The Developing Human: Clinically Oriented Embryology, 10e PDF

392 THE DEVEL OP I NG HU M A N midbrain and forebrain, and the alar and basal plates are recognizable only in the midbrain and hindbrain (see CAUS...

392 THE DEVEL OP I NG HU M A N midbrain and forebrain, and the alar and basal plates are recognizable only in the midbrain and hindbrain (see CAUSES OF NEURAL TUBE DEFECTS Figs. 17-5C and 17-19C). Nutritional and environmental factors undoubtedly play * demarcates - separate a role in the production of NTDs. Gene-gene and gene- Hindbrain environment interactions are likely involved in most cases. Food fortification with folic acid and folic acid The cervical flexure demarcates the hindbrain from the supplements taken before conception and continued for spinal cord (see Fig. 17-19A). Later, this junction is arbi- at least 3 months during pregnancy reduce the incidence trarily defined as the level of the superior rootlet of of NTDs. In 2015, the Centers for Disease Control and the first cervical nerve, which is located roughly at the Prevention urged “all women of childbearing age who foramen magnum. The pontine flexure, located in the future pontine region, divides the hindbrain into caudal can become pregnant to get 0.4 mg of folic acid every (myelencephalon) and rostral (metencephalon) parts. day to help reduce the risk of neural tube defects” (for The myelencephalon becomes the medulla oblongata more information, go to http://www.cdc.gov/folicacid). (commonly called the medulla), and the metencephalon Epidemiologic studies have also shown that low maternal becomes the pons and cerebellum. The cavity of the hind- B12 levels may significantly increase the risk of NTDs. brain becomes the fourth ventricle and the central canal Certain drugs (e.g., valproic acid) increase the risk of in the medulla (see Fig. 17-19B and C). meningomyelocele. This anticonvulsant drug causes NTDs in 1% to 2% of pregnancies if taken during early Myelencephalon pregnancy, when the neural folds are fusing (Fig. 17-17). The caudal part of the myelencephalon (closed part of the medulla) resembles the spinal cord developmentally and structurally (see Fig. 17-19B). The neural canal of the neural tube forms the small central canal of the myel- encephalon. Unlike those of the spinal cord, neuroblasts DEVELOPMENT OF BRAIN from the alar plates in the myelencephalon migrate into the marginal zone and form isolated areas of gray matter: 16 The brain begins to develop during the third week, when the gracile nuclei medially and the cuneate nuclei laterally the neural plate and tube are developing from the neuro- (see Fig. 17-19B). These nuclei are associated with cor- ectoderm (see Fig. 17-1). The neural tube, cranial to the respondingly named nerve tracts that enter the medulla fourth pair of somites, develops into the brain. Neuro- from the spinal cord. The ventral area of the medulla progenitor cells proliferate, migrate, and differentiate to contains a pair of fiber bundles (pyramids) that consist form specific areas of the brain. Fusion of the neural folds of corticospinal fibers descending from the developing in the cranial region and closure of the rostral neuropore cerebral cortex (see Fig. 17-19B). form three primary brain vesicles from which the brain The rostral part of the myelencephalon (open part develops (Fig. 17-18): of the medulla) is wide and rather flat, especially opposite the pontine flexure (see Fig. 17-19C and D). The pontine Forebrain (prosencephalon) flexure causes the lateral walls of the medulla to move Midbrain (mesencephalon) laterally like the pages of an open book. As a result, its Hindbrain (rhombencephalon) roof plate is stretched and greatly thinned (see Fig. During the fifth week, the forebrain partly divides into 17-19C). The cavity of this part of the myelencephalon two secondary brain vesicles, the telencephalon and dien- (part of the future fourth ventricle) becomes somewhat cephalon; the midbrain does not divide. The hindbrain rhomboidal (diamond shaped). As the walls of the partly divides into two vesicles, the metencephalon and medulla move laterally, the alar plates become lateral to myelencephalon. Consequently, there are five secondary the basal plates. As the positions of the plates change, the brain vesicles. motor nuclei usually develop medial to the sensory nuclei (see Fig. 17-19C). Neuroblasts in thee basal plates of the medulla, like Brain Flexures those in the spinal cord, develop into motor neurons. The During the fifth week, the embryonic brain grows rapidly neuroblasts form nuclei (groups of nerve cells) and orga- 16 and bends