assume a spherical form. These spherical cells have large deeply staining nuclei, and they are termed germinal cells.

For many years it was believed that the germinal cells were the predecessors of the primitive nerve elements or neuroblasts, and that the remaining cells, called spongioblasts, became transformed into the reticular sustentacular tissue of the central nervous system. It appears, however, from the results of more recent researches, that some of the descendants of the germinal cells become spongioblasts whilst others become neuroblasts or primitive nerve-cells. Moreover, there appear to be two groups of germinal cells; the descendants of one group are directly transformed into the ependymal or lining cells of the central canal, whilst those of the other group form in the first instance indifferent cells, some of whose descendants become neuroblasts and others spongioblasts: The fate of the cells present before the germinal cells appear, and which do not become germinal cells, is uncertain, but they probably take part in the formation of the spongioblastic tissue.

It is believed, therefore, that all the nerve-cells are the descendants of the germinal cells, and that the spongioblasts which become developed into the cells of the neuroglia or sustentacular reticulum are derived partly from the nongerminal cells of the primitive neural tube and, partly, they are descendants of the germinal cells.

As differentiation proceeds three layers and two membranes are gradually defined in the walls of the neural tube: (1) a central layer of columnar ependyma cells immediately surrounding the central canal; (2) an intermediate or mantle layer consisting of neuroblasts and their processes, the nerve-fibres, intermingled with spongioblasts; (3) a peripheral reticular layer consisting, at first, of processes of the bodies of the spongioblasts. The membranes are an external limiting membrane, surrounding the exterior of the tube, formed by the fused outer ends of the spongioblastic cells, and an internal limiting membrane bounding the central canal and continuous with the inner ends of the ependyma cells. Throughout the whole of the spinal medulla and the brain, the ependyma cells become transformed into the columnar ciliated cells which line the cavities of the adult brain and spinal medulla. The mantle layer becomes converted into the gray matter of the adult central nervous system.

The peripheral reticular layer, in the spinal region, becomes permeated by nerve-fibres, which are merely processes of the nerve-cells, and it is thus converted into the white matter of the adult spinal medulla. In the brain region it is either transformed in the same way into white matter, or it remains in a more rudimentary condition as a thin peripheral layer of neuroglia on the surface of the gray matter. On the other hand, in the brain region white matter is formed internal to the gray matter by the growth of nerve-fibres which insinuate themselves between the mantle layer externally and the bodies of the ependyma cells internally.

As the histological differentiation of the walls of the neural tube is proceeding each lateral wall is divided into a dorsal part, the alar lamina, and a ventral part, the basal lamina, by a sulcus-like dilatation of the central canal called the sulcus limitans. After the limiting sulci are formed the parts of the walls of the neural tube are a roof-plate, a floor-plate, and two lateral walls, each of which consists of an alar lamina, essentially sensory in function, and a basal lamina, essentially motor in function (Fig. 44).

The Fate of the Cavities of the Primitive Brain. The cavity of the spinal portion of the primitive neural tube becomes the central canal of the spinal medulla of the adult. The cavities of the primitive brain vesicles are transformed into the ventricles, foramina, and aqueduct of the adult brain. The cavities of the telencephalic divisions of the secondary fore-brain become the right and left lateral ventricles of the adult brain. The cavity of the undivided portion of the secondary fore-brain vesicle, together with the cavity of the primary fore-brain, become the third ventricle or cavity of the diencephalon, and the apertures of communication between the third ventricle and the cerebral hemispheres are the interventricular foramina (O.T. foramina of Monro).

The cavity of the hind-brain vesicle becomes the fourth ventricle, and the

cavity of the primitive mid-brain is converted into the aqueductus cerebri, which connects the third with the fourth ventricle.

After the anterior and posterior neuropores (p. 31) are closed, the cavity of the neural tube is, for a time, a completely enclosed space. Subsequently the mesoderm, which in the meantime has surrounded the tube, becomes differentiated, in its immediate neighbourhood, into three membranes. The innermost of the three is closely connected with the walls of the neural tube and is called the pia mater. The outermost, known as the dura mater, is dense and resistant, and the intermediate membrane is a thin lamella called the arachnoid.

As the membranes are formed, spaces are differentiated between them. The space between the dura mater and the arachnoid is the subdural space, and that between the arachnoid and the pia mater is the subarachnoid space.

After a time a median perforation, the median aperture of the fourth ventricle (O.T. foramen of Magendie), and two lateral perforations pierce the dorsal wall of the fourth ventricle and the pia mater which covers it, and thus the fourth ventricle becomes connected with the subarachnoid space. It is stated also that a perforation passes through the medial wall and the covering pia mater of a portion of each lateral ventricle which is called its inferior horn, throwing those portions of the lateral ventricles also into communication with the subarachnoid space, but it is doubtful if the statement is correct.

