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Recent studies have also implicated O<jats:sub>2<\/jats:sub> and its signal transduction pathways in controlling cell proliferation, fate, and morphogenesis during the development of many tissues, including the nervous system. O<jats:sub>2<\/jats:sub> tensions in the intact brain are much lower than in room air, and there is evidence that dynamic control of O<jats:sub>2<\/jats:sub> availability may be a component of the in vivo neural stem cell (NSC) niche. At lower O<jats:sub>2<\/jats:sub> tensions, hypoxia\u2010inducible factor 1\u03b1 (HIF1\u03b1) facilitates signal transduction pathways that promote self\u2010renewal (e.g., Notch) and inhibits pathways that promote NSC differentiation or apoptosis (e.g., bone morphogenetic proteins). Increasing O<jats:sub>2<\/jats:sub> tension degrades HIF1\u03b1, thus promoting differentiation or apoptosis of NSCs and progenitors. These dynamic changes in O<jats:sub>2<\/jats:sub> tension can be mimicked to optimize ex vivo production methods for cell replacement therapies. Conversely, disrupted O<jats:sub>2<\/jats:sub> availability may play a critical role in disease states such as stroke or brain tumor progression. Hypoxia during stroke activates precursor proliferation in vivo, while glioblastoma stem cells proliferate maximally in a more hypoxic environment than normal stem cells, which may make them resistant to certain anti\u2010neoplastic therapies. These findings suggest that O<jats:sub>2<\/jats:sub> response is central to the normal architecture and dynamics of NSC regulation and in the etiology and treatment of brain diseases. J. Cell. Physiol. 220: 562\u2013568, 2009. \u00a9 2009 Wiley\u2010Liss, Inc.<\/jats:p>","DOI":"10.1002\/jcp.21812","type":"journal-article","created":{"date-parts":[[2009,5,13]],"date-time":"2009-05-13T16:16:57Z","timestamp":1242231417000},"page":"562-568","source":"Crossref","is-referenced-by-count":220,"title":["The role of oxygen in regulating neural stem cells in development and disease"],"prefix":"10.1002","volume":"220","author":[{"given":"David M.","family":"Panchision","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2009,5,13]]},"reference":[{"key":"e_1_2_9_2_1","first-page":"77","article-title":"Effects of oxygen tension in the gas atmosphere during in vitro maturation, in vitro fertilization and in vitro culture on the efficiency of in vitro production of mouse embryos","volume":"52","author":"Adam AA","year":"2004","journal-title":"Jpn J Vet 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