Melanocytogenesis and melanogenesis: genetic regulation and comparative clinical diseases

Murine models recently provided important information on the pathogenesis of pigmentation disorders. Multiple factors influence melanocyte function at various levels, such as melanoblast development and migration from the neural crest to peripheral sites, melanoblast differentiation into melanocytes, melanocyte survival and, finally, synthesis of melanosomes and melanins. Mutations affecting any of these steps result in hereditary hypomelanoses. In some of these diseases, melanocytes are absent, either because of a defect in migration of melanoblasts from the neural crest, their inability to survive and/or proliferate in colonized territories (piebaldism and Waardenburg syndromes), or because of programmed melanocyte destruction (e.g. vitiligo). In other entities, the melanocytes are present but functionally deficient (oculocutaneous albinisms and pigmentary dilutions). This comprehensive review will introduce the genetic regulation of melanocytogenesis and melanogenesis and the correlations between genetic abnormalities and hypopigmentation clinical disorders.