Function of a cell cycle regulator, the CDC25B phosphatase, in Vertebrate neurogenesis


  • Fabienne Pituello
  • Sophie Bel-Vialar

In the last few years, our group has shown that expression of the phosphatase CDC25B, a positive regulator of the G2/M transition, shortens the duration of the G2 phase and promotes neuronal production in the developing spinal cord. CDC25B has been indirectly linked to the development of microcephaly in humans and, we are now investigating its function during corticogenesis. The cerebral cortex is the most evolutionarily recent tissue of the central nervous system. Its development is more complex and involves greater cellular diversity than in the spinal cord. Cortical neurons are produced in a temporally regulated sequence from apical progenitors, directly, or indirectly through the production of intermediate basal progenitors. The balance between these major progenitor types is essential for the production of the appropriate number and types of neurons. We have recently shown that in the neocortex of developing mice of both sexes, deletion of CDC25B in apical progenitors results in a transient increase in the production of TBR1+ neurons at the expense of TBR2+ basal progenitors. This phenotype is associated with a lengthening of the G2 phase of the cell cycle, with the total cell cycle time being unaffected. Using in utero electroporation and cortical slice cultures, we demonstrated that the defect in TBR2+ basal progenitor production requires interaction with CDK1 and is due to G2 phase elongation in CDC25B mutants. Overall, this study identifies a novel role for CDC25B and G2 phase length in direct versus indirect neurogenesis at early stages of cortical development. We are now investigating whether this function is conserved in humans using brain organoids. In addition, we have implemented an RNASeq strategy to identify the molecular mechanisms involved downstream of CDC25B to promote neuronal production.



  • Sophie BEL-VIALAR:

Université Paul Sabatier
118 Route de Narbonne

31062 TOULOUSE Cedex

05 61 33 58 00

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