Jagged-mediated lateral induction patterns Notch3 signaling within adult neural stem cell populations

Abstract

Abstract In the adult brain, Notch3 signaling promotes neural stem cell (NSC) quiescence and stemness. It remains unknown how Notch3 signaling levels are controlled and relate to these NSC decisions. Here we directly measure the nuclear translocation of the Notch3 intracellular fragment (N3ICD) and quantify Notch3 signaling in NSCs of the zebrafish adult telencephalon in situ. We report that Notch3 signaling levels match NSC quiescence and stemness levels. In physical space, Notch3 signaling is patterned and high signaling levels surround N3ICD low cells, which also express the deltaA (dla ) ligand. Another ligand, jagged1b ( jag1b ), expressed in all NSCs, activates Notch3 signaling and sustains expression of the stemness factor Sox2. Finally, lowering jag1b preserves the structured distribution of Notch3 signaling levels in space but attenuates their variance. We propose that Notch3 signaling integrates Dla-mediated lateral inhibition and Jag1b-mediated lateral induction to control quiescence and stemness and their spatiotemporal dynamics in adult NSCs.