Dynamic spatiotemporal coordination of neural stem cell fate decisions through local feedback in the adult vertebrate brain

Abstract

Neural stem cell (NSC) populations persist in the adult vertebrate brain over a life time, and their homeostasis is controlled at the population level. The nature and properties of these coordination mechanisms remain unknown. Here we combine dynamic imaging of entire NSC populations in their in vivo niche over weeks, pharmacological manipulations, mathematical modeling and spatial statistics, and demonstrate that NSCs use spatiotemporally resolved local feedbacks to coordinate their decision to divide. These involve a Notch-mediated inhibition from transient neural progenitors, and a dispersion effect from dividing NSCs themselves, exerted with a delay of 9-12 days. Simulations from a stochastic NSC lattice model capturing these interactions demonstrate that they are linked by lineage progression and control the spatiotemporal distribution of output neurons. These results highlight how local and temporally delayed interactions occurring between brain germinal cells generate self-propagating dynamics that maintain NSC population homeostasis with specific spatiotemporal correlations.