Direct regulation of nacre, a zebrafish MITF homolog required for pigment cell formation, by the Wnt pathway

We have shown that Wnt signals are necessary and sufficient for neural cres t cells to adopt pigment cell fates. nacre, a zebrafish homolog of MITF, is required for pigment cell differentiation. We isolated a promoter region o f nacre that contains Tcf/Lef binding sites, which can mediate Wnt responsi veness. This promoter binds to zebrafish Lef1 protein in vitro, and a nacre reporter construct is strongly repressed by dominant-negative Tcf in melan oma cells. Mutation of Tcf/Lef sites abolishes Lef1 binding and reporter fu nction in vivo. Wnt signaling therefore directly activates nacre, which in turn leads to pigment cell differentiation.