ventrally with the head fold. The bending nize into three cell columns on each side (see Fig. 17-19D). produces the midbrain flexure in the midbrain region and - From medial to lateral, the columns are named as follows: the cervical flexure at the junction of the hindbrain and General somatic efferent, represented by neurons of spinal cord (Fig. 17-19A). Later, unequal growth of the the hypoglossal nerve brain between these flexures produces the pontine flexure Special visceral efferent, represented by neurons inner- in the opposite direction. This flexure results in thinning vating muscles derived from the pharyngeal arches (see of the roof of the hindbrain (see Fig. 17-19C). Chapter 9, Fig. 9-6) Initially, the primordial brain has the same basic struc- General visceral efferent, represented by some ture as the developing spinal cord; however, the brain neurons of the vagus and glossopharyngeal nerves (see flexures produce considerable variation in the outline Chapter 9, Fig. 9-6) of transverse sections at different levels of the brain and in the position of the gray and white matter. The Neuroblasts in the- alar plates of the medulla form sulcus limitans extends cranially to the junction of the neurons that are arranged in four columns on each side.  C H A P T E R 17 | N E RVOU S S Y ST EM 393 Neural tube Neural fold Rostral neuropore Caudal neuropore Somite Defective closure of Defective closure of rostral neuropore caudal neuropore 1. Incomplete development Neural groove of brain with degeneration Neural fold 2. Incomplete development of calvaria 3. Alteration in facies (facial appearance) +/– auricle Mass of brain tissue Neural deficit Unfused vertebral caudal to lesion Meningomyelocele arch Meroencephaly +/– Clubfoot +/– Hydrocephalus Spina bifida occulta Tuft of hair Dura mater Skin Subarachnoid space Incomplete vertebral arch Myeloschisis Spinal cord Vertebra Clubfoot F I G U R E 1 7 – 1 7 Schematic illustration shows the embryologic basis of neural tube defects. Meroencephaly (partial absence of = brain) results from defective closure of the rostral neuropore, and meningomyelocele results from defective closure of the caudal neuropore. (Modified from Jones KL: Smith’s recognizable patterns of human malformations, ed 4, Philadelphia, 1988, Saunders.) 394 THE DEVEL OP I NG HU M A N 3 Primary 5 Secondary Adult derivatives vesicles vesicles of Walls Cavities Wall Cavity Cerebral Lateral ventricles Telencephalon hemispheres Forebrain (prosencephalon) Thalami, etc. Third ventricle Diencephalon Midbrain Aqueduct area where CSF is Midbrain - synthesized Mesencephalon > (mesencephalon) ventricles no Pons Upper part of fourth ventricle Metencephalon Cerebellum Hindbrain (rhombencephalon) Medulla Lower part of fourth ventricle Myelencephalon Spinal cord F I G U R E 1 7 – 1 8 Diagrammatic sketches of the brain vesicles indicate the adult derivatives of their walls and cavities. The rostral part of the third ventricle forms from the cavity of the telencephalon. Most of this ventricle is derived from the cavity of the diencephalon. Cerebellum Pontine flexure Central canal Gracile nucleus Hindbrain Level of section B Cuneate nucleus Central gray matter Blood vessel Midbrain flexure Spinal cord Pyramids ventral Cervical flexure A B (composed of corticospinal fibers) Roof plate Sulcus limitans Ependymal roof Tela choroidea Choroid plexus Special somatic afferent Fourth ventricle General somatic afferent General visceral Special visceral afferent efferent General visceral afferent Special visceral efferent Alar plate Basal plate Olivary nucleus C D General somatic efferent F I G U R E 1 7 – 1 9 A, Sketch of the developing brain at the end of the fifth week of gestation shows the three primary divisions of the brain and brain flexures. B, Transverse section of the caudal part of the myelencephalon (developing closed part of medulla). C and D, Similar sections of the rostral part of the myelencephalon (developing open part of medulla) show the position and succes- sive stages of differentiation of the alar and basal plates. The arrows in C show the pathway taken by neuroblasts from the alar plates to form the olivary nuclei.  