Primary Neurulation

Primary neurulation forms brain and spinal cord as far caudal as S2 (1, 2, 3, 4). Primary neurulation occurs between POD 17 and 27, resulting in the formation of a neural tube and separation of cutaneous from neuroectoderm. Primary neurulation comprises two distinct processes, neural plate shaping and neural plate bending, which then culminate in fusion.

Neural Plate Shaping

• Cell division and alteration of shape: Neural plate shaping is due to both directed cell division and changes in the shape of individual neural plate cells (converting neural plate cells from cuboidal to columnar through the action of microtubules).
• Changes in neural plate: This process expands the neural plate cranial to Hensen’s node, which will form the brain, and narrows and elongates the neural plate flanking either side of the primary streak, which will form the spinal cord.

Neural plate: Shown is the neural plate at onset of primary neurulation as cells begin division and alteration of shape (4).

Neural Plate Bending

Components of bending

• Formation of neural groove: The formation of a midline neural groove (or median hinge point) directly overlies the notochord and is induced by it.
• Elevation of lateral walls: The laterally paired neural folds surrounding the neural groove are elevated.
• Formation of dorsolateral hinge points: Bilaterally paired dorsolateral hinge points (by mechanisms similar to those that form the neural groove) are formed, and the neural folds converge toward the midline.

Formation of neural groove: Midline bending of the neural plate over the notochord forms the neural folds (4).

Convergence of neural folds: Lateral bending occurs at the hinge points with convergence of the neural folds (4).

Fusion and closure

• Midline dorsal fusion of neural folds: Convergence of the neural folds results in apposition and fusion of the neural folds to one another, with separation of the cutaneous ectoderm from the neuroectoderm (dysjunction).
• Initial point of contact at cervicomedullary junction: Neural fold fusion occurs first near the cervicomedullary junction and proceeds both cranially and caudally from this point.
• Discontinuous waves of primary neurulation: Closure is likely discontinuous, and secondary waves of closure may occur at other levels of the neuraxis as well. The process is not simply a zippering up of the neural tube in a cranial-caudal direction.
• Neuropores: Points where waves of closure meet are called neuropores.
• Completion of closure between POD 24 and 26: The last two (and most important) points of closure are the anterior neuropore, which is represented by the lamina terminalis at POD 24, and the caudal neuropore, represented by S2, at POD 26. The time of closure of the caudal neuropores is an estimate since not all of the somites are visible at the time of the closure. Embryologists have made these estimates by measuring the length of the somites and estimating how many would fit between the last formed somite and the posterior neuropore.

Fusion: Shown is the neural fold fusion with dysjunction of the overlying ectoderm (4).

Neural Crest Cells

Neural crest cells lie near the junction of cutaneous ectoderm and neuroectoderm and are destined to form a variety of tissues including the following:

• Branchial arch derivatives: These contribute to head and neck structures.
• Dorsal roots and dorsal root ganglia
• Autonomic ganglia: Neural crest cells form both sympathetic and parasympathetic ganglia.
• Adrenal medulla: Neural crest cells form the adrenergic cells of the adrenal medulla.