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First published online November 11, 2004
doi: 10.1242/10.1242/dev.01520
1 Molecular and Cellular Biology Program, University of Washington School of
Medicine, Seattle, WA 98195, USA
2 Howard Hughes Medical Institute, Department of Pharmacology and Center for
Developmental Biology, Box 357750, University of Washington School of
Medicine, Seattle, WA 98195, USA
3 Neurobiology and Behavior Graduate Program, University of Washington School of
Medicine, Seattle, WA 98195, USA
Author for correspondence (e-mail:
rtmoon{at}u.washington.edu)
Accepted 27 September 2004
Wnt signaling pathways in vertebrates use the phosphoprotein Dishevelled
(Dvl). The cellular responses to Wnt signaling may in part be modulated by
Dvl-associated proteins, including Dapper (Dpr). We have cloned and
characterized the zebrafish Dpr paralogs Dpr1 and Dpr2. Loss-of-function
studies reveal that endogenous Dpr1 but not Dpr2 is required to enhance
Wnt/ß-catenin activity in zebrafish embryos that are hypomorphic for
Wnt8. Conversely, Dpr2 but not Dpr1 is required for normal convergence
extension movements in embryos that are hypomorphic for Stbm or Wnt11,
supporting a functional interaction of Dpr2 with Wnt/Ca2+-PCP
signaling. In gain-of-function experiments, Dpr1 but not Dpr2 induces
Wnt/ß-catenin target genes. Dpr1 synergizes with zebrafish Dvl2, and with
the Dvl-interacting kinases CK1
, Par1 and CK2, in activating target
genes. We conclude that two Dvl-associated paralogs, Dpr1 and Dpr2,
participate in distinct Wnt-dependent developmental processes.
Key words: Dishevelled, Dapper, Zebrafish, Wnt signaling
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