Effects of growth factors on the differentiation of neural crest cells and neural crest cell-derivatives

Abstract

During neurulation, neural crest cells migrate to many regions of the body to give rise to a wide variety of cell types. Many premigratory neural crest cells are pluripotent, their potency for differentiation being gradually restricted as they migrate along definite pathways and interact with factors present in the microenvironment. Effects of growth factors on these cells have been discussed in the present review. Mediation of growth factors in differentiation varies with the cell type. Growth factors exert a direct influence on the differentiation of neural and other related neural crest-derived tissues such as endocrinal tissues but evidence for such influences on neural crest-derived mesenchymal tissues is limited. For example, NGF, BDNF, and other factors present in neural tube extracts and glioma cell conditioned medium are essential for the differentiation of sensory neurons. Similarly, NGF, insulin, IGFs and possibly other undescribed factors are necessary for the differentiation of sympathetic neurons. IGFs also enhance the proliferation of mesenchymal derivatives of both neural crest and mesodermal origin. Glucocorticoid-mediated differentiation of neural crest-derived chromaffin endocrine cells that are ontogenetically closely related to sympathetic neurons can be inhibited by NGF, and chromaffin cells can be induced to express the neuronal phenotype by NGF. Some growth factors, such as NGF, act on neural crest- and not on placodally-derived neurons, whether the former are sensory or sympathetic. Placodal sensory neurons possess NGF receptors, but only display a limited response to NGF, perhaps because of low affinity of the receptors. Other growth factors, such as BDNF, selectively act upon sensory neurons, whether neural crest- or placodally-derived. Although extracellular matrix products play a role in initiating the differentiative process, signals from growth factors are necessary for the establishment of the functionally competent phenotype of neural crest-derived neurons, a situation that does not apply for neural crest-derived mesenchymal cells. It is interactions with ECM components deposited by epithelia that govern the differentiation of mesenchymal derivatives. Growth factors do effect proliferation of mesenchymal derivatives and inhibit mesenchymal differentiation. Although direct involvement of single growth factors in transformation o f one mesenchymal phenotype to another has not been reported so far, their localization at sites of epithelial-mesenchymal interactions in palate teeth and mandible, and the ability of excess growth factors to interrupt normal development is suggestive of their possible involvement. One group of growth factors, BMPs, can influence differentiation of cartilage, including those of neural crest origin.(ABSTRACT TRUNCATED AT 400 WORDS)