Development Of The Nervous System PDF

DEVELOPMENT OF THE NERVOUS SYSTEM Lec. Gözde Öğütçü Near East University Department of Histology and Embryology [email protected]  The nervous system is derived from the ectoderm, which is...

DEVELOPMENT OF THE NERVOUS SYSTEM Lec. Gözde Öğütçü Near East University Department of Histology and Embryology [email protected]  The nervous system is derived from the ectoderm, which is the outermost layer of the embryonic disc  Developing nervous system appear during the third week as the neural plate and neural groove develop on the posterior aspect of the trilaminar embryo. The CNS is derived from the neuroectoderm: notochord induces the formation of the neural plate (thickening of the ectodermal layer), which further differentiates to form neural folds with a neural groove in between, leading to the formation of the neural tube (via neurulation).  At the begining of the 4th week Notochord and paraxial mesoderm induce ectoderm, neural plate is formed(Fibroblast growth factor,Transforming growth factor)is effective. Neural plate deepens, neural groove is formed. The two ends fuse and neural tube is formed. The cells separated during the unity form the neural crest. Neural tube:CNS Neural crest: Cranial,spinal and autonomic ganglia of PNS and OSS  The neural tube differentiates into the CNS. The neural crest gives rise to cells that form most of the PNS and ANS. Neurulation (formation of the neural plate and neural tube) begins during the fourth week (22–23 days) in the region of the fourth to sixth pairs of somites. At this stage, the cranial two thirds of the neural plate and tube as far caudal as the fourth pair of somites represent the future brain, and the caudal one third of the plate and tube represents the future spinal cord.  Fusion of the neural folds and formation of the neural tube begins at the fifth somite and proceeds in cranial and caudal directions until only small areas of the tube remain open at both ends. The lumen of the neural tube becomes the neural canal, which communicates freely with the amniotic cavity. The cranial opening (rostral neuropore) closes at approximately the 25th day, and the caudal neuropore closes at approximately the 27th day. DEVELOPMENT OF THE SPINAL CORD The primordial spinal cord develops from the caudal part of the neural plate and caudal eminence. The neural tube caudal to the fourth pair of somites develops into the spinal cord. Initially, the wall of the neural tube is composed of a thick, pseudostratified, columnar neuroepithelium. These neuroepithelial cells constitute the ventricular zone (ependymal layer), which gives rise to all neurons and macroglial cells (macroglia) in the spinal cord. A marginal zone composed of the outer parts of the neuroepithelial cells becomes recognizable. This zone gradually becomes the white matter of the spinal cord as axons grow into it from nerve cell bodies in the spinal cord, spinal ganglia, and brain. Middle layer = mantle layer becomes gray matter  These embryonic cells form an intermediate zone (mantle layer) between the ventricular and marginal zones. Neuroblasts become neurons as they develop cytoplasmic processes. The supporting cells of the CNS, called glioblasts (spongioblasts), differentiate from neuroepithelial cells, mainly after neuroblast formation has ceased. The glioblasts migrate from the ventricular zone into the intermediate and marginal zones.  When the neuroepithelial cells cease producing neuroblasts and glioblasts, they differentiate into ependymal cells, which form the ependyma (ependymal epithelium) lining the central canal of the spinal cord.  Proliferation and differentiation of neuroepithelial cells in the developing spinal cord produce thick walls and thin roof plates and floor plates. Differential thickening of the lateral walls of the spinal cord soon produces a shallow longitudinal groove on each side, the sulcus limitans. This groove separates the dorsal part (alar plate) from the ventral part (basal plate).  Cell bodies in the alar plates form the dorsal gray horns. Neurons in these horns constitute afferent nuclei and groups of them form the dorsal gray columns. As the alar plates enlarge, the dorsal median septum forms. Cell bodies in the basal plates form the ventral and lateral gray columns. Axons of ventral horn cells grow out of the spinal cord and form the ventral roots of the spinal nerves. As the basal plates enlarge, they bulge ventrally on each side of the median plane. As this occurs the ventral median septum forms, and a deep longitudinal groove (ventral median fissure) develops on the ventral surface of the spinal cord.  