C H A P T E R 17 | N E RVOU S S Y ST EM 395 From medial to lateral, the columns are designated as in eachE basal plate develop into motor nuclei and orga- follows: nize into three columns on each side. The cerebellum develops from thickenings of dorsal General visceral afferent, which receives impulses from parts of the alar plates. Initially, the cerebellar swellings the viscera project into the fourth ventricle (see Fig. 17-20B). As the Special visceral afferent, which receives taste fibers swellings enlarge and fuse in the median plane, they over- General somatic afferent, which receives impulses grow the rostral half of the fourth ventricle and overlap from the surface of the head the pons and medulla (see Fig. 17-20D). Special somatic afferent, which receives impulses from the ear Some neuroblasts in the intermediate zone of the =>alar plates migrate to the marginal zone and differentiate into s Some neuroblasts from the alar plates migrate ven- the neurons of the cerebellar cortex. Other neuroblasts trally and form the neurons in the olivary nuclei (see from these plates give rise to the central nuclei, the largest Fig. 17-19C and D). of which is the dentate nucleus (see Fig. 17-20D). Cells from the alar plates also give rise to the pontine nuclei, Metencephalon - cochlear and vestibular nuclei, and the sensory nuclei of The walls of the metencephalon form the pons and cer- the - - - trigeminal nerve. ebellum, and the cavity of the metencephalon forms the The structure of the cerebellum reflects its phylogenetic superior part of the fourth ventricle (Fig. 17-20A). As in (evolutionary) development (see Fig. 17-20C and D): the rostral part of the myelencephalon, the pontine flexure causes divergence of the lateral walls of the pons, which The archicerebellum (flocculonodular lobe), the oldest spreads the gray matter in the floor of the fourth ventricle part phylogenetically, has connections with the ves- (see Fig. 17-20B). As in the myelencephalon, neuroblasts tibular apparatus, especially the vestibule of the ear. Ependymal roof Level of section B Pia mater Cerebellar swelling (primordium of cerebellum) Developing cerebellum Somatic afferent - General visceral afferent Fourth ventricle General visceral efferent Special visceral efferent Pontine nucleus General somatic efferent Developing pons and medulla A B Primary fissure Capillary Cerebellar Developing anterior Anterior lobe cortex Midbrain lobe of cerebellum (paleocerebellum) Posterior lobe Nodule (neocerebellum) Choroid plexus Cerebral Flocculonodular lobe aqueduct (archicerebellum) Tela choroidea Dentate nucleus Fourth ventricle C Pons Medulla D Pons Choroid plexus Medulla F I G U R E 1 7 – 2 0 A, Sketch of the developing brain at the end of the fifth week. B, Transverse section of the metencephalon (developing pons and cerebellum) shows the derivatives of the alar and basal plates. C and D, Sagittal sections of the hindbrain at 6 and 17 weeks, respectively, show successive stages in the development of the pons and cerebellum.  396 THE DEVEL OP I NG HU M A N The paleocerebellum (vermis and anterior lobe), of Neuroblasts (Greek blastos, germ) are embryonic more recent development, is associated with sensory nerve cells that migrate from the alar plates of the mid- data from the limbs. brain into the tectum (roof-like covering) and aggregate - The neocerebellum (posterior lobe), the newest part to form four large groups of neurons, the paired superior phylogenetically, is concerned with selective control of and inferior colliculi (see Fig. 17-21C to E), which are limb movements. concerned with visual and auditory reflexes, respectively. Neuroblasts from the basal plates may give rise to groups - Nerve fibers connecting the cerebral and cerebellar of neurons in the tegmentum of the midbrain (red nuclei, cortices with the spinal cord pass through the marginal nuclei of third and fourth cranial nerves, and reticular layer of the ventral region of the metencephalon. This nuclei). The substantia nigra, a broad layer of gray matter region of the brainstem is the pons (Latin bridge) because adjacent to the crus cerebri (cerebral peduncles) may also of the robust band of nerve fibers that crosses the median differentiate from the basal plate (see Fig. 17-21B, D, plane and forms a bulky ridge on its anterior and lateral and E); however, some authorities think the substantia aspects (see Fig. 17-20C and D). nigra is derived from cells in the alar plate that migrate ventrally. Choroid Plexuses and Fibers growing from the cerebrum (principal part of brain, including the diencephalon and cerebral hemi- 16 Cerebrospinal Fluid spheres) form the crus cerebri (cerebral peduncles) The thin ependymal roof of the fourth ventricle is covered anteriorly (see Fig. 17-21B). The peduncles become pro- externally by pia mater, which is derived from mesen- gressively more prominent as more descending fiber chyme associated with the hindbrain (see Fig. 17-20B to groups (corticopontine, corticobulbar, and corticospinal) D). This vascular membrane, together with the ependy- pass