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

Abstract

SUMMARY 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.

Mapping p53 Mutations in Low-Grade Glioma: A Voxel-Based Neuroimaging Analysis

“…12,20,30 Our results, in some way, support the neural stem cell hypothesis. This finding is because of the 182…”

Roles for Hedgehog signaling in adult organ homeostasis and repair

“…Dispersed SHH-positive neurons have been detected throughout the adult cortex and could also be the source of HH ligand for astrocytes (Garcia et al, 2010). Alternatively or perhaps in addition to these cells, a population of Shh gfpCre fate-mapped calretinin+ neurons in the DG hilus region has also been proposed to serve as a local source of ligand for the postnatal SGZ region (Li et al, 2013); however, it remains to be determined whether these cells continue to express SHH in adulthood. Finally, delivery of HH ligand through the cerebrospinal fluid (CSF) in the brain ventricular system has been reported in the developing brain , and increased levels of SHH protein are detected in the adult CSF following brain injury (Sirko et al, 2013).…”

RB: An essential player in adult neurogenesis

“…They are believed to originate embryonically, whether during mid-development for slowly-dividing SVZ qNSCs. 8,9 or late development for SGZ qNSCs, in advance of postnatal SGZ formation 10,11 These quiescent cells undergo reversible transition into an activated state, which is believed to be mediated by factors including Ascl1, 12 and BMP signaling specifically in the DG. 13 The second key process is the maintenance of an adult-born neuron population; guiding activated NSCs through self-renewal or commitment to neuronal differentiation, and ensuring their postmitotic survival.…”