Homeostatic neurogenesis in the adulthippocampus does not involve amplificationof Ascl1 high intermediate progenitors

摘要

Neural stem/progenitor cells generate neurons in the adult hippocampus. neural stem cellsproduce transient intermediate progenitors (type-2 cells), which generate neuroblasts (type-3cells) that exit the cell cycle, and differentiate into neurons. The precise dynamics of neuronproduction from the neural stem cells remains controversial. Here we lineage trace notchdependent neural stem cells in the dentate gyrus and show that over 7–21 days, the progeny ofthe neural stem cells progress through an Ascl1highintermediate stage (type-2a) to neuroblasts.However, contrary to predictions, this Ascl1high population is not an amplifying intermediate,but it differentiates into mitotic Tbr2+early neuroblasts, which in turn expand the lineage.After 100 days, the majority of the neural stem cell progeny are neuroblasts or postmitoticneurons. Hence, the neural stem cells require many weeks to generate differentiated neurons.on the basis of this temporal delay in differentiation and population expansion, we propose thatthe neural stem cell and early neuroblast divisions drive dentate gyrus neurogenesis and notthe amplification of type-2a intermediate progenitors as was previously thought.