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

Nicolas Dray, Laure Mancini, Udi Binshtok, Felix Cheysson, Willy Supatto, Pierre Mahou, Sébastien Bedu, Sara Ortica, Emmanuel Than-Trong, Monika Krecsmarik, Sébastien Herbert, Jean Baptiste Masson, Jean Yves Tinevez, Gabriel Lang, Emmanuel Beaurepaire, David Sprinzak, Laure Bally-Cuif

Research output: Contribution to journalArticlepeer-review

Abstract

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.

Original languageEnglish
Pages (from-to)1457-1472.e12
JournalCell Stem Cell
Volume28
Issue number8
DOIs
StatePublished - 5 Aug 2021

Keywords

  • Notch signaling
  • adult neural stem cell
  • analytical modeling
  • intrinsic niche
  • pallium
  • population behavior
  • quiescence
  • spatial statistics
  • spatiotemporal homeostasis
  • zebrafish

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