The Ventral Hippocampus Is the Embryonic Origin for Adult Neural Stem Cells in the Dentate Gyrus

Adult neurogenesis represents a unique form of plasticity in the dentate gyrus requiring the presence of long-lived neural stem cells (LL-NSCs). However, the embryonic origin of these LL-NSCs remains unclear. The prevailing model assumes that the dentate neuroepithelium throughout the longitudinal axis of the hippocampus generates both the LL-NSCs and embryonically produced granule neurons. Here we show that the NSCs initially originate from the ventral hippocampus during late gestation and then relocate into the dorsal hippocampus. The descendants of these cells are the source for the LL-NSCs in the subgranular zone (SGZ). Furthermore, we show that the origin of these cells and their maintenance in the dentate are controlled by distinct sources of Sonic Hedgehog (Shh). The revelation of the complexity of both the embryonic origin of hippocampal LL-NSCs and the sources of Shh has important implications for the functions of LL-NSCs in the adult hippocampus. •Dentate NSCs are descendants of Shh-responsive cells in the ventral hippocampus•Extracortical Sonic Hedgehog is required for production of dentate stem cells•Local neuronal sources of Sonic Hedgehog are required for SGZ maintenance•Adult dentate long-lived NSCs are the progeny of embryonic Shh-responsive cells Li et al. show that long-lived neural stem cells in the dentate gyrus derive from the ventral hippocampus. These cells, together with granule cells produced at all septotemporal levels, reveal that the dentate gyrus has a mosaic organization.