Dominant Negative Mitf Allele Impacts Melanophore and Xanthophore Development and Reveals Collaborative Interactions With Tfec in Zebrafish Chromatophore Lineages

Abstract

Ectothermic vertebrates exhibit a diverse array of pigment cell types—chromatophores—that provide valuable opportunities to uncover mechanisms of fate specification and how they evolve. Like melanocytes of mammals, the melanophores of teleosts and other ectotherms depend on basic helix–loop–helix leucine zipper transcription factors encoded by orthologues of MITF. A different chromatophore, the iridescent iridophore, depends on the closely related transcription factor Tfec. Requirements for the specification of other chromatophore lineages remain largely uncertain. Here we identify a new allele of the zebrafish Mitf gene, mitfa, that results in a complete absence of not only melanophores but also yellow-orange xanthophores. Harboring a missense substitution in the DNA-binding domain identical to previously isolated alleles of mouse, we show that this new allele has defects in chromatophore precursor survival and xanthophore differentiation that extend beyond those of mitfa loss-of-function. Additional genetic analyses revealed interactions between Mitfa and Tfec as a likely basis for the observed phenotypes. Our findings point to collaborative roles for Mitfa and Tfec in promoting chromatophore development, particularly in xanthophore lineages, and provide new insights into evolutionary aspects of MITF functions across vertebrates.