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Related Concept Videos

Neurogenesis and Regeneration of Nervous Tissue01:15

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

Maria Delgado-Esteban1, Irene García-Higuera, Carolina Maestre

  • 11] Instituto de Investigación Biomédica de Salamanca (IBSAL), Hospital Universitario de Salamanca, Fundación IECSCYL, 37007 Salamanca, Spain [2] Instituto de Biología Funcional y Genómica (IBFG), CSIC/Universidad de Salamanca, IBSAL, 37007 Salamanca, Spain.

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|December 5, 2013
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Summary

The anaphase-promoting complex/cyclosome (APC/C) cofactor Cdh1 is essential for brain development. Loss of Cdh1 disrupts neurogenesis, leading to smaller brain size and potentially neurodevelopmental disorders.

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Area of Science:

  • Neuroscience
  • Developmental Biology
  • Molecular Biology

Background:

  • Brain morphology depends on neural progenitor proliferation and neurogenesis during embryonic development.
  • The anaphase-promoting complex/cyclosome (APC/C) cofactor Cdh1 regulates cell cycle progression, specifically mitosis exit and G1-phase duration.

Purpose of the Study:

  • To investigate the role of APC/C-Cdh1 in regulating neurogenesis in vivo.
  • To determine if Cdh1 is essential for the terminal differentiation of cortical neurons and overall brain development.

Main Methods:

  • Utilized an embryo-restricted Cdh1 knockout mouse model.
  • Assessed the impact of Cdh1 ablation on progenitor cell cycle exit, neurogenesis, and cortical neuron differentiation.
  • Analyzed replicative stress, p53-mediated apoptosis, and resulting effects on cortex size.

Main Results:

  • Functional APC/C-Cdh1 ubiquitin ligase activity is crucial for both in vitro cortical neuron differentiation and in vivo neurogenesis.
  • Genetic ablation of Cdh1 delays progenitor cell cycle exit, impairing APC/C's ability to promote neurogenesis.
  • This leads to replicative stress, p53-mediated apoptosis, reduced cortical neuron numbers, and smaller cortex size.

Conclusions:

  • APC/C-Cdh1 plays a critical role in coordinating cortical neurogenesis and determining brain size.
  • Dysregulation of Cdh1 may contribute to the molecular pathogenesis of congenital neurodevelopmental disorders like microcephaly.