EMBRYOLOGICAL

DEVELOPMENT
OF
THE CENTRAL NERVOUS SYSTEM

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Introduction
CNS originates in the ectoderm -----Neural plate, Neural folds, Neural tube. BRAIN + 3 VESICLE
Rhombencephalon (hind brain). Mesencephalon (mid brain). Proencephalon (fore brain).

Rhombencephalon (mesencephalon(medulla) &metencephalon (basal efferent and alar afferent). &cerebellum (coordinating center) + pons (pathway). Mesencephalon (midbrain)+ spinal cord ) (basal efferent & alar afferent) alar part anterior visual and posterior auditory. Diencephalon (posterior portion of the forebrain (thin roof + thick plate) thalamus & hypothalamus. Rathkes pouch adenohypophysis, intermediate lobe & pass tuberalis. Diencephalon --- posterior lobe (neurohypophysis). Telencephalon (rostral brain vesicle) ---= 2 outpockting (cereberal hemisphere medina portion (lamina terminalis connects the 2 hemispheres).

Central Nervous System

The central nervous system (CNS) appears at the beginning of the third week as a slippershaped plate of thickened ectoderm, the neural plate, in the middorsal region in front of the primitive node. Its lateral edges soon elevate to form the neural folds.
Scanning electron micrograph of a mouse embryo at approximately 18 days

Central Nervous System

With further development, the neural plate (thickened ectoderm) forms the neural tube. Fusion between neural folds begins in the cervical region and proceeds in cephalic and caudal directions. Once fusion is initiated, the open ends of the neural tube form the cranial and caudal neuropores that communicate with the overlying amniotic cavity. Closure of the cranial neuropore proceeds cranially from the initial closure site in the cervical region and from a site in the forebrain that forms later.

AC. Transverse sections through successively older embryos showing formation of the neural groove, neural tube, and neural crest. Cells of the neural crest, migrate from the edges of the neural folds and develop into spinal and cranial sensory ganglia (AC).

Dorsal view of a human embryo

A. Dorsal view of a human embryo at approximately day 22. Seven distinct somites are visible on each side of the neural tube.

B. Dorsal view of a human embryo at approximately day 23. The nervous system is in connection with the amniotic cavity through the cranial and caudal neuropores.

Central Nervous System

The cephalic end of the neural tube shows three dilations, the primary brain vesicles: 1. The prosencephalon, or forebrain; 2. The mesencephalon,or midbrain; 3. The rhombencephalon, or hindbrain. Simultaneously it forms two flexures: A. The cervical flexure at the junction of the hindbrain and the spinal cord. B. The cephalic flexure in the midbrain region. When the embryo is 5 weeks old, the prosencephalon consists of two parts: i. The telencephalon, formed by a midportion and two lateral outpocketings, the primitive cerebral hemispheres, ii. The diencephalon, characterized by outgrowth of the optic vesicles.
Asterisk, outpocketing of the telencephalon; arrow, rhombencephalic isthmus; arrowheads, roof of the fourth ventricle; o, optic stalk.

Central Nervous System

A deep furrow, the rhombencephalic isthmus, separates the mesencephalon from the rhombencephalon. The rhombencephalon also consists of two parts:
1)

2)

The metencephalon, which later forms the pons and cerebellum, The myelencephalon. The boundary between these two portions is marked by the pontine flexure. The lumen of the spinal cord, the central canal, is continuous with that of the brain vesicles. The cavity of the rhombencephalon is the fourth ventricle, that of the diencephalon is the third ventricle, and those of the cerebral hemispheres are the lateral ventricles. The lumen of the mesencephalon connects the third and fourth ventricles. This lumen becomes very narrow and is then known as the aqueduct of Sylvius. The lateral ventricles communicate with the third ventricle through the interventricular foramina of Monro.

Neural Crest Cells

These neural crest cells are ectodermal in origin and extend throughout the length of the neural tube.

Crest cells migrate laterally and give rise to sensory ganglia (dorsal root ganglia) of the spinal nerves and other cell types.

