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

Abstract

SUMMARYNeural 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.

LocalZProjectorandDeProj: A toolbox for local 2D projection and accurate morphometrics of large 3D microscopy images

“…To understand NSC populattion homeostasis it is essential to integrate large-scale and long-term imaging of the NSC pool and the zebrafish telencephalon has recently emerged as a unique model for these studies (5, 31). To study cellular and mechanical functions of NSC over the entire over the entire dorsal telencephalon (pallium) we can image whole-mount immunostainings against ZO1 (4), highlighting apical domains of the NSCs. However, since the pallial hemispheres are highly curved we so far could not extract the geometrical parameters of many NSCs (falling in periphery, in sulci, etc.…”

“…In vertebrate adult brains, neural stem cells (NSCs) are organized in a pool forming an epithelium. The coordination of their behavior, such as division or differentiation, are in part regulated via local cell-cell interactions (4) but is also regulated via large-scale coordination (5). Thus, the elucidation of biological questions related to processes involving complex epithelia now require the imaging of large tissues, while reaching single cell resolution and single cell shape quantitation.…”

“…In vertebrate adult brains, neural stem cells (NSCs) are organized in a pool forming an epithelium. The architecture and size of the brain relies on the rate of division and differentiation of stem cells which is in part regulated by local cellcell interactions (5). All these examples illustrates an essential challenge of tissue and developmental biology: namely bridging the gap between the cellular scales and emerging properties at the tissue level.…”

Know thy neighbor: Modeling spatiotemporal cell-fate patterns in a neural stem cell niche

“…In this issue of Cell Stem Cell, Dray and colleagues take a significant step toward overcoming these barriers by bringing together an elegant in vivo lineage labeling paradigm at cellular resolution with spatial point process modeling to make causal inferences on the spatiotemporal distribution of activated neural stem cells, and their divisions, in the adult zebrafish brain (Dray et al, 2021).…”