APC/C-Cdh1 coordinates neurogenesis and cortical size during development
| Autor: | Carolina Maestre, Angeles Almeida, Sergio Moreno, Maria Delgado-Esteban, Irene García-Higuera |
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| Přispěvatelé: | Instituto de Salud Carlos III, European Commission, Ministerio de Economía y Competitividad (España), Junta de Castilla y León, Fundación Científica Asociación Española Contra el Cáncer |
| Rok vydání: | 2013 |
| Předmět: |
Male
Microcephaly Cell division Neurogenesis General Physics and Astronomy Apoptosis Cell Cycle Proteins Biology Anaphase-Promoting Complex-Cyclosome Cdh1 Proteins General Biochemistry Genetics and Molecular Biology Mice medicine Animals Progenitor cell Mitosis Progenitor Cerebral Cortex Mice Knockout Neurons Multidisciplinary Cell Cycle Organ Size General Chemistry Cell cycle medicine.disease Cell biology Knockout mouse Female Cell Division |
| Zdroj: | Digital.CSIC. Repositorio Institucional del CSIC instname |
| ISSN: | 2041-1723 |
| DOI: | 10.1038/ncomms3879 |
| Popis: | The morphology of the adult brain is the result of a delicate balance between neural progenitor proliferation and the initiation of neurogenesis in the embryonic period. Here we assessed whether the anaphase-promoting complex/cyclosome (APC/C) cofactor, Cdh1 - which regulates mitosis exit and G1-phase length in dividing cells - regulates neurogenesis in vivo. We use an embryo-restricted Cdh1 knockout mouse model and show that functional APC/C-Cdh1 ubiquitin ligase activity is required for both terminal differentiation of cortical neurons in vitro and neurogenesis in vivo. Further, genetic ablation of Cdh1 impairs the ability of APC/C to promote neurogenesis by delaying the exit of the progenitor cells from the cell cycle. This causes replicative stress and p53-mediated apoptotic death resulting in decreased number of cortical neurons and cortex size. These results demonstrate that APC/C-Cdh1 coordinates cortical neurogenesis and size, thus posing Cdh1 in the molecular pathogenesis of congenital neurodevelopmental disorders, such as microcephaly. © 2013 Macmillan Publishers Limited. This work was funded by Instituto de Salud Carlos III (PS09/0366, PI12/0685; RD06/0026/1008), FEDER (European regional development fund), Ministerio de Economía y Competitividad (BFU2011-28274, CSD2007-00015) and Junta de Castilla y León (CSI240A12-1). I.G.-H. is supported by Fundación Científica de la Asociación Española contra el Cáncer (AECC). M.D.-E. is supported by Instituto de Salud Carlos III (RD12/0014/0007). |
| Databáze: | OpenAIRE |
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