Development of the Nervous System
Henry Gray (1821–1865). Anatomy of the Human Body. 1918. 2. Development of the Nervous System The entire nervous system is of ectodermal origin, and its first rudiment is seen in the neural groove which extends along the dorsal aspect of the embryo (Fig. 17). By the elevation and ultimate fusion of the neural folds, the groove is converted into the neural tube (Fig. 19). The anterior end of the neural tube becomes expanded to form the three primary brain-vesicles; the cavity of the tube is subsequently modified to form the ventricular cavities of the brain, and the central canal of the medulla spinalis; from the wall the nervous elements and the neuroglia of the brain and medulla spinalis are developed.
FIG. 640– Section of medulla spinalis of a four weeks’ embryo. (His.) (Picture From the Classic Gray's Anatomy)
FIG. 641– Transverse section of the medulla spinalis of a human embryo at the beginning of the fourth week. The left edge of the figure corresponds to the lining of the central canal. (His.) (Picture From the Classic Gray's Anatomy)
FIG. 642– aged about four and a half weeks. (Picture From the Classic Gray's Anatomy)
FIG. 643– aged about three months. (Picture From the Classic Gray's Anatomy) The Medulla Spinalis—At first the wall of the neural tube is composed of a single layer of columnar ectodermal cells. Soon the side-walls become thickened, while the dorsal and ventral parts remain thin, and are named the roof- and floor-plates (Figs. 640, 642, 643). A transverse section of the tube at this stage presents an oval outline, while its lumen has the appearance of a slit. The cells which constitute the wall of the tube proliferate rapidly, lose their cell-boundaries and form a syncytium. This syncytium consists at first of dense protoplasm with closely packed nuclei, but later it opens out and forms a looser meshwork with the cellular strands arranged in a radiating manner from the central canal. Three layers may now be defined—an internal or ependymal, an intermediate or mantle, and an external or marginal. The ependymal layer is ultimately converted into the ependyma of the central canal; the processes of its cells pass outward toward the periphery of the medulla spinalis. The marginal layer is devoid of nuclei, and later forms the supporting framework for the white funiculi of the medulla spinalis. The mantle layer represents the whole of the future gray columns of the medulla spinalis; in it the cells are differentiated into two sets, viz., ('a') spongioblasts or young neuroglia cells and ('b') germinal cells which are the parents of the neuroblasts or young nerve cells (Fig. 641). The spongioblasts are at first connected to one another by filaments of the syncytium; in these, fibrils are developed, so that as the neuroglial cells become defined they exhibit their characteristic mature appearance with multiple processes proceeding from each cell. The germinal cells are large, round or oval, and first make their appearance between the ependymal cells on the sides of the central canal. They increase rapidly in number, so that by the fourth week they form an almost continuous layer on each side of the tube. No germinal cells are found in the roof- or floor-plates; the roof-plate retains, in certain regions of the brain, its epithelial character; elsewhere, its cells become spongioblasts. By subdivision the germinal cells give rise to the neuroblasts or young nerve cells, which migrate outward from the sides of the central canal into the mantle layer and neural crest, and at the same time become pear-shaped; the tapering part of the cell undergoes still further elongation, and forms the axiscylinder of the cell. The lateral walls of the medulla spinalis continue to increase in thickness, and the canal widens out near its dorsal extremity, and assumes a somewhat lozengeshaped appearance. The widest part of the canal serves to subdivide the lateral wall of the neural tube into a dorsal or alar and a ventral or basal lamina (Figs. 642, 643), a subdivision which extends forward into the brain. At a later stage the ventral part of the canal widens out, while the dorsal part is first reduced to a mere slit and then becomes obliterated by the approximation and fusion of its walls; the ventral part of the canal persists and forms the central canal of the adult medulla spinalis. The caudal end of the canal exhibits a conical expansion which is known as the terminal ventricle The ventral part of the mantle layer becomes thickened, and on cross-section appears as a triangular patch between the marginal and ependymal layers. This thickening is the rudiment of the anterior column of gray substance, and contains many neuroblasts, the axis-cylinders of which pass out through the marginal layer and form the anterior roots of the spinal nerves (Figs. 640, 642, 643). The thickening of the mantle layer gradually extends in a dorsal direction, and forms the posterior column of gray substance. The axons of many of the neuroblasts in the alar lamina run forward, and cross in the floor-plate to the opposite side of the medulla spinalis; these form the rudiment of the anterior white commissure. About the end of the fourth week nerve fibers begin to appear in the marginal layer. The first to develop are the short intersegmental fibers from the neuroblasts in the mantle zone, and the fibers of the dorsal nerve roots which grow into the medulla spinalis from the cells of the spinal ganglia. By the sixth week these dorsal root fibers form a well-defined oval bundle in the peripheral part of the alar lamina; this \??