title: Non-redundant roles for Profilin2 and Profilin1 during vertebrate gastrulation.
abstract: Gastrulation is a critical morphogenetic event during vertebrate embryogenesis, and it is comprised of directional cell movement resulting from the polarization and reorganization of the actin cytoskeleton. The non-canonical Wnt signaling pathway has emerged as a key regulator of gastrulation. However, the molecular mechanisms by which the Wnt pathway mediates changes to the cellular actin cytoskeleton remains poorly defined. We had previously identified the Formin protein Daam1 and an effector molecule XProfilin1 as links for Wnt-mediated cytoskeletal changes during gastrulation. We report here the identification of XProfilin2 as a non-redundant and distinct effector of Daam1 for gastrulation. XProfilin2 interacts with FH1 domain of Daam1 and temporally interacts with Daam1 during gastrulation. In the Xenopus embryo, XProfilin2 is temporally expressed throughout embryogenesis and it is spatially expressed in cells undergoing morphogenetic movement during gastrulation. While we have previously shown XProfilin1 regulates blastopore closure, overexpression or depletion of XProfilin2 specifically affects convergent extension movement independent of mesodermal specification. Specifically, we show that XProfilin2 modulates cell polarization and axial alignment of mesodermal cells undergoing gastrulation independent of XProfilin1. Together, our studies demonstrate that XProfilin2 and XProfilin1 are non-redundant effectors for Daam1 for non-canonical Wnt signaling and that they regulate distinct functions during vertebrate gastrulation.
authors.affiliation: Department of Biochemistry, Robert Wood Johnson School of Medicine, Piscataway, NJ 08854, USA.
authors.forename: Deepak K
authors.initials: DK
authors.lastname: Khadka
authors.forename: Wei
authors.initials: W
authors.lastname: Liu
authors.forename: Raymond
authors.initials: R
authors.lastname: Habas
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics / Q000378:metabolism; D000595:Amino Acid Sequence; D000818:Animals; D002460:Cell Line; D003599:Cytoskeleton / Q000378:metabolism; D054262:Gastrulation / Q000502:physiology*; D018507:Gene Expression Regulation, Developmental; D006801:Humans; D008648:Mesoderm / Q000502:physiology; D051379:Mice; D008840:Microfilament Proteins; D008969:Molecular Sequence Data; D010802:Phylogeny; D051304:Profilins / Q000235:genetics / Q000378:metabolism*; D051381:Rats; D016415:Sequence Alignment; D015398:Signal Transduction / Q000502:physiology*; D020798:Two-Hybrid System Techniques; D051153:Wnt Proteins / Q000235:genetics / Q000378:metabolism; D014982:Xenopus laevis / Q000196:embryology*; D020741:rho GTP-Binding Proteins
chemical_list: D048868:Adaptor Proteins, Signal Transducing; C499094:DAAM1 protein, human; D008840:Microfilament Proteins; D051304:Profilins; D051153:Wnt Proteins; D020741:rho GTP-Binding Proteins