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

  1. Richard I. Dorsky1,3,4,
  2. David W. Raible2,3, and
  3. Randall T. Moon1,3,5
  1. 1Howard Hughes Medical Institute and Department of Pharmacology, 2Department of Biological Structure, 3Center for Developmental Biology, University of Washington School of Medicine, Seattle, Washington 98195 USA

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 activatesnacre, which in turn leads to pigment cell differentiation.

Keywords

Footnotes

  • 4 Requests for materials should be directed to .

  • 5 Corresponding author.

  • E-MAIL rtmoon{at}u.washington.edu; FAX (206) 543-0858.

    • Received November 9, 1999.
    • Accepted December 3, 1999.
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