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Knockout of the PKN family of Rho effector kinases reveals a non-redundant role for PKN2 in developmental mesoderm expansion

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Item Type:Article
Title:Knockout of the PKN family of Rho effector kinases reveals a non-redundant role for PKN2 in developmental mesoderm expansion
Creators Name:Quétier, I., Marshall, J.J.T., Spencer-Dene, B., Lachmann, S., Casamassima, A., Franco, C., Escuin, S., Worrall, J.T., Baskaran, P., Rajeeve, V., Howell, M., Copp, A.J., Stamp, G., Rosewell, I., Cutillas, P., Gerhardt, H., Parker, P.J. and Cameron, A.J.M.
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.
Keywords:Antineoplastic Agents, Apoptosis, Cell Line, Cell Movement, Cell Proliferation, Embryonic Development, Heart, Inbred C57BL Mice, Knockout Mice, Mammalian Embryo, Mesoderm, Myocardium, Protein Kinase C, Reporter Genes, Scanning Electron Microscopy, Tamoxifen, Animals, Mice
Source:Cell Reports
ISSN:2211-1247
Publisher:Cell Press / Elsevier
Volume:14
Number:3
Page Range:440-448
Date:26 January 2016
Official Publication:https://doi.org/10.1016/j.celrep.2015.12.049
PubMed:View item in PubMed

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