Skip to Content
Merck
  • APC/C-Cdh1 coordinates neurogenesis and cortical size during development.

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

Nature communications (2013-12-05)
Maria Delgado-Esteban, Irene García-Higuera, Carolina Maestre, Sergio Moreno, Angeles Almeida
ABSTRACT

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.

MATERIALS
Product Number
Brand
Product Description

Sigma-Aldrich
Anti-phospho-Histone H2A.X (Ser139) Antibody, clone JBW301, biotin conjugate, clone JBW301, Upstate®, from mouse
Sigma-Aldrich
Anti-phospho-Histone H3 (Ser10) Antibody, Mitosis Marker, Upstate®, from rabbit