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 crest cells to adopt pigment cell fates. nacre, a zebrafish homolog of MITF, is required for pigment cell differentiation. We isolated a promoter region of nacre that contains Tcf/Lef binding sites, which can mediate Wnt responsiveness. This promoter binds to zebrafish Lef1 protein in vitro, and a nacre reporter construct is strongly repressed by dominant-negative Tcf in melanoma cells. Mutation of Tcf/Lef sites abolishes Lef1 binding and reporter function in vivo. Wnt signaling therefore directly activates nacre, which in turn leads to pigment cell differentiation.
Dorsky
R I
RI
Howard Hughes Medical Institute and Department of Pharmacology, University of Washington School of Medicine, Seattle, Washington 98195, USA. rdorsky@u.washington.edu
Raible
D W
DW
Moon
R T
RT
D000818:Animals; D002455:Cell Division / Q000235:genetics; D004268:DNA-Binding Proteins / Q000235:genetics*; D018507:Gene Expression Regulation, Developmental; D008547:Melanophores / Q000502:physiology*; D051739:Microphthalmia-Associated Transcription Factor; D008969:Molecular Sequence Data; D010858:Pigmentation / Q000235:genetics*; D011505:Protein-Tyrosine Kinases / Q000378:metabolism / Q000502:physiology; D011518:Proto-Oncogene Proteins / Q000502:physiology*; D012689:Sequence Homology, Nucleic Acid; D015398:Signal Transduction / Q000235:genetics; D014157:Transcription Factors; D051153:Wnt Proteins; D015027:Zebrafish / Q000235:genetics*; D029961:Zebrafish Proteins
D004268:DNA-Binding Proteins; D051739:Microphthalmia-Associated Transcription Factor; D011518:Proto-Oncogene Proteins; D014157:Transcription Factors; D051153:Wnt Proteins; D029961:Zebrafish Proteins; C497237:mitfa protein, zebrafish; C094522:wnt8b protein, zebrafish; D011505:Protein-Tyrosine Kinases