\ gradually increases in size, and spreading toward the middle line forms the rudiment of the posterior funiculus. The long intersegmental fibers begin to appear about the third month and the cerebrospinal fibers about the fifth month. All nerve fibers are at first destitute of medullary sheaths. Different groups of fibers receive their sheaths at different times—the dorsal and ventral nerve roots about the fifth month, the cerebrospinal fibers after the ninth month. By the growth of the anterior columns of gray substance, and by the increase in size of the anterior funiculi, a furrow is formed between the lateral halves of the cord anteriorly; this gradually deepens to form the anterior median fissure. The mode of formation of the posterior septum is somewhat uncertain. Many believe that it is produced by the growing together of the walls of the posterior part of the central canal and by the development from its ependymal cells of a septum of fibrillated tissue which separates the future funiculi graciles. Up to the third month of fetal life the medulla spinalis occupies the entire length of the vertebral canal, and the spinal nerves pass outward at right angles to the medulla spinalis. From this time onward, the vertebral column grows more rapidly than the medulla spinalis, and the latter, being fixed above through its continuity with the brain, gradually assumes a higher position within the canal. By the sixth month its lower end reaches only as far as the upper end of the sacrum; at birth it is on a level with the third lumbar vertebra, and in the adult with the lower border of the first or upper border of the second lumbar vertebra. A delicate filament, the filum terminale extends from its lower end as far as the coccyx. The Spinal Nerves—Each spinal nerve is attached to the medulla spinalis by an anterior or ventral and a posterior or dorsal root. The fibers of the anterior roots are formed by the axons of the neuroblasts which lie in the ventral part of the mantle layer; these axons grow out through the overlying marginal layer and become grouped to form the anterior nerve root (Fig. 641). The fibers of the posterior roots are developed from the cells of the spinal ganglia. Before the neural groove is closed to form the neural tube a ridge of ectodermal cells, the ganglion ridge or neural crest (Fig. 644), appears along the prominent margin of each neural fold. When the folds meet in the middle line the two ganglion ridges fuse and form a wedge-shaped area along the line of closure of the tube. The cells of this area proliferate rapidly opposite the primitive segments and then migrate in a lateral and ventral direction to the sides of the neural tube, where they ultimately form a series of oval-shaped masses, the future spinal ganglia. These ganglia are arranged symmetrically on the two sides of the neural tube and, except in the region of the tail, are equal in number to the primitive segments. The cells of the ganglia, like the cells of the mantle layer, are of two kinds, viz., spongioblasts and neuroblasts The spongioblasts develop into the neuroglial cells of the ganglia. The neuroblasts are at first round or oval in shape, but soon assume the form of spindles the extremities of which gradually elongate into central and peripheral processes. The central processes grow medialward and, becoming connected with the neural tube, constitute the fibers of the posterior nerve roots, while the peripheral processes grow lateralward to mingle with the fibers of the anterior root in the spinal nerve. As development proceeds the original bipolar form of the cells changes; the two processes become approximated until they ultimately arise from a single stem in a T-shaped manner. Only in the ganglia of the acoustic nerve is the bipolar form retained. More recent observers hold, however, that the T-form is derived from the branching of a single process which grows out from the cell.
FIG. 644– Two stages in the development of the neural crest in the human embryo. (Lenhossèk.) (Picture From the Classic Gray's Anatomy) The anterior or ventral and the posterior or dorsal nerve roots join immediately beyond the spinal ganglion to form the spinal nerve which then divides into anterior, posterior, and visceral divisions. The anterior and posterior divisions proceed directly to their areas of distribution without further association with ganglion cells (Fig. 645). The visceral divisions are distributed to the thoracic, abdominal, and pelvic viscera, to reach which they pass through the sympathetic trunk, and many of the fibers form arborizations around the ganglion cells of this trunk. Visceral branches are not given off from all the spinal nerves; they form two groups, viz., ('a') thoracico-lumbar from the first or second thoracic, to the second or third lumbar nerves; and ('b') pelvic from the second and third, or third and fourth sacral nerves.
