Cell Reports
Volume 14, Issue 3, 26 January 2016, Pages 440-448
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Knockout of the PKN Family of Rho Effector Kinases Reveals a Non-redundant Role for PKN2 in Developmental Mesoderm Expansion

https://doi.org/10.1016/j.celrep.2015.12.049Get rights and content
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Highlights

  • PKN2, but not PKN1 or PKN3, is essential during mouse embryogenesis

  • PKN2 knockout causes severe cardiovascular and morphogenetic abnormalities

  • PKN2 is required for mesenchymal growth and neural crest migration in vivo

Summary

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.

Keywords

PKC
protein kinase C
PKN
Protein kinase N
MEF
mouse embryonic fibroblasts
ES cells
Embryonic stem cells
4-OHT
4-hydroxytamoxifen
NCCs
neural crest cells

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This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).