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Neurulation

Neural Tube

The nervous system develops when the notochord induces its overlying ectoderm to become neuroectoderm and to develop into the neural plate.  The neural plate folds along its central axis to form a neural groove lined on each side by a neural fold.  The two neural folds fuse together and pinch off to become the neural tube. Fusion of the neural folds begins in the middle of the embryo and moves cranially and caudally.  The cranial open end of the tube is the anterior (rostral) neuropore, and the caudal open end of the tube is the posterior (caudal) neuropore.  The anterior neuropore closes on or before day 26 and the caudal neuropore closes before the end of the fourth week.

Neural Crest

Some cells from the neural folds give rise to pleuripotent neural crest cells that migrate widely in the embryo and give rise to many nervous structures:

·       Spinal ganglia (dorsal root ganglia)

·       Ganglia of the autonomic nervous system

·       Ganglia of some cranial nerves

·       Sheaths of peripheral nerves

·       Meninges of brain and spinal cord

·       Pigment cells

·       Suprarenal medulla

·       Skeletal and muscular components in the head

Central Nervous System

Development of Brain

The neural tube forms three primary brain vesicles.  The primary brain vesicles give rise to five secondary brain vesicles, which give rise to various adult structures.

Figure 5 - Structure of embryonic brain

Development of Spinal Cord

The neural tube consists of three cellular layers from inner to outer: the ventricular zone (ependymal layer), the intermediate zone (mantle layer), and the marginal zone (marginal layer).  The ventricular zone gives rise to neuroblasts (future nerve cells) and glioblasts (future supporting cells) which migrate into the intermediate zone form two collections of cells (the alar plate and the basal plate) separated by a groove called the sulcus limitans.  Cells in the alar plate become afferent (sensory) neurons and form the dorsal (posterior) horn of the spinal cord.  Cells in the basal plate become efferent (motor) neurons and form the ventral (anterior) horn of the spinal cord.  The two ventral horns bulge ventrally to create ventral median fissure.  The dorsal horns merge to create the dorsal median septum.  The lumen of the neural tube becomes the central canal of the spinal cord.

The spinal cord extends the entire length of the vertebral canal at week 8 of development.  At birth, the conus medullaris extends to the L3 vertebra.  In the adult, the conus medullaris extends to the L1 vertebra.  Spinal lumbar punctures must be performed caudally to the conus medullaris to avoid damaging the spinal cord.

Development of Meninges

The dura mater arises from paraxial mesoderm that surrounds the neural tube.  The pia mater and arachnoid mater arise from neural crest cells.

Hypophysis (Pituitary Gland)

The anterior pituitary gland (adenohypophysis) arises from an evagination of the oropharyngeal membrane known as Rathke’s pouch.  The posterior pituitary gland (neurohypophysis) arises from an evagination of neuroectoderm from the diencephalon.

Clinical Correlations

Spina Bifida

·       Spina bifida occulta is a defect of the vertebral column only, and is a common problem affecting as many as 10% of live births.

·       Spina bifida with meningocele (spina bifida cystica) is a defect of the vertebral column with protrusion of the meninges through the defect.

·       Spina bifida with myelomeningocele is a defect of the vertebral column protrusion of the meninges and herniation of the spinal cord through the defect.

·       Spina bifida with myeloschisis results from the failure of the caudal neuropore to close at the end of the fourth week of development.  Newborn infants are paralyzed distal to the lesion.

These defects usually occur in the cervical and/or lumbar regions and may cause neurologic deficits in the lower limbs and urinary bladder.  Neural tube defects can be detected by the presence of alpha-fetoprotein (AFP) in the fetal circulation after the fourth week of development.

Anencephaly

Anencephaly is the failure of the anterior neuropore to close, resulting in a failure of the brain to develop.

Microcephaly

Microcephaly (small head) results from microencephaly (small brain), or the failure of the brain to grow normally.  This can be the result of exposure to large doses of radiation up to the sixteenth week of development, or from certain infectious agents (cytomegalovirus, herpes simplex virus, and toxoplasma gondii)

Hydrocephalus

Hydrocephalus is an accumulation of CSF in the ventricles of the brain, caused most commonly by stenosis of the cerebral aqueduct.  In the absence of surgical treatment in extreme cases the head may swell to three times its normal size.

Arnold-Chiari Malformation

Arnold-Chiari malformation is herniation parts of the cerebellum (medulla oblongata and cerebellar vermis) through the foramen magnum of the skull.

Fetal Alcohol Syndrome

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