1) APP as a vascular niche signal to control NSC growth in the SVZ 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. Through 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), we found soluble amyloid beta precursor protein (APP) secreted from SVZ endothelial cells function as a vascular niche signal that negatively regulates 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. 2) CNS lymphatic vessel development We have pursued studies in the molecular and cellular mechanisms underlying blood vessel and lymphatic vessel development in the developing brain. We have developed a novel whole-mount staining of the skull to visualize the dural lymphatic vasculature in embryonic and postnatal stages (Izen et al. 2018 Dev Dyn). The dural lymphatic vessels originate along the side of the skull after birth and extend alongside the dural blood vessels towards the Superior Saggital Sinus. Between postnatal days 13 - 20, lymphatic vessels in the Transverse Sinuses enter the Superior Saggital Sinus and extend along the sinus to the olfactory bulb. Compared to lymphatic vessel development in other tissues, i.e. skin where lymphatic vasculature develops from embryonic day 13.5 onward, this dramatic developmental delay suggests a tissue-specific source of the dural lymphatic endothelial cells and a unique mechanism that controls the dural lymphatic vessel development.
