Notch controls retinal blood vessel maturation and quiescence
Notch controls retinal blood vessel maturation and quiescence
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DOI：
10.1242/dev.093351
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发表时间：
2013-07-15
期刊：
影响因子：
4.6
通讯作者：
Adams, Ralf H.
中科院分区：
文献类型：
--
作者：
Ehling, Manuel;Adams, Susanne;Adams, Ralf H.
血管形成动脉、毛细血管和静脉的分层组织网络，其通过一系列生长、修剪和成熟过程发育。与对控制血管生长，特别是内皮发芽和增殖的过程的快速增加的了解相反，未成熟血管转化为功能齐全的静止血管系统仍然知之甚少。在这里，我们使用可诱导的细胞类型特异性遗传方法来证明内皮Notch信号传导对于静脉和静脉周围毛细血管丛的重塑至关重要，这发生在青春期小鼠视网膜中初始血管生成生长阶段完成后。突变血管表现出异位增殖和发芽，支持壁细胞的招募缺陷，并未能下调VEGF受体的表达。令人惊讶的是，相比之下，Notch在重塑出生后动脉的内皮中被抑制。两者合计，我们的研究结果确定了关键的过程，有助于血管重塑，成熟和收购的静止表型在最后阶段的发展血管生成。
Blood vessels form a hierarchically organized network of arteries, capillaries and veins, which develops through a series of growth, pruning and maturation processes. In contrast to the rapidly increasing insight into the processes controlling vascular growth and, in particular, endothelial sprouting and proliferation, the conversion of immature vessels into a fully functional, quiescent vasculature remains little understood. Here we used inducible, cell type-specific genetic approaches to show that endothelial Notch signaling is crucial for the remodeling of veins and the perivenous capillary plexus, which occurs after the completion of the initial angiogenic growth phase in the retina of adolescent mice. Mutant vessels showed ectopic proliferation and sprouting, defective recruitment of supporting mural cells, and failed to downregulate the expression of VEGF receptors. Surprisingly, by contrast Notch was dispensable in the endothelium of remodeling postnatal arteries. Taken together, our results identify key processes contributing to vessel remodeling, maturation and the acquisition of a quiescent phenotype in the final stage of developmental angiogenesis.