through the developing midbrain on their way to the mal roof, forms the tela choroidea, the sheet of pia cover- brainstem (the medulla is the caudal subdivision of the ing the lower part of the fourth ventricle (see Fig. 17-19D). brainstem that is continuous with the spinal cord) and Because of the active proliferation of the pia, the tela spinal cord (see Fig. 17-21C). choroidea invaginates the fourth ventricle, where it dif- ferentiates into the choroid plexus, infoldings of choroi- dal arteries of the pia (see Figs. 17-19C and D and 17-20C Forebrain and D). Similar plexuses develop in the roof of the third As closure of the rostral neuropore occurs (see Fig. ventricle and the medial walls of the lateral ventricles. 17-3B), two lateral outgrowths (optic vesicles) appear The choroid plexuses secrete ventricular fluid, which (see Fig. 17-4A), one on each side of the forebrain. becomes CSF as additions are made to it from the sur- These vesicles are the primordia of the retinae and faces of the brain, spinal cord, and the pia-arachnoid optic nerves (see Chapter 18, Figs. 18-1C, F, and H and layer of the meninges. Various signaling morphogens 18-11). A second pair of diverticula, the telencephalic are found in CSF and the choroid plexus that are vesicles, soon arise more dorsally and rostrally (see Fig. necessary for brain development. The thin roof of the 17-21C). They are the primordia of the cerebral hemi- fourth ventricle evaginates in three locations. These out- spheres, and their cavities become the lateral ventricles pouchings rupture to form openings, the median and (see Fig. 17-26B). lateral apertures (foramen of Magendie and foramina of The rostral (anterior) part of the forebrain, including Luschka, respectively), which permit the CSF to enter the the primordia of the cerebral hemispheres, is the telen- subarachnoid space from the fourth ventricle. Specific cephalon; the caudal (posterior) part of the forebrain is neurogenic molecules (e.g., retinoic acid) control the the diencephalon. The cavities of the telencephalon and proliferation and differentiation of neuroprogenitor diencephalon contribute to the formation of the third cells. The epithelial lining of the choroid plexus is derived ventricle, although the cavity of the diencephalon con- from neuroepithelium, whereas the stroma develops from tributes more (Fig. 17-22E). mesenchymal cells. The main site of absorption of CSF into the venous Diencephalon system is through the arachnoid villi, which are protru- Three swellings develop in the lateral walls of the third sions of arachnoid mater into the dural venous sinuses ventricle, which later become the thalamus, hypothala- (large venous channels between the layers of the dura mus, and epithalamus (see Fig. 17-22C to E). The thala- mater). The arachnoid villi consist of a thin cellular layer mus is separated from the epithalamus by the epithalamic derived from the epithelium of the arachnoid and the sulcus and from the hypothalamus by the hypothalamic endothelium of the sinus. sulcus (see Fig. 17-22E). The latter sulcus is not a con- tinuation of the sulcus limitans into the forebrain, and it does not, like the sulcus limitans, divide sensory and Midbrain motor areas (see Fig. 17-22C). The midbrain (mesencephalon) undergoes less change The thalamus (large, ovoid mass of gray matter) devel- than other parts of the developing brain (Fig. 17-21A), ops rapidly on each side of the third ventricle and bulges except for the caudal part of the hindbrain. The neural into its cavity (see Fig. 17-22E). The thalami meet and canal narrows and becomes the cerebral aqueduct (see fuse in the midline in approximately 70% of brains, Figs. 17-20D and 17-21D), a channel that connects the forming a bridge of gray matter across the third ventricle, third and fourth ventricles. which is the interthalamic adhesion (variable connection  C H A P T E R 17 | N E RVOU S S Y ST EM 397 Primordia of colliculi Level of section B Midbrain Hindbrain Substantia nigra Crus cerebri B (cerebral peduncle) A Mesencephalic nucleus (CN V) Inferior colliculus Cerebral aqueduct Trochlear nucleus Telencephalic vesicle (somatic efferent) (primordial cerebral hemisphere) Decussation of superior cerebellar peduncle Substantia nigra Levels of sections E D Interpeduncular fossa Crus cerebri D Inferior colliculus Superior colliculus Mesencephalic Cerebellum nucleus (CN V) Oculomotor nucleus (CN III) Red nucleus Crus cerebri C Pons Medulla Substantia nigra E F I G U R E 1 7 – 2 1 A, Sketch of the developing brain at the end of the fifth week. B, Transverse section of the developing midbrain shows