Stratman Amber N, Pezoa Sofia A, Farrelly Olivia M, Castranova Daniel, Dye Louis E, Butler Matthew G, Sidik Harwin, Talbot William S, Weinstein Brant M
Program in Genomics of Differentiation, National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD 20892, USA.
Microscopy & Imaging Core, National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD 20892, USA.
Development. 2017 Jan 1;144(1):115-127. doi: 10.1242/dev.143131. Epub 2016 Dec 2.
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.
壁细胞(血管平滑肌细胞和周细胞)在脉管系统发育中起重要作用,通过与内皮细胞相互作用促进血管静止和长期血管稳定。然而,壁细胞如何稳定血管的机制细节尚未完全了解。我们利用斑马鱼研究了早期发育过程中包绕背主动脉的壁细胞的出现及其功能作用。与先前文献一致,我们的数据表明,包绕背主动脉的细胞源自相邻体节中的一个细胞亚群。通过破坏血小板衍生生长因子受体(pdgfr)信号传导来抑制壁细胞向背主动脉募集,会导致血管基底膜减少,进而导致背主动脉血管弹性增强以及无法限制主动脉直径。我们的结果提供了直接的体内证据,证明壁细胞通过产生和维持血管基底膜以防止主动脉异常扩张和弹性异常,从而在早期脉管系统的模式形成和稳定中发挥功能性作用。