| First Author | Delgado-Esteban M | Year | 2013 |
| Journal | Nat Commun | Volume | 4 |
| Pages | 2879 | PubMed ID | 24301314 |
| Mgi Jnum | J:206142 | Mgi Id | MGI:5548005 |
| Doi | 10.1038/ncomms3879 | Citation | Delgado-Esteban M, et al. (2013) APC/C-Cdh1 coordinates neurogenesis and cortical size during development. Nat Commun 4:2879 |
| abstractText | 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. |
