Journal
STEM CELL RESEARCH
Volume 12, Issue 2, Pages 492-505Publisher
ELSEVIER SCIENCE BV
DOI: 10.1016/j.scr.2013.12.009
Keywords
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Funding
- MEXT
- Ministry of Education, Culture, Sports Science, and Technology of Japan [17082008, 2230023]
- Intramural Program of the NIDCR, National Institutes of Health
- program Investissements d'avenir [ANR-10-IAIHU-06]
- Grants-in-Aid for Scientific Research [17082008, 25670426] Funding Source: KAKEN
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In the adult subventricular zone (neurogenic niche), neural stem cells double-positive for two markers of subsets of neural stem cells in the adult central nervous system, glial fibrillary acidic protein and CD133, lie in proximity to fractones and to blood vessel basement membranes, which contain the heparan sulfate proteoglycan perlecan. Here, we demonstrate that perlecan deficiency reduces the number of both GFAP/CD133-positive neural stem cells in the subventricular zone and new neurons integrating into the olfactory bulb. We also show that FGF-2 treatment induces the expression of cyclin D2 through the activation of the Akt and Erk1/2 pathways and promotes neurosphere formation in vitro. However, in the absence of perlecan, FGF-2 fails to promote neurosphere formation. These results suggest that perlecan is a component of the neurogenic niche that regulates FGF-2 signaling and acts by promoting neural stem cell self-renewal and neurogenesis. (C) 2013 The Authors. Published by Elsevier B. V. All rights reserved.
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