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

AuthorsDelgado-Esteban, María ; García-Higuera, Irene ; Maestre, Carolina; Moreno, Sergio ; Almeida, Angeles
Issue Date2013
PublisherNature Publishing Group
CitationNature Communications 4: 2879 (2013)
AbstractThe 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.
Identifierse-issn: 2041-1723
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