Duplicate mitf genes in zebrafish: Complementary expression and conservation of melanogenic potential

Mutations in the zebrafish nacre/mitfa gene, expressed in all embryonic mel anogenic cells, perturb only neural crest melanocytes, suggesting redundanc y of mitfa with another gene in the zebrafish retinal pigment epithelium (R PE). Here, we describe a second zebrafish mitf gene, mitfb, which may fulfi ll this role. The proteins encoded by the two zebrafish mitf genes appear h omologous to distinct isoforms generated by alternately spliced mRNAs of th e single mammalian Mitf gene, suggesting specialization of the two zebrafis h genes following a duplication event. Consistent with this hypothesis, exp ression of mitfa and mitfb is partially overlapping. mitfb is coexpressed w ith mitfa in the RPE at an appropriate time to compensate for loss of mitfa function in the nacre mutant but is not expressed in neural crest melanobl asts. Additionally, mitfb is expressed in the epiphysis and olfactory bulb where mitfa is not, and where Mitf expression has not previously been repor ted in other species. mitfb, but not a zebrafish ortholog of the closely re lated gene tfe3, can rescue neural crest melanophore development in nacre/m itfa mutant embryos when expressed via the mitfa promoter. These data sugge st that mitfa and mitfb together may recapitulate the expression and functi ons of a single ancestral Mitf gene, and that mitfb may serve additional no vel functions. (C) 2001 Academic Press.