血流-Klf6a-Tagln2 轴通过调节内皮细胞重排和肌动蛋白细胞骨架动力学来驱动斑马鱼血管修剪。
The blood flow-klf6a-tagln2 axis drives vessel pruning in zebrafish by regulating endothelial cell rearrangement and actin cytoskeleton dynamics.
机构信息
Key Laboratory for Biorheological Science and Technology of Ministry of Education, Bioengineering College of Chongqing University, Chongqing, China.
State and Local Joint Engineering Laboratory for Vascular Implants, Bioengineering College of Chongqing University, Chongqing, China.
出版信息
PLoS Genet. 2021 Jul 28;17(7):e1009690. doi: 10.1371/journal.pgen.1009690. eCollection 2021 Jul.
Recent studies have focused on capillary pruning in various organs and species. However, the way in which large-diameter vessels are pruned remains unclear. Here we show that pruning of the zebrafish caudal vein (CV) from ventral capillaries of the CV plexus in different transgenic embryos is driven by endothelial cell (EC) rearrangement, which involves EC nucleus migration, junction remodeling, and actin cytoskeleton remodeling. Further observation reveals a growing difference in blood flow velocity between the two vessels in CV pruning in zebrafish embryos. With this model, we identify the critical role of Kruppel-like factor 6a (klf6a) in CV pruning. Disruption of klf6a functioning impairs CV pruning in zebrafish. klf6a is required for EC nucleus migration, junction remodeling, and actin cytoskeleton dynamics in zebrafish embryos. Moreover, actin-related protein transgelin 2 (tagln2) is a direct downstream target of klf6a in CV pruning in zebrafish embryos. Together these results demonstrate that the klf6a-tagln2 axis regulates CV pruning by promoting EC rearrangement.
最近的研究集中在各种器官和物种中的毛细血管修剪上。然而，大直径血管被修剪的方式尚不清楚。在这里，我们展示了斑马鱼尾静脉（CV）从 CV 丛的腹侧毛细血管的修剪是由内皮细胞（EC）重排驱动的，这涉及 EC 核迁移、连接重塑和肌动蛋白细胞骨架重塑。进一步的观察揭示了在斑马鱼胚胎 CV 修剪过程中，两条血管之间血流速度的差异不断增大。通过这个模型，我们确定了 Krüppel 样因子 6a（klf6a）在 CV 修剪中的关键作用。klf6a 功能的破坏会损害斑马鱼的 CV 修剪。klf6a 对于 EC 核迁移、连接重塑和斑马鱼胚胎中的肌动蛋白细胞骨架动力学是必需的。此外，肌动蛋白相关蛋白转胶蛋白 2（tagln2）是 klf6a 在斑马鱼胚胎 CV 修剪中的直接下游靶标。这些结果共同表明，klf6a-tagln2 轴通过促进 EC 重排来调节 CV 修剪。
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