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Neurulation is the embryological process that forms the precursors of the central nervous system, occurring after gastrulation establishes the three primary cell layers. During neurulation, the central portion of the ectoderm—initially a flat sheet of cells—folds upward and inward, sealing to form a hollow neural tube. The anterior neural tube develops into the brain, while the remainder forms the spinal cord.

Protein signals cause the midline ectoderm to thicken, forming the neural plate above a condensed mesodermal rod called the notochord. Notochord-attached cells transform from columns into wedges, causing the neural plate to bend upward and inward. Neural folds form at the plate's edges and move toward each other, eventually fusing and detaching from the surface ectoderm to create the hollow neural tube.

Neural crest cells are a population located at the junction between neural and surface ectoderm. As neural folds elevate and fuse during neurulation, neural crest cells appear at the fold tips, identifiable by markers like the Pax7 transcription factor. These cells subsequently migrate throughout the embryo via cell migration to generate diverse tissue types, including peripheral nervous system components like intestinal ganglia.

Neural crest cells downregulate specific adhesive proteins, allowing them to detach from other cells in the neural tube. This reduction in cell-cell adhesion enables neural crest cells to travel throughout the embryo, populating different regions to generate various tissue types including elements of the peripheral nervous system.

Primary neurulation forms most of the central nervous system in humans through folding of three distinct ectoderm cell sheets. Secondary neurulation, which forms a small posterior spinal cord region, involves loosely-packed cells that condense into a medullary cord, which then hollows out and merges with the anterior primary neural tube to form a continuous structure.

Although secondary neurulation plays a relatively minor role in forming the human central nervous system, defects in this process can cause developmental consequences such as certain types of spina bifida. These defects occur when the medullary cord fails to properly hollow out or merge with the primary neural tube.

The notochord is a condensed rod of mesodermal cells positioned beneath the neural plate. Notochord-attached cells initially resemble columns but transform into wedges over time. This transformation, along with other factors, causes the entire neural plate to bend upward and inward as if on a hinge, driving the folding mechanism essential to neural tube formation.