Mural cell contractility regulates vessel diameter by controlling cell morphology and vessel coverage

Abstract Mural cells are key regulators of vascular architecture, yet how their contractility and morphology jointly influence vessel diameter in vivo remains poorly understood. Here, using high-resolution live imaging and single-cell morphometric analysis in zebrafish, we show that vascular smooth muscle cells (vSMCs) and pericytes undergo a developmental reduction in cell size through the progressive retraction of actin-rich primary and secondary processes during vascular remodelling. By specifically manipulating RhoA activity to alter mural cell contractility and shape, we uncover vessel-specific roles for mural cells in diameter regulation. We find that vSMC contractility is dispensable for the initial constriction of the dorsal aorta but is required to stabilise its diameter following vasoconstriction and to maintain vascular tone. In contrast, pericyte contractility is dispensable for both the constriction and stabilisation of intersegmental vessels. In the brain vasculature, vessel diameter is governed by the balance between contractile force and the extent of vessel coverage by vSMCs. Together, our findings redefine the role of mural cell contractility in the control of vessel constraint, demonstrating that morphology and vessel coverage, rather than contractility alone, are key determinants of vascular diameter in vivo.