Society for Neuroscience, Journal of Neuroscience, 50(34), p. 16713-16719, 2014
DOI: 10.1523/jneurosci.4590-13.2014
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HIF-1α is a hypoxia-inducible protein that regulates many cell and molecular processes, including those involved in angiogenesis and stem cell maintenance. Prior studies demonstrated constitutive HIF-1α stabilization in neural stem cells (NSCs) of the adult mouse SVZ, but its role there has not been elucidated. Here, we tested the hypothesis that HIF-1α plays an essential role in the maintenance of adult NSCs and stabilization of the SVZ vascular niche using conditional, tamoxifen-inducibleHif1aknock-out mice. We generated nestin-CreERT2/R26R-YFP/Hif1afl/fltriple transgenic mice, to enable tamoxifen-inducibleHif1agene inactivation in nestin-expressing NSCs within the adult SVZ.Hif1agene deletion resulted in a significant loss of YFP+NSCs within the SVZ by 45 d post recombination, which was preceded by significant regression of the SVZ vasculature at 14 d, and concomitant decrease of VEGF expression by NSCs. Loss of YFP+NSCs followingHif1agene inactivationin vivowas likely an indirect consequence of vascular regression, since YFP+neurosphere formation over serial passage was unaffected. These results identify NSC-encoded HIF-1α as an essential factor in the maintenance of the adult SVZ, and demonstrate that NSCs within the SVZ maintain the integrity of their vascular niche through HIF-1α-mediated signaling mechanisms.