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First published online 4 October 2006
doi: 10.1242/dev.02590


Development 133, 4219-4231 (2006)
Published by The Company of Biologists 2006


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

Akira Sato1, Deepak K. Khadka1, Wei Liu1, Ritu Bharti1, Loren W. Runnels2, Igor B. Dawid3 and Raymond Habas1,4,*

1 Department of Biochemistry, University of Medicine and Dentistry of New Jersey-Robert Wood Johnson School of Medicine, Piscataway, NJ 08854, USA.
2 Department of Pharmacology, University of Medicine and Dentistry of New Jersey-Robert Wood Johnson School of Medicine, Piscataway, NJ 08854, USA.
3 Laboratory of Molecular Genetics, National Institutes of Child Health and Human Development, Bethesda, MD 20892-2790, USA.
4 The Cancer Institute of New Jersey, 195 Little Albany Street, New Brunswick, NJ 08903-2681, USA.

* Author for correspondence (e-mail: habasra{at}umdnj.edu)

Accepted 23 August 2006

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.

Key words: Profilin, Xenopus, Daam1


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