Piezo1-dependent regulation of pericyte proliferation by blood flow during brain vascular development

Abstract

Blood flow is known to regulate cerebrovascular development through acting on vascular endothelial cells (ECs). As an indispensable component of the neurovascular unit, brain pericytes physically couple with ECs and play vital roles in blood-brain barrier integrity maintenance and neurovascular coupling. However, it remains unclear whether blood flow affects brain pericyte development. Using in vivo time-lapse imaging of larval zebrafish, we monitored the developmental dynamics of brain pericytes and found that they proliferate to expand their population and increase their coverage to brain vessels. In combination with pharmacological and genetic approaches, we demonstrated that blood flow enhances brain pericyte proliferation through Piezo1 expressed in ECs. Moreover, we identified that EC-intrinsic Notch signaling is downstream of Piezo1 to promote the activation of Notch signaling in pericytes. Thus, our findings reveal a role of blood flow in pericyte proliferation, extending the functional spectrum of hemodynamics on cerebrovascular development.

Keywords: CP: Developmental biology; Notch signaling; Piezo1; blood flow; cerebral vasculature; pericyte; zebrafish.