Neural Crest Migration

 

Image modified from http://www.med.unc.edu/embryo_images/

Neural crest cells migrate and ultimately differentiate into a wide variety of adult structures. The migrations begin cranially and gradually extend caudally. They are determined by both intrinsic properties of the neural crest cells and the features of the external environment encountered by the migrating cells - extracellular matrices and substrates.

Early Experimentation

Neural crest cells that are grafted into a different position along the neural tube do not seek out their original path, but instead migrate along paths typical of their new location. Weston and Johnson first used radio-labeled cells to track neural crest migration. Using this procedure, they identified two streams of migratory trunk neural crest cells - a dorsolateral and a ventral population. In addition, they tracked the cranial migrations.

Details of Migration

Migration ends when neural crest cells run into barriers and accumulate. Barriers can include basal laminae, blood vessels, somites, or other cell clusters. Chondroitin sulfate and other glycoconjugates also present barriers to crest cell migration.

 

Neural crest cells migrate from the developing dorsal neural tube. The induced neural crest cells express slug; slug is characteristic of cells that break away from an epithelial layer and subsequently migrate as mesenchymal cells. The migration of neural crest cells involves the loss of cell-to-cell adhesion molecules. This includes the loss of cadherins, which use calcium ions to attach to like cells. The migrating neural crest cells travel to the basal lamina. They can either penetrate through the basal lamina or travel along it. Neural crest cells may also travel along extracellular matrices that are present in the area using integrins. Crest cells travel to many areas of the developing embryo and give rise to multiple parts of the mature body, including sensory ganglia and melanocytes.

Sequential images of neural crest cell migration.

Modified from "Molecular Biology of the Cell", Alberts, Bray, et. al.

As early as the 1920's, scientists such as Bartelmey and Holmdahl have observed neural crest cell migration. Bartelmey and Holmdahl observed the migration of cells from the neural plate and also from the forebrain to different regions of the embryo, such as the mandibular and hyoid arches. Initially, the investigation into where these neural crest cells go and what they develop into was performed by extirpation, which involved the complete removal and destruction of these cells. After extracting the cells, the scientists observed that certain parts of the embryo did not develop. This gave them proof that the neural crest cells that they removed played an integral role in forming those areas. These experiments also helped scientists understand the migration of neural crest cells. A better technique was implemented in the 1960's. Instead of extracting the neural crest cells, scientists began to label the cells radio-isotopically. Johnston was one of the pioneers of this new technique. In the 1960's, he mapped the migratory pathway of cranial neural crest as they travelled around the developing eye in three main pathways, forming the maxillary, mandibular, median, and lateral nasal processes. These cells developed into a variety of tissues, such as connective tissue, cartilage, and bone. Weston, another pioneer that worked with Johnston, discovered two migratory pathways of the trunk neural crest cells.

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