In the hippocampus, neural stem cells (NSCs) are present even in adulthood, and the granule cells continue to be generated throughout life. Therefore, the hippocampal NSCs presumably possess the special mechanisms to maintain stemness for long-term period. Unlike general embryonic NSCs, adult hippocampal NSCs are known to express glial fibrillary acidic protein (GFAP). However, it remains unclear about the embryonic origin of adult hippocampal NSCs. Our previous analysis using the transgenic mice expressing GFP under the control of Gfap promoter (Gfap-GFP mice) reveals that GFP⁺ cells are confined to the dentate primordium at early stage of neurogenesis, hence we assumed that Gfap-expressing cells in the developing hippocampus are candidates for the source of the adult NSCs. Here we studied the mechanisms to generate Gfap-expressing NSCs in the developing hippocampus.
First, to examine whether the Gfap-expressing cells have NSC property, hippocampal cells were isolated from Gfap-GFP mouse embryos and were cultured in the medium with FGF2. Gfap-expressing cells expressed NSC markers and were able to form neurospheres, suggesting that they contain NSCs. Next, we focused on bone morphogenetic proteins 4 (BMP4), since BMP4 are strongly expressed by the developing hippocampus compared to the neocortex where few Gfap-expressing cells exist. BMP4 promoted Gfap-expressing NSCs from neocortical cells. Conversely, Gfap-expressing cells in the developing hippocampus were reduced by suppression of BMP signaling. Furthermore, production of Prox1⁺ granular cells in the dentate gyrus were also reduced by suppression of BMP signaling. Taken together, BMP signaling endows the special NSCs that express Gfap and produce granular cells in the developing hippocampus.