Identification of a sustained neurogenic zone at the dorsal surface of the adult mouse hippocampus and its regulation by the chemokine SDF‐1

Abstract

We identified a previously unknown neurogenic region at the dorsal surface of the hippocampus; (the “subhippocampal zone,” SHZ) in the adult brain. Using a reporter mouse in which SHZ cells and their progeny could be traced through the expression of EGFP under the control of the CXCR4 chemokine receptor promoter we observed the presence of a pool of EGFP expressing cells migrating in direction of the dentate gyrus (DG), which is maintained throughout adulthood. This population appeared to originate from the SHZ where cells entered a caudal migratory stream (aCMS) that included the fimbria, the meninges and the DG. Deletion of CXCR4 from neural stem cells (NSCs) or neuroinflammation resulted in the appearance of neurons in the DG, which were the result of migration of NSCs from the SHZ. Some of these neurons were ectopically placed. Our observations indicate that the SHZ is a neurogenic zone in the adult brain through migration of NSCs in the aCMS. Regulation of CXCR4 signaling in these cells may be involved in repair of the DG and may also give rise to ectopic granule cells in the DG in the context of neuropathology.

Nestin‐expressing cell types in the temporal lobe and hippocampus: Morphology, differentiation, and proliferative capacity

“…In rodents, the hippocampal fissure, equivalent to the sulcus in humans, has also been identified as a niche and further potential source of progenitor cells in adult animals . A further migratory stream has been described in mice extending from the hippocampal fimbra to dentate, composed of radial-glial like cells, which persists into adulthood (Belmadani et al, 2015). Recent studies of human hippocampal development also identify the fimbria as a further source of progenitor cells for the dentate gyrus (Cipriani et al, 2015).…”

The Dentate Gyrus and Temporal Lobe Epilepsy: An “Exciting” Era

“…Afterwards, an explanation for mismigration was proposed: It was shown that HIPP cells secrete reelin, which normally prevents cells from migrating to the source of reelin, whereas after HIPP cell death, hilar reelin was reduced. 53 Many years later, it was also shown that the GCs might emerge from the septohippocampal zone, 54 or the hilus itself, because progenitors and young GCs appear to be present in the hilus normally. 55 When recordings were made of the hilar "ectopic" granule cells (EGCs), it was shown that they have axons that innervate normal GCs and CA3 pyramidal cells, possibly mediating the synchronization needed for a seizure focus.…”

SDF-1 and CXCR4 play an important role in adult SVZ lineage cell proliferation and differentiation

“…SDF-1 was initially defined as a regulatory signaling protein required by peripheral hematopoietic stem cells (HSCs). However, SDF-1 also plays an important role in maintaining embryonic and adult NPCs (Addington et al, 2014;Belmadani et al, 2015;Nagasawa, 2014). Additionally, SDF-1 is predicted to contribute to the recruitment of NPCs to damaged regions to enhance recovery (Li et al, 2012;Merino et al, 2015).…”