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Item Type: | Article |
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Title: | YAP and TAZ regulate adherens junction dynamics and endothelial cell distribution during vascular development |
Creators Name: | Neto, F., Klaus-Bergmann, A., Ong, Y.T., Alt, S., Vion, A.C., Szymborska, A., Carvalho, J.R., Hollfinger, I., Bartels-Klein, E., Franco, C.A., Potente, M. and Gerhardt, H. |
Abstract: | 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 cell migration whilst maintaining barrier function. 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. |
Source: | eLife |
ISSN: | 2050-084X |
Publisher: | eLife Sciences Publications |
Volume: | 7 |
Page Range: | e31037 |
Date: | 5 February 2018 |
Official Publication: | https://doi.org/10.7554/eLife.31037 |
PubMed: | View item in PubMed |
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