title: The TORC2 component, Sin1, controls migration of anterior mesendoderm during zebrafish gastrulation.
abstract: TORC2 is a serine-threonine kinase complex conserved through evolution that recently emerged as a new regulator of actin dynamics and cell migration. However, knockout in mice of its core components Sin1 and Rictor is embryonic lethal, which has limited in vivo analyses. Here, we analysed TORC2 function during early zebrafish development, using a morpholino-mediated loss of function of sin1. Sin1 appears required during gastrulation for migration of the prechordal plate, the anterior most mesoderm. In absence of Sin1, cells migrate both slower and less persistently, which can be correlated to a reduction in actin-rich protrusions and a randomisation of the remaining protrusions. These results demonstrate that, as established in vitro, the TORC2 component Sin1 controls actin dynamics and cell migration in vivo. We furthermore establish that Sin1 is required for protrusion formation downstream of PI3K, and is acting upstream of the GTPase Rac1, since expression of an activated form of Rac1 is sufficient to rescue sin1 loss of function.
authors.affiliation: INSERM U1024, Paris, France; CNRS UMR 8197, Paris, France; IBENS, Institut de Biologie de l'Ecole Normale Supérieure, Paris, France; Department of Physiology, Development and Neuroscience, University of Cambridge, Cambridge, United-Kingdom.
authors.forename: Julien G
authors.initials: JG
authors.lastname: Dumortier
authors.affiliation: INSERM U1024, Paris, France; CNRS UMR 8197, Paris, France; IBENS, Institut de Biologie de l'Ecole Normale Supérieure, Paris, France.
authors.forename: Nicolas B
authors.initials: NB
authors.lastname: David
mesh_terms: D000199:Actins / Q000378:metabolism; D000818:Animals; D030801:Animals, Genetically Modified / Q000254:growth & development / Q000378:metabolism; D002465:Cell Movement; D054262:Gastrulation; D000076225:Mechanistic Target of Rapamycin Complex 2; D008648:Mesoderm / Q000378:metabolism*; D046912:Multiprotein Complexes / Q000037:antagonists & inhibitors / Q000378:metabolism*; D016376:Oligonucleotides, Antisense / Q000378:metabolism; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D021122:Protein Subunits / Q000037:antagonists & inhibitors / Q000378:metabolism; D058570:TOR Serine-Threonine Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism*; D059008:Time-Lapse Imaging; D015027:Zebrafish / Q000254:growth & development* / Q000378:metabolism; D029961:Zebrafish Proteins / Q000378:metabolism*; D020830:rac1 GTP-Binding Protein / Q000235:genetics / Q000378:metabolism
chemical_list: D000199:Actins; D000076225:Mechanistic Target of Rapamycin Complex 2; D046912:Multiprotein Complexes; D016376:Oligonucleotides, Antisense; D019869:Phosphatidylinositol 3-Kinases; D021122:Protein Subunits; D058570:TOR Serine-Threonine Kinases; D029961:Zebrafish Proteins; D020830:rac1 GTP-Binding Protein