Embryonic Stem Cells as a Model for Studying Melanocyte Development

Melanocytes residing in the skin, inner ear, and uveal tract are derived from neural crest cells. They are highly dendritic, heavily pigmented, and are generally located in the epidermal basal cell layer of these areas, including hair follicles ( 1 ). The most convincing fact demonstrating the neural crest origin of these melanocytes came from mice mutated at the c-Kit W and Mgf Sl loci, in which all melanocytes were lost ( 2 ). Retinal pigmented epithelial (RPE) cells, the melanin-producing polygonal cells forming epithelium in the retina, are directly induced from the neuroepithelium of the optic vesicle and are not affected by c-Kit W and Mgf Sl mutations. Another mutant, Edn3 ls , which lacks endothelin 3 (ET3), shows a severe defect in hair pigmentation ( 3 ). Disruption of the receptor for ET3 is also known to cause a hair pigmentation defect. These genetic observations indicate that steel factor (also known as MGF, SCF) and ET3 are normally essential for melanocyte development (Fig. 1 ).   Fig. 1.  Scheme describing the development of the melanocyte lineage. The stage at which steel factor and ET3 function is indicated. The melanin-containing stage is shaded.