p600 Plays Essential Roles in Fetal Development

Takeo Nakaya, Kei ichiro Ishiguro, Camille Belzil, Anna M. Rietsch, Qunyan Yu, Shin ichi Mizuno, Roderick T. Bronson, Yan Geng, Minhng Da Nguyen, Koichi Akashi, Piotr Sicinski, Yoshihiro Nakatani

Research output: Contribution to journalArticle

8 Citations (Scopus)

Abstract

p600 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.

Original languageEnglish
Article numbere66269
JournalPloS one
Volume8
Issue number6
DOIs
Publication statusPublished - Jun 18 2013

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fetal development
Fetal Development
embryo (animal)
Embryonic Structures
Defects
Proteolysis
placenta
Placenta
Proteasome Endopeptidase Complex
Calmodulin
Ubiquitin
Integrins
Liver
Brain
cytoskeletal proteins
Placentation
Chemical activation
mutants
Calcium Signaling
Ventricular Heart Septal Defects

All Science Journal Classification (ASJC) codes

  • Biochemistry, Genetics and Molecular Biology(all)
  • Agricultural and Biological Sciences(all)

Cite this

Nakaya, T., Ishiguro, K. I., Belzil, C., Rietsch, A. M., Yu, Q., Mizuno, S. I., ... Nakatani, Y. (2013). p600 Plays Essential Roles in Fetal Development. PloS one, 8(6), [e66269]. https://doi.org/10.1371/journal.pone.0066269

p600 Plays Essential Roles in Fetal Development. / Nakaya, Takeo; Ishiguro, Kei ichiro; Belzil, Camille; Rietsch, Anna M.; Yu, Qunyan; Mizuno, Shin ichi; Bronson, Roderick T.; Geng, Yan; Da Nguyen, Minhng; Akashi, Koichi; Sicinski, Piotr; Nakatani, Yoshihiro.

In: PloS one, Vol. 8, No. 6, e66269, 18.06.2013.

Research output: Contribution to journalArticle

Nakaya, T, Ishiguro, KI, Belzil, C, Rietsch, AM, Yu, Q, Mizuno, SI, Bronson, RT, Geng, Y, Da Nguyen, M, Akashi, K, Sicinski, P & Nakatani, Y 2013, 'p600 Plays Essential Roles in Fetal Development', PloS one, vol. 8, no. 6, e66269. https://doi.org/10.1371/journal.pone.0066269
Nakaya T, Ishiguro KI, Belzil C, Rietsch AM, Yu Q, Mizuno SI et al. p600 Plays Essential Roles in Fetal Development. PloS one. 2013 Jun 18;8(6). e66269. https://doi.org/10.1371/journal.pone.0066269
Nakaya, Takeo ; Ishiguro, Kei ichiro ; Belzil, Camille ; Rietsch, Anna M. ; Yu, Qunyan ; Mizuno, Shin ichi ; Bronson, Roderick T. ; Geng, Yan ; Da Nguyen, Minhng ; Akashi, Koichi ; Sicinski, Piotr ; Nakatani, Yoshihiro. / p600 Plays Essential Roles in Fetal Development. In: PloS one. 2013 ; Vol. 8, No. 6.
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