Neural Crest Cells

Hence, neuroblasts of the sensory ganglia derived from neural crest cells give rise to the dorsal root neurons. In addition to forming sensory ganglia, cells of the neural crest differentiate into sympathetic neuroblasts, Schwann cells, pigment cells, odontoblasts, meninges, and mesenchyme of the pharyngeal arches.

Spinal Nerves
Motor nerve fibers begin to appear in the fourth week, arising from nerve cells in the basal plates (ventral horns) of the spinal cord. These fibers collect into bundles known as ventral nerve roots. Dorsal nerve roots form as collections of fibers originating from cells in dorsal root ganglia (spinal ganglia). Almost immediately, spinal nerves divide into dorsal and ventral primary rami.

16 Lumbosacral region of patients with neural tube defects. A. Patient with a large meningomyelocele. B. Patient with a severe defect in which the neural folds failed to elevate throughout the lower thoracic and lumbosacral regions, resulting in rachischisis.

CLINICALCORRELATES Neural Tube Defects

Most defects of the spinal cord result from abnormal closure of the neural folds in the third and fourth weeks of development. The resulting abnormalities, neural tube defects (NTDs), may involve the meninges, vertebrae, muscles, and skin. Severe NTDs involving neural and non-neural structures occur in approximately 1 in 1000 births

Neural Tube Defects

Spina bifida is a general term for NTDs affecting the spinal region. It consists of a splitting of the vertebral arches and may or may not involve underlying neural tissue. Two different types of spina bifida occur: 1) Spina bifida occulta is a defect in the vertebral arches that is covered by skin and usually does not involve underlying neural tissue. It occurs in the lumbosacral region (L4 to S1) and is usually marked by a patch of hair overlying the affected region. 2) Spina bifida cystica is a severe NTD in which neural tissue and/or meninges protrude through a defect in the vertebral arches and skin to form a cyst like sac.

Neural Tube Defects

Occasionally the neural folds do not elevate but remain as a flattened mass of neural tissue (spina bifida with myeloschisis or rachischisis). Hydrocephaly develops in virtually every case of spina bifida cystica because the spinal cord is tethered to the vertebral column.

Neural Tube Defects/ Dx +Rx

A new treatment for the defect is to perform surgery in utero at approximately 28 weeks of gestation.
The baby is exposed by cesarean section, the defect is repaired, and the infant is placed back in the uterus. Preliminary results indicate that this approach reduces the incidence of hydrocephalus, improves bladder and bowel control, and increases motor development to the lower limbs.

RHOMBENCEPHALON HINDBRAIN
The rhombencephalon consists of the myelencephalon, the most caudal of the brain vesicles, and the metencephalon, which extends from the pontine flexure to the rhombencephalic isthmus.

Lateral view of the brain vesicles in an 8-week embryo (crown-rump length approximately 27 mm). The roof plate of the rhombencephalon has been removed to show the intraventricular portion of the rhombic lip. Note the origin of the cranial nerves.

Myelencephalon
The myelencephalon is a brain vesicle that gives rise to the medulla oblongata. The basal plate, similar to that of the spinal cord, contains motor nuclei. These nuclei are divided into three groups: 1. Medial somatic efferent group, 2. Intermediate special visceral efferent group, 3. Lateral general visceral efferent group .

A. Dorsal view of the floor of the fourth ventricle in a 6week embryo after removal of the roof plate. Note the alar and basal plates in the myelencephalon. The rhombic lip is visible in the

B and C. Position and differentiation

Metencephalon
The metencephalon, similar to the myelencephalon, is characterized by basaland alar plates. Two new components form:
1. 2. 1) 2) The cerebellum, The pons, Each basal plate of the metencephalon contains three groups of motor neurons: The medial somatic efferent group, which gives rise to the nucleus of the abducens nerve; The special visceral efferent group, containing nuclei of the trigeminal and facial nerves, which innervate the musculature of the first and second pharyngeal arches; The general visceral efferent group, whose axons supply the submandibular and sublingual glands.

