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

Abstract

Summary 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.

Neuron-radial glial cell communication via BMP/Id1 signaling maintains the regenerative capacity of the adult zebrafish telencephalon

“…This process bears resemblance to lateral inhibition initially proposed to select the precursor cell of sensory bristles in the Drosophila cuticle (Simpson, 1990). Thus, the dynamics of the NSCs generate an intrinsic cue that assures their long-term maintenance (Dray et al, 2021a). Our data here suggest that intrinsic Notch signaling is not the only mechanism that safeguards maintenance of NSCs in the zebrafish telencephalon but also BMP mediated cross-talk between neurons and the stem cells.…”

“…In particular, Notch3 has been implicated in the control of RGC quiescence (Alunni et al, 2013). Notch signaling appears to act on short-range between NSCs and activated neural precursors (type III cells) (Dray et al, 2021a). This process bears resemblance to lateral inhibition initially proposed to select the precursor cell of sensory bristles in the Drosophila cuticle (Simpson, 1990).…”

“…In agreement, when we checked for expression of the proliferation marker PCNA, the id1/her4.1 double-positive cells expressed PCNA less frequently than the single id1 or her4.1 expressing cells. It is, however, also possible that these id1+/her4.1-/PCNA+ and the id1-/her4.1+/PCNA+ cells are transition state cells that are on the way back to quiescence or in transition to neuroblasts (Type IIIa cells (März et al, 2010) also called activated neural progenitors (aNPs) (Dray et al, 2021a)).…”

“…Specifically, in the zebrafish telencephalon Notch3 is expressed in RGCs and promotes quiescence of NSCs (Alunni et al, 2013). This signaling originates, at least in part, from the progenitor population itself (Dray et al, 2021a;Dray et al, 2021b). Notch signaling appears to serve as an intrinsic signaling cue for the regulation of quiescence and the maintenance of the stem cell population in mammals and fish (Diotel et al, 2020;Alunni and Bally-Cuif, 2016).…”

Multi-Dimensional Transcriptome Analysis Reveals Modulation of Cholesterol Metabolism as Highly Integrated Response to Brain Injury

“…Their thin processes span the entire parenchyma. RGCs differentiate into either neuronal cells or, in self-renewing cycles, into more radial glial cells (Than-Trong and Bally-Cuif, 2015;Dray et al, 2021). In response to injury, RGCs undergo mostly symmetric divisions (Barbosa et al, 2015).…”