLLIKER'S account, during the fourth month, in a manner that here, as well as in other Mammals, is still incompletely explained.
 
LiEBEEKi'JKN remarks that the zonula is distinctly recognisable in eyes which have attained half their definite size. If one takes out of an eye the vitreous body together with the lens, and then removes the latter by opening the capsule on the front side, the margin of the capsule appears surrounded by blood-vessels which pass from the posterior over on to the anterior surface.
 
" At the places where the processus ciliares are entirely removed, tufts of fine fibres are to be seen which correspond to, and fill up, the depressions between the ciliary processes ; but between these tufts is also to be seen a thin layer of the same kind of finely striate masses, which must have lain at the same level as the ciliary processes." Furthermore LIEBERKUKN states that " there lie within this striated tissue numerous cell-bodies of the same appearance as those that are found elsewhere in the embryonic vitreous body at a later period."
ANG-ELUCCI believes that the zonula arises from the anterior part of the vitreous body ; at the time when iris and ciliary processes are developed he finds the vitreous body traversed by fine fibres, which extend from the ora serrata to the margin of the lens. He describes as lying between the fibres sparse migratory cells, which are maintained, however, to have no share in the formation of the fibres.
 
The fundus of the optic cup (figs. 266, 267, 270) furnishes the most important part of the eye the retina. The inner lamella of the cup (r) becomes greatly thickened, and, in consequence of its cells being elongated into spindles and overlapping one another in several layers, acquires an appearance similar to that of the wall of the embryonic brain. Subsequently it becomes marked off by an indented line, the ora serrata (at the place indicated by a star in fig. 270), from the adjoining attenuated part of the optic vesicle, which furnishes the ciliary folds. It also early acquires at its two surfaces a sharp limitation through the secretion of two delicate membranes : on the side toward the fundament of the vitreous body it is bounded by the membrana limitans interim ; on that toward the outer lamella, which becomes pigmented epithelium, by the membrana limitans externa.
 
In the course of development its cells, all of which are at first alike, become specialised in very different ways, as a result of which there are produced the well-known layers distinguished by MAX SCHULTZE. I shall not go into the details of this histological differentiation, but shall mention some further points of general importance.
 
As WILHELM MULLER in his " Stammesentwicklung des Sehorgans der Wirbelthiere " has clearly shown, the development of the originally similar epithelial cells of the retina takes place in all Vertebrates in two chief directions : a part of them become sensory epithelium and the specific structures of the central nervous system ganglionic cells and nerve-fibres ; another part are metamorphosed into supporting and isolating elements into MULLER'S radial fibres and the granular [reticular or molecular] layers, which can be grouped together as epithelial sustentative tissue (fulcrum). Finally, with the descendants of the epithelium are associated connective-tissue elements, which grow from the surrounding connective tissue into the epithelial layer for its better nutrition, in the same manner as in the central nervous system. These ingrowths are branches of the arteria centralis retinae with their extremely thin connective-tissue sheaths. The Lampreys alone form an exception, their retina remaining free from blood-vessels. In all other Vertebrates bloodvessels are present, but they are limited to the inner layers of the retina, leaving the outer granular (Kb'rner) layer and that of the rods and cones free ; the latter have been distinguished as sensory epitheliuni from the remaining portions with their nerve-fibres and ganglionic cells the brain-part of the retina.
 
Of all the parts of the retina the layer of rods and cones is the last to be developed. According to the investigations of KOLLIKER, BABUCHIN, MAX SCHULTZE, and W. MULLER, it arises as a product of the outer granular (Korner) layer, which, composed of fine spindle-shaped elements, is held to be, as has been stated, the essential sensory epithelium of the eye. In the Chick the development of the rods and cones can be made out on the tenth day of incubation. MAX SCHULTZE states concerning young Cats and Rabbits, which are born blind, that the fundament of the rods and cones can be distinguished for the first time in the early days after birth ; in other Mammals and in Man, on the contrary, they are formed before birth.
 
In all Vertebrates, as long as rods and cones are not present, the inner layer of the optic cup is bounded on the side toward the outer layer by an entirely smooth contour, due to the membrana limitans externa. Then there appear upon the latter numerous, small, lustrous elevations, which have been secreted by the outer granules or visual cells. The elevations, which consist of a protoplasmic substance and are stained red in carmine, become elongated and acquire the form of the inner limb of the retinal element. Finally there is formed at their outer ends the outer limb, which MAX SCHULTZE and W. MULLER compare to a cuticular product, on account of its lamellate structure.
 
Inasmuch as the rods and cones of the retinal cells grow out in this way beyond the membrana limitans externa, they penetrate into the closely applied outer lamella of the optic cup, which becomes the pigmented epithelium of the retina (figs. 266, 267, 270 pi} ; their outer limbs come to lie in minute niches of the large, hexagonal pigment-cells, so that the individual elements are separated from one another by pigmented partitions.
 
A few additional words concerning the connective tissue enveloping the fundament of the optic cup. It acquires here, as on the ciliary body and the iris, a special, and for this region characteristic, stamp. It is differentiated into vascular [choroid] and fibrous [sclerotic] membranes, which in Man are distinguishable in the sixth week (KOLLIKER). The former is characterised by its vascularity at an early period, and develops on the side toward the optic cup a special layer, provided with a fine network of capillary vessels, the membrana choriocapillaris, for the nourishment of the pigment-layer and the layer of rods and cones, which have no blood-vessels of their own. It further differs from the ciliary body in the fact that at
/ 4/
the fundament of the optic cup the choroid membrane is easily separable from the adjoining membranes of the eye, whereas in the ciliary body a firm union exists between all the membranes.
 
If we now glance back at the processes of development last described, one thing will appear clear to us from this short sketch : that the changes in the form of the secondary optic cup are of preeminent importance for the origin of the individual regions of the eye. Through different processes of growth, which have received a general discussion in Chapter IV., there have been formed in the cup three distinct portions. By means of an increase in thickness and various differentiations of the numerous cell-layers, there is formed the retina ; by an increase of surface, on the contrary, is produced an anterior, thinner part, which bounds the pupil and is subdivided into two regions by the formation of folds in the vicinity of the lens. From the folded part, which joins the retina at the ora serrata, is
 
 
THE ORGANS OF THE OUTER GERM-LAYER. 483
formed the epithelial lining of the ciliary body ; from the thin portion which surrounds the pupil and which remains smooth, the pigniented epithelium (uvea) of the iris. Consequently there are now to be distinguished on the secondary optic cup three regions, as retinal, ciliary, and iridal parts. To each of these territories the contiguous connective tissue, and especially the part which becomes the middle tunic of the eye, is adapted in a particular manner ; here it furnishes the connective- tissue plate of the iris with its non-striated musculature, there the connective-tissue framework of the ciliary body with the ciliary muscle, and in the third region the vascular choroidea with the choriocapillaris and lamina fusca.
 
In the development of the optic cup there arose on its lower wall a fissure (fig. 265 cms), which marks the place at which the fundament of the vitreous body grew into the interior of the cup. What is the ultimate fate of this fissure, which is usually referred to in the literature as choroid fissure 1
It is for a time easily recognisable, after pigment has been deposited in the outer lamella of the optic cup. It then appears on the lower median side of the eyeball as a clear, unpigmented streak, which reaches forward from the entrance of the optic nerve to the margin of the pupil.
 
The name choroid fissure takes its origin from this phenomenon. It was given at a time when the formation of the optic cup was not adequately known, when the pigmented epithelium was still referred to the choroidea. Therefore in the absence of pigment along a clear streak on the under side of the eyeball it was supposed that a defect of the choroidea a choroid fissure had been observed.
 
The clear streak afterwards disappears. The fissure of the eye is closed by the fusion of its edges and the deposition of pigment in the raphe. In the Chick this takes place on the ninth day, in Man during the sixth or seventh week.
 
In still another respect is the choroid fissure noteworthy.
 
In many Vertebrates (Fishes, Reptiles, Birds) a highly vascular process of the choroidea grows through the fissure, before its closure, into the vitreous body and there forms a lamellar projection, which extends from the optic nerve to the lens. In Birds it has received the name " pecten," because it is folded into numerous parallel ridges. It consists almost entirely of the walls of blood-vessels, which are held together by a small amount of a black pigmented connective tissue.
 
In Mammals such a growth into the vitreous body is wanting.
 
The closure of the choroid fissure takes place at an early period and completely.
 
Occasionally in Man the normal course of development is interrupted, so that the margins of the choroid fissure remain apart. The usual consequence of this is a defective development of the vascular tunic of the eye at the corresponding place an indication of the extent to which the development of the connective-tissue envelope is dependent on the formative processes of the two epithelial layers, as has already been stated. Both retinal and choroidal pigment are therefore wanting along a streak which begins at the optic nerve, so that the white solera of the eye shows through to the inside and can be recognised in examinations with the ophthalmoscope. When the defect reaches forward to the margin of the pupil, a fissure is formed in the iris which is easily recognised upon external observation of the eye. The two structures resulting from this interrupted development are distinguished from each other as choroidal and iridal fissures (coloboma choroidere and coloboma iridis).
 
 
 
(d) The Development of the Optic Nerve.
 
The stalk of the optic vesicle (fig. 272), by which the vesicle is united with the between-brain, is in direct connection with both
lamellae of the optic cup, the primary optic vesicle having been infolded from below by the fundament of the vitreous body to form the cup. Its dorsal wall is continuous with the outer lamella or pigment-epithelium of the retina ; its ventral wall is prolonged into the inner lamella, which becomes the retina. Thus, aside from the formation of the vitreous body, the development of a choroid fissure also has a significance in view of the persistence of the direct connection between retina and optic nerve. For if we conceive the optic vesicle invaginated merely at its anterior face by the lens, the wall of the optic nerve would be continued into the outer, uninvaginated lamella only; direct connection with the retina itself, or the invaginated part, would be wanting.
 
 
 
 
(il'K
 
 
Fig. 272. Plastic representation of the optic cup with lens and vitreous body.
 
ab, Outer wall of the cup; ib, its inner wall ; h, space between the two walls, which afterwards entirely disappears ; Sn, fundament of the optic nerve (stalk of the optic vesicle with groove-formation along its lower face) ; ims, choroid fissure ; yl, vitreous body ; I, lens.
 
 
 
THE ORGANS OF THE OUTER GERM-LAYER. 485
Originally the optic nerve is a tube with a small lumen, which unites the cavity of the optic vesicle Avith the third ventricle (tig. 264 A). It is gradually converted into a solid cord. In the case of most Vertebrates this is produced simply by a thickening of the walls of the stalk, due to cell-proliferation, until the cavity is obliterated. In Mammals only the larger portion, that which adjoins the brain, is metamorphosed in this manner ; the smaller part, that which is united with the optic vesicle, is, on the contrary, infolded by the prolongation of the choroid fissure backward for some distance, whereby the ventral wall is pressed in against the dorsal. Consequently the optic nerve here assumes the form of a groove, in which is imbedded a connective-tissue cord with a blood-vessel that becomes the arteria centralis retinae. By the growing together of the edges of the groove, the cord afterwards becomes completely enclosed.
 
For a time the optic nerve consists exclusively of spindle-shaped, radially arranged cells in layers, and resembles in its finer structure the wall of the brain and the optic vesicle. Different views are held concerning its further metamorphoses, and especially concerning the origin of nerve-fibres in it. Differences similar to those concerning the origin of the peripheral nerve-fibres are maintained. Upon this point three theories have been brought forward.
 
According to the older view, which LTEBERKUHN shares, the optic fibres are developed in loco by the elongation of the spindle-shaped cells. According to His, KOLLIKER, and W. MULLER, 011 the contrary, the wall of the optic vesicle furnishes the sustentative tissue only, whereas the nerve-fibres grow into it from outside, either from the brain toward the retina (His, KOLLIKER), or in the reverse direction (MULLER). The stalk of the optic vesicle would constitute, according to this view, only a guiding structure as it were would predetermine the way for its growth. When the ingrowth has taken place, the sustentative cells are, as KOLLIKER describes them, arranged radially and so united with one another that they constitute a delicate framework with longitudinally elongated spaces. In the latter are lodged the small bundles of very fine non-nuclear nervefibres and numerous cells, arranged in longitudinal rows, which likewise belong to the epithelial sustentative tissue and help to complete the trestle-work.
 
The embryonic optic nerve is enveloped in a connective-tissue sheath, which is separated, as in the case of the brain and secondary optic cup, into an inner, soft, vascular and an outer compact
 
 
486 EMBRYOLOGY.
 
fibrous layer. The former, or the pial sheath, unites the pia mater of the brain and the choroid membrane of the eye ; the latter, or the dural sheath, is a continuation of the dura mater and at the eyeball becomes continuous with the sclerotica. Later the optic nerve acquires a still more complicated structure, owing to the fact that vascular processes of the pial sheath grow into it and provide the nerve-bundles and the epithelial sustentative cells belonging to them wit] i connective-tissue investments.
 
As has been previously stated, the direction in which optic fibres grow into the stalk of the optic vesicle is still a subject of controversy. His, with whom KOLLIKER is in agreement, maintains that they grow out from groups of ganglionic cells (thalamus opticus, corpora quadrigemina), and are only secondarily distributed in the retina. He supports his view on the one hand by the agreement in this particular which exists with the development of the remaining peripheral nerves, and on the other by the circumstance that the nerve-fibres are first distinctly recognisable in the vicinity of the brain.
 
W. MULLEE, on the contrary, believes that the outgrowth takes place in the opposite direction ; he maintains that the nerve-fibres arise as prolongations of the ganglionic cells located in the retina, and that they enter into union with the central nervous apparatus only secondarily. He is strengthened in his opinion by the conditions in Petromyzon, which he declares to be one of the most valuable objects for the solution of the controversy concerning the origin of the optic nerve. I refer, moreover, in connection with this controversy, to the section which treats of the development of the peripheral nervous system (p. 452).
 
(e) The Development of the Accessory Apparatus of the Eye.
 
There are associated with the eyeball auxiliary apparatus, which serve in different ways for the protection of the cornea : the eyelids with the Meibomian glands and the eyelashes, the lachrymal glands and the lachrymal ducts.
 
The eyelids, the upper and under, are developed at an early period by the formation, at some distance from the margin, of the cornea, of two folds of the skin, which protrude beyond the surface. The folds grow over the cornea from above and below until their edges meet and thus produce in front of the eyeball the conjunctival sac, which opens out through the fissure between the lids. The sac derives its name from the fact that the innermost layer of the lid-fold, which is reflected on to the anterior surface of the eyeball at the fornix conjuiictme, is of the nature of a mucous membrane, and is designated as the conjunctiva, or connecting membrane, of the eye.
 
In many Mammals and likewise in Man there is during embryoniclife a temporary closure of the conjunctival sac. The edges of the lids
 
 
THE ORGANS OF THE OUTER GERM-LAYER. 487
become united throughout their whole extent, their epithelial investments fusing with each other. In Man the concrescence begins in the third month, and usually undergoes retrogression a short time before birth. But in many Reptiles (Snakes) the closure is permanent. Thus a thin transparent membrane is formed in front of the cornea.
 
In Man during the concrescence of the eyelids there are developed at their margins the Meibomian glands. The cells of the rete Malpighii begin to proliferate and to send into the middle connectivetissue plate of the eyelid solid rods, which afterwards become covered with lateral buds. The glands, at first entirely solid, acquire a lumen by the fatty degeneration and dissolution of the axial cells.
 
At about the time of the development of the Meibomian glands, the formation of the eyelashes takes place ; this corresponds with the development of the ordinary hair, and therefore will be considered along with the latter in a subsequent section of this chapter.
 
In most of the Vertebrates there is associated with the upper and under lids still a third, the nictitating membrane or membrana nictitaiis, which is formed at the inner [median] side of the eye as a vertical fold of the conjunctiva. In Man it is present only in a rudimentary condition as plica semilunaris. A number of small glands which are developed in it produce a small reddish nodule, the caruncula lacrymalis.
 
The lachrymal gland is an additional auxiliary organ of the eye, which is destined to keep the sac of the conjunctiva moist and the anterior surface of the cornea clean. In Man it is developed in the third month through the formation of buds from the epithelium of the conjunctival sac on the outer side of the eye, at the place where the conjunctiva of the upper lid is continuous with that of the eyeball. The buds form numerous branches, and are at first solid, like the Meibomian glands, but gradually become hollow, the cavity beginning with the chief outlet and extending toward the finer branches.
 
A special efferent lachrymal apparatus, which leads from the inner angle of the eye into the nasal cavity, has been developed for the removal of the secretions of the various glands collected in the conjunctival sac, but particularly the lachrymal fluid. Such an apparatus is present in all classes of Vertebrates from the Amphibia upward ; its development has been especially investigated by BORN in a series of researches.
 
In the Amphibia it begins to be formed at the time the process of chondrification becomes observa.ble in tho membranous nasal capsule. At that time the mucous layer of the epidermis, along a line that extends from the median side of the eye directly to the nasal cavity, undergoes proliferation and sinks into the underlying connectiveI issue layer as a solid ridge. Then from the nose to the eye the ridge becomes constricted off, subsequently acquires a lumen, whereby it is converted into a canal lined with epithelium, and opens out into the nasal cavity. Toward the eye-end the canal is divided into two tubules, which at the time of detachment from the epidermis remain in connection with the conjunctival sac and suck up out of it the lachrymal fluid.
 
In Birds and Mammals, including Man (fig. 273), the place where the lachrymal duct is located is early marked externally by a furrow
which runs from the inner angle of the eye to the nasal chamber. By means of this furrow two ridges, which play an important part in the formation of the face, the maxillary process and the outer nasal process, are sharply marked off from each other ; these will engage our attention later. According to COSTE and KOLLIKER the lachrymal duct arises by the simple approximation and concrescence of the edges of the lachrymal groove. These older conclusions have been contradicted by BORN and LEGAL, one of whom has investigated Reptiles and Birds, the other Mammals. According to them there arises, in nearly the same manner as in Amphibia, through proliferation of the mucous epithelium, at the bottom of the lachrymal groove an epithelial ridge, which becomes detached but is not converted into a canal until a rather late period. When we raise the question, how phylogenetically the lachrymal duct may have first originated, we shall doubtless find that it has been derived from a groove, by means of which the sac of the conjunctiva and the nasal chamber are first put into connection. When, therefore, we see the lachrymal duct established from the very beginning simply as a solid ridge, as for example in the Amphibia, we must call to mind how in other cases also originally groove-like fundaments, such as the medullary furrow, make their appearance, under special circumstances, as solid ridges,
 
 
 
Fig. 273. Head of a human embryo, from which the mandibular processes have been removed to allow a survey of the roof of the primitive oral cavity.
 
 
Finally, as far as regards the development of the lachrymal tubules in Birds and Mammals, BORN and LEGAL refer the upper tubule to the proximal part of the epithelial ridge, and maintain that the lower one buds out from the upper. EWETSKY, on the contrary, declares that the proximal end of the epithelial ridge expands at the inner angle of the eye, and becomes divided by the ingrowth of underlying connective tissue, and metamorphosed into the two tubules, so that both arise from a common fundament.
 
 
 
SUMMARY.
 
1. The lateral walls of the primary fore- brain vesicle are evaginated to form the optic vesicles.
 
2. The optic vesicles remain united by means of a stalk, the future optic nerve, with that part of the primary fore-brain vesicle which becomes the bet ween -brain.
 
3. The optic vesicle is converted into the optic cup through the imagination of its lateral and lower walls by the fundaments of the lens and vitreous body.
 
4. At the place where the lateral wall of the primary optic vesicle encounters the outer germ-layer, the latter becomes thickened, then depressed into a pit, and finally constricted off as a lens-vesicle.
 
5. The cells of the posterior wall of the lens-vesicle grow out into lens-fibres, those of the anterior wall become the lens-epithelium.
 
6. The fundament of the lens is enveloped at the time of its principal growth by a vascular capsule (tunica vasculosa lentis), which afterwards entirely disappears.
 
7. The membrana capsulo-pupillaris is the anterior part of the tunica vasculosa lentis and lies behind the pupil.
 
8. The development of the vitreous body causes the choroid fissure.
 
9. The optic cup has double walls ; it consists of an inner and an outer epithelium, which are continuous with each other at the opening of the cup, which embraces the lens, and at the choroid fissure.
 
10. Mesenchymatic cells from the vicinity grow in between the lens and the somewhat closely applied epidermis to form the cornea and DESCEMET'S membrane, the latter being separated from the tunica vasculosa lentis by a fissure, the anterior chamber of the eye.
 
1 1 . The optic cup is differentiated into a posterior portion, within the territory of which its inner layer becomes thickened and constitutes the retina, and an anterior portion, which begins at the ora
 
 
490 EMBRYOLOGY.
 
serrata, becomes very much reduced in thickness, and extends over the front surface of the lens, growing into the anterior chamber of the eye until the originally wide opening of the cup is reduced to the size of the pupil.
 
12. The anterior attenuated portion of the cup is, in turn, divided into two zones, of which the posterior becomes folded at the periphery of the equator of the lens to form the ciliary processes, whereas in front it remains smooth ; so that in the whole cup three parts may now be distinguished, as retina, pars ciliaris, and pars iridis retinae.
 
13. Corresponding to the three portions of the epithelial optic cup, the adjoining connective -tissue envelope takes on somewhat different conditions as the choroid proper, and as the connective-tissue framework of the ciliary body and that of the iris.
 
14. The skin surrounding the cornea becomes infolded to form the upper and lower eyelids and the nictitating membrane, of which the last is rudimentary in Man, persisting only as the plica semilunaris.
 
15. The epithelial layers of the edges of the two eyelids grow together in the last months of development, but become separated again before birth.
 
16. The lachrymal groove in Mammals passes from the inner angle of the eye, between the maxillary and outer nasal processes, to the nasal chamber.
 
17. The lachrymal duct for carrying away the lachrymal fluid is formed by the downgrowth and constricting off of an epithelial ridge from the bottom of the lachrymal groove, the ridge becoming hollow.
 
18. The two lachrymal tubules are developed by the division of the epithelial ridge at the angle of the eye.
 
 
 
B. The Development of the Organ of Hearing.
 
In the case of the ear numerous parts of quite different origin unite, in much the same manner as in the case of the eye, to form a single very complicated apparatus ; of these, too, it is the portion to which the auditory nerve is distributed the membranous labyrinth with its auditory epithelium that is by far the most important, outstripping as it does all the remaining parts in its development : it must consequently be considered first.
 
 
 
THE ORGANS OF THE OUTER . GERM-LAYER.
 
 
 
491
 
 
(a) The Development of the Otocyst into the Labyrinth.
 
The membranous labyrinth is preeminently a product of the outer germ-layer. However great its complication in the adult is, a complication that has given it the name labyrinth, its earliest fundament is exceedingly simple. It arises on the dorsal surface of the embryo in the region of the medulla oblongata (fig. 263 gb), above the first visceral cleft and the attachment of the second visceral arch (fig. 274 above the numeral 3). Here over a circular territory the outer germ-layer becomes thickened and soon sinks down into an auditory pit. This process can be traced very easily in the embryo Chick on and after the end of the second day of incubation, and in the embryo Rabbit fifteen days old. The auditory nerve makes its way from the brain, near at hand, to the fnndus of the pit, where it terminates in a ganglionic enlargement.
 
The Bony Fishes alone exhibit a deviation from these conditions. Just as the central nervous system was in their case formed not as a tube, but as a solid body, and the eye not as a vesicle, but as an epithelial ball, so we see here that instead of an auditory pit there is formed by means
of the proliferation of the outer germ-layer a solid epithelial plug. This, like the brain-tube and the eye-vesicle, acquires an internal chamber at a later period only namely, after being constricted off.
 
The next stage shows the pit converted into an auditory vesicle. In the Chick this takes place in the course of the third day. The invagination of the outer germ-layer grows deeper and deeper, and by the approximation of its margins becomes pear-shaped ; soon the connection with the outer germ-layer becomes entirely lost, as is shown by a section through the head of an embryo Sheep (fig. 275 Ib).
 
In nearly all Vertebrates the auditory vesicle is constricted off from the ectoderm in the same manner. The Selachians are an exception : here the auditory vesicle which is metamorphosed into the labyrinth retains permanently its connection with the surface of the
 
 
 
Fig. 274. Head of a human embryo 7'5 mm. long, neck measurement. From His, "Menschliehe Embryonen."
The auditoiy vesicle lies atove the first visceral cleft. In the circumference of the visceral cleft there are to be seen six elevations, designated by numerals, from which the external ear is developed.
 
 
 
492
 
 
EM BRYOLOGY.
 
 
 
nh
rl Ih
 
 
dc
 
 
body in the form of a long narrow tube, which traverses the cartilaginous primordial cranium and is in union dorsally with the epidermis at the sin-face of the body, where it possesses an external opening.
 
In its first fundament the organ of hearing in Vertebrates resembles in the highest degree those structures wliicli, in the Invertebrates are interpreted as organs of hearing. These are lymph-filled vesicles lying under the skin, which are likewise developed out of the epidermis. Either they are wholly constricted off from the epidermis, or they remain connected with it by means of a long, ciliate, epithelial canal, as in the Cephalopods, even after they have become surrounded
by connective tissue. In both cases the vesicles are lined with epithelium which consists of two kinds of cells : first of low, flat elements, which ordinarily exhibit ciliary movements and thereby put in motion the fluid within the vesicle, and secondly of longer cylindrical, or thread-like, auditory cells with stiff hairs, which project into the endolymph. The auditory cells are either distributed individually over the inner surface of the auditory vesicle or arranged in groups, or they are united at a particular place into an auditory epithelium, the auditory patch (macula acustica) or the auditory ridge (crista acustica), which may be either single or double. To all the auditory vesicles of the Invertebrates there is sent, moreover, a nerve which ends at the sensory cells in fine fibrillre. Finally, there is present as a characteristic structure a firm, crystalline body, the otolith, which is suspended in the midst of the endolymph and is ordinarily set in vibration by the motion of the cilia. It consists of crystals of phosphate or carbonate of lime.
 
Sometimes there is only a single large, in most cases concentrically laminated, spherical body, sometimes a number of small calcareous crystals, which are held together by means of a soft pulpy substance.
 
 
 
 
Fig. 275. Vertical [cross] section through the vesicle of the labyrinth of an embryo Sheep 1-3 cm. long, after BOETTCHER. Magnified 30 diameters.
 
'iih, Wall of the after-brain ; rl, recessus labyrinth! ; Ib, vesicle of the labyrinth ; </c, ganglion cochleare, which is in contact with a part of the labyrinth-vesicle (dc) that grows out into the ductns cochlearis.
 
 
 
THE ORGANS OF THE OUTER GERM-LAYER.
 
 
 
493
 
 
rl
 
 
am (>:b)
^
"in"
vV
hb
dc
 
 
It is difficult to follow the formation of the otoliths within the otocyst. In one case, which FOL was able to follow, they were developed by an epithelial cell in the wall of the vesicle. The cell secretes small calcareous concretions in its protoplasm, becomes enlarged in consequence, and protrudes as an elevation into the endolymph. When it has become more heavily loaded with calcic salts, it is connected with the wall by means of a stalk only, and finally it becomes entirely detached from the wall and falls into the cavity of the vesicle, in which it is kept floating and rotating by the ciliate cells.
 
In Vertebrates the otocyst, which, as we have seen, agrees in its first fundament with the organ of hearing in Invertebrates, is converted into a very complicated structure, the membranous labyrinth, -the evolution of which in Mammals I shall describe in some detail. It undergoes metamorphoses, in which the formation of folds and constrictions plays the principal part (fig. 276). The auditorv sac de
/
tached from the epidermis, and lying at the side of the after-brain, soon exhibits a small, dorsally directed projection, the recessus labyrinthi or ductus endoly niphaticus (fig. 275 rl). Probably we have to do in this with the remnant of the original stalk by means of which the auditory vesicle was connected with the epidermis. According to some investigators, on the contrary, the .stalk disappears entirely and this evagination is a new structure. The first assumption is favored especially by the previously mentioned condition in the Selachians the presence of a long tube, which maintains a permanent connection between labyrinth and epidermis.
 
 
 
 
Fig. 276. Membranous labyrinth of the left side of a [human] embryo, after a wax model by KRAUSE.
 
//, Recessus labyrinth! ; dc, ductus cochlearis ; hb, pocket from which the horizontal semicircular canal is formed ; a in', enlargement of the pocket which becomes the ampulla of the horizontal canal ; am (rb), vb', * common pocket from which the two vertical semicircular canals are developed ; am (vb), enlargement of the common pocket from which the ampulla of the anterior vertical canal arises. An opening (w) has been formed in the pocket, through which one sees the recessus labyrinthi. * Region of the pocket which becomes the common arm of the two vertical canals (sinus superior) ; rb', part of the common pocket which furnishes the posterior vertical canal.
 
 
 
494
 
 
EMBRYOLOGY.
 
 
 
Later this appendage of the labyrinth (figs. 276-9 rl) grows out dorsally to a great length, during which its walls come into dose contact with each other, excepting at the blind end, which is enlarged into a small sac (fig. 279 rl*).
 
Meanwhile the auditory sac itself (figs. 275-7) begins to be elongated and to be formed into a ventrally directed conical process (dc), the first fundament of the ductus cochlearis, which is curved inward a little toward the brain (fig. 277 nh), and the concave side of which
 
 
hn vb
 
 
dc
 
 
 
Fig, 277. Cross section through the head of a Sheep embryo 1'6 cm. long, in the region of the labyrinth-sac. On the right side is represented a section which passes through the middle of the sac ; on the left, one that is situated somewhat farther forward. After BOETTCHER.
 
hn, Auditory nerve ; vb, vertical semicircular canal ; gc, ganglion cochleare (spirale) ; dc, ductus cochlearis ; /, inward-projecting fold, whereby the sac of the labyrinth is divided into utriculus and sacculus ; rl, recessns labyrinth! ; tth, after-brain.
 
lies in close contact with the previously mentioned ganglionic enlargement (yc) of the auditory nerve (hn).
 
It will be serviceable in the following description if we now distinguish an upper and a lower division of the labyrinth. They are not yet, it is true, distinctly delimited from each other, but in later stages they become more sharply separated by an inward-projecting fold (figs. 277-9/).
 
The upper part (pars superior} furnishes the utriculus and the semicircidar canals. Of the latter the two vertical canals arise first, the horizontal canal being formed later. The method of their origin
 
 
THE ORGANS OF THE OUTER GERM-LAYER.
 
 
 
495
 
 
was early ascertained by the zoologist RATHKE in the case of Coluber. Recently KRAUSE has still further elucidated the interesting processes by the construction of wax models of the conditions in mammalian embryos.
 
As is to be seen from the various sections (figs. 277, 278), but still better from the model (fig. 276) produced by reconstruction, the semicircular canals are developed by the protrusion of several evaginations of the wall of the sac, which have the form of thin pockets or discs (hb, vb) with a semicircular outline. The marginal part of each such e vagination now becomes con side i 1 ably enlarged, whereas the
 
 
remaining
 
 
 
vb
 
 
U J
hb
 
 
dc
 
 
portions
of the two epithelial layers come into close contact and begin to fuse. As the result of this simple process -the enlargement at the margin and the fusion of the walls which takes place in the middle there is formed a semicircular canal, which communicates at two places with the original cavity of the vesicle. At one of its openings the canal is early enlarged into an ampulla (fig. 276 am and am'}. The middle part, in which the fusion has taken place, soon disappears, the epithelial membrane being broken through by a growth of the connective tissue (fig. 276 6).
 
There exists an interesting difference between the development of the horizontal and the two vertical canals, which was discovered by KRAUSE. Whereas the horizontal canal is established as a small pocket by itself (fig. 276 hb), the two vertical canals arise together from a single large pocket-like fundament (fig. 276 am (vb), *, vb').
 
 
 
Fig. 278. Cross section through half of the head of a foetal Sheep 2 cm. long, in the region of the labyrinth, after BOETTCHEK. Magnified 30 diameters.
 
rl, Recessus labyrinth! ; vb, hb, vertical and horizontal semicircular canals; U, utriculus ; f, inward-projecting fold, by which the labyrinth-sac is divided into utriculus and sacculus ; dc, ductus cochlearis ; yc, ganglion cochleare.
 
 
 
496
 
 
EMBRYOLOGY.
 
 
 
The walls of this large pocket come into contact with each other and fuse at two different places. At one of them there has already been formed, in the preparation from which this model (fig. 276) was constructed, an opening (o) by the resorption of the fused epithelial areas, whereas at the second place (vb 1 ) the epithelial membrane is still preserved. Between the fused parts of the pocket there remains open a middle region, which is indicated in the model by an asterisk,
 
 
 
 
i '<:!&,.
 
i f. ;mj$\..
 
J
w P ''"
 
 
Jck
 
 
 
Fig. 279. View produced by combination from two cross sections through the labyrinth of a
Sheep embryo 2-8 cm. long, after BOETTCHKR. rl, Recessus labyrinth! ; rl*, its flask-like enlargement ; vb, hb, vertical and horizontal canals ;
U, utriculus ; S, sacculus ; /, fold by means of which the labyrinth is divided into saccuhis
and utriculus ; cr, canalis reunions ; dc, ductus cochlearis ; kk, cartilaginous capsule of the
cochlea ; sp, sinus petrosus inferior.
 
and this becomes the common arm (sinus superior) of the two vertical canals. Thus embryology furnishes for this peculiarity, too, a simple satisfactory explanation.
 
That which remains of the upper portion of the auditory vesicle, after the semicircular canals have grown forth from its wall, is called the utriculus (figs. 278-80 U).
 
Meanwhile no less significant and fundamental alterations take place in the lower part of the auditory sac and lead to the formation of sacculus and ductus coc/ilearis.
 
 
 
THE ORGANS OF THE OUTER GERM-LAYER.
 
 
 
497
 
 
By a continually deepening constriction (fig. 279 /) the lower portion (S) is delimited from the utriculus (U), and finally remains connected with it by a very narrow tubule only (canalis utriculo-saccularis figs. 280 R and 282 2 ). Since the constriction affects exactly that place of the labyrinth-sac from which the recessus labyrinth! arises, the opening of the latter subsequently comes to lie within the territory of the canalis utriculo-saccularis, at about its middle (figs. 280 R and 282 2 ). In this manner there is produced an appearance as though the recessus labyrinthi were split at its beginning into two narrow tubules, one of which leads into the sacculus, the other into the utriculus.
 
By a second deep constriction (figs. 279, 280, 282) the sacculus (S) is separated from the developing ductus cochlearis (dc). Here also a connection is maintained by means of an extraordinarily fine connecting tubule only (cr), which HENSEN discovered and has described as canalis reuniens. The ductus cochlearis itself increases greatly in length, and at the same
 
 
 
U
 
 
time begins to be rolled
 
 
Fig. 280. Diagram to illustrate the ultimate condition of the membranous labyrinth [after WALDEYER].
 
U, Utriculus ; S, sacculus; Cr, canalis reunions ; R, recessus labyrinthi ; C, cochlea ; K, blind sac of the cupola ; V, vestibular blin 1 sac of the ductus cochlearis.
 
 
 
up in spiral turns in the soft, envt loping, embryonic connective tissue, until in Man it describes two and a half turns (figs. 280 C and 282 Con). Since the first whorl is the largest, and the others are successively narrower, it acquires a great resemblance to a snail-shell.
 
The alterations in the external form of the vesicle are accompanied by changes in the nature of its epithelium also. This is separated into the indifferent epithelial cells, which simply serve as a lining, and the real auditory cells. The former are flattened, becoming cubical or scale-like, and cover the greater part of the inner surface of the semicircular canals, the sacculus, the utriculus, the recessus labyrinthi, and the ductus cochlearis. The auditory cells, on the contrary, are elongated, become cylindrical or spindle-shaped, and acquire at the free surface hairs, which project into the endolymph. By the separation of the vesicle into its various divisions the
32
 
 
498 EMBRYOLOGY.
 
auditory epithelium is distributed into an equal number of separate patches, to which then the auditory nerve is distributed. Accordingly the auditory epithelium is resolved into a macula acustica in the sacculus and another in the utriculus, into a crista acustica, in each of the ampulla} of the semicircular canals, and into an especially complicated termination in the ductus cochlearis. Hero the auditory epithelium grows out into a long spiral band, which is known under the name of CORTI'S organ.
 
Upon the separation of the auditory epithelium into maculae, cristae, and organ of CORTI, the originally single auditory nerve distributed to the auditory vesicle is likewise resolved into separate branches. We distinguish in the case of the auditory nerve the nervus vestibuli, which is in turn divided into numerous branches distributed to the maculae and cristse, and the nervus cochlece.
 
The originally single ganglion acusticum belonging to the auditory nerve also becomes differentiated into two separate portions. The portion belonging to the nervus vestibuli is in the adult located in the internal auditory meatus far from the terminal distribution, forming here the well-known intumescentia gangliformis Scarpae ; the portion belonging to the nervus cochleae, on the contrary, adjoins the terminal distribution of the nerve. In the embryo it (figs. 277, 278 gc) is closely united with the fundament of the ductus cochlearis, and as the latter increases in size grows out to the same extent in the form of a thin band, which reaches to the blind end of the ductus and is known under the name of ganglion spirale (fig. 283 gsp).
 
(b] Development of the Membranous Ear-Capsule into the Bony Labyrinth and the Perilymphatic Sj)aces.
 
All of the changes which have been mentioned hitherto have proceeded from the epithelial vesicle which was constricted off from the outer germ-layer. It is now my purpose to direct attention to a series of processes which take place around the epithelial cavities, in the mesenchyme in which they are imbedded. The processes lead to the formation of the bony labyrinth, the perilymphatic spaces and soft connective-tissue layers, which are intimately joined to the purely epithelial structures hitherto treated of, and with the latter are embraced in descriptive anatomy under the name of membranous labyrinth. Changes take place here similar to those in the development of the neural tube and of the eye, in which cases also the connective-tissue surroundings are modified in a special manner and with
 
 
THE ORGANS OF THE OUTER GERM-LAYER. 499
reference to the epithelial parts. In the present instance there are produced structures which are comparable with those existing in the former cases, as has already been pointed out by Ko" LLIKER, SCHWALBE, and others.
 
The comparison may be carried into details. The parts arising from the primitive auditory vesicle are at first surrounded by a soft, vascular connective-tissue layer, as the neural tube and the epithelial optic cup are. To the pia mater of the brain corresponds the vascular membrane of the eye and the soft ear-capsule, or the connective-tissue wall of the membranous labyrinth. Around all three organs a firm envelope has been developed for the purpose of protection ; around the brain the dura mater with the cranial capsule, around the eye the sclerotica, and around the organ of hearing the bony labyrinth with its periosteum. To these is to be added still a third noteworthy agreement. In all three cases the soft and firm envelopes are separated by more or less considerable fissure-like spaces, which belong to the lymphatic system. Around the neural tube the subdural and the subarachnoid spaces are found, around the eye the perichoroid fissure, around the organ of hearing the perilymphatic spaces, which have received in the cochlea the special names of scalse (fig. 283 ST and SV}.
 
The details of the formation of the enveloping structures around the epithelial auditory vesicle are as follows :
Soon after the auditory sac is constricted off from the epidermis it is enveloped on all sides by a richly cellular mesenchyme, the individual cells of which lie in an extremely scanty, soft, and homogeneous intercellular substance, and possess each a large nucleus with a thin protoplasmic covering having short processes. Gradually the envelope is differentiated into two layers (figs. 279, 281). In the vicinity of the epithelial canals the soft intercellular substance increases in amount ; the cells become either stellate or spindle-shaped, in the former case sending out long processes in various directions. There is formed here that modification of connective substance known as mucous or gelatinous tissue (figs. 281 and 283 </), in which there are also blood-vessels. Outside of this the cells remain smaller and more closely crowded together, and are separated from one another by thin partitions of a firm intermediate substance. With an increase of the latter the tissue soon acquires the character of embryonic cartilage (&&).
 
The further changes must be followed separately in the semicircular canals, the utriculus and sacculus and the ductus cochlearis,
 
 
500
 
 
EMBRYOLOGY.
 
 
 
The throe semicircular canals do not lie exactly in the middle of the cavities of the embryonic cartilage containing the gelatinous tissue, but are so situated that their convex borders are in almost immediate contact with the cartilage, whereas their concave sides are separated from it by a thick layer of gelatinous tissue. The latter is differentiated into three layers : into a middle portion, in which the gelatinous intercellular substance is greatly increased in volume, and becomes at the same time more fluid, and into two limiting layers, which are converted into fibrous connective tissue. One of the two [the inner] is intimately united to the epithelial tube, for the nutrition of which
 
 
dc
 
 
dc
 
 
Cdc
 
 
kk
 
 
 
dc
 
 
kl
 
 
nc
 
 
nc gs ns
 
 
S U
 
 
Fig. 281. Section through the cochlea of a Sheep embryo 7 cm. long, after BOKTTCHER. Magnified 20 diameters.
 
/,/, Cartilaginous capsule of the cochlea ; S, sacculus with the nerve (ns) distributed to it ; U, utricle ; gs, ganglion connected with the cochlear nerve (nc) and sending nerve-fibres (ns) to the sacculus ; gsp, ganglion spirale ; dc, ductus cochlearis ; C, CORTI'S organ ; g, gelatinous tissue in the periphery of the ductus cochlearis ; x, more compact connective-tissue layers.
 
it provides by means of a close network of blood-vessels distributed through it ; the other [the outer] lies on the inner surface of the cartilaginous envelope and becomes its perichondrium.
 
The gelatinous tissue of the middle layer is of only short duration. It soon shows signs of degeneration. The stellate cells become filled with fat granules in the vicinity of their nuclei and in their long processes ; later they disintegrate. In the gelatinous matrix there are formed, by a continually advancing process of softening, cavities filled with fluid. These increase in size and then become confluent, until finally there has arisen between the connective-tissue membrane of the semicircular canals and the perichondrium, in place of the
 
 
THE ORGANS OF THE OUTER GERM-LAYER.
 
 
 
501
 
 
gelatinous tissue, a large space filled with perilymph, which is indicated in the diagram, fig. 282, in black. Here and there, however, connective-tissue cords remain running from one layer of connective tissue to the other, and serving as bridges for the nerves and bloodvessels which are distributed to the semicircular canals.
 
Finally, a last alteration takes place in the cartilaginous envelope
 
 
\
 
 
 
Fig. 282. Diagrammatic representation of the whole organ of hearing in Man, from WIEDKKSHEIM.
 
Outer air: M, <!/, auricle; Mac, meatus auditorius externus ; 0, its wall; Mt, membrana tympani. Middle car: Ct, Ct, cavum tympani ; O l , its wall; SAp, sound-conducting apparatus, which i.s drawn as a simple rod-like body in place of the auditory ossicles ; the place f corresponds to the stapedial plate, which closes the fenestra ovalis ; Tb, tuba Eustachii ; Tb 1 , its opening- into the pharynx; 0", its wall. Inner car: the bony labyrinth (KL, KL') for the most part cut away ; S, sacculus ; a, b, the two vertical membranous and osseous semicircular canals ; S.e, D.e, saccus and ductus endolymphaticus, of which the latter is divided at 2 into two arms ; Cp, cavum perilyinphaticum ; Cr, canalis reunions ; Con, membranous cochlea, which produces at + the vestibular cceciun ; Con 1 , bony cochlea ; Sv and St, scala vestibuli and scala tympini, which at * communicate with each other at the cupula tenninalis (Ct) ; D.p, ductus perilymphaticus, which arises from the scala tympani at (I and opens out at D.p 1 . The horizontal semicircular canal is not specially designated, but is easily recognisable.
 
by its becoming converted into bone-substance by endochondral ossification. Thus the membranous semicircular canals are enclosed in the bony semicircular canals (fig. 282 a and 1> KL], which are enlarged reproductions of the former.
 
Corresponding changes (iig. 282) are also accomplished in the periphery of the utriculus and sacculus (#), and lead to the formation of (1) a perilymphatic space (Cp), which is in communication with
 
 
502 EMBRYOLOGY.
 
the perilymphatic spaces of the semicircular canals, and (2) a bony envelope (A"7/') of the atrium or vestibulum, which constitutes the middle region of the bony labyrinth.
 
The envelope of the epithelial cochlear duct, which becomes the bony cochlea with its scalse, undergoes a more complicated alteration. It is already differentiated, at the time when the duct (fig. 279 dc) makes only half of a spiral turn, into an inner, soft and an outer, firm layer, the latter becoming cartilage (kk). The cartilaginous capsule (fig. 281 kk), which is continuous with the cartilaginous mass of the remaining parts of the labyrinth and together with them constitutes a part of the ospetrosum, afterwards encloses a lenticular cavity and possesses below a broad opening, through which the cochlear nerve (no) enters. The resemblance to a snail-shell is not yet observable ; it takes place gradually and is produced by two changes : by the outgrowth of the epithelial duct and by the differentiation of the soft tissue surrounding it into parts which are fluid and such as become more firm.
 
In its outgrowth the epithelial ductus cochlearis describes within its capsule the previously mentioned spiral turns (dc), shown in cross section in fig. 283 ; at the same time it remains quite closely approximated to the inner surface of the capsule (kk). The cochlear nerve (nc) ascends from its place of entrance straight up through the centre of the turns, consequently in the axis of the capsule, and gives off numerous lateral branches to the concave side of the cochlear duct (dc), where they are enlarged into the ganglion (gsp), which has now also grown out into a spiral band. The nutritive blood-vessels have taken the same course as the nerves.
 
When the development has advanced as far as this, there still remains to be accomplished only an histological differentiation in the soft mesenchyme which fills the cartilaginous capsule in order to produce the parts of the finished cochlea that are still wanting the modiolus, the lamina spiralis ossea, the bony cochlea, and the vestibular and tympanic scalse (fig. 283). Here, as in the vicinity of the semicircular canals the utriculus and the sacculus, the mesenchyme is differentiated into a firmer connective substance, which becomes fibrous, and into a gelatinous tissue (g), which is continually becoming softer. Fibrous connective substance is developed first around the trunks of the nerves (nc) and blood-vessels that enter the cartilaginous capsule ; furnishing the foundation of the future bony axis of the snail-shell (M), secondly it furnishes an envelope for nerve-fibres (N) that run from the axis to the epithelial cochlear duct, for the gangli
 
 
THE ORGANS OF THE OUTER GERM-LAYER. 503
onic cells (ysp), and for the blood-vessels, and constitutes a connectivetissue plate which is subsequently ossified to form the lamina spiralis ossea. Thirdly, it clothes with a thin layer the epithelial ductus, serving for the distribution of the blood-vessels on the latter, and together with it is designated as the membranous ductus cochlearis. Fourthly, it lines the inner surface of the cartilaginous capsule as perichondrium (P). Finally, fifthly, there is formed a connective tissue plate (Y) extending between the cartilaginous ridge which, as previously described, projects inward from the capsule and the connective -tissue axis of the cochlea (M). It is stretched out between and separates the successive turns of the membranous cochlear duct, so that the latter now comes to lie in a large canal, the wall of which is in part cartilaginous, in part membranous. This canal is the foundation of the bony cochlea.
 
