YAP and TAZ regulate adherens junction dynamics and endothelial cell distribution during vascular development

Elife. 2018 Feb 5;7:e31037. doi: 10.7554/eLife.31037.

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 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.

Keywords: BMP; TAZ; VE-Cadherin; YAP; cell biology; developmental biology; mouse; stem cells; vascular development.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adaptor Proteins, Signal Transducing / metabolism*
  • Adherens Junctions / metabolism*
  • Animals
  • Bone Morphogenetic Protein Receptors / metabolism
  • Cadherins / metabolism
  • Cell Cycle Proteins
  • Cell Movement
  • Cell Proliferation*
  • Endothelial Cells / physiology*
  • Mice
  • Neovascularization, Physiologic*
  • Phosphoproteins / metabolism*
  • Signal Transduction*
  • Transcription Factors / metabolism*

Substances

  • Adaptor Proteins, Signal Transducing
  • Cadherins
  • Cell Cycle Proteins
  • Phosphoproteins
  • Transcription Factors
  • Wwtr1 protein, mouse
  • Yap protein, mouse
  • Bone Morphogenetic Protein Receptors