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

Ivan Quétier, Jacqueline J.T. Marshall, Bradley Spencer-Dene, Sylvie Lachmann, Adele Casamassima, Claudio Franco, Sarah Escuin, Joseph T. Worrall, Priththivika Baskaran, Vinothini Rajeeve, Michael Howell, Andrew J. Copp, Gordon Stamp, Ian Rosewell, Pedro Cutillas, Holger Gerhardt, Peter J. Parker*, Angus J.M. Cameron

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

30 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)440-448
Number of pages9
JournalCell Reports
Volume14
Issue number3
DOIs
Publication statusPublished - 26 Jan 2016
Externally publishedYes

Keywords

  • 4-hydroxytamoxifen
  • 4-OHT
  • Embryonic stem cells
  • ES cells
  • MEF
  • Mouse embryonic fibroblasts
  • NCCs
  • Neural crest cells
  • PKC
  • PKN
  • Protein kinase C
  • Protein kinase N

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