That portion of the mesenchyme which is not converted into fibrous connective tissue becomes gelatinous tissue (g and </). It forms bet\veen the parts just mentioned two spiral tracts, one of \vhich is located above and the other below the membranous ductus cochlearis and the membranous lamina spiralis. The tracts therefore occupy the place of the scala vestibuli (SV) and the scala tympani (>ST). The latter arise, even before the process of ossification begins, in exactly the same w r ay as the perilymphatic spaces in the case of the semicircular canals and the vestibule. In the gelatinous tissue the matrix becomes softer and more fluid, and the cells begin to undergo fatty degeneration. Small fluid-filled cavities make their appearance ; these become joined to one another, and finally the \vhole space occupied by gelatinous tissue is filled with perilymph. The process of softening begins at the base of the cochlea in the region of the first spiral (ST and SV), and advances slowly toward the cupola. Here vestibular and tympanic scalse finally unite, after the last remnant of the gelatinous tissue has been dissolved. Figure 283 exhibits a stage in which, at the base of the cochlea, the perilymphatic spaces (SV and >ST) have been formed, and only small remnants of the gelatinous tissue ((/') are present, whereas at the apex of the cochlea the process of liquefaction of the gelatinous tissue (y) has not yet taken place.
 
With the development of the scala? the membranous ductus cochlearis changes form. Whereas its cross section was formerly oval, it now assumes the form of a triangle (dc). For those portions of the wall which are adjacent to the vestibular and tympanic scalse, and which have been named from them, gradually become flattened,
 
 
504
 
 
EMBRYOLOGY.
 
 
 
efc
 
 
 
lek
 
 
Fig. 283. Part of a section through the cochlea of an embryo Cat 9 cm. long, after BOETTCHER.
 
kk, Cartilaginous capsule, in which the cochlear duct describes ascending spiral turns; dc, ductus cochleares ; C, organ of Coim ; ie, lamina vestibularis ; x, outer wall of the membranous ductus cochlearis with ligamentum spirale ; <ST, scala vestibuli ; ST, ST', scala tympani ; g, gelatinous tissue, which still fills the scala vestibuli (.si/) in its last turns ; //, remnant of the gelatinous tissue, which is not yet liquefied ; M, firm connective tissue surrounding the cochlear nerve (nc) ; gsp, ganglion spirale ; N, nerve which runs to CORTI'S organ in the future lamina spiralis ossea ; Y, compact connective-tissue layer, which becomes ossified and shares in bounding the bony cochlear duct ; P, perichondrium.
 
 
 
THE ORGANS OF THE OUTER GERM-LAYER. 505
and are stretched out smoothly between the free margin of the lamina spiralis and the inner wall of the cartilaginous capsule. In this process the tympanic wall (C) comes to lie in the same plane as the lamina spiralis, the vestibular wall (Iv) forms with the tympanic an acute angle, and the third wall (x) is everywhere in close contact with the perichondrium of the cartilaginous capsule.
 
The epithelial lining of the membranous duct us cochlearis assumes very different conditions in the three corresponding regions of its wall. Whereas the epithelial cells of the vestibular and the outer walls become in part cubical, in part quite flat, those of the tympanic wall become elongated, and are in connection with the terminal filaments of the cochlear nerve ; they produce the complicated organ of CORTI (C), which, like the auditory ridges and auditory patches of the ampullre, the sacculus and utriculus, contains the terminal ends of the auditory nerve.
 
The construction of the intricate cochlea approaches completion with the beginning of the process of ossification. The latter is accomplished by two methods. First, the cartilaginous capsule ossifies in the endochoiidral manner, as does the whole cartilaginous os petrosum, of which it constitutes a small part. The osseous tissue thus formed is for a long time spongy and provided with large medullary spaces. Secondly, the previously mentioned fibrous connective-tissue layersthe partitions between the cochlear canals, the connective-tissue axis or the niodiolus and the lamina spiralis undergo direct ossification. At the same time compact bone-lamell?e are laid down from within on the spongy bone-tissue formed from the cartilaginous capsule; these lamelke are formed, as BOETTCHER has shown, by the original perichondrium, which becomes the periosteum. Consequently the bony cochlear capsule, since it is produced by periosteal secretion, may be easily detached from the loose osseous tissue of endochoiidral origin during early post-natal years.
 
(c) Development of the Accessory Apparatus of the Organ of Hearing.
 
(Middle and External Ear.}
With the membranous and bony labyrinth, which are together called the inner ear, there is associated a subsidiary apparatus, in the same way that the eye-muscles, the lids, and the lachrymal glands and ducts are added to the eyeball. It is made up of structures which are wanting in the lower Vertebrates (Fishes), but, beginning to be developed in the Amphibia, become more and more complete in
 
 
506 EMBRYOLOGY.
 
the higher forms. Their function is to transmit vibrations to the labyrinth, and consequently they are together called the conducting apparatus. From their position they are also known as middle and outer ear. The former consists in Mammals, where it attains its highest development (diagram, fig. 284), of the tympanic cavity (67), the Eustachian tube (Tb), and the three auditory ossicles ($Ap] ; the latter, of the tympanic membrane (M), the external meatus (Mae), and the external ear or auricle (M). The statement just made, that these parts are wanting in Fishes, is to be taken cum grano salis : it is as a sound-conducting apparatus only that they are wanting, for they are present even in the case of Fishes, but only as structures of a different function and in a more simple condition. For the various accessory apparatus of the, organ of hearing are developed out of the first visceral cleft and certain parts which are located in its periphery.
 
Here also it will be well to acquaint ourselves with the originalthe initial condition, for which the Selachians may serve as an example.
 
In them the greater part of the first visceral cleft, which is situated between the mandibular and hyoid arches and between the nervus trigeminus and n. acustico-facialis, disappears ; at the side of the throat it becomes closed, remaining open only at the origin, or base, of the two visceral arches. It then has the form of a short canal, which possesses a small round opening at its inner and another at its outer end, and which passes in very close proximity to the labyrinth-region of the skull, in which the organ of hearing is located. The canal, here called the spiracle, has no longer anything to do with respiration, since the branchial leaflets on its wall have undergone degeneration. Owing to its position in the immediate vicinity of the labyrinth, it presents, even in the Selachians, the best course for the propagation of the sound-waves to the inner ear, and this is the chief ground for its entering wholly into the service of the organ of hearing in the remaining Vertebrates, and for its being developed in a more serviceable manner for this particular function.
 
The structures in the higher Vertebrates corresponding to the spiracle of the Selachians are (fig. 284) the tympanic cavity (Ct), the Eustachian tube (77>), and the external meatus (Mae). They likewise are developed out of the upper part of the first visceral cleft. Although it lias recently been asserted by certain investigators (URBANTSCHITSCH) that they have nothing to do with the first visceral cleft, but are established independently by the evagina
 
 
THE ORGANS OF THE OUTER GERM-LAYER.
 
 
 
507
 
 
tion of the pharynx, this view is opposed not only to comparativeanatomical considerations, but also to statements of KOLLIKER, MOLDENHAUER, and HOFFMANN, which relate to the development in Reptiles, Birds, and Mammals.
 
In the classes of Vertebrates just mentioned the first visceral
 
 
 
Fig. 284. Diagrammatic representation of the whole organ of hearing in Man, from WIKDEKSHEIM.
 
Outer car: M, M, auricle; Mac, meat/us axiditorius externus ; O, its wall; Mt, membrana tympani. Middle car: Ct, Ct, cavum tympani ; O 1 , its wall; SAj>, sound-conducting apparatus, which is drawn as a simple rod-like body in place of the auditory ossicles; the place t corresponds to the stapedial plate, which closes the fenestra ovalis ; Tb, tuba Eustachii ; Tb 1 , its opening into the pharynx; 0", its wall, fiitu .rmr: the bony labyrinth (KL, A'Z 1 ) for the most part cut away ; S, sacculus ; a, b, the two vertical membranous and osseous semicircular canals ; S.e, D.e, saccus and ductus endolymphaticus, of which the latter is divided at 2 into two arms ; Cp, cavum perilymphaticum ; Or, canalis reuiiiens ; Con, membranous cochlea, which produces at -t- the vestibular ccecuru ; Con 1 , bony cochlea ; Sv aad St, scala vestibuli and scala tympani, which at * communicate with each other at the cupula terminalis (Ct) ', D.z>, ductus perilymphaticus, which arises from the scala tympani a b d and opens out at D.p\ The horizontal semicircular canal is not specially designated, but is easily recognisable.
 
cleft is closed in its upper part also, contrary to the condition in Selachians.*
The closure becomes more firm and complete owing to the ingrowth of a connective-tissue layer between the inner and outer epithelial plates. Remnants of the first visceral cleft are preserved
* See the statements discussed in a previous chapter (p. 2X7), concerning the mooted question whether the visceral clefts remain closed by means oi' an epithelial membrane or are temporarily open.
 
 
 
508 EMBRYOLOGY.
 
on both sides of the closing membrane as depressions of greater or less depth ; an inner one on the side toward the pharyngeal cavity, and an outer one which is surrounded by ridges of the first and second visceral arches.
 
The inner depression, which is called canalis or sulcus tubo-tym panicus (pharyngo-tympanicus), is located, like the spiracle, between trigeminus and acustico-faeialis, It becomes the middle ear, and is enlarged by an evagination that is directed upward, outward, and backward. The evagination inserts itself between the labyrinth and the place of closure of the first visceral cleft, and takes the form of a laterally compressed space, which is now to be distinguished as tympanic cavity from the tubular remnant of the sulcus tympanicus, or Eustachian tube. Its lumen is very small, especially in the case of advanced embryos of Man and Mammals, its lateral and median walls being almost in immediate contact. This results chiefly from the fact that there is present beneath the epithelial lining of the middle ear a richly developed gelatinous tissue. The latter still encloses at this time structures, the auditory ossicles and the chorda tympani, which later come to lie, as it were, free in the tympanic cavity.
 
The tympanic membrane also is now in a condition very unlike that which it afterwards acquires. The history of its formation is by no means so simple as was formerly supposed. For it is not derived exclusively from, the narrow closing membrane of the first visceral cleft ; the neighboring parts of the first and second membranous visceral arches also participate in its production. The embryonic tympanic membrane is therefore at first a thick connective-tissue plate, and encloses at its margins the auditory ossicles, the tensor tympani, and the chorda tympani. The reduction in the thickness of the tympanic membrane takes place at a late period, simultaneously with an increasing enlargement of the tympanic cavity. Both are brought about by shrinkage of the gelatinous tissue, and by an accompanying growth of the mucous membrane lining the tympanic cavity. Wherever the gelatinous tissue disappears the mucous membrane takes its place, inserting itself between the individual ossicles and the chorda tympani, which thus come to lie apparently free in the tympanic cavity. In reality, however, they lie outside of it, for they continue to be clothed on all sides by the growing mucous membrane, and are connected with the wall of the tympanic cavity by means of folds of that membrane (malleusfold, incus-fold, etc.), in much the same manner as the abdominal
 
 
THE ORGANS OF THE OUTER GERM-LAYER.
 
 
 
509
 
 
organs which grow into the body-cavity are invested by the peritoneum and supported from its walls by the mesenteries.
 
With a reduction in the thickness of the tympanic membrane there occurs a condensation of its connective-tissue substance, whereby it is enabled to fulfil its ultimate function as a vibrating membrane.
 
A more extended discussion of the development of the auditory ossicles will be deferred to a subsequent section, which deals with the origin of the skeleton. At present, only a few words further concerning the formation of the external ear, which, as has already been stated, is derived from a depression on the outer side of the place of closure of the first visceral cleft. Its __
development has been minutely investigated in the Chick by MOLDENHAUER and in the human embryo by His. As the lateral view of a very young human embryo (fig. 274) shows, the first visceral cleft is surrounded by ridge-like margins, which belong to the first and second visceral arches, and are early divided into six elevations designated by Arabic numerals. From these is derived the auricle, which therefore involves a rather extensive tract of the embryonic head (the pars auricularis). The pocket between the ridges, at the bottom of which the tympanic membrane is met with, becomes the external meatus, This is continually growing deeper owing to the surrounding wall of the side of the face becoming greatly thickened ; finally it is developed into a long canal, the wall of which is in part bony, in part cartilaginous. The six elevations mentioned, which surround the orifice of the external ineatus, together constitute a bulky ring. The accompanying representation (fig. 285) shows clearly its metamorphosis into the external ear. It shows that out of the elevations 1 and 5 the tragus and antitrasrus are
O O
developed, out of 2 and 3 the helix, and out of 4 the antihelix. The lobule of the ear remains for a long time small ; it is not until the fifth month that it becomes more distinct. It is derived from the hillock marked with the numeral 6. At the close of the second month all the essential parts of the external ear are easily
 
 
 
Fig. 285. _ Fundament of the outer ear of a human embryo, after His.
 
The elevation marked 1 produces the tragus ; 5, the antitragus. The elevations 2 and 3 produce the helix ; 4, the antihelix. From the ti'act (3 is formed the lobule. A", Lower jaw.
 
 
 
510 EMBRYOLOGY.
 
recognisable ; from the third month onward tho upper and posterior part of the auricle grows out more from the surface of the head ; and it acquires greater firmness upon the differentiation of the auricular cartilage, which had already begun at the end of the second month,
SUMMARY.
 
1. The most essential part of the organ of hearing, the membranous labyrinth, is developed at the side of the after -brain above the first visceral cleft from, a pit-like depression of the outer germlayer.
 
2. By closure the auditory pit becomes the auditory vesicle ; it sinks down and becomes imbedded in embryonic connective tissue, from which the cranial capsule is subsequently developed.
 
3. The auditory vesicle acquires the complicated form of the membranous labyrinth by various evaginations of its wall, and becomes differentiated into the utriculus, with the three semicircular canals, into the sacculus with the canalis reunions and the cochlea, as well as into the recessus vestibuli, by means of which sacculus and utriculus remain permanently connected with each other.
 
4. The auditory nerve and the auditory epithelium, which are at first single, are likewise divided as soon as the vesicle is differentiated into a number of regions into several nerve-branches (nervus vestibuli, n. cochlea?) and nerve-terminations (the cristse acusticse of the three ampullae, a macula acustica for the utriculus and another for the sacculus, and the organ of CORTI).
 
5. The embryonic connective tissue, in which are enclosed the auditory vesicle and the products of its metamorphosis, is differentiated into three parts :
) Into a thin connective-tissue layer, which is closely applied to the epithelial wall and together with it constitutes the membranous labyrinth ;
Into a gelatinous tissue, which becomes liquefied during embryonic life and furnishes the perilymphatic spaces (in the cochlea the scala vestibuli and the scala tympani) ; (c) Into a cartilaginous capsule, from which there arises by a
process of ossification the bony labyrinth.
 
G. The middle and outer ear are derived from the upper part of the first visceral cleft (the spiracle of Selachians) and its periphery.
 
 
 
THE ORGANS OF THE OUTER GERM-LAYER. 511
7. The tympanic membrane, which at first is rather thick and only gradually becomes reduced to a thin, tense membrane, is developed out of the closing plate of the first visceral cleft and the adjacent parts of the visceral arches.
 
8. The tympanic cavity and the Eustachian tube are developed out of a depression on the median side of the tympanic membrane, the sulcus tubo-tympanicus, and out of an evagination. from it extending upward, outward, and backward.
 
9. The tympanic cavity is at first extremely small, the connective tissue of the mucous membrane that surrounds it being gelatinous [and voluminous].
 
10. The auditory ossicles and the chorda tympani lie at first outside the tympanic cavity in the gelatinous tissue of its wall ; it is only after shrivelling of the gelatinous tissue that they come to lie in folds of the mucous membrane, which project into the now more capacious tympanic cavity (incus-fold, malleus-fold).
 
11. The external meatus is developed from the periphery of the depression that lies on the lateral side of the tympanic membrane ; the auricle arises from six elevations, which are converted into tragus, antitragus, helix, antihelix, and the lobule of the ear.
 
 
 
0. The Development of the Organ of Smell.
 
The organ of smell is, like the eye and ear, a product of the outer germ-layer, from which it is developed somewhat later than the two higher sensory organs. It first becomes noticeable, at either side of the broad frontal process (fig. 274) previously described, as a thickening of the outer germ-layer which His has designated in human embryos as nasal area. Both fundaments soon become more distinct owing to the fact that each nasal area becomes depressed into a kind of trough, the edges of which rise up as folds (fig. 286). An olfactory lobe, which has been formed meantime by an evagination of the cerebral vesicle, grows out on either side to the thickened epithelium of this area, where its nerve-fibrillce terminate.
 
The two olfactory pits, which are formed in a similar manner in all Vertebrates with the exception of the Cyclostomes, in which only an unpaired pit arises, are separated from each other by a considerable distance. They therefore appear at first as distinctly paired structures, whereas in their ultimate condition in the higher Vertebrates they have approached each other toward the median plane and become an apparently unpaired organ, the nose,
 
 
512
 
 
EMBRYOLOGY.
 
 
 
 
The study of tho development of tin 1 origin of smell acquires
additional interest, when one lakes into account the comparative - anatomical conditions. It is then found that the various stages through which the organ of smell passes during embryonic life, in Mammals for example, have been preserved as permanent conditions in lower classes of Vertebrates. Thus in the case of many groups of Fishes the organ of smell is preserved, as it were, in its initial stage in the form of a pair of pits. Upon closer histological investigation, however, this condition acquires a special interest, because it presents points of comparison with simpler sensory organs which are distributed over the integument. As BLAUE especially has shown in a meritorious work, the olfactory nerve does not terminate in this case in a continuous olfactory epithelium, but in individual, sharply
 
 
Fig. 286. Frontal reconstruction of the oro-pharyngeal cavity of a human embryo (Ry of His) 11'5 mm. long, neck measurement. From His, " Menschliche Bmbryonen." Magnified 12 diameters.
 
The upper jaw is seen in perspective, the lower jaw in section. The posterior visceral arches are not visible from the outside, since they have moved into the depths of the cervical sinus.
 
 
 
 
 
 
,,. .?>. >
 
 
 
'2T<s
f? %^-'
'f ' '
 
 
<?.& .
 
" i 1'IS
 
 
 
 
 
.
 
 
 
n
 
 
Fig. 287. Longitudinal section through three olfactory buds from the regio olfactoria of Belone, after BLAUE. Highly magnified.
 
r/t, Olfactory bud ; fo, indifferent ciliate epithelium in several layers ; n, branch of the olfactory nerve.
 
 
 
differentiated organs (fig. 287 rk), which, although closely crowded in an indifferent ciliate epithelium (fe), are nevertheless separated from each other.
 
 
 
THE ORGANS OF THE OUTER GERM-LAYER.
 
 
 
513
 
 
The organs (rk) consist of numerous fine, rod-like cells, which at their free ends bear fine bristles and are united into bundles that are distinctly delimited from the ordinary cells of the epidermis. They closely resemble the sensory nerve-terminations which are abimd;intly and widely distributed in the epidermis of Fishes and other lower Vertebrates the beaker-like oryans or the nervous end-buds. BLAUE has therefore named them olfactory buds. He proceeds from the conception that, like the similarly constructed gustatory buds of the oral cavity, they are descended from the sensory organs distributed over the whole integument. The organ of smell is simply a depressed patch of the skin richly provided with terminal nerve-buds, which, undergoing a change of function, has come to subserve a specific sense. The continuous olfactory epithelium of the higher Vertebrates has arisen from the originally scattered, isolated olfactory buds (fig. 287 rk} by a process of fusion, the indifferent epithelium (fe) having gradually disappeared. In certain species of Fishes and Amphibia such a transition can be demonstrated.
 
The further development of the organ of smell is especially characterised by the olfactory pits coming into relation with the oral cavity. Each of them (fig. 286) develops a furrow which runs downward to the upper margin of the mouth and receives on its outer
side the previously described lachrymal groove, coming in an oblique direction from the eye. Nasal pit and nasal furrow become deeper in older embryos (fig. 288), owing to their margins protruding outward as ridges and forming the so-called inner and outer nasal processes. The two inner nasal processes are separated from each other by a shallow furrow running from above downward ; they together produce a thick partition between the two olfactory pits that in the higher Vertebrates subsequently becomes more and more reduced in thickness. They also furnish the middle of the roof <i)f the mouth. The outer nasal processes (also called the lateral frontal processes by His) form on either side a ridge protruding between the eye and the organ of smell, and furnish the material for the formation of the lateral walls of the nose and the alee. Their lower margins meet
33
 
 
 
Fig. 288. Fundament of the nose and the roof of the primitive mouthcavity of a human embryo (C. II. of His), seen from below after removal of the lower jaw. From His, "Menschliche Embryonen." Magnified 12 diameters.
 
 
 
514
 
 
EMBRYOLOGY.
 
 
 
the front end of the transversely located maxillary processes, from which they are delimited externally by the lachrymal grooves.
 
On the median wall of the nasal pit there exists a special small depression, which was first found by Dims Y in mammalian embryos, and which is also observable in human embryos at a very early stage (His). It is the fundament of JACOBSON'S oryan, which afterwards makes its way into the septum of the nose. It receives from the olfactory nerve a special branch, which is indeed of remarkable size in embryos.
 
The stage with the nasal groove exists as the permanent condition in many Selachians. In these cases the deep nasal pits, which are enclosed )in a cartilaginous capsule, and the mucous membrane of which is raised up into
numerous parallel folds, lie on the under surface of the elongated snout or rostrum. Deep grooves, which are bounded by folds of the skin containing muscles, and which can be closed as if by valves, lead to the front margin of the mouth at some distance from its angle.
 
 
 
The next stage, which in human embryos is reached in the second half of the second month,
exhibits the organ of smell converted into two canals, which have been produced by the fusion of the margins of the two grooves, especially that of the inner nasal process with the maxillary process, which advances toward the median plane. The canals now possess two openings, the external and the internal nasal orifice (fig. 289) or the nares. The two external nares lie only a little above the border of the mouth-opening ; the internal, in the roof of the primitive oral cavity, on account of which they have been named by DURSY the primitive palatal clefts. They are located far forward, only a little removed from the edge of the mouth, a position which they retain permanently in the case of the Dipnoi and Amphibia. At first round, they afterwards become elongated and assume the form of a fissure running from in front backward.
 
With the metamorphosis of the organ of smell into a canal leading
 
 
 
Fig. 289. Roof of the oral cavity of a human embryo with the fundaments of the palatal processes, after His. Magnified 10 diameters.
 
 
 
THE ORGANS OF THE OUTER GERM-LAYER. 515
into the oral cavity, which has been effected in all Vertebrates that breathe by means of lungs, a second function has been assumed. It is now not exclusively a sensory organ for the perception of odors, but serves at the same time to conduct currents of air both to and from the oral and pharyngeal cavities and the lungs. It has become a kind of respiratory atrium for the apparatus of respiration. The assumption of this accessory function gives a special stamp to the later stages of the development of the organ, and is to be taken into account in a proper estimate of it. For the course of the further development is most of all determined by the tendency to an extensive enlargement of the surface of the olfactory chamber. The increase of surface, however, does not affect the real olfactory mucous membrane or sensory epithelium, to which the olfactory nerve is distributed, but rather the ordinary ciliate mucous membrane. It is therefore less connected with an improvement of the sense of smell than with an accessory function in the process of respiration. By an increase of the surface of the soft, vascular mucous membrane the air that is swept over it becomes warmed and freed from particles of dust, which are caught by the moist surface. From this time forward therefore one must distinguish a regio olfactoria and a regio respiratoria. The former, which is derived from the sensory epithelium of the original olfactory pit, remains relatively small, receives the terminations of the olfactory nerve, and is limited in the case of Man to the region of the upper turbinal process and a part of the septum nasi. It is the respiratory function that causes the vast dimensions which the organ of smell attains in the higher Vertebrates.
 
The increase in the surface of the nasal cavity is produced by three different events : (1) by the formation of the hard and soft palate, (2) by the development of the turbinal bones, (3) by the appearance of the accessory cavities of the nose.
 
The first event begins in Man toward the end of the second month. There is then formed on the inner surface of the maxillary process (fig. 289) a ridge, which projects into the wide primitive oral cavity and grows out horizontally into a plate. The right and left palatal plates at first embrace between them a broad fissure, through which may be seen the original roof of the oral cavity and on this the inner nasal orifices, which become more and more slit-like and are separated by a bridge of substance which has arisen from the median frontal process and can now be designated as the nasal septum. In the third month fae embryonic palatal fissu/re becomes gradually narrower.
 
 
 
516
 
 
EMBRYOLOGY.
 
 
 
 
Fig. 290. Cross section through the head of an embryo Pig 3 cm. long, crown-rump measurement.
 
The nasal cavities are seen to be in communication with the oral cavity at the places designated by a * ; A', cartilage of the nasal septum ; m, turbinal cartilage ; /, organ of JACOBSON ; /', the place where it opens into the nasal cavity ; gf, palatal process ; of, maxillary process ; zl, dental ridge.
 
 
 
The horizontal palatal processes of the upper jaw increase in size,
and finally their free edges encounter in the median plane the still broad nasal septum, which has grown down yet
f^Jj \ farther into the
'' fe* a Di
oral cavity. Then the parts mentioned begin to fuse with one another from before backward.
 
Two stages of this process are illustrated by the accompanyin g figures (figs. 290,
291), in which cross sections through the anterior end of two embryo
Pigs are represented. Figure
290 shows the
stage at which
the palatal
plate (gf ) of
the maxillary
process (of)
has advanced
close to the
lower margin
of the nasal
septum. Oral
and nasal cavities are still
in communication by means
of the very
narrow palatal fissure indicated by an asterisk.
 
In figure 291 the fusion has taken place. In this manner the
 
 
 
u
k
m J
 
 
Fig. 291. Cross section through the head of an embryo Pig 5 cm.
 
long, crown-rump measurement. k, Cartilaginous nasal septum ; m, nasal turbinal process ; /, JACOBSON'S
organ with jk, JACOBSON'S cartilage ; zl, dental ridge ; bl, covering
bone.
 
 
 
THE ORGANS OP THE OUTER GERM-LAYER. 517
primitive oral cavity is divided into two storeys, one above the other. One, the upper part, becomes associated with the organ of smell, to the enlargement of which it contributes ; it is distinguished from the space that arose from the original olfactory pit, or the olfactory labyrinth, as naso-pliaryngeal passage,. This opens behind into the pharynx by means of the posterior nares. The lower part becomes the secondary oral cavity. The partition that has been formed from the maxillary process is the palate, which later, when the development of the bones of the head can be traced, is differentiated into the hard and the soft palate.
 
A small portion of the palatal fissure, which in young embryos traverses the palate from in front backward and unites oral and nasal cavities (fig. 290 *), is preserved in most Vertebrates and constitutes the ductus nasopalatinus or STEXSON'S duct. A probe may be passed through it from the nasal to the oval cavity. In Man the duct of STENSON is closed during embryonic life ; there is preserved, however, in the palatal process of the bony maxilla at the corresponding place a vacuity, the canalis indsivus, occupied by connective tissue, blood-vessels, and nerves.
 
Where the ducts of STENSON are present, there are found in their vicinity the organs of JACOBSON, concerning which the statement has already been made that they are established very early as special depressions of the two olfactory pits. In Man this organ is converted into a narrow tube, which lies a little above the canalis incisivus and " pursues a straight course backward and slightly upward close to the cartilaginous partition, ending blindly " (SCHWALBE). In Mammals the organ is more highly developed (figs. 290, 291 J) ; it is enveloped in a special cartilaginous capsule (JACOBSON'S cartilage, jlc] and receives a special branch of the olfactory nerve, which terminates in a sensory epithelium, which agrees with that of the regio olfactoria. Frequently (e.g., in Ruminantia) it opens into the beginning of STENSON'S canal, which in this case remains open as a communication between nasal and oral cavities.
 
I cited the formation of folds as the second means of increasing the internal surface of the organ of smell. These are developed in Mammals (figs. 290, 291) and in Man on the lateral walls of the nasal chambers; they run parallel to one another from in front backward ; their free margins grow downward, and in consequence of the forms which they assume are called the three nasal turbinated processes, while the spaces between them are designated as upper, middle, and lower nasal 2 )assa 9 es - From the cartilaginous cranial
 
 
518 EMBRYOLOGY.
 
capsule they receive in Man as early as the second month a support, which subsequently ossifies. In many Mammals the turbinated processes acquire a complicated form owing to the production upon the first fold of numerous smaller secondary and tertiary folds, which become peculiarly bent and rolled up. On account of the complicated form resulting from, the production of the turbinated processes the olfactory sac has received the name of olfactory labyrinth.
 
Thirdly and lastly, the mucous membrane of the nose is increased in extent by the formation of evaginations which grow out partly into the ethmoid region of the cranial capsule, which consists of cartilage during early stages of development, and partly into a number of the covering bones (Belegknocheii).
 
In this manner are formed the numerous small cribriform pits in the cartilaginous cribriform plate. Somewhat later (in Man during the sixth month) an evagination into the upper jaw is developed into the antrum of HIGHMORE. Finally, after birth evaginations penetrate into the body of the sphenoid bone and into the frontal bone, producing the sinus sphenoidales and sinus frontales, which, however, attain their full development only at the time of sexual maturity. In many Mammals the enlargement of the nasal cavity takes place even farther backward into the body of the occipital bone (sinus occipitales). Inasmuch as the accessory cavities of the nose take the place of bone-substance, they naturally contribute to the diminution of the weight of the cranial skeleton.
 
In connection with the account of the organ of smell the formation
of the external nose ought now to be briefly considered. It is
developed out of the frontal process and the parts designated as
nasal processes (figs. 286, 288, and 289), these becoming elevated more
and more above the level of the surrounding parts. At first broad
and bulky, the nose later becomes thinner and longer arid acquires
characteristic forms. The nostrils, which at their formation are far
apart, come together in the median plane. Whereas the distance
in an embryo five weeks old is, as His has shown by measurements,
1-7 mm., it has become reduced in an embryo seven weeks old to
1-2 mm., and in one somewhat older to O'S mm. The median frontal
process is correspondingly reduced in thickness and furnishes the
nasal septum,
SUMMARY.
 
1. The organ of smell is developed out of two pit-like depressions of the outer germ-layer, which are formed on the frontal process at a considerable distance from each other.
 
 
 
THE ORGANS OF THE OUTER GERM-LAYER. 519
2. At a later stage the pits are united with the angle of the oral cavity by means of the nasal grooves.
 
3. The inner and outer margins of the olfactory pits and the nasal grooves project out as ridges arid constitute the inner and outer nasal processes.
 
4. By fusion of the margins of the nasal grooves the organ of smell is converted into two nasal passages, which open out on the frontal process by means of the external nares and on the roof of the primitive oral cavity a little back of the upper lip by means of the internal nares.
 
5. The internal nares afterwards become fissure-like and move nearer together, owing to the nasal septum becoming thinner and growing downward somewhat into the primitive oral cavity.
 
6. The upper part of the primitive oral cavity shares in the formation of the organ of smell and serves for the increase of its respiratory region, since horizontal ridges (the palatal processes) grow inward from, the maxillary processes toward the lower margin of the nasal septum, with which they fuse, and produce the hard and soft palate.
 
7. In the organ of smell a further enlargement of the spaces serving for respiratory purposes is produced by
() The formation of folds of its mucous membrane, by which the turbinated processes arise ;
(6) Evaginations of its mucous membrane into the adjacent parts of the cartilaginous and bony cephalic skeleton (formation of the " cells " in the cribriform plate, the frontal and sphenoidal sinuses, and the antrum of HIGHMORE).
 
8. In human embryos there is early formed in the olfactory pit a special depression of the outer germ -layer as fundament of the organ of JACOBSON, which receives a special branch of the olfactory nerve.
 
9. JACOBSON'S organ comes to lie at the base of the nasal septum remote from the olfactory region.
 
10. The ducts of STENSON in many Mammals and the canales incisivi in Man are preserved as remnants of the so-called palatal fissures the original fissure-like communications between nasal cavities and secondary oral cavity.
 
 
 
520 EMBRYOLOGY.
 
III. The Development of the Skin and its Accessory Organs.
 
Having now become acquainted with the physiologically more important functions of the outer germ-layer, which consist in the production of the nervous system and the sensory organs, I give a short survey of the changes which take place in the remaining part, which is now designated as primitive epidermis (Hornblatt). This furnishes the whole outer skin of the body or epidermis and the numerous and various organs that are differentiated out of it, such as the nails, the hair, and the sweat-, sebaceous, and milk-glands.
 
(a) The Skin.
 
The epidermis of Man is, according to the statements of KOLLIKER, very thin during the first two months of development, and consists of only two single layers of epithelial cells. Of these the superficial layer exhibits flattened, transparent, hexagonal elements ; the deeper one, on the contrary, consists of smaller cells ; so that already there is indicated by this a differentiation into a corneous and a mucous layer. Even now, too, a detachment of epidermal cells begins to manifest itself. For the outer cell-layer is soon found to be in process of decay, with obliterated cell -contours and indistinct nuclei, while a supplementary layer arises beneath it. In many Mammals the dying layer of cells is detached as a continuous sheet and then constitutes for a time a kind of envelope around the whole embryo, to which WELCKEII has given the name epitrichium, because the outgrowing hairs are developed beneath it.
 
From the middle of embryonic life onward both layers of the epidermis become thicker and the outermost of them contains cornified scales, the nuclei of which have degenerated. From this time onward a more extensive desquaination takes place at the surface, while the loss is made good by cell-divisions in the mucous layer and by the metamorphosis of these products of division into cornified cells. In consequence of this the surface of the embryo becomes up to the time of birth more and more covered with a yellowish-white, greasy mass the siiieynia eiiibryonum or vernix caseosa. This consists of a mixture of detached epidermal scales and of sebaceous secretions, which have been produced by the dermal glands that have arisen meantime. It forms a thick layer, especially on the flexor-side of the joints, on the sole of the foot, the palm of the hand, and on the head. Detached portions of it get into the
 
 
THE ORGANS OF THE OUTER GERM-LAYER. 521
amniotic fluid and make it turbid. Finally these, as well as some of the detached downy hairs, may be swallowed by the embryo with the amniotic fluid, and thus become a component of the meconium accumulated in the intestine.
 
The epidermis constitutes only one component of the skin of the adult or of the integument ; the other and more voluminous part the derma or corium is produced by the mesenchyme. The same thing takes place here as in the case of the other membranes and organs of the body. The epithelial layers derived from the primary yennlayers enter into close relationship with the mesenchyme, since they acquire from the latter a connective -tissue foundation that serves for their mechanical support and nutrition. Just as the inner germlayer unites with the intermediate layer to form the mucous membrane of the alimentary canal, as the epithelium of the auditory vesicle with the adjacent connective substance to form the meiiibr;inous labyrinth, and as the epithelial optic vesicle with the choroid and sclera to form the eyeball, so here also the epidermis unites with the corium to constitute the integument.
 
During the lirst months the corium forms in Man a layer of closely packed, spindle-shaped cells, and is delimited from the epidermis by a delicate, structureless, smooth-surfaced, bounding membrane (basement membrane), such as exists permanently in the case of the lower Vertebrates. In the third month it is differentiated into the corium proper and the looser subcutaneous tissue, in which there are soon developed clusters of fat cells. From the middle of pregnancy onward the latter so increase in number that the subcutaneous tissue soon becomes a layer of fat covering the whole body. At this time the smooth contour between epidermis and corium is lost, owing to the development on the surface of the latter of small papilla?, which grow into the mucous layer and produce the corpus papilla/re of the skin. The papilla? serve partly for the reception of loops of capillary blood-vessels, and thus effect a better nutrition of the mucous layer ; in part they receive the terminations of tactile nerves (tactile corpuscles), and thus are divided into vascular papilla? and nervous papilla?.
 
The skin of Vertebrates attains a higher degree of development in consequence of processes similar to those described for the intestinal canal. The epidermis increases its surface outward by the formation of folds, inward by invayinations. Because the evaginated and invaginated parts at the same time alter in many ways their histological peculiarities, there arises a large number of organs of
 
 
522 EMBRYOLOGY.
 
different kinds, which are developed in different ways in the separate classes of Vertebrates and which preeminently determine the external appearance of the animals.
 
As external processes arise the dermal teeth, and scales, the feathers, hair, and nails. As invaginations of the epidermis are developed the sweat-, sebaceous, and milk-glands. We will begin with the former, and. not to go too far into details, will limit ourselves to the organs of the skin in Mammals.
 
(b) The Hair.
 
The most characteristic epidermoidal structures of Mammals and Man are the hairs. One can distinguish two modifications in the method of their development. The ordinary method of development is that which is known in Man. In this case, at the end of the third embryonic month, the mucous layer grows at certain places and forms small solid plugs, the hair-germs, which sink into the underlying corium (fig. 292 B M). By afterwards elongating and becoming thickened at the deep end they assume the shape of a flask. Then there ensues a process similar to that which takes place upon the formation of the teeth. At the bottom of the epithelial plug the adjacent corium grows and forms a richly cellular nodule (yrt), which grows into the epithelial tissue and is the fundament of the connective-tissue hair-papillae, which is early provided with loops of blood-vessels. Around the whole ingrowing germ of the hair the surrounding parts of the corium are afterwards more and more distinctly arranged into special courses of fibres some of which run lengthwise, others in a circular manner and constitute a special, vascular, nutritive envelope, the hair-follicle (fig. 292 G, D, A6).
 
A somewhat different method of hair-formation has been observed by REISSNER, GOETTE, and FEIERTAG in certain Mammals.
 
In these the first impulse to the formation of the fundament of a hair is produced by a limited cell-growth of the corium immediately below the epidermis. It produces a small elevation (fig. 292 ^1), \vhich is simply the hair-papilla itself, projecting into the epidermis. Then the papilla is forced farther and farther away from the surface of the skin by the growth of the epidermal cells that cover it, and at last is found far removed from its place of origin and at the deep, somewhat thickened end of a long epithelial plug.
 
The final result is therefore the same in both cases, only the time of the formation of the first fundament of the papilla and of the
 
 
THE ORGANS OF THE OUTER GERM-LAYER. 523
epithelial plug is different. In the latter case the papilla arises at the surface of the skin and is forced down by a plug-like epithelial growth ; in the former the epithelial plug first sinks into the underlying tissue and then at its deep end the hair-papilla is formed by a growth of the corium.
 
The question arises, Which of these two methods of development is to be considered the more primitive? In my opinion it is the formation of the hair^apUla at the surf ace of the skin. For this is unquestionably the simpler and less complete condition, from which the latter is derivable and through which it is explainable. The hairs sink into the underlying tissue for the purpose of better nourishment and attachment. A parallel is furnished by the development of the teeth. In the Selachians the latter arise (so far as they are developed as protective structures in the skin) from papillae which grow from the corium into the epidermis ; in Teleosts and Amphibia, on the contrary, the teeth, which are found distributed over extensive areas in the oral mucous membrane, are established deep down in that membrane, for epithelial growths in the form of plugs first .sink down into the connective tissue, and it is only subsequently that the dental papillre are formed by a process of growth in the connective tissue at the bottom of the epithelial
 
 
downgrowth.
 
 
 
Let us return after this comparison to the further development of the hair ; this takes place in the same manner in both the cases distinguished above. Tbe epithelial cells which cover the papilla3 multiply and are differentiated into two parts (fig. 292 C) ; first, into cells that are more remote from the papillse, that become spindle-shaped and united into a small cone, and that by cornification produce the first point of the hair (ha), and secondly into cells which immediately invest the papilla, remain protoplasmic, and constitute the matrix the hair- bulb (hz) by means of which the further growth of the hair takes place. The cells of the hair-bulb, which rapidly increase by division, are added below to the first-formed part of the hair, and by cornification contribute to its elongation.
 
The hair in process of development on the papilla at first lies wholly concealed in the skin and is enveloped on all sides by cells of the epithelial plug, at the bottom of which the first trace of it was formed. From this investment are formed the outer and the inner sheaths of the root (fig. 292 C and D aw and iw). Of these the outer (aw) consists of small protoplasmic cells and is continuous externally with the mucous layer of the epidermis (schl), internally
 
 
524
 
 
EMBRYOLOGY.
 
 
 
with the hair-bulb (/is). The cells in the inner slieath of the root (iw) assume a flattened form and become cornified.
 
In consequence of the growth which proceeds from the bulb the hairs are gradually shoved up toward the surface of the epidermis, and at the end of the fifth month in the case of Man begin to break forth to the outside (fig. 292 D ha'}. They protrude more and more above the surface of the skin, even in the embryo, and constitute at many places of the skin, especially on the head, a rather
A n
 
 
 
 
 
 
D
ha'
ho
 
 
id
hb io
iw It a
hz pa
 
 
 
 
 
pa
C
ho
 
 
lib
 
 
ha
 
 
pa
 
 
Fig. 292 A !>. Four diagrams of the development of the hair. A, Development of the hairpapilla on the free surface of the skin, as it occurs, according to GOKTTE, in many Mammals. B, C, 1), Three different stages of the development of the hair in human embryos.
 
ho. Corneous layer of the epidermis ; scltl, mucous layer ; pa, hair-papilla ; hk, germ of hair ; hz, bulb of hair ; ha, yuung hair ; ha', tip of the hair protruding from the hair-follicle ; aw, iw, outer and inner sheath of the root of the hair ; lib, hair-follicle ; td, sebaceous gland.
 
thick covering. On account of their minute size and fineness, and because they fall out soon after birth, they are called the downy hair or lanuyo.
 
Each hair is a transitory structure of short duration. Af ter a time it falls out and is replaced by a new one. This process begins even during embryonic life. The hairs that fall off get into the anmiotic fluid, and since with this fluid they are swallowed by the embryo, they form one of the components of the meconmm accumulated in the intestinal canal. A more extensive change takes place in Man soon
 
 
THE ORGANS OF THE OUTER GERM-LAYER. 525
after birth with the shedding of the downy hair, which is replaced on many parts of the body by a more vigorous growth of hair. In Mammals the shedding of the old and the formation of new hair exhibits a certain periodicity, which is dependent on the warmer and colder periods of the year. Thus they develop a summer and a winter coat. Even in Man the shedding of the hair is influenced, although less noticeably, by the time of year.
 
The falling off of the hair is initiated by changes in the part resting on the papilla and called the bulb. The cell-multiplication, by means of which the addition of new corneous substance takes place, ceases ; the falling hair becomes detached from its matrix and its deep end looks as though it were split into shreds ; but it is still retained in the hair-follicle by its closely investing sheath, until it is forcibly removed or is crowded out by the supplementary hair that takes its place.
 
The opinions of investigators still differ concerning the manner in which the supplementary hairs are developed. An especial subject of controversy is the point whether the young hair is formed from an entirely new papilla (STIEDA, FEIERTAG) or from the old one (LANGER, v. EBNER), or whether both methods occur (KOLLIKER, UNNA). It seems to me that the first view is the correct one, and that the shedding of the hairs is due to the atrophy of their papilke. During this slowly occurring process of degeneration, perhaps even before it begins, the substitution is initiated by the occurrence of an active cell-proliferation at a place in the outer sheath of the root which indeed consists of cells rich in protoplasm and by the formation of a new plug, which grows out deeper into the derma from the bottom of the fundament of the old hair. At the blind [deep] end of this secondary hair -form there is then developed from the derma a new papilla, upon which is formed the new hair and its sheaths alongside of and below the old one, in the manner previously described. When it begins to increase in length, it presses against the old hair lying above it, crowds the latter out of its sheaths, until it falls off, and finally itself takes the place of it.
 
According to this account there would be a certain similarity between the shedding of the hair and that of the teeth, inasmuch as in both cases secondary epithelial processes, from which the new tooth- or hair-papilla begins, arise from the primary fundament, and inasmuch as the new structures by their growth displace the old.
 
 
 
526 EMBRYOLOGY.
 
In addition to the development of hairs from old fundaments, a second method of formation, which one might designate as direct or primary, is maintained by many writers (GoETTE, KOLLIKER). It is assumed that even after birth, both in the case of Man and other Mammals, hair-germs are formed directly from the mucous membrane of the epidermis, in the same manner as in the embryo. In how far, at what regions, and up to what age such a direct formation of hair takes place, demands still more detailed and exhaustive investigation.
 
(c) The Nails.
 
A second organ resulting from a cornification of the epidermis is the nail, which corresponds in a comparative-anatomical way to the claw- and hoof -like structures of other Mammals. In human embryos only seven weeks old there appear proliferations of the epidermis at the ends of the fingers, which are noticeably short and thick, and likewise at the ends of the toes, which are always less developed than the fingers. In consequence of the proliferations there arise from the loose epidermal cells complicated claw-like appendages, which have been described by HENSEN as predecessors of the nails or primitive nails.
 
In somewhat older embryos, from the ninth to the twelfth week, ZANDER found the epidermal growth marked off from its surroundings by a ring-like depression. The growth consists of a single layer of cylindrical cells with large nuclei lying on the side toward the derma and corresponding to the rete Malpighii, of two or three layers of polygonal spinous cells, and of a corneous layer.
 
The territory thus distinguished by a depression and by an altered condition of the cells ZANDER calls the primary basis of the nail (Nagelgrund), and describes it as occupying a greater part of the dorsal, but also a smaller part of the ventral surface of the terminal segment. He infers from this that the nails in Man originally had, like the claws of the lower Vertebrates, a terminal position on the toes and fingers, and that they have secondarily migrated on to the dorsal surface. Thus he explains the fact that the region of the nail is supplied with the ventral nerves of the fingers.
 
GEGENBAUR subscribes to ZANDER'S view of the terminal position of the fundament of the nail, but, supported by the investigations of BOAS, opposes ZANDER'S assumption of a migration of the fundament of the nail dorsally. He distinguishes in the development of nails and claws two parts (fig. 293), the dorsally located firm nail
 
 
THE ORGANS OF THE OUTER GERM-LAYER.
 
 
 
527
 
 
plate (np} and the plantar horn (Sohlenhorn, sh} connected with it ventrally. Of these the latter arises from the smaller ventral surface of the primary basis of the nail. In unguiculate and ungulate Vertebrates it (fig. 294 sh) is developed to a great extent ; in Man it atrophies, and is recognisable only in an exceedingly reduced condition as nail-iuelt. By this term is meant the welt-like thickening of the epidermis which forms the transition from the bed of the nail to the corrugated skin of the ball of the finger. The nail-plate, on the contrary, is from the beginning exclusively a product of the dorsal surface of the basis of the nail. There is therefore neither in Man nor in other Mammals a dorsal migration of the terminal fundament of the nail, but only a degeneration of
nw sh np
 
 
 
B
 
 
 
 
Fig. 204.
 
Fig. 293. A, Longitudinal section through the toe of a Cercopithecus. B, Longitudinal section
through the second finger of Macacus ater. After GEGENBAUR. np, Nail-plate ; sh, plantar horn (Sohlenhorn) ; mo, nail-wall.
 
Fig. 294. Section through a Dog's toe. After GEGEXBAUR. np, Nail-plate ; sh, plantar horn ; b, ball of toe.
 
its ventral portion, which otherwise furnishes a more complete plantar horn.
 
So far as regards the particular events in the development of the nail-plate, the structure is demonstrable in human embryos four months old as a thin flat layer of cornified, closely united cells 011 the dorsal surface of the primary basis of the nail or the bed of the nail. It is produced by the mucous layer upon which it immediately lies, but continues for a time to be covered by the thin corneous layer that is present at all points of the epidermis. This investment UNNA'S eponychium is not lost until the fifth month. However, notwithstanding their investment, the nails are easily recognisable some weeks before this from their whiteness, in distinction from the reddish or dark red color of the surrounding skin,
 
 
528 EMBRYOLOGY.
 
Owing to tho addition of now cells from tbo mucous membrane, both from below and from the posterior margin, the nail-plate grows it becomes thickened and increased in surface extent. It is now pushed forward from behind over the bed of tho nail, and at the seventh month its free margin begins to project beyond the latter.
 
With this the nail has acquired essentially the appearance and condition which it has in the adult. In new-born infants it possesses a margin which projects far over the ball of the finger, and which because it was formed at an early embryonic period is both much thinner and also narrower than the part formed later, which rests on the bed of the nail. This margin is therefore detached soon after birth.
 
(d) The Glands of the Skin.
 