THE FORMATION OF THE EMBRYO.

The transformation of the relatively flat embryonic area into the form of the embryo is due, in the first instance, to the rapid extension of the median part

of the area, as contrasted with

embryo is due to different rates Cephalic end of

of growth in different parts of the embryonic region.

embryonic area.
Pericardial

mesoderm
Mesoderm of.

Entoderm
Notochord

FIG. 48.-SCHEMA OF SAGITTAL SECTION OF EMBRYONIC AREA AND
AMNION BEFORE THE FOLDING OF THE AREA HAS COMMENCED.

Amnion cavity
Neural tube.

By the rapid proliferation entoderm vesicle of cells from the nodal growing point, at the cephalic end of the primitive streak, the cephalo-caudal length of the area is increased, whilst the cephalic and caudal ends of the area remain relatively fixed, consequently the area becomes folded longitudinally. At the same time, the cephalic end of the neural groove is pushed away from the nodal point, until it lies at first dorsal and then cephalad to the cephalic border of the area.

As

a result of this movement the bucco-pharyn

Region of anterior neuropore

Bucco-pharyngeal

Ectoderm of amnion

membrane | Pericardium

Mid-gut

Fore-gut (heart not shown)

FIG. 49. SCHEMA OF SAGITTAL SECTION OF EMBRYONIC AREA SHORTLY AFTER THE FOLDING HAS COMMENCED. The pericardial mesoderm is carried into the ventral wall of the fore-gut and the cœlom has extended through it. The cephalic end of the neural tube and the caudal part of the primitive streak are bent ventrally, and the latter now forms the cloacal membrane.

geal and the pericardial areas become reversed in position, and a cephalic or head fold is formed. This fold is bounded, dorsally, by what is now the cephalic portion of the embryo, ventrally, by the reversed pericardial region, and its cephalic end is formed by the extremity of the head region and the bucco-pharyngeal

membrane.

The growth at the nodal point not only produces a head fold, but at the same time it forces the cephalic end of the primitive streak caudally over the caudal end of the embryonic area, thus forming a tail fold.

As the head and tail folds of the embryo are produced by the longitudinal increase of the embryonic area, transverse growth of the area results in the formation of right and left lateral folds (Figs. 37, 39), and as the various folds are formed the embryo rises, like a mushroom, into the interior of the amnion cavity.

The portion of the entodermal sac which is enclosed within the hollow embryo, formed by the folding of the embryonic area, is the primitive entodermal alimentary canal. The part which remains outside the embryo is the yolk sac, and the passage of communication between the two is the vitello-intestinal duct.

That portion of the primitive entodermal alimentary canal which lies in the head fold is termed the fore-gut, the part in the tail fold is the hind-gut, and the intermediate portion which is in free communication with the yolk-sac is the mid-gut.

As the extension of the embryonic area and its folding proceed the margin of the area, which remains relatively stationary, becomes the margin of an orifice, on

FIG. 50.-SCHEMA OF SAGITTAL SECTION OF EMBRYO AFTER THE FOLDING HAS DEFINED BOTH THE FORE-GUT AND HIND-GUT AREAS.

the ventral aspect of the embryo, through which the primitive alimentary canal of the embryo and the intra-embryonic part of the cœlom communicate, respectively, with the yolk sac and the extra-embryonic portion of the cœlom. This orifice is the primitive umbilical orifice.

Not only does the primitive alimentary canal communicate with the yolk sac, and the intra-embryonic with the extra-embryonic cœlom, at the margin of the umbilical orifice, but also the body walls of the embryo, formed by the somatopleure, becomes continuous, at the same margin, with the wall of the amnion.

The young embryo is connected also with the inner surface of the chorion by a band of tissue which is part of the median portion of the caudal part of the wall of the amnion sac. The mesoderm in this region is thickened, and contains in its interior a diverticulum, allantoic diverticulum, which is primarily derived from the entodermal sac, but is afterwards connected with the hind-gut. This strand consists of ectoderm and mesoderm, and it contains not only the allantoic diverticulum but also the blood-vessels passing between the embryo and the chorion. It was called, by His, the body stalk, but the term is not fortunate, for it takes no part in the formation in the body of the embryo. On the other hand, its mesodermal and entodermal constituents represent a diverticulum from the wall of the hind-gut, present in many mammals and known as the allantois; it might with advantage, therefore, be termed the allantoic stalk.

At first the umbilical orifice is relatively large as contrasted with the total size

of the embryo, but as the embryo rapidly extends, in all directions, from the margin of the orifice, the latter soon becomes relatively small. Ultimately the various parts of the margin of the orifice are approximated until they fuse together, closing the opening and forming a cicatrix on the ventral wall of the abdomen which is known as the umbilicus or navel.

