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Résumé |
We are interested in understanding how single cell and population events combine
to ensure the maintenance of neural stem cell (NSC) pools in the adult brain. We
focus on the dorsal telencephalon(pallium), which hosts NSCs in all adult
vertebrates. In teleost fish such as the zebrafish, the pallial NSC pool consists
of a monolayer of tightly juxtaposed radial glial cells. NSCs are mostly
quiescent, but can transiently activate (ie. enter the cell cycle and divide) to
divide and generate other NSCs and/or neurons. The NSC decision to activate, and
the fate choices it makes at division, are two key events that condition NSC
maintenance. These events are controlled at both the single-cell and the
population levels, and we are taking quantitative and dynamic approaches to
understand these processes in time and space. For this, we developed an intra-
vital imaging method to directly record, over weeks and with single cell
resolution, the behavior of NSCs in their niche (>1,000 cells per pallial
hemisphere). With this method, we generated a 4D map of NSC activation and
division events. Using spatial statistics and mathematical modeling in an NSC
lattice, we showed that NSC activation events are spatiotemporally correlated by
local and temporally delayed interactions that occur between brain germinal cells
and generate self-propagating dynamics. We also observed that NSC apical size is
highly predictive of NSC fate decisions at division, and are analyzing the
mechanisms involved and their cell- and non-cell-autonomous impact. Together, this
work will highlight how NSCs across the germinal sheet coordinate their state and
fate decisions for the harmonious and long-lasting maintenance of the NSC pool. |