The glandular structures of the epidermis, which are established by imagination, are of three kinds : sebaceous, sweat-, and urilkglands. They all arise as proliferations of the mucous layer which grow down as solid plugs into the derma, and then undergo further development either according to the tubular or the alveolar type.
 
The sweat-glands and the ear-wax glands are developed on the tubular plan. They begin in the fifth month to penetrate from the mucous membrane into the cerium ; in the seventh month they acquire a small lumen, take a winding course in consequence of increased growth in length, and become coiled especially at their deep ends, thereby giving rise to the first fundament of the glomerulus.
 
Sebaceous glands and milk-glands are alveolar structures. The former are either developed directly from the epidermis, as, for example, at the edges of the lips, on the prepuce and on the glans penis, or they are in close connection with the hairs, which is the ordinary condition. In the latter case they are formed as solid thickenings of the outer sheath of the root of the hair near the orifice of the follicle, even before the hairs are completely developed (fig. 292 0, D, td) ; at first they have the form of a flask, then they send out a few lateral buds, which develop club-shaped enlargements at their ends. The glands acquire cavities by the fatty degeneration and disintegration of the interior cells, which are eliminated as a secretion.
 
The development of the milk-glands, which are more voluminous organs entrusted with an important function and peculiar to the class Mammalia, is of greater interest. Of the numerous works that have appeared concerning them, the comparative-anatomical investigations of GEGENBAUR especially have led to valuable results.
 
 
 
THE ORGANS OF THE OUTER GERM-LAYER.
 
 
 
529
 
 
g
 
 
I present at the very beginning of the discussion the following proposition, which is of importance in interpreting the conditions found : each milk-gland in Man is not a simple organ, like an eargland or a submaxillary salivary gland, witli a, simple outlet, but a great glandular complex. Its earliest fundament has been observed in the human embryo at the end of the second month as a considerable thickening of the epidermis (fig. 295) upon the right and left sides of the breast. It has arisen as the result of a special proliferation of the mucous layer, which has sunk into the derma in the form of a hemispherical knob (df). But modifications arise afterwards in the corneous layer also, by its becoming thickened and projecting as a corneous plug into the proliferation of the mucous layer. Ordinarily there is found a small depression (g) at the middle of the whole epithelial fundament.
 
The proliferation of the epidermis that first appears is not precisely, as assumed by REIN, the first fundament of the glandular parenchyma ; it therefore does not correspond to the epithelial plugs which sink into the derma in the development of the sweat and sebaceous glands, because the further course of development and especially comparativeanatomical studies show, that by
the thickening of the epidermis there is only an early delimitation of a tract of the skin, which is subsequently metamorphosed into the nipple-area and papilla, and from the floor of which the separate milk-producing glands at length sprout forth.
 
The correctness of this view is shown by the following changes : In older embryos the lens-shaped thickening produced by the proliferation of the epidermis has increased at the periphery and has thereby become flattened (fig. 296 df). At the same time it is more sharply defined at the surface, owing to the derma becoming thickened and elevated into a wall (dw) the cutis-wall. Therefore the whole fundament now has the form of a shallow depression (df) of the skin, for which the name gland alar area is very appropriate. For there early grow out from its mucous layer into the derma solid
34
 
 
 
Fig. 295. Section through the fundament of the milk-gland of a female human embryo 10 cm. long, after Hi'ss.
 
df, Fundament of the glandular area ; g, small depression at its surface.
 
 
 
530
 
 
EMBRYOLOGY.
 
 
 
buds (dg), just as at other places the sebaceous glands arise from the epidermis. In the seventh month they are already well developed, and radiate out below and laterally from the pit-like depression. Their number increases up to the time of birth, and the larger ones become covered with solid lateral buds (dfy. Each sprout is the fundament of a milk-producing gland, which opens out on the glandular area (df) by means of a special orifice ; each is morphologically comparable with a sebaceous gland, although its function has become different.
 
The name glandular area is also a happily selected one because it presents a point of comparison with the primitive conditions of the Monotremes. For in these animals one does
 
 
dJb
 
 
dg
 
 
 
Fig. 296. Section throuh the fundament of the milk-gland of a female human embryo 32 cm.
 
long, after Huss. (?/, Glandular area ; dw, gland-wall ; dg, duct of gland ; db, vesicle of gland.
 
not find, as in the higher Mammals, a sharply differentiated single complex of milk-glands, but instead a somewhat depressed area of the skin, even provided with small hairs, over which are distributed single small glands, the secretion of which is licked up with the . tongue by the young, which are born in a very immature state.
 
In the remaining Mammals the glands, in the former case opening separately upon the area, are united into a single organ, which better serves the young in sucking, namely a papilla [nipple] or teat, which encloses all the outlets of the glands and is grasped by the mouth of the suckling. In Man their development begins after birth. The glandular area, which is encircled by the cutis-wall and which before birth was depressed into a pit,
 
 
THE ORGANS OF THE OUTER GERM-LAYER. 531
now becomes flattened until it lies in the same niveau with the surrounding skin. It is distinguished from the latter by its redder color, which is due to its greater vascularity and the thinner condition of its epidermis. Then during the first years after birth the middle of the glandular area, together with the outlets (ductus lactiferi), which there open out close to one another, is raised up and becomes the nipple, in the derma of which nonstriate muscle-fibres are formed in great numbers ; the remaining part of the area as far as the cutis-wall becomes the areola mammae. The metamorphosis takes place somewhat earlier in the female than in the male.
 
Soon after birth alterations take place in the still feebly developed glandular tissue. There occurs a transitory swelling of the pectoral glands accompanied with increased blood-pressure, and it becomes possible to press out of the gland a small quantity of a milky fluid, the so-called witches' milk. According to KOLLIKER its formation is due to the originally solid ducts of the glands acquiring at this time a lumen by the fatty degeneration of the central cells, which are dissolved, and, suspended in a fluid, are discharged from the ducts. According to the investigations of BARFURTH, on the contrary, the so-called witches' milk of infants is the product of a genuine transitory secretion, and is like the real milk of the mother both in its morphological and chemical components.
 
After birth great differences arise between the two sexes in the condition of the milk-glands. Whereas in the male the glandular parenchyma remains stationary in its development, in the female it begins to increase, especially at the time of sexual maturity and still more after the beginning of pregnancy. From the first-formed ducts of the glands there grow out numerous lateral, hollow branches, which become covered with hollow vesicular glands (alveoli) lined with a single layer of cylindrical epithelium. At the same time there are developed in the connective tissue, between the separate lobules of the gland, numerous islands of fat-cells. In consequence the region at which the complex of milk-glands has been formed swells into a more or less prominent elevation, the mamma.
 
SUMMARY.
 
1. The development of the hair is inaugurated in human embryos by the growing down of processes of the mucous layer of the epidermis- the hair^germs-^-into the underlying derma.
 
 
 
532 EMBRYOLOGY.
 
2. At the deep end of the hair-germ the vascular hair-papilla is begun by a growth of connective tissue.
 
3. The epithelial hair-germ is differentiated into :
(a) A young hair, by the cornification of a part of the cells ;
(b) An actively growing cell-layer situated between the shaft
of the hair and the papilla, the bulb, which furnishes the material for the growth of the hair ;
(c) The outer and the inner sheaths of the root.
 
4. Around the epithelial part of the fundament of the hair there is formed from the surrounding connective tissue the hairfollicle.
 
5. The nails in Man and the claws in other Mammals are developed from a dorsal fundament the nail-plate and a ventral fundament the plantar horn.
 
6. The plantar horn in Man is reduced to the nail-welt.
 
7. The thin nail-plate which is formed at first is for a time covered with a layer of cornified cells, the eponychium, which in Man is shed in the fifth month.
 
8. The milk-gland is a complex of alveolar glands.
 
9. At first there arises a thickening of the mucous layer of the epidermis, which is converted into the glandular area that is afterwards marked off from the surrounding parts by a wall and becomes somewhat depressed.
 
10. From the bottom of the glandular area there grow forth in great numbers the fundaments of alveolar glands.
 
11. After birth the glandular area, embracing the excretory ducts of the glands, is elevated above the surface of the skin, and converted into the nipple and the areola mammse.
 
12. After birth there is a transitory secretion of a small quantity of milk- like fluid the witches' milk.
 
 
 
LITERATURE.
 
(1) Development of the Nervous System.
 
Ahlborn. Ueber die Bedeutung der Zirbeldriise. Zeitschr. f. wiss. Zoologie.
 
Bd. XL. 1884, Altmann, R. Bemerkungen scur Hensen'schen Hypothese von der Nerven
entstehung. Archiv f. Anat. u. Physiol. Physiol. Abth. 1885. Balfour. On the Development of the Spinal Nerves in Elasmobranch Fishes.
 
Philos. Trails. Eoy. Hoc. London. Vol. CLXVI. 1876.
 
 
 
LITERATURE. 533
Balfour. On the Spinal Nerves of Amphioxns. Quart. Jour. Micr. Sci.
 
Vol. XX. isso. Beard, J. The System of P.ranrhial Sense Organs and their Associated
Ganglia in Ichthyopsida. Quart, Jour. Micr. Sci. Vol. XXVI. 1S85. Beard, J. A Contribution to the Morphology and Development of the
Nervous System of Vertebrates. Anat. Anzeiger. 188s. Beard, J. The Development of the Peripheral Nervous System of Vertebrates.
 
Quart, Jour. Micr, Sci. Vol. XXIX. 1888. Bedot. Recherches sur le developpement des nerfs spinaux chez les Tritons.
 
Recueil zool. Suisse. T. I. 1884. Also appeared as Dissertation Geneve
1884. Beraneck, E. Recherches sur le developpement des nerfs craniens chez les
Lezards. Recueil zool. Suisse. T. I. 1884, p. 519. Beraneck, E. Etude sur les replis mc'-dullaires du poulet, Recueil zool.
 
Suisse. T. IV. 1888, p. 205. Beraneck, E. Ueber das Parietalange der Reptilien. Jena. Zeitschr.
 
?,d. XXL 1888.
 
Bidder uncl KupfFer. Untersuch. iiber das Ruckenmark. Lnpz'nj 1857. Chiarugi, G. Lo sviluppo dei nervi vago, accessorio, ipoglosso e prirni
cervicali nei sauropsidi e nei mammiferi. Atti Soc. Toscana di Sci. nat.
 
I'isa. Vol. X. 1SN!>. Dohrn. Ueber die erste Anlage und Entwicklung der motorischen Rilcken
marksnerven bei den Selachiern. Mitth. a. d. zool. Station Neapel.
 
P.d. VIII. 1888. Ecker, A. Zur Entwicklungsgeschichte der Furchen und Windungeu der
Grosshirnhemispharcn im Foetus des Menschen. Archiv f. Anthropologie.
 
lid. III. 1868. Ehlers, E. Die Epiphysc am Gehirn der Plagiostomen. Zeitschr. f. wiss.
 
Zoologie. Bd. XXX. Suppl. 1878, p. 607. Flechsig. Die Leitungsbahnen im Gehirn und Ruckenmark des Menschen.
 
Auf Grand entwicklungsgesch. Untersuchungen dargestellt. Leipzig 1870. Froriep, August. Ueber ein Ganglion des Hypoglossus u. Wirbelanlagen
in der Occipitalregion. Archiv f. Anat. u. Physiol. Anat. Abth. 1882. Froriep, August. Ueber Anlagen von Sinnesorganen am E'acialis, Glosso
pharyngeus uud Vagus etc. Archiv f. Anat, u. Physiol. Anat. Abth.
 
 
 
Goronowitsch. Studien iiber die Entwicklung des Medullarstranges bei
Knochenfischen, nebst P>eobachtungen iiber die erste Anlage der Keim
bliitter und der Chorda bei Salmoniden. Morphol. Jahrb. Bd. X. 1885.
 
p. 376. Hensen, V. Zur Entwicklung des Nervensystems. Virchow's Archiv.
 
Bd. XXX. 1864. Hensen, V. Ueber die Nerven im Schwanz der Froschlarven. Archiv f.
 
raikr. Anat. Bd. IV. 1868, p. 111. Hensen, V. Beitrag zur Morphologie der Korperformen und des Gehirns
des menschlichen Embryos. Archiv f. Anat. u. Entwicklungsg. 1877. Hertwig, Oscar und Richard. Das Nervensystem und die Sinnesorgane
der Medusen. Monographisch dargestellt. Leipzig 1878. His. Zur Geschichte des menschlichen Riickenmarkes und der Nerven
wurzeln. Abhancll. d. math.-physik. Cl. d. Kgl, Sachs, Gesellsch. d,
Wissensch. Nr. IV. Bd. XIII. 1886.
 
 
 
534 EMBRYOLOGY.
 
His. Ucbor die An Hinge des peripherischen Nervensvslcms. Archiv f. Anat.
 
n. Entwicklungsg. Jnhrg. isjj). His. Ueber das Auftreten dor weisscn Substanz mid dor Wurzelfasern am
Riickenmark menschlicher Embryonen. Archiv f. Anat. u. Physiol.
 
Anat. Abtli. 18S3. His. Die Ncnroblastcn mid cleren Entstehung im embryonalen Mark.
 
Abhandl. d. math.-physik. Cl. d. Kgl. Sachs. Gesellsch. d. Wissensch.
 
Bd. XV. Nr. IV. 1889. His. Die Formentwicklung des menschlichen Vorderhirns vom ersten bis
zum Beginn des dritten Monats. Abhandl. d. math.-physik. Cl. d. Kgl.
 
Sachs. Gesellsch. d. Wissensch. Bd. XV. 1889. His. Die Entwicklung der ersten Nervenbahnen beim menschlichen Embryo.
 
Archiv f. Anat, u. Physiol. Anat. Abth. 1887. His, W., jun. Znr Entwicklungsgeschichte des Acustico-facialis-Gebietes
beim Menschen. Archiv f. Anat. u. Physiol. Anat. Abth. 1889. Suppl.
Bd. pp. 1-28. Julin, Ch. De la signification morphologique de I'epiphyse des vertebres.
 
Bull. sci. du depart, du Nord. Ser. II. T. X. 1888. Kollmann, J. Die Entwicklung der Adergeflechte. Ein Beitrag zur
Entwicklungsgesch. des Gehirns. Leipzig 1861. Krause, W. Ueber die Doppelnatur des Ganglion ciliare. Morphol. Jahrb.
 
Bd. VII. 18S2, p. 43. Kraushaar, Richard. Die .Entwicklung der Hypophysis u. Epiphysis bei
Nagethieren. Zeitschr. f. wiss. Zoologie. Bd. XLI. 1884, p. 79. (Complete catalogue of the literature.) Kupffer. Primiire Metamerie des Neuralrohrs der Vertebraten. Sitzungsb.
 
d. k. bair. Akad. Munchen. Bd. XV. 1886, p. 469. Lowe, L. Beitrage zur Anatomie und Entwicklung des Nervensy stems der
Saugethiere u. des Menschen. Berlin 1880. Marshall, Milnes. The Development of the Cranial Nerves in the Chick.
 
Quart. Jour. Micr. Sci. Vol. XVIII. 1878. Marshall, Milnes. On the Early Stages of Development of the Nerves in
Birds. Jour. Anat, and Physiol. Vol. XI. 1877. Marshall, Milnes. On the Head Cavities and Associated Nerves of Elasmo
branchs. Quart. Jour. Micr. Sci. Vol. XXI. 1881. Mihalkovics, v. Wirbelsaite und Hirnanhang. Archiv f. mikr. Anat.
 
Bd. XI. 1875. Mihalkovics, v. Entwicklungsgeschichte des Gehirns. Nach Untersuch
ungen an hoheren Wirbelthieren und dem Menschen dargestellt. Leipzig
1877. (Catalogue of the older literature.) Miiller, W. Ueber Entwicklung und Bau der Hypophysis und cles Processus
infundibuli cerebri. Jena. Zeitschr. Bd. VI. 1871. Onodi. Ueber die Entwicklung des sympath. Nervensystems. Archiv f.
 
mikr. Anat. Bd. XXVI. 1886. Onodi. Ueber die Entwicklung der Spinalganglien und der Nervenwurzeln.
 
Internat. Monatsschr. f. Anat, u. Histol. Bd. I. 1884. Osborn, H. F. The Origin of the Corpus Callosum, a Contribution upon the
Cerebral Commissures of the Vertebrata. Morphol. Jahrb. Bd. XII.
 
1887. Rabl. Bemerkung iiber die Segmentirung des Hirns, Zool. Anzeiger,
Jahrg. VIII. 1885, p. 192.
 
 
 
LITERATURE. 535
Rabl-Riickhard. Das gegenseitige Verhaltniss der Chorda, Hypophysis
uncl des mittleren Schadelbalkens bei Haifischembryonen etc. Morphol.
 
Jahrb. Bd. VI. 1880. Rabl-Riickhard. Zur Deutung uncl Entwicklung des Gehirns der Knochen
fische. Archiv f. Anat. u. Physiol. Anat. Abth. 1882. Rabl-Riickhard. Das Grosshirn der Knochenfische und seine Anhangs
gebilde. Archiv 1 Anat. u. Physiol. Anat. Abth. 1883. Rathke, H. Ueber die Entstehung der Glandula pituitaria. Archiv f. Auat.
 
u. Physiol. Bd. V. 1838.
 
Reichert. Der Bau des menschlichen Gehirns. Leipzig 1859 and 1861. Sagemehl. Untersnchungen iiber die Entwicklung der Spinalnerven. Dor pat
1882. Schmidt, F. Beitrage zur Entwicklungsgeschichte des Gehirns. Zeitschr.
 
f. wiss. Zoologie. Bd. XI. 1S62. Schultze, O. Ueber die Entwicklung der Medullarplatte des Froscheies.
 
Verhandl. der phys.-med. Gesellsch. Wiirzburg. N. F. Bd. XXIII. 18*9. Schwalbe, G. Das Ganglion oculomotorii. Jena. Zeitschr. Bd. XIII.
 
 
 
Schwalbe, G. Lehrbuch der Neurologic. Erlangen 1880.
 
Spencer, W. Baldwin. On the Presence and Structure of the Pineal Eye
in Lacertilia. Quart. Jour. Micr. Sci. Vol. XXVII. 1886. Suchannek. Bin Fall von Persistenz des Hypophysenganges. Anat. Anzeiger.
 
Jahrg. II. Nr. 16. 1887. Tiedemann, Fr. Anatomic und Bildungsgeschichte des Gehirns im Foetus
des Menschen. Ni'mibcry 1816. Wijhe, J. ~W. v. Ueber die Mesodermsegmente und die Entwicklung der
Nerven des Selachierkopfes. Verhandl. d. koninkl. Akad. d. Wetenschappen
Amsterdam. 1882. Deel XXII.
 
 
 
(2) Development of the Eye.
 
Angelucci, A. Ueber Entwicklung und Bau des vorderen Uvealtractus der
Vertebraten. Archiv f. mikr. Anat. Bd. XIX. 1881, p. 152. Arnold, Jul. Beitrage zur Entwicklungsgeschichte des Anges. Heidelberg
1874. Babuchin. Beitrage zur Entwicklungsgesch. des Auges. Wiirzburger
Xaturwiss. Zeitschr. Bd. IV. 1863, p. 71. Bambeke. Contribution a 1'histoire du developpement de 1'oeil humain. Ann.
 
de la Soc. de med. de Gand. 1879. Ewetsky, v. Beitrage zur Entwicklungsgeschichte des Auges. Archiv f.
 
Augenheilkunde. Bd. VIII. 1879. Gottschau. Zur Entwickluiig der Saugethierlinse. Anat. Anzeiger. Jahrg. I.
 
 
 
Keibel, Fr. Zur Entwicklung des Glaskorpers. Archiv f. Anat. u. Physiol.
 
Anat. Abth. 1886. Kessler. Untersuchungen iiber die Entwicklung des Auges, angestellt am
Hiihnchen und Triton. Dissertation. Dorpat 1871. Kessler. Zur Entwicklung des Auges der Wirbelthiere. Leipzig 1877. Kolliker. Ueber die Entwicklung der Linse. Zeitschr. f. wiss. Zoologie.
 
Bd. VI. 1855.
 
 
 
536 EMBRYOLOGY.
 
Kolliker. Zur Entwicklung dcs Auges und Geruohsorgancs menschlicher
Kmbrvnnrn. Xum Jubiliium dor Univorsitiit Ziirirh. Wiirzlurf] 1883. Koranyi, Alexander. P.oitmgo zur Entwioklung dor Kvystalllinse bei den
\Yirbeltliioivn. .Internat. Monntssc.hr. f. An,- it. u. riist.nl. I'd. III. 1SXC,. Kupffer. CTntersuchungen liber die Entwicklung des Augenstiels. Sitzungsb.
 
d. Gcscllsch. f. Morphol. u. Physiol. Miinchcn. Bd. I. 1885, p. 174. Lieberkuhn, 3ST. Ucber das Auge des Wirbelthierembryos. Schriften d.
 
Gcsellsc.h. z. P.eford. d. gcs. Naturwiss. Marburg. Bd. X. 1872, p. 299. Iiieberkiihn, N. Zur Anatomie des embryonalen Auges. Sitzungsb. d.
 
Gesellscli. z. Beford. d. ges. Naturwiss. Marburg. 1877, p. 125. Lieberkiihn, N. Beitrage zur Anatomic des embryonalen Auges. Archiv
f. Anat. u. Entwicklungsg. Anat. Abth. Jahrg. 1879, pp. 1-29. Manz. Entwicklungsgeschichte des menschlichen Auges. Graefe u. Saemisch.
 
Handbuch d. Augenheilkunde. Bd. II. Leijtziri 1875, pp. 1-57. Milialkovics, v. Ein Beitrag zur ersten Anlage der Augenlinse. Archiv f.
 
rnikr. Anat. Bd. XI. 1875. Miiller, W. Ueber die Stammesentwicklung des Sehorgans der Wirbelthiere.
 
Festgabe an Carl Ludwig. Leipzig 1874. Rumschewitsch. Zur Lebre von der Entwicklung des Auges. Schriften
d. Gesellscb. d. Naturf. Kiew. Bd. V. Heft 2, 1878, p. 144. (Russian.) Wiirzburg, A. Zur Entwicklungsgeschichte des Saugethierauges. In
auguraldissertation der Berliner Universitiit. 1870.
 
 
 
(3) Development of the Ear.
 
Boettcher, A. Ueber Entwicklung u. Bau des Gehorlabyrinths. Nach
Untersuchungen an 81iugethieren. Verhandl. d. Kaiserl. Leop.-Carol.
 
Acad. Bd. XXXV. 1869. Gradenigo, G. Die embryonale Anlage der Gehb'rknochelchen und des tubo
tympanalen Baurnes. Centralbl. f. d. med. Wiss. 1886. Nr. 35. Gradenigo, G. Die embryonale Anlage des Mittelohres. Die inorpholog.
 
Bedeutung der Gehorknochelchen. Mitth. a. d. embryol. Inst. d. Univ.
 
Wien. Heft 1887, p. 85. Hasse. Die vergleich. Morphologie u. Histologie d. hautigen Gehb'rorgans
der Wirbelthiere. Leipzig 1873. Hensen. Zur Morphologie der Schnecke. Zeitschr. f. wiss. Zoologie. Bd.
 
XIII. 1863.
 
His, W. Anatomie menschlicher Embryonen. Leipzig 1880, 1882, 1885. Hoffmann, C. K. Ueber die Beziehung der ersten Kiementasche zu der
Anlage der Tuba Eustachii u. des Cavum tympani. Archiv f. mikr. Anat.
 
Bd. XXIII. 1884. Huschke. Ueber die erste Bildungsgesch. d. Auges u. Ohres beim bebriiteten
Hiilmchen. Oken's Isis, 1831, p. 950. Huschke. Ueber die erste Entwicklung des Auges. Meckel's Archiv.
 
1832. Moldenhauer. Zur Entwicklung des mittleren und iiusseren Ohres. Morphol.
 
Jahrb. Bd. III. 1877. Noorden, C. v. Die Entwicklung des Labyrinths bei Knochenfischen.
 
Archiv f. Anat. u. Physiol. Anat Abth. 1883. Reissner. De Auris internae formatione. Inaiig.-Diss. Dorpat 1851.
 
 
 
LITERATURE. 537
Rosenberg, E. Untersuchungen liber die Entwickl. des Canalis cochlearis
d. Saugethiere. Diss. Dor pat 1868. R/iidinger Zur Entwicklung der hautigen Bogengange des inneren Ohres.
 
Sitzungsb. d. math.-physik. Cl. d. Acad. d. Wissensch. Miinchen. 1888. Tuttle. The Eolation of the External Meatus, Tympanum and Eustachian
Tube to the First Visceral Cleft. Proceed. Amer. Acad. Arts a. Sci. 1883-4Urbantschitsch. Ueber die erste Anlage des Mittelohres u. d. Trornmelfelles.
 
Mitth. a. d. embryol. Inst. Wien. Heft I. 1877.
 
 
 
(4) Development of the Ore/an of Smell.
 
Blaue, J. Untersuchungen liber den Bau der Nasenschleimhaut bei Fischen.
 
u. Amphibien etc. Archiv f. Anat. u. Physiol. Anat, Abth. 1884. Born, G. Die Naseuhohlen und der Thranennasengang der Amphibien.
 
Morphol. Jahrb. Bd. II. 1876. Born, G. Die Nasenhohle u. d. Thranennasengang der amnioten Wirbelthiere.
 
Morphol. Jahrb. Bd. V. 1879 u. Bd. VIII. 1883. Diirsy. Zur Entwicklungsgeschichte des Kopfes. Tubingen 1869. Fleischer, R. Beitriige zur Entwicklungsgeschichte des Jacobson'schen
Organs u. zur Anat. der Nase. Sitzungsb. d. physic. -med. Soc. Erlaugen.
 
1877. Herzfeld. Ueber das Jacobson'sche Organ des Menschen u. d. Siiugethiere.
 
Zool. Jahrbiicher. Bd. III. 1888, p. 551. Xb'lliker, A. Ueber die Jacobson'schen Organe des Meuschen. Gratula
tionsschrift d. Wiirzb. Medic. Facultiit fur Kinecker. 1877. Kolliker, A. Zur Entwicklung des Auges und Geruchsorgans menschlicher
Embryonen. Festschrift der Schweizerischen Universitiit Ziirich zur
Feier ihres 50ja'hr. Jubiliiums gewidmet. Wiirzlmrg 1883. Kolliker, Th. Ueber das Os intermaxillare des Menschen etc. Nova acta
L.-C, Acad. Bd. XLII. p. 325. Halle 1881. Legal. Die Nasenhohle und der Thranennasengang der amnioten Wirbelthiere.
 
Morphol. Jahrb. Bd. VIII. 1883. Legal. Zur Entwicklungsgeschichte des Thranennasengangs bei Siiugethieren.
 
Inaug.-Diss. Breslau LS82 (?). Marshall, Milnes. The Morphology of the Vertebrate Olfactory Organ.
 
Quart. Jour. Micr. Sci. Vol. XIX. 1879.
 
(5) Development of the Skin and its Organs.
 
Barfurth. Zur Entwicklung der Milchdriise. Bonn 1882.
 
Boas, J. E. V. Ein Beitrag zur Morphol. der Nagel, Krallen, Hufe und
Klauen d. Saugethiere. Morphol. Jahrb. Bd. IX. 1884. Creighton, C. On the Development of the Mamma and of the Mammary
Function. Jour. Anat. and Physiol. Vol. XI. 1877, pp. 1-32. Feiertag. Ueber die Bildung der Haare. Inaug.-Diss. Dor pat 1875. Gegenbaur, C. Zur Morphologic des Nagels. Morphol. Jahrb. Bd. X.
 
1885. Gegenbaur, C. Bemerkungen liber die Milchdrlisenpapillen der Saugethiere.
 
Jena. Zeitschr. Bd. VII. 1873. Gegenbaur, C. Zur genaueren Kenntniss der Zitzen der Saugethiere.
 
Morphol. Jahrb. Bd. I. 1875.
 
 
 
538 KM BRYOLOGY.
 
Gotte. Zur Morphologie der Haare. Archiv f. mikr. Anat. Ed. IV. 1808,
p. 27:5. Hensen. Beitrag zur Morphologie der Korperform und cles Gehirns des
menscbl. Embryos. Archiv f. Anat. u. Kntwicklungsg. Anat. Abth.
 
Jahrg. 1ST 7. Huss, M. Beitrage zur Entwicklung der Milchdriisen bei Menschen und bei
Wiederkauern. Jena. Zeitschr. Bd. VII. 1873. Klaatsch, Hermann. Zur Morphologie der Saugethier-Zitzen. Morphol.
 
Jahrb. Bd. IX. 1884. Kolliker, A. Zur Entwicklungsgeschichte der aussern Haut. Zeitschr. f .
 
wiss. Zoologie. Bd. II. 1850, p. 67. Kolliker, Th. Beitrage zur Kenntniss der Brustdriise. Verhandl. Wurzburg.
 
physical.-med. Gesellsch. Bd. XIV. 1879. Langer, C. Ueber den Bau und die Entwicklung der Milchdriisen. Denkschr.
 
d. k. Acad. d. Wissenscb. Wien. Bd. III. 1851. Rein, G. Untersuchungen liber die embryonale Entwicklungsgeschichte der
Milchdriise. Archiv f. mikr. Anat. Bde. XX. u. XXI. 1882. Reissner. Beitrage zur Kenntniss der Haare des Menschen und der Thiere.
 
Breslau 1854. Toldt, C. Ueber die Altersbestimmung menschlicher Embryonen. Prager
med. Wochenschr. 1879. Unna, P. Z. Beitrage zur Histologie und Entwicklungsgeschichte der
menschlichen Oberhaut und ihrer Anhangsgebilde. Archiv f . mikr. Anat.
 
Bd. XII. 187G. Zander, R. Die friihesten Stadien der Nagelentwicklung und ihre Beziehungen
zu den Digitalnerven. Archiv f. Anat. u. Entwickluugsg. Jahrg. 1884.
 
 
 
CHAPTER XVII.
 
THE ORGANS OF THE INTERMEDIATE LAYER OR,
MESENCIIYME.
 
THE grounds which made it appear necessary to distinguish in addition to the four epithelial germ-layers a special intermediate layer or mesenchyme have already been given in the first part of this text-book. This distinction is also warranted by the further progress of development. For all the various tissues and organs which are derived in many ways from the intermediate layer allow, even subsequently, a recognition of their close relationship. Histologically the various kinds of connective substance have been for a long time considered as constituting a single family of tissues.
 
It will be my endeavor to emphasise the relationship of the organs of the intermediate layer, and whatever is characteristic of them from a morphological point of view, more than has been hithei'to customary in text-books, and to do the same in a forma]
 
 
THE ORGANS OF THE INTERMEDIATE LAYER OR MESENCHYME. 539
way by embracing these organs in a chapter by themselves and discussing them apart from the organs of the inner, middle, and outer germ-layers.
 
It is the original province of the intermediate layer to form a packing and sustentative substance between the epithelial layers, a fact which stands out with the greatest distinctness particularly in the lower groups, as for example in the Ccelenterates. It is therefore closely dependent upon the epithelial layers in the matter of its distribution. When the germ-layers are raised up into folds, it penetrates between the layers of the fold as a sustentative lamella ; when the germ-layers are folded inwards, it receives the parts that are being differentiated as for example in the Vertebrates, the neural tube, the masses of the transversely striped muscles, the secretory parenchyma of glands, the optic cups, and the auditory vesicles and provides them with a special envelopment that adjusts itself to them (the membranes of the brain, the perimysium, and the connective-tissue substance of the glands). In consequence of this the intermediate layer, in the same proportion as the germ-layers become more fully organised, becomes itself converted into an extraordinarily complicated framework, and resolved into the most divergent organs, by the formation of evaginations and invaginations and the constricting off of parts.
 
The form of the intermediate layer thus produced is of a secondary nature, for it is dependent upon the metamorphosis of the germlayers, with which it is most intimately connected. But in addition, the intermediate layer, owing to its own great power of metamorphosis, acquires in all higher organisms, particularly in the Vertebrates, an intricate structure, especially in the way of liistological differentiation or metcvnwrphosis. In this way it gives rise to a long series of various organs the cartilaginous and bony skeletal parts, the fasciae, aponeuroses, and tendons, the blood-vessels and lymphatic glands, etc.
 
It is therefore fitting to enter here some\vhat more particularry upon a discussion of the principle of histoloyical differentiation, and especially to inquire in what manner it is concerned in the origin of organs differentiated in the mesenchyme.
 
The most primitive and simplest form of mesenchyme is gelatinous tissue. Not only does it predominate in the lower groups of animals, but it is also the first to be developed in all Vertebrates, out of the embryonic cells of the intermediate layer, and is here the forerunner and the foundation of all the remaining forms of sustentative substance.
 
 
 
540 EMBRYOLOGY.
 
In a homogeneous, soft, quite transparent matrix, which chemically considered contains mucous substance or mucin, and therefore does not swell in warm water or acetic acid, there lie at short and regular intervals from one another numerous cells, which send out in all directions abundantly branched protoplasmic processes and by means of these are joined to each other in a network.
 
In the lower Vertebrates the gelatinous tissue persists at many places, even when the animals are fully grown ; in Man and other Mammals it early disappears, being converted into two higher forms of connective substance, either intojlbrillar connective tissue or into cartilaginous tissue. The first-named arises in the gelatinous matrix by the differentiation of connective-tissue fibres on the part of the cells, which are sometimes close together, sometimes widely scattered. These fibres consist of collagen and upon boiling produce glue. At first sparsely represented, these glue-producing fibres continually increase in volume in older animals. Thus transitional forms, which are designated as foetal or immature connective tissue, lead from gelatinous tissue to mature connective tissue, which consists almost exclusively of fibres and the cells which have produced them. This is capable of a great variety of uses in the organism, according as its fibres cross one another in various directions without order, or are arranged parallel to one another and grouped into special cords and strands. Thus, in connection with other parts derived from the germlayers, it gives rise to a great variety of organs. In some places it forms the foundation for epithelial layers of great superficial extent ; together with them it produces the integument, composed of epidermis, corium, and subcutaneous connective tissue, and the various mucous and serous membranes ; in others it unites with masses of transversely striped muscle, and arranges itself under the influence of their traction into parallel bundles of tense fibres, furnishing tendons and aponeuroses. Again at other places it takes the form of firm sheets of connective tissue, which serve for the separation or enveloping of masses of muscle, the intermuscular ligaments and the fasciae of muscles.
 
The second metamorphic product of the primary mesenchyme, cartilage, is developed in the following manner : At certain places the embryonic gelatinous tissue acquires as a result of proliferation a greater number of cells, and the cells secrete between them a cartilaginous matrix, chondrin. The parts which have resulted from the process of chondrification exceed in rigidity to a considerable extent the remaining kinds of sustentative substance, the gelatinous
 
 
THE ORGANS OF THE INTERMEDIATE LAYER OR MESENCHYME. 541
and the glue-producing intermediate tissue ; they are sharply differentiated from their softer surroundings, and become adapted, in consequence of their peculiar physical properties, to the assumption of special functions. Cartilage serves in part to keep canals open (cartilage of the larynx and bronchial tree), in part for the protection of vital organs, around which they form a firm envelope (cartilaginous cranium, capsule of the labyrinth, vertebral canal, etc.), and in part for the support of structures projecting from the surface of the body (cartilage of the limbs, branchial rays, etc.). At the same time they afford firm points of attachment for the masses of muscle imbedded in the mesenchyine, neighboring parts of the muscles entering into firm union with them. In this manner there has arisen through histological metamorphosis a differentiated skeletal apparatus, which increases in complication in the same proportion as it acquires more manifold relations with the musculature.
 
Cartilaginous and connective tissues, finally, are capable of a further histological metamorphosis, since the last form of sustentative substance, osseous tissue, is developed from them in connection with the secretion of salts of lime. There are therefore bones that have arisen from a cartilaginous matrix ami others from one of connective tissue. With the appearance of bone, the skeletal apparatus of Vertebrates has reached its highest perfection.
 
Even if the rnesenchyme has by these processes experienced an extraordinarily high degree of differentiation and a great diversity of form, the histological processes of differentiation which take place in it are nevertheless not yet exhausted. In the gelatinous or connective-tissue matrix canals and spaces arise in which blood and lymph move in accomplishing their function of intermediating in the metastasis of the organism, not only conveying the nutritive fluids to the individual organs, but also conducting away both the substances which owing to the chemical processes in the tissues
-have become useless and the superfluous fluids. Out of these first beginnings arises a very complicated organic apparatus. The larger cavities constitute arteries and veins, and acquire peculiarly constructed thick walls, provided with non-stria te muscle-cells and elastic fibres, in which three different layers can be distinguished as tunica intinia, media, and adventitia. A small part of the blood-passages, especially distinguished by an abundance of muscle-cells, is converted into a propulsive apparatus for the fluid
-the heart. The elementary corpuscles that circulate in the
 
 
542 EMBRYOLOGY.
 
currents of the fluid, the blood-cells and lymph-cells, demand renewal the more frequently the more complex the metastasis becomes. This leads to the formation of special breeding places, as it were, for the lymph-corpuscles. In the course of the lymphatic vessels and spaces there takes place at certain points in the connective tissue an especially active proliferation of cells. The substance of the connective-tissue framework assumes here the special modification of reticular or adenoid tissue. The surplus of cells produced enters into the lymphatic current as it sweeps past. According as these lymphoid organs exhibit a simple or a complicated structure, they are distinguished as solitary or aggregated follicles, as lymphatic ganglia and spleen.
 
Finally there are formed at very many places in the intermediate layer, as especially in the whole course of the intestinal canal, organic [non-striate] muscles.
 
After this brief survey of the processes of differentiation in the intermediate layer, which are primarily of an histological nature, I turn to the special history of the development of the organs which arise from it, the blood-vessel and skeletal systems.
 
 
 
I. The Development of the Blood-vessel System.
 
The very first fundament of the blood-vessels and the blood has already been treated of in the first part of this text-book. We will therefore here concern ourselves with the special conditions of the vascular system, with the origin of the heart and chief blood-vessels, and with the special forms which the circulation presents in the various stages of development, and which are dependent on the formation of the foetal membranes. In this I shall treat separately, both for the heart and for the rest of the vascular system, the first fundamental processes of development and the succeeding alterations, from which the ultimate condition is finally evolved.
 
 
 
A. The first DeveloyMientcd Conditions of the Vascular System.
 
(a) Of the Heart.
 
The vascular system of Vertebrates can be referred back to a very simple fundamental form namely, to two blood-vessel trunks of which the one runs above and the other below the intestine in the direction of the longitudinal axis of the body. The dorsal trunk, the
 
 
THE ORGANS OF THE INTERMEDIATE LAYER OR MESENCHYME. 543
aorta, lies in the attachment of the dorsal mesentery, by means of which the intestine is connected to the vertebral column ; the other trunk, on the contrary, is imbedded in the ventral mesentery, as far, at least, as such a structure is ever established in the Vertebrates ; it is almost completely metamorphosed into the heart. The latter is therefore nothing else than a peculiarly developed part of a main blood-vessel provided with especially strong muscular walls.
 
In the first fundament of the heart there are two different types to be distinguished, one of which is present in Selachians, Ganoids, Amphibia, and Cyclostomes, the other in Bony Fishes and the higher Vertebrates Reptiles, Birds, and Mammals.
 
In the description of the first type, I select as an example the
 
 
 
ep
 
 
Fig. 297. Cross section through the region of the heart of an embryo of Salamandra maculosa,
in which the fourth visceral arch is indicated, after RABL. d, Epithelium of the intestine ; cm, visceral middle layer ; ep, epidermis ; Ih, anterior part of
the body-cavity (pericardio-thoracic cavity) ; end, endocardium ; p, pericardium ; vhg, meso
cardium anterius.
 
development of the heart in the Amphibia, concerning which a detailed account has very recently been published by RABL.
 
In Amphibia the heart is established very far forward in the embryonic body, underneath the pharynx or cavity of the head-gut (figs. 297, 298). The embryonic body-cavity (IK) reaches into this region, and in cross sections appears upon both sides of the median plane as a narrow fissure. The lateral halves of the body-cavity are separated from each other by a ventral mesentery (vhy), by means of which the under surface of the pharynx is united with the wall of the body. If we examine the ventral mesentery more closely, we observe that in its middle the two mesodermic layers from which it has been developed separate from each other and allow a small cavity (h) to appear, the primitive cardiac cavity. This is stir
 
 
544
 
 
EMBRYOLOGY.
 
 
 
rounded by a single layer of cells, which is afterwards developed into the endocardium (end).* Outside of the latter the adjacent cells of the middle germ-layer are thickened ; they furnish the material out of which the cardiac musculature (the myocardium) and the superficial membrane of the heart (pericardium viscerale) arise. The fundament of the heart is attached above [dorsally] to the pharynx (d) and below to the body-wall by the remnant of the mesentery, which persists as a thin membrane. We designate these two parts as the suspensory ligaments of the heart, as back [dorsal] and front [ventral] cardiac mesenteries (hhg, vhy), or as mesocardium posterius and anterius. At this time there is nothing to be seen of a pericardial sac, unless we should designate as such the anterior
[ventral] region of the bodycavity, from which, as the further course of development will show, the pericardium is chiefly derived.
 
In the second type, the heart arises from distinct and widely separated halves, as the conditions in the Chick and the Rabbit most distinctly teach.
 
In the Chick the first traces of the fundament may be demonstrated at an early period, in embryos with four to six primitive segments. They appear here at a time when the various germ-layers are still spread out flat, at a time when the front part of the embryonic fundament first begins to be elevated as the small cephalic protuberance, and the cephalic portion of the intestine is still in the first phases of development. As has already been stated, the intestinal cavity in the Chick is developed by the folding together and fusion of the intestinal plates [splanchnopleure]. If one examines carefully the ridge of an intestinal fold in the very process of being formed (fig. 299 A df) t one observes that its visceral middle layer is somewhat thickened, composed of large cells, and separated from the entoblast by a space filled with a jelly-like matrix. In the latter there lie a few isolated cells, which subsequently
* Relative to the origin of the endothelial sac of the heart, compare the observations given on page 186.
 
 
 
 
Fig. 298. Cross section from the same series as that from which fig. 297 was drawn, after KABL.
 
</, Epithelium of the intestine ; vm, visceral, pm, parietal middle layer ; hhg, posterior, vlig, anterior mesocardium ; end, endocardium ; h, cavity of the heart ; Ik, ventral part of the body-cavity ; ep, epidermis.
 
 
 
THE ORGANS OF THE INTERMEDIATE LAYER OR MESENCHYME. 545
 
 
Fig. 299. Three diagrams to illustrate the formation of the heart in the Chick.
 
.', Xeural tube; m, mesenchyma of the head ; d, intestinal cavity ; df, folds of the intestinal plate [splanchnopleure], in which the endothelial sacs of the heart are established ; h, endothelial sac of the heart ; ch, chorda ; Ih, bodycavity ; ale, outer, ik, inner germ-layer ; 'nilc 1 , parietal middle layer ; ink", visceral middle layer, from the thickened portion of which the musculature of the heart is developed ; dn, intestinal suture, in which the two intestinal folds are fused ; db, part of the entoblast which has become detached from the epithelium of the cephalic portion of the intestine at the intestinal suture and lies on the yolk ; + dorsal mesocardium ; * ventral mesocardium.
 
A, The youngest stage shows the infolding of the splanchnopleure, by means of which the cephalic part of the intestine is formed. In the angles of the intestinal folds the two endothelial sacs of the heart have been established between the inner germ-layer and the visceral middle layer.
 
B, Somewhat older stage. The two folds (A df) have met in the intestinal suture (dn), so that the two endothelial sacs of the heart lie close together in the median plane below the head-gut.
 
C, Oldest stage. The part of the entoblast which lines the head-gut (<?) has become separated at the intestinal suture (B dn) from the remaining part of the entoblast, which (J6) lies upon
 
 
ak
 
 
d m
 
 
n
 
 
 
ik Ih mk- h df
 
 
d
 
 
B
 
 
n
 
 
 
mk" h d
 
 
Ih
 
 
I
 
 
n
 
 
 
h db h mk y lit
 
 
the yolk, so that the two endothelial sacs of the heart are in contact ; they subsequently fuse. They lie in a cardiac suspensorhun formed by the visceral middle layers, the mesocardium, on which one can distinguish an upper [dorsal] and an under part mesocardium superius(-f )and inferius (*). By means of this mesocardium the primitive body-cavity is temporarily divided into two portions.
 
 
 
35
 
 
546 EMBRYOLOGY.
 
surround n, small cavity, tho primitive cardiac cavity (A). These cells .issuine more of an endothelial character. While the intestinal folds grow toward each other, the two endothelial tubes become enlarged and ])iish the thickened part of the visceral middle layer before them, so that the latter forms a low, ridge-like elevation into the primitive body-cavity. hi the embryos of higher Vertebrates also, just as in the Amphibia, this stretches forward into the embryonic fundament as far as the last visceral arch, and has here received the special name of neck-cavity or parietal cavity.
 
In older embryos (fig. 299 7>) the edges of the two folds have met in the median plane, and consequently the two cardiac tubes have moved close together. A process of fusion then takes place between the corresponding parts of the two intestinal folds.
 
First the entoblastic layers fuse, and in this way is produced (fig. 299 7>) beneath the chorda dorsalis (ck) the cavhVy of the head-gut (d), which then detaches itself from the remaining part of the entoblast (fig. 299 G db) ; the latter is left lying on the yolk and becomes the yolk-sac. Under the cavity of the head-gut the two cardiac sacs have come close together, so that their cavities are separated from each other by their own endothelial walls only. By the breaking through of these there soon arises from them (7i) a single cardiac tube. On the side toward the body-cavity this is covered by the visceral middle layer (mk 2 ), the cells of which are distinguished in the region of the fundament of the heart by their great length and furnish the material for the cardiac musculature, while the inner endothelial membrane becomes only the endocardium.
 
The whole fundament of the heart lies, as in the Amphibia, in a ventral mesentery, the upper [dorsal] part of which, extending from the heart to the head-gut (fig. 299 G +), can here also be called the dorsal suspensory of the heart or mesocardium postering, and the lower [ventral] part (*) mesocardium anterius. In the Chick, when the cardiac tube begins to be elongated and bent into an S- shaped form, the mesocardium anterius quickly disappears.
 
Similar conditions are furnished by cross sections through Rabbit embryos 8 or 9 days old. In the latter the paired fundaments of the heart are indeed developed still earlier and more distinctly than in the Chick, even at a time when the entoderm is still spread out flat and has not yet begun to be infolded. Upon cross sections one sees (fig. 301), in a small region at some distance from the median plane, the splanchnopleure separated from the somatopleure by a small fissure (pfi), which is the front end of the primitive body-cavity. At
 
 
THE ORGANS OF THE INTERMEDIATE LAYER OR MESENCHYME. 547
this place the visceral middle layer (ahh) is also raised up somewhat from the entoderm (sw), so that it causes a projection into the bodycavity (ph). Here there is developed between the two layers a small cavity, which is surrounded by an endothelial membrane (lhh\ the primitive cardiac sac. At their first appearance the halves of the heart lie very far apart. They are to be seen both in the very slightly magnified cross section (fig. 300) and also in the surface view of an embryo Rabbit (fig. 302) at the place indicated by h. They
 
 
 
Fig. 300.
 
 
 
 
Fig. 301.
 
Figs. 300, 301. Cross section through the head of an embryo Rabbit of the same age as that shown in fig. 302. From KOLLIKER. Fig. 301 is a part of fig. 300 more highly magnified.
 
Fig. 300. h, h', Fundaments of the heart ; sr, cesophageal groove.
 
