Neurulation: Formation of the Brain and Spinal Cord

Neurulation is a foundational process in early embryonic life where a portion of the ectoderm, the outermost germ layer, becomes the nervous system. This series of cellular movements and differentiations establishes the rudimentary structures that develop into the brain and spinal cord, ensuring their correct placement. Successful completion is necessary for the formation of a functional central nervous system.

The Process of Neurulation

Neurulation begins in the third week of human gestation when the notochord signals the ectoderm layer above it. These signals cause the ectodermal cells to thicken and form the neural plate. The cells in this plate are committed to a neural fate, distinguishing them from the surrounding ectoderm that will form the skin. The neural plate then elongates along the embryo’s head-to-tail axis and narrows.

The neural plate’s lateral edges then begin to rise, creating the neural folds on either side of a central depression called the neural groove. This folding is driven by changes in cell shape and proliferation. The neural folds continue to elevate and move toward the embryo’s midline, similar to closing a zipper.

The neural folds converge and fuse, transforming the open plate into a closed, hollow cylinder called the neural tube. Fusion begins in the future neck region and proceeds toward the head and tail. This primary neurulation process forms most of the brain and spinal cord, while secondary neurulation forms the very bottom of the spinal cord by hollowing out a solid cord of cells.

As the neural tube separates from the overlying ectoderm, a population of neural crest cells emerges from the crest of the neural folds. These cells detach and migrate throughout the embryo. Their journey and differentiation are separate from the neural tube itself.

Structures Originating from Neurulation

The neural tube is the direct precursor to the central nervous system (CNS), which includes the brain and spinal cord. Shortly after forming, the tube’s cranial (head) end expands to form three primary brain vesicles: the forebrain, midbrain, and hindbrain. These vesicles further subdivide and develop into all the structures of the adult brain.

The remainder of the neural tube elongates to become the spinal cord. Its internal hollow space persists as the brain’s ventricular system and the spinal cord’s central canal, which contain cerebrospinal fluid. The walls of the neural tube are composed of neuroepithelial cells that differentiate into the neurons and most glial cells of the CNS.

Distinct from the neural tube, the neural crest cells that separated during neurulation are multipotent and migratory. These cells travel along specific pathways to various destinations throughout the embryo, giving rise to a diverse array of cell types.

The fates of neural crest cells are numerous. They give rise to:

• The entire peripheral nervous system, which includes all nerves and ganglia outside of the brain and spinal cord.
• Melanocytes, the pigment-producing cells found in the skin.
• Cartilage and bone, particularly in the face and skull.
• Parts of the adrenal glands and the connective tissues of many other organs.

Neurulation: Importance and Developmental Issues

The proper progression of neurulation is necessary for healthy embryonic development. The formation of the neural tube properly separates the future central nervous system from the skin and establishes the basic body plan. Any disruption in this sequence of events can have severe consequences, affecting the embryo’s viability or leading to lifelong disabilities.

Errors in the fusion of the neural folds result in birth defects known as neural tube defects (NTDs). The specific defect depends on where the closure fails. If failure occurs at the cranial end, it results in anencephaly, a condition marked by the absence of major portions of the brain and skull, and infants with this condition are not viable.

When closure failure occurs along the developing spinal cord, it causes spina bifida, which varies in severity. The mildest form, spina bifida occulta, involves a small gap in the vertebrae and often has no symptoms. More severe forms include meningocele, where protective membranes push out, and myelomeningocele, where the spinal cord itself protrudes, resulting in nerve damage and paralysis.

Maternal intake of folic acid (vitamin B9) can reduce the incidence of neural tube defects, so supplementation is recommended for women who may become pregnant. The folding and fusion events occur between the third and fourth weeks of gestation, often before an individual knows they are pregnant. Therefore, supplementation must begin before conception to be most effective. While other factors can contribute, adequate folic acid is the primary preventive measure against NTDs.