the early migration of cells from the basal and alar plates. C, Sketch of the developing brain at 11 weeks. D and E, Transverse sections of the developing midbrain at the level of the inferior and superior colliculi, respectively. between the two thalamic masses across the third ven- pathway has been implicated in the proliferation and dif- tricle); the bridge is absent in about 20% of brains. ferentiation of pituitary progenitor cells. The pituitary The hypothalamus arises by proliferation of neuro- develops from two sources: blasts in the intermediate zone of the diencephalic walls, An upgrowth from the ectodermal roof of the stomo- ventral to the hypothalamic sulci (see Fig. 17-22E). Dif- deum, the hypophyseal diverticulum (Rathke pouch) ferential expression of Wnt/β-catenin signaling is involved A downgrowth from the neuroectoderm of the dien- in the patterning of the hypothalamus. Later, a number cephalon, the neurohypophyseal diverticulum of nuclei concerned with endocrine activities and homeo- stasis develop. A pair of nuclei forms pea-sized swellings This double origin explains why the pituitary gland is (mammillary bodies) on the ventral surface of the hypo- composed of two different types of tissue: pituitary glund ( has postinor) thalamus (see Fig. 17-22C). nor o · and The adenohypophysis (glandular tissue), or anterior The epithalamus develops from the roof and dorsal lobe, arises from oral ectoderm an trior - - portion of the lateral wall of the diencephalons (see Fig. The neurohypophysis (nervous tissue), or posterior 17-22C to E). Initially, the epithalamic swellings are lobe, arises from neuroectoderm up postri in A ADI connectedeons large, but later they become relatively small. porch the's ↳D derived curoo from The pineal gland (pineal body) develops as a median By the third week, the hypophyseal diverticulum proj- diverticulum of the caudal part of the roof of the dien- ects from the roof of the stomodeum and lies adjacent to cephalon (see Fig. 17-22D). Proliferation of cells in its the floor (ventral wall) of the diencephalon (see Fig. walls soon converts it into a solid, cone-shaped gland. 17-23C). By the fifth week, the diverticulum has elon- The pituitary gland (hypophysis) is ectodermal in gated and constricted at its attachment to the oral epithe- origin (Fig. 17-23 and Table 17-1). The Notch signaling lium. By this stage, it has come into contact with the 398 THE DEVEL OP I NG HU M A N Midbrain Cerebellum Hindbrain Cerebral hemisphere Forebrain Optic cup A B Olfactory bulb Optic nerve Epithalamus Mesencephalon Pineal gland Cerebral hemisphere Thalamus Epithalamus Alar plate Cerebellum Sulcus limitans Basal plate Cerebellum Thalamus Hypothalamus Mammillary body Optic chiasma Level of section E Hypothalamus Infundibulum D Infundibulum C Optic chiasm & Ependymal roof Epithalamus Epithalamic sulcus Third Thalamus ventricle Hypothalamic sulcus Hypothalamus E F I G U R E 1 7 – 2 2 A, Sketch shows an external view of the brain at the end of the fifth week. B, Similar view at 7 weeks. C, Median section of the brain at 7 weeks shows the medial surface of the forebrain and midbrain. D, Similar section at 8 weeks. E, Transverse section of the diencephalon shows the epithalamus dorsally, the thalamus laterally, and the hypothalamus ventrally. infundibulum (derived from the neurohypophyseal diver- extension, the pars tuberalis, grows around the infun- ticulum), a ventral downgrowth of the diencephalon (see dibular stem (see Fig. 17-23E). The extensive prolifera- Figs. 17-22C and D and 17-23). tion of the anterior wall of the hypophyseal diverticulum The stalk of the hypophyseal diverticulum passes reduces its lumen to a narrow cleft (see Fig. 17-23E). The between the chondrification centers of the developing residual cleft is usually not recognizable in the adult presphenoid and basisphenoid bones of the cranium (see pituitary gland; however, it may be represented by a zone Fig. 17-23E). During the sixth week, the connection of of cysts. Cells in the posterior wall of the hypophyseal the diverticulum with the oral cavity degenerates (see Fig. pouch do not proliferate; they give rise to the thin, poorly 17-23D and E). Cells of the anterior wall of the hypophy- defined pars intermedia (see Fig. 17-23F). seal diverticulum proliferate and give rise to the pars The part of the pituitary gland that develops from the anterior of the pituitary gland (see Table 17-1). Later, an neuroectoderm (neurohypophyseal diverticulum) is the  C H A P T E R 17 | N E RVOU S S Y ST EM 399 Hypophyseal pouch of stomodeum Infundibulum of diencephalon (upgrowth from roof