.Fig. 301. rf, Dorsal groove; mp, medullary plate; no, medullary ridge ; h, outer germ-layer; d<l, inner germ-layer ; dd', its chordal thickening ; sp, undivided middle layer ; hp, parietal, dfp, visceral middle layer ; -ph, pericardial part of the body-cavity ; ahh, muscular wall of the heart ; ihh, endothelial layer of the heart ; mes, lateral undivided part of the middle layer ; sw, intestinal fold, from which the ventral wall of the pharynx is formed.
 
 
 
afterwards move toward each other in the same manner as in the Chick by the infolding of the splanchnopleure, and come to lie on the under side of the head-gut, where they fuse and are temporarily attached above and below by means of a dorsal and ventral mesentery. Concerning the processes of development just sketched the question may be raised : What relation do the paired and the unpaired fundaments of the heart sustain to each other ? It is to be answered to this, that the impaired fundament of the heart, ivhich is present in the lower Vertebrates, is to be regarded as the original form. The double
 
 
548
 
 
EMBRYOLOGY.
 
 
 
heart-formation, however aberrant it at f,rst si </Ji f appears, can be
easily referred back to this.
 
A single cardiac tube cannot bn developed in tlie higher
Vertebrates, because at the time of its formation a headgut does not yet exist, but only the fundament of it is formed in the still flat entoderm. The parts which will subsequently form the ventral wall of the head -gut, and in which the heart is developed, are still two separated territories ; they still lie at some distance from the median plane at the right and at the left. If therefore it is necessary for the heart to be formed at this early period, it must arise in the separated regions, which by the process of infolding are joined into a single ventral tract. The vessel must arise as two parts, which, like the two intestinal folds, subsequently fuse.
 
Whether the heart is formed
Fig. 302. Embryo Rabbit of the ninth day, seen j n one wav or t} ie other, in
n it ^ i _ i _ _ *i_ T T" _ _ _ TUT .-, *
 
 
 
a
 
 
from the dorsal side, after KOLLIKER. Magnified 21 diameters.
 
The axial (stem-) zone (stz) and the parietal zone (2?z) are to be distinguished. In the former 8 pairs of primitive segments have been formed at the side of the chorda and neural tube.
 
p, Area pellncida ; rf, dorsal groove ; r/t, fore brain; ab, optic vesicle; mil, mid -brain; Mi, hind-brain ; uw, primitive segment ; stz, axial zone ; pz, parietal zone ; h, heart ; ph, pericardial part of the body-cavity ; rd, margin of the anterior intestinal portal showing through the overlying structures ; af, fold of the aninion ; vo, \ena omphalomesenterica.
 
 
 
either case it has for a time the form of a straight sac lying ventral to the head -gut and composed of two tubes one within the other, which are separated by a large space assumably filled with a gelatinous matrix. The inner, endothelial tube becomes the
 
 
endocardium ; the outer tube,
which is derived from the visceral middle layer, furnishes the foundation for the myocardium and the pericardial membrane that immediately invests the surface of the heart.
 
 
 
THE ORGANS OF THE INTERMEDIATE LAYER OR MESENCHYME. 549
(/>) The First Developmental Conditions of the Large Vessels. Vitelline Circulation, Allantoic and Placental Circulation.
 
At both ends, in front and behind, the heart is continuous with the trunks of blood-vessels, which have been established at the same time with it. The anterior or arterial end of the cardiac tube is elongated into an unpaired vessel, the truncus arteriosus, which continues the forward course under the head-gut, and is divided in the region of the first visceral arch into two arms, which embrace the head-gut on the right and left and ascend within the arch to the dorsal surface of the embryo. Here they bend around and run backward in the longitudinal axis of the body to the tail-end. These two vessels are the primitive aortcv (figs. 107, 116 ao) ; they take their course on either side of the chorda dorsalis, above the entoderm and below the primitive segments. They give off lateral branches, among which the arterice omplialomesentericw are in the Amniota distinguished by their great size. These betake themselves to the yolk-sac and conduct the greatest portion of the blood from the two primitive aortas into the area vasculosa, where it goes through the vitelline circulation.
 
In the Chick, the conditions of which form the basis of the following account (fig. 303), the two vitelline arteries (R.Of.A, L.Of.A) quit the aortaj at some distance from their tail-ends, and pass out laterally from the embryonic fundament between entoderm and visceral middle layer into the area pellucida, traverse the latter, and distribute themselves in the vascular area. They are here resolved into a fine network of vessels, which lie, as a cross section (fig. 116) shows, in the mesenchyme between the entoderm and the visceral middle layer, and which are sharply bounded at their outer edge (toward the vitelline area) by a large marginal vessel (fig. 303 S.T), the sinus terminalis. The latter forms a ring which is everywhere closed, with the exception of a small region which lies in front, at the place where the anterior amniotic sheath has been developed.
 
From the vascular area the blood is collected into several large venous trunks, by means of which it is conducted back to the heart. From the front part of the marginal sinus it returns in the two vence vitellinai anter lores, which run in a straight line from in front backwards and also receive lateral branches from the vascular network. From the hind part of the sinus terminalis the blood is taken up by the venae vitellinie posteriores, of which the one of the left side is larger than the one of the right ; the latter afterwards
 
 
550
 
 
EMBRYOLOGY.
 
 
 
degenerates more and more. From the sides likewise there come still larger collecting vessels, the vense vitellinre laterales. All the vitelline veins of either side now unite in the middle of the embryonic body to form a single large trunk, the vena omphalo
 
 
Vitelline ;nva.
 
 
 
Vitelline area.
 
 
 
SJF.
 
 
 
S.CnV.
 
 
 
4.0
 
 
 
SX,
 
 
Fig. 303. Diagram of the vascular system of the yolk-sac at the end of the third day of incubation, after BALFOUB.
 
Tlie whole blastoderm has been removed from the egg and is represented as seen from below. Hence what is really at the right appears at the left, and vice vtrsd. The part of the area opaca in which the close vascular network has been formed is sharply terminated at its periphery by the sinus terminalis, and forms the vascular area ; outside of the latter lies the vitelline area. The immediate neighborhood of the embryo is free from a vascular network, and now, as previously, is distinguished by the name area pellucida.
 
H. Heart; A A, aortic arches; Ao, dorsal aorta; L.Of.A, left, R.Of.A, right vitelline artery; S. T, sinus terminalis ; L.Of, left, R.Of, right vitelline vein ; S. V, sinus venosus ; D.C, diictus Cuvieri ; S.Ca.V, superior, V. Ca, inferior cardinal vein. The veins are left in outline; the arteries are black.
 
mesenterica (A'.O/and L.Of), which enters the posterior end of the heart (//).
 
The motion of the blood begins to be visible in the case of the Chick as early as the second day of incubation. At this time the blood is still a clear fluid, which contains only few formed
 
 
THE ORGANS OF THE INTERMEDIATE LAYER OR MESENCHYME. 551
components. For the most of the blood-corpuscles still continue to lie in groups on the walls of the tubes, where they constitute the previously described blood-islands (fig. 114), which cause the redbesprinkled appearance of the vascular area. The contractions of the heart, by which the blood is set in motion, are at first slow and then become more and more rapid. On the average, according to PREYER, the strokes then amount to 130 150 per minute. However, the frequency of pulsations is largely dependent upon external influences; it increases with the elevation of the temperature of incubation and diminishes at every depression of it, as well as when the egg is opened for study. At the time when the heart begins to pulsate, no muscle-fibrillse have been demonstrated in the myocardium ; from this results the interesting fact that purely protoplasmic, still undifierentiated cells are in a condition to make strong rhythmical contractions.
 
At the end of the third or fourth day the vitelline circulation in the Chick is at its highest development ; it has undergone some slight changes. We find instead of a single vascular network a double one, an arterial and a venous. The arterial network, which receives the blood from the vitelline arteries, lies deeper, nearer to the yolk, while the venous spreads itself out above the former and is adjacent to the visceral middle layer. The circulating blood is distinguished by the abundance of its blood-corpuscles, the bloodislands having entirely disappeared.
 
The function of the vitelline circulation is twofold. First it serves to provide the blood with oxygen, opportunity for acquiring which is afforded by the whole vascular network being spread out at the surface of the egg. Secondly it serves to bring nutritive substances to the embryo. The yolk-el einents below the entoblast are disassociated, liquefied, and taken up into the blood-vessels, by which they are carried to the embryo, where they serve as nutrition for the rapidly dividing cells. Thus far the embryonic body increases in size at the expense of the yolk-material in the yolksac, which becomes liquefied and absorbed.
 
The system of vitelline blood-vessels in Mammals agrees in general with that of the Chick, and is distinguished from the latter only in some unimportant points, which do not need to be discussed. However, this question certainly arises* What signification has a vitelline circulation in Mammals (fig. 134 ds) in which the egg is furnished with only a small amount of yolk-material ?
Two things are here to be kept in mind ; first, that the eggs of
 
 
552 EblttRYOLOGY.
 
Mammals were originally provided with abundant yolk-material, like those of Reptiles (compare p. 222), and, secondly, that the blastodermic vesicle, which arises after the process of cleavage, becomes greatly distended by the accumulation within it of a fluid very rich in albumen, furnished by the walls of the uterus. Out of this vesicle likewise the vitelline blood-vessels undoubtedly take up nutritive material and convey it to the embryo, until a more ample nutrition is provided by means of the placenta.
 
In addition to the vitelline blood-vessels there arises in the higher Vertebrates a second system of vessels, which is distributed in the foetal membranes outside the embryo and for a time is more developed than the remaining vessels of the embryo. It serves for the allantoic circulation of Birds and Reptiles and the placenta! circulation of Mammals.
 
When in the Chick the allantois (PI. I., fig. 5 al] is evaginated from the front [ventral] wall of the hind-gut, and as an ever increasing sac soon grows out of the body-cavity through the dermal umbilicus into the coalom of the blastodermic vesicle between the serosa and the yolk-sac, there appear in its walls two blood-vessels, which grow forth from the ends of the two primitive aortse the umbilical vessels, or arterice umbilicales. The blood is again collected from the fine capillary network, into which these vessels have been resolved, into the two umbilical veins (veme \ umbilicales), which, after having arrived at the navel, pass on to the two Cuvierian ducts (see p. 577) and pour their blood into these near the entrance of the latter into the sinus venosus. The terminal part of the right vein soon atrophies, whereas the left receives the lateral branches of the right side and is correspondingly developed into a larger trunk. This now also loses its original connection with the ductus Cuvieri, since it effects with the left hepatic vein (vena hepatica revehens) an anastomosis, which continually becomes larger and finally carries the whole stream of blood. Together with the left hepatic vein the left umbilical vein then empties directly into the sinus venosus at the posterior margin of the liver (HOCHSTETTER).
 
The umbilical and vitelline veins undergo opposite changes in calibre during development : while the vitelline circulation is well developed, the umbilical veins are inconspicuous stems ; afterwards, however, with the increase in the size of the allantois they enlarge, whereas the venae omplialomesentericae undergo degeneration and in the same proportion as the yolk-sac by the absorption of the yolk becomes smaller and loses in significance.
 
 
 
THE ORGANS OF THE INTERMEDIATE LAYER OR MESENCHYME. 553
So far as regards the purpose of the umbilical circulation, it subserves in Reptiles and Birds ihe function of respiration. For the allantois, when it has become larger, in the Chick for example, applies itself closely to the serosa and spreads itself out in the vicinity of the air-chamber and underneath the shell, so that the blood circulating in it can enter into an exchange of gases with the atmospheric air. It loses its importance for respiration in the egg only at the moment \vhen the Chick with its beak breaks through the surrounding embryonic membranes, and breathes directly the air contained in the air-chamber. For the conditions of the circulation are now altered throughout the whole body, since with the beginning of the process of respiration the lungs are in a condition to take up a greater quantity of blood, resulting in a degeneration of the umbilical vessels (compare also p. 584).
 
The umbilical or placental circulation in Mammals (fig. 139 Al) plays a still more important role ; for here the tw r o umbilical arteries convey the blood to the placenta. After the blood has been laden in this organ with oxygen and nutritive substances, it flows back again to the heart, at first through two, afterwards through a single umbilical vein (p. 584).
 
B. The further Development of the Vascular System up to the
Mature Condition.
 
(a) The Metamorphosis of the Tubular Heart into a Heart
vnth Chambers.
 
As has been .shown in a preceding section, the heart of a Vertebrate originally has for a short time the form of a straight sac, which sends off at its anterior end the two primitive aortic arches, while it receives at its posterior end the two omphalomesenteric veins. The sac lies far forward immediately behind the head on the ventral side of the neck (fig. 304 /*,), in a prolongation of the body-cavity (the parietal or cervical cavity). It is here attached by means of a mesentery of only brief duration, which stretches from the alimentary canal to the ventral wall of the throat, and which is divided by the cardiac sac itself into an upper [dorsal] and an under part, or mesocarclium posterius and anterius.
 
During the first period of embryonic development the heart is distinguished by a very considerable growth, especially in the longitudinal direction ; consequently it soon ceases to find the necessary
 
 
554
 
 
EMBRYOLOGY.
 
 
 
 
room for itself as a straight sac, and is therefore compelled to bend itself into an S-shaped loop (lig. 304). It then takes such a position in the neck that one of the bends of the S, which receives the vitelline veins or, let us say briefly, the venous portion, conies to lie behind and at the left ; the other or arterial portion, which sends off' the aortic arches, in front and at the right (fig. 305).
 
But this initial position is soon altered (figs. 305, 313) by the two
curves of the S assuming another relation to each other. The venous portion moves headwards, the arterial, on the contrary, in the opposite direction, until both lie approximately in the same transverse plane. At the same time they become turned around the longitudinal axis of the embryo, the venous loop moving dorsally, the arterial, on the contrary, ventrally. Seen from in front [ventral aspect] one hides the other, so that it is only in a side view that the S-shaped curvature of the cardiac sac is distinctly recognisable.
 
By the increase in the size of this viscus the anterior part of the bodycavity is already greatly distended, and becomes still more so in later stages, when there is produced a very thin-walled elevation, that projects out to a great distance (figs. 157 h, 314). Inasmuch as the heart completely fills the cavity, and is covered in by only the thin, transparent, and closely applied wall of the trunk, the niembrana reuniens
inferior of KATHKE, it appeal's as though at this time the heart were located entirely outside of the body of the embryo.
 
After the completion of the twisting, there is effected a division of the S-shaped sac into several successive compartments (figs. 306, 308). The venous portion, which has become broader, and the arterial part are separated from each other by a deep constriction (ok} and can now be distinguished as atrium (vli) and ventricle, while the constricted region between the two may be indicated, by a designation introduced
 
 
Fig. 304. Head of a Chick incubated 58 hours, seen from the dorsal face, after MIHALKOVICS. Magnified 40 diameters.
 
The brain is divided into 4 vesicles: prli, primary fore-brain vesicle ; iiih, mid-brain vesicle ; kh, hindbrain vesicle ; nil, after-brain vesicle; an, optic vesicle ; k, heart (seen through the Jast brainvesicle) ; -co, vena omphalomesenterica ; us, primitive segment ; rm, spinal cord ; x, anterior wall of brain, which is evanii'ated to form the cerebrum.
 
 
 
THE ORGANS OF THE INTERMEDIATE LAYER OR MESENCHYME. 555
by HALLER, as auricular canal (ok). The atrium thereby acquires a striking form, since its two lateral walls develop large out-pocketings (ho), the auricles of the heart (auriculae corclis) ; the free edges of the latter, which in addition soon acquire notches, are turned forward, and subsequently enfold more and more the arterial part of the heart, the truncus arteriosus (Ta), and a part of the surface of the ventricle.
 
The auricular canal (fig. 308 o)is in embryos a well-distinguished narrowed place in the cardiac tube. Owing to the great flattening of its endothelial tube in the sagittal direction, its walls almost
 
 
 
 
 
 
Ta
 
 
 
Fig. 305.
 
 
 
306.
 
 
 
Fig. 305. Heart of a human embryo, the body of which was 2 - 15 mm. long (embryo Lg), after
His. [Compare fig. 313.] K, Ventricle ; Ta, truncus arteriosus ; V, venous end of the S-shaped cardiac sac.
 
Fig. 306. Heart of a human embryo that was 4'3 mm. long, neck measurement (embryo 1),
after His. k, Ventricle ; Ta, truncus arteriosus ; ok, canalis auricularis ; vh, atrium with the heart-auricles
ho (auriculas cordis).
 
coming into contact, the passage between atrium and ventricle is reduced to a narrow transverse fissure. It is here that the atrioventricular valves are afterwards developed.
 
The fundament of the ventricle at first presents the form of a curved tube (figs. 305, 306 k), which however soon changes its form. For at a very early period there is observable on its anterior [ventral] and posterior surfaces a shallow furrow running from above downward, the sulcus interventricularis (fig. 307 si), which allows a left and a right half of the ventricle to be distinguished externally. The latter is the narrower, and is continued upward into the truncus arteriosus (Ta), the beginning of which is somewhat enlarged and
 
 
556
 
 
EMBRYOLOGY.
 
 
 
Ihn rko
 
 
Ta.
 
 
 
designated as bulbus. Between bulbus and ventricle lies a place that is only slightly constricted, called the /return Halleri ; it was recognised even by the older anatomists, then remained for a time little regarded, and now has been again described as noteworthy by His. For it marks the place at which subsequently the semilunar valves are established.
 
During the externally visible changes of form, some alterations are also progressing in the finer structure of the walls of the heart. As previously remarked, the fundament of the heart consists in the beginning of two sacs, one within the other an inner endothelial tube lined with flat cells, and an outer muscular sac consisting of cells
with abundant protoplasm and derived from the middle germ-layer. The two are completely separated from each other by a considerable space, which is probably filled with gelatinous substance.
 
The endothelial tube is in general a tolerably faithful copy of the muscular sac, yet the narrower and wider regions are more sharply marked off from one another in the former than in the latter ; "as regards its form, it sustains such a relation to the whole heart
as it would if it were a greatly shrivelled, internal cast of it " (His). In the muscular sac distinct traces of muscle-fibres can be recognised even at the time when the S-shaped curvature makes its appearance. At later stages in the development differences appear between atrium and ventricle. In the atrium the muscular wall is uniformly thickened into a compact plate, with the inside of which the endothelial tube is in immediate contact. In the ventricle, on the contrary, there occurs a loosening, as it were, of the muscular wall. There are formed numerous small trabeculse of muscular cells, which project into the previously mentioned space between the two sacs and become united to one another, forming a large-meshed network (fig. 311 A). The endothelial tube of the heart, by forming out-pocketings,
 
 
 
SI
rk Ik
 
 
Fig. 307. Heart of a human embryo of the fifth week,
after His. rk t Right, Ik, left ventricle ; si, sulcus interventricn
laris ; Ta, truncus arteriosus ; Iho, left, rho, right
auricle of the heart.
 
 
 
THE ORGANS OF THE INTERMEDIATE LAYER OR MESENCHYME. 557
soon comes into intimate contact with the trabeculse, and envelops each one of them with a special covering (His). Thus there arise in the spongy wall of the ventricle numerous spaces lined with endothelium, which toward the surface of the heart end blindly, but which communicate with the central cavity and like this receive into them the stream of blood.
 
The embryonic heart of Man and Mammals resembles in its first condition that which has been described up to this point the heart of the lowest Vertebrates, the Fishes. In the former as in the latter it consists of a region, the atrium, which receives the venous blood from the body, and of another, the ventricle, which drives the blood into the arterial vessels. Corresponding to this condition of the heart, the whole circulation in embryos of this stage and in Fishes is still a single and a single one. This becomes changed in the evolution of Vertebrates, as in the embryonic life of the individual, with the development of the lungs, upon the appearance of which a doubling of the heart and of the blood-circulation is introduced.
 
The cause of such a change is clear, from the topographical relation of the two lungs to the heart, the former arising in the immediate vicinity of the heart by evagination of the fore-gut (fig. 314 la). The lungs therefore receive their blood from an arterial stem lying very near the heart, from the fifth [sixth] pair of aortic arches that arise from the trimcus arteriosus. Similarly they give back again the venous pulmonary blood directly to the heart through short stems, the pulmonary veins, which, originally united into a single collecting trunk (BoRN, ROSE), open into the atrium at the left of the great venous trunks. Therefore the blood that flows directly out of the heart into the lungs also flows directly back again to the heart. Herein is furnished the prerequisite for a double circulation. This comes into existence when the pulmonary and the body currents are separated from each other by means of partitions throughout the short course of the vascular system which both traverse in common (viz., atrium, ventricle, and trimcus arteriosus).
 
The process of separation begins in the vertebrate phylum with the Dipnoi and Amphibia, in which pulmonary respiration appears for the first time and supplants bronchial respiration. In the amniotic Vertebrates it is accomplished during their embryonic development. Therefore we now have to follow out further the manner in which, in the case of Mammals and especially of Man, according to the recent investigations of His, BORN, and ROSE, the partitions are formed how atrium and ventricle are each divided into right and
 
 
558
 
 
EMBRYOLOGY.
 
 
 
left compartments, and the truncus arteriosus into arteria pulmonalis and aorta, and how in this way the heart attains its definite form.
 
The partitions arise independently in each of the three divisions of the heart mentioned.
 
Let us first take into consideration the atrium, which is for a time the largest and most capacious region of the cardiac sac (fig. 308). In Man a separation into left and right halves (Iv and rv) is observable even in the fourth week, since there is then formed
on its hinder [dorsal] and upper wall a perpendicular projection inward, the first trace of the atrial partition (vs) or septum atriorum.
 
The halves are even now distinguished by the fact that they receive different venous trunks. The vitelline and umbilical veins, as well as the Cuvierian ducts to be discussed later, empty their blood into the right compartment, not directly, however, and by means of separate orifices, but after they have united with one another in the vicinity of the heart to form a large venous sinus (sr) the sinus venosus or s. reunions. This is immediately adjacent to the atrium and communicates with it by means of a large opening in its posterior [dorsal] wall, which is flanked on the right and on the left by a large venous valve (*). Only one small vessel, which traverses the musculature of the heart obliquely, opens, near the atrial partition, into the left compartment ; it is the previously mentioned unpaired pulmonary vein, which is formed immediately outside the atrium by the union of four branches, two of which come from each of the two wings of the lung now being established.
 
In the further course of development the atrial partition grows
 
 
 
Ps
IS
sr
rv Iv
ok
 
 
rk ks
Ik
 
 
Fig. 308. Heart of a human embryo 10 mm. long, neck measurement ; posterior [dorsal] half of the heart, the front walls of which have been removed. After His.
 
/.s 1 , 1'artitiou of the ventricle ; Ik, left, rk, right ventricle ; ok, auricular canal ; Iv, left, re, right atrhini ; sr, mouth of the sinus reunions ; vs, partition of the atrium (atrial crescent, His ; septam primuin, BORN) ; * Eustachiau valve ; Ps, septum spurium.
 
 
 
THE ORGANS OF THE INTERMEDIATE LAYER OR MESENCHYME. 559
 
 
from above downward until it reaches the middle of the atrial canal (fig. 309 si). In this manner two completely separated atria would have come into existence at a very early period, if there had not been formed in the upper part of the partition, while it was still growing downward, an opening, the future foramen ovale, which maintains a connection between the two chambers (fig. 309) up to the time of birth. The opening has arisen either from the septum atriorum having become thin and having broken through at a certain region, or from its having been incomplete at this place from the very beginning, as is the case with the Chick for example, where it is traversed by numerous small orifices. Afterwards the foramen ovale, adapting itself to the conditions of the circulation existing at the time, becomes
 
 
still larger.
 
 
 
do\vngrowth
 
 
The
of the atrial partition has, moreover, the immediate result of separating the auricular canal into the left and right atrio
 
 
 
Ps
vs
sr rv
Iv
 
 
SI
rk ks
lie
 
 
Fig. 309. Posterior [dorsal] half of the heart of a human embryo of the fifth week, cut open, after His.
 
ks, Ventricular partition ; Ik, left, rk, right ventricle ; si, lower [posterior] part of the atrial partition (septum intermedium, His) ; to, left, rv, right atrium ; sr, mouth of the sinus reunions ; vs, atrial partition (atrial crescent, His ; septum secundum, BORX) ; Ps, septum spurium ; * E\istachian valve.
 
 
 
ventricular orifices (compare fig. 308 ok with fig. 309). The auricular canal, even
very soon after its formation, undergoes important alterations both from without and within. At first visible from the outside (fig. 308 o&), it afterwards disappears from view (fig. 309) by being in a manner overgrown on all sides by the ventricle, and thereby incorporated in its walls, which enlarge upward and, in consequence of a vigorous growth of the musculature, acquire considerable thickness. The opening of the atrial canal into the ventricle, or the foramen atrioventriculare commune (fig. 310 A F.av.c), now has the form of a fissure extending from left to right, which is bounded on either side by two ridge-like lips (o.ek and u.ek}the atrioventricular lips of LINDES, or the endotbelial cushions of
 
 
5GO EMBRYOLOGY.
 
SCHMIDT. The ridges have arisen from a growth of the endocardium, and consist of a, gelatinous connective substance and an endothelial investment. The atrial partition, when it has grown down to the auricular canal, soon fuses along its free lower margin with these lips (fig. 309 si) ; the auricular canal is thereby divided into a left and a right atrioventricular opening, ostium atrioventriculare sinistruin and clextrum (fig. 310 B F.av.s and F.av.d], and at the same time both the dorsal and ventral endocardial ridges, which originally bound the opening, are divided in the middle (o.ek and n.ek). The dorsal components soon fuse with the corresponding pieces of the opposite [ventral] side, and thus there arise at the lower margin of the atrial partition (fig. 309 si) two new ridges, one of which projects into the left, the other into the right atrioventricular opening, which furnish the foundation of the median cuspidate valves.
 
The development of the atrial partition and the division of the auricular canal into the two atrioventricular openings are closely related processes, the former being the cause of the latter. This is clearly proved by pathological -anatomical conditions of arrested development of the heart. In all cases in which the formation of the atrial partition has been for any reason w r hatever interrupted and the lower part of it has been altogether wanting, there has always been only one atrioventricular opening (an ostium venosum commune) present (ARNOLD).
 
Before we progress further in the history of the development of the atrium, we must add an account of the metamorphoses which have taken place meanwhile in the territory of the ventricle and truncus arteriosus.
 
The ventricle begins to acquire its partition not much later than the atrium. By the end of the first month its musculature has become considerably thickened (fig. 311 A). Muscular trabeculre have arisen, which project far into the interior of the chamber and are joined to one another, so as to constitute a spongy tissue, the numerous fissures in which are continuous with the narrowed cavity of the heart and likewise allow the current of the blood to pass through them. At one place the musculature is especially thickened and forms a crescent-shaped fold projecting inward, the fundament of the ventricular partition (septum ventriculorum) (figs. 308, 309, 310 ks). This takes its origin from the lower and posterior [dorsal] wall of the ventricle, in the region which is marked externally by the previously mentioned sulcus interventricularis (fig. 307 si). Its
 
 
THE ORGANS OF THE INTERMEDIATE LAYER OR MESENCHYME. 561
 
 
free edge is directed upwards and grows toward the bulbus arteriosus and the atrioventricnlar opening. The latter originally lies more in the left half of the ventricle (fig. 310 A F.av.c), but it gradually moves over more to the right, and finally assumes such a position that the ventricular partition by its growth upwards meets it exactly
 
 
Oi
 
 
 
o.ek F.av.s
 
 
- Ik
 
 
Fig. 310. Two diagrams (after BORX) to elucidate the changes in the mutual relations of the ostium atrioventriculare and the ostium interventriculare, as well as the division of the ventricle and large arteries. The ventricles are imagined to have been divided into halves ; one looks into the posterior [dorsal] halves, in which, moreover, the cardiac trabeculse, etc., have been omitted for the sake of simplifying the view.
 
J, Heart of an embryo Rabbit, in which the head is 3-5 5-8 mm. long. The ventricle is divided by the ventricular partition (ks) into a left and a right half as far as the ostium interventriculare (Oi). The right end of the foramen atrioventriculare commune (F.av.c) extends into the right ventricle ; the endocardia! cushions (o.ek, u.ek) are developed.
 
B, Heart of an embryo Rabbit, head 7'5 mm. long. The endocardial cushions (o.ek, u.ek) of the foramen atrioventriculare commune are fused, and thereby the for. atrioventr. com. is now separated into a for. atrioventr. dextrum (F.av.d) and sinistrum (F.av.s). The ventricular partition (ks) has likewise fused with the endocardial cushions, and has grown forward as far as the partition (s) of the trunciis arteriosus. By the closure of the remnant of the ostium interventriculare (Oi) the septum membranaceum is formed.
 
rk, Right, Ik, left ventricle ; ks, ventricular partition ; Pu, arteria pulmonalis ; Ao, aorta ; s, partition of the truncus arteriosus ; Oi, ostium interventriculare ; F.av.c, foramen atrioventriculare commune ; F.ae.d and F.av.s, foramen atrioventriculare dextrum and sinistrum ; o.ek, u.ek, upper and lower endothelial or endocardial cushions.
 
in the middle and fuses with its edges directly opposite the atrial partition (figs. 309, 310 B).
 
The division of the ventricle in Man is completed as early as the seventh week. From the atrium, the two compartments of which are united by the foramen ovale, the blood is now conducted through a right and a left ostium atrioventriculare into completely separated right and left ventricles.
 
The two atrioventricular openings are narrow at the time of their origin ; they are in part surrounded by the previous!} mentioned
36
 
 
562
 
 
EMBRYOLOGY.
 
 
 
endocardial ridges that project from the partition, in part by corresponding growths of the endocardium at their lateral circumference. The membranous projections are comparable with primitive pocketvalves, such as are also established in the bulbus arteriosus (GEGENBAUR) ; they constitute the starting-point for the development of the large atrioventricular valves, but furnish, as GEGENBAUR and BERNAYS have shown, only a part the membranous marginal thickening (mk l ) which subsequently disappears almost completely, whereas the compact main part of the valve arises from that portion of the thickened muscular wall of the ventricle itself that surrounds the atrioventricular opening (fig. 311 B mfc).
 
As was previously stated, in the case of Man the wall of the ventricle during the first months consists of a close spongy network
 
 
 
mi 1
 
 
 
Fig. 311. Diagrammatic representation of the formation of the atrioventricular valves. A , Earlier,
B, later condition. After GEGENBAUR. mk, Membranous valve ; mk\ the primitive part of the same ; cht, chordae tendinese ; v, cavity
of the ventricle ; b, trabecular network of cardiac musculature ; 21111, papillary muscles ;
tc, trabeculfe carnese.
 
of muscular trabeculae, which are invested by the endocardium and the interstices of which communicate with the small central cavity (fig. 311 A). Such a spongy condition of the wall of the heart persists permanently in Fishes and Amphibia ; in the higher Vertebrates and Man, on the contrary, metamorphoses occur. Toward its external surface the wall of the heart becomes more compact, in that the muscular trabeculae become thicker and the spaces between them narrower, in some parts even disappearing entirely (fig. 311 B tc). The reverse of this process takes place toward the inside. In the vicinity of the atrioventricular opening the trabeculse become thinner and the interstices larger. In this way a part of the thick wall of the ventricle, which looks toward the atrium and encloses the opening, is undermined, as it were, by the blood-current. In this part the muscle-fibres afterwards become entirely rudimentary;
 
 
THE ORGANS OF THE INTERMEDIATE LAYER OR MESENCHYME. 563
there are formed from the interstitial connective-tissue substance tendinous plates, which with the endocardial cushions attached to their margins become the permanent atrioventricular valves (fig. 311 B ink). The latter therefore arise from a part of the spongy wall of the ventricle.
 
The remnants of the shrivelled muscular trabecuke (fig. 311 B cht), which are attached to the valve from below, become still more rudimentary in the immediate vicinity of the attachment : here also a part of the muscular fibres disappears entirely ; the connective tissue, on the contrary, is preserved, and is converted into the tendinous cords which, known under the name of chordca tendinete, serve to hold in place the valves. At some distance from the latter the trabeculse projecting into the ventricle preserve their fleshy condition and become the papillary muscles (pvi), from the apices of which the chordae tendinere arise. " Whatever of the primitive trabecular network still persists on the inner surface of the ventricle forms a more or less stout ineshwork of muscles, the fleshy pillars of the heart (tc), or trabeculfe carnese."
In consequence of all these alterations the originally small cavity of the ventricle has become considerably enlarged at the expense of a part of its spongy wall. For the whole of the space which in fig. 311 B lies below the valves has been produced from the system of originally narrow spaces (fig. 311 A), and has been employed for the enlargement of the central cavity by the degeneration of the fleshy columns into slender tendinous cords.
 
It still remains for us to investigate the division of the truncus arteriosus and the final metamorphosis of the atrium.
 
At about the time when the formation of the partition in the ventricle takes place, the truncus arteriosus, which arises from it, becomes somewhat flattened, and thus acquires a fissure-like lumen. On the flat sides two ridge-like thickenings make their appearance (fig. 310 A and B s), grow toward each other, and by their fusion divide the cavity into two passages which are triangular in cross section. Now, too, the beginning of the internal separation makes itself visible externally as two longitudinal furrows, in the same way that the formation of a partition in the ventricle is indicated by the sulcus interventricularis. The two canals resulting from the division are the aorta and the pulmonary artery (Ao and Pu). For a time they continue to be surrounded by a common adventitia, then they become widely separated and also externally detached from each other. The whole process of separation in the truncus arteriosus
 
 
 
 
564 . EMBRYOLOGY.
 
takes place independently of the development of a partition in the ventricle, beginning as it does at first above and advancing from there downwards. Finally the aortic septum penetrates also into the cavity of the ventricle itself (fig. 310 It s and ks), there unites with the independently developed ventricular partition, furnishes the part known as pars membranacea (Oi), and thus completes the separation of the vessels leading out from the heart, the aorta falling to the lot of the left ventricle, the art. pulmonalis to the right.
 
The pars membranacea indicates therefore in the finished heart the place at which the separation between the right and left halves of tlu heart is completed (fig. 310 B Oi}. "It is, as it were, the keystone in the final separation of the primitive simple cardiac sac into the four secondary cardiac cavities, as they are formed in Birds and Mammals " (ROSE). From a comparative-anatomical point of
view this place presents a special interest from the fact that in Eeptiles there exists here a permanent opening between the two ventricles, the foramen Pannizzse.
 
Even before the division of the truncus Fig. 3112. Diagram of the ar- arteriosus, the semilunar valves have become
rangement of the arterial ,, ., ... ,.
 
valves. From GEGENBAUR. established as Jour ridges, consisting ot A, Undivided truncus arteriosus gelatinous tissue with a covering of enclo
with four fundaments of , , i i
valves. B, Division into pui- thelium, at the contracted place which is monaiis (p) and aorta (>, designated as the /return Halleri. Two of
each of which possesses three . , , . .
 
valves. them are halved at the time ot tne divi
sion of the truncus into aorta and art.
 
pulmonalis. For each vessel, therefore, there are now three ridges, which, owing to a shrivelling of the gelatinous tissue, assume the form of pockets. Their arrangement, to which GEGENBAUR has called attention, is intelligible from their method of development, as the accompanying diagram (fig. 312) shows. "By the division of the originally single bulbus arteriosus (A) into two canals (7>), the nodule-like fundaments of the four original valves are distributed in such a manner that the anterior [ventral] one and the anterior halves of the two lateral ones fall to the anterior arterial trunk (pulmonalis), the posterior and the posterior halves of the lateral ones to the posterior arterial trunk (aorta)."
Finally, as regards the atrium, it is to be said that the sinus venosus, mentioned at p. 558, the mouth of the pulmonary vein, and the foramen ovale undergo important alterations.
 
The sinus venosus disappears as an independent structure, since it
 
 
THE ORGANS OF THE INTERMEDIATE LAYER OR MESENCHYME. 565
is gradually merged into the wall of the atrium. In consequence of this the great venous trunks, which originally emptied their blood into it and which have meanwhile been converted into the superior and inferior vense cavre and into the sinus coronarius (the details of which are given in section d), empty directly into the right half of the atrium, and here gradually separate farther and farther from one another. Of the two valves which surround, as was previously stated, the mouth of the sinus venosus, the left becomes rudimentary (figs. 308, 309) ; the right (*), on the contrary, persists at the mouth of the inferior vena cava and of the sinus coronarius, and is divided, corresponding to these, into a larger and a smaller portion, of which the former becomes the valvula Eustachii, the latter the valvula Thebesii.
 
The four pulmonary veins are united for a time into a common short trunk, which empties into the left half of the atrium. Subsequently the common terminal portion becomes greatly enlarged and merged with the wall of the heart, in the same way as the sinus venosus does. In consequence the four pulmonary veins then open separately and directly into the atrium.
 
The foramen ovale, the formation of whicli was previously described, maintains a broad communication between the two sides of the atrium during the entire embryonic life. It is bounded behind and below by the atrial partition, a connective-tissue membrane that subsequently receives the name of valvula foraminis ovalis (fig. 309 si). Also from above and in front there is formed a sharp limitation, since a muscular ridge projects inward from the atrial partition, the anterior atrial crescent or the limbus Vieussenii (?;s). Even in the third month all of these parts are distinctly developed ; the valvula foraminis ovalis already reaches nearly to the thickened margin of the anterior muscular crescent, but is deflected obliquely into the left half of the atrium, so that a broad fissure remains open and permits the blood of the inferior vena cava to enter into the left part of the atrium. After birth the margins of the anterior and posterior folds come into contact, and, with occasional exceptions, fuse completely. The posterior fold furnishes the membranous partition of the foramen ovale ; the anterior, with its thickened muscular margin, produces above and in front the linibus Vieussenii. With this the heart has attained its permanent structure.
 
While the cardiac sac undergoes these complicated differentiations, it changes its position in the body of the embryo and acquires at an
 
 
566
 
 
EMBRYOLOGY.
 
 
 
period a. special investment, the pericardium. Tn connection with llic latter the diaphragm is formed as a partition between the thoracic and abdominal cavities. This is consequently the most suitable place at which to acquaint ourselves better with these important processes, a part of which are not easily understood. The most of the discoveries in this field we owe to the investigations of CADIAT, His, BALFOUR, USKOW, and others.
 
 
 
(I>) The Development of the Pericardial Sac and the Diaphragm. The Differentiation of the Primary Body-cavity into Pericardial, Thoracic, and Abdominal Cavities.
 
Originally the body-cavity is widely extended in the body of the embryo, for it can be traced in the lower Vertebrates into the fundament of the head, where it furnishes the cavities of the visceral arches. After the latter have become closed, during which muscles arise from the cells composing their walls, the body-cavity extends forward as far as the last visceral arch and constitutes a large space (fig. 313), in which the heart is developed within the ventral mesentery (mesocardium anterius and posterius). REMAK and KOLLIKER named this space throatcavity ; His introduced the name parietal cavity. But it will be most appropriate if one designates it, after the permanent organs which are derived from it, as the pericardio - thoracic cavity. The more the cardiac tube is thrown into curves, the more extensive this cavity becomes, and it soon acquires in the embryo a comparatively enormous size. By this its front wall is protruded ventrally like a hernia between the head and the navel of the embryo (figs. 314, 157).
 
 
 
 
Fig. 313. Human embryo (Lg of His) 2 15 mm. long, neck measurement. Reconstruction figure, after His (" Menschliche Embryonen "). Magnified 40 diameters.
 
M/>, Oral sinus ; Ab, aortic bulb ; Vm, middle part of the ventricle ; Vc, vena cava superior or ductus Cuvieri ; Sr, sinus reunions ; Vii, vena nmbilicalis ; VI, left part of the ventricle ; //o, auricle of the heart ; D, diaphragm ; V.om, vena omphalomesenterica ; Lb, solid fundament of the liver ; Lbg, hepatic duct.
 
 
 
THE ORC4ANS OF THE INTERMEDIATE LAYER OR MESENCHYME. 567
The peiicardio-thoracic cavity begins very early to be sharply marked ofT from the future abdominal cavity by a transverse fold (figs. 313, 314 s-f 0> which begins at the front [ventral] and Literal walls of the trunk, and the free edge of which projects dorsalwards and median wards (fig. 314 z-\-l) into the primitive body-cavity. It marks the course which the terminal part of the vena omphalomesenterica takes in order to reach the heart. Subsequently there are found imbedded in the fold all of the venous trunks which empty into the atrial sinus of the heart (figs. 313, 314), the omphalomesenteric and umbilical veins and the Cuvierian ducts (dc), which collect the blood from the walls of the trunk. Therefore the formation of the transverse fold is most intimately connected ivith the development of the veins. It takes the name of septum transversum (massa transversa, USKOW), and has the form of a transverse bridge of substance uniting the two lateral walls of the trunk (fig. 313), which inserts itself between the sinus venosus and the stomach, and is united with both as well as with the ventral mesentery. Its posterior portion (fig. 314 z + l) contains abundant embryonic connective tissue and blood-vessels, and constitutes a mass described as prekepatieus (Vorleber), since the two liver-sacs (fig. 313 Lb + Lbg) grow out from the duodenum into it and produce the hepatic cylinders. In proportion as this takes place, and the hepatic cylinders spread out from the ventral mesentery laterally into the septum transversum, the latter increases in thickness and now embraces two different fundaments, in front, a plate of substance in which the Cuvierian ducts and other veins run to the heart (the primary diaphragm) ; behind, the two lobes of the liver, which produce ridges that project into the body cavity.
 
By means of the septum transversum the pericardio-thoracic and the abdominal cavities are almost completely separated (fig. 314). There remain only two narrow canals (brh) (thoracic prolongations of the abdominal cavity, His), which establish a connection behind with the abdominal cavity at either side of the intestinal tube and its dorsal mesentery. The two canals (brh) receive the two fundaments of the lungs (Ig) when they grow out from the ventral wall of the intestinal tube. They afterwards become the two thoracic or pleura! cavities (brh), whereas the larger cavity communicating with them (hh), in which the heart has developed, becomes the pericardial chamber. The latter takes up the whole ventral side of the embryo ; the thoracic cavities, on the contrary, lie quite dorsal next to the posterior wall of the trunk.
 
 
 
568
 
 
EMBRYOLOGY.
 
 
 
How does the closure of these three originally communicating spaces take place, and how do they attain their altered, final position in relation to one another?
The pericardia! sac is the first to be separated off. The impulse to separation is furnished by the Cuvierian ducts (fig. 314 dc). One portion of the latter runs down from the dorsum, where it arises by the confluence of the jugular and cardinal veins, along the lateral walls of the trunk to the transverse septum (fig. 314 dc} ; it thereby
 
 
 
Fig. 314. Sagittal reconstruction of a human embryo 5 mm. long, neck measurement (embryo
R, His), to elucidate the development of the pericardio-thoracic cavity and the diaphragm,
after His. al>, Bnlbus arberiosus ; brh, thoracic cavity (recessus parietalis, His) ; hh, pericardia! cavity ;
dc, ductus Cuvieri ; dv, vena omphalomesenterica ; nr, umbilical vein ; vca, cardinal vein ;
rj, jugular vein ; lg. lung ; z + I, fundament of the diaphragm and liver ; ilk, mandible.
 
 
 
crowds the pleura into the pericardio-thoracic cavity, and in this manner produces the pleuro-pericardial fold. Since the latter is carried farther and farther inward, it continues to narrow the communication between the pericardial cavity (hli) and the two pleural cavities (brh} ; finally, it cuts off the communication entirely, when its free edge has grown [median wards] as far as, and has fused with, the mediastinum posterius, in which the rcsophagus lies. By this migration of the Cuvierian ducts is also explained the position of the superior vena cava, which later opens into the atrium from above, for it is derived from the Cuvierian duct. Originally located in
 
 
THE ORGANS OF THE INTERMEDIATE LAYER OR MESENCHYME. 569
the lateral wall of the trunk, its terminal part is afterwards enclosed in the mediastinum.
 
After the closure of the pericardia! sac, the narrow, tubular thoracic cavities (fig. 314 Mi) continue for a time to remain in communication behind with the abdominal cavity. The fundaments of the lungs (ly] meantime grow farther into them, and their tips finally come in contact with the upper surface of the liver, which also has now become larger. Then a closure is effected at these places also. From the lateral and posterior walls of the trunk project folds (the pillars of USKOW), which fuse with the septum transversum, and thus form the dorsal part of the diaphragm. One can therefore distinguish a ventral older part and a dorsal younger one.
 
As GEGENBAUR points out, this explains the course of the phrenic nerve, which runs in front of [ventral to] the heart and lungs and approaches the diaphragm from in front.
 
Occasionally the fusion of the dorsal and ventral fundaments is interrupted on one side. The consequence of such arrested development is a diaphragmatic hernia i.e., a permanent connection between abdominal and thoracic cavities by means of a hernial orifice, through which loops of the intestine can pass into the thoracic chamber.
 
When the four large serous spaces of the body have been completely shut off from one another, the individual organs must still undergo extensive alterations of position, in order to attain their ultimate condition. The pericardial sac at first takes up the whole ventral side of the breast, and over a large area is connected with the anterior wall of the thorax and with the upper wall of the diaphragm. Moreover, the latter is united with the liver along its whole under surface. The lungs lie hidden in narrow tubes at the dorsal side of the embryo.
 
There are two factors that come into the account in this connection (fig. 315). With the increase in the extent of the lungs (/(/), the thoracic cavities (pl.p) extend farther ventrally, and thereby detach the wall of the pericardial sac (jpc), or the pericardium, on the one hand from the lateral and anterior walls of the thorax, and on the other from the surface of the diaphragm. Thus the heart (ht\ with its pericardial sac, is displaced step by step toward the median plane, where, together with the large blood-vessels (ao), the oesophagus (al), and the bronchial tubes, it helps to form a partition the mediastinum -between the greatly enlarged thoracic cavities. In front the pericardial sac then remains in contact with the wall of
 
 
570
 
 
EMBRYOLOGY.
 
 
 
the thorax (st} and below with tho diaphragm for a little distance only.
 
The, second factor is the separation of the liver from the primary diaphragm, with ivhich it was united to form the septum transversum. This takes place as follows : At the margin of the liver the peritoneum, which originally covered only its under surface, grows over on to its upper surface, separating it from the primary diaphragm. A connection is retained near the wall of the trunk only. Thus is explained the development of the ligamentum coronarium hepatis,
 
 
 
Z ^-^ xi? s^BP=^-,
 
 
Fig. 315. Cross section through an advanced embryo of a Rabbit, to show how the pericardial
cavity becomes surrounded by the pleural cavities, from BALFOUR. ht, Heart ; pc, pericardial cavity ; pl.p, thoracic or pleural cavity ; Ig, lung ; al, alimentary
canal ; no, dorsal aorta ; ch. chorda ; r'p, rib ; st, sternum ; sp.c, spinal cord.
 
 
 
which was disregarded in the section which treated of the ligamentous supports of the liver (p. 330).
 
The diaphragm finally acquires its permanent condition by the ingrowth of muscles from the wall of the trunk into the connectivetissue lamella.
 
(c) The Metamorphoses of the Arterial System.
 
The development of the large arterial trunks lying in the vicinity of the heart is of great interest from a comparative-anatomical point of view. As in all Vertebrates at least five pairs of visceral arches
 
 
THE ORGANS OF THE INTERMEDIATE LAYER OR MESENCHYME. 571
 
 
are established on the two sides of the fore-gut (permanently in the gill-breathing Fishes, Dipnoi, and a part of the Amphibia, transitorily in the higher Vertebrates), so also there are developed at the corresponding places on the part of the vascular system five pairs of vascular arches* (fig. 316 1 ' 5 ). They take their origin from the truncus arteriosus (figs. 316, 317), which runs forward under the fore-gut, then follow along the visceral arches up to the dorsal surface of the embryo, and here unite on either side of the vertebral column into longitudinal vessels, the two primitive aortse (fig. 317 ad}. On this account they are called aortic arches, but they are more appropriately designated as visceral-arch vessels.
 
