This project is to determine the molecular basis of how the neuro-vascular interactions lead to their functional interdependence in tissue homeostasis. Given the importance of the vascular niche to support a variety of stem cells, we discovered vascular paracrine signals for neural stem cell (NSC) maintenance. Our genetic ablation of endothelial capillaries in the neurogenic subventricular zone (SVZ) of adult brain demonstrated the importance of the vascular niche in NSC maintenance. We utilize a systematic multi-faceted approach to identify and validate the vascular niche signals involved in maintenance, self-renewal, proliferation and differentiation of neural stem cells (Lee et al. 2012). We are now evaluating the physiological relevance of the candidate niche signals in vitro and in vivo. Understanding the mechanisms by which vascular niche signals maintain NSCs is an essential prerequisite for the manipulation of NSCs for transplantation therapy of neurological diseases.

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National Heart, Lung, and Blood Institute
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Arnold, Thomas D; Niaudet, Colin; Pang, Mei-Fong et al. (2014) Excessive vascular sprouting underlies cerebral hemorrhage in mice lacking αVβ8-TGFβ signaling in the brain. Development 141:4489-99
Okabe, Keisuke; Kobayashi, Sakiko; Yamada, Toru et al. (2014) Neurons limit angiogenesis by titrating VEGF in retina. Cell 159:584-96
Kim, Kee K; Nam, Joseph; Mukouyama, Yoh-Suke et al. (2013) Rbfox3-regulated alternative splicing of Numb promotes neuronal differentiation during development. J Cell Biol 200:443-58
Lee, Cheol; Hu, Jingqiong; Ralls, Sherry et al. (2012) The molecular profiles of neural stem cell niche in the adult subventricular zone. PLoS One 7:e50501