1) Macrophage control of CNS development We have demonstrated a comprehensive atlas of the YS-derived CNS macrophages including parenchymal microglia as well as non-parenchymal meningeal and perivascular macrophages, in the developing CNS tissues, with their spatial, cellular, and molecular characteristics. We are also investigating an unexpected role for CNS meningeal macrophages in regulating radial glial cells, the primary source of cortical neurons in early brain development (Liu et al. Under Review). We are currently attempting to characterize what controls the unique distribution, differentiation, and inflammatory state of these CNS macrophages. 2) CNS blood and lymphatic vessel development CNS endothelial cell-pericyte interaction is essential for the BBB formation and maintenance. Our recent studies have revealed that an ECM protein, perlecan, influences the endothelial cell-pericyte interaction to maintain BBB integrity (Nakamura et al. J Cell Biol. Accepted). We have also pursued studies in lymphatic vessels, which function to return excess tissue fluid into blood circulation and to provide a route for immune cell trafficking, stemming from the idea about what controls the CNS immune privileged microenvironment. Indeed, our extensive immunohistochemical studies have clearly demonstrated that no lymphatic vasculature is found in the brain and spinal cord parenchyma, while lymphatic vessels form in the dura mater, the outermost of the three meningeal membranes that envelop the CNS (Izen et al. 2018 Dev Dyn). We are currently attempting to study inhibitory mechanisms underlying the lack of lymphatic vasculature in the CNS immune-privileged microenvironment.