In the Vertebrates that breathe by means of gills, the vessels of the visceral arches become of importance in the process of respiration, and early lose their simple structure. From their ventral initial portions there arise numerous lateral branches running to the branchial lamella?, which have arisen in large numbers from the mucous membrane investing the visceral arches ; here they are resolved into fine capillary networks. From these the blood is re-collected into venous branches, which open into the upper end of the visceral-arch vessels. The larger the ventral and dorsal lateral branches, the more inconspicuous does the middle part of the
vessel of the visceral arch become. At length it has separated into an initial part, the branchial artery, which is distributed to the branchial lamellae in numerous branches, and an upper part, the branchial vein, into which the blood is re-collected. The two are connected with each other by means of the close network only, which, from its superficial position in the mucous membrane, presents a suitable condition for the removal of the gases from the blood.
 
Since in the Amniota there are no branchial lamellae produced, branchial arteries and veins also fail to be developed, the vessels of
* [The existence of six pairs of vascular arches has recently been shown to be the typical condition, the newly discovered pair, situated between the fourth and fifth pairs of RATHKE'S scheme (fig. 316), being of short duration in Amniota.]
 
 
 
Fig. 316. Diagram of the arrangement of the vessels of the visceral arches from an embryo of an amniotic Vertebrate.
 
1 5, First to fifth aortic arches ; a<l, aorta dorsalis ; ci, carotis interna ; ce, carotis externa ; v, vertebralis ; s, subclavia ; p, pulmonalis.
 
 
 
572
 
 
EMBRYOLOGY.
 
 
 
the visceral arches retaining their original simple condition. But thoy are in part of only short duration; they soon suffer, by the complete degeneration of extensive portions, a profound metamorphosis, which is effected in a somewhat different manner in Reptiles, Birds, and Mammals. An exposition of the changes in the case of Man only will be given here.
 
In human embryos only a few millimetres long, the truncus arteriosus, which emerges from the still single cardiac tube, is divided in the vicinity of the first visceral arch into a left and a right branch, which surround the pharynx, and are continuous above with the two primitive aortse. It is the first pair of aortic arches. In
 
 
 
 
Fig. 317. Development of the large arterial trunks, represented from embryos of a Lizard (A),
the Chick (), and the Pig (C), cifter RATHKE. The first two pairs of arterial arches have in all cases disappeared . In A and B the third,
fourth, and fifth pairs are still fully preserved ; in C only the two latter are still complete. p, Pulmonary artery arising from the fifth arch, but still joined to the dorsal aorta by means of
a ductus Botalli ; c, external, c', internal carotid ; aJ, dorsal aorta ; o, atrium ; r, ventricle ;
n, nasal pit ; m, fundament of the anterior limb.
 
only slightly older embryos their number is rapidly increased by the formation of new connections between the ventral truncus arteriosus and the dorsal primitive aorta?. Soon a second, a third, a fourth, and, finally, a fifth pair make their appearance in the same sequence in which the visceral arches are established in the case of Man as well as the remaining Vertebrates.
 
The five pairs of vascular arches give off lateral branches to the neighboring organs at a very early period ; of these several acquire a great importance and become carotis externa and interna, vertebralis and subclavia as well as pulrnonalis. The carotis externa (fig. 316 ce and fig. 317 c) arises from the beginning of the first vascular arch, and is distributed to the region of the upper and
 
 
THE ORGANS OF THE INTERMEDIATE LAYER OR MESENCHYME. 573
lower jaws. The carotis iiiterna (tigs. 316 ci, 317 c') likewise arises from the first arch, but farther dorsally, at the point where the arch bends around to become continuous with the root of the aorta ; it conducts the blood to the embryonic brain and to the developing eye-ball (arteria ophthalmica). From the dorsal region of the fourth vascular arch (fig. 316 4 ) a branch is given off which is soon divided into two branches, one of which goes headwards to the medulla oblongata and the brain, the arteria vertebralis (v), whereas the other (s) supplies the upper limb (arteria subclavia). In the course of development these two arteries interchange relations in respect to calibre. In young embryos the vertebralis is by far the more important, while the subclavia is only a small inconspicuous lateral branch. But the more the upper extremity increases in size, the more the subclavia is elevated into the position of" the main trunk, and the more the vertebralis sinks to the rank of an accessory branch. Finally, from the fifth [sixth] arch there bud forth branches to the developing lungs (figs. 316, 317 p}.
 
As the simple diagram shows, the fundament of the arterial trunks which arise from the heart is originally strictly symmetrical. But at an early period there occur reductions of certain vascular tracts even to their complete disappearance ; in this way the symmetrical arrangement is (jradually converted into an unsymmetrical one.
 
The accompanying diagram (fig. 318) in which the parts of the vascular course that degenerate are left free, and those which continue to be functional are marked by a heavy central line will serve to illustrate this metamorphosis.
 
First, as early as the beginning of the nuchal flexure, the first and second vascular arches with the exception of the connecting portions through which the blood flows to the carotis externa (b) disappear.
 
The third arch (c) persists, but loses its connection with the dorsal end of the fourth, and therefore now conveys all its blood toward the head into the carotis iiiterna (), of which it has now become the initial part.
 
The chief role in the metamorphosis is assumed by the fourth arid fifth arches (fig. 317 C). They soon exceed all other vessels in size, and as they lie nearest to the heart, they are converted into the two chief arteries which arise from it, the aortic arch and the arteria pulmonalis. An important modification is effected at the place of their origin from the tnmcus arteriosus when the latter is divided lengthwise by means of the development of the partition previously
 
 
574
 
 
EMBRYOLOGY.
 
 
 
r-Ot
 
 
 
mentioned. The fourth arch (fig. 318 e) then remains in connection with the trunk (d) which arises from the left ventricle and receives blood exclusively from that source. The fifth arch (n), on the contrary, forms the continuation of that half (m) of the truncus arteriosus which emerges from the right ventricle. Thus the division of the blood into two separate currents initiated in the heart is also continued into the nearest vessels, but for a short distance only, since the fourth and fifth pairs of vascular arches (fig. 317) still empty their blood together into the aorta cominunis (ad), with the
exception of a certain portion which runs through their accessory branches, in part to the head (c.c) and upper limbs, in part to the still diminutive lungs. Gradually, however, the, process of separation thus introduced is continued still farther into the region of the peripheral vessels and finally leads to the establishment of the entirely distinct major and minor circulations. The final condition is attained by the degeneration of certain portions of the vessels and the enlargement of others.
 
A preponderance of the vascular arches of the left side over those of the right is soon recognisable (fig. 318). The former continually increase in size, while those of the right side become less and less apparent and finally in places disappear altogether. They are retained only in so far as they conduct the blood to the lateral branches which, arising from them, go to the head, the upper limbs, and the lungs. Consequently of the right aortic arch there remains only the tract which gives rise to the right carotis cominunis (c) and the right subclavia (i-\-l). We designate its initial part as the arteria anonyma brachiocephalica. With this the permanent condition is now established. The remnant of the right fourth vascular arch appears as a side branch only of the aorta (e), which forms an arch 011 the left side of the body, and here gives rise to the carotis cominunis sinistra (c) and the subclavia sin. (A) as additional lateral branches.
 
The right half of the fifth [sixth] pair of vascular arches likewise undergot'H degeneration, except for the portion that conveys blood
 
 
m
 
 
Fig. 318. Diagrammatic representation of the metamorphosis of the bloodvessels of the visceral arches in a Mammal, after RATHKE.
 
a, Carotis intei'na ; b, carotis externa ; c, carotis communis ; d, body or systemic aorta ; e, fourth arch of the left side ; /, dorsal aorta ; g, left, k, right vertebral artery ; /i, left subclavian artery ; i, right subclavian (fourth arch of the right side) ; I, continuation of the right subclavian ; m, pulmonary artery ; n, its ductus Botalli.
 
 
 
THE ORGANS OF THE INTERMEDIATE LAYER OR MESENCHYME. 575
 
 
to the right lung. On the left side of the body, on the contrary, the pulmonary arch still persists for a long time and conducts blood into the left lung and also through the ductus arteriosus Botalli (n), into the aorta. After birth, in connection with pulmonary respiration, the duct of BOTALLI also degenerates. For the lungs, when they are expanded by the first act of inspiration, are in a condition to receive a greater quantity of blood. The consequence is that blood no longer flows into the ductus Botalli, and that the latter is converted into a connective-tissue cord, which extends between aorta and art. pulmonalis.
 
In addition to the regressive changes mentioned, there are effected meantime alterations of position in the large vascular trunks that arise from the heart. They move at the same time with the heart from the neck region into the thoracic cavity. In this fact lies the explanation of the peculiar course of the nervus laryngeus inf. or recurrens. At the time when the fourth
 
 
 
vascular arch still lies forward in the region
 
 
Fig. 319. Diagrammatic representation of the metamorphosis of the arterial arches in Birds, after RATHKE.
 
, Intez-nal, b, external, c, common carotid ; d, systemic aorta ; e, fourth arch of the right side (root of the aorta) ; /, rightsubclavian; g, dorsal aorta ; h, left subclavian (fourth arch of the left side) ; i, pulmonary artery ; k and I, right and left ductus Botalli of the pulmonary arteries.
 
 
 
of its formation in the fourth visceral arch,
the vagus sends to the larynx a small nerve
branch, which, to reach its destination,
passes below [caudad of] the vascular arch.
 
When the latter migrates downwards, the
nervus laryngeus must thereby be carried
down with it into the thoracic cavity, and
must form a loop, one portion of which,
arising in the thoracic cavity from the vagus,
bends around the arch of the aorta on the
left side of the body (but around the subclavia on the right side of
the body) to become continuous with the second portion, which takes
the opposite or upward course to the region of its distribution.
 
The processes of development discussed also throw light on a series of abnormalities which are quite frequently observed in the large vascular trunks. I shall cite and explain two of the most important of these cases.
 
Occasionally in the territory of the vessels of the fourth visceral arches the original symmetrical condition is retained. The aorta is then divided in the adult into right and left vascular arches, which
 
 
576 EMBRYOLOGY.
 
convey the blood into the unpaired aorta. From each of them there arises, as in the embryo, a separate carotis commnnis and subclavia.
 
Another abnormality is brought about by the development of the aortic arch of the right side of the body instead of that of the left, a condition which is met with in the class of Birds (fig. 319) as the normal state. This malformation is always connected with an altered position of the organs of the chest, a situs inversus viscerum. Of the other changes in the region of the arterial system the metamorphosis of the primitive aorta is to be mentioned before all others. As in the other Vertebrates (fig. 127 o), so in Man, there are formed a right and a left aorta ; but they subsequently move close together and fuse. This, again, explains an abnormality, which, it is true, has very rarely been observed in Man. The aorta is divided into right and left halves by means of a longitudinal partition ; the process of fusion, therefore, has not been fully effected.
 
The aorta gives off at an early period as branches the unpaired mesenterica sup. and rnesenterica inf. to the intestinal canal ; furthermore, near its posterior end, the two voluminous navel vessels, arteries unibilicales (fig. 139 Al). These run from the dorsal wall of the trunk along the sides of the pelvic cavity ventrally to that part of the allantois which is subsequently differentiated into urinary bladder and urachus, here bend upward and pass on either side of the latter in the abdominal wall to the navel, enter the umbilical cord, and are resolved in the placenta into a capillary network, from which the blood is re-collected into the veme unibilicales. During their passage through the pelvic cavity the umbilical arteries give off lateral branches that are at first inconspicuous, the iliacae internee, to the pelvic viscera, the iliacae externse to the posterior limbs now sprouting forth from the trunk as small knobs. The more the latter increase in size in older embryos, the larger do the iliacse externse and their continuations, the femorales, become.
 
After giving off the two umbilical arteries, the aorta becomes smaller and is continued to the end of the vertebral column as an inconspicuous vessel, the aorta caudalis or sacralis media.
 
At birth an important alteration occurs in this part of the arterial system also. With the detachment of the umbilical cord, the umbilical arteries can 110 longer receive blood ; they therefore waste away with the exception of the proximal portion, which has given off as lateral branches the internal and external iliacs, and is
 
 
THE ORGANS OF THE INTERMEDIATE LAYER OR MESENCHYME. 577
now designated as the iliaca communis. However, two connectivetissue cords result from the degenerating vessels, the ligamenta vesico-umbilicalia lateralia, which run to the navel on. the right and left of the bladder.
 
(cZ) Meta/niorphoses of the Venous System.
 
The older excellent works of KATHKE and the more recent meritorious investigations of His and HOCHSTETTER constitute the foundation of our knowledge in the difficult field with which we are now concerned. They show us that originally all of the chief trunks of the venous system, with the exception of the inferior vena cava, are established in pairs and sij HI metrically. This holds true not only for the vessels which collect the blood from the walls of the trunk and from the head, but also for the veins of the intestinal tube and the embryonic appendages which arise from it.
 
In the first place, so far as regards the veins of the body, the venous blood is collected from the head into the two jugular veins (fig. 320 vj and fig. 321 A je, ji), which run downwards along the dorsal side of the visceral clefts and unite in the vicinity of the heart with the cardinal veins (fig. 320 vca and fig. 321 A ca). The latter advance in the opposite direction, from below upwards, in the dorsal wall of the trunk, and collect the blood especially from the niesonephros. There arise from the confluence of the two veins the Cuvierian ducts (figs. 320, 321 A dc), from which are subsequently developed the two superior venae cavse. The veins of the trunk in Fishes exhibit a symmetrical arrangement like this throughout life.
 
In the earliest stages the Cuvierian ducts lie for some distance in the lateral wall of the pericardio-pleural cavity, where they run downwards from the dorsum to the front [ventral] wall of the trunk (fig. 320). On arriving at this point, they enter into the septum transversum, KOLLIKER'S mesocardiuni laterale, in order to reach the atrium of the heart. This important embryonic structure forms a point of collection for all the venous trunks emptying into the heart. In it there are joined to the Cuvierian ducts the veins from the viscera (fig. 313 V.om and Vu, fig. 320 dv and nv), the paired yolk veins and umbilical veins, all of which are joined into the common sinus venosus, which was previously (p. 558) mentioned apropos of the development of the heart, and which is situated directly between atrium and septum transversum.
 
The two vitelline veins (v. omphalomeseiitericre) return the blood
37
 
 
578
 
 
EMBRYOLOGY.
 
 
 
from the yolk-sac ; they are the two oldest and largest venous trunks of the body, but they become inconspicuous in the same ratio as the yolk-sac shrinks to an umbilical vesicle. They run close together along the intestinal tube, and come to lie at the sides of the duodenum and stomach, where they are united to each other by transverse anastomoses even at a very early period.
 
The navel veins (vena? umbilicales) are also originally double. At first very small, they subsequently become, in contrast with the vitelline veins, more and more voluminous, as the placenta, from
 
 
ab uk
Ith
 
 
 
Fig. 320. Sagittal reconstruction of a human embryo 5 mm. long, neck measurement (embryo R, His), to illustrate the development of the pericardio-thoracic cavity and the diaphragm, after His.
 
ab, Aortic bulb ; brh, thoracic cavity (recessus parietalis,jHis) ; hit, pericardial cavity ; tie, ductus Cuvieri ; dc, vitelline vein (v. omphalomesenterica) ; nv, umbilical vein ; vca, cardinal vein ; vj, jugular vein ; Ig, lung ; z + I, fundament of the diaphragm and the liver ; uk, lower jaw.
 
which they convey the blood back to the body of the embryo, is further developed. At the time of their first appearance the umbilical veins are found to be imbedded in the lateral wall of the abdomen (fig. 313 Vu), in which they make their way to the septum transversuni and the sinus venosus (sr).
 
The inferior vena cava (fig. 321 A ci] is established later than any of these paired trunks. It makes its appearance as an inconspicuous, from the beginning unpaired, vessel (in the Rabbit on the twelfth day, HOCHSTETTER) on the right side of the aorta in the tissue between the two primitive kidneys ; caudalwards it is connected by
 
 
THE ORGANS OF THE INTERMEDIATE LAYER OR MESENCHYME. 579
lateral anastomoses with the cardinal veins. At the heart it opens into the sinus venosus.
 
From this primitive form of the venous system (fig. 321 A) is derived the ultimate condition in Man. There are three changes which are conspicuous in this connection. (1) The veins empty directly into the atrium instead of a venous sinus. (2) The symmetrical arrangement in the region of the Cuvierian ducts and the jugular and cardinal veins gives place to an unsymmetrical arrange
 
 
 
 
 
Fig. 321. Diagram of the development of the venous system of the body.
 
dc, Ductus Cuvieri ; je, ji, vena jugularis externa, interna ; s, v. subclavia ; ch, v. hepatica revehens ; U, v. umbilicalis ; ci (ci 2 ), v. cava inferior ; ca (ca l , cor, ca 3 ), v. cardinalis ; ilcd, ilcs, v. iliaca communis dextra, sinistra ; ad, us, v. anonym a brachiocephalica dextra, sinistra ; cs, v. cava superior ; csd, v. cava superior dextra ; ess, rudimentary portion of v. cava superior sinistra ; cc, v. coronaria cordis ; o.z, v. azygos ; liz (kz 1 ), v. hemiazygos ; He, v. iliaca externa ; ill, v. iliaca interna ; /, v. renalis.
 
meiit accompanied by a degeneration or stunting of some of the chief trunks. (3) With the development of the liver there is formed a special portal system.
 
The alteration first mentioned is accomplished by the incorporation of the sinus venosus in the atrium. At first enclosed in the septum transversum, the sinus elevates itself above the upper surface of the latter, from which it detaches itself, and conies to lie as an appendage to the atrium in the anterior trunk-cavity. Finally it fuses completely with the heart and furnishes the smooth region of the atrial wall, which is destitute of the pectinate muscles (His).
 
 
 
580 EMBRYOLOGY.
 
There are in it separate openings for the two Cuvierian ducts the future venae cavae superiores and an opening distinct from them for the veins coming from the viscera below (the future cava inferior).
 
The metamorphoses in the region of the Cuvierian ducts begin with a change in their position. Their course from above downward becomes more direct. At the same time, like the sinus venosus, they emerge from the niveau of the transverse septum and lateral walls of the trunk into the body-cavity and carry before them the serous membrane, with which they are covered, as a crescentshaped fold, which contributes to the formation of the pericardial sac, and has been already described as the j)leuro-j)ericardial fold. By fusing with the mediastinum the Cuvierian ducts pass from the walls of the trunk into the latter and come to lie nearer together in the median plane. Of their affluents the jugular veins gradually predominate over the cardinal veins (fig. 322 B). There are three reasons for this. First, the anterior part of the body, and especially the brain, far outstrips in growth the posterior part ; secondly, there arises in this region a competitor of the cardinal veins, the inferior vena cava, which assumes in place of them the function of returning the blood. Thirdly, when the anterior limbs are established, the venae subclavise (s) empty into the jugulares. Consequently the lower portion of the jugular, from the entrance of the subclavia onward, now appears as the immediate continuation of the Cuvierian duct, and together with it is designated as superior vena cava (fig. 322 B csd).
 
There exists between the right and left sides a difference in the course of the superior venae cavae, which, as GEGENBAUR has pointed out, is the cause of the asymmetry that is developed in Man. While the right vena cava superior (fig. 322 B csd) descends more directly to the heart, the left (ess) describes a somewhat longer course. Its terminal portion is bent from the right to the left around the posterior [dorsal] wall of the atrium, where it is imbedded in the coronal furrow and receives the blood from the coronal vein (cc) of the heart.
 
In Reptiles, Birds, and many Mammals a stage of this kind, with two venae cavae superiores, becomes permanent ; in Man it exists only during the first months. Then there is a partial degeneration of the left vena cava superior. The degeneration is initiated by the formation of a transverse anastomosis (fig. 322 B as) between the right and left trunks. This conveys the blood from the left to the right side, where the conditions are more favorable for the
 
 
THE ORGANS OF THE INTERMEDIATE LAYER OR MESENCHYME. 581
return of the blood to the heart. In consequence of this the proximal end of the right cava becomes much larger, the left, on the contrary, proportionately smaller. Finally, there is a complete wasting away of the latter blood course (fig. 322 ess] as far as the terminal part (cc), which is lodged in the coronal groove. This part remains open, because the cardiac veins convey blood to it, and is now distinguished as sinus coronarius.
 
A process in many respects similar to this is repeated in the case
 
 
 
 
 
Fig. 322. Diagram of the development of the venous system of the body.
 
ilc, Ductus Cuvieri ; je, ji, vena jugularis externa, interna ; s, v. subclavia ; r/<, v. hepatica revehens ; U, v. umbilical is ; cl (cl~), v. cava inferior; ca (ca l , ca' 2 , ccr), v. cardinal is ; ilcd, ilcs, v. iliaca communis dextra, sinistra ; ail, *, v. anonyma brachiocephalica dextra, sinistra ; cs, v. cava superior ; csd, v. cava superior dextra ; c.s-.s, nidimentary portion of v. cava superior sinistra ; cc, v. coronaria cord is ; az, v. azygos ; hz (/<:'), v. hemiazygos ; He, v. iliaca externa ; Hi, v. iliaca iuterna ; r, v. renalis.
 
of the cardinal veins (fig. 322 A ca). The latter collect the blood from the primitive kidneys and the posterior wall of the trunk, from the pelvic cavity and the posterior limbs. From the pelvic cavity they receive the vente hypogastrica? (Hi), and from the limbs the v. iliacae externae (He) and their continuation, the v. crurales. In this way the cardinal veins are at first, as in Fishes, the chief collecting trunks of the lower half of the body. Subsequently, however, they diminish in importance, since the inferior vena cava becomes the main collecting trunk instead of them.
 
It is only within the last few years that the development of the
 
 
582 EMBKYOLOflY.
 
inferior vena cava has been (by HOCHSTETTER) explained. According to his investigations there are to be distinguished two tracts which are of dill'erent origin, a shorter anterior and a longer posterior. The former, as previously mentioned, makes its appearance as an inconspicuous vessel on the right side of the aorta in the tissue between the two primitive kidneys (fig. 322 A and B ci) ; the latter, on the contrary, is developed subsequently out of the posterior region of the right cardinal vein (fig. 322 B ci 2 ). The anterior, independently arising part of the inferior vena cava, soon after its establishment, unites with the two cardinal veins by means of transverse branches in the vicinity of the vena renalis (?*). In consequence of this increase of drainage territory, it soon increases considerably in calibre, and since it presents more favorable conditions for the conveyance of blood from the lower half of the body than the upper portion of the cardinal veins does, it finally becomes the chief conduit.
 
If the stage thus far described were to become the permanent condition (fig. 322 It), we should have an inferior vena cava, which forks in the region of the renal veins (r) into two parallel trunks, that descend at both sides of the aorta to the pelvis. Such cases, as is known, are found among the varieties of the venous system ; they are derived from the previously described stages of development as malformations by arrested growth. However, they are only rarely observed, for in the normal course of development there is established at an early period an asymmetry between the lower portions of the two cardinal veins, from the moment, indeed, when they have united themselves to the lower part of the inferior vena cava by means of anastomoses. The right portion acquires a preponderance, becomes enlarged, and finally alone persists (fig. 322 B, C), whereas the left lags behind in growth and withers. This results from two conditions. First, the right cardinal vein (ci 2 ) lies more in the direct prolongation of the vena cava inferior than does the left, and thus occupies a more favorable situation ; secondly, there is formed in the pelvic region an anastomosis (ilcs) between the two cardinal veins, which conducts the blood of the left hypogastrica and the left iliaca externa and cruralis to the right side. Owing to this anastomosis, which becomes the vena iliaca communis sinistra, the portion of the left cardinal vein lying between the renal veins and the pelvis (fig. 322 C c 3 ) is rendered functionless, and with the degeneration of the primitive kidney disappears. The right cardinal vein has now become for a certain distance a direct continuation of the inferior
 
 
THE ORGANS OF THE INTERMEDIATE LAYER OR MESENCHYME, 583
vena cava; it furnishes that portion of the latter which is situated between the renal veins and the division into the two ven;i> iliacse cornmunis (fig. 322 B and C ci 2 }.
 
While the abdominal part of the left cardinal vein (fig. 322 C e 3 ) succumbs and the corresponding region of the right cardinal vein produces the lower part of the inferior vena cava (ci 2 ), their thoracic portions persist in a reduced form, since they receive the blood from, the intercostal spaces (fig. 322 7? c). In this region occurs still another and last metamorphosis, by which likewise an asymmetry is brought about between the halves of the body. In the thoracic part of the body the original conditions of the circulation are altered by the degeneration of the left cava superior (fig. 322 C ess). The direct flow of the left cardinal vein to the atrium is thereby rendered more difficult, and finally ceases altogether, the tract designated by ca 2 undergoing complete degeneration. Meanwhile a transverse anastomosis (hz l ], which has been formed in front of the vertebral column and behind the aorta between the corresponding vessels of both sides, receives the blood of the left side of the body and transports it to the right side. In this manner the thoracic part of the left cardinal vein and its anastomosis become the left hemiazygos (hz and hz l ) ; the right and larger cardinal vein becomes the azygos (az).
 
Thus by many indirect ways, is attained the permanent condition of the venous system of the trunk, with its asymmetry and its preponderance of the venous trunks in the right half of the body.
 
A third series of metamorphoses, which we shall now take into consideration, concerns the development of a liver circulation.
 
The liver receives its blood in different stages of the embryonic development from various sources : for a time from the vitelline veins ; during a second period from the umbilical veins ; after birth, finally, from, the veins of the intestines the portal vein. This threefold alteration finds its explanation in the conditions of growth of the liver, the yolk-sac, and the placenta. As long as the liver is small, the blood corning from the volk-sac suffices for its
O v
nourishment. But when it increases greatly in size the yolk-sac, on the contrary, growing smaller other blood-vessels at this time, the umbilical veins, must supply the deficiency. When, finally, at birth the placental circulation ceases, the venous trunks of the intestinal canal, which meanwhile have become very large, can supply the needs.
 
These circumstances must be kept in mind, in order to comprehend
 
 
584 EMBRYOLOGY.
 
the shifting conditions of circulation in the liver and the profound altrr.il ions lo which the venous trunks connected with it the vitelline, imihilic:il, and portal veins are naturally subjected in the changing supply of blood.
 
When the hepatic ducts grow out from the duodenum into the ventral mesentery and septum transversnm and send out shoots, they enclose the two vitelline veins accompanying the intestine, which are at tins place connected with each other by ring-like anastomoses (sinus annularis, His) which surround the duodenum (fig. 320 dv). They are supplied with blood by lateral branches given oft' from these veins. The more the liver increases in size, the larger do the lateral branches (venae hepaticse advehentes) become. Between the network of hepatic cylinders (fig. 187 lc] they are resolved into a capillary network (<y), from which at the dorsal margin of the liver large efferent vessels (vena? hepaticse revehentes) re-collect the blood and convey it back into the terminal portion of the vitelline vein, which empties into the atrium. In consequence of this the portion of the vitelline vein which lies between the vena3 hepaticse advehentes and revehentes continually becomes smaller, and finally atrophies altogether, since all the blood from the yolk-sac is employed for the hepatic circulation. The same process in the main is accomplished here as in the vessels of the visceral arches of gill -breathing Vertebrates, which upon the formation of branchial lamellae are converted into branchial arteries, branchial veins, and a capillary network interpolated between the two.
 
The two umbilical veins participate, even at an early period, in the hepatic circulation. Originally they run from the umbilical cord in the front [ventral] wall of the abdomen (fig. 313 Vu], from which they receive lateral branches, and then enter the sinus venosus (/Sr) above the fundament of the liver. They pursue, therefore, an entirely different course from that which they do later, when the terminal part of the umbilical vein is situated under the liver. According to His, this change in their course takes place in the following manner : The right umbilical vein in part atrophies (as also in the Chick, p. 552) and becomes, as far as it persists, a vein of the ventral wall of the abdomen. The left umbilical vein, on the contrary, gives off anastomoses in the septum transversum to neighboring veins, one of which makes its way under the liver to the sinus annularis of the vitelline veins, and thereby conducts a part of the placental blood into the hepatic circulation. Since by its rapid growth the liver demands a large accession of blood, the
 
 
THE ORGANS OF THE INTERMEDIATE LAYER OR MESENC'HYME. 585
 
 
anastomosis soon becomes the chief course, and finally with the degeneration of the original tract receives all the blood of the umbilical veins. This, mingled with the blood of the yolk-sac, circulates through the liver in the vessels which took their origin from the vitelline veins in the venae hepaticre advehentes and revehentes. Then it flows into the atrium through the terminal part of the vitelline vein. The latter also receives the inferior vena cava, which at this time is still inconspicuous, and can therefore be designated even now, in view of the ultimate condition, as the cardiac end of the inferior vena cava.
 
During a brief period all of the placental blood must first traverse the hepatic circuit in order to reach the heart. A direct passage to the. inferior vena cava through the ductus venosus Arantii does not yet exist. But such an outlet becomes necessary from the moment when, by the growth of the embryo and the placenta, the blood of the umbilical veins has so increased in amount that the hepatic circu
 
 
c.i'
 
 
 
- r.le
 
 
n.v
 
 
lation is no longer able
 
 
Fig. 323. Liver of an 8-months human embryo, seen from
the under surface, from GKGENBAUR. Lie, Left lobe of the liver ; r.le, right lobe ; n.r, umbilical
vein ; d.A, ductus venosus Arantii ; j>f.a, portal vein ;
ha. .v, Jta.il, vena hepatica advehens sinistra and dextra ;
/(./, vena hepatica revehens ; c.i', cava inferior; c.i",
terminal part of the cava inferior, which receives the
vente hepaticae revehentes (/<./).
 
 
 
to contain it. There is then developed on the
under surface of the liver out of anastomoses a more direct connecting branch, the ductus venosus Arantii (fig. 323 d.A), between umbilical vein (n.v) and inferior vena cava (c.i"). Thus is established and it persists until birth a condition by which the placental blood (n.v) is divided at the porta into two currents : one passing through the ductus venosus Arantii (d.A) into the inferior vena cava (c.i ") ; the other pursuing a round-about way, passing through the venae hepaticse advehentes (ha.s and ha.d) into the liver, here mingling with the blood brought to the liver through the vitelline vein (pf.a) from the yolk-sac and from the intestinal canal, which has in the meantime become enlarged, and finally passing through the venae hepaticse revehentes (h.r), also to reach the inferior vena cava (c.i").
 
There is still something to be added concerning the development of
 
 
586 EMBRYOLOOY.
 
tin' portal vein. It is to be seen in fig. 323 as an unpaired vessel (/>/'.}. It. empties into the rig-lit aflerent hep.-itie vein, derives its roots from the region of the intestinal canal, and conveys the venous blood from the latter into the right lobe of the liver. It takes its origin from the two primitive vitelline veins.
 
According to the account of His, the two vitolline veins fuse along the tract where they run close together on the intestinal canal ; on the contrary, in the region where they run to the liver and are connected with each other to form two ring-like anastomoses, each of which encircles the duodenum, an unpaired trunk is formed by the atrophy of the right half of the lower [posterior] ring and the left half of the upper one. The portal vein thus formed therefore runs first to the left and backward [dorsad] around the duodenum, and then emerges on the right side of it ; it draws its blood partly from the yolk-sac and partly from the intestinal canal through the vena mesenterica. Afterwards the first source is exhausted with the regressive metamorphosis of the yolk-sac, but the other becomes more and more productive with the enlargement of the intestine, the pancreas, and the spleen, and during the last months of pregnancy conveys a large stream of blood to the liver.
 
The additional changes, which occur at birth, are easily comprehended (fig. 323). With the detachment of the after-birth the placental circulation ceases. The umbilical vein (n.v) conveys no more blood to the liver. That portion of its tract which extends from the umbilicus to the porta hepatis degenerates and becomes a fibrous ligament (the lig. hepato-umbilicale or lig. teres hepatis), Likewise the ductus Arantii (d.A) produces the well-known ligament enclosed in the left sagittal fissure (lig. venosum). The right and left venas hepaticre advehentes (ha.d, ha.s) again receive their blood, as in the beginning of the development, from the intestinal canal through the portal vein (pf.a).
 
Now that we have become acquainted with the details of the morphological changes, I close this section on the vascular system with a short sketch of the fcetal circulation of the blood. It is characteristic of this that no division into two separate circulations, into the major or systemic and the minor or pulmonary, has yet taken place ; further, that in most of the vessels neither purely arterial nor purely venous blood circulates, but a mixture of the two. Purely arterial blood is contained only in the umbilical veins as they come from the placenta, whence we will follow the circulation.
 
Having arrived at the liver, the current of the umbilical veins is
 
 
THE ORGANS OF THE INTERMEDIATE LAYER OR MESEXCHYME. 587
divided into two branches. One stream goes directly through the ductns Arantii into the inferior vena cava, and is here mingled with the venous blood which returns to the heart from the posterior limbs and the kidneys. The other stream passes through the liver, where there is added to it the venous blood of the portal vein coming from the intestine ; by this circuitous course it also reaches, through the venae hepaticse revehentes, the inferior vena cava. From the latter the mixed blood flows into the right atrium, but, in consecjuence of the position of the Eustachian valve and because the foramen ovale is still open, the greater part of it passes through the latter into the left atrium. The other smaller part is again mingled with venous blood, which has been collected by the superior vena cava from the head, the upper limbs, and (through the azygos) from the walls of the trunk, and is propelled into the right ventricle and from there into the pulmonaiis. The latter sends a part of its highly venous blood to the lungs, the other part through the ductns Botalli to the aorta, where it is added to the arterial current coming from the left ventricle.
 
The blood of the left ventricle comes principally from the inferior cava, only a small part of it from the lungs, which pour their blood, which at this time is venous, into the left atrium. It is driven into the aortic arch and part of it is given off through lateral branches to the head and upper limbs (carotis communis, subclavia) ; the rest is carried on downwards in the aorta descendens, where the venous current of blood from the right atrium by the way of the cluctus Botalli is united with it. The mixed blood is distributed to the intestinal canal and the lower limbs, but the most of it reaches the placenta through the umbilical veins, where it is again made arterial.
 
In the distribution of the blood in the anterior and the posterior regions of the body a noteworthy difference is easily recognised. The former receives through the carotis and subclavia a more arterial blood, since to the stream in the aorta descendens is added the venous blood of the right ventricle through the ductus Botalli. Especially in the middle of pregnancy is this difference important. There has been an endeavor to refer to this fact the more rapid growth of the upper part of the body in comparison with the lower.
 
As this sketch has shown, there is everywhere a mingling of the different kinds of blood. This, it is true, is not uniform in the different months of embryonic life, because, indeed, the separate organs do not alter in size uniformly, and especially because the lungs during the later stages are in a condition to receive more blood, and finally because the foramen ovale and the ductus Botalli become narrower
 
 
588 EMBRYOLOGY.
 
during the last months. On account of theso facts, less blood passes, even before birth, from the inferior vena, cava into the left atrium, and likewise less from the pulmonary artery into the descending aorta, than was the case in earlier months. Thus there is gradually introduced toward the end of pregnancy a separation into a right and a left heart, with their separate blood-currents (HASSE). But it is almost at a single stroke that this separation, in consequence of birth, becomes complete.
 
Great alterations are now brought about by the beginning of pulmonary respiration and by the cessation of the placental circulation. Both events cooperate to increase the blood-pressure in the left heart, and to diminish that in the right. The blood -pressure becomes reduced because no more blood runs into the right atrium from the umbilical vein and because the right ventricle must furnish more blood to the expanding lungs. In consequence of this the ductus Botalli (fig. 318 n) is closed and then converted into the ligamentuiu Botalli. Since, moreover, a greater quantity of blood now flows from the lungs into the left atrium, the pressure in the latter is increased, and since at the same time the pressure is diminished in the right atrium, the closure of the foramen ovale, owing to the peculiar valvular arrangements, is now effected. For the margin of the valvula foraminis ovalis applies itself firmly to the limbus Vieussenii and fuses with it.
 
By the closure of the oval foramen and the Botallian duct the division of the blood -current into a major, systemic circuit and a minor, pulmonary circuit, which was initiated before birth, is now completed.
 
SUMMARY. Development of the Heart.
 
1. In the first fundament of the heart two different types can be distinguished in Vertebrates.
 
First Type. In Gyclostomes, Selachians, Ganoids, and Amphibia the heart is developed from the beginning as an unpaired structure on the under [ventral] surface of the cavity of the head-gut, in the ventral mesentery, which is thereby divided into a mesocardium anterius and posterius.
 
Second Type. In Birds and Mammals the heart is developed out of separate halves, which afterwards fuse with each other into a single tube, which then has the same position as in the first type.
 
 
 
THE ORGANS OF THE INTERMEDIATE LAYER OR MESENCHYME. 589
2. The second type is to be derived from the first, and is explainable as an adaptation to the great size of the yolk, in that the heart is established at a time when the splanchnopleure is still spread out flat upon the yolk and is not yet folded together to form the headgut.
 
3. The cells which are united to form the endothelium of the heart are split off from a proliferating, thickened place of the entoderm.
 
4. The heart is first established in all Vertebrates in the cervicocephalic region behind the last visceral arch.
 
5. The posterior or venous end of the single cardiac tube receives the blood from the body through the oniphalomesenteric veins ; the anterior or arterial end gives off the blood to the body through the truncus arteriosus.
 
6. In the arnniotic Vertebrates the single cardiac sac is converted by a series of metamorphoses (1) by flexures, constrictions, and changes of position, and (2) by the formation of partitions inside of it into a heart composed of two ventricles and two atria.
 
7. The straight sac assumes the form of a letter S.
 
8. The venous portion of the 8 comes to lie more dorsal, the arterial more ventral ; the two are marked off from each other by a constriction, the auricular canal, and are now to be distinguished as atrium and ventricle.
 
9. The venous portion or the atrium forms lateral evaginations, the auricles of the heart, which surround from behind the truncus arteriosus.
 
10. The formation of partitions, by which atrium, ventricle, and truncus arteriosus are divided into right and left halves, begins at three different places.
 
(a) First of all, the atrium is divided by an atrial partition into a right and a left half ; but the separation is incomplete, since there exists a passage in the partition, the foramen ovale, which remains open up to the time of birth.
 
(6) By its downward growth the atrial partition reaches the auricular canal (septum intermedium of His) and divides the opening in it into a right and left ostium atrioventriculare.
 
(c) The ventricle is divided into right and left halves by a partition (septum ventriculi) beginning at the apex of the heart ; the division is also indicated externally by the sulcus interventricularis,
 
 
590 EMBRYOLOGY.
 
(d) The truncus arteriosus is divided into pulmonary artery and aorta by the development of a special partition, which begins above, grows downward, arid joins the ventricular partition.
 
() The complete separation of the atria first takes place after birth by the permanent closure of the foramen ovaie.
 
11. At the ostium atrioventriculare and at the ostium arteriosum the first fundaments of the valves are formed as thickenings of the endocardium (endocardia! cushions) projecting inward.
 
Development of the C kief Arterial Trunks of Man and Mammals.
 
12. From, the truncus arteriosus there arise five pairs of visceral arch vessels (aortic arches), which run along the visceral arches, embrace the head-gut laterally, and unite dorsally to form the two primitive aortas.
 
13. The two vessels fuse at an early period to form the unpaired aorta lying under the vertebral column.
 
14. In Mammals, of the five pairs of visceral-arch vessels the first and second degenerate ; the third furnishes the proximal part of the carotis interna ; the fourth arch becomes on the left side the aortic arch, on the right side the arteria anonyma brachiocephalica and the proximal part of the subclavia ; [the fifth early disappears ;] the fifth [sixth] arch gives off branches to the lungs, and becomes the pulmonary artery, but on the left side remains until the time of birth in open communication with the aortic arch through the ductus Botalli, whereas the corresponding portion 011 the right side atrophies.
 
15. After birth the ductus Botalli is closed and converted into the ligament of the same name.
 
16. From the aorta two pairs of large arterial trunks go to the fcetal membranes to the yolk-sac the vitelline arteries (arterise omphalornesentericse), to the allantois and placenta the umbilical arteries.
 
17. The vitelline arteries subserve the vitelline circulation, and afterwards, with the reduction of the umbilical vesicle, degenerate.
 
18. The umbilical arteries, which continually become larger with the increasing development of the placenta, arise from the lumbar portion of the aorta, pass forward [ventral] in the lateral wall of the pelvis, then at the side of the bladder and along the inner surface of the abdominal wall to the umbilicus and umbilical cord.
 
 
 
THE ORGANS OF THE INTERMEDIATE LAYER OR MESENCHYME. 591
19. The umbilical arteries give off the iliaca interna to the cavity of the pelvis, the iliaca externa to the lower limbs.
 
20. After birth the umbilical artery degenerates into the ligamentuni vesico-unibilicale laterale, with the exception of its proximal part, which persists as the iliaca comniunis.
 
Development of the Chief Venous Trunks.
 
21. With the exception of the inferior vena cava, all venous trunks are established in pairs.
 
22. The two jugulars collect the blood from the head, the two cardinals from the trunk, but especially from the primitive kidneys.
 
23. The jugular and cardinal veins of either side unite to form the Cuvierian ducts, which pass transversely from, the lateral wall of the trunk to the posterior end of the heart, imbedded in a transverse fold of the front wall of the trunk, the septum transversum.
 
24. The two vitelline veins collect the blood from the yolk-sac ; from the navel onward they run in the ventral mesentery to the septum transversum.
 
25. The two umbilical veins collect the blood from the placenta ; from the attachment of the umbilical cord they run at first in the abdominal wall to the transverse septum.
 
26. In the septum transversum the Cuvierian ducts and the vitelline and umbilical veins unite to form the sinus reunions, which subsequently disappears as an independent structure and is incorporated in the atrium.
 
27. The cardinal veins diminish in importance (1) in consequence of the degeneration of the primitive kidneys, and (2) from the fact that the blood from the lower half of the body is conveyed back to the heart by the inferior vena cava.
 
28. The upper part of the inferior vena cava arises as an unpaired, independent vessel between the two cardinal veins, and then, at the place where the renal veins empty in, unites with the right cardinal vein. The latter is in this way converted into the lower portion of the inferior cava.
 
29. The Cuvierian ducts with the beginning of the jugular veins are designated as the venae cavse superiores.
 
30. An asymmetry in the embryonic venous trunks, which are established in pairs, is brought about by the fact that the two superior vena3 cavse, and also at their middle the remnants of the two cardinal veins, are joined together by transverse trunks:
 
 
592 EMBRYOLOGY.
 
31. Since through these cross anastomoses more and more of the blood, and finally the whole of it, is conveyed from the trunks of the left half of the body into those of the right half, the proximal part of the left superior vena cava, except a small portion, v/hich lies in the coronary groove of the heart, degenerates, receives the cardiac veins, and becomes the sinus.coronarius cordis. Likewise the cardiac end of the left cardinal vein disappears.
 
32. From the paired fundaments of the venous trunks are formed the single superior vena cava, the sinus coronarius cordis, and the vena azygos and hemiazygos.
 
33. The vitelline veins, which afterwards become unpaired, give rise, when the liver is developed, to the portal circulation (the venae hepaticee advehentes and revehentes).
 
34. The umbilical veins, of which the right early degenerates, originally run in the abdominal wall above the liver to the sinus reunions ; then the left forms an anastomosis with the vitelline vein under the liver, whereby its current shares in the portal circulation.
 
35. There arises out of an anastomosis between the umbilical vein and the cardiac end of the inferior vena cava on the under surface of the liver the ductus venosus Arantii, which results in the division of the blood of the umbilical vein into two currents.
 
36. After birth the umbilical vein degenerates into the ligamentum teres hepatis, and the ductus venosus Arantii is obliterated ; the veme hepaticse advehentes now receive their blood from the terminal part of the original vitelline vein or the portal vein only, which collects the blood from the intestinal canal.
 
37. The septum transversum, in which run the venous trunks on their way to the heart, is the starting-point for the development of the diaphragm and the pericardial sac, and forms at first an incomplete partition between the abdominal cavity and pleuro-pericardial cavity, which still communicate with each other on either side of the vertebral column.
 
38. The pericardial sac is separated off from the thoracic cavity as follows : (1) the Cuvierian ducts or future superior vense cavse, instead of running transversely, run more and more obliquely from above downward, detach themselves from the septum transversum, and elevate the pleura into pericardial folds, which run from above downward and project inward ; (2) the margin of the pericardial fold fuses with the mediastinum posterius, in which are enclosed ossophagus and aorta, whereby the superior venaB cavee are transferred to the mediastinum.
 
 
 
THE ORGANS OF THE INTERMEDIATE LAYER OR MESENCHYME. 593
39. The thoracic cavities have for a time the form of tubular spaces lying on the dorsal side of the heart and on either side of the spinal column ; they receive the developing lungs, and still communicate caudad with the abdominal cavity.
 
40. The two thoracic cavities are separated from the abdominal cavity by the fusion of the dorsal rim of the septum transversum with peritoneal folds of the dorsal wall of the trunk (the pillars of
USKOW).
 
41. The diaphragm is composed of two parts, the ventral septum transversum, and a dorsal part, the pillars.
 
42. Upon its first establishment the liver grows into the septum transversum, but subsequently detaches itself from the latter and remains united to the diaphragm by means of its peritoneal covering only, the coronal ligament.
 
II. The Development of the Skeleton.
 
With the exception of the chorda dorsalis, which takes its origin from the inner germ-layer, the skeleton of Vertebrates is a product of the intermediate layer, resulting from a series of histological differentiations, a general survey of which has already (p. 540) been given. There have appeared many articles treating on this very complicated apparatus in the higher Vertebrates from a developmental and also especially from a comparative-anatomical standpoint. By an exhaustive treatment of this subject this part of the work would attain to greater proportions than the plan of the present textbook permits. I shall therefore limit myself to the more important conditions of organisation and for what remains refer to the textbooks of comparative anatomy.
 
Two chief parts are distinguishable in the skeleton of Vertebrates : (1) the axial skeleton, which is in turn divisible into that of the trunk and that of the head, and (2) the skeleton of the limbs. The former is the older and more primitive, being possessed by all Vertebrates ; the latter has been developed later, and is entirely wanting in the lower groups (Amphioxus, Cyclostomes).
 
 
 
A. The Development of the Axial /Skeleton.
 
The original foundation of the axial skeleton of all Vertebrates is the notochord or chorda dorsalis. By this is understood a flexible, rod-like structure, which is situated in the axis of the body
38
 
 
594
 
 
EMBRYOLOGY.
 
 
 
K
 
 
below the neural tube and above the intestine and aorta. It reaches from the front end of the base of the mid-brain to the end of the tail.
 
For a time after its establishment the front end of the chorda remains in union jit a small pla.ee with the epithelium of the fore-gut. This place is immediately behind the upper attachment of the primitive pharyngeal membrane (Kachenhaut). There is here found, a little behind the hypophysial pocket, a slight depression in the epithelial lining of the fore-gut SEESSEL'S pocket or the palatal pocket of SELENKA. It is only some time after the rupture of the pharyngeal membrane that the chorda becomes
detached from the intestinal epithelium and terminates free in the mesenchyma, often with a hook-like end (KEIBEL, KANN, CARIUS).
 