of primitive mouth) (downgrowth from floor of forebrain) Diencephalon Neurohypophyseal diverticulum Infundibulum Floor of Cerebral diencephalon vesicle Hypophyseal diverticulum Stalk of hypophyseal diverticulum Hypophyseal diverticulum Oral ectoderm B C Stomodeum Notochord (primordial oral cavity) Former site of oropharyngeal A membrane Optic chiasm Median eminence Pars intermedia Pars tuberalis Infundibular stem Anterior lobe Pars tuberalis (anterior lobe) Pars intermedia Pars nervosa Developing (posterior lobe) sphenoid bone Colloid-containing vesicles Regressing stalk of hypophyseal D diverticulum Former site of Pharyngeal roof E hypophyseal stalk Intracranials and intraosseus Pharyngeal F accessory anterior lobe tissue hypophysis F I G U R E 1 7 – 2 3 Diagrammatic sketches illustrate development of the pituitary gland. A, Sagittal section of the cranial end of an embryo at approximately 36 days shows the hypophyseal diverticulum, an upgrowth from the stomodeum, and the neurohypophy- seal diverticulum, a downgrowth from the forebrain. B to D, Successive stages of the developing pituitary gland. By 8 weeks, the diverticulum loses its connection with the oral cavity and is in close contact with the infundibulum and posterior lobe (neurohypophysis) of the pituitary gland. E and F, Sketches of later stages show proliferation of the anterior wall of the hypophyseal diverticulum to form the anterior lobe (adenohypophysis) of the pituitary gland. O-memonce Table 17–1 Pituitary Gland Derivation and Terminology DERIVATION TISSUE TYPE PART LOBE Oral ectoderm Hypophyseal diverticulum from the roof of Adenohypophysis (glandular tissue) Pars anterior Anterior lobe the stomodeum Pars tuberalis Pars intermedia Neuroectoderm Neurohypophyseal diverticulum from the floor Neurohypophysis (nervous tissue) Pars nervosa Posterior lobe of the diencephalon Infundibular stem Median eminence 400 THE DEVEL OP I NG HU M A N neurohypophysis (see Fig. 17-23B to F and Table 17-1). involved in the formation of the anterior and intermedi- The infundibulum - gives rise to the median eminence, ate lobes of the pituitary gland. The LIM homeobox infundibular stem, and pars nervosa. Initially, the walls gene LHX2 appears to control development of the pos- of the infundibulum are thin, but the distal end of the terior lobe. infundibulum soon becomes solid as the neuroepithelial cells proliferate. These cells later differentiate into pitui- Telencephalon cytes, the primary cells of the posterior lobe of the pitu- The telencephalon consists of a median part and two itary gland, which are closely related to neuroglial cells. lateral diverticula, the cerebral vesicles (see Fig. 17-23A). Nerve fibers grow into the pars nervosa from the hypo- These vesicles are the primordia of the cerebral hemi- thalamic area, to which the infundibular stem is attached spheres (see Figs. 17-22B and 17-23A). The cavity of the (see Fig. 17-23F). median portion of the telencephalon forms the extreme Studies indicate that secreted inductive molecules (e.g., anterior part of the third ventricle (Fig. 17-25). At first, FGF8, BMP4, and WNT5A) from the diencephalon are the cerebral hemispheres are in wide communication with the cavity of the third ventricle through the interventricu- lar foramina (Fig. 17-26B; see Fig. 17-25). Along the choroid fissure, part of the medial wall of PHARYNGEAL HYPOPHYSIS AND the developing cerebral hemisphere becomes very thin CRANIOPHARYNGIOMA (see Figs. 17-25 and 17-26A and B). Initially, this epen- dymal portion lies in the roof of the hemisphere and is A remnant of the stalk of the hypophyseal diverticulum continuous with the ependymal roof of the third ventricle may persist and form a pharyngeal hypophysis in the roof (see Fig. 17-26A). The choroid plexus of the lateral ven- of the oropharynx (see Fig. 17-23F). Rarely, masses of tricle later forms at this site (Fig. 17-27; see Fig. 17-25). anterior lobe tissue develop outside the capsule of the As the cerebral hemispheres expand, they cover suc- pituitary gland, within the sella turcica of the sphenoid cessively the diencephalon, midbrain, and hindbrain. The bone (Fig. 17-24). A remnant of the hypophyseal diverticu- hemispheres eventually meet each other in the midline, lum, the basipharyngeal canal, is visible in sections of the and their medial surfaces become flattened. The mesen- neonate’s sphenoid bone in approximately 1% of cases. It chyme trapped in the longitudinal fissure between them can also be identified in a small number of radiographs of gives rise to the cerebral falx (falx cerebri), a median fold crania of neonates (usually