PUBLICATION

The TORC2 Component, Sin1, Controls Migration of Anterior Mesendoderm during Zebrafish Gastrulation

Authors
Dumortier, J.G., David, N.B.
ID
ZDB-PUB-150225-2
Date
2015
Source
PLoS One   10: e0118474 (Journal)
Registered Authors
David, Nicholas
Keywords
none
MeSH Terms
  • Actins/metabolism
  • Animals
  • Animals, Genetically Modified/growth & development
  • Animals, Genetically Modified/metabolism
  • Cell Movement
  • Gastrulation*
  • Mesoderm/metabolism*
  • Multiprotein Complexes/antagonists & inhibitors
  • Multiprotein Complexes/metabolism*
  • Oligonucleotides, Antisense/metabolism
  • Phosphatidylinositol 3-Kinases/metabolism
  • Protein Subunits/antagonists & inhibitors
  • Protein Subunits/metabolism
  • TOR Serine-Threonine Kinases/antagonists & inhibitors
  • TOR Serine-Threonine Kinases/metabolism*
  • Time-Lapse Imaging
  • Zebrafish/growth & development*
  • Zebrafish/metabolism
  • Zebrafish Proteins/metabolism*
  • rac1 GTP-Binding Protein/genetics
  • rac1 GTP-Binding Protein/metabolism
(all 21)
PubMed
25710382 Full text @ PLoS One
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.
Genes / Markers
Figures
Figure Gallery (4 images)
Show all Figures
Expression
Phenotype
Mutations / Transgenics
Allele Construct Type Affected Genomic Region
ml1TgTransgenic Insertion
    1 - 1 of 1
    Show
    Human Disease / Model
    No data available
    Sequence Targeting Reagents
    Target Reagent Reagent Type
    mapkap1MO1-mapkap1MRPHLNO
    mapkap1MO2-mapkap1MRPHLNO
    1 - 2 of 2
    Show
    Fish
    Antibodies
    No data available
    Orthology
    No data available
    Engineered Foreign Genes
    Marker Marker Type Name
    GFPEFGGFP
    1 - 1 of 1
    Show
    Mapping
    No data available