Neurulation is the embryological process which forms the precursors of the central nervous system and occurs after gastrulation has established the three primary cell layers of the embryo: ectoderm, mesoderm, and endoderm. In humans, the majority of this system is formed via primary neurulation, in which the central portion of the ectoderm—originally appearing as a flat sheet of cells—folds upwards and inwards, sealing off to form a hollow neural tube. As development proceeds, the anterior portion of the neural tube will give rise to the brain, with the rest forming the spinal cord.

Neurulation and the Neural Crest

The central portion of the ectoderm that bends to generate the neural tube is aptly called the neural ectoderm, while the areas that flank it—along the periphery of the embryo—are the surface ectoderm. However, at the junction of the neural and surface ectoderm lies another population of cells, called the neural crest. As the neural folds (the edges of the elevating neural tube) begin to appear, neural crest cells (NCCs) can be visualized in their tips through the expression of characteristic markers, like the Pax7 transcription factor. As development proceeds and the neural folds fuse, NCCs can be observed either in the top-most portion of the neural tube or migrating along this structure’s sides towards lower regions of the embryo. To migrate, NCCs downregulate specific adhesive proteins, which allows them to detach from the other cells in the neural tube. Importantly, NCCs travel throughout the embryo, populating different regions to generate a variety of tissue types, including elements of the peripheral nervous system (like the ganglia of the intestines).

Primary vs. Secondary Neurulation

While primary neurulation forms most of the central nervous system in humans, a small area of the posterior spinal cord results from a distinct process called secondary neurulation. In this region, rather than having three distinct cell sheets, the embryo contains a mixture of loosely-packed cells covered by a thin layer of ectoderm. Some of these “loose” cells condense to generate a rod-like structure called the medullary or neural cord. This cord eventually hollows out, and merges with the more anterior primary neural tube, forming a continuous structure. Although secondary neurulation plays a relatively minor role in the formation of the human central nervous system, defects in this process can still have developmental consequences, such as certain types of spina bifida.