Séminaire IBPS - Single cell and population mechanisms controlling adult neural stem cell maintenance

We aim to understand how single cell and population events interplay to ensure the maintenance of neural stem cell (NSC) ensembles in the adult brain. We focus on the dorsal telencephalon (pallium), which hosts NSCs in all adult vertebrates. In the zebrafish, pallial NSCs are a monolayer of tightly juxtaposed radial glia. These cells are mostly quiescent but can transiently activate (ie. enter the cell cycle) 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 conditioning 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 record, over weeks and with single cell resolution, the behavior of all NSCs in their niche. With this, 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 (Dray et al., 2021). Dynamic intravital imaging also revealed two parameters respectively predicting NSC activation propensity and division mode: NSC apical size and expression of the Notch ligand DeltaA (Mancini et al., unpub.). We 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 ensemble.