Development of Spinal Ganglia The unipolar neurons in the spinal ganglia (dorsal root ganglia) are derived from neural crest cells. The axons of cells in the spinal ganglia are at first bipolar, but the two processes soon unite in a T-shaped fashion. Both processes of spinal ganglion cells have the structural characteristics of axons, but the peripheral process is a dendrite in that there is conduction toward the cell body. The central processes enter the spinal cord and constitute the dorsal roots of spinal nerves.  The meninges (membranes covering the spinal cord) develop from cells of the neural crest and mesenchyme between 20 and 35 days. The cells migrate to surround the neural tube (primordium of the brain and spinal cord) and form the primordial meninges. The external layer of these membranes thickens to form the dura mater and the internal layer, the pia arachnoid, is composed of pia mater and arachnoid mater (leptomeninges). Three membranous layers cover the whole CNS: Dura mater: derived from surrounding mesenchyme and is tough and durable. Arachnoid mater: derived from neural crest; forms as a single layer with Pia mater. Pia mater: derived from neural crest; intimately covers the CNS.  Myelination begins at the end of the fetal period and continues postnatally. The cells responsible for myelination in the CNS are oligodendrocytes. Schwann cells do this job in the periphery. Myelin is seen in peripheral nerves from the 20th week. Motor roots are myelinated before sensory roots.  Positional Changes of Spinal Cord The spinal cord in the embryo extends the entire length of the vertebral canal. The spinal nerves pass through the intervertebral foramina opposite their levels of origin. The vertebrae and dura mater grow faster than the MS, resulting in the lower end of the MS remaining elevated. In a 24-week-old fetus, it lies at the level of the first sacral vertebra. The spinal cord in neonates terminates at the level of the second or third lumbar vertebra. In adults, the cord usually terminates at the inferior border of the first lumbar vertebra. The lower end of the MS is defined as the conus medullaris. Although the dura mater and arachnoid mater usually end at the S2 vertebra in adults, the pia mater does not. Distal to the caudal end of the spinal cord, the pia mater forms a long fibrous thread, the filum terminale (terminal filum), which indicates the original level of the caudal end of the embryonic spinal cord. The filum extends from the medullary cone and attaches to the periosteum of the first coccygeal vertebra. Medulla Spinalis Anomalies Spina bifida develops as a result of the failure of the vertebral arches to close. Spina bifida occulta: (often L5-S1) It is defined as a hollow, hairy area from the outside. It does not show clinical findings, it can be detected by chance. Spinal dermal sinus: Hollow in the sacral region, median region. Posterior neuropore closure area. Spina bifida cystica: The arch defect is large. If the meninges and CSF protrude, it is called spina bifida with meningocele. If the nerve roots are also involved, it is called spina bifida with meningomyelocele. Myeloschisis: A serious condition. The defect area is large, the neural tube is not closed. The spinal cord is open. DEVELOPMENT OF BRAIN The neural tube, cranial to the fourth pair of somites, develops into the brain. Neuroprogenitor cells proliferate, migrate, and differentiate to form specific areas of the brain. Fusion of the neural folds in the cranial region and closure of the rostral neuropore form three primary brain vesicles from which the brain develops: Forebrain (prosencephalon) Midbrain (mesencephalon) Hindbrain (rhombencephalon) During the fifth week, the forebrain partly divides into two secondary brain vesicles, the telencephalon and diencephalon; the midbrain does not divide. The hindbrain partly divides into two vesicles, the metencephalon and myelencephalon. Consequently, there are five secondary brain vesicles.  During the fifth week, the embryonic brain grows rapidly and bends ventrally with the head fold. The bending produces the midbrain(cephalic) flexure in the midbrain region and the cervical flexure at the junction of the hindbrain and spinal cord. Later, unequal growth of the brain between these flexures produces the pontine flexure in the opposite direction. This flexure results in thinning of the roof of the hindbrain.  