Identification of as the Gene Responsible for the Medaka Pigment Cell Mutant .

The body coloration of animals is due to pigment cells derived from neural crest cells, which are multipotent and differentiate into diverse cell types. Medaka () possesses four distinct types of pigment cells known as melanophores, xanthophores, iridophores, and leucophores. The () mutant of medaka is characterized by reduced numbers of melanophores and leucophores. We here identify () as the gene whose mutation gives rise to the phenotype. This identification was confirmed by generation of knockout medaka and the findings that these fish also manifest reduced numbers of melanophores and leucophores and fail to rescue the mutant phenotype. We also found that expression of , , , and genes is down-regulated in both and knockout medaka, implicating c-Kit signaling in regulation of the expression of these genes as well as the encoded transcription factors in pigment cell specification. Our results may provide insight into the pathogenesis of c-Kit-related pigmentation disorders such as piebaldism in humans, and our knockout medaka may prove useful as a tool for drug screening.