In the case of Arnphioxus the chorda is the only skeletal structure present in the whole of the soft body; in the lower Vertebrates (Cyclostomes, Fishes, Amphibia) it exists even in the adult animals as a more or less important organ ; but in the Amniota it is reduced almost to obliteration, and only in the earliest stages of development plays a role as the forerunner, as it were, of the higher form of axial skeleton which finally Tig 324 Cross section takes its place. While reference is made through the vertebral to previous portions of the text-book for inSaimon, after GEGEN- formation about the first development of the BAUR - chorda, its further metamorphosis may be
o*. Sheath of the chorda;
k, neural arch; ', treated or here more at length. 1 his varies
according as the chorda becomes a really functional organ or soon begins to degenerate.
 
In the first instance, when the band of chordal cells has been constricted off from the inner germ-layer, it becomes more sharply limited at its periphery by the secretion of a firm, homogeneous envelope, the sheath of the chorda (fig. 324 cs). Then the cells increase in size by the accumulation of fluid within their protoplasm, which finally exists in the form of a thin superficial layer only ; the cells become enveloped in firm membranes, thus acquiring exactly the appearance of plant cells. But directly beneath the sheath of the chorda (fig. 324) the cells remain small and protoplasmic and constitute a special layer, the chordal epithelium, which by proliferation and metamorphosis of its elements causes an increase of the substance of the chorda.
 
 
 
 
haemal arch ; m, spinal cord ; a, dorsal aorta ; r, cardinal veius.
 
 
 
THE ORGANS OF THE INTERMEDIATE LAYER OR MESENCHYME. 595
Immediately after its formation the chorda is in contact above with the neural tube, below with the entoderm. and laterally with the primitive segments. This relation is altered as soon as the intermediate layer makes its appearance between the first embryonic fundaments. Then a layer of cells grows around the chorda (fig. 262), spreads itself out from here around the neural tube above, and furnishes the foundation from which are developed the segmented vertebral column and in front, in the region of the five brain-vesicles, the cranial capsule ; it has therefore received the name of membranous vertebral column and of membranous cranial capsule (membranous primordial cranium) ; it is also appropriately designated as skeletogenous layer, the envelope which invests the chorda being called the skeletogenous sheath of the chorda. (Compare p. 172 for an account of the first formation of it.)
The mesenchyme also spreads out laterally in the embryo, penetrates into the spaces between primitive segments, and is. converted into thin plates of connective tissue (ligamenta interinuscularia), by means of which the musculature of the trunk is parted into separate muscle segments (myomeres). The muscle-fibres find attachment and support upon both the anterior and posterior faces of these plates.
 
Such a condition is permanently preserved in Amphioxus lanceolatus. The chorda, with its sheath, is the only firm skeletal structure. Fibrous connective tissue (membranous vertebral column) envelops it and the neural tube, and sends out into the musculature of the trunk the intermuscular ligaments.
 
When the originally membranous tissue surrounding the chorda and neural tube is followed in its further development in the embryos of the higher Vertebrates, it is to be seen that it successively undergoes two metamorphoses : that at first it is partially chondrified, and that subsequently the cartilaginous pieces are converted into osseous tissue ; or, in other words, the first-established membranous vertebral column is soon converted into a cartilaginous, and this in turn is replaced by a bony one, and in the same manner the membranous primordial cranium is transformed into a cartilaginous, and this in turn into a bony cranial capsule.
 
The three stages which succeed one another in the development of the higher Vertebrates are also encountered in a comparativeanatomical investigation of the axial skeleton in the series of Vertebrates, and in such a manner that the condition, which in many classes appears only as a transitory embryonic one, is i-etained
 
 
596
 
 
EMBRYOLOGY.
 
 
 
permanently in the lower classes. As Amphioxus possesses a membranous axial skeleton, so the Selachians and certain of the Ganoids are representatives of the stage with cartilaginous vertebral column. The third stage in the evolution of the axial skeleton is more or less completely attained by all the higher Vertebrates.
 
Tli is, again, is a very instructive example of which the embryology of the skeleton presents many others of the parallelism which exists between the development of the individual and that of the race ; it
teaches how embryological and comparative-anatomical investigations are mutually complemental. In the detailed description of the conditions which are observed in the development of the cartilaginous and bony axial skeleton, I shall limit myself to Man and Mammals, and since great differences exist between the posterior region, which encloses the spinal cord, and the anterior, which envelops the vesicles of the brain, I shall treat of them separately.
 
 
 
 
Fig. 325. Longitudinal [frontal] section through the thoracic region of the vertebral column of a human embryo 8 weeks old, after KOLLIKEB.
 
v, C a r t i 1 a g i n o u s body of vertebra,; U, intervertebral 1 i g a m e n t ; cJt, chorda.
 
 
 
() Development of the Vertebral Column.
 
The process of chondrification commences in Man at the beginning of the second month. At certain places in the tissue enveloping the chorda the cells secrete between themselves a cartilaginous matrix, and move farther apart, whereas at other intervening and narrower tracts the character of the tissue is not altered (fig. 325). In this manner the skeletogenous layer is differentiated into numerous vertebral bodies (v), which in longitudinal sections are the more translucent, and into the intervertebral discs (ligamenta intervertebralia) which separate them (li).
 
The process of chondrification, as FEOEIEP has followed it in the case of the embryo calf, proceeds as follows : there arise on both sides of the chorda masses of cartilage which are united on the ventral side of it by a thinner layer. Somewhat later the cartilaginous half-cylinder is closed on the dorsal side also.
 
Upon the appearance of a segmented vertebral column the chorda loses its function of a supporting skeletal rod. From this time forward it therefore suffers a gradual obliteration. The parts enclosed in the bodies of the vertebrae are restricted in their growth,
 
 
THE ORGANS OF THE INTERMEDIATE LAYER OR MESENCHYME. 597
whereas the shorter portions lying in. the soft intervertebral discs continue to enlarge (fig. 325 ch). Thus the chorda now acquires the appearance of a string of beads, since thickened spheroidal portions are joined to one another by small connecting thread-like portions. Subsequently it entirely disappears in the bodies of the vertebrae, especially when the latter begin to ossify (fig. 326) ; the intervertebral portion (li) alone persists, although indistinctly limited from the
 
 
 
li
 
 
Pig. 326. Longitudinal [sagittal] section through the intervertebral ligament and the adjacent parts of two vertebrae from the thoracic region of an advanced embryo Sheep, after KOLLIKEB.
 
la, Ligament longitudinale anterius ; ^>, lig. long, posterius ; li, lig. inter vertebrale ; k, k', cartilaginous caps (epiphyses) of the vertebrae ; w and w', anterior and posterior vertebrae ; c, inter vertebral, c' and c", vertebral enlargements of the chorda.
 
surrounding tissue, and produces by the proliferation of its cells the gelatinous core of the intervertebral disc.
 
Soon after the appearance of the bodies of the vertebrae the fundaments of the corresponding arches are observable. According to FRORIEP'S account, there arise small, independent pieces of cartilage in the membrane enveloping the spinal cord, in the immediate vicinity of the bodies of the vertebrae, with which they soon fuse. Their growth is rather slow. During the eighth week they still appear in Man as short processes from the bodies of the vertebrae, so that the spinal cord is still covered dorsal ly by the membranous skeleton. In the third month they grow into contact with each other at the dorsuni ; however, it is only in the following month
 
 
598 EMBRYOLOGY.
 
that a complete fusion takes place, and that cartilaginous neural spines are formed. The part of the membrane which lies between the cartilaginous arches furnishes the ligamentous apparatus.
 
In the process of chondrification the nascent bodies of the vertebrae have a fixed position relative to the primitive or muscle-segments ; it is such that on either side of the body they are adjacent to two of the latter, one half to a preceding segment, the other half to a following one ; or, in other words, the ladies of the vertebras and the muscle-segments do not coincide, but in their 'positions alternate with each other.
 
The necessity of such an arrangement follows from the very function which vertebral column and musculature together have to fulfil. The axial skeleton must possess two opposite properties united : it must be firm, but also flexible, firm, in order to serve as a support for the trunk ; flexible, so as not to impede the motions of the latter. Since a continuous cartilaginous rod would not have possessed sufficient flexibility, the process of chondrification could not take place throughout the whole extent of the skeletogenous layer, but there must be left more elastic tracts, which allow a movement of the cartilaginous pieces on one another. But a movement of the cartilaginous pieces would obviously be impossible if they should lie so that the muscle fibres had their origin and insertion on one and the same vertebral element. In order that the fibres of a musclesegment may operate upon two vertebra?, the muscular and vertebral segments must alternate in position.
 
This process, which is easily intelligible in the way in which it has been outlined, has given occasion for the assumption of a " resegmentation of the vertebral column." This conception originated with EEMAK, and since then has been for a long time tenaciously held to in the literature.
 
REMAK, like other einbryologists before him (BAER), perceived in the primitive segments of the Chick the material for the establishment of the vertebral column, and therefore gave them the name " protovertebrre." But inasmuch as he found that the cartilaginous vertebrse did not afterwards correspond in position with the protovertebrse, he announced the proposition that a new " segmentation of the vertebral column takes place, from which arise the secondary, permanent bodies of the vertebra 5 ."
Both the name " protovertebra " and the assumption of a resegmentation of the vertebral column should be dropped, and for the following reasons :
 
THE ORGANS OF THE INTERMEDIATE LAYER OR MESENCHYME. 599
The signification of the primitive segments consists, if not exclusively, at least principally, in this, that they are the fundaments of the musculature of the body. But in the arrangement of the musculature is expressed the original and oldest segmentation of the vertebrate body. It is present even in Amphioxus and the Cyclostomes. The segmentation of the vertebral column, on the contrary, ivas acquired much later, and has resulted, as was explained above, from a necessary dependence on the segmentation of the musculature. A primary segmentation of the vertebral column as understood by REMAK and his followers has never existed, for the cartilaginous vertebrie are formed from an unsegmented mass of tissue enveloping the chorda from the skeletogenous layer. One cannot speak of a segmentation of the vertebral column until the beginning of the process of chondrification, by reason of which alone it became necessary.
 
Even before the cartilaginous vertebral column has been completely established, it enters in Mammals upon the third stage, which begins in Man at the end of the second month.
 
The ossification of every cartilage takes place in the main in a corresponding, typical manner. Blood-vessels at one or several places grow from the surface into its interior, dissolve the matrix of the cartilage of a limited region, so that there arises a small cavity filled with vascular capillaries and marrow-cells. In the vicinity of this salts of lime are deposited in the cartilage. By a portion of the proliferated medullary cells, which become osteoblasts, bone substance is then secreted (fig. 326 w). In this manner there arises in the midst of the cartilaginous tissue a so-called bone nucleus or centre of ossification, around which the destruction of the cartilage and its replacement by osseous tissue advance further and further.
 
The places where the separate bone nuclei are formed, as well as their number, are tolerably uniform for the different cartilages.
 
In general the ossification of each vertebra proceeds from three points. At first a centre of ossification is established in the base of each half of the vertebral arch, to which there is added somewhat later a third centre in the middle of the body of the vertebra. In the fifth month the ossification has advanced up to the surface of the cartilage. Each vertebra is now distinctly composed of three pieces of bone, which for a, long time continue to be joined to one another by bridges of cartilage at the base of each half of the arch and at the union of the latter with the vertebral spines. The last remnants of cartilage do not ossify until after birth. During the first year with the development of a bony spinous process the halves
 
 
600 EMBRYOLOGY.
 
of the arch are fused. Each vertebra is then separable after destruction of the soft parts into two pieces, into the body and the arch. These are united between the third and eighth years.
 
In addition to the pieces of bone just described, accessory centres of ossification appear on the vertebras in subsequent years ; it is in this way that there arise the epiphysial plates at the end-surfaces of the body and the small bony pieces at the ends of the vertebral processes (the spinous processes and the transverse processes). SCHWEGEL gives detailed information concerning the time of their appearance and their fusion.
 
Cartilaginous skeletal parts, which serve for the support of the lateral and ventral walls of the body, the ribs and the breast bone, contribute to the completion of the axial skeleton.
 
The ribs are developed independently of the vertebral column, in Man during the second month, by the chondrification of strips of tissue in the mterrnuscular ligaments between the successive musclesegments. They are at first visible as small bent rods in the immediate vicinity of the body of the vertebra, and from here they rapidly extend vent rally.
 
In early stages of development ribs are established from the first to the last segment of the vertebral column (the coccyx in Man excepted), but only in the case of the lower Vertebrates (Fishes, many Amphibia, and Reptiles) are they developed into large bows supporting the wall of the trunk in a uniform manner in all regions, whereas in Mammals and in Man they exhibit in the separate regions of the vertebral column different conditions. In the neck, lumbar and sacral regions, they appear from the beginning in a rudimentary condition only, and undergo metamorphoses to be described later. It is exclusively in the thoracic region that they attain important dimensions, and here at the same time they give rise to a new skeletal part the breast bone, or sternum.
 
The sternum, which is wanting in Fishes and Dipnoi, but is present
in Amphibia, Reptiles, Birds, and Mammals, is a formation derived
from the thoracic ribs, and is originally established, as RATHKE was the
first to discover, as a paired structure, 'which early fuses into an
unpaired skeletal piece.
 
HUGE has followed the development of the sternum in Man in a very thorough manner, and has found that in embryos 3 cm. long the first five to seven thoracic ribs have become prolonged into the ventral surface of the breast and by a broadening of their ends have united at some distance from the median plane to form a cartilaginous band, whereas the following ribs end free and at a greater distance from
 
 
THE OEGANS OF THE INTERMEDIATE LAYER OR MESENCHYME. 601
 
 
the median plane. The two sternal bars are separated from each other by membranous tissue ; later they approach each other in the median plane, and commencing in front, begin to fuse together into an unpaired piece, from which the individual ribs which gave rise to them are afterwards separated by the formation of joints.
 
The paired origin of the sternum serves to explain some of its abnormalities. For example, in the adult there is sometimes seen a fissure, which, although closed by connective tissue, passes quite through the sternum (fissura sterni), or a few larger or smaller gaps are found in the body and xyphoid process of the sternum. All these abnormal cases are explained by the complete or partial failure of the two sternal bars to fuse in the usual way during embryonic life.
 
The ossification of ribs and sternum is in part accomplished by the development of special centres of ossification, that of the ribs beginning as early as the second month, the sternum somewhat late, in the sixth foetal month.
 
Each rib contains at lirst one centre of ossification, through the enlargement of which the bony part is formed, while next to the sternum a portion remains cartilaginous throughout life. In the eighth to the fourteenth year there appear in the capitulum and tuberculum of the rib, according to SCHWEGEL and KOLLIKER, accessory centres, which fuse with the main piece between the fourteenth and the twentyfifth year.
 
The sternum (fig. 327) ossifies from numerous centres, of which one arises in the manubrium, and from six to twelve in its body. Between the sixth and twelfth years the latter begin to fuse together into the three or four large pieces of which the body of the sternum is composed. The xyphoid process remains partly cartilaginous, but acquires a centre of ossification during childhood.
 
Regarding the episternal pieces which appear on the manubrium, the textbooks of comparative anatomy and the article by RuG-E should be consulted.
 
Through inequalities in the development of the separate vertebral and costal fundaments and through the fusions which take place here and there are produced the different regions of the skeleton of the trunk : the cervical, dorsal, and lumbar regions of the vertebral column, the sacrum and coccyx. A correct understanding of these skeletal parts is to be acquired only through embryology.
 
 
 
 
Fig. 327. Cartilaginous sternum, with portions of the ribs attached and with several centres of ossification (kk\ from a child two years old.
 
k, Cartilage ; kk, centres of ossification ; sch, xyphoid process.
 
 
 
602 EMBRYOLOGY.
 
The rudimentary fundaments of the cervical ribs at their first appearance fuse with the cervical vertebra, at one end with the body of the vertebra, at the other with an outgrowth of the neural arch, and with the latter enclose an opening through which the vertebral artery runs the foramen transversarium. The so-called transverse process of the cervical vertebra is therefore a compound structure, and were better designated lateral fwocess, for the bony rod that lies dorsad of the foramen transversum is formed by an. outgrowth from the vertebra and alone corresponds to the transverse process of a dorsal vertebra ; the ventral rod, on the contrary, is a rudimentary rib, which possesses in fact a separate centre of ossification.
 
The fundament of the rib of the seventh cervical vertebra occasionally attains greater size, does not fuse with the vertebra which consequently does not possess any foramen transversarium and is described under the abnormalities of the skeleton as free cervical rib. Its presence is explained therefore as being the result of a more voluminous development of a part which in all cases exists as a fundament.
 
The transverse fwocess of the himbar vertebrce is also better designated as lateral process, because it encloses the rudiment of a rib. This explains the phenomenon of a thirteenth or small lumbar rib occasionally observed in Man.
 
The sacral region is the one that is most modified. A large number of vertebrae in this region by becoming firmly united with the pelvic girdle have lost the power of moving on one another, and are fused together into a large bone : the sacrum. This consists in human embryos of five separate cartilaginous vertebras, the first three of which especially are characterised by very broad, well-developed lateral processes.
 
I say lateral processes because comparative-anatomical grounds and embryological evidence both indicate that there are included in them rudimentary sacral ribs, such as in lower Vertebrates make their appearance as independent structures. On the embryological side, the method of their ossification favors this view, for each sacral vertebra undergoes ossification from five centres. To the three typical centres, those of the body and the neural arches, are added in the lateral processes large bone-nuclei (centres), which are comparable with the centres of ossification of a rib. They produce the well-known lateral masses of the sacrum (massse late rales), which bear the articular surfaces for union with the ilium.
 
The fusion of the five bony pieces of a sacral vertebra, at first separated by strips of cartilage, takes place later than in other parts
 
 
 
THE ORGANS OF THE INTERMEDIATE LAYER OR MESEXCHYME. 603
of the vertebral column, namely, between the second and the sixth year after birth. For a long time the five sacral vertebrae remain separated from one another by their intervertebral discs, which begin to ossify in the eighteenth year ; the process has usually come to an end by the twenty -fifth year.
 
Behind the sacrum there follow four or five rudimentary coccygeal vertebra3, which represent the caudal skeleton of Mammals and do not acquire centres of ossification until very late. In the thirtieth year or later they may fuse with one another, and sometimes with the sacrum.
 
Atlas and episiropheus (axis) now demand special mention. These vertebra acquire their peculiarities of form by an early fusion of the cartilaginous body of the atlas (fig. 3'2Sa) with the epistropheus (e) to form the odontoid process of the latter. The one therefore contains less, the other more than a normally developed vertebra.
 
That the odontoid process is the real body of the atlas is recognisable even later by means of two facts. First, like every other vertebral ,
body, it is traversed, as long as it remains cartilaginous, by the chorda, which at the tip
Fig. 328. Median section
of the process is continued into the ligamentuni through the body and
suspensoriuni and from this into the base of the odontoid pr cess of
the epistropheus.
 
cranium. Secondly, it acquires in the fifth iu the cartilage two ceamonth of development a separate centre of tra of ossification (e
and a) are to be seen.
 
ossification (fig. 328 a), which is not completely fused with the body of the epistropheus until the seventh year.
 
The neural arches of the atlas, which have remained independent, are joined together on the ventral side of the odontoid process by a tract of tissue in which an independent piece of cartilage is formed (hypochordal cartilage-rod of FRORIEP) a structure which, according to FRORIEP, is present in every vertebra in the case of Birds. This piece of cartilage develops in the first year after birth a special centre of ossification, fuses between the fifth and the sixth year with the lateral halves, and constitutes the. anterior [ventral] arch (KOLLIKEK).
 
(b) Development of the Head-8kelcton.
 
From its position the skeleton of the head appears as the most anterior part of the axial skeleton, but it is on the whole very unlike the posterior part, the vertebral column, because it is adapted to
 
 
604 EMBRYOLOGY.
 
peculiar purposes. For in the morphological plan of Vertebrates the head takes, in comparison with the trunk, a preeminent position ; it is furnished with especially numerous and highly developed organs concentrated into a short space.
 
The neural tube has here become differentiated into the voluminous brain, with its dissimilar regions. In its immediate vicinity have arisen complicated sensory organs such as nose, eye, and ear. Likewise the part of the digestive tube enclosed within the head bears in many ways its peculiar stamp, since it contains the mouth op ening and is provided with organs for the reception and trituration of the food, and is pierced by visceral clefts. All of these parts exercise a determining influence on the form of the skeleton, which adapts itself most accurately to the brain, to the sensory organs, and to the functions of the head-gut, and thereby becomes a very complicated apparatus, especially in the higher Vertebrates.
 
Embryology sheds a flood of light on the method of the origin of the cephalic skeleton of Vertebrates ; it shows the relations to one another of widely different lower and higher forms, and also answers the question, What relation do the vertebral column and head -skeleton sustain to each other in the plan of organisation of Vertebrates ? Consequently the development of the cephalic skeleton proves to be an especially interesting subject, which has always attracted rnorphologists, and which has incited to careful investigation.
 
During the account some comparative-anatomical digressions will be made, which will contribute to the better comprehension of certain facts, especially those treated of in the final section, in which the vertebral theory of the skull will be briefly discussed.
 
As in the case of the vertebral column, there are to be distinguished three stages of development according to the histological character of the sustentative substance : a membranous, a cartilaginous, and a bony.
 
The chorda serves as the foundation for the membranous skeleton of the head, and extends forward to the between-brain. At its anterior end there is formed in Amniota the cephalic flexure, by which the axis of the first two brain-vesicles makes an acute angle with the three following ones (fig. 153). Here also the mesenchyme early grows around the chorda and envelops it in a skeletogenous layer, which spreads out from this region laterad and dorsad, enveloping the five brain-vesicles, and is subsequently differentiated into the membranes of the brain and a layer of tissue, which
 
 
THE ORGANS OF THE INTERMEDIATE LAYER OR MESENCHYME. 605
becomes the foundation of the cranial capsule, and has received the name of membranous primordial cranium.
 
Thus far there is an agreement in the development of the vertebral column and of the cranium. With the beginning of the process of chondrification the conditions become more peculiar. Whereas in the region of the spinal cord the skeletogenous layer undergoes a regular differentiation into cartilaginous and connectivetissue parts into vertebrae and vertebral ligaments and is thereby divided into successive movable segments, such a segmentation does not take place in the head.
 
The layer of tissue called membranous primordial cranium undergoes continuous chondrification into a non-articulate capsule enveloping the brain-vesicles. If we go through the whole series of Vertebrates down to the lowest, in no one of them is there exhibited a separation into movable segments corresponding to vertebrae. Therefore the anterior part and the remaining part of the axial skeleton pursue from an early period different directions in their development.
 
The contrast is intelligible in view of the different duties to be fulfilled in the two regions, and especially in consideration of the different influences which the action of the muscles exercises upon the form of the skeleton.
 
In water-inhabiting animals the trunk-musculature is the most important organ of locomotion, for it bends the trunk now in this direction, now in that, and thereby propels it forwards through the water. If, however, the head region were likewise flexible and movable, it would be disadvantageous for forward motion, inasmuch as a rigid part operates as a cut-water. Moreover, the musculature developed on the head assumes a different function, inasmuch as in the grasping of food and in the process of respiration which is accompanied by an enlargement and reduction of the respiratory tract of the alimentary tube it now adducts and then abducts the ventrally situated parts of the axial skeleton. Besides, it is advantageous here to have the skeletal axis present firm points of attachment for the muscles. Finally, the voluminous development of the brain and the higher sensory organs is likewise a participating influence tending to make the part of the head that serves for their reception an inflexible region.
 
In view of these various factors working in the same direction, it becomes intelligible that in the head a segmentation of the axial skeleton is wanting from the beginning.
 
In other respects there prevails a great agreement with the
 
 
GOG
 
 
EMBRYOLOGY.
 
 
 
vertebral column, especially in the manner in which the metamorphosis into cartilaginous tissue takes place in the membranous primordial cranium. In both the chondrifi cation first begins at the surface of the chorda dorsalis (fig. 329 A).
 
As a foundation for the base of the skull there arise two pairs of elongated cartilages : behind, on either side of the chorda, the two parachordal cartilages (PS) ; in front, the two trabeculce cranii (Tr) of RATHKE, which begin at the tip of the chorda and from there run forward beneath the between- and the fore-brain.
 
 
 
 
B
 
 
 
Fig. 329 A and B. First fundament of the cartilaginous primordial cranium, from WIEDERS
TIKIM.
 
A, First stage. C, Chorda ; PE, parachordal cartilage ; Tr, RATHKE'S trabeculse cranii ; PR,
passage for the hypophysis ; N, A, 0, nasal pit, optic vesicle, otocyst.
 
B, Second xtaye. C, Chorda ; B, basilar plate ; T, trabeculse cranii, which have become united
in front to constitute the nasal septum (S) and the ethmoid plate ; Ct, AF, processes of the ethmoid plate enclosing the nasal organ ; 01, foramina olfactoria for the passage of the olfactory nerves; PF, post-orbital process; NK, nasal pit; A, 0, optic and labyrinthine vesicles.
 
The four pieces soon fuse with one another (fig. 329 B}. The two parachordal elements grow around the chorda, first below, then above, thus enveloping it and producing the basilar plate (B). Its anterior margin rises far up into the angle of the flexure between mid -brain and between-brain and corresponds to the future clorsum sellre. The trabeculce cranii (T] spread out at their anterior ends, which become fused to constitute the ethmoid plate (>S'), the foundation of the anterior portion of the cranium, which acquires its particular stamp through its reception of the organ of smell. In the middle of their length they remain separate a long time, and enclose an opening,
 
 
THE ORGANS OF THE INTERMEDIATE LAYER OR MESENCHYME. 607
which corresponds to the sella tnrcica, and has been caused by the formation of the hypophysial pocket from the oral sinus and by its growing through the membranous basis of the cranium toward the infundibulum of the brain. Rather late there is also formed, as the floor of the sella turcica, beneath the hypophysis, a thin cartilaginous plate, which is pierced only by the holes for the internal carotids.
 
After the base of the cranium has been developed, the process of chondrification involves the side walls and at last the roof of the membranous primordial cranium, precisely as the halves of the neural arch grow out from the body of the vertebra and finally terminate in the dorsal spine.
 
In this manner there is developed around the brain in the case of the lower Vertebrates, in which the axial skeleton remains in the cartilaginous condition throughout life (fig. 330), a closed, tolerably thick-walled capsule, the cartilaginous primordial cranium,.
 
In the higher Vertebrates, in which to a greater or less degree processes of ossification occur later, the primordial cranium attains a less complete development, as is shown by the fact that its walls remain thinner, and indeed acquire at some places openings, which are closed by connective -tissue membranes. In Mammals the latter condition occurs very extensively in the roof of the skull, which becomes cartilaginous only around the foramen magnum, whereas in the region in which afterwards the frontal and parietal bones are located the cranium remains membranous. The cartilage attains a greater thickness only at the base of the cranium and in the regions of the olfactory organ and the membranous labyrinth, where it gives rise to the nasal and ear capsules.
 
For the sake of better orientation, it is useful to distinguish in the primordial cranium different regions. There are two different principles of division that may be employed in this connection.
 
Following GEGENBAUR, one can divide the primordial cranium, in accordance with its relation to the chorda dorsalis, into a posterior and an anterior portion.
 
The posterior region reaches up to the dorsum sillse and encloses in its basal portion the chorda, which in Man enters into it from the odontoid process through the ligamentum suspensorium dentis. The anterior portion is developed in front of the pointed end of the chorda out of RATHKE'S cranial trabeculae. GEGENBAUR designates the two as vertebral and evertebral regions (for which KOLLIKER employs the names chordal and prechordaT) ; he shows that the vertebral region must be, on account of its relation to the chorda, the
 
 
608
 
 
EMBRYOLOGY.
 
 
 
older part and alone comparable with the remainder of the axial skeleton, that the non- vertebral part, on the contrary, is a later acquisition and constitutes a new structure, which has boen caused by the forward extension of the fore-brain vesicle and by the development of the ovgjin of smell, to the enclosing of which (nasal capsule) it contributes.
 
The second method of division is based upon the different appearance which the individual regions of the primordial cranium acquire through their relations to the sense orc/ans. The anterior end of
 
 
N
 
 
Au
 
 
2V
 
 
OcGI. V
 
 
rl
 
 
 
o v
 
 
zb
 
 
zb
 
 
Fig. 330. Diagrammatic representation of the cartilaginous cranial capsule and the cartilaginous visceral skeleton of a Selachian and of the larger nerve trunks of the head.
 
N, Nasal capsule (ethmoid region of the prin.ordial cranium) ; Au, cavity for the eye (orbital region) ; la, region of the labyrinth ; Oc, occipital region of the cranium ; O, palato-quadratum ; U, lower jaw (mandibulare) ; Ik, labial cartilage ; zb, hyoid arch ; kb, first to fifth branchial arches ; Tr, nervus trigeminus ; Fa, facialis ; Gl, glosso-pharyngeus ; Fa, vagus ; rl, ramus lateralis of the vagus ; rb, rami branchiales of the vagus.
 
the cartilaginous capsule (fig. 330) receives the organ of smell ; a following portion contains depressions for the eyeballs ; in a third are imbedded the membranous auditory labyrinths ; finally, a fourth effects a union with the vertebral column. Consequently one may distinguish an ethmoidal, an orbital, a labyrinthine, and an occipital region.
 
In addition to the cartilaginous primordial cranium, there are developed in the head numerous cartilaginous pieces (which serve as supports to the walls of the head-gut) in a manner similar, although not directly comparable, to that in which the ribs (fig. 330) have
 
 
THE ORGANS OF THE INTERMEDIATE LAYER OR MESENCHYME. 609
 
 
Cl '
 
 
 
Br.t
 
 
Lch
 
 
S-n.jp
 
 
arisen in the walls of the trunk in the region of the vertebral column. Together they constitute a skeletal apparatus which undergoes in the series of Vertebrates very profound and interesting metamorphoses. Whereas it attains in the lower Vertebrates a great development, it becomes in part rudimentary in Reptiles, Birds, and Mammals. The part, however, which remains furnishes the foundation for the facial skeleton. I begin with a short sketch of the original conditions in the lower Vertebrates, especially in the Selachians.
 
As has been described in a previous chapter, the lateral walls of the head-gut are traversed by the visceral clefts, of w r hich there are ordinarily as many as six in Sharks (fig. 331). The bands of substance intervening between the clefts are called the membranous throat- or visceral arches. They consist of a connective-tissue foundation invested with epithelium, of transversely striped muscle -fibres, and of the visceral-arch bloodvessels (see p. 571). Inasmuch as they have different functions to fulfil, and consequently acquire different forms, they are distinguished as jaw-, hyoid, and branchial arches. The most anterior of them is the jaw-arch, which serves to bound the oral opening. Following this, and separated from it by only a rudimentary visceral cleft, the spiracle, is the hyoid arch, which is connected with the origin of the tongue. Ordinarily this is followed by five branchial arches.
 
At the time when the membranous primordial cranium is converted into cartilage, chondrification also takes place in the connective tissue of the membranous visceral arches, thus producing the cartilaginous visceral arches (fig. 331). These exhibit a regular segmentation into several pieces, placed end to end and articulated with one another by connective tissue.
 
The jaw-arch is divided on either side into a cartilaginous palatoquadratuin (fig. 330 0) and a lower jaw (mandibulare). These
39
 
 
Fig. 331. Head of a Shark embryo 11 lines long.
 
From PARKER AND BI;TTANV. Tr, RATHKK'S trabecuhe cnmii ; PI. PI, ptcrygo-quad
rntum ; jl//', mandibular cartilage; Hy, hyoiil
arch; Er.l, first branchial arch; Sj>, spiracle;
C/', first bran cliia I cleft; Lch, groove under the
eye; JK'a, fundament of the nose; E, eyeball;
An, auditory vesicle; C.I, C.2, C.3, brain-vesicles;
Hut, cerebral hemispheres; /.>'./, fronto-nasal
process.
 
 
 
610 EMBRYOLOGY.
 
carry, in the mucous membrane investing them, the teeth of the jaws. The two mandibular elements are united to each other in the median plane by means of a mass of tense connective tissue. The following visceral arches, on the contrary, are alike in having their lateral halves, which are divided into several pieces, joined ventrally by means of an unpaired connecting piece, the copula, in a manner similar to that in which the ribs are united by the sternum. The pieces of the hyoid arch are designated, in sequence from the dorsal to the ventral side, hyomandibular, hyoid, and (the copula) os entoglossum.
 
In Mammals and Man (figs. 154, 157) structures similar to those of the Selachians are formed in the membranous stage, but subsequently they are only in part converted into cartilaginous pieces, which in turn never acquire a great size, having meantime lost their original function. They help to form the facial part of the head-skeleton, and have already been treated of partially in previous chapters in the discussion of the head-gut and of the organ of smell. I am therefore compelled for the sake of continuity to repeat much that has already been presented concerning the visceral skeleton.
 
In very young human arid mammalian embryos the mouth-opening is bounded on the sides and below by the paired maxillary and mandibular processes (tig. 156, compare p. 284). The former are widely separated from each other, because the unpaired frontal process, in the form of a broad, rounded projection, is at first inserted from above between them. Afterwards this projection becomes divided by the development, on its rounded surface, of the two nasal pits with the nasal grooves leading down to the upper margin of the mouth (compare p. 513); it is then divided into the outer and inner nasal processes. The former are separated from the maxillary process by a groove, which runs from the eye to the nasal furrow, and is the first fundament of the lachrymal duct.
 
Behind the first visceral arch comes the hyoid arch (figs. 157, 158 &), the two being separated by a small visceral cleft, which becomes the tympanic cavity and Eustachian tube. This is followed by three additional visceral arches with three visceral furrows (or clefts), which are of only short duration.
 
During a later stage fusions take place between the .processes that surround the oral opening (fig. 332).
 
The maxillary processes, by growing farther inward, meet the inner nasal processes, fuse with them, and produce a continuous
 
 
THE ORGANS OF THE INTERMEDIATE LAYER OR MESENCHYME. 611
 
 
 
Fig. 332. Roof of the oral cavity of a human embryo with fundaments of the palatal processes, after His. Magnified 10 diameters.
 
 
 
upper boundary to the mouth. In this way each olfactory pit with its nasal groove is converted into a canal, which leads into the oral cavity through an inner opening close behind the margin of the upper jaw. The membranous margins of the upper and lower jaws also lose their superficial positions, because the skin that covers them is raised up into externally projecting folds, and forms the lips, which from this time forward constitute the boundary of the oral opening.
 
A third stage, with the development of the palate, practically completes the formation of the face. (Compare pp. 515-17.) From the membranous upper jaw there arise two ridges projecting into the mouth-cavity (fig. 290) ; these become enlarged into the palatal plates, which grow horizontally.
 
The plates meet in the median plane and fuse with each other and with the median part of the frontal process, which has meantime become reduced by the enlargement of the olfactory organ to the thin nasal septum. Thus there is cat off from the primary oral cavity an upper chamber, which contributes to the enlargement of the nasal cavity, and which opens into the pharynx through the posterior nares ; at the same time [as the result of this growth] there has arisen a new roof of the mouth-cavity, the palate, which is afterwards differentiated into hard and soft palate.
 
A further differentiation of the face, which is now in the membranous stage of development, is brought about by the process of chondrification. This produces, however, in Mammals, as compared with Selachians, only small and unimportant skeletal structures. Some of these structures undergo degeneration (MECKEL'S cartilage), some are utilised as auditory ossicles in the function of hearing, and others are united to form the fundament of the hyoid bone. They arise from the soft tissue of the first, second, and third visceral arches ; in the case of the fourth and fifth arches there is not even a process of chondrification in Mammals, so that with the closure of
 
 
612
 
 
EMBRYOLOGY.
 
 
 
ant
 
 
am ha ink
 
 
zb
 
 
ntk
 
 
 
the fissures they are no longer recognisable as distinct parts,
perhaps the thyroid cartilage is to be referred to them (DUBOIS). I will describe the conditions in detail, first in the case of sheep
embryos of different stages of development, and then in the case of
a human embryo.
 
In a sheep embryo 2 cm, long there are to be found, according
to the account of SALENSKY (fig. 333), two long and slender cylindrical cartilaginous rods, one in front, the other behind the first visceral cleft ; their posterior (proximal) ends abut upon the labyrinthregion of the primordial cranium, and are here united to each other by means of embryonic connective tissue. In older embryos (fig. 334) the first visceral arch becomes at its upper
st hah zb [proximal] end more
and more distinctly
Figs. 333, 334. The dissected-out cartilages of MECKEL and Segmented by means
 
 
Fig. 333.
 
 
 
am' am ha
 
 
nik
 
 
 
EEICHERT with the fundament of the auditory ossicles,
from a sheep embryo 2'7 cm. long. After SALENSKY. Fig. 333. mk, MECKEL'S cartilage ; ha, hammer (malleus) ;
am, aiivil (inc\is) (long process) ; am', its short process ;
zb, cartilaginous hyoid arch. Fig. 334. am, Anvil; am', its short process; ha, hammer;
/Kill, hammer-handle; si, stirrup (stapes); mk, MECKEL'S
cartilage ; zb, cartilaginous hyoid arch.
 
 
 
of constrictions, into two smaller pieces and a larger one. The first small piece, the one lying next
 
 
to the wall of the
labyrinth, gradually assumes the form of the incus (ani) with its processes, the second becomes the malleus (7ia) ; the two are joined by means of a mass of connective tissue. The third piece (ink} is of considerable length, and haw the form of a cylindrical rod ; it is enclosed in the membranous lower jaw, and is designated in honor of its discoverer as MECKEL'S cartilage. It remains for a long time in union with the fundament of the malleus by means of a narrow
 
 
THE ORGANS OF THE INTERMEDIATE LAYER OR MESENCHYME. 613
cartilaginous bridge, upon which the long process (pr. gracilis) of the malleus is afterwards developed by periosteal ossification. The second visceral arch (zb) becomes incorporated in the hyoid bone.
 
In a human embryo of the fifth month one observes structures similar to those just described, only somewhat further developed. Figure 335 exhibits the incus (am\ easily recognised by its form, lying on the wall of the labyrinth ; with it is articulated the malleus (ha\ the long process of which is continuous with MECKEL'S cartilage (MK). This extends ventrally as far as the median line, where it is united with the cartilage of the opposite side by means of connective tissue a kind of symphysis.
 
The second visceral cartilage, called also REICHERT'S cartilage, has become divided into three portions. The uppermost portion is fused with the labyrinth-region the petrous portion of the temporal bone and constitutes the fundament of the processus styloideus (yrf) ; the middle portion has become fibrous tissue in Man, and forms a strong ligament, the lig. stylohyoideum [Ist/t], whereas in many Mammals it becomes a large cartilage ; the third and lowest portion produces the lesser cornu (M) of the hyoid bone. This sometimes becomes developed to a great length by the chondrification of the lower part of the ligamentum stylohyoideum, and reaches up very close to the lower end of the stylohyoid process.
 
In the third visceral arch chondrification takes place only in the ventral tracts, producing upon the sides of the neck the greater cornua of the hyoid bone (yh). Greater and lesser cornua are attached to an unpaired median piece of cartilage, which corresponds to a copula of the visceral skeleton of Selachians and becomes the body of the hyoid bone.
 
The third auditory ossicle, the stapes (fig. 335 st), also belongs to the visceral apparatus ; it has been left unmentioned until now, because there is, even at present, a wide difference of opinion concerning its development. According to the original view of REICHERT, which GEGENBAUR is also inclined to adopt, the stapes arises from the uppermost end of the hyoid arch. KOLLIKER refers it to the first visceral arch. ' According to GRUBER and PARKER, on the contrary, it arises in connection with the fenestra ovalis, as though it were cut directly out of the outer wall of the labyrinth.
 
According to the recent investigations of SALENSKY, GRADENIGO, and RABL, it appears to me that the stapes has a double origin, arising from two different parts.
 
The plate of the stapes, which is let into the fenestra ovalis, is
 
 
614
 
 
EMBRYOLOGY.
 
 
 
differentiated in the manner first emphasised by GRUBER and PARKER, and now again by GRADENIGO, out of the cartilaginous capsule of the labyrinth. Its development therefore agrees with that of the operculum of the Amphibia, as described by STOHR. The ring-like part of the stapes, on the contrary, comes from the upper end of the second visceral [hyoid] arch, which lies in contact with the capsule of the labyrinth (GRADENIGO, EABL). Its ring-like condition results
 
 
ha
 
 
si
 
 
 
u
 
 
MK
 
 
pr
 
 
l*t h tjh
Fig. 335. Head and neck of a human embryo 18 weeks old with the visceral skeleton exposed,
after KOLLIKER. Magnified. The lower jaw is somewhat depressed in order to show MECKEL'S cartilage, which extends to the
malleus. The tympanic membrane is removed arid the annulus tympanicus is visible. 1m, Malleus, which passes uninterruptedly into MECKEL'S cartilage, MK ; v.k, bony lower jaw
(dentale), with its condyloid process articulating with the temporal bone ; am, incus ;
*, stapes \ pr, annulus tympanicus ; c/rf, processus styloideus ; Ixth, ligamentum stylo
hyoideum ; ///, lesser cornu of the hyoid bone ; gli, its greater cornu.
 
 
 
from the fact that the tissue from which it is formed is traversed by a small branch of the carotis interna, the arteria mandibularis or perforans stapedia. In Man and certain of the Mammals this subsequently degenerates entirely, whereas in others (Rodents, Insectivores, etc.) it remains as a vessel of considerable size.
 
Both fundaments of the stapes fuse with each other very early and form a small cartilage, which on the one hand articulates with the incus by means of a lenticular connecting element (os lentiforme),
 
 
THE ORGANS OF THE INTERMEDIATE LAYER OR MESENCHYME. 615
and on the other reposes with its plate -like base in the fenestra ovalis.
 
The view here adopted that the stapes belongs to the second, the malleus and incus to the first visceral arch is supported by the important relation of the nerves in their distribution to the musculus stapedius and to the tensor tympani, as has recently been rightly pointed out by RABL. The muscle of the stapes is supplied from the nerve of the second visceral arch, the nervus facialis ; it forms part of a group embracing the in. stylohyoideus, and the posterior belly of the digastric; the muscle of the malleus receives a branch of the trigeminus, which is the nerve of the mandibular arch.
 
The separation of the territories of innervation prevails, moreover, with the muscles of the palate, one of which the tensor veil palatini arises in front of the Eustachian tube the remnant of the first visceral cleft and is therefore supplied by the n. trigerninus, whereas the levator veil palatini and azygos uvulae lie behind it, and, because belonging to the hyoid arch, receive branches from the n. facialis (EABL).
 
At first all the auditory ossicles lie imbedded in a soft gelatinous tissue outside the tympanic cavity, which still has the form of a narrow fissure. These conditions are not altered until after birth. The tympanic cavity, taking in air, then becomes enlarged, its mucous membrane is evaginated between the auditory ossicles, and the gelatinous tissue just mentioned undergoes a process of shrinkage. Auditory ossicles and chorda tympani thus come to lie apparently free in the tympanic cavity ; accurately considered, however, they are only crowded out into it, for even in the adult they are enclosed in folds of the mucous membrane, and by means of these they preserve their original and genetically established connection with the wall of the tympanic cavity.
 
Up to the present stage the construction of the head-skeleton is, on the whole, simple. In the third stage of development, on the contrary, upon the beginning of the process of ossification, it attains in a short time a high degree of complication, which is effected especially by the development of two entirely different kinds of bone, one of which has been called primordial bone, the other covering bone (Deck- oder Belegknochen).
 
Primordial bones are such as are developed out of the cartilaginous skeleton. Either there arise centres of ossification within the cartilage after softening and dissolution of its matrix, as was described in the ossification of the vertebral column, the ribs, and the sternum, or the perichondrium alters its formative activity, and secretes, in
 
 
1 G EMBRYOLOGY.
 
place of layers of cartilage, bony tissue upon tin- already formed cartilage. In the first instance one can speak of an endochondral, in the second instance of a perichondral ossification. The cartilaginous primordial skeleton can be crowded out and replaced by a bony one in both ways, remnants of cartilage of greater or less magnitude being preserved in the several classes of Vertebrates.
 
The covering bones, on the contrary, arise outside the primordial cranium in the connective tissue enveloping it, either in the skin which covers its surface or in the mucous membrane that lines the head-gut. They are therefore ossifications which do not occur on any other part of the axial skeleton and which are also at first foreign to the skeleton of the head. Consequently in early stages of development, and in many classes of Vertebrates even in the adult animal, they can be dissected off without in any way injuring the primordial cranium. It is otherwise with the primary bones, the removal of which always causes a partial destruction of the cartilaginous skeleton.
 
If, as just now stated, the covering bones are at first foreign to the skeleton of the head, there arises the question of their source. To answer this I must go back a little.
 
In lower Vertebrates there is developed, besides the internal cartilaginous axial skeleton, an external or dermal skeleton, which serves for the protection of the surface of the body, and is also continued at the mouth for some distance into the cavity of the head-gut, where it may be designated as mucous-membrane skeleton. In the simplest condition it consists, like the scaly armor of the Selachians, of small close-set denticles, the placoid scales, which have arisen from ossifications of dermal and mucous-membrane papillse. In other groups of the Fishes the dermal armor is composed of larger or smaller bony plates, which bear upon their surfaces numerous denticles or simple spines. They are described according to their form and size as scales, scutes, plates, or dermal bones ; they are explainable in a very simple manner as derivatives from the Selachian armor of placoid scales, by the fusion at their bases of larger or smaller groups of denticles, which thus produce larger or smaller skeletal pieces. The larger bony pieces arise principally in the region of the head, and especially at the places where cartilaginous parts of the cranial capsule or of the visceral arches approach close to the surface. Thus in many Ganoids and Teleosts the brain is found to be enveloped by a double capsule an inner capsule, either purely cartilaginous or provided with centres of ossification, and a bony armor lying directly upon it.
 
 
 
THE ORGANS OF THE INTERMEDIATE LAYER OR MESENCHYME. 617
In the higher Vertebrates the most of the dermal skeleton has completely degenerated, but on the head it is in large part preserved, and furnishes the previously mentioned covering bones, which serve to supplement and complete the internal skeleton.
 
An interesting insight into the original method of the development of covering bones can still be acquired in many of the Amphibians (fig. 336). For example, the vorner and the palatinum, which are covering bones, arise in very young Triton larvae by the formation of small denticles (z'} in the mucous membrane of the oral cavity, and by the fusion of their bases to form small tooth-bearing plates of bone (z, z). These plates increase in size for a time, owing to the establishment in the Fig. 336. Vomer of an Axoioti
IT- i PIT larva 1 - 3 cm. long.
 
neighboring mucous membrane of addi- By the fnsiou of t * th (=< 2) a tioiial dental spines, which become attached tooth-bearing plate of bone
P. P . h;is arisen in the mucous
to their margins; afterwards they often ln , m brane. c', Apices of
 
 
 
lose the equipment of denticles, which are teeth in P TOC ess of
. ment, which are subsequently
destroyed by being resorbed. attached to the margin of tiu
It may be said that the original process bon ^ i )late aml contribute to
4-1 ! l C i its growth.
 
in the development or covering bones here
described is abbreviated in most of the Amphibia. For at the places in the mucous membrane which the vorner and the palatinum occupy, the tips of denticles are not even begun ; but in the layer of tissue in which otherwise the bases of the denticles would have been fused, a process of direct ossification takes place. In the same abbreviated way the covering bones arise in all Reptiles, Birds, and Mammals.
 
The skulls of many Amphibia (Frog, Axolotl) likewise afford the best explanation of the original relation of the covering bones to the primordial skeleton (fig. 337). The covering bones are found to be loosely superposed upon the primordial cranium, from which they can be easily removed. Thus upon the left side of the accompanying figure the premaxillaria (Pmx), maxillaria (M), vorner (To), palatinum (Pal), pterygoid (Ft], and parasphenoid (Ps) have been detached, whereas upon the right side they have been retained. After their detachment there is left the inner head-skeleton proper a capsule still consisting in great part of the original cartilaginous tissue (N, N l , PP, Qu], into which, however, there are introduced at some places bony pieces : the occipitalia (Olat), petrosa (Pro), sphenoidea [sphenethmoid] (E), etc.
 
