XB-ART-34367Development November 1, 2006; 133 (21): 4219-31.
Profilin is an effector for Daam1 in non-canonical Wnt signaling and is required for vertebrate gastrulation.
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
Genes referenced: actl6a daam1 dvl2 fmn1 gsc otx2 pfn1 rho rho.2 sox2 tbxt
Morpholinos: pfn1 MO1
Article Images: [+] show captions
|Fig. 7. Profilin1 does not interfere with mesoderm induction. Embryos injected dorsally with Profilin1 (2 ng) or XProfilin1 MO (50 ng) show normal mesoendoderm and neural induction, but abnormal tissue localization due to gastrulation defects. No effects were observed with injections of the control MO (50 ng) after gastrulation defects. The phenotype induced by the XProfilin1 MO can be rescued by co-expression of ΔN-Profilin1 (50 pg). Injected embryos show normal expression of mesodermal Xbra, and dorsal Gsc and Otx2 at st 10.5, but exhibit an Xbra expression surrounding a large blastopore that does not close at st 12. Gsc expression in control embryos at st 13 is observed in anterior mesoendoderm far from the closed blastopore (arrowheads), but in Profilin or XProfilin1 MO-injected embryo remains trapped near the open blastopore. Otx-2 is expressed anteriorly in both mesodermal and overlying neural tissues in control embryos at st 13 but in Profilin or XProfilin1 MO-injected embryos, two separate Otx-2 expression domains are obvious. Sox-2 is expressed in the neural plate at st 14 (arrowheads), but in Profilin or XProfilin1 MO-injected embryos, Sox-2 expression is seen surrounding the open blastopore.|