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Reference : UMR5547-SOPVIA-001
Workplace : TOULOUSE
Date of publication : Tuesday, October 08, 2019
Scientific Responsible name : Sophie Bel-vialar
Type of Contract : PhD Student contract / Thesis offer
Contract Period : 36 months
Start date of the thesis : 1 December 2019
Proportion of work : Full time
Remuneration : 2 135,00 € gross monthly
Description of the thesis topic
Function of CDC25B phosphatase during neurogenesis
The control of the proliferation / differentiation balance of neural stem or progenitor cells is essential for the development and homeostasis of the vertebrate nervous system since a deregulation of this equilibrium is associated with neuro-developmental diseases and may be at the origin of tumors. Deciphering the mechanisms that control this balance in a physiological situation is therefore of major importance in basic research and can open up new perspectives for diagnosis and therapeutic innovation. Many studies show that some cell cycle regulators are able to alter the proliferation / differentiation balance of neural progenitors and we have shown that this is the case of CDC25B phosphatase, a positive regulator of the cell cycle. We have just shown, using gain and loss of function experiments in the chicken or mouse embryo, that in the developing spinal cord, CDC25B promotes neuronal differentiation by increasing, in the progenitors that expresses it, the rate neurogenic divisions (which produce at least one neuron). The use of a mutated form of CDC25B (CDC25BdelCDK, that no longer interacts with CDK1) shows that part of the neurogenic activity of CDC25B can be decoupled from its activity on the cell cycle. Preliminary results suggest that in the developing brain, CDC25B promotes the maturation of neuronal progenitors and that this function depends this time on its action on the cell cycle. The aim of this thesis project is to dissect the molecular mechanisms involved downstream of CDC25B in its dependent and independent cell cycle functions during neurogenesis. The strategy will be to compare, in the brain and spinal cord, the signaling pathways and transcriptional programs recruited by CDC25B or CDC25BdelCDK, using a transcriptomic approach by RNASeQ. We will also use a candidate approach in order to characterize the possible epistatic links between CDC25B and the BMP, FGF, Wnt, Notch and Shh signaling pathways, known to control both proliferation and neurogenesis, or proneural transcription factors, major players of neuronal differentiation. This work will allow identifying gene networks involved in controlling the proliferation / differentiation balance downstream of CDC25B during neurogenesis.
The entire thesis will be done at the Integrative Biology Center of Toulouse (http://cbi-toulouse.fr/fr/).
This laboratory brings together teams from Developmental Biology, Cell Biology, Eukaryotic and Prokaryotic Molecular Biology and Animal Cognition. It also has in its immediate environment, a group of platforms to develop approaches ranging from the molecule to populations (microscopy, bioinformatics, proteomics ... etc .. https://www.genotoul.fr/), including some are hosted in the laboratory (TRI, GeT ...).
Constraints and risks
no particular risk
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