those with cranial defects). of dura mater. Occasionally, a rare, benign tumor (craniopharyngi- The corpus striatum appears during the sixth week oma) develops in or superior to the sella turcica. Less as a prominent swelling in the floor of each cerebral often, these tumors form in the pharynx or basisphenoid hemisphere (see Fig. 17-27B). The floor of each hemi- (posterior part of the sphenoid) from remnants of the stalk sphere expands more slowly than its thin cortical walls of the hypophyseal diverticulum (see Fig. 17-24). These because it contains the rather large corpus striatum, and tumors arise along the path of the hypophyseal diverticu- the cerebral hemispheres become C shaped (Fig. 17-28A lum from epithelial remnants (see Fig. 17-23D to F). and B). The growth and curvature of the cerebral hemispheres affect the shape of the lateral ventricles. They become pituitary gland aginates Form - near down -nebedeFombran n r Rathkets pouch ↓ Remnants of e Rathhe's pouch cranio antioa around pinilar pharygiote Corpus callosum F I G U R E 1 7 – 2 4 Sagittal magnetic resonance image of the brain of a 4-year- Thalamus old boy whose presenting symptoms were headaches and optic atrophy (vision loss). A large mass (4 cm) occupies an enlarged Midbrain sella turcica, expanding inferiorly into the sphenoid bone and superiorly into the Cerebellum suprasellar cistern. A craniopharyngioma Craniopharyngioma was confirmed by surgery. The inferior half Pons of the mass is solid and appears dark, whereas the superior half is cystic and appears brighter. 402 THE DEVEL OP I NG HU M A N Level of sections Parietal lobe Third ventricle B and C Occipital lobe Frontal lobe Habenular commissure Choroid plexus Pallium Pineal gland Interventricular Hippocampal foramen commissure Posterior commissure Lateral Corpus ventricle callosum Colliculi Corpus Cerebellum striatum Lamina = terminalis - Thalamus Hypothalamus Anterior commissure Pons Ependymal roof Third ventricle Infundibulum of third ventricle A Optic chiasm Mamillary body B Cerebral cortex Choroid plexus of lateral and third ventricles Caudate nucleus Projection fibers of internal capsule Thalamus Lentiform nucleus C Hypothalamus Plane of subsequent fusion F I G U R E 1 7 – 2 7 A, Drawing of the medial surface of the forebrain of a 10-week embryo shows the diencephalic derivatives, the main commissures, and the expanding cerebral hemispheres. B, Transverse section of the forebrain at the level of the interventricular foramina shows the corpus striatum and choroid plexuses of the lateral ventricles. C, Similar section at approximately 11 weeks shows division of the corpus striatum into the caudate and lentiform nuclei by the internal capsule. The developing relationship of the cerebral hemispheres to the diencephalon is also illustrated. roughly C-shaped cavities filled with CSF. The caudal end Cerebral Commissures of each hemisphere turns ventrally and then rostrally, As the cerebral cortex develops, groups of nerve fibers forming the temporal lobe (Fig. 17-29C); in so doing, it (commissures) connect corresponding areas of the cere- carries the lateral ventricle (forming its temporal horn) bral hemispheres with one another (see Fig. 17-27). The and choroid fissure with it (see Fig. 17-28B and C). The most important of these commissures crosses in the thin medial wall of the hemisphere is invaginated along lamina terminalis, which is the rostral (anterior) end of the choroid fissure by vascular pia mater to form the the forebrain (see Fig. 17-26A and B and 17-27A). This choroid plexus of the temporal horn (see Fig. 17-27B). lamina extends from the roof plate of the diencephalon As the cerebral cortex differentiates, fibers coursing to to the optic chiasm (decussation or crossing of the optic and from it pass through the corpus striatum and divide nerve fibers). The lamina terminalis is the natural pathway it into caudate and lentiform nuclei. This fiber pathway from one hemisphere to the other. (internal capsule) (see Fig. 17-27C) becomes C shaped as The first commissures to form are the anterior com- the hemisphere assumes this form. The caudate nucleus missure and hippocampal commissure. They are small becomes elongated and C shaped, conforming to the fiber bundles that connect phylogenetically older parts of outline of the lateral ventricle (see Fig. 17-28C). Its pear- the brain (see Fig. 17-27A). The anterior commissure shaped head and elongated body lie in the floor of the connects the olfactory bulb (rostral extremity of the frontal horn and body of the lateral ventricle, whereas its olfactory tract) and related areas of one hemisphere with tail makes a U-shaped turn to gain the roof of the tem- those of the opposite side. The hippocampal commissure poral or inferior horn. connects the hippocampal formations.  