2025/08/01 by Sara Ortica, Miguel Martinez Herrera, Louis Degroux +3 · 1 voice
Biochemistry, Genetics and Molecular Biology · Neuroscience · #Developmental Biology and Gene Regulation #Neurogenesis and neuroplasticity mechanisms #Zebrafish Biomedical Research Applications
paper · pdf · doi:10.1101/2025.07.29.667421
openalex publication_date 2025/08/01 · openalex created_date 2025/10/10 · openalex updated_date 2026/07/22
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, positively interacts with Notch3 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.