Dynamic spatiotemporal coordination of neural stem cell fate decisions through local feedback in the adult vertebrate brain
N. Dray, L. Mancini, U. Binshtok, F. Cheysson, W. Supatto, P. Mahou, S. Bedu, S. Ortica, M Krecsmarik, S Herbert, JB Masson, J.Y. Tinevez, G. Lang, E. Beaurepaire, D. Sprinzak, and L. Bally-Cuif
Cell Stem Cell 28, 1457-1472 (2021) [Accès à la revue]
Ce travail utilise une visualisation en 3D et une analyse quantitative de la distribution spatiale et temporelle de l’activation des cellules souches neurales dans le cerveau adulte d’un modèle vertébré, le poisson zèbre. Les observations démontrent pour la première fois que les événements d’activation de ces cellules sont coordonnés dans le temps et dans l’espace. Ces résultats pourraient permettre notamment une meilleure compréhension des processus de régulation engagés dans la formation de tumeurs cérébrales.
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.
Thème : None
Equipe : UMR 3738 ():Zebrafish Neurogenetics