Neural Tube Formation

• Neural Tube Formation begins at the start of the 3rd week of development.
• The ectodermal germ layer is shaped like a disc, wider in the cephalic region than the caudal region.
• The notochord and prechordal mesoderm induce the overlying ectoderm to thicken, forming the slipper-shaped neural plate in the mid-dorsal region in front of the primitive node.
• Neuroectoderm cells make up the neural plate.
• Induction of these cells is the initial event in neurulation, which is the formation of the central nervous system (CNS; brain + spinal cord).
• Neurocrest cells are migratory cells.

Neural Tube Formation Process

• The lateral edges of the neural plate elevate, forming neural folds.
• The depressed mid-region forms the neural groove.
• Neural folds elevate, approach each other in the midline, and fuse, forming the neural tube.
• Fusion starts in the cervical region (5th somite) and proceeds in cephalic and caudal directions.
• The open ends of the neural tube form the cranial and caudal neuropores, which communicate with the overlying amniotic cavity.
• Closure of the cranial neuropore proceeds cranially from the initial closure site in the cervical region.
• Final closure of the cranial neuropore occurs at the 18 to 20-somite stage around the 25th day.
• Closure of the caudal neuropore occurs approximately 2-3 days later around the 27th to 28th day.

Neural Tube Derivatives

• The cephalic end of the neural tube shows three dilations, forming the primary brain vesicles: Prosencephalon (forebrain), Mesencephalon (midbrain), and Rhombencephalon (hindbrain).
• Two flexures form simultaneously: Cervical flexure at the junction of the hindbrain and the spinal cord, and Cephalic flexure in the midbrain region.
• At 5 weeks, the prosencephalon consists of two parts: Telencephalon and Diencephalon.
• The telencephalon is formed by a midportion and two lateral outpocketings called the primitive cerebral hemispheres.
• The diencephalon is characterized by the outgrowth of the optic vesicles.
• A deep furrow, the rhombencephalic isthmus, separates the mesencephalon from the rhombencephalon.
• The rhombencephalon consists of two parts: Metencephalon (pons and cerebellum) and Myelencephalon (medulla oblongata).
• The boundary between these two portions is marked by the pontine flexure.

Neural Tube Formation and Cavities

• The lumen of the spinal cord, known as the central canal, is continuous with that of the brain vesicles.
• The rhombencephalon's cavity becomes the fourth ventricle.
• The diencephalon's cavity becomes the third ventricle.
• The cerebral hemispheres' cavities become the lateral ventricles.
• The mesencephalon's lumen connects the third and fourth ventricles.
• The mesencephalon's lumen becomes the aqueduct of Sylvius (cerebral aqueduct).
• Each lateral ventricle communicates with the third ventricle through the interventricular foramina of Monro.

Brainstem

• The brain can be divided into the brainstem and higher centers.
• The brainstem consists of the mesencephalon (midbrain), pons (from the metencephalon), and Myelencephalon (medulla oblongata).
• The higher centers include the cerebellum and cerebral hemispheres.
• The brainstem is a direct continuation of the spinal cord and has a similar organization.

Neurocrest Cells

• Neurocrest cells originate from the ectoderm and extend along the neural tube's length.
• They migrate laterally and give rise to sensory ganglia (dorsal root ganglia) of the spinal nerves and other cell types.
• Derivatives of the neural crest cells include: melanocytes, glial cells, sensory ganglia, sympathetic and enteric neurons, Schwann's cells, arachnoid and pia mater (leptomeninges), chromaffin cells of the adrenal medulla, contributes to the craniofacial skeleton as well as neurons for cranial ganglia, conotruncal septum in the heart, and C cells of the thyroid gland.

Clinical Correlates

• Meningocele, Meningoencephalocele, and Meningohydroencephalocele all are 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).
• If the defect is large, part of the brain also bulges through it (meningoencephalocele).
• If part of the ventricle penetrates through the opening into the meningeal sac, it is called meningohydroencephalocele.
• These defects occur in 1/2000 births.
• In most cases, the origin of these defects is due to abnormal neural tube closure, and many can be prevented by maternal use of folic acid (400 µg daily) prior to and during pregnancy.
• 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 and exposed brain.
• This tissue degenerates, leaving a mass of necrotic tissue.
• This defect is called anencephaly, although the brainstem remains intact.
• In some cases, the closure defect of the neural tube extends caudally into the spinal cord, termed craniorachischisis.
• Anencephaly is a common abnormality (1/1500) and occurs 4 times more often in females than in males.
• Up to 70% of cases of spina bifida can be prevented by women taking 400 µg of folic acid per day before and during pregnancy.
• Hydrocephalus is characterized by an abnormal accumulation of cerebrospinal fluid within the ventricular system.
• In most cases in newborns, it results from obstruction of the aqueduct of Sylvius (aqueductal stenosis).
• This obstruction prevents cerebrospinal fluid from passing into the fourth ventricle and from there into the subarachnoid space, where it would be resorbed.
• Fluid accumulates in lateral ventricles, pressing on the brain and bones of the skull.
• Microcephaly describes a cranial vault that is smaller than normal.
• Because the size of the cranium depends on the brain's growth, the underlying defect is in brain development.
• Closure of the neuropores requires folic acid.
• One of the reasons for giving mothers folic acid during pregnancy.