Neural Tube vs. Neural Crest: Key Differences & Fates

Early in vertebrate development, the nervous system’s foundation is established through a process called neurulation. This period sees the emergence of two structures from the embryonic ectoderm: the neural tube and the neural crest. Though they arise in close proximity, their developmental paths diverge, leading to the formation of different parts of the body. Understanding their distinct origins, behaviors, and contributions is fundamental to embryonic development.

The Neural Tube: Formation and Central Nervous System Primordium

The formation of the neural tube, an event known as primary neurulation, begins during the third and fourth weeks of human gestation. It starts when the embryonic notochord sends signals that cause the overlying ectoderm to thicken and form the neural plate. This plate then begins to fold inward, with its lateral edges rising to form neural folds on either side of a central neural groove. These folds continue to elevate and move toward each other at the dorsal midline.

The process culminates when the neural folds meet and fuse, creating a hollow, cylindrical structure separate from the overlying ectoderm. This neural tube is the primordium of the entire central nervous system (CNS). Its cells will proliferate and differentiate to generate all the neurons and most of the glial cells of the brain and spinal cord.

Almost immediately after its formation, the neural tube begins to take on regional identities. The anterior portion undergoes expansions to form the primary brain vesicles—the forebrain, midbrain, and hindbrain. The posterior portion remains more uniform and elongates to become the spinal cord, establishing the basic architecture of the adult CNS.

The Neural Crest: Origins and Migratory Cell Population

Arising alongside the neural tube is the neural crest, a transient population of cells. These cells originate from the neural plate border, the junction where the edges of the neural plate meet the surface ectoderm. As the neural folds elevate and fuse, the cells at this border are positioned at the dorsal-most aspect of the newly formed structure.

Unlike the cells of the neural tube that remain as a cohesive tube, neural crest cells are defined by their motility. They undergo a transformation known as an epithelial-to-mesenchymal transition (EMT). During EMT, these cells lose their tight connections to neighboring cells and acquire the ability to migrate away from their site of origin. This delamination allows them to disperse throughout the embryo.

This migratory capability is coupled with multipotency, meaning a single neural crest cell can give rise to a wide variety of cell types. Often called the “fourth germ layer” for their versatility, these cells travel along specific pathways to their destinations.

Key Differences in Development and Cellular Characteristics

The divergence between the neural tube and neural crest begins with their origins, which are driven by different molecular cues. The neural tube arises from the central neural plate, while neural crest cells are specified at the neural plate border. This difference is a direct consequence of exposure to varying concentrations of signaling molecules. For instance, high levels of Bone Morphogenetic Proteins (BMPs) specify surface ectoderm, low levels specify the neural plate, and intermediate levels at the border induce neural crest formation.

Their fundamental cellular state also presents a sharp contrast. The neural tube is an epithelial structure, with cells that are tightly bound, stationary, and organized into a tube. Conversely, neural crest cells transition into a mesenchymal state, becoming individualistic and highly migratory. This transition is controlled by a specific set of genes that initiate EMT.

The method of their separation is another distinction. The neural tube forms via folding and fusion, where a sheet of cells collectively changes shape. In contrast, neural crest cells delaminate, a process where individual cells actively separate from the dorsal neural tube after its closure to begin their migration.

Distinct Fates: Structures Arising from Neural Tube Versus Neural Crest

The ultimate contributions of the neural tube and neural crest are profoundly different. The destiny of the neural tube is focused, as it gives rise to the entirety of the central nervous system (CNS). This includes the brain, with its major divisions like the cerebrum and cerebellum, as well as the full length of the spinal cord. All neurons within the CNS, such as motor neurons and interneurons, originate from the neural tube.

Additionally, the neural tube generates most of the CNS’s supporting glial cells, including astrocytes and oligodendrocytes that produce the myelin sheath. The retina and the optic nerve are also derivatives of the neural tube, forming as outgrowths of the forebrain. The ependymal cells lining the brain’s ventricles and the spinal cord’s central canal also come from the neural tube.

In stark contrast, the fates of the migratory neural crest cells are exceptionally diverse and widespread. They are primary contributors to the peripheral nervous system (PNS), forming:

• Sensory neurons
• Autonomic ganglia that control involuntary functions
• The entire enteric nervous system that governs the gut
• Schwann cells that myelinate peripheral nerves

Beyond the PNS, their contributions are vast. Neural crest cells differentiate into melanocytes that provide pigment to the skin and hair. They also form a significant portion of the craniofacial skeleton, the dentin of teeth, smooth muscle of certain large arteries, and parts of the heart and adrenal medulla.

Clinical Significance: When Neural Development Falters

Errors in the formation of the neural tube or the development of neural crest cells can lead to significant congenital conditions. Defects in neural tube closure are called neural tube defects (NTDs). If the anterior part of the tube fails to fuse, it results in anencephaly, where major portions of the brain and skull are absent. Failure of the posterior tube to close causes spina bifida, which can range from a mild vertebral defect to severe forms where the spinal cord protrudes.

The migratory nature of neural crest cells means that errors in their development, known as neurocristopathies, can cause a wide spectrum of disorders. For example, Hirschsprung’s disease occurs when neural crest cells fail to fully colonize the large intestine. This results in a segment of the bowel that cannot perform peristalsis, leading to severe constipation and obstruction in newborns.

Other neurocristopathies highlight the varied roles of these cells. Waardenburg syndrome can cause hearing loss and changes in pigmentation, like a white patch of hair or differently colored eyes, due to defects in neural crest cells. DiGeorge syndrome, caused by a genetic deletion affecting neural crest development, can lead to heart defects, facial anomalies, and immune system problems.