In the higher Vertebrates, especially in Mammals, the primordial
 
 
618
 
 
EMBRYOLOGY.
 
 
 
cranium, the primary ossifications, ;intl lln 1 covering bones, which in Fishes and Amphibia aro easily distinguishable from one another even in the adult animals, are to be recognised as separate parts only in very early stages of development ; later it becomes more difficult
to distinguish them, at last impossible. This is due to several things :
First, the cartilaginous primordial cranium is laid down from the beginning in a rudimentary condition: then, too, a large part of the roof is wanting, the opening being closed by a connective -tissue membrane.
 
Secondly, the cartilaginous primordial cranium subsequently disappears almost entirely, partly by being dissolved, partly byconversion into primordial bones. There persist small remnants, which have been retained only in the cartilaginous septum narium and the cartilages of the outer
 
 
 
C'occ
 
 
Fig. 337. Skull of a Frog (Rana esculenta). View from beneath. After ECKER.
 
The lower jaw is removed. On the left side of the figure the covering bones have been removed from the cartilaginous part of the skull .
 
C'occ, Condyli occipitales ; Olat, occipitale laterals ; GK, auditory capsule ; Qu, quadratum ; Qjcj, quadrate.jugale ; Pro, prooticum ; P.s 1 , parasphenoid ; As, alisphenoid; Ft, osseous pterygoid ; PP, palato-quadratum; FP, fronto-parietale ; E, ethmoid (os en ceinture) ; Pal, palatinum ; Vo, vomer ; M, maxilla ; Pnix, premaxillare ; N, N 1 , cartilaginous nasal framework ; //, V, VI, places of emergence of n. opticus, n. trigeminus, and n. abdiicens.
 
 
 
nose connected with it.
 
Thirdly, in the fully developed skull the primordial bones and the covering bones are no longer distinguishable ; for the latter lose their superficial position, become intimately united to the bones derived from the primordial cranium, and with them, filling up the gaps, constitute a firm, closed, bony receptacle of mixed origin.
 
Fourthly, in the adult animal, bones which in the embryo are formed separately, and in lower Vertebrates always remain thus, are often fused. There is a fusion not only between bones of like origin, but also between primordial and covering bones, whereby it finally becomes altogether impossible to distinguish them. Many of the bones of the human cranium are consequently bone -complexes.
 
 
 
THE ORGANS OF THE INTERMEDIATE LAYBR OR MESENCHYME. 619
It may be stated as a general rule that the ossifications on the base and sides of the cranium are primordial, but that on the roof and in the face covering bones make their appearance.
 
The following parts of the human skull belong to the primordial elements : (1) occipitale, except the upper part of the squauious portion ; (2) the sphenoidale, except the internal pterygoid plate ;
(3) ethmoidale and turbiiiatum ; (4) petrosum and raastoid portions of the temporale ; (5) the auditory ossicles malleus, incus, and stapes ; (6) the body of the hyoicles, with its greater and lesser cornua.
 
The following are covering bones: (1) the upper part of the squamous portion of the occipitale ; (2) the parietale ; (3) the frontale;
(4) the squamous portion of the temporale ; (5) the internal pterygoid plate of the sphenoidale ; (G) the annulus tympanicus; (7) palatinum ; (8) voiner ; (9) nasale ; (10) lachrymale ; (11) zygomaticum; (12) maxillse sup. ; (13) maxillse inf.
 
I will now, after this survey, give a somewhat more detailed account of the development of the bones of the head enumerated above.
 
I. f>ones of the Cranial Capsule.
 
(1) The occipitale is at first a cartilaginous ring surrounding the foramen magnum ; it begins to ossify early in the third month at four points. One centre of ossification is formed below the foramen, another above, and two more at its sides. In this way there arise four bones, which are joined by broader or narrower bands of cartilage, according to the degree of their development. In the lower Vertebrates Fishes, Amphibia (fig. 337 Olat) they remain in this condition as separate bones, and are designated as occipitale basilare, oc. superius, and oc. laterale.
 
To these are added in Mammals and Man a covering bone, which arises from two centres of ossification in the connective tissue farther above the foramen the interparietale. This begins, even in the third foetal month, to fuse with the superior occipital bone to constitute the squama ; however, up to the time of birth furrows running in from right and from left mark the boundary of the two genetically different parts. In the new-born child squama, occipitalia lateralia and oc. basilare are still separated from each other by thin remnants of cartilage. Then in the first year the squama fuses with the lateral parts (partes condyloidese), and finally there is united with these, in the third or fourth year, the pars basilaris. The occipitale
 
 
G20 EMBRYOLOGY.
 
is therefore a complex that has originated from five separate bones.
 
(2) The sphenoidale also arises from numerous centres of ossification, which appear in the base of the primordial cranium, and which in the lower classes of Vertebrates represent parts of the cranial capsule that remain separate. In the anterior prolongation of the pars basilaris of the occipitale there appear in the vicinity of the sella turcica an anterior and a posterior pair of centres, which constitute the fundaments of the bodies of the anterior and posterior sphenoidea. At the sides of these there are developed special centres of ossification for the lesser and for the greater wings.
 
In most Mammals the lesser wings fuse with the anterior, the greater with the posterior body. Thus there are formed two sphenoidea, an anterior and a posterior, which are placed in front of the occipitale, and are separated from each other by a thin strip of cartilage. In Man these two bones become joined together, by the ossification of the cartilaginous strip mentioned, to constitute the unpaired single sphenoidale, with its many processes. The fusions of the numerous separate ossifications take place in the following order. In the sixth foetal month the lesser wings of the sphenoid fuse with the anterior body ; shortly before birth the latter unites with the posterior body, and in the first year after birth the greater wings are united with the rest. From the latter the outer pterygoid plates grow downward, whereas the inner ptery //aid plates are formed as covering bones. For in the connective tissue of the lateral wall of the oral cavity there is developed a special region of ossification ; this furnishes a thin bony lamella, which is preserved in many Mammals as a special skeletal element (os pterygoideurn) lying on the pterygoid process of the sphenoidale. In Man it early fuses with the sphenoidale, notwithstanding it has an entirely different origin from the latter.
 
(3) The temporale is a complex of various bones, the greater part of which are still separate in the new-born infant. The os petrosum with the mastoid process is developed from numerous centres of ossification in that part of the primordial cranium which encloses the organ of hearing, and has therefore been designated as cartilaginous ear-capsule. With it is united after birth the styloid process, which in the embryo is a cartilaginous rod that is derived from the upper end of the second visceral arch and that ossifies from its own independent centre.
 
To the primordial bones there are added in Man two covering
 
 
THE ORGANS OF THE INTERMEDIATE LAYER OR MESENCHYME. 621
bones, squama and pars tympanicus, which are as foreign to the primordial cranium as the parietal or frontal bones. Of these the pars tympanicus (fig. 335 pr) is at first a narrow bony ring, which serves as a frame for the tympanic membrane. It is developed in connective tissue outside of the auditory ossicles, and, in particular, outside the malleus (ha) and the connected MECKEL'S cartilage (MK). Thus is explained the position of the long process of the malleus in the fissura petrotympanica, when, soon after birth, the primordial and covering bones fuse with each other. For the annulus tympanicus gradually becomes broadened into a bony plate, which serves as a support for the external meatus. This plate then fuses with the petrosal bone, except along a narrow cleft, the fissura petrotympanica or Glaseri, which remains open, because here the chorda tynipani and the long process of the malleus were in the embryo shoved in between the bones, while they were still separate.
 
In lower Vertebrates, and also in many Mammals, the pieces mentioned remain separate, and are distinguished in comparative anatomy as os petrosum, os tympanicum, and os squamosum.
 
(4) The ethmoidale and the turbinatum of the nose are primordial bones, which are developed out of the posterior part of the cartilaginous nasal capsule, whereas the anterior part remains cartilaginous and becomes the cartilaginous septum nasoruin and the external nasal cartilages.
 
" The ossification begins in the lamina papyracea in the fifth month. Then follows the ossification of the lower and middle turbinals. At birth these are united by means of cartilaginous portions of the ethmoidale. After birth the vertical plate with the crista galli is the first to ossify; then follows the ossification of the upper turbinal and of the gradually developed labyrinth, from which the ossification advances to the corresponding halves of the cribriform plate. The union of the two lateral halves with the lamina perpendicularis does not take place until between the fifth and the seventh year." (GEGENBAUR.)
Of the covering bones of the primordial cranium, which in general begin to ossify at the beginning of the third month, the following remain separate : the parietale, frontale, nasale, lachrymale, and vomer. Of these the frontale is originally, like the others, a paired structure, and still continues in this condition into the second year after birth, when the closure of the frontal suture begins. Nasale and lachrymale are covering bones of the cartilaginous nasal capsule. The vomer arises as a paired structure at the sides of the
 
 
622 EMBRYOLOGY.
 
cartilaginous septum of the nose in the third month. The two lamellre afterwards fuse, the cartilage between them disappearing.
 
II. Bones of the Visceral Skeleton.
 
*/
The remaining bones of the head, which have not been mentioned hitherto, belong to the visceral skeleton, some of them being primordial, others covering bones.
 
The hyoid bone and the auditory ossicles (perhaps also the thyroid cartilage) are primordial parts ; they are characterised by very diminutive size and occupy a very subordinate position in comparison with the enormously developed covering bones. The hy aides begins toward the end of embryonic life to ossify at several points. The auditory cartilages acquire from the periosteum as early as the fourth month a bony investment, within which here and there remnants of cartilage persist even in the adult. According to recent researches, the malleus is a confound skeletal piece. The long process is developed as a covering bone on that part of MECKEL'S cartilage which penetrates between petrosal and annulus tympanicus. While the cartilage undergoes degeneration, the covering bone fuses with the larger, primordial part of the malleus. It probably corresponds with the os angulare of lower Vertebrates.
 
The covering bones of the visceral skeleton, the maxillare superius, palatinum, pterygoideum, zygomaticum, and maxillare inferius, are developed in the vicinity of the mouth-opening in the connective tissue of the superior and inferior maxillary processes,
The maxillaria superiores are a complex of two pairs of bones, which indeed remain separate in most Vertebrates. One pair is developed on the two superior maxillary processes laterad of the cartilaginous nasal capsule. The other pair appears in the eighth or ninth week, according to TH. KOLLIKER'S detailed investigations, upon the part of the frontal process that lies between the nasal orifices. It corresponds to an actual paired intermaxillary (prernaxillare), and subsequently encloses the fundaments of the four incisors.
 
The two intermaxillaries in Man early fuse with the fundaments of the two superior maxillaries, the two membranous superior maxillary processes having previously united with the inner nasal processes. The boundary between maxillary and intermaxillary is indicated on the crania of young persons by a suture-like place (sutura incisiva), running transversely outward from the foramen incisivum, which is occasionally retained even in the adult.
 
 
 
THE ORGANS OF THE INTERMEDIATE LAYER OR MESENCHYME. 623
There early grow out from the two superior maxillaries into the palatal processes horizontal lamellae which produce the two palatal bones the hard or bony palate.
 
Palatals and pterygoids are developed in the roof and side walls of the oral cavity they are consequently mucous-membrane bones. The pterygoids apply themselves, as was stated on p. 620, to the cartilaginous downgrowths of the greater wings of the sphenoid. In many Mammals they remain separate from the latter throughout life, but in Man they unite with it and are now distinguished as inner pterygoid plates from the outer plates, which arise by ossification of cartilage.
 
 
 
The development of the visceral skeleton, which has been discussed here and in previous sections (pp. 284, 515), furnishes the basis for the interpretation of the malformations which are quite frequently met with in the maxillary and palatal region in Man. I refer to the labial, maxillary, and palatal fissures, which are simply malformations due to arrested development. They result when the separate fundaments from which are formed the upper lip, the upper jaw, and the palate do not come into normal union (figs. 288-91).
 
The malformations of arrested development can present very different variations, according as the coalescence is wholly or only partly omitted, and according to whether it affects one or both sides of the face.
 
In the case of total arrest, in palatal, maxillary, arid labial fissures of both sides, both nasal cavities are broadly in communication with the oral cavity by means of a right and a left fissure running from in front backward. From above there projects free into the oral cavity the nasal septum, which is enlarged in front, and here bears the incompletely developed intermaxillary with its rudimentary incisor teeth. In front of it lies a small dermal ridge, the fundament of the middle part of the upper lip. At the sides of the fissures and the nasal openings, which have not been closed in below, there lie the two separated maxillary processes, with the bony upper jaw and the fundaments of the canine and molar teeth. The horizontal palatal plates project as ridges only a little distance into the oral cavity, and have not effected a junction with the nasal septum. A malformation of this kind is very instructive for the comprehension of the normal processes of development previously described.
 
When the arrest is only partial, coalescence may fail either on the
 
 
624 EMBRYOLOGY.
 
superior maxillary processes only, or on the palatal plates only, and either on one or on both sides. In the first case there is produced a labio-maxillary fissure, or even a labial fissure (hare-lip) only, while hard and soft palates are formed normally. In the other case the upper jaw is well developed and no external evidence of malformation is visible, while there is a fissure on one or both sides which passes through the soft palate, and sometimes through the hard palate also (cleft palate).
 
 
 
The development of the lower jaw is coupled with fundamental metamorphoses. As has been previously explained, in the youngest embryos the oral cavity is limited below by the membranous inferior maxillary processes. Within this there is developed (fig. 338) MECKEL'S cartilage (MK\ the cranial end of which becomes (compare p. 611) the fundament of the malleus (ha), by means of which MECKEL'S cartilage is articulated with the incus (cmi). At its ventral end in Mammals it unites in the middle line with the corresponding part of the other side, whereas in Man a small space remains between them.
 
Inasmuch as the small cartilages mentioned have arisen in the first visceral arch, they correspond both in position, and also in their mutual connections and many other relations, to the large cartilaginous elements with which we have already become familiar in the Selachians (fig. 330) as palato-quadraturn (0) and mandibulare (U). In the Selachians the palato-quadratum and mandibulare are functional as a genuine jaw-apparatus, for they bear on their margins the teeth, which are attached in the mucous membrane only, and the masticatory muscles are inserted on their surface.
 
In Mammals and Man the function of the skeletal parts corresponding to them has become essentially different, for they have entered into the service of the auditory apparatus ; a profound, and in its final results wonderful and highly important metamorphosis has taken place here. In order to explain this it is necessary to touch briefly upon a few comparative-anatomical facts.
 
With the beginning of ossifications the primary lower jaw loses in Teleosts, Amphibia, and Reptiles its simple condition, and is converted into an apparatus which is often very complicated. The ossifications are here, just as was the case in the other parts of the head-skeleton, of two different kinds, primary and secondary. One
 
 
THE ORGANS OF THE INTERMEDIATE LAYER OR MESENCHYME. 625
bone, which makes its appearance in the articular part of the cartilage and produces the os articulare, is a primary bone. With this are associated several covering bones arising in the surrounding connective tissue, two of which, the angulare and the dentale, acquire special importance. Both are attached to the outer surface of the cartilaginous [Meckelian] rod, the angulare near the joint, the dentale in front of it and extending to the syrnphysis.
 
 
 
Jut
 
 
III,!
 
 
 
uk
 
 
MK
 
 
1"'
 
 
Fig. 338. Head and neck of a human embryo 18 weeks old with the visceral skeleton exposed,
after KOLLIKF.R. Magnified. The lower jaw is somewhat depressed in order to show MECKEL'S cartilage, which extends to the
malleus. The tympanic membrane is removed and the annnlns tympaiiicus is visible. lie, Malleus, which passes uninterruptedly into M ECKEL'S cartilage, A/A" ; ulc, bony lower jaw
(dentale), with its condyloid pmcess articulating with the temporal bone; am, incus;
st, stapes; pr, aunulus tympaiiicus; grf, processus styloidens ; lath, ligamentnm stylo
liyoideum ; kh, lesser cornu of the hyoid bone ; t/h, its greater cornu.
 
 
 
The latter is an important skeletal element, which attains a considerable size, receives into its upper margin the teeth, and grows around the cartilage of MECKEL in such a manner that the cartilage is almost completely enclosed in a bony cylinder. The whole complicated apparatus, composed of several bones and the original cartilage enclosed within them, articulates at the primary joint of the jaio between palato-quadratum and os articulare.
 
The same fundaments are again met with in Mammals and Man.
 
40
 
 
62G EMBRYOLOGY.
 
In tho articular part of the cartilage of the lower jaw, which has assumed the form of the malleus (figs. 334, 338 ha), there arises a special centre of ossification, which corresponds to the articulare of other Vertebrates. In its vicinity appears, as a, covering hone, an exceedingly small angulare, which subsequently fuses with it, producing the long process of the malleus. The second covering bone, the dentale (fig. 338 uk), attains, on the contrary, a great size and alone becomes the subsequently functioning lower jaw, whereas the remaining parts, which in the compound mandibular apparatus of Teleosts, Amphibia, Reptiles, and Birds participate in the function of chewing (palato-quadratum, or quadratum, articulare, angulare, and MECKEL'S cartilage), lose their original function and are employed in another manner.
 
The most important motive to this profound metamorphosis is to be found in the fact that in Mammals and Man there is developed in place of the primary articulation of the jaw a secondary one. The primary articulation, upon which the tooth-bearing dentale is moved, lies, as we have seen, between palato-quadratum and articulare. Inasmuch as these elements correspond respectively to the incus and malleus of Mammals, the primary articulation of the jaw of lower Vertebrates is to be sought in the incus-malleus articulation of the higher Vertebrates. In Mammals and Man the dentale is no longer moved at this joint, because the dentale itself forms a direct articulation with the cranial capsule by means of a bony projection, -the processus coiidyloideus (fig. 338), which it sends upward, and through which it is united to the squamous portion of the temporal bone at some distance in front of the primary articulation. This union constitutes the secondary articulation of the jaw, in which only covering bones participate.
 
The natural result of the formation of a new articulation is, that the primary lower-jaw apparatus has become superfluous for the act of mastication, and that its development is restricted. Incus, malleus, and angulare, which is united with the malleus, are converted into parts of the auditory organ (see p. 613). The remaining part of MECKEL'S cartilage (JOT) begins to degenerate, in Man in the sixth month. A portion of it, which is a prolongation of the long process of the malleus, extending from the fissura petrotympanica as far as the entrance into the bony lower jaw at the foramen alveolar e, is converted into a connective -tissue cord, the ligamentum laterale internum maxillae inferioris. A small portion near the front end early acquires a special centre of ossification and
 
 
THE ORGANS OF THE INTERMEDIATE LAYER OR MESENCHYME. 627
fuses with the covering bone. The remainder of that portion of MECKEL'S cartilage which is enclosed in the canal of the lower jaw, from the foramen alveolare onward, is gradually broken down and dissolved ; however, remnants of the cartilage are found even in the new-born infant at the symphysis.
 
At first the bony lower jaw is a paired structure, consisting of tooth-bearing halves. These remain in many Mammals as separate bones, being united in a symphysis by means of connective tissue. In Man they are united in the first year after birth into a single piece by the ossification of the intervening tissue.
 
A special peculiarity is exhibited by the articular end of the lower jaw, phylogenetically a covering bone. Instead of beginning to be formed, in the manner of the anterior portion, by direct ossification of the connective-tissue foundation, there first arises here a cartilaginous tissue consisting of large vesicular cells and soft intercelluar substance, which is gradually converted into bone. This presents a certain similarity to the development of the primordial bones. But that the resemblance is only superficial is shown by the difference in the structure of the articulation, to which I shall return in a subsequent section.
 
(c) Concerning the Relation of the Head-Skeleton to the
Trunk-Skeleton.
 
In different sections of this text-book in discussing the primitive segments, the nervous system, and especially now in the discussion of the axial skeleton reference has been made to many points of agreement that have been recognised between the structural conditions of the head and those of the trunk. In a critical comparison of these two regions of the body there arise many important questions which have for several decades engaged the attention of the best morphologists. It may therefore be well here, after having given the pertinent facts, to take up these questions more particularly, and determine the relation which head and trunk, and especially that which head-skeleton and trunk-skeleton, sustain to each other.
 
Before I elucidate the present state of the question, I will give a brief survey of the history of these researches, which have been grouped together under the name
" The Vertebral Theory of the Skull" The relation which the anterior and posterior parts of the skeleton
 
 
G28 EMBRYOLOGY.
 
of the trunk sustain to each other in the morphology of Vertebrates was for the first time subjected to a thorough scientific discussion at the beginning of the present century, when the school of the " Natural Philosophers " began its career. An attempt to solve the problem was made in very similar ways by two persons, by the natural philosopher OKEN and by the poet GOETHE, without either of them having been influenced by the other.
 
According to the OKEN-GOETHE vertebral theory, the skull is the most anterior part of the vertebral column, and is composed of a small number of modified vertebrae. OKEN distinguished three vertebra? in his " Programme " entitled " Ueber die Bedeutung der Schadelknochen," which appeared in 1807, when he entered upon a professorship conferred upon him in Jena. He named them the ear-, eye-, and jaw-vertebra?.
 
Each head-vertebra, like a trunk- vertebra, consisted in his opinion of several parts a body, two arch-pieces, and a dorsal spine. OKEN, GOETHE, and their numerous followers believed that this composition was most distinctly recognisable in the last cranial vertebra, the OGcipitcde, the base of which was compared to the body of the vertebra, the condyloid parts to the lateral arches, and the squama to the spine of the vertebra.
 
A second cranial vertebra was discerned in the body of the %)osterior sphenoidale, which together with its greater wings and the two parietal bones formed a second bony ring around the brain.
 
A third vertebra was constructed out of the body of the sphenoidale, anterius, the lesser wings and the frontale.
 
The ethmoidale was cited by many investigators as a fourth the most anterior cranial vertebra. A number of bones, which would not fit into this scheme, were considered to be structures sui generis, and were in part associated with the sensory organs as sensory bones, in part compared with the ribs of the thorax.
 
In this form, which underwent numerous modifications in details, the OKEN-GOETHE vertebral theory of the cranium dominated morphology for decades and formed the foundation of many investigations. It had a stimidating and fruitful effect until, with a deeper insight into the structure of Vertebrates, it was abandoned as defective and erroneous, giving way before the force of numerous newly discovered facts.
 
For neither the comparative osteology of the skull nor growing embryological research could point out in a satisfactory way which bones were really to be interpreted as parts of vertebrae. The most
 
 
THE ORGANS OF THE INTERMEDIATE LAYER OR MESENCHYME. 629
dissimilar, and more or less arbitrary, opinions upon this subject made their appearance. An agreement even as to the number of vertebrse contained in the skeleton of the head could not be reached. Some investigators assumed six, others five or four, or even three only.
 
HUXLEY, in his "Elements of Comparative Anatomy," by a critique based upon facts, was the first to prepare the way for a termination of this unpleasant state of affairs, in which the vertebral theory was held to with tenacity, notwithstanding the contradictions that everywhere arose. In his discussion he argued from a series of facts 'which embryological investigation had brought to light. As such the following, important for the problem of the skull, should be cited before all others.
 
First, the discovery that the skeleton of the head, like the vertebral column, is developed out of a cartilaginous condition, and that the brain is first enclosed by a primordial cartilaginous cranium (BAER, DUGES, JACOBSON).
 
Secondly, the doctrine established mainly by KOLLIKER, that the bones of the head-skeleton are separable into two groups according to their development into the primordial bones, which arise in the primordial cranium itself, and the secondary or covering bones, which have their origin in the enveloping connective tissue.
 
Thirdly, the insight which was acquired, through the important works of RATHKE and REICHERT, into the metamorphoses of the visceral skeleton, and thereby into the development of the palatomaxillary apparatus and the auditory ossicles.
 
Through an examination of these various facts, HUXLEY was led to the important and fully justified conclusion, that not a single cranial bone can be recognised as a modification of a vertebra, that the skull is no more a modified vertebral column than the vertebral column is a modified skull ; that, rather, both are essentially distinct and different modifications of one and the same structure.
 
While HUXLEY stopped at the negative standpoint, simply denying the vertebral theory, GEGENBAUR has made the question of the relation of skull and vertebral column, raised by GOETHE and OKEN, but from ignorance of the facts incorrectly answered by them, again the object of profound comparative study. Rightly recognising that the problem can be solved only by detailed investigation of the primordial skeleton, he selects as the object for his studies the cartilaginous skull of the Selachians, and endeavors in his revolutionising work, " Das Kopfskelet der Selachier als Grundlage zur Beurtheilung der Genese des Kopfskelets der Wirbelthiere," to
 
 
630 EMBRYOLOGY.
 
produce the evidence that the primordial cranium has arisen by fusion from a number of segments equivalent to vertebral. Instead of the OKEN-GOETIIE vertebral theory he propounds the seymental theory oj the skull, as I suggest the doctrine of GEGENBAUR be called.
 
GEGENBAUR proceeds from the correct conception that the segmentation of a region of the body is recognisable not only in the metamerism of the vertebral column, but also in many other structures in the method of the arrangement of the chief nerve-trunks, and in the ventral arch-structures attached to the axial skeleton. He investigates, accordingly, the cranial nerves of the Selachians, and arrives at the conclusion that, with the exception of the olfactory and optic nerves, which are metamorphosed parts of the brain itself, they deport themselves like spinal nerves both in their origin and their peripheral distribution. He determines that there are nine pairs of them ; and therefore concludes that the portion of the headskeleton which is traversed by the nine segmentally arranged cranial nerves must be equivalent to nine vertebral segments, and that it must have arisen by their very early fusion.
 
The visceral skeleton of Selachians is regarded by GEGENBAUR from the same instructive point of view. He discerns in the maxillary, hyoid, and branchial arches skeletal elements which are represented in the vertebral column by the ribs.
 
Inasmuch as a vertebral segment belongs to each pair of ribs, a similar relation is also assumed as the original arrangement for the visceral arches. Thus this method of considering the question leads to the same result : that the primordial cranium since at least nine visceral arches belong to it as ventral arch-structures has been produced from at least nine segments.
 
Such an origin GEGENBAUR accepts for the posterior chordatraversed region of the skull only, in which alone the emerging nerves agree with spinal nerves. He therefore distinguishes this as vertebral from the anterior or non-vertebral portion, which does not allow the recognition of any segmentation, and which begins in front of the anterior end of the chorda. He interprets the latter as a new formation which has been established by the enlargement in front of the vertebral part of the skull.
 
GEGENBAUR explains the great differences which exist between skull and vertebral column as adaptations, partly to the enormous development of the brain, partly to the sensory organs of the head, which are received into pits and cavities of the primordial cranium.
 
Since the time when GEGENBAUR with keen discrimination pro
 
 
THE ORGANS OF THE INTERMEDIATE LAYER OR MESENCHYME. 631
pounded his segmental theory of the skull, the way has been prepared in many directions, chiefly through embryological investigation, for a better comprehension of the skeleton of the head.
 
Investigations which I undertook on the dermal skeleton of Selachians, Ganoids, and Teleosts, as well as 011 the head-skeleton of Amphibia, showed that the difference between primordial and covering bones is much greater than it was originally assumed to be. For as their development shows, the covering bones are at first structures quite foreign to the axial and head-skeleton, formed at the surface of the body in the skin and mucous membrane. They are parts of a dermal skeleton, which in lower Vertebrates protect the surface of the body as a scaly armor, parts which have entered into union with the superficially located portions of the inner, primordial cartilaginous skeleton. Therefore the covering bones of the lower Vertebrates are often tooth -bearing bony plates, which have originated from a fusion of isolated dental fundaments, a condition which may be regarded for many reasons as the primitive one.
 
A further acquisition of broad significance is the discovery of the primitive segments of the head, which we owe to BALFOUR, MILNES MARSHALL, GOETTE, WIJHE, and FRORIEP.
 
By it an important point of agreement between head and trunk has been made out. The two body-sacs penetrate even into the head ; here also the two middle germ -layers are separated into a dorsal portion, lying in contact with the chorda arid neural tube, which is divided into nine pairs of primitive segments,* and into a ventral portion (see p. 351).
 
The head is therefore segmented similarly to the trunk, even at a time when the first traces of the fundament of a vertebral column or a head-skeleton are not yet present.
 
Thirdly, the insight into the development of the cranial nerves (BALFOUR, MARSHALL, WIJHE, and others) is important. An agreement with the development of the spinal nerves has been established in so far as some cranial nerves have a dorsal origin from a neural crest, like the sensory roots of spinal nerves, while others grow out ventrally from the brain-vesicles like anterior roots.
 
Finally, I would mention as a step in advance, which is not without significance for the interpretation of the head-skeleton, the altered conception of the, meaning of the primitive segments which embrijological evidence has compelled us to form.
 
The primitive segments are the real fundaments of the musculature
* [Sea footnote p. 458.]
 
 
632 EMBRYOLOGY.
 
of the body. The iirst segmentation of the vertebrate body affects the body -sacs and the musculature arising from them. The formation of the primitive segments is only remotely and indirectly connected with the development and segmentation of the vertebral column. It is only after muscle-segments have existed for a long time that, at a comparatively late stage of development, the fundaments of a segmented vertebral column are established. But these arise, by histological metamorphosis, from an unsegmented connective-tissue matrix, in consequence of the appearance of a process of chondriiication.
 
All the conditions here only briefly touched upon are of farreaching significance for the question of the relation of the head- and trunk-skeletons to each other. For, as GEGENBAUR rightly points out, since the establishment of his segmental theory " the vertebral theory of the skull has become more and more a problem of the phylogenesis of the whole head."
I desire to give briefly and connectedly my own views upon this subject :
Theory concerning the Relation of the Head and its Skeleton to the Skeleton of the Trunk.
 
The segmentation of the vertebrate body begins with the walls of the primary body-sacs, the dorsal portion of which, abutting upon the chorda and neural tube, is divided by the formation of folds into successive compartments, the primitive segments.
 
Inasmuch as the voluntary musculature is developed from the walls of the primitive segments, it is the first system of organs in Vertebrates to be segmented.
 
The myomeric condition " myomerism ' -is the direct cause of a segmental arrangement of the peripheral nerve-tracts, for the motor nerves pertaining to a segment unite to form an anterior [ventral] root as they emerge from the spinal cord, and in the same manner the sensory nerves which come from a corresponding part of the skin together constitute a sensory root.
 
At a time when the segmentation of the musculature and of the peripheral nerve-tracts has already been effected, the skeleton is still unsegmented ; for it is represented by the chorda dorsalis alone. The soft mesenchyme, which envelops the chorda and the neural tube, and which becomes the matrix of the subsequently formed segmented axial skeleton, is still a continuous mass of cells, filling in the spaces between these organs.
 
 
 
THE ORGANS OF THE INTERMEDIATE LAYER OR MESENCHYME. 633
At this time the differentiation of head and trunk has already taken place. This is accomplished, first by the establishment of the higher sensory organs in the anterior portion of the body, secondly by the enlargement of the neural tube into the voluminous brainvesicles, thirdly by the formation of a regular series of visceral clefts in the walls of the head-gut, which thus also undergo a kind of segmentation (branchiomerism).
 
The reyion of the body which is thus metamorphosed into a head is from the beginning segmented, and is composed, as the Selachians show, of at least nine primitive segments.
 
The development of visceral clefts produces still further differences between head and trunk. By the appearance of visceral clefts, the front part of the body-cavity is divided up into several successive headcavities. By the disappearance of these cavities, parts corresponding to the thoracic and abdominal cavities have become obliterated. Further, there are developed out of the cells composing the walls of the head-cavities important masses of transversely striped muscles for moving and constricting the separate portions of the branchial region of the alimentary canal, whereas in the trunk the voluntary musculature arises exclusively from the primitive segments. In the trunk these masses of muscle spread out both dorsally over the neural tube and also ventrally into the wall of the thorax and abdomen, whereas in the head they remain limited to a small space and do not undergo any extensive development.
 
It is only after head and trunk have thus already become in a high
degree different that the cartilaginous axial skeleton begins to be formed.
 
The latter Ls therefore a structure of comparatively recent origin,
as it also is peculiar to the phylum, Vertebrata, and even here is
wanting in the lowest representative, Ainphioxus lanceolatus.
 
The development of the cartilaginous axial skeleton in the two chief regions of the body is from the beginning partly similar, partly dissimilar.
 
The development is similar in so far as the process of chondrification begins in both head and trunk in the perichordal connective tissue, then extends around the chorda both above and below, ensheathing it, and finally is continued into the connective-tissue layer that envelops the neural tube.
 
The dissimilarity is expressed in the occurrence or omission of segmentation. In the trunk under the influence of the musculature there arises a segmentation of the cartilaginous axial skeleton into firm vertebral pieces, alternating with mtervertebral ligaments which
 
 
634 EMBRYOLOGY.
 
remain in the connective-tissue state. In the head there is developed at once a continuous cartilaginous capsule around the brain-vesicles. The segmentation, which in this region is expressed in other systems of organs, in the formation of primitive segments and in the arrangement of the cranial nerves, does not occur in the corresponding part of the axial skeleton. Never in the course of the development of any Vertebrate has there been observed, as the first fundament of the primordial cranium, a succession of cartilaginous pieces, alternating with connective -tissue discs, and there seems to be no ground for assuming that a condition of this kind existed in earlier times. In the slight development of the muscles derived from the primitive segments of the head, and in the voluminous condition attained by the brain and sensory organs, are to be discerned, on the contrary, factors which have converted the head, at an early period, into a more rigid portion than the trunk. The cause, which in the trunk has made the segmentation of the axial skeleton necessary, has been wanting in the head.
 
During the last few years the opinion has been expressed by a number of persons (ROSENBERG, STOHII, FRORIEP) that in some classes of Vertebrates the occipital region of the primordial cranium is increased by fusion with vertebral fundaments of the neck-region, and thus, as it were, " is constantly advancing caudad." I leave undetermined to what extent this is true. GEGENBAUR combats the interpretation of STOHR, but describes a quite frequently occurring fusion of the cranial capsule with vertebrae in Bony Fishes. One thing only would I point out : the conception of the first unsegmented fundament of the primordial cranium which I have presented is not irreconcilable with the view that subsequently new vertebral segments may be added behind.
 
Besides the segmented condition of the vertebrce, a segmentation of the axial skeleton is also expressed in the appearance of ventral arches, which are repeated in regular order from before backwards. On the head they are designated as visceral arches, on the trunk as ribs.
 
The position of these skeletal parts also is dependent upon the first segmentation which affects the organisation of Vertebrates. For the ribs are developed between the muscle-segments by a process of chondrification in the connective-tissue plates separating themthe intermuscular ligaments ; while the visceral arches are dependent upon the visceral clefts, by which the ventral part of the head-region is divided into a number of successive segments.
 
It cannot be concluded from the existence of ribs and visceral
 
 
THE ORGANS OF THE INTERMEDIATE LAYER OR MESENCHYME. 635
arches that the corresponding skeletal axis must likewise have been segmented. They are only an indication of the segmentation of the region of the body to which they belong.
 
That the segmentation of the head which is present in the embryo is more or less obliterated in the adult Vertebrate depends upon two causes. First the primitive segments are only slightly developed, furnishing unimportant muscles, and in part wholly degenerate ; secondly the visceral skeleton is subjected to profound metamorphoses. Especially in the higher Vertebrates it experiences such a degeneration and metamorphosis, that finally nothing of the original seginental arrangement of its parts (palato-maxillary apparatus, auditory ossicles, hyoid bone) is left.
 
 
 
B. The Development of the Skeleton of the Extremities.
 
A description of the skeleton of the extremities should be preceded by a few words in regard to the fundaments of the limbs themselves. These at first appear as small elevations [limbbuds] at the sides of the trunk in front and behind (tig. 339). That they belong more to the ventral than to the dorsal surface of the body is evident from the fact that they are innervated by the ventral branches of the spinal nerves.
 
Moreover, the
limbs appear to
belong to a large number of tr link-segments. This is to be inferred both
from the method of the distribution of nerves and also from the source
 
 
oe
 
 
 
Fig. 339. Very young human embryo of the fourth w eek 4 mm long, neck-rump measurement ; taken from the uterus of a suicide 8 hours after her death, after RABL.
 
au, Eye ; ng, nasal pit ; uk; lower jaw ; zb, hyoid arch ; s", *, third and fourth visceral arches ; li t protrusion of the wall of the trunk caused by the growth of the heart ; us, boundary between two primitive segments ; oc, ue, anterior and posterior linibs.
 
 
 
636 EMBRYOLOGY.
 
of their musculature. For the anterior and posterior limbs always receive their nerves from a large number of spinal nerves. The muscles are derived from the same source as the whole musculature of the trunk from the primitive segments.
 
It has not yet been possible to establish the derivation of the musculature in Mammals and Man. For the limb-buds consist of a mass of small, closely crowded cells ; it is impossible to state which of these belong to the mesenchyme, which to the musculature, or which to the nerves. The conditions in lower Vertebrates, on the contrary, are much more favorable.
 
In Selachians the fins, which correspond to the limbs of the higher Vertebrates, contain, even at the time of their formation as small plates, distinctly recognisable embryonic gelatinous tissue, which is covered in by the epidermis. An important discovery by DOHRN has established that there grow into the gelatinous tissue of the fin two buds from each of a large number of primitive segments ; the buds then become detached from their parent tissue and each is divided into a dorsal and a ventral half the fundaments of extensor and flexor musculature. Each fin therefore contains a series of muscular fundaments, which have arisen segmentally and are arranged one behind another, a fact which has its weight in many other questions touching the origin of the limbs.
 
In Man the fundaments of the limbs take on a definite form as early as the fifth week. The outgrowths have become enlarged and divided into two regions, of which the distal becomes the hand, or foot. In the case of the anterior extremity the front margin of the hand already begins to acquire indentations, by which the first fundaments of the fingers are indicated. In the sixth week the three chief divisions of the limbs are recognisable, for the proximal portion is now marked off by a transverse furrow either into arm and fore-arm or into thigh and leg. Now, too, on the foot the toes are indicated by constrictions, but less distinctly than are the fingers on the hand.
 
In the seventh week there are to be observed at the tips of the fingers claw-like appendages, consisting of epidermal cells the primitive nails. As HENSEN remarks, " The similarity of the hand at this stage to the anterior extremity of a Carnivore viewed from the sole is striking ; in addition to the toe-like brevity and thickness of the fingers, the pads are well developed."
With their enlargement the limbs apply themselves to the ventral surface of the embryo, being directed obliquely from in front back
 
 
THE ORGANS OF THE INTERMEDIATE LAYER OR MESENCHYME. 637
ward [and ventracl], the anterior limbs more obliquely than the posterior. In both of them the future extensor side lies dorsal, the flexor side ventral. Both the radial and tibial margins with the thumb and great toe are directed cephalad, the fifth finger and the fifth toe caudad.
 
By this and by the fact that the limbs belong to several trunksegments are explained certain conditions in the distribution of the nerves of the upper extremity. In the case of the arm "the radial side is supplied with nerves (axillaris, musculo-cutaneus), whose fibres are referable to the fifth, sixth, and seventh cervical nerves. Upon the ulnar side, on the contrary, are found nerves (n. cutaneus medialis, 11. medius, and n. ulnaris) whose origin from the lower secondary trunk of the plexus discloses their derivation from the eighth cervical and first dorsal nerves " (SCIIWALBE).
 
In the further course of development both limbs alter their original position, the anterior to a greater extent than the posterior, inasmuch as they undergo a torsion around their long axes in opposite directions. In this way the extensor side of the upper arm becomes directed backward [caudad], that of the thigh forward ; radius and thumb are now directed laterad, tibia and great toe mediad. These alterations in position due to torsion are naturally to be taken into account in determining the homologies of the anterior and posterior extremities, so that radius corresponds to tibia and ulna to fibula.
 
In the originally homogeneous cell-mass the fundaments of the skeleton and musculature are gradually differentiated from each other, owing to the fact that the cells acquire a more definite histological character. In this connection the following phenomenon is to be observed :
The parts of the skeleton of the extremity are not all established at the same time, but follow a definite sequence, in somewhat the same manner as, in the development of the axial skeleton, the process of segmentation begins in front and progresses backward. So in the limbs the proximal skeletal elements (i.e., those which are situated nearer to the trunk) are formed sooner than the distal ones.
 
This is the most strikingly apparent in the case of the fingers and toes. Whereas the first phalanx has been differentiated from the surrounding tissue in embryos of the fifth and sixth week, the second and third are not at that time distinguishable ; the ends of the fundaments of fingers and toes still consist of a mass of small cells in process of growth. In this mass the second phalanx is then differentiated, and at last the third.
 
 
 
638 EMBRYOLOGY.
 
Furthermore the formation of the anterior limbs outstrips somewhat that of the posterior.
 
In the development of the skeleton of the extremities there are to be recognised, as in the vertebral column and the skull, three different stages, the stage of the membranous, that of the cartilaginous, and that of the osseous fundament.
 
After these general remarks I turn to the detailed description of (1) the pectoral and pelvic girdles, (2) the skeleton of the appendage, which projects free from the surface of the trunk, and (3) the formation of joints.
 
() Pectoral and Pelvic Girdles.
 
The fundaments of the girdles of the limbs consist each of a pair of curved pieces of cartilage, which are imbedded under the skin in the muscles of the trunk, and which bear near the middle an articular surface for the reception of the skeleton of the free extremity. By this each cartilage is divided into a dorsal half, near the vertebral column, and a ventral half. The former is converted in Mammals and Man into a broad shovel-shaped piece ; the ventral half, which reaches to, or nearly to, the median plane, is, on the contrary, divided into two diverging processes, an anterior and a posterior. The cartilaginous pieces thus distinguishable ossify from special centres, and thereby acquire a higher degree of independence.
 
The shoulder-blade (scapula) of Man is at first a cartilage of a form similar to that of the adult, except that the basis scapulae is less developed. In the third month ossification begins at the collum scapulse. However, the margins, the spine, and the acromion remain for a long time cartilaginous, and indeed are in part so even at the time of birth. There arise in them here and there accessory centres during childhood.
 
From the articular part of the shoulder-blade there runs ventrally a cartilaginoiis process, which is short in Man, but in other Vertebrates is of considerable size and reaches down to the sternum. It corresponds to the posterior of the previously mentioned diverging processes into which the ventral part of the cartilaginous arch is divided, and is known in comparative anatomy as pars coracoidea. In Man it is only slightly developed. Its great independence, however, is made evident by its acquiring in the first year after birth a separate centre of ossification. From this there gradually arises a bony element (os coracoideum), which is joined to the shoulder-blade until
 
 
THE ORGANS OF THE INTERMEDIATE LAYER OR MESENCHYME. 639
the .seventeenth year by a strip of cartilage, and may therefore be detached. Afterwards it is united with the scapula by bony substance and constitutes the coracoid process. Still later the fusion of the accessory centres previously mentioned takes place, to which, however, no great morphological importance attaches.
 
There are two different views concerning the place which the clavicle takes in the shoulder-girdle.
 
According to GOETTE, HOFFMANN, and others, it belongs to the primordial skeletal parts, which are preformed in cartilage, and corresponds to the anterior ventral process, which was present in the primitive form of the shoulder-girdle. According to GEGENBAUR it is a covering bone which has entered into union with the cartilaginous skeleton in the same way as the covering bones of the skull have with the primordial cranium.
 
It is the peculiar method of the development of the clavicle that has caused this divergence of opinion. This is the first bone to be formed in Man ; it begins to be ossified as early as the seventh week. The earliest bony piece, as GEGENBAUR was the first to ascertain, is developed out of wholly indifferent tissue. Then there are added at both ends masses of cartilage, which are softer and provided with less intermediate substance than the ordinary embryonic cartilage. They serve, as in other bones that are preformed in cartilage, for the elongation of the clavicle at both ends. There is also developed in the sternal end, between the fifteenth and twentieth years, a kind of epiphysial centre, as KOLLIKER states ; this fuses sometimes as late as the twenty-fifth year with the main piece.
 
The original conditions are the most faithfully preserved in the pelvic girdle, even in Man and Mammals. The first fundament of the girdle consists of a right and a left pelvic cartilage, which are united ventrally in the symphysis by means of connective tissue, and each of which has at its middle an articular fossa. Each pelvic cartilage is composed of an expanded part extending dorsally from the articular depression, the iliac cartilage, which is joined to the sacral region of the spinal column, and two ventral cartilaginous rods, pubis and ischium, which, meeting in the symphysis, enclose the foramen obturatorium.
 
It is stated by ROSENBERG that the pubic cartilage is at first formed independently, but that it soon fuses with the other cartilages at the acetabulum.
 
Ossification begins at the end of the third month in three places, and thus are formed a bony ilium, os puhis, and ischium at the
 
 
640 EMBRYOLOGY.
 
expense of the cartilage, of which, however, considerable remnants are still present at the time of birth. .For tho, whole crest of the ilium, the rim and fimdus of tho acetabulum, and the whole tract from the tnberosity of the ischium to tho spine of the pnbis is still cartilaginous.
 
After birth the growth of the three bony pieces advances toward tho acetabulum, where they all meet, being however separated, up to the time of puberty, by strips of cartilage, which together form a three-rayed figure. At about the eighth year both the ascending and descending rami of pubis and ischium fuse with each other, so that at this time each hip-bone consists of two pieces joined by cartilage at the acetabulum the ilium and an ischio-pubic bone. These do not become united into one piece until the time of puberty.
 
As in the pectoral girdle, so also in the pelvic girdle, there occur accessory centres of ossification ; of these one, which sometimes arises in the cartilage of the acetabulum, is the most important, and is described as os acetabuli. Others arise in the cartilaginous crest of the ilium, in the spines and tubercles, and in the tuberosity of the ischium. They are not united with the chief bones until the end of the period of growth.
 
(b) Skeleton of the Free Extremity.
 
All skeletal parts of the hand, fore-arm, and arm, as well as of the foot, leg, and thigh, are originally solid pieces of hyaline cartilage, which early acquire the general forms of the bones that subsequently replace them. They are marked off from their surroundings by a special fibrous layer of connective tissue, the perichondrium.
 
From the beginning of the third month the process of ossification takes place in the larger skeletal pieces, by means of which the cartilaginous tissue is destroyed and replaced by osseous tissue, in the same manner as in the vertebral column. In this process several general phenomena regularly make their appearance ; I shall go somewhat into the details of these, without however taking into account the complicated histological changes, information concerning which is given in text-books of histology.
 
The process of ossification takes externally a somewhat different turn according as the cartilages are small and uniformly developed in all directions, as in the wrist and ankle, or have become more elongated,
In the first case the course of development is more simple. From
 
 
THE ORGANS OF THE INTERMEDIATE LAYER OR MESENPHYME. 041
the perichondriurn vascular, richly cellular connective-tissue processes grow into the cartilage, dissolve its matrix, and unite with one another in its centre. There arises a network of medullary [marrow] cavities, in the vicinity of which there is a deposit of salts of lime (a provisional calcification). The medullary spaces extend farther and farther by destruction of the cartilaginous substance. Then there are secreted by the superficially located medullary cells bone-lamella?, which gradually increase in thickness. The osseous nucleus thus formed slowly increases in size, until finally the cartilage is almost entirely replaced, only a thin layer of it remaining at the surface as a covering to the bone.
 
