The growing brain faces the challenge to establish neural stem cell (NSC) populations that accomplish both stable NSC maintenance and dynamic generation of progenitors. Lineage-specific scRNA-seq and time series transcriptome analyses upon overexpression of Notch signaling components in the larval zebrafish brain reveal differential contributions of Notch signaling and Notch-independent Her6, a HES1 homolog, to NSC regulation. Notch signaling and Her6 distinctly regulate cell cycle genes to control G0/G1 or G2 exit and promote quiescence. Her6 and Notch activity combined differentially control delta, jagged, lfng and notch3 expression to potentially shift Notch signaling from Delta-driven lateral inhibition to Jagged-Notch3-mediated lateral induction. We propose that Her6 integrates cell-autonomous lineage-based information and lateral induction-mediated non-autonomous self-organization of neural proliferation zones. Her6-dependent lateral induction maintains persistent NSC patches in ventricular compartments with ongoing neurogenesis, and establishes coherent populations of long-term NSCs in active proliferation zones.
Rothenpieler, J., Veit, R., Stefanovska, D., Schwab, J., Sigloch, C. E., Gruen, D., Driever, W.
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