Functional heterogeneity of Wnt-responsive and Hedgehog-responsive neural stem cells in the murine adult hippocampus

Neural stem cells (NSCs) in the adult hippocampus are composed of multiple subpopulations. However, their origin and functional heterogeneity are still unclear. Here, we found that the contribution of murine Wnt-responsive (Axin2+) and Hedgehog-responsive (Gli1+) embryonic neural progenitors to adult NSCs started from early and late postnatal stages, respectively. Axin2+ adult NSCs were intended to actively proliferate, whereas Gli1+ adult NSCs were relatively quiescent and responsive to external stimuli. Moreover, Gli1+ NSC-derived adult-born neurons exhibited more complex dendritic arborization and connectivity than Axin2+ NSC-derived ones. Importantly, genetic cell ablation analysis identified that Axin2+ and Gli1+ adult NSCs were involved in hippocampus-dependent learning, but only Axin2+ adult NSCs were engaged in buffering stress responses and depressive behavior. Together, our study not only defined the heterogeneous multiple origins of adult NSCs but also advanced the concept that different subpopulations of adult NSCs may function differently.