APC/C-Cdh1 coordinates neurogenesis and cortical size during development

作者：Delgado Esteban Maria; Garcia Higuera Irene; Maestre Carolina; Moreno Sergio; Almeida Angeles^*

来源：Nature Communications, 2013, 4(1): 2879.

DOI：10.1038/ncomms3879

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.

• 出版日期2013-12