As the tube grows in diameter, it also bends due to the rapid proliferation and ventral folding of the embryo. The resulting flexures that occur in the brain are called primary brain flexures. Three flexures occur: cervical flexure occurs between the brain and the spinal cord. cephalic flexure pushes the mesencephalon upwards pontine flexure occurs in the opposite direction from the other two; it generates the 4th ventricle Hindbrain The cervical flexure demarcates the hindbrain from the spinal cord. The pontine flexure, located in the future pontine region, divides the hindbrain into caudal (myelencephalon) and rostral (metencephalon) parts. The myelencephalon becomes the medulla oblongata (commonly called the medulla), and the metencephalon becomes the pons and cerebellum. The cavity of the hindbrain becomes the fourth ventricle and the central canal in the medulla  Myelencephalon Unlike those of the spinal cord, neuroblasts from the alar plates in the myelencephalon migrate into the marginal zone and form isolated areas of gray matter: the gracile nuclei medially and the cuneate nuclei laterally The ventral area of the medulla contains a pair of fiber bundles (pyramids) that consist of corticospinal fibers descending from the developing cerebral cortex The pontine flexure causes the lateral walls of the medulla to move laterally like the pages of an open book. As a result, its roof plate is stretched and greatly thinned. The cavity of this part of the myelencephalon (part of the future fourth ventricle) becomes diamond shaped.  Metencephalon The walls of the metencephalon form the pons and cerebellum, and the cavity of the metencephalon forms the superior part of the fourth ventricle. As in the rostral part of the myelencephalon, the pontine flexure causes divergence of the lateral walls of the pons, which spreads the gray matter in the floor of the fourth ventricle. As in the myelencephalon, neuroblasts in each basal plate develop into motor nuclei and organize into three columns on each side. The cerebellum develops from thickenings of dorsal parts of the alar plates. Initially, the cerebellar swellings project into the fourth ventricle. As the swellings enlarge and fuse in the median plane, they overgrow the rostral half of the fourth ventricle and overlap the pons and medulla  The structure of the cerebellum reflects its phylogenetic (evolutionary) development: The archicerebellum (flocculonodular lobe), the oldest part phylogenetically, has connections with the vestibular apparatus, especially the vestibule of the ear. The paleocerebellum (vermis and anterior lobe), of more recent development, is associated with sensory data from the limbs. The neocerebellum (posterior lobe), the newest part phylogenetically, is concerned with selective control of limb movements.  Nerve fibers connecting the cerebral and cerebellar cortices with the spinal cord pass through the marginal layer of the ventral region of the metencephalon. This region of the brainstem is the pons (Latin bridge) because of the robust band of nerve fibers that crosses the median plane and forms a bulky ridge on its anterior and lateral aspects  Cerebellum It means small brain (Latin) Although the cerebellum is only 10 percent of the brain's volume, it contains more than 50 percent of its total neurons (69 billion neurons) It is reported that the cerebellum is not only associated with motor coordination, proprioception and balance, but also plays a role in social thinking, cognitive and emotional behaviors.  Midbrain (mesencephalon) Undergoes less change than any other part of developing brain Neural canal narrows and becomes: –cerebral aqueduct: channel that connects third and fourth ventricles  Migrating neuroblasts from the alar laminae form the colliculus (bud)superior (vision) and colliculus inferior (hearing) structures. A thick layer -substantia nigra(associated with Parkinson's disease)(dopaminergic neurons have a lot of neuromelanin -black substance) developing from the basal lamina is formed. The ventral region where the fibers from the cerebrum pass is defined as the Crus (leg)cerebri. FOREBRAIN The rostral (anterior) part of the forebrain, including the primordia of the cerebral hemispheres, is the telencephalon; the caudal (posterior) part of the forebrain is the diencephalon. The cavities of the telencephalon and diencephalon contribute to the formation of the third ventricle.  