Frontiers in Cell and Developmental Biology (Oct 2020)

The Planar Polarity Component VANGL2 Is a Key Regulator of Mechanosignaling

  • Sek-Shir Cheong,
  • Khondoker M. Akram,
  • Carlos Matellan,
  • Sally Yunsun Kim,
  • David C. A. Gaboriau,
  • Matthew Hind,
  • Matthew Hind,
  • Armando E. del Río Hernández,
  • Mark Griffiths,
  • Mark Griffiths,
  • Charlotte H. Dean,
  • Charlotte H. Dean

DOI
https://doi.org/10.3389/fcell.2020.577201
Journal volume & issue
Vol. 8

Abstract

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VANGL2 is a component of the planar cell polarity (PCP) pathway, which regulates tissue polarity and patterning. The Vangl2Lp mutation causes lung branching defects due to dysfunctional actomyosin-driven morphogenesis. Since the actomyosin network regulates cell mechanics, we speculated that mechanosignaling could be impaired when VANGL2 is disrupted. Here, we used live-imaging of precision-cut lung slices (PCLS) from Vangl2Lp/+ mice to determine that alveologenesis is attenuated as a result of impaired epithelial cell migration. Vangl2Lp/+ tracheal epithelial cells (TECs) and alveolar epithelial cells (AECs) exhibited highly disrupted actomyosin networks and focal adhesions (FAs). Functional assessment of cellular forces confirmed impaired traction force generation in Vangl2Lp/+ TECs. YAP signaling in Vangl2Lp airway epithelium was reduced, consistent with a role for VANGL2 in mechanotransduction. Furthermore, activation of RhoA signaling restored actomyosin organization in Vangl2Lp/+, confirming RhoA as an effector of VANGL2. This study identifies a pivotal role for VANGL2 in mechanosignaling, which underlies the key role of the PCP pathway in tissue morphogenesis.

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