Zebrafish Dapper1 and Dapper2 play distinct roles in Wnt-mediated developmental processes

Abstract

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/β-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/β-catenin target genes. Dpr1 synergizes with zebrafish Dvl2, and with the Dvl-interacting kinases CK1ϵ, Par1 and CK2, in activating target genes. We conclude that two Dvl-associated paralogs, Dpr1 and Dpr2,participate in distinct Wnt-dependent developmental processes.