FIG. 645– Reconstruction of periphera nerves of a human embryo of 10.2 mm. (After His.) The abducent nerve is not labelled, but is seen passing forward to the eye under the mandibular and maxillary nerves. (Picture From the Classic Gray's Anatomy) The Brain—The brain is developed from the anterior end of the neural tube, which at an early period becomes expanded into three vesicles, the primary cerebral vesicles (Fig. 18). These are marked off from each other by intervening constrictions, and are named the fore-brain or prosencephalon the mid-brain or mesencephalon and the hind-brain or rhombencephalon—the last being continuous with the medulla spinalis. As the result of unequal growth of these different parts three flexures are formed and the embryonic brain becomes bent on itself in a somewhat zigzag fashion; the two earliest flexures are concave ventrally and are associated with corresponding flexures of the whole head. The first flexure appears in the region of the mid-brain, and is named the ventral cephalic flexure (Fig. 650). By means of it the fore-brain is bent in a ventral direction around the anterior end of the notochord and fore-gut, with the result that the floor of the fore-brain comes to lie almost parallel with that of the hind-brain. This flexure causes the mid-brain to become, for a time, the most prominent part of the brain, since its dorsal surface corresponds with the convexity of the curve. The second bend appears at the junction of the hind-brain and medulla spinalis. This is termed the cervical flexure (Fig. 652), and increases from the third to the end of the fifth week, when the hind-brain forms nearly a right angle with the medulla spinalis; after the fifth week erection of the head takes place and the cervical flexure diminishes and disappears. The third bend is named the pontine flexure (Fig. 652), because it is found in the region of the future pons Varoli. It differs from the other two in that ('a') its convexity is forward, and ('b') it does not affect the head. The lateral walls of the brain-tube, like those of the medulla spinalis, are divided by internal furrows into alar or dorsal and basal or ventral laminæ (Fig. 646).
FIG. 646– Diagram to illustrate the alar and basal laminæ of brain vesicles. (His.) (Picture From the Classic Gray's Anatomy)
FIG. 647– Transverse section of medulla oblongata of human embryo. X 32. (Kollmann.) (Picture From the Classic Gray's Anatomy)
FIG. 648– Transverse section of medulla oblongata of human embryo. (After His.) (Picture From the Classic Gray's Anatomy) The Hind-brain or Rhombencephalon—The cavity of the hind-brain becomes the fourth ventricle. At the time when the ventral cephalic flexure makes its appearance, the length of the hind-brain exceeds the combined lengths of the other two vesicles. Immediately behind the mid-brain it exhibits a marked constriction, the isthmus rhombencephali (Fig. 650, Isthmus), which is best seen when the brain is viewed from the dorsal aspect. From the isthmus the anterior medullary velum and the superior peduncle of the cerebellum are formed. It is customary to divide the rest of the hind-brain into two parts, viz., an upper, called the metencephalon and a lower, the myelencephalon The cerebellum is developed by a thickening of the roof, and the pons by a thickening in the floor and lateral walls of the metencephalon. The floor and lateral walls of the myelencephalon are thickened to form the medulla oblongata; its roof remains thin, and, retaining to a great extent its epithelial nature, is expanded in a lateral direction. Later, by the growth and backward extension of the cerebellum, the roof is folded inward toward the cavity of the fourth ventricle; it assists in completing the dorsal wall of this cavity, and is also invaginated to form the ependymal covering of its choroid plexuses. Above it is continuous with the posterior medullary velum; below, with the obex and ligulæ. 13
FIG. 649– Hind-brain of a human embryo of three months—viewed from behind and partly from left side. (From model by His.) (Picture From the Classic Gray's Anatomy)