Choroid fissure C H A P T E R 17 | N E RVOU S S Y ST EM ventricular, intermediate, and marginal; later a fourth O 403 Interventricular foramen one, the subventricular zone, appears. Cells of the inter- Lateral ventricle mediate zone migrate into the marginal zone and give rise to the cortical layers. The gray matter is located peripher- Corpus striatum ally, and axons from its cell bodies pass centrally to form the large volume of white matter (medullary center). Initially, the surface of the cerebral hemispheres is smooth (see Fig. 17-29A); however, as growth proceeds, A sulci (grooves) between the gyri (tortuous convolutions) develop (Fig. 17-30A; see Fig. 17-29B and D). The gyri are caused by infolding of the cerebral cortex. The sulci and gyri permit a considerable increase in the surface area Choroid fissure Corpus striatum of the cerebral cortex without requiring an extensive increase in the size of the neurocranium (see Fig. 17-30B Frontal horn of Lateral ventricle and C). As each cerebral hemisphere grows, the cortex lateral ventricle covering the external surface of the corpus striatum grows relatively slowly and is soon overgrown (see Fig. 17-29D). This buried cortex, hidden from view in the depths of the lateral sulcus of the cerebral hemisphere (see Fig. 17-30A), is the insula (Latin island). BIRTH DEFECTS OF BRAIN B Temporal horn of lateral ventricle Because of the complexity of its embryologic history, abnormal development of the brain is common (approxi- mately 3 of 1000 births). Most major birth defects, such Head of caudate nucleus Tail of caudate nucleus as meroencephaly and meningoencephalocele, result from defective closure of the rostral neuropore (an NTD) during the fourth week (Fig. 17-31C) and involve the overlying tissues (meninges and calvaria). The factors causing NTDs are genetic, nutritional, and environmental. Birth defects of the brain can be caused by alterations in the morpho- genesis or histogenesis of the nervous tissue, or they can result from developmental failures occurring in associated structures (notochord, somites, mesenchyme, and cranium). Abnormal histogenesis of the cerebral cortex can result Lentiform nucleus in seizures (Fig. 17-32) and various degrees of mental Temporal horn Occipital horn deficiency. Subnormal intellectual development may C of lateral ventricle of lateral ventricle result from exposure of the embryo or fetus during the F I G U R E 1 7 – 2 8 Schematic diagrams of the medial surface 8- to 16-week period to viruses such as Rubella virus and of the developing right cerebral hemisphere show development high levels of radiation (see Table 20-6). Prenatal risk of the lateral ventricle, choroid fissure, and corpus striatum. A, At factors, such as maternal infection or thyroid disorder, Rh 13 weeks. B, At 21 weeks. C, At 32 weeks. factor incompatibility, and some hereditary and genetic conditions, cause most cases of cerebral palsy, but the The largest cerebral commissure is the corpus callosum central motor deficit may result from events during birth. (see Figs. 17-27A and 17-28A), which connects neocorti- Text continued on p. 412 cal areas. The corpus callosum initially lies in the lamina terminalis, but fibers are added to it as the cortex enlarges, and it gradually extends beyond the lamina terminalis. ENCEPHALOCELE The rest of the lamina terminalis lies between the corpus callosum and the fornix. It becomes stretched to form the Encephalocele is a herniation of intracranial contents septum pellucidum, a thin plate of brain tissue containing resulting from a defect in the cranium (cranium bifidum). nerve cells and fibers. Encephaloceles are most common in the occipital region At birth, the corpus callosum extends over the roof of (Figs. 17-33 and 17-34; see Fig. 17-31A to D). The hernia the diencephalon. The optic chiasm, which develops in may contain meninges (meningocele), meninges and the ventral part of the lamina terminalis (see Fig. 17-27A), part of the brain (meningoencephalocele), or meninges, consists of fibers from the medial halves of the retinae part of the brain, and part of the ventricular system (layer at back of the eyeball that is sensitive to light) that (meningohydroencephalocele). Encephalocele occurs in cross to join the optic tract of the opposite side. approximately 1 of 2000 births. The walls of the developing cerebral hemispheres initially show three typical zones of the neural tube: