Arterial-venous network formation during brain vascularization involves hemodynamic regulation of chemokine signaling

摘要: During angiogenic sprouting, newly forming blood vessels need to connect the existing vasculature in order establish a functional circulatory loop. Previous studies have implicated genetic pathways, such as VEGF and Notch signaling, controlling angiogenesis. We show here that both pathways similarly act during vascularization of zebrafish central nervous system. In addition, we find chemokine signaling specifically controls arterial-venous network formation brain. Zebrafish mutants for receptor cxcr4a or its ligand cxcl12b decreased number connections, leading an unperfused interconnected vessel network. further expression brain capillaries is negatively regulated by flow. Accordingly, continue express cxcr4a, whereas connection these arterial circulation leads rapid downregulation loss characteristics endothelial cells, filopodia formation. Together, our findings indicate hemodynamics, addition influence vascular morphogenesis regulating proangiogenic factor necessary correct pathfinding sprouting capillaries.