Neural crest

The neural crest is a ridge-like structure that is formed transiently between the epidermal ectoderm and neural plate during vertebrate development. Neural crest cells originate from this structure through the epithelial-mesenchymal transition, and in turn give rise to a diverse cell lineage—including melanocytes, craniofacial cartilage and bone, smooth muscle, dentin, peripheral and enteric neurons, adrenal medulla and glia.

After gastrulation, the neural crest is specified at the border of the neural plate and the non-neural ectoderm. During neurulation, the borders of the neural plate, also known as the neural folds, converge at the dorsal midline to form the neural tube. Subsequently, neural crest cells from the roof plate of the neural tube undergo an epithelial to mesenchymal transition, delaminating from the neuroepithelium and migrating through the periphery, where they differentiate into varied cell types. The emergence of the neural crest was important in vertebrate evolution because many of its structural derivatives are defining features of the vertebrate clade.

Underlying the development of the neural crest is a gene regulatory network, described as a set of interacting signals, transcription factors, and downstream effector genes, that confer cell characteristics such as multipotency and migratory capabilities. Understanding the molecular mechanisms of neural crest formation is important for our knowledge of human disease because of its contributions to multiple cell lineages. Abnormalities in neural crest development cause neurocristopathies, which include conditions such as frontonasal dysplasia, Waardenburg–Shah syndrome, and DiGeorge syndrome.

Defining the mechanisms of neural crest development may reveal key insights into vertebrate evolution and neurocristopathies.

The neural crest was first described in the chick embryo by Wilhelm His Sr. in 1868 as "the cord in between" (Zwischenstrang) because of its origin between the neural plate and non-neural ectoderm. He named the tissue "ganglionic crest," since its final destination was each lateral side of the neural tube, where it differentiated into spinal ganglia. During the first half of the 20th century, the majority of research on the neural crest was done using amphibian embryos which was reviewed by Hörstadius (1950) in a well known monograph.

Cell labeling techniques advanced research into the neural crest because they allowed researchers to visualize the migration of the tissue throughout the developing embryos. In the 1960s, Weston and Chibon utilized radioisotopic labeling of the nucleus with tritiated thymidine in chick and amphibian embryo respectively. However, this method suffers from drawbacks of stability, since every time the labeled cell divides the signal is diluted. Modern cell labeling techniques such as rhodamine-lysinated dextran and the vital dye diI have also been developed to transiently mark neural crest lineages.

The quail-chick marking system, devised by Nicole Le Douarin in 1969, was another instrumental technique used to track neural crest cells. Chimeras, generated through transplantation, enabled researchers to distinguish neural crest cells of one species from the surrounding tissue of another species. With this technique, generations of scientists were able to reliably mark and study the ontogeny of neural crest cells.

A molecular cascade of events is involved in establishing the migratory and multipotent characteristics of neural crest cells. This gene regulatory network can be subdivided into the following four sub-networks described below.