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dc.contributor.authorNakaya, Takeoen_US
dc.contributor.authorIshiguro, Kei-ichiroen_US
dc.contributor.authorBelzil, Camilleen_US
dc.contributor.authorRietsch, Anna M.en_US
dc.contributor.authorYu, Qunyanen_US
dc.contributor.authorMizuno, Shin-ichien_US
dc.contributor.authorBronson, Roderick T.en_US
dc.contributor.authorGeng, Yanen_US
dc.contributor.authorNguyen, Minh Dangen_US
dc.contributor.authorAkashi, Koichien_US
dc.contributor.authorSicinski, Piotren_US
dc.contributor.authorNakatani, Yoshihiroen_US
dc.date.accessioned2014-02-18T18:11:53Z
dc.date.issued2013en_US
dc.identifier.citationNakaya, T., K. Ishiguro, C. Belzil, A. M. Rietsch, Q. Yu, S. Mizuno, R. T. Bronson, et al. 2013. “p600 Plays Essential Roles in Fetal Development.” PLoS ONE 8 (6): e66269. doi:10.1371/journal.pone.0066269. http://dx.doi.org/10.1371/journal.pone.0066269.en
dc.identifier.issn1932-6203en
dc.identifier.urihttp://nrs.harvard.edu/urn-3:HUL.InstRepos:11717645
dc.description.abstractp600 is a multifunctional protein implicated in cytoskeletal organization, integrin-mediated survival signaling, calcium-calmodulin signaling and the N-end rule pathway of ubiquitin-proteasome-mediated proteolysis. While push, the Drosophila counterpart of p600, is dispensable for development up to adult stage, the role of p600 has not been studied during mouse development. Here we generated p600 knockout mice to investigate the in vivo functions of p600. Interestingly, we found that homozygous deletion of p600 results in lethality between embryonic days 11.5 and 13.5 with severe defects in both embryo and placenta. Since p600 is required for placental development, we performed conditional disruption of p600, which deletes selectively p600 in the embryo but not in the placenta. The conditional mutant embryos survive longer than knockout embryos but ultimately die before embryonic day 14.5. The mutant embryos display severe cardiac problems characterized by ventricular septal defects and thin ventricular walls. These anomalies are associated with reduced activation of FAK and decreased expression of MEF2, which is regulated by FAK and plays a crucial role in cardiac development. Moreover, we observed pleiotropic defects in the liver and brain. In sum, our study sheds light on the essential roles of p600 in fetal development.en
dc.language.isoen_USen
dc.publisherPublic Library of Scienceen
dc.relation.isversionofdoi:10.1371/journal.pone.0066269en
dc.relation.hasversionhttp://www.ncbi.nlm.nih.gov/pmc/articles/PMC3688873/pdf/en
dash.licenseLAAen_US
dc.subjectBiologyen
dc.subjectDevelopmental Biologyen
dc.subjectMorphogenesisen
dc.subjectBirth Defectsen
dc.subjectHeart Developmenten
dc.subjectEmbryologyen
dc.subjectOrganism Developmenten
dc.subjectHistologyen
dc.subjectImmunologyen
dc.subjectImmunologic Techniquesen
dc.subjectImmunoassaysen
dc.subjectImmunohistochemical Analysisen
dc.subjectModel Organismsen
dc.subjectAnimal Modelsen
dc.subjectMouseen
dc.titlep600 Plays Essential Roles in Fetal Developmenten
dc.typeJournal Articleen_US
dc.description.versionVersion of Recorden
dc.relation.journalPLoS ONEen
dash.depositing.authorBronson, Roderick T.en_US
dc.date.available2014-02-18T18:11:53Z
dc.identifier.doi10.1371/journal.pone.0066269*
dash.authorsorderedfalse
dash.contributor.affiliatedSicinski, Piotr
dash.contributor.affiliatedNakatani, Yoshihiro Pat
dash.contributor.affiliatedGeng, Yan
dash.contributor.affiliatedBronson, Roderick


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