Role of cell cycle in cell fate decision
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Research engineer Researcher
Associate professor Technical staff PhD student
- Eric Agius
- Sophie Bel-Vialar
- Fabienne Pituello
- Sofiane Omerani
- Delphine Bretonniere
- Julie Pignolet
During embryonic and adult development, the control of the balance between proliferation and differentiation of stem/progenitor cells is essential for the formation and homeostasis of tissues and organs, requiring close coordination of cell cycle regulation and differentiation mechanisms. A deregulation of this coordination can lead to excessive proliferation and/or a defect in differentiation, leading to the development of pathologies such as cancers or developmental defects. Understanding how this balance is regulated and how it is coordinated with differentiation processes in physiological situations is essential for a better understanding of the mechanisms involved in pathophysiological conditions.
Our team is interested in the control of the proliferation/differentiation balance of embryonic neural stem/progenitor cells. We have shown that during early neurogenesis in mouse and chicken embryo models, CDC25B phosphatase, a positive regulator of the G2/M transition, promotes neuronal differentiation while inducing a shortening of the G2 phase and a lengthening of the G1 phase. Our work is now focused on studying the mechanisms involved in this regulation and the consequences for neural progenitor heterogeneity and fate.
Our aim is to understand how the cell cycle affects cell fate decisions in organ development and homeostasis using as a paradigm the developing nervous system. Deciphering the core machinery of cell cycle has been mostly the focus of cell biologists, while, developmental biologists identified the signaling pathways and transcriptional programs controlling cell fate choices. The interplay between these two fundamental aspects of biology remained largely unexplored. The goal of our project is to implement molecular analyses with advanced technique in time-lapse imaging to elucidate how changes in cell cycle features switch a proliferating neural progenitor into a differentiating neuron.
Spinal neurogenesis:From modeling to experimentation
Function of a cell cycle regulator, the CDC25B phosphatase, in Vertebrate neurogenesis
Role of cell cycle in cell fate decision during organogenesis: Insight into the developing nervous system using single cell high resolution time lapse imaging
- Roussat M, Jungas T, Audouard C, Omerani S, Medevielle F, Agius E, Davy A, Pituello F and Bel-Vialar S..
Control of G2 Phase duration by CDC25B modulates the switch from direct to indirect neurogenesis in the neocortex.
Journal of Neuroscience
- Angie Molina, Frederic Bonnet, Julie Pignolet, Valerie Lobjois, Sophie Bel-vialar, Jacques Gautrais, Fabienne Pituello, Eric Agius.
Single-cell imaging of the cell cycle reveals CDC25B-induced heterogeneity of G1 phase length in neural progenitor cells
- Bonnet F, Molina A, Roussat M, Azais M, Bel-Vialar S, Gautrais J, Pituello F, Agius E.
Neurogenic decisions require a cell cycle independent function of the CDC25B phosphatase.
- Lacomme M, Medevielle F, Bourbon HM, Thierion E, Kleinjan DJ, Roussat M, Pituello F, Bel-Vialar S..
A long range distal enhancer controls temporal fine-tuning of PAX6 expression in neuronal precursors.
- Angie Molina, Fabienne Pituello.
Playing with the cell cycle to build the spinal cord
2017 Dec review
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