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
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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
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
Eukaryotic cells depend on exocytosis to direct intracellularly synthesized material toward the extracellular space or the plasma membrane, so exocytosis constitutes a basic function for cellular homeostasis and communication between cells. The secretory pathway includes biogenesis of secretory granules (SGs), their maturation and fusion with the plasma membrane (exocytosis), resulting in release of SG content to the extracellular space. The larval salivary gland of Drosophila melanogaster is an excellent model for studying exocytosis. This gland synthesizes mucins that are packaged in SGs that sprout from the trans-Golgi network and then undergo a maturation process that involves homotypic fusion, condensation, and acidification. Finally, mature SGs are directed to the apical domain of the plasma membrane with which they fuse, releasing their content into the gland lumen. The exocyst is a hetero-octameric complex that participates in tethering of vesicles to the plasma membrane during constitutive exocytosis. By precise temperature-dependent gradual activation of the Gal4-UAS expression system, we have induced different levels of silencing of exocyst complex subunits, and identified three temporarily distinctive steps of the regulated exocytic pathway where the exocyst is critically required: SG biogenesis, SG maturation, and SG exocytosis. Our results shed light on previously unidentified functions of the exocyst along the exocytic pathway. We propose that the exocyst acts as a general tethering factor in various steps of this cellular process.