THE EMBRYO.

Whilst the embryonic area is being folded into the form of the embryo, the neural groove on the surface of the area is being converted into the neural tube. After the neural tube is completely closed and separated from the surface, during the third week, the embryo is an elongated organism possessing a larger cephalic end, a smaller caudal end, attached by the body stalk to the chorion (Fig. 49), a continuous and unbroken dorsal surface, a ventral surface separated into cephalic and caudal portions by the umbilical orifice, two lateral surfaces right and left, and it contains within its interior three cavities: (1) The cavity of the neural tube, which becomes the cavities of the brain and the spinal medulla (Fig. 50); (2) the primitive alimentary canal, which is a portion of the entodermal vesicle constricted off during the folding of the embryonic area (Figs. 37, 40); (3) the embryonic cœlom. The cœlom consists of right and left portions which communicate at the margin of the umbilicus with the extra-embryonic cœlom, and with each other through the pericardial portion of the intra-embryonic cœlom in the ventral wall of the fore-gut of the embryo (Figs. 49, 90).

At this period the embryo is easily distinguished from the remainder of the zygote, and it is so far developed that indications of its general plan of organisation are discernible.

It has, as yet, no limbs, but the general contour of the head and body are defined. It possesses a notochord or primitive skeletal axis, afterwards replaced by the permanent vertebral column. On the dorsal aspect of the notochord lies the neural tube, which is the rudiment of the future brain and the spinal medulla. At the sides of the neural tube and the notochord are the mesodermal somites and the nerve ganglia (Figs. 40, 43).

Ventral to the notochord is the primitive alimentary canal (Fig. 50), closed at its cephalic end by the bucco-pharyngeal membrane, and at its caudal end by what was originally the caudal portion of the primitive streak, but which is now called the cloacal membrane because it separates the caudal end of the hind-gut, which becomes the entodermal cloaca, from the amniotic cavity (Fig. 50).

At the sides of the primitive alimentary canal are the right and left lateral parts of the cœlom, and between the dorsal angle of each half of the coelom and the mesodermal somites of the same side lies the intermediate cell tract which is the rudiment of the greater part of the genito-urinary system (Figs. 39, 40).

Ventral to the fore-gut is the pericardial mesoderm, traversed by the pericardial portion of the cœlom, which is connected dorsally, on each side, with the corresponding lateral portions of the cœlom; and ventral to the hind-gut is the cloacal membrane. Between the pericardial region at the one end and the cloacal membrane at the other lies the umbilical orifice, through which the mid-gut communicates with the yolk sac, the intra-embryonic part of the cœlom with the extra-embryonic cœlom, and the allantoic diverticulum with the cloaca (Figs. 39, 50).

THE LIMBS.

When it is first defined the embryo is entirely devoid of limbs (Fig. 51). During the third week a superficial ridge appears on each side, along the line of the intermediate cell tract in the interior. This is the Wolffian ridge, and upon it the rudiments of the fore and hind limbs, the limb buds, are formed, as secondary elevations; the fore-limb buds preceding the hind-limb buds in time of appearance (Fig. 52).

Shortly after it has appeared, each limb bud assumes a semilunar outline; it projects at right angles from the surface of the body, and it possesses dorsal and ventral surfaces, and cephalic or preaxial, and caudal or postaxial borders. The

bud is the rudiment of the distal segment of the future limb, the hand in the case of the fore-limb, and the foot in the case of the hind-limb.

As the limb-rudiment increases in length the more proximal segments of the limb are differentiated, the forearm and arm in the case of the fore-limb, and the

FIG. 53. LATERAL VIEW OF A HUMAN EMBRYO-2.1 mm. greatest length, showing limb buds projecting from the Wolffian ridge.

(Keibel and Elze, Normaltafeln.)

leg and the thigh in the case of the hind-limb. At the same time the limbs are folded ventrally, so that their original ventral surfaces become medial and their original dorsal surfaces lateral, and the convexities of the elbows and knees are directed laterally. At a later period, on account of a rotation which takes place in opposite directions in the fore- as contrasted with the hindlimbs, the convexity of the elbow is turned towards the caudal end of the body and that of the knee towards the cephalic end. It is only at much later periods of development, as the erect posture is assumed, that the convexity of the elbow is directed dorsally and the convexity of the knee ventrally. The terminal or distal seg

ment of each limb is, at first, a flat plate with a rounded margin, but it soon differentiates into a proximal or basal part and a more flattened marginal portion. It is along the line where these two parts are continuous that the rudiments of the digits appear. They become evident as small elevations on the dorsal surface of the limb bud about the fifth week; they extend peripherally, and by the sixth week the fingers project beyond the margins of the hand segment, but the toes do not attain to a corresponding stage of development until the early part of the seventh week.