Long-term ex vivo live imaging combined with unbiased sampling of cycling precursors shows that macaque outer subventricular zone (OSVZ) includes four distinct basal radial glial (bRG) cell morphotypes, bearing apical and/or basal processes in addition to nonpolar intermediate progenitors (IPs). Each of the five precursor types exhibits extensive self-renewal and proliferative capacities as well as the ability to directly generate neurons, albeit with different frequencies. Cell-cycle parameters exhibited an unusual stage-specific regulation with short cell-cycle duration and increased rates of proliferative divisions during supragranular layer production at late corticogenesis. State transition analysis of an extensive clonal database reveals bidirectional transitions between OSVZ precursor types as well as stage-specific differences in their progeny and topology of the lineage relationships. These results explore rodent-primate differences and show that primate cortical neurons are generated through complex lineages by a mosaic of precursors, thereby providing an innovative framework for understanding specific features of primate corticogenesis.

Neural stem and progenitor cells (NSPCs) generate neurons throughout life in the mammalian hippocampus. We used chronic in vivo imaging and followed genetically labeled individual NSPCs and their progeny in the mouse hippocampus for up to 2 months. We show that NSPCs targeted by the endogenous Achaete-scute homolog 1 (Ascl1) promoter undergo limited rounds of symmetric and asymmetric divisions, eliciting a burst of neurogenic activity, after which they are lost. Further, our data reveal unexpected asymmetric divisions of nonradial glia-like NSPCs. Cell fates of Ascl1-labeled lineages suggest a developmental-like program involving a sequential transition from a proliferative to a neurogenic phase. By providing a comprehensive description of lineage relationships, from dividing NSPCs to newborn neurons integrating into the hippocampal circuitry, our data offer insight into how NSPCs support life-long hippocampal neurogenesis.