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Development November 1, 2006; 133 (21): 4219-31.

Profilin is an effector for Daam1 in non-canonical Wnt signaling and is required for vertebrate gastrulation.

Sato A , Khadka DK , Liu W , Bharti R , Runnels LW , Dawid IB , Habas R .

Non-canonical Wnt signaling plays important roles during vertebrate embryogenesis and is required for cell motility during gastrulation. However, the molecular mechanisms of how Wnt signaling regulates modification of the actin cytoskeleton remain incompletely understood. We had previously identified the Formin homology protein Daam1 as an important link between Dishevelled and the Rho GTPase for cytoskeletal modulation. Here, we report that Profilin1 is an effector downstream of Daam1 required for cytoskeletal changes. Profilin1 interacted with the FH1 domain of Daam1 and was localized with Daam1 to actin stress fibers in response to Wnt signaling in mammalian cells. In addition, depletion of Profilin1 inhibited stress fiber formation induced by non-canonical Wnt signaling. Inhibition or depletion of Profilin1 in vivo specifically inhibited blastopore closure in Xenopus but did not affect convergent extension movements, tissue separation or neural fold closure. Our studies define a molecular pathway downstream of Daam1 that controls Wnt-mediated cytoskeletal reorganization for a specific morphogenetic process during vertebrate gastrulation.

PubMed ID: 17021034
Article link: Development
Grant support: [+]
Genes referenced: actl6a daam1 dvl2 fmn1 gsc otx2 pfn1 rho rho.2 sox2 tbxt
Morpholinos: pfn1 MO1

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