Knockout of the PKN Family of Rho Effector Kinases Reveals a Non-redundant Role for PKN2 in Developmental Mesoderm Expansion
| Autor: | Quétier I, Jj, Marshall, Spencer-Dene B, Lachmann S, Casamassima A, Franco C, Escuin S, Jt, Worrall, Baskaran P, Rajeeve V, Howell M, Aj, Copp, Stamp G, Rosewell I, Cutillas P, Holger Gerhardt, Pj, Parker, Aj, Cameron |
|---|---|
| Přispěvatelé: | Repositório da Universidade de Lisboa |
| Rok vydání: | 2016 |
| Předmět: |
Embryonic stem cells
animal structures Protein Kinase C/deficiency mouse embryonic fibroblasts Myocardium/metabolism Embryonic Development Antineoplastic Agents Apoptosis Cell Movement/drug effects Heart/growth & development Cell Line Protein kinase N Mesoderm Cell Proliferation/drug effects Mice Cell Movement Genes Reporter Report Animals PKC lcsh:QH301-705.5 Cell Proliferation Embryonic Development/drug effects Mice Knockout neural crest cells MEF Myocardium Apoptosis/drug effects Heart Embryo Mammalian ES cells PKN 4-hydroxytamoxifen Tamoxifen/analogs & derivatives Mice Inbred C57BL Tamoxifen Embryo Mammalian/cytology lcsh:Biology (General) Mesoderm/cytology Cardiovascular and Metabolic Diseases embryonic structures Microscopy Electron Scanning NCCs 4-OHT Antineoplastic Agents/pharmacology protein kinase C |
| Zdroj: | Cell Reports Cell Reports, Vol 14, Iss 3, Pp 440-448 (2016) 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 & Cameron, A J M 2016, ' Knockout of the PKN Family of Rho Effector Kinases Reveals a Non-redundant Role for PKN2 in Developmental Mesoderm Expansion ', Cell Reports, vol. 14, no. 3, pp. 440-448 . https://doi.org/10.1016/j.celrep.2015.12.049 Europe PubMed Central |
| ISSN: | 2211-1247 |
| DOI: | 10.1016/j.celrep.2015.12.049 |
| Popis: | 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. Graphical Abstract 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 The Rho effector PKN kinases regulate diverse cellular functions, but their in vivo function is unexplored. By systematically targeting the PKN family, Quetier et al. reveal a unique role for PKN2 during developmental growth and morphogenesis. These findings impact on developmental disorders and the targeting of PKN in disease. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|