As closure of the rostral neuropore occurs two lateral outgrowths (optic vesicles) appear one on each side of the forebrain. These vesicles are the primordia of the retinae and optic nerves. A second pair of diverticula, the telencephalic vesicles, soon arise more dorsally and rostrally. They are the primordia of the cerebral hemispheres, and their cavities become the lateral ventricles Telencephalon Arise at beginning of fifth week as bilateral evaginations of lateral wall of prosencephalon Consists of two lateral outpocketings called cerebral or telencephalic vesicles : --primordia of cerebral hemispheres and their cavities lateral ventricles Telencephalon The cerebral vesicles are connected to the 3rd ventricular cavity by the foramen interventriculare (foramen of Monro). The basal parts of the cerebral hemispheres, formed by the elongation of the thalamus,grow, and form a bulge into the lateral ventricle, towards the base of the Foramen of Monro. This thick bulge grows slowly and takes on a striated appearance in cross-sections - it is called the corpus striatum. The increase in neuroblasts in the region adjacent to the diencephalon is quite low, this region remains thin,and the choroid plexus forms here. The plexus extends into the ventricle, following the choroidal fissure. The hemisphere wall thickens just above the fissure and forms the hippocampus (smell, memory, stem cells). The corpus striatum expands, axons to and from the cortex pass through it (internal capsule), and the caudate and lentiform nuclei are formed.  Walls of Developing Cerebral Hemispheres Initially show three typical zones of neural tube 1.Ventricular 2.Intermediate 3.Marginal Intermediate zone cells migrate into marginal zone and give rise to –cortical layers; Gray matter is thus located peripherally – axons from its cell bodies pass centrally to form; large volume of white matter, medullary center Cerebral Hemispheres  Diencephalon Three swellings develop in the lateral walls of the third ventricle, which later become the thalamus, hypothalamus, and epithalamus. The thalamus is separated from the epithalamus by the epithalamic sulcus and from the hypothalamus by the hypothalamic sulcus. The pineal gland (pineal body) develops as a median diverticulum of the caudal part of the roof of the diencephalon Cerebral Commissures As the cerebral cortex develops, groups of nerve fibers (commissures) connect corresponding areas of the cerebral hemispheres with one another. The most important of these commissures crosses in the lamina terminalis, which is the rostral (anterior) end of the forebrain The lamina terminalis is the natural pathway from one hemisphere to the other. The first commissures to form are the anterior commissure and hippocampal commissure. The anterior commissure connects the olfactory bulb (rostral extremity of the olfactory tract) and related areas of one hemisphere with those of the opposite side. The hippocampal commissure connects the hippocampal formations. The largest cerebral commissure is the corpus callosum, which connects neocortical areas.  Corpus callosum: the most important commissure. It connects areas other than the olfactory and related areas. Initially, it courses within the lamina terminalis, and with the expansion of the neopallidum, it forms an arch over the thin roof of the diencephalon.  The hemispheres grow in anterior, dorsal and inferior directions, and the frontal, temporal and occipital lobes are formed. Growth slows down on the corpus striatum, and the area between the frontal and temporal lobes remains sunken; it is called the insula (desire, hatred, pride,guilt, apology, pleasure-music- eating-work,dream, humiliation, addiction). With the growth of neighboring lobes, this area is covered.  Surface of Cerebral Hemispheres Initially, smooth As growth proceeds, the following develop: – gyri are rounded surface elevations – sulci are grooves or furrows between gyri Sulci and gyri permit a considerable increase in surface area of cerebral cortex without requiring an extensive increase in cranial size BIRTH DEFECTS OF BRAIN Because of the complexity of its embryologic history, abnormal development of the brain is common (approximately 3 of 1000 births). Most major birth defects, such as meroencephaly and meningoencephalocele, result from defective closure of the rostral neuropore (an NTD) during the fourth week 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 morphogenesis or histogenesis of the nervous tissue, or they can result from developmental failures occurring in associated structures (notochord, somites, mesenchyme, and cranium). Prenatal risk factors, such as maternal infection or thyroid disorder, Rh factor incompatibility, and some hereditary and genetic conditions, cause most cases of cerebral palsy, but the central motor deficit may result from events during birth.  Posterior fonticle and occipital region openings may occur. It occurs most frequently in the occipital region. If the meninges and CSF protrude from the opening region, it is called Cranial Meningocele (B). If nerve tissue is also located in the protrusion, Meningoencephalocele (C), If the ventricular cavity is also accompanied, disorders called meningo-hydroencephalocele (D)occur.  Meningoencephalocele consists of a protrusion of part of the cerebellum that is covered by meninges and skin. References 1. Langman, Medical Embryology 2. Moore-Persaud, Human Embryology