Frodo interacts with Dishevelled to transduce Wnt signals

Abstract

Dishevelled (Dsh) is required for the specification of cell fate and polarity by secreted Wnt proteins. Frodo, a novel conserved Dsh-binding protein, synergized with Xenopus Dsh (XDsh) in secondary axis induction in Xenopus laevis embryos. A dominant inhibitory construct and antisense oligonucleotide-mediated depletion of Frodo inhibited axial development in response to XDsh and XWnt8, and suppressed transcriptional activation of a reporter construct. At later embryonic stages, both dominant negative Frodo and antisense oligonucleotides interfered with the expression of regional neural markers and caused eye deficiencies, indicating that Frodo is required for normal eye and neural tissue development. Full-length Frodo RNA suppressed these loss-of-function phenotypes, attesting to their specificity. These findings establish a function for Frodo as an essential positive regulator of Wnt signalling.

Regulation of the early expression patterns of the zebrafish Dishevelled-interacting proteins Dapper1 and Dapper2

“…The Dapper/Frodo family of molecules can act as both activators and inhibitors of Wnt/␤-catenin signaling (Cheyette et al, 2002;Gloy et al, 2002;Hikasa and Sokol, 2004;Waxman et al, 2004). Our recent work supports the idea that zebrafish dpr1 functions as a positive regulator of the ventroposteriorizing Wnt8 signal during gastrulation (Waxman et al, 2004).…”

“…The Dapper(Dpr)/Frodo(Frd) family of proteins was identified in Xenopus laevis as Dishevelled-interacting proteins (Cheyette et al, 2002;Gloy et al, 2002). Dishevelled (Dsh or Dvl) is an important upstream component of the Wnt/␤-catenin pathway, which contributes to stabilization of ␤-catenin through an as yet unclear mechanism.…”

“…Dishevelled (Dsh or Dvl) is an important upstream component of the Wnt/␤-catenin pathway, which contributes to stabilization of ␤-catenin through an as yet unclear mechanism. In different assays Dpr/Frd members can act as either inhibitors or activators of Wnt/␤-catenin signaling (Cheyette et al, 2002;Gloy et al, 2002;Hikasa and Sokol, 2004). All currently sequenced vertebrate genomes, except Xenopus laevis, have two conserved Dpr paralogs, Dpr1 and Dpr2 (Gillhouse et al, 2004;Waxman et al, 2004).…”

“…A genome duplication event in Xenopus laevis has led to two proteins orthologous to the Dpr1 isoform, XDpr1a and Frodo/XDpr1b, that are 90% identical to each other (Waxman et al, 2004), whereas Xenopus Dpr2 orthologs have not been identified yet. Both XDpr1a and Frodo/ XDpr1b are expressed maternally in oocytes and zygotically in the dorsal lip of embryos (Cheyette et al, 2002;Gloy et al, 2002). They act redundantly to pattern some aspects of organizer gene expression, axial mesoderm, and anterior neural tissue formation (Cheyette et al, 2002;Hikasa and Sokol, 2004).…”

Identification of the Wnt signaling activator leucine-rich repeat in Flightless interaction protein 2 by a genome-wide functional analysis

“…Each of these domains likely mediates protein-protein interactions that allow the Dvl proteins to act as scaffolding proteins during Wnt signaling (27)(28)(29)(30)(31)(32)(33)(34)(35)(36). To determine which of these domains binds LRRFIP2, a series of truncation mutants of Dvl3 (Fig.…”