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 PLoS One). Further extensive gene expression profiling in the SVZ vasculature and in-depth functional experiments have revealed that soluble amyloid beta precursor protein (APP) secreted from SVZ endothelial cells function as a vascular niche signal that negatively regulate NSC growth to control the number of SVZ NSCs (Sato et al. 2017 Development). In a similar line of research, we are currently examining whether APP influences the growth of glioblastoma. We have also pursued studies in the molecular and cellular mechanisms underlying blood vessel and lymphatic vessel development in the central nervous system (CNS). We are interested in what signals control the CNS-specific vascular architecture and immune privileged microenvironment (Izen et al. Submitted).
