Identification ofkit-ligand aas the Gene Responsible for the Medaka Pigment Cell Mutantfew melanophore

Abstract

ABSTRACTThe body coloration of animals is due to pigment cells derived from neural crest cells, which are multipotent and differentiate into diverse cell types. Medaka (Oryzias latipes) possesses four distinct types of pigment cells known as melanophores, xanthophores, iridophores, and leucophores. Thefew melanophore(fm) mutant of medaka is characterized by reduced numbers of melanophores and leucophores. We here identifykit-ligand a(kitlga) as the gene whose mutation gives rise to thefmphenotype. This identification was confirmed by generation ofkitlgaknockout medaka and the findings that these fish also manifest reduced numbers of melanophores and leucophores and fail to rescue thefmmutant phenotype. We also found that expression ofsox5,pax7a,pax3a, andmitfagenes is down-regulated in bothfmandkitlgaknockout 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 ourkitlgaknockout medaka may prove useful as a tool for drug screening.