The Developmental Biology of Melanocytes and Its Application to Understanding Human Congenital Disorders of Pigmentation

Abstract

In the past 15 years, a fruitful interplay between the description of mutations associated with human congenital disorders of pigmentation, the discovery of the molecular basis of murine coat color mutants, and the elucidation of determinants of melanocyte development from the neural crest has led to rapid advancement in the understanding of these disorders and the developmental biology underlying them. The insight gained about these human disorders from similar mouse models has facilitated progress that might not otherwise have occurred so rapidly. Clearly more work remains to be done, especially on the discovery of additional genes in humans that underlie the majority of WS2 cases not attributable to mutations in MITF. Sensitized genetic screens, using random mutagenesis in combination with existing mutant coat color alleles, may help uncover additional genes regulating melanocyte development in mice. Such studies would provide examples whose human homologues could be tested for mutations in patients who have pigmentation disorders that are currently unclassifiable. Intervention in developmental disorders is a challenging prospect. Nonetheless, it is imaginable that additional studies of the determinants of melanocyte survival during and after development could lead to strategies designed to maintain or replace functionally defective melanocytes, especially in localized regions such as the inner ear. The growing interest among investigators in the melanocyte as a model cellular system, with striking phenotypes across species, ensures that the field of melanocyte development and the studies of congenital disorders of pigmentation will remain vibrant in the foreseeable future.