Grant: CIHR-ICRH Travel Awards - General pool

Pericytes are structural support cells that wrap around the endothelial cells that line the capillaries to promote blood flow regulation and maintain vascular stability. Major vascular diseases like stroke, Alzheimer's disease, and vascular dementia are associated with a significant loss of brain pericytes. The aim of this study is to understand how pericytes are formed on newly emerging blood vessels in the brain. To accomplish this, we reduced blood vessel growth using pharmacological inhibitors of endothelial cell signaling (VEGFR and Wnt), which allowed us to understand the connection between sprouting vessels and pericyte behavior. Blocking VEGFR and Wnt reduces the number of sprouting vessels and endothelial cells while disproportionately reducing the number of pericytes on these capillaries. Similarly, we observed the depressed pericyte phenotype when we used GPR124 knockdown, which specifically inhibits brain vessel sprouting. Pericyte coverage of vessels and density was also reduced, leaving the vessels naked when they should be supported. This made us believe that the ratio of endothelial cells to pericytes is not fixed, and that endothelial signals are necessary for recruiting the correct number of pericytes. To further understand how pericytes are recruited on the vessels, we used time-lapse imaging to study pericyte origin, proliferation, and migration. We found the majority of pericytes originated from precursor cells, with the remaining percentage arising through pericyte migration and division. We also characterized how pericytes grow to circumferentially envelop the vessels and the consequences of inhibited vessel growth on pericyte maturation. Our work gives insight into the reciprocal relationships between brain blood vessel development and pericyte recruitment necessary to support cognitive development and function.