title: Direct regulation of nacre, a zebrafish MITF homolog required for pigment cell formation, by the Wnt pathway.
abstract: 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.
authors.affiliation: Howard Hughes Medical Institute and Department of Pharmacology, University of Washington School of Medicine, Seattle, Washington 98195, USA. rdorsky@u.washington.edu
authors.forename: R I
authors.initials: RI
authors.lastname: Dorsky
authors.forename: D W
authors.initials: DW
authors.lastname: Raible
authors.forename: R T
authors.initials: RT
authors.lastname: Moon
mesh_terms: 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
chemical_list: 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