Journal
CELL STEM CELL
Volume 28, Issue 8, Pages 1457-+Publisher
CELL PRESS
DOI: 10.1016/j.stem.2021.03.014
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Funding
- ANR (Labex Revive)
- La Ligue Nationale Contre le Cancer
- CNRS
- Institut Pasteur, DIM ELICIT
- European Research Council (ERC) [AdG 322936]
- Labex Revive
- Fondation pour la Recherche Medicale (FRM)
- ERC under the EU Horizon 2020 research and innovation program [682161]
- Marian Gertner Institute for Medical Nanosystems at Tel Aviv University
- ANR [ANR-10-INSB-04, ANR-11-EQPX-0029]
- European Research Council (ERC) [682161] Funding Source: European Research Council (ERC)
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The study shows that neural stem cells coordinate their decision to divide in the adult zebrafish brain using spatiotemporally resolved local feedback signals, including short-range inhibition from transient neural progenitors and a dispersion effect from the dividing NSCs themselves. These signals are linked by lineage progression and control the spatiotemporal distribution of output neurons, generating self-propagating dynamics that maintain NSC population homeostasis.
Neural stem cell (NSC) populations persist in the adult vertebrate brain over a lifetime, and their homeostasis is controlled at the population level through unknown mechanisms. Here, we combine dynamic imaging of entire NSC populations in their in vivo niche over several weeks with pharmacological manipulations, mathematical modeling, and spatial statistics and demonstrate that NSCs use spatiotemporally resolved local feedback signals to coordinate their decision to divide in adult zebrafish brains. These involve Notch-mediated short-range inhibition from transient neural progenitors and a dispersion effect from the dividing NSCs themselves exerted with a delay of 9-12 days. Simulations from a stochastic NSC lattice model capturing these interactions demonstrate that these signals 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 and coordinate specific spatiotemporal correlations.
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