The chordate central nervous system (CNS) is composed of neurons and glia, which stem from cells of a regionalized neural plate. Neural cells exit the cell cycle at specific developmental times before their terminal differentiation.
The timing of this exit is often important for the final fate of the cell. This project focuses on the links between cell cycle exit and cellular differentiation during CNS formation in a basal chordate, the ascidian Ciona intestinalis.
This system was chosen for its phylogenetic position as well for the simplicity of its embryogenesis (small cell numbers, invariant cleavages), which will enable to study with cellular resolution the communication between cell cycle regulation and differentiation.
In addition, Ciona genome has bee n sequenced, annotated and shown to be remarkably small and compact. Finally, powerful molecular tools including a Unigene cDNA set, microarrays, and efficient Gateway electroporation vectors are available.
I will address the following issues:
- Establish 4D multiphoton confocal live imaging and characterize the spatio-temporal pattern of mitosis of the progeny of each neural plate cell.
- Characterize the spatio-temporal expression pattern of all predicted cell cycle regulators and their upstream candidate regulators in the CNS.
- Carry out a functional analysis of the effect on the differentiation program of interfering with the cell cycle status of neural progenitors.
Special emphasis will be given to the search for mitotic domains and to the regulation of the last cell division. This project will provide a first comprehensive view of the communication between cell cycle regulation and differentiation at play in a chordate CNS.
In addition to its interest for developmental studies, this project may unravel novel connections between cell cycle and differentiation, which may help understand tumourigenesis.
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