Cilia Control Vascular Mural Cell Recruitment in Vertebrates

Publication date: 24 January 2017
Source:Cell Reports, Volume 18, Issue 4
Author(s): Xiaowen Chen, Dafne Gays, Carlo Milia, Massimo M. Santoro
Vascular mural cells (vMCs) are essential components of the vertebrate vascular system, controlling blood vessel maturation and homeostasis. Discrete molecular mechanisms have been associated with vMC development and differentiation. The function of hemodynamic forces in controlling vMC recruitment is unclear. Using transgenic lines marking developing vMCs in zebrafish embryos, we find that vMCs are recruited by arterial-fated vessels and that the process is flow dependent. We take advantage of tissue-specific CRISPR gene targeting to demonstrate that hemodynamic-dependent Notch activation and the ensuing arterial genetic program is driven by endothelial primary cilia. We also identify zebrafish foxc1b as a cilia-dependent Notch-specific target that is required within endothelial cells to drive vMC recruitment. In summary, we have identified a hemodynamic-dependent mechanism in the developing vasculature that controls vMC recruitment.

Graphical abstract

Teaser

Chen et al. find that primary cilia are responsible for blood-flow-driven Notch activation in arterial vessels of zebrafish embryos. This pathway leads to specific expression of foxc1b, which then drives vMC recruitment and supports vascular myogenesis in zebrafish.


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