The TORC2 component, Sin1, controls migration of anterior mesendoderm during zebrafish gastrulation.

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 func...

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Main Authors: Julien G Dumortier, Nicolas B David
Format: Article
Language:English
Published: Public Library of Science (PLoS) 2015-01-01
Series:PLoS ONE
Online Access:https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0118474&type=printable
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author Julien G Dumortier
Nicolas B David
author_facet Julien G Dumortier
Nicolas B David
author_sort Julien G Dumortier
collection DOAJ
description 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.
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spelling doaj-art-542bcd7528ef4536880adce3b1d8a9ed2025-08-20T02:15:12ZengPublic Library of Science (PLoS)PLoS ONE1932-62032015-01-01102e011847410.1371/journal.pone.0118474The TORC2 component, Sin1, controls migration of anterior mesendoderm during zebrafish gastrulation.Julien G DumortierNicolas B DavidTORC2 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.https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0118474&type=printable
spellingShingle Julien G Dumortier
Nicolas B David
The TORC2 component, Sin1, controls migration of anterior mesendoderm during zebrafish gastrulation.
PLoS ONE
title The TORC2 component, Sin1, controls migration of anterior mesendoderm during zebrafish gastrulation.
title_full The TORC2 component, Sin1, controls migration of anterior mesendoderm during zebrafish gastrulation.
title_fullStr The TORC2 component, Sin1, controls migration of anterior mesendoderm during zebrafish gastrulation.
title_full_unstemmed The TORC2 component, Sin1, controls migration of anterior mesendoderm during zebrafish gastrulation.
title_short The TORC2 component, Sin1, controls migration of anterior mesendoderm during zebrafish gastrulation.
title_sort torc2 component sin1 controls migration of anterior mesendoderm during zebrafish gastrulation
url https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0118474&type=printable
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