Neurogenic decisions require a cell cycle independent function of the CDC25B phosphatase
- Université de Toulouse, CNRS, UPS, France
Abstract
A fundamental issue in developmental biology and in organ homeostasis is understanding the molecular mechanisms governing the balance between stem cell maintenance and differentiation into a specific lineage. Accumulating data suggest that cell cycle dynamics play a major role in the regulation of this balance. Here we show that the G2/M cell cycle regulator CDC25B phosphatase is required in mammals to finely tune neuronal production in the neural tube. We show that in chick neural progenitors, CDC25B activity favors fast nuclei departure from the apical surface in early G1, stimulates neurogenic divisions and promotes neuronal differentiation. We design a mathematical model showing that within a limited period of time, cell cycle length modifications cannot account for changes in the ratio of the mode of division. Using a CDC25B point mutation that cannot interact with CDK, we show that part of CDC25B activity is independent of its action on the cell cycle.
Data availability
All data generated or analysed during this study are included in the manuscript and supporting files
Article and author information
Author details
Funding
Centre National de la Recherche Scientifique
- Frédéric Bonnet
- Angie Molina
- Melanie Roussat
- Manon Azais
- Sophie Vialar
- Jacques Gautrais
- Fabienne Pituello
- Eric Agius
Ministère de l'Enseignement Supérieur et de la Recherche Scientifique
- Frédéric Bonnet
- Melanie Roussat
- Manon Azais
Fondation ARC pour la Recherche sur le Cancer
- Angie Molina
Fédération pour la Recherche sur le Cerveau
- Angie Molina
Université de Toulouse
- Jacques Gautrais
- Fabienne Pituello
- Eric Agius
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Ethics
Animal experimentation: Experiments were performed in accordance with European Community guidelines regarding care and use of animals, agreement from the Ministère de l'Enseignement Supérieur et de la Recherche number: C3155511, reference 01024.01 and the CNRS recommendations
Reviewing Editor
- Constance L Cepko, Harvard Medical School, United States
Publication history
- Received: October 18, 2017
- Accepted: June 8, 2018
- Accepted Manuscript published: July 3, 2018 (version 1)
- Version of Record published: July 18, 2018 (version 2)
- Version of Record updated: September 17, 2020 (version 3)
Copyright
© 2018, Bonnet et al.
This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.
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Neurogenic decisions require a cell cycle independent function of the CDC25B phosphatase
eLife 7:e32937.
https://doi.org/10.7554/eLife.32937
Further reading
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- Cell Biology
- Developmental Biology
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