Site of gene action of the white allele (Miwh) of the microphthalmia locus: a dermal-epidermal recombination study.

The white allele Miwh of the microphthalmia locus, when homozygous, causes a complete absence of neural crest-derived melanocytes in skin and internal organs. The site(s) of gene action of Miwh on melanoblast differentiation were examined by making dermal-epidermal recombinant grafts with skin from 13-14-day embryos of the following genotypes: normal (+/+), heterozygous white (Miwh/+), homozygous white (Miwh/Miwh), and dominant spotting (W/W). Based on results from these grafts, the following conclusions were reached: Miwh/Miwh epidermis is as effective as W/W epidermis in supporting the differentiation of +/+ follicular melanocytes. Miwh/Miwh dermis is completely permissive to in situ differentiation of +/+ follicular melanocytes. Thirteen-fourteen-day embryonic Miwh/Miwh skin, both epidermis and dermis, alters of blocks the differentiation of +/+ melanoblasts into dermal melanocytes. By 13 days of development, melanoblasts from both Miwh/+ and Miwh/Miwh skin, even when presented with a permissive W/W environment, are irreversibly redirected into abnormal developmental pathways resulting in either a reduction in follicular pigmentation (Miwh/+) or a complete absence of follicular melanocytes (Miwh/Miwh).