Knockout of the PKN Family of Rho Effector Kinases Reveals a Non-redundant Role for PKN2 in Developmental Mesoderm Expansion

Cell Reports
Ivan QuétierAngus J M Cameron

Abstract

In animals, the protein kinase C (PKC) family has expanded into diversely regulated subgroups, including the Rho family-responsive PKN kinases. Here, we describe knockouts of all three mouse PKN isoforms and reveal that PKN2 loss results in lethality at embryonic day 10 (E10), with associated cardiovascular and morphogenetic defects. The cardiovascular phenotype was not recapitulated by conditional deletion of PKN2 in endothelial cells or the developing heart. In contrast, inducible systemic deletion of PKN2 after E7 provoked collapse of the embryonic mesoderm. Furthermore, mouse embryonic fibroblasts, which arise from the embryonic mesoderm, depend on PKN2 for proliferation and motility. These cellular defects are reflected in vivo as dependence on PKN2 for mesoderm proliferation and neural crest migration. We conclude that failure of the mesoderm to expand in the absence of PKN2 compromises cardiovascular integrity and development, resulting in lethality.

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Citations

Jan 20, 2017·Genes to Cells : Devoted to Molecular & Cellular Mechanisms·Sally DannoHideyuki Mukai
Mar 2, 2018·The Journal of Clinical Investigation·Stephanie zur NeddenGabriele Baier-Bitterlich
Aug 28, 2019·Nature Cell Biology·Alexander WallrothVolker Haucke
Jul 20, 2017·American Journal of Physiology. Endocrinology and Metabolism·Maxwell A RubyJuleen R Zierath
Mar 5, 2020·Scientific Reports·Hitesh PatelMargaret Frame
Oct 15, 2019·Developmental Cell·Joseph H R HetmanskiPatrick T Caswell
Feb 2, 2021·Biochemical Society Transactions·Georgios SophocleousHelen R Mott
Nov 13, 2020·Nature Reviews. Cancer·Peter J ParkerLisa Watson
Feb 25, 2021·Archives of Biochemistry and Biophysics·Alexander V MaltsevYury M Kokoz
Feb 23, 2021·Frontiers in Synaptic Neuroscience·Motahareh Solina SafariStephanie Zur Nedden
Oct 12, 2020·Advances in Biological Regulation·Peter J Parker Silvia Martini
Sep 10, 2021·The Journal of Clinical Investigation·Young-June JinStefan Offermanns

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Methods Mentioned

BETA
Knockout
GTPases
fluorescence-activated cell sorting
dissections

Software Mentioned

GraphPad Prism
KSEA

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