Cilia Control Vascular Mural Cell Recruitment in Vertebrates.
Cilia Control Vascular Mural Cell Recruitment in Vertebrates.
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DOI：
10.1016/j.celrep.2016.12.044
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发表时间：
2017-01-24
期刊：
影响因子：
8.8
通讯作者：
Santoro MM
中科院分区：
文献类型：
--
作者：
Chen X;Gays D;Milia C;Santoro MM
血管壁细胞（vMC）是脊椎动物血管系统的重要组成部分，控制着血管的成熟和稳态。离散的分子机制与vMC的发育和分化有关。血流动力学在控制vMC募集中的作用尚不清楚。使用标记斑马鱼胚胎中发育中的vMCs的转基因系，我们发现vMCs由动脉血管募集，并且该过程是流量依赖性的。我们利用组织特异性CRISPR基因靶向来证明血流动力学依赖性Notch激活和随后的动脉遗传程序是由内皮初级纤毛驱动的。我们还确定斑马鱼foxc1b作为纤毛依赖性Notch特异性靶标，其在内皮细胞内需要驱动vMC募集。总之，我们已经确定了一个血流动力学依赖性机制，在发展中的血管系统，控制vMC的招聘。血流量和纤毛是斑马鱼血管壁细胞（vMC）覆盖所必需的。纤毛依赖性Notch信号驱动动脉血管的vMC募集。发现初级纤毛负责斑马鱼胚胎动脉血管中血流驱动的Notch激活。该途径导致foxc1b的特异性表达，然后驱动vMC募集并支持斑马鱼的血管肌发生。
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. Blood flow and cilia are required for vascular mural cell (vMC) coverage in zebrafish Cilia-dependent Notch signaling drives vMC recruitment of arterial-fated vessels Foxc1b is necessary and sufficient to drive vascular myogenesis in zebrafish 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.