The ossification of the wrist- and ankle-bones is therefore purely endochondral, and proceeds ordinarily from one, sometimes from two, centres of ossification. It does not begin until very late in the first year after birth. The only exception occurs in the foot, where the os calcis and astragalus acquire a bony nucleus in the sixth and seventh months, and the cuboid begins to ossify a short time before birth. In the others ossification takes place after birth, and, as KO'LLIKER states, in the following order :
I. In the hand. (1) Os magnum and unciform (first year) ; (2) cuneiform (third year) ; (3) trapezium and lunar (fifth year) ; (4) scaphoid and trapezoid (sixth to eighth year) ; (5) pisiform (twelfth year).
 
II. In the foot. (1) Os scaphoideum (first year) ; (2) internal and middle cuneiform (third year) ; (3) external cuneiform (fourth year).
 
Concerning the cartilaginous fundaments of a special centrale carpi, which usually is not retained as a separate carpal element (ROSENBERG), as well as a special intermedium tarsi or trigonum (BARDELEBEN), the text-books of comparative anatomy are to be consulted.
 
The process of ossification is more complicated in the long cartilages, in which, moreover, it begins much earlier, usually even in the third month of embryonic life. The course of ossification is fairly typical.
 
At first a perichondral ossification takes place midway between the ends of each cartilage in the humerus and femur, tibia and fibula, radius and ulna. From the perichondrium there is deposited upon the already formed cartilage bony tissue instead of a cartilaginous matrix, so that the middle portion of the cartilage becomes ensheathed in a bony cylinder, which is continually increasing in thickness.
 
4J
 
 
042 EMBRYOLOGY
The further growth of the skeletal element thus composed of two tissues proceeds in two ways : first by growth of the cartilage, and secondly by increase of bony substance.
 
The cartilaginous tissue increases at both ends of the skeletal piece and contributes to the increase of the latter both in length and thickness. In the middle, on the contrary, where it is enveloped in a bony cylinder, it ceases to grow. Here there is a continual addition of new bony lamellae upon those already formed ; they are produced by the original perichondrium, or, as one may now more properly say, by the periosteum.
 
In this process the successive lamellae extend farther and farther toward the two ends of the skeletal piece ; new portions of the cartilage are being continually ensheathed in bone and restricted in their growth.
 
The periosteal bony sheath assumes in consequence the form of two funnels united at their apices.
 
The cartilage which fills up the funnels early undergoes a gradual metamorphosis and degeneration. From the osseous sheath there grow into it connective-tissue strands with blood-vessels, which dissolve the matrix and produce larger and smaller marrow-cavities. Then, by the secretion of osseous tissue at the surface of the persisting remnants of cartilage, there is developed a spongy bonesubstance, which fills up the funnel -shaped cavities of the compact bony mantle produced by the periosteum. The spongy bone is, however, only an evanescent structure. It in turn is gradually dissolved, beginning at the middle of the skeletal element, and its place is occupied by a very vascular marrow. In this way there arises in the originally quite compact cartilaginous fundament the large central medullary cavity of the long bones.
 
During these processes the two ends still remain cartilaginous, and serve for a long time by their growth to increase the length of the skeletal element. They are designated as the two epipliyses, in distinction from the middle piece, which is the first to ossify, and which has received the name diaphysis. The latter increases in size at the expense of the epiphysial cartilages, for the endochondral process of ossification progresses, with a very distinct line of ossification, toward both ends.
 
A new complication in the development of the tubular (long) bones arises either a short time before or in the first years after birth. There are then developed in the middle of each epiphysis special centres of ossification, the so-called epipliysial nuclei ; there
 
 
THE ORGANS OF THE INTERMEDIATE LAYER OR MESENCHYME. 643
are first produced, in the manner previously described, vascular canals, which arise by the dissolution of the cartilaginous substance ; the canals unite to constitute large medullary spaces, at the surfaces of which osseous tissue is then secreted.
 
By a slowly progressing enlargement of the bony nucleus, which continues for years, the epiphysial cartilage is gradually converted into a spongy osseous disc, being finally reduced to small remnants. First, there is preserved, as an investment of the free surface, a layer only a few millimetres thick, which constitutes the " articular cartilage." Secondly, there remains for a long time a thin layer of cartilage between the older, bony middle piece and the bony disc-like epiphysis, and this serves to keep up the elongation of the skeletal part. For the cartilage grows vigorously by the proliferation of its cells, and thus is being renewed as fast as its two flat surfaces are dissolved away by the endochondral ossification which takes place at its expense, both by the growth of the bony epiphyses and, to a much greater extent, by that of the more rapidly elongating diaphysis.
 
Thus it happens that long bones which have not yet ceased .growing can be divided into three pieces, if the organic parts are removed by maceration. A fusion into a single osseous piece does not take place until, at the time of maturity, the increase in the length of the body has ceased. Then the thin plates of cartilage between the diaphysis and its two epiphyses are broken down and converted into bony tissue. From this time forward a further increase in the length of the bone is impossible.
 
Besides the three typical and chief centres already described, from which the ossification of the cartilaginous fundament of a tubular bone proceeds, there are established in many cases smaller centres of ossification of secondary importance, which are denominated accessory bone-nuclei. They always arise in the later years, when the epiphyses are well developed, and sometimes not until they are in process of fusion with the diaphysis. They then appear at places where the cartilaginous fundament possesses elevations and projections, as in the tubercles of the humerus, in the trochanters of the femur, the epicondyles, etc. They serve for the conversion of these elevations into osseous masses, which are generally the last to fuse with the chief bone.
 
After this general description, I add some detailed statements about the formation and the number of the move important bony nuclei in the fundaments of the separate tubular bones, concerning which we have the extensive investigations of SCHWEGEL.
 
 
 
G44 EMBRYOLOGY.
 
1. The diaphysis of the humerus ossifies in the eighth week. Epiphysial nuclei are not formed until after birth, at the end of the first or beginning' of the second year. In the second year there appear accessory nuclei in the tuberculum majus and minus ; during and after the fifth year in the epicondyles also.
 
2. The diaphyses of the radius and ulna also begin to ossify in the eighth week. Epiphysial nuclei do not appear until between the second and the fifth years. Accessory nuclei are observed rather late in the styloid processes.
 
3. The metacarpals begin to ossify in the ninth week, but, with the exception of the metacarpal of the thumb, there arises only one epiphysis, which is at the distal end. This acquires in the third year its own centre of ossification.
 
4. The ossification begins in the phalanges at the same time as in the metacarpals.
 
5. The femur begins to ossify in the seventh week. A sliort time before birth there is formed in the distal ejiipJiysis a centre of ossification, which is a part of the evidence that a child has been carried to the full time, and therefore possesses a certain importance for forensic purposes. After birth an epiphysial nucleus soon appears in the head of the femur. Accessory nuclei are formed in the fifth year in the trochanter major, in the thirteenth or fourteenth in the trochanter minor.
 
G. Tibia and fibula acquire epiphysial nuclei in the first and third years after birth, first at the proximal, then at the distal end, the ossification in the fibula occurring about a year later than that in the tibia. GEGENBAUR regards this as indicating a subordination of the functional importance of the fibula in comparison with the tibia.
 
7. The patella begins to ossify in the third year.
 
8. To the metatarsals and the phalanges of the toes applies in general all that has been said about the corresponding parts of the hand.
 
 
 
(c) Development of the Joints.
 
Inasmuch as the separate pieces of cartilage in the body are formed by histological differentiation in the connective-tissue layers, they are at first united to one another by remnants of the parent tissue. This generally acquires a more compact fibrous condition and is converted into a special ligament.
 
Such a union of the separate skeletal elements is the prevailing method in the lower Vertebrates, as, e.g., in the Sharks. In the higher Vertebrates, including Man, it is retained in many, but not all, place?, as, e.g., in the vertebral column, where the bodies of the vertebrae are joined to each other by intervertebral discs of connective tissue. But at the places where the apposed skeletal parts acquire greater freedom of motion upon each other, there appears, in place of the simpler connective-tissue union, the more complicated articular connection.
 
 
 
THE ORGANS OF THE INTERMEDIATE LAYER OR MESENCHYME. 645
In the development of the joints the following general phenomena occur :
Young cartilaginous fundaments, as, e.g., those of the thigh and leg, are in early stages separated at the place where the articular cavity is subsequently formed by a very cellular intermediate tissue (the intermediate disc of HENKE UND EEYHER). This subsequently diminishes in extent, because the ends of the cartilages grow at its expense. In many cases it disappears entirely, so that the terminal surfaces of the skeletal parts concerned are for some distance in immediate contact.
 
The specific curvature of the articular surfaces is by this time more or less well established. This is accomplished at a time when there is as yet no articular cavity, and when, moreover, movements of the skeletal parts cannot be executed, because the muscles are not capable of functioning.
 
From this it follows that during embryonic life the articular surfaces cannot acquire their specific form under the influence of muscular activity, and that they are not formed, as it were, by attrition and adaptation to each other in consequence of definite recurrent movements in a simply mechanical way, as has been assumed by many. The early appearing typical form of the joint seems therefore to be inherited (BERNAYS). Muscular activity can be effective only for alterations at later stages; it is, however, not without influence in the further development and formation of the articular surfaces.
 
When, after the disappearance of the intermediate tissue, the surfaces at the ends of the developing cartilages come into immediate contact, there arises between them a narrow fissure as the first fundament of the articular cavity. This is bounded directly by the hyaline articular cartilage, which does not here possess any perichondrium. Then a sharper delimitation of the articular cavity from the surrounding connective tissue gradually takes place, inasmuch as a firmer connective- tissue layer, which becomes the capsular ligament, is developed from one cartilage to the other, and additional fibrous tracts are converted into separate tense articular ligaments.
 
The process of development takes a somewhat different course when the articular surfaces do not fit into each other. In these cases the ends of the cartilages cannot come into immediate contact in the manner previously described ; they now remain separated by more or less considerable remnants of the richly cellular intermediate
 
 
646 EMBRYOLOGY.
 
tissue, which then assumes more and more the condition of compact fibrous tissue.
 
When the intermediate tissue is preserved in its whole extent, there arises a fibro- cartilaginous interarticular disc (intermediate or interpolated cartilage), which is inserted as an elastic cushion between the skeletal pieces. There is formed an articular fissure between the ligamentous disc and the terminal surfaces of each of the articular cartilages, or, in other words, there is developed an articular cavity, which is divided into two by means of an interpolated disc.
 
Finally, a special modification of the joint occurs when the cartilages are partly in contact and partly remain separated by intermediate tissue. In this case there appears at the place of contact a single articular cavity ; laterally, however, this is enlarged by the incongruent parts of the cartilaginous surfaces becoming split off from the intermediate tissue separating them. Thus there arises an articular cavity which, it is true, is single, but into which are thrust from the articular capsule the metamorphosed products of the intermediate tissue, which constitute the so-called semi-lunar fibre-cartilages or the menisci, as in .the case of the knee-joint.
 
As was previously described in treating of the development of the bones of the extremities, there is preserved, even after the termination of the process of ossification, an exceedingly small remnant of the cartilaginous fundament, which forms on the articular surfaces a cartilaginous covering only a few millimetres thick. The articular ends of all bones that are developed out of a cartilaginous fundament possess such a covering.
 
It is different when bones that have been produced directly in connective tissue (the covering bones) are united to each other by a veritable joint. Such a case occurs in the articulation of the lower jaw in Mammals. The glenoid process of the lower jaw. as well as the glenoid fossa of the squamous portion of the temporal bone, is in this case covered with a thin layer of unossified tissue. It looks like cartilage, and usually is described as such. But microscopic examination shows that it is composed exclusively of layers of connective-tissue fibres.
 
As there are bones which are preformed, in cartilage and others which are preformed in connective tissue, so a distinction must be made between joints with a covering of hyaline cartilage and joints witli a covering of fibrous connective substance.
 
 
 
THE ORGANS OF THE INTERMEDIATE LAYER OR MESENCHYME. 647
SUMMARY. A. The Vertebral Column.
 
1. During development the vertebral column passes through several (from lower to higher) morphological conditions, of which the lower are permanently preserved in the inferior classes of Vertebrates, whereas in the higher classes they appear only at the beginning of development and are then replaced.
 
2. In the axial skeleton three different stages of development are distinguished :
(1) As chorda dorsalis (notochord),
(2) As cartilaginous and
(3) As osseous vertebral column.
 
3. The chorda is developed out of a tract of cells (chorda-entoblast, fundament of the chorda) lying below the neural tube and belonging to the inner germ-layer, from which it is detached by abstriction. (chordal folds).
 
4. The chorda is a rod composed of vesiculated cells and bounded superficially by a firm sheath ; it begins with a pointed end beneath the mid-brain vesicle (in the region of the future sella turcica of the cranial floor) and reaches to the blastopore (primitive groove).
 
5. The chorda persists as a permanent skeletal structure in Amphioxus and the Cyclostomes.
 
6. A cartilaginous vertebral column is found in the adults of the Selachians and some of the Ganoids, while in the remaining Vertebrates it appears more or less during development as a forerunner of the bony vertebral column.
 
7. The cartilaginous vertebral column is developed by histological metamorphosis out of embryonic connective tissue, a part of which envelops the chorda as skeletogenous chordal sheath, and a part forms a thin continuous envelope (membranous vertebral arches) around the neural tube.
 
8. The process of chondrification begins 011 both sides of the chorda, progresses around it both above and below, and thus forms a cartilaginous ring, the body of the vertebra, from which the process of chondrification advances dorsally into the membranous envelope of the neural tubes, producing the arches of the vertebrae and ceasing with the formation of the vertebral spines.
 
9. It is not until the beginning of the process of chondrification in the unsegmented, connective-tissue, skeletogenous chordal sheath
 
 
048 EMBRYOLOGY.
 
that the axial skeleton undergoes a segmentation into separate like portions, which are situated one behind another ; to accomplish this, remnants of the parental tissue do not chondrify, but become, between the bodies of the vertebrae, the intervertebral discs, and, between the arches, the ligamenta intercruralia, etc.
 
10. The segmentation of the vertebral column has been dependent in its origin upon the segmentation of the musculature, and has been effected in such a way that skeletal segments and muscular segments alternate with one another, and that the longitudinal muscle-fibres, which lie alongside the axial skeleton, are attached by their anterior and posterior ends to two [adjacent] vertebrae and are capable of moving them upon each other.
 
11. The chorda is more or less restrained in its growth by the cartilaginous bodies of the vertebrae surrounding it, and degenerates in different ways in the different classes of Vertebrates ; in Mammals the part located in the body of tne vertebra is completely obliterated, whereas a remnant of it is preserved between vertebrae and becomes the jelly-core of the intervertebral disc.
 
12. The cartilaginous vertebral column is converted in most Vertebrates into a bony one, by the breaking down of the cartilaginous tissue, which begins at different places, and its replacement by bony tissue. (Formation of bone-nuclei or centres of ossification.)
13. The ossification of each cartilaginous vertebral fundament in Mammals and Man proceeds from three centres, from one in the body and one in each half of the arch, to which subsequently certain accessory centres are added.
 
14. With each vertebral segment there is associated a pair of ribs, which arise by a process of chondrification in the layers of tissue which separate the muscle-segments (the ligamenta intermuscularis).
 
15. In Man the various regions of the vertebral column are produced by metamorphosis of the vertebral and costal fundaments.
 
(1) The thoracic part of the vertebral column (dorsal vertebrae)
is characterised by the following peculiarities : the ribs attain to complete development ; a part of them become expanded at their ventral ends, and united to form the two sternal bars, by the fusion of which the unpaired sternum is produced. (Fissura sterni, an arrested formation.)
(2) In the cervical and lumbar regions of the column the funda
ments of the ribs remain small, and fuse with outgrowths from the vertebrae the transverse processes to form
 
 
THE ORGANS OF THE INTERMEDIATE LAYER OR MESENCHYME. 649
the lateral processes. In the neck-region there is retained, between the transverse process and the rudiment of the rib, the foramen transversarium for the vertebral artery.
 
(3) Atlas and epistropheus [axis] assume special forms, owing to
the fact that the body of the atlas remains separate from the fundaments of its arch, and unites with the body of the axis to form its odontoid process. (Separate centre of ossification in the odontoid process.)
(4) The sacrum results from the fusion of five vertebrae and the
sacral ribs belonging to them. The latter by their fusion produce the so-called massse laterales, which bear the articular surfaces for the ilium.
 
B. The Head- Skeleton.
 
16. The skull, like the vertebral column, passes through three morphological conditions, which are designated as membranous and as cartilaginous primordial cranium and as bony cranial capsule.
 
17. The membranous primordial cranium consists of
(1) The anterior end of the chorda, which extends to the anterior
margin of the mid-brain vesicle, and
(2) A connective-tissue layer, which surrounds the chorda as
skeletogenous layer, and also furnishes a membranous investment around the five brain- vesicles.
 
18. The cartilaginous primordial cranium arises by a histological metamorphosis of the membranous one.
 
(1) At the sides of the chorda there are first formed two car
tilaginous rods, the two parachordals, which soon grow around the chorda both above and below, and become united into a single cartilaginous plate.
 
(2) In front of the parachordals RATHKE'S trabeculse cranii
make their appearance ; their posterior ends soon unite with the parachordal cartilages, their anterior ends become enlarged and by fusing with each other produce the ethmoid plate ; in the middle they remain for a long time separate and embrace the hypophysis (region of sella turcica).
 
(3) From the cartilaginous base of the cranium thus produced,
the process of chondrification, as in the development of the vertebral column, first extends into the lateral walls, and at last into the roof of the membranous primordial cranium, partly enclosing the higher sensory organs.
 
 
 
650 EMBRYOLOGY.
 
19. In the Selachians the cartilaginous primordial cranium is a permanent structure, and possesses rather thick uniform walls ; in Mammals and Man, on the contrary, it is of only short duration, serving as foundation for the bony cranial capsule that takes its place; it is therefore less completely developed than in Selachians, for only the base and lateral parts are in all cases cartilaginous, whereas the roof presents large openings closed by dermal membranes.
 
20. From its relation to the chorda dorsalis, there are distinguishable in the cartilaginous primordial cranium two chief portions, a vertebral (chorda!) and a non-vertebral (prechordal), or, according to its relations to the sensory organs, it may be divided into four regions ethmoidal, orbital, labyrinthal, and occipital.
 
21. As the ribs are associated with the vertebral column in the form of ventral arched structures, so also the visceral skeleton is united to the primordial cranium in the head-region.
 
22. The visceral skeleton is composed of segmented cartilaginous rods, which have arisen by a process of chondrification in the tissue of the membranous visceral arches between the successive visceral clefts.
 
23. The cartilaginous throat- or visceral arches are well developed only in the lower Vertebrates (permanently in the Selachians), and are distinguished, according to differences of position and form, as jawarch, hyoid arch, and branchial arches, the last being variable in number.
 
24. The jaw-arch is divided into the cartilaginous upper jaw (palato-quadratum) and the cartilaginous lower jaw (rnandibulare) ; the hyoid arch into the hyomandibulare, the hyoides, and the unpaired copula.
 
25. In Mammals and Man the cartilaginous visceral skeleton attains only a very rudimentary condition, and is converted into the cartilaginous fundaments of the three auditory ossicles and the hyoid bone.
 
26. In the membranous jaw-arch arise
() The incus, which corresponds to the palato-quadratum of lower Vertebrates ;
(b) The malleus, which is the representative of the articular
part of the cartilaginous mandibulare ; and
(c) The cartilage of MECKEL, which corresponds to the remain
ing portion of the mandibulare, but which afterwards completely degenerates.
 
 
 
THE ORGANS OF THE INTERMEDIATE LAYER OR MESENCHYME. 651
'27. The membranous hyoid arch furnishes, [beginning with] its uppermost part,
(a) The bow of the stapes, whereas its plate is derived from the cranial capsule and is, as it were, cut out to form the fenestra ovalis, (6) The processus styloideus,
(c) The ligamentum stylohyoideum, and
(d) The lesser horn and body of the hyoid bone.
 
28. The third membranous visceral arch is chondrified only in its lowest [ventral] part, to form the greater horn of the hyoid bone.
 
29. At no stage of its development does the primordial cranium exhibit evidence that, like the vertebral column, it is composed of separate segments.
 
30. The original segmentation of the head is expressed in only three ways in the appearance of several primitive segments (myotomes), in the arrangement of the cranial nerves, and in the fundament of the visceral skeleton.
 
31. The primordial cranium is therefore an unsegmented skeletal fundament in a region of the body that is segmented in another manner.
 
32. The ossification of the head-skeleton is a much more complicated process than that of the vertebral column.
 
33. Whereas in the vertebral column there are developed bones of only one kind, through substitution for cartilage, there are to be distinguished in the ossification of the head-skeleton, according to their formation and source, two different kinds of bone primary and secondary.
 
34. The primary bones of the head arise in the cartilaginous primordial cranium and visceral skeleton, like the separate bonenuclei in the cartilaginous vertebral column.
 
35. The secondary bones, covering or membrane-bones, arise outside the primordial skeleton of the head in the connective-tissue foundation of the skin and mucous membrane ; they are therefore dermal and mucous-membrane ossifications, and constitute in lowerVertebrates a portion of a dermal skeleton that covers the surface of the whole body.
 
36. The covering bones are developed in some instances, which can be regarded as reproductions of the original method, by fusion of the bony bases of numerous denticles which arise in the skin and mucous membrane.
 
 
 
052 EMBRYOLOGY.
 
37. Primary and secondary bones sometimes remain separate in later stages, sometimes they fuse with each other to form bonecomplexes, like the temporale and sphenoidale.
 
38. After the conclusion of the process of ossification only unimportant remnants of the primordial cranium persist as the cartilaginous partition of the nose and as the nasal cartilages.
 
C. The Skeleton of the Extremities.
 
39. The skeleton of the limbs, excepting the clavicle, the development of which exhibits many peculiarities, is established in the cartilaginous stage. (Cartilaginous shoulder-girdle, cartilaginous pelvic girdle, cartilages of arm and leg.)
40. The ossification takes place, in the same manner as in the vertebral column and primordial cranium, from centres of ossification by disintegration of cartilaginous tissue and its replacement by osseous tissue.
 
41. The most of the small cartilages of the wrist and ankle ossify from a single bone-nucleus, but the larger flat cartilages of the shoulder and pelvic girdles from several centres.
 
42. The cartilaginous fundaments of the tubular [long] bones ossify at first in the middle, which region is designated as diaphysis, whereas their two ends the epiphyses remain for a long time cartilaginous, and are the means of the elongation of the skeletal element.
 
43. In Man the cartilaginous epiphyses begin to ossify from centres of their own (epiphysial nuclei), some of them in the last month before, others not until after birth.
 
44. The fusion of the bony diaphysis with the bony epiphyses does not take place until the termination of the growth of the skeleton and body in length, and is accompanied by the removal of the intervening cartilaginous tissue.
 
45. Before growth is at an end the tubular bones can be divided into a larger middle piece (diaphysis) and two small bony epiphyses.
 
46. Of the cartilaginous fundament of a tubular bone there is preserved only a small remnant as a cartilaginous covering of the articular ends (articular cartilage).
 
47. The medullary cavity of the tubular bones is formed by the resorption of the spongy bone-substance that first replaced the cartilage.
 
48. Whereas the articular ends of bones preformed in cartilage are covered over with hyaline cartilage, the articular surfaces of
 
 
LITERATURE. 653
bones of connective-tissue origin (covering bones) present an investment of fibrous connective substance (articulation of the jaw).
 
49. The form of the articular surfaces is determined at a time when an influence on the part of the musculature is not to be considered.
 
 
 
LITERATURE.
 
Development of the Diaphragm and Pericardium.
 
Cadiat, M. Du developpement de la partie cephalothoracique de 1'embryon,
de la formation du diaphragma, des pleures, du pericarde, du pharynx et
de 1'oesophage. Jour, de VAnat. et de la Physiol. T. XIV. 1878. Faber. Ueber den angeborenen Mangel des Herzbeutels in anatomischer,
entwicklungsgeschichtlicber und klinischer Beziebung. Yirchow's Archiv.
 
Bd. LXXIV. 1878, p. 173. His, W. Mittheilungen zur Embryologie der Saugethiere und des Menscben.
 
Arcbiv f. Anat. u. Physiol. Anat, Abth. 1881. Lockwood. The Early Development of the Pericardium, Diaphragm and
Great Veins. Philos. Trans. Roy. Soc. London, 1888. Vol. CLXXIX. P..
 
1889, p. 365. And Proceed. Pioy. Soc. London. Vol. XLIII. 1888, p. 273. Ravn. Bildung der Scheidewand zwischen Brust- und Bauchhohle in Sauge
thier-Embryonen. Biol. Centralblatt, Bd. VII. 1887. Ravn. Ueber die Bildung der Scheidewand zwischen Brust- und Bauchhohle
in Saugethier-Embryonen. Archiv f. Anat. u. Physiol. Anat. Abth. 1889. Ravn. Untersuchungen liber die Entvvicklung des Diaphragmas und der
benachbarten Organe bei den Wirbelthieren. Archiv f. Anat. u. Physiol.
 
Anat. Abth. 1889. Suppl.-Band. Uskow, W. Ueber die Entwicklung des Zwerchfells, des Pericardiums und
des Coeloms. Archiv f. mikr. Anat. Bd. XXII. 1883. Waldeyer. Ueber die Beziehungen der Hernia diaphragmatica congenita
zur Entwicklungsweise des Zwerchfells. Deutsche medic. Wochenschrift.
 
No. 14. 1884.
 
Development of the Heart and Blood-vessels.
 
Bernays, A. C. Entwicklungsgeschichte der Atrioventricularklappen. Mor
phol. Jahrb. Bd. II. 1876. Born, G. Beitrage zur Entwicklungsgeschichte des Saugethierherzens.
 
Archiv f. mikr. Anat. Bd. XXXIII. 1889. Brenner, A. Ueber das Verhaltniss des N. laryngeus inf. vagi zu einigen
Aortenvarietaten des Menschen und zu dem Aortensystem der durch
Lungen athmenden Wirbelthiere iiberhaupt. Archiv f. Anat. u. Physiol.
 
Anat. Abth. 1883. Gasser. Ueber die Entstehung des Herzens bei Vogelembryonen. Archiv f.
 
mikr. Anat. Bd. XIV. 1877. Hasse, C. Die Ursachen des rechtzeitigen Eintritts der Geburtsthatigkeit
bcim Menschen. Zeitschr. f. Geburtshilfe u. Gynakologie. Bd. VI.
 
1881, pp. 1-9.
 
 
 
654 EMBRYOLOGY.
 
Hochstetter, F. Ucber die Bildung der hinteren Hohlvene bei den Saugethieren. Anat. Anzeiger. Jahrg. II. No. 16, 1S87, ]). 517.
 
Hochstetter, F. Ueberden Einfluss der Entwicklung der bleibenden Nieren auf die Laare des Urnierenabschnittes der binteren Cardinalvenen. Anat.
 
o
Anzeiger. Jabrg. III. 1888. Hochstetter, F. Beitrage zur vergleichenden Anatomic und Entwicklungs
geschicbte des Venensystems der Amphibien und Fische. Morphol. Jabrb.
 
Bd. XIII. 1888. Hochstetter, F. Ueber das Gekrb'se der hinteren Hohlvene. Anat. Anzeiger.
 
Jahrg. III. 188.S. Hochstetter, F. Beitrage zur Entwicklungsgeschichte des Venensystems
der Anmioten. Morphol. Jahrb. Bd. XIII. 1888.
 
Lindes. Ein Beitrag zur Entwicklungsgeschichte des Herzens. Inauguraldissert. Dorpat 18G5. Marshall, J. On the Development of the Great Anterior Veins in Man and
Mammalia. Philos. Trans. Roy. Soc. London. 1850. Masius. Quelques notes sur le developpement du coeur chez le poulet.
 
Archives de Biologic. T. IX. 1889. Oellacher. Ueber die erste Entwicklung des Herzens und der Pericardial
oder Herzhohle bei Bufo cinereus. Archiv f. mikr. Anat. Bd. VII. 1871,
p. 157. Peremeschko. Ueber die Entwicklung der Milz. Sitzungsb. d. k. Akacl. d.
 
Wissensch. Wien. Math.-naturw. Cl. Bd. LVI. Abth. 2. 1867, p. 31. Rabl, Carl. Ueber die Bildung des Herzens der Amphibien. Morphol.
 
Jahrb. Band XII. 1887, p. 252. Rathke, H. Ueber die Bildung der Pfortader und der Lebervenen bei Sauge
tbieren. Meckel's Archiv. 1830. Rathke, H. Ueber den Bau und die Entwicklung des Venensystems der
Wirbelthiere. Bericht u'ber das naturhist. Seminar der Universitiit Kouigs
berg. 1838. Rathke, H. Ueber die Entwicklung der Arterien, welche bei den Sauge
thieren von dem Bogen der Aorta ausgehen. Archiv f. Anat. u. Physiol.
 
Jahrg. 1843. Rose, C. Zur Entwicklungsgeschichte des Saugethierherzens. Morphol.
 
Jahrb. Bd. XV. 1889, p. 436. Sabatier. Observations sur les transformations du systeme aortique dans la
serie des Vertebres. Ann. d. Sci. Nat. Ser. 5. T. XIX. 1874. Schmidt, F. J. Bidrag til Kundskaben om Hjertets Udviklingshistorie.
 
Nordiskt medicinskt Arkiv. Bd. II. 1870. Sertoli. Ueber die Entwicklung der Lymphdriisen. Sitzungsb. d. k. Akad.
 
d. Wissensch. Wien. Math.-naturw. Cl. Bd. LIV. Abth. 2. 1866. Strahl, H., und Carius. Beitrage zur Entwicklungsgeschichte des Herzens
und der Korperhohlen. Archiv f. Anat. u. Physiol. Anat. Abth. 1889. Tiirstig. Mittheilung iiber die Entwicklung der primitiven Aorten nach
Untersuchungen an Huhnerembryonen. Dissertation. Dorpat 1886. Wertheimer, E. Recherches sur la veine ombilicale. Jour, de 1'Anat. et de
la Physiol. T. XXII. 1886, pp. 1-17.
 
Development of the Skeleton.
 
Ahlborn, Fr. Ueber die Segmentation des Wirbeltbierkorpers. Zeitschr. f. wiss. Zoologie. Bd. XL. 1884, p. 309.
 
 
 
LITERATURE. 655
Albrecht, P. Sur la valeur morphologique rle 1'articulation rnandibulaire,
du cartilage de Meckel et des osselets de 1'ouie, etc. Bruxelles 1883. Balfour. On the Development of the Skeleton of the Paired Fins of Elasmo
branchii considered in Relation to its Bearings on the Nature of the Limbs
of the Vertebrata. Proceed. Zool. Soc. London. 1881. Bardeleben, K. Das Os intermedium tarsi der Saugethiere. Zool. Anzeis;er.
 
Jahrg. VI. 1883. Bardeleben, K. Ueber neue Bestandtheile der Hand- und Fusswurzel der
Saugethiere, etc. Jena. Zeitschr. Bd. XIX. Suppl.-Heft III. 1886 (?) Baumiiller. Ueber die letzten Veranderungen des Meckei'schen Knorpels.
 
Zeitschr. f. wiss. Zoologie. Bd. XXXII. 1879. Bernays, A. Die Entwicklungsgeschichte des Kniegelenks des Menschen
mit Bemerkungen liber die Gelenke im Allgemeinen. Morphol. Jahrb.
 
Bd. IV. 1878. Brock. Ueber die Entwicklung des Unterkiefers der Saugethiere. Zeitschr.
 
f. wiss. Zoologie. Bd. XXVII. 1876, p. 287. Carius. Ueber die Entwicklung der Chorda und der primitiven Eachenhaut
bei Meerschweinchen und Kaninchen. In.-Diss. Marburg 1888. Decker. Ueber den Primordialschadel einiger Saugethiere. Zeitschr. f.
 
wiss. Zoologie. Bd. XXXVIII. 1883. Dohrn, A. Studien zur Urgeschichte des Wirbelthierkb'rpers :
IV. Die Entwicklung und Differenzirung der Kiemenbogen der Selachier. V. Zur Entstehung und Differenzirung der Visceralbogen bei Petromy
zon Planeri. VI. Die paarigen und unpaaren Flossen der Selachier.
 
Mitth. a. d. Zool. Station Xeapel. Bd. V. 1884, p. 102.
 
Duges. Recherches sur 1'osteologie et la myologie des Batraciens a leurs differents ages. Paris 1834.
 
Dursy, E. Zur Entwicklungsgeschichte des Kopfes des Menschen und der hoheren Wirbelthiere. Tubingen 1869.
 
Ebner, von. Urwirbel und Neugliederung der Wirbelsaule. Sitzungsb. d. k. Akad. d. Wissensch. Wien. Math.-naturw. Cl. Bd. XCVII. Abth. 3. 1889, p. 194.
 
Fraser. On the Development of the Ossicula Auditus in the Higher Mammalia. Proceed. Roy. Soc. London. Vol. XXXIII. 1882, pp. 446-7.
 
Frenkel, F. Beitrag zur anatomischen Kenntuiss des Kreuzbeines der Saugethiere. Jena. Zeitschr. Bd. VIII. 1873.
 
Froriep, August. Zur Entwicklungsgeschichte der Wirbelsaule. insbesondere des Atlas und Epistropheus und der Occipitalregion.
 
I. Beobachtung an Hiihnerembryonen. Archiv f. Anat. u. Physiol.
 
Anat. Abth. 1883.
 
II. Beobachtung an Saugethierembryonen. Archiv f . Anat. u. Physiol. Anat. Abth. 1886.
 
Froriep, August. Ueber ein Ganglion des Hypoglossus und Wirbelanlagen in der Occipitalregion. Archiv f. Anat. u. Physiol. Anat. Abth. 1882.
 
Gadow. On the Modifications of the First and Second Visceral Arches, with especial Reference to the Hornologies of the Auditory Ossicles. Philos. Trans. Roy. Soc. London. 1888. Vol. CLXXIX. B. 1889, pp. 451-87.
 
Gegenbaur. Ueber die Entwicklung der Clavicula. Jena. Zeitschr. Bd. I. 1864, pp. 1-16.
 
 
 
G5G EMBRYOLOCJY.
 
Gegenbaur. Zur Morphologic der Gliedmaasson dcr Wirbelthierc. Morphol.
 
Jahrb. Bd. II. 1876. Gegenbaur.
 
(1) Ueber die Kopfncrven von Hexanchus und ihr Verhaltniss zur Wirbeltheorie des SchJidels. Jena. Zeitschr. Bd. VI. 1871, p. 497.
 
(2) Das Kopfskelet der Selachier, ein Beitrag zur Erkcnntniss der Genese des Kopfskelets der Wirbelthiere. Leipzig 1872.
 
(3) Ueber das Archipterygium. Jena. Zeitschr. Bd. VII. 1873, p. 131.
 
(4) Die Metamerie des Kopfes und die Wirbeltheorie des Kopfskelets. Morphol. Jahrb. Bd. XIII. 1887.
 
Gotte, A. Beitrage zur vergleichenden Morphologic des Skeletsystems der
Wirbelthiere (Brustbein und Schultergurtel). Archiv f. mikr. Anat.
 
Bd. XIV. 1877. Gradenigo, G. Die embryonal e Anlage des Mittelohres: die morphologische
Bedeutung der Gehb'rknochelchen. Mitth. a. d. embryol. Inst. d. Univ.
 
Wien. Heft 1887, p. 85. Hannover, A. Primordialbrusken og dens Forbening i det menneskelige
Kranium for fodselen. Danske Videnskabernes Selskabs Skrif ter. K^joben
harn. Ser. 5, Bd. XI. p. 349. 1880. Hannover, A. Primordialbrusken og dens Forbening i Truncus og Ex
tremiteter hos Mennesket for Fodselen. (Table des matieres et Extrait
en francais.) Kjobenliavn. Ser. 6, Bd. IV; p. 2G5. 1887. Hasse, C. Die Entwicklung des Atlas und Epistropheus des Menschen und
der Saugethiere. Anatomische Studien. Bd. I. Leipzig 1872. Henke und Reyher. Studien iiber die Entwickelung der Extremitaten des
Menschen, insbesondere der Gelenkflachen. Sitzungsb. d. k. Akad. d.
 
Wissensch. Wien. Bd. LXX. 1875. Hertwig, Oscar. Ueber das Zahnsystem der Amphibien und seine Bedeutung
fiir die Genese des Skelets der Mundhohle. Eine vergleichend anato
mische, entwicklungsgeschichtliche Untersuchung. Archiv f. mikr. Anat.
 
Bd. XI. Snpplementheft. 1874. Hoffmann, C. K. Beitrage zur vergleichenden Anatomic der Wirbelthiere.
 
Xieder. Archiv f. Zool. Bd. V. 1875).
 
Huxley. Lectures on the Elements of Comparative Anatomy. London 1864. Jacobson. Abstract by Hannover in Jahresbericht, p. 36, Archiv f. Anat.
 
u. Physiol. Jahrg. 1844. Julin, Charles. Kecherches sur 1'ossification du maxillaire inferieur chez le
foetus de la balaenoptera. Archives de Biologic. T. I. 1880. Kann. Das vordere Chordaende. Inauguraldissert. Erlangen 1888. Keibel. Zur Entwicklungsgeschichte der Chorda bei Saugern. Archiv f.
 
Anat. u. Physiol. Anat. Abth. 18s<). K6 Hiker, A. Allgemeine Betrachtungen iiber die Entstehung des kncicher
nen Schadels der Wirbelthiere. Berichte von der kb'nigl. zoot. Anstalt.
 
Wiirzburg. Leipzig 1849. Kolliker, Theodor. Ueber das Os intermaxillare des Menschen und die
Anatomic der Hasenscharte und des Wolfsrachens. Nova acta Acad.
 
Leop.-Carol. Bd. XLIII. 1882. Leboucq., H. Kecherches sur le mode de disparition de la corcie dorsale
chez les vertebres superieurs. Archives de Biologic. Vol. I. 1880. Magitot et Robin. Memoire sur un orgaue transitoire de la vie foetale
 
 
LITERATURE. 657
clesigne sous le noni de cartilage de Meckel. Ann. des. tSci. Nat. T. XVIII.
 
1862. Masquelin. Ilecherches sur le developpement du maxillaire infcrieur de
1'homme. Bull, de 1'Acad. roy. de Belgique. 2e serie. T. XLV. 1*7*. Oken. Ueber die Bedeutung der Schadelknochen. Jena 1807. Parker, W. K., and Bettany. The Morphology of the Skull. London
1877. German translation by Vetter. 1*79. Perenyi. Ent wicklung der Chorda dorsalisbei Torpedo niarrnorata. Math. u.
 
Naturw. Berichte aus Ungarn. Budapest. Bd. IV. p. 214. u. V. p. 218.
 
1886, 1887. Rabl, Carl. Ueber das Gebiet des Xervus facialis. Anat. Anzeiger. Jahrg.
 
II. 1887. Reichert, C. Ueber die Visceralbogen der Wirbelthiere im Allgemeinen und
deren Metamorphose bei den Vb'geln und 8augethieren. Archiv f. Anat.
 
u. Physiol. 1837. Rosenberg, E. Untersuchungen iiber die Occipitalregion des Cranium und
den proximalen Theil der Wirbelsiiule einiger Selachier. Dorpat ISsl. Rosenberg, E. Ueber die Entwicklung der Wirbelsaule und das Centrale
carpi des Menschen. Morphol. Jahrb. Bd. I. 1875. Ruge. Untersuchungen iiber Entwicklungsvorgiinge am Brustbein und an
der 8ternoclavicularverbindang des Menschen. Morphol. Jahrb. Bd. VI.
 
1880. Salensky, W. Beitrlige zur Entwicklungsgeschichte der knorpeligen Gehbr
knb'chelchen bei Siiugethieren. Morphol. Jahrb. Bd. VI. 1880. Schwegel. Die Entwicklungsgescbichte der Knochen des Stanimes und der
Extremitiiten mit Klicksicht auf Chirurgie, Geburtskunde und gerichtliche
Medicin. 8itzungsb. d. k. Akad. d. Wissensch. Wien. Math.-naturw. Cl.
 
Bd. XXX. 1858, p. 337. Spondli, H. Ueber den rrimordialschadel der Saugethiere und des Menschen.
 
Inaugural-Dissertation. Zurich 1846.
 
Stohr. Zur Entwicklungsgeschichte des Kopfskelets der Teleostier. Festschrift d. medicin. Facultiit Wiirzburg. Leipzig 1882. Stohr. Zur Entwicklungsgeschichte des Urodelenschadels. Zeitschr. f. wiss.
 
Zoologle. Bd. XXXIII. 1879. Stohr. Zur Entwicklungsgeschichte des Anurenschadels. Zeitschr. f. wiss.
 
Zoologie. Bd. XXXVI. 1881. Stohr. Ueber Wirbeltheorie des Schadels. Sitzungsb. d. physik.-med.
 
Gesellsch. Wiirzburg. 1881. Wiedersheim. Ueber die Entwicklung des Schulter- und Beckengiirtels.
 
Anat. Anzeiger. Jahrg. IV. 1889 u. Jahrg. V. 1890.
 
 
 
658 EMBRYOLOGY.
 
Besides the writings treating of the development of the separate systems of organs, the following larger monographic works should be cited :
Embryology of Man.
 
Coste. Histoire generate et particuliere du developpement des corps organises.
 
18471859.
 
Ecker. Icones physiologicae. Leipzig 1851 185$. Erdl. Die Entwicklung cles Menschen und HUhnchens im Eie. Leipzig
1845. His. Anatomie menschlicher Embryonen.
 
Heft I. Embryonen des ersten Monats. Leipzig 1880.
 
Heft II. Gestalt und Grossenentwicklung bis zum Schluss des zweiten
Monats. Leipzig 1882. Heft III. Zur Geschichte der Organe. Leipzig 1885.
 
Embryology of Mammals.
 
Baer, C. E. von. Ueber Entwickhmgsgeschichte der Thiere. Beobacbtung und Reflexion. Konigsberg 1828 u. 1887.
 
Balfour. A Monograph on the Development of Elasmobranch Fishes. London 1878.
 
BischofF. Entwicklungsgescbicbte des Kaninchens. Braunschweig 1842.
 
Bischoff. Entwicklungsgeschicbte des Hundeeies. 1845.
 
BischofF. Entwicklungsgeschichte des Meerschweinchens. 1852.
 
Bischoif. Entwicklungsgeschichte des Eehes. 1 854.
 
Bonnet. Beitriige zur Embryologie der Wiederkauer, gewonnen am Schaf ei. Archiv f. Anat. u. Physiol. Anat. Abth. 1884 u. 1889.
 
Duval. Atlas d'embryologie. Paris 1889.
 
Gotte. Entwicklungsgeschichte der Unke. Leipzig 1875.
 
Hatschek, B. Studien liber Entwicklung des Amphioxus. Arbeiten a. d. zool. Inst. d. Universitiit Wien. 1882.
 
Hensen. Beobachtungen Uber die Befruchtung und Entwicklung des Kaninchens und Meerschweinchens. Zeitschr. f. Anat. u. Entwicklungsg. Bd. I. 1870.
 
His, W. Untersuclmngen iiber die erste Anlage des Wirbeltbierleibes. Die erste Entwicklung des Hiihnchens im Ei. Leipzig 1868.
 
Hubrecht. Studies in Mammalian Embryology. Placentation of Erinaceus, etc. Quart, Jour. Mic. Sci. Vol. XXX. 1890, p. 283.
 
Rathke. Entwicklungsgeschichte der Xatter. Konigsberg 1839.
 
Remak. Untersuphungen Uber die Entwicklung der Wirbelthierc. Berlin 1855.


Riickert. Ueber die; Entstehung der Excretionsorgane bei Selachiern. Archiv f. Anat. u. Physiol. Anat. Abth. 1888.
[[Book_-_Text-Book of the Embryology of Man and Mammals 16-3|The Development of the Skin and its Accessory Organs]]
*  the skin
*  hair
*  nails
*  glands of the skin


Schultze, M. Die Entwicklungsgeschicbte von Petromyzon Planeri. 185B.


Selenka. Studien Uber Entwicklungsgeschicbte der Thiere. Wiesbaden 1886, etc.
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Hertwig O. Text-book of the embryology of man and mammals. (1892) Translated 1901 by Mark EL. from 3rd German Edition. S. Sonnenschein, London.

Textbook Contents  
Text-Book of the Embryology of Man and Mammals: Description of the Sexual Products | The Phenomena of the Maturation of the Egg and the Process of Fertilisation | The Process of Cleavage | General Discussion of the Principles of Development | The Development of the Two Primary Germ-Layers | The Development of the Two Middle Germ-Layers | History of the Germ-Layer Theory | Development of the Primitive Segments | Development of Connective Substance and Blood | Establishment of the External Form of the Body | The Foetal Membranes of Reptiles and Birds | The Foetal Membranes of Mammals | The Foetal Membranes of Man | The Organs of the Inner Germ-Layer - The Alimentary Tube with its Appended Organs | The Organs of the Outer Germ-Layer | The Development of the Nervous System | The Development of the Sensory Organs | The Development of the Skin and its Accessory Organs | The Organs of the Intermediate Layer or Mesenchyme | The Development of the Blood-vessel System | The Development of the Skeleton
--Mark Hill 21:14, 10 May 2011 (EST) This historic embryology textbook is at only an "embryonic" editing stage with many typographical errors and no figures.
Historic Disclaimer - information about historic embryology pages 
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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)

The Organs of the Outer Germ-Layer

16 The Organs of the Outer Germ-Layer

The Development of the Nervous System

  • the development of the central nervous system
    • the development of the spinal cord
    • the development of the brain (1) metamorphosis of the fifth brain- vesicle (2) fourth (3) third (4) second development of the pineal gland (epiphysis cerebri)., hypophysis (pituitary body) (5) fore-brain vesicle
  • the development of the peripheral nervous system
    • the development of the spinal ganglia
    • the development of the peripheral nerves
    • the development of the sympathetic system

The Development of the Sensory Organs

  • the development of the eye
    • the development of the lens
    • vitreous body
    • secondary optic cup and the coats of the eye
    • optic nerve
    • accessory apparatus of the eye
  • the development of the organ of hearing
    • the development of the otocyst into the labyrinth
    • membranous ear-capsule into the bony labyrinth and the perilymphatic spaces
    • middle and external ear
  • the development of the organ of smell

The Development of the Skin and its Accessory Organs

  • the skin
  • hair
  • nails
  • glands of the skin


Text-Book of the Embryology of Man and Mammals: Description of the Sexual Products | The Phenomena of the Maturation of the Egg and the Process of Fertilisation | The Process of Cleavage | General Discussion of the Principles of Development | The Development of the Two Primary Germ-Layers | The Development of the Two Middle Germ-Layers | History of the Germ-Layer Theory | Development of the Primitive Segments | Development of Connective Substance and Blood | Establishment of the External Form of the Body | The Foetal Membranes of Reptiles and Birds | The Foetal Membranes of Mammals | The Foetal Membranes of Man | The Organs of the Inner Germ-Layer - The Alimentary Tube with its Appended Organs | The Organs of the Outer Germ-Layer | The Development of the Nervous System | The Development of the Sensory Organs | The Development of the Skin and its Accessory Organs | The Organs of the Intermediate Layer or Mesenchyme | The Development of the Blood-vessel System | The Development of the Skeleton

Historic Disclaimer - information about historic embryology pages 
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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)

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Cite this page: Hill, M.A. (2024, April 26) Embryology Book - Text-Book of the Embryology of Man and Mammals 16. Retrieved from https://embryology.med.unsw.edu.au/embryology/index.php/Book_-_Text-Book_of_the_Embryology_of_Man_and_Mammals_16

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© Dr Mark Hill 2024, UNSW Embryology ISBN: 978 0 7334 2609 4 - UNSW CRICOS Provider Code No. 00098G
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