nacre encodes a zebrafish microphthalmia-related protein that regulates neural-crest-derived pigment cell fate

We report the isolation and identification of a new mutation affecting pigm ent cell fate in the zebrafish neural crest. Homozygous nacre (nac(w2)) mut ants lack melanophores throughout development but have increased numbers of iridophores, The non-crest-derived retinal pigment epithelium is normal, s uggesting that the mutation does not affect pigment synthesis per se. Expre ssion of early melanoblast markers is absent in nacre mutants and transplan t experiments suggested a cell-autonomous function in melanophores. We show that nac(w2) is a mutation in a zebrafish gene encoding a basic helix-loop -helix/leucine zipper transcription factor related to micraphthalmia (Mitf) , a gene known to be required for development of eye and crest pigment cell s in the mouse. Transient expression of the wild-type nacre gene restored m elanophore development in nacre(-/-) embryos. Furthermore, misexpression of nacre induced the formation of ectopic melanized cells and caused defects in eye development in wild-type and mutant embryos. These results demonstra te that melanophore development in fish and mammals shares a dependence on the nacre/Mitf transcription factor, but that proper development of the ret inal pigment epithelium in the fish is not nacre-dependent, suggesting an e volutionary divergence in the function of this gene.