MUTATIONS IN MICROPHTHALMIA, THE MOUSE HOMOLOG OF THE HUMAN DEAFNESS GENE MITF, AFFECT NEUROEPITHELIAL AND NEURAL CREST-DERIVED MELANOCYTESDIFFERENTLY

The mouse microphthalmia (Mitf) gene encodes a basic-helix-loop-helix- zipper transcription factor whose mutations are associated with abnorm alities in neuroepithelial and neural crest-derived melanocytes. In wi ld type embryos, Mitf expression in neuropithelium and neural crest pr ecedes that of the melanoblast marker Dct, is then co-expressed with D ct, and gradually fades away except in cells in hair follicles. In emb ryos with severe Mitf mutations, neural crest-derived Mitf-expressing cells are rare, lack Dct expression, and soon become undetectable. In contrast, the neuroepithelial-derived Mitf-expressing cells of the ret inal pigment layer are retained, express Dct, but not the melanogenic enzyme genes tyrosinase and Tyr1, and remain unpigmented. The results show that melanocyte development critically depends on functional Mitf and that Mitf mutations affect the neural crest and the neuroepitheli um in different ways. (C) 1998 Elsevier Science Ireland Ltd.