3)

Figure 19.20 A. Dorsal view of the mesencephalon and rhombencephalon in an 8-week embryo. The roof of the fourth ventricle has been removed, allowing a view of its floor. B. Similar view in a 4-month embryo. Note the choroidal fissure and the lateral and medial apertures in the roof of the fourth ventricle.

Cerebellum
As a result of a further deepening of the pontine flexure, the rhombic lips compress cephalocaudally and form the cerebellar plate. In a 12-week embryo, this plate shows a small midline portion, the vermis, and two lateral portions, the hemispheres. flocculonodular lobe is phylogenetically the most primitive part of the cerebellum.

Sagittal sections through the roof of the metencephalon showing development of the cerebellum. A. 8 weeks (approximately 30 mm). B. 12 weeks (70 mm). C. 13 weeks. D. 15 weeks. Note formation of the external granular layer on the surface of the cerebellar plate (B and C).

During later stages, cells of the external granular layer migrate inward to mingle with Purkinje cells and form the definitive cortex of the cerebellum. The dentate nucleus is one of the deep cerebellar nuclei. Note the anterior and posterior velum.

Cerebellum
In the sixth month of development, the external granular layer gives rise to various cell types. Basket and stellate cells are produced by proliferating cells in the cerebellar white matter.
22 Stages in development of the cerebellar cortex. A. The external granular layer on the surface of the cerebellum forms a proliferative layer from which granule cells arise. They migrate inward from the surface (arrows). Basket and stellate cells derive from proliferating cells in the cerebellar white matter. B. Postnatal cerebellar cortex showing differentiated Purkinje cells, the molecular layer on the surface, and the internal granular layer beneath the Purkinje cells.

PROSENCEPHALON: FOREBRAIN
The prosencephalon consists of the
1. Telencephalon, which forms the cerebral hemispheres, 2. Diencephalon, which forms the optic cup and stalk, pituitary, thalamus, hypothalamus, and epiphysis.

 CLINICALCORRELATES Hypophyseal Defects Occasionally a small portion of Rathkes pouch persists in the roof of the pharynx as a pharyngeal hypophysis. Craniopharyngiomas arise from remnants of Rathkes pouch. They may form within the sella turcica or along the stalk of the pituitary but usually lie above the sella. They may cause hydrocephalus and pituitary dysfunction (e.g., diabetes insipidus, growth failure).

CLINICALCORRELATES Cranial Defects

Holoprosencephaly (HPE) refers to a spectrum of abnormalities in which a loss of midline structures results in malformations of the brain and face. In severe cases, the lateral ventricles merge into a single telencephalic vesicle (alobar HPE), the eyes are fused, and there is a single nasal chamber along with other midline facial defects.

CLINICALCORRELATES Cranial Defects

Schizencephaly is a rare disorder in which large clefts occur in the cerebral hemispheres, sometimes causing a loss of brain tissue Meningocele, meningoencephalocele, and meningohydroencephalocele are

all caused by an ossification defect in the bones of the skull. The most frequently affected bone is the squamous part of the occipital bone, which may be partially or totally lacking. If the opening of the occipital bone is small, only meninges bulge through it

(meningocele).

Figure 19.36 AD. Various types of brain herniation due to abnormal ossification of the skull.

CLINICALCORRELATES Cranial Defects

Exencephaly is characterized by failure of the cephalic part of the neural tube to close. As a result,

the vault of the skull does not form, leaving the malformed brain exposed. Later this tissue degenerates, leaving a mass of necrotic tissue. This defect is called anencephaly, although the brainstem remains intact. Since the fetus lacks the mechanism for swallowing, the last 2 months of pregnancy are characterized by

hydramnios. The abnormality can be recognized on a radiograph, since the vault of the skull is absent.

CLINICALCORRELATES Cranial Defects

Hydrocephalus is characterized by an abnormal accumulation of cerebrospinal fluid within the of Sylvius (aqueductal stenosis). This prevents the cerebrospinal fluid of the lateral and third ventricles from

ventricular system. In most cases, hydrocephalus in the newborn is due to an obstruction of the aqueduct

passing into the fourth ventricle and from there into the subarachnoid space, where it would be resorbed.