FIG. 650– Exterior of brain of human embryo of four and a half weeks. (From model by His.) (Picture From the Classic Gray's Anatomy) The development of the medulla oblongata resembles that of the medulla spinalis, but at the same time exhibits one or two interesting modifications. On transverse section the myelencephalon at an early stage is seen to consist of two lateral walls, connected across the middle line by floor- and roof-plates (Figs. 647 and 648). Each lateral wall consists of an alar and a basal lamina, separated by an internal furrow, the remains of which are represented in the adult brain by the sulcus limitans on the rhomboid fossa. The contained cavity is more or less triangular in outline, the base being formed by the roof-plate, which is thin and greatly expanded transversely. Pear-shaped neuroblasts are developed in the alar and basal laminæ. and their narrow stalks are elongated to form the axis-cylinders of the nerve fibers. Opposite the furrow or boundary between the alar and basal laminæ a bundle of nerve fibers attaches itself to the outer surface of the alar lamina. This is named the tractus solitarius (Fig. 648), and is formed by the sensory fibers of the glossopharyngeal and vagus nerves. It is the homologue of the oval bundle seen in the medulla spinalis, and, like it, is developed by an ingrowth of fibers from the ganglia of the neural crest. At first it is applied to the outer surface of the alar lamina, but it soon becomes buried, owing to the growth over it of the neighboring parts. By the fifth week the dorsal part of the alar lamina bends in a lateral direction along its entire length, to form what is termed the rhombic lip (Figs. 648, 649). Within a few days this lip becomes applied to, and unites with, the outer surface of the main part of the alar lamina, and so covers in the tractus solitarius and also the spinal root of the trigeminal nerve; the nodulus and flocculus of the cerebellum are developed from the rhombic lip. 14 Neuroblasts accumulate in the mantle layer; those in the basal lamina correspond with the cells in the anterior gray column of the medulla spinalis, and, like them, give origin to motor nerve fibers; in the medulla oblongata they are, however, arranged in groups or nuclei, instead of forming a continuous column. From the alar lamina and its rhombic lip, neuroblasts migrate into the basal lamina, and become aggregated to form the olivary nuclei, while many send their axis-cylinders through the floor-plate to the opposite side, and thus constitute the rudiment of the raphé of the medulla oblongata. By means of this thickening of the ventral portion, the motor nuclei are buried deeply in the interior, and, in the adult, are found close to the rhomboid fossa. This is still further accentuated: ('a') by the development of the pyramids, which are formed about the fourth month by the downward growth of the motor fibers from the cerebral cortex; and ('b') by the fibers which pass to and from the cerebellum. On the rhomboid fossa a series of six temporary furrows appears; these are termed the rhombic grooves They bear a definite relationship to certain of the cranial nerves; thus, from before backward the first and second grooves overlie the nucleus of the trigeminal; the third, the nucleus of the facial; the fourth, that of the abducent; the fifth, that of the glossopharyngeal; and the sixth, that of the vagus. 15 The pons is developed from the ventro-lateral wall of the metencephalon by a process similar to that which has been described for the medulla oblongata. 16
FIG. 651– Brain of human embryo of four and a half weeks, showing interior of fore-brain. (From model by His.) (Picture From the Classic Gray's Anatomy) The cerebellum is developed in the roof of the anterior part of the hind-brain (Figs. 649 to 654). The alar laminæ of this region become thickened to form two lateral plates which soon fuse in the middle line and produce a thick lamina which roofs in the upper part of the cavity of the hind-brain vesicle; this constitutes the rudiment of the cerebellum, the outer surface of which is originally smooth and convex. The fissures of the cerebellum appear first in the vermis and floccular region, and traces of them are found during the third month; the fissures on the cerebellar hemispheres do not appear until the fifth month. The primitive fissures are not developed in the order of their relative size in the adult—thus the horizontal sulcus in the fifth month is merely a shallow groove. The best marked of the early fissures are: ('a') the fissura prima between the developing culmen and declive, and ('b') the fissura secunda between the future pyramid and uvula. The flocculus and nodule are developed from the rhombic lip, and are therefore recognizable as separate portions before any of the other cerebellar lobules. The groove produced by the bending over of the rhombic lip is here known as the floccular fissure when the two lateral walls fuse, the right and left floccular fissures join in the middle line and their central part becomes the post-nodular fissure 17 On the ventr