Mural cells (vascular smooth muscle cells and pericytes) play an essential role in the development of the vasculature, promoting vascular quiescence and long-term vessel stabilization through their interactions with endothelial cells. However, the mechanistic details of how mural cells stabilize vessels are not fully understood. We have examined the emergence and functional role of mural cells investing the dorsal aorta during early development using the zebrafish. Consistent with previous literature, our data suggest that cells ensheathing the dorsal aorta emerge from a sub-population of cells in the adjacent sclerotome. Inhibition of mural cell recruitment to the dorsal aorta through disruption of pdgfr signaling leads to a reduced vascular basement membrane, which in turn results in enhanced dorsal aorta vessel elasticity and failure to restrict aortic diameter. Our results provide direct in vivo evidence for a functional role for mural cells in patterning and stabilization of the early vasculature through production and maintenance of the vascular basement membrane to prevent abnormal aortic expansion and elasticity.
The authors declare no competing or financial interests.
A.N.S., S.A.P., O.M.F., D.C., M.G.B., H.S. and L.E.D. performed experiments; A.N.S., S.A.P., O.M.F., D.C., L.E.D., W.S.T. and B.M.W. analyzed results and made the figures; A.N.S., S.A.P., O.M.F., D.C. and B.M.W. designed the research and wrote the paper.
This work was supported by the intramural program of the Eunice Kennedy Shriver National Institute of Child Health and Human Development (ZIA-HD001011 and ZIA-HD008915 to B.M.W.), the National Institutes of Health (R01NS050223 to W.S.T.), an Agency for Science, Technology and Research (A*STAR) fellowship (to H.S.) and a National Heart, Lung, and Blood Institute/NIH K99 Pathway to Independence Award (to A.N.S.). Deposited in PMC for release after 12 months.
Supplementary information available online at http://dev.biologists.org/lookup/doi/10.1242/dev.143131.supplemental
- Received August 1, 2016.
- Accepted November 17, 2016.