YAP and TAZ regulate adherens junction dynamics and endothelial cell distribution during vascular development
YAP and TAZ regulate adherens junction dynamics and endothelial cell distribution during vascular development
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DOI：
10.7554/elife.31037
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发表时间：
2018-02-05
期刊：
影响因子：
7.7
通讯作者：
Gerhardt, Holger
中科院分区：
文献类型：
--
作者：
Neto, Filipa;Klaus-Bergmann, Alexandra;Gerhardt, Holger
血管新生形成的血管网络对组织生长、体内平衡和再生至关重要。内皮细胞如何以足够的数量出现并适当地排列以形成功能性血管网络尚不清楚。本研究表明，YAP/TAZ促进拉伸诱导的内皮细胞增殖和重排，同时防止血管出血。在机制上，YAP/TAZ增加VE-Cadherin的周转和连接相关中间板足的形成，促进细胞迁移和屏障功能维持。这部分是通过降低BMP信号来实现的。因此，小鼠中YAP/TAZ的缺失导致发芽发育迟缓，局部聚集，内皮细胞稀缺，分支不规则和连接缺陷。TAZ的强迫核活动反而导致了过度发芽和血管增生。我们提出了一种新的模型，其中YAP/TAZ将机械信号与BMP信号相结合，以维持连接的顺应性和完整性，同时平衡血管生成血管中的内皮细胞重排。
Formation of blood vessel networks by sprouting angiogenesis is critical for tissue growth, homeostasis and regeneration. How endothelial cells arise in adequate numbers and arrange suitably to shape functional vascular networks is poorly understood. Here we show that YAP/TAZ promote stretch-induced proliferation and rearrangements of endothelial cells whilst preventing bleeding in developing vessels. Mechanistically, YAP/TAZ increase the turnover of VE-Cadherin and the formation of junction associated intermediate lamellipodia, promoting both cell migration and barrier function maintenance. This is achieved in part by lowering BMP signalling. Consequently, the loss of YAP/TAZ in the mouse leads to stunted sprouting with local aggregation as well as scarcity of endothelial cells, branching irregularities and junction defects. Forced nuclear activity of TAZ instead drives hypersprouting and vascular hyperplasia. We propose a new model in which YAP/TAZ integrate mechanical signals with BMP signaling to maintain junctional compliance and integrity whilst balancing endothelial cell rearrangements in angiogenic vessels.