A novel stem cell type at the basal side of the subventricular zone maintains adult neurogenesis

Abstract

According to the current consensus, murine neural stem cells (NSCs) apically contacting the lateral ventricle generate differentiated progenitors by rare asymmetric divisions or by relocating to the basal side of the ventricular–subventricular zone (V‐SVZ). Both processes will ultimately lead to the generation of adult‐born olfactory bulb (OB) interneurons. In contrast to this view, we here find that adult‐born OB interneurons largely derive from an additional NSC‐type resident in the basal V‐SVZ. Despite being both capable of self‐renewal and long‐term quiescence, apical and basal NSCs differ in Nestin expression, primary cilia extension and frequency of cell division. The expression of Notch‐related genes also differs between the two NSC groups, and Notch activation is greatest in apical NSCs. Apical downregulation of Notch‐effector Hes1 decreases Notch activation while increasing proliferation across the niche and neurogenesis from apical NSCs. Underscoring their different roles in neurogenesis, lactation‐dependent increase in neurogenesis is paralleled by extra activation of basal but not apical NSCs. Thus, basal NSCs support OB neurogenesis, whereas apical NSCs impart Notch‐mediated lateral inhibition across the V‐SVZ. image Basal neural stem cells are the most abundant stem cell type in the adult mouse V‐SVZ from birth onwards and the main contributors to olfactory bulb neurogenesis. Basal NSCs do not contact the lateral ventricle unlike the apical radial glia‐like counterpart. Basal NSCs are the main source of adult‐born olfactory bulb interneurons. Apical NSCs regulate niche proliferation by promoting Notch‐mediated lateral inhibition of proliferation.