FOR 2325 - TP06: Notch and the intercellular crosstalk in the neurovascular unit

Basic data for this project

Description

he vasculature of the brain has an important barrier function that prevents the transmigration of immune cells and controls the entry of potentially harmful substances from the circulation. This blood-brain-barrier requires a highly specialized structure, the neurovascular unit, which is composed of tightly associated endothelial cells, supporting pericytes and astrocytic end-feet. While critical roles of the neurovascular unit in the healthy and diseased organism are well appreciated, the interactions between its cellular components and the underlying molecular regulation remain poorly understood. Our preliminary data indicate that Notch signaling suppresses a harmful, hypercontractile phenotype in pericytes and is thereby indispensable for the formation of an intact blood-brain-barrier.Here, we propose to characterize the role of the Notch signaling pathway in pericytes of the central nervous system with cell type-specific and inducible genetic approaches in the mouse, which will be combined with high-resolution imaging and cell biology and biochemistry experiments. In addition, to gain insight into the molecular pathways mediating mural cell maturation in the brain vasculature, we will employ powerful genetically encoded RiboTag profiling in developing and adult mice. The sum of this work will provide important insights into the role of Notch and other signaling pathways in the regulation of neurovascular interactions and blood-brain-barrier function.