AUTHOR=Cheong Sek-Shir , Akram Khondoker M. , Matellan Carlos , Kim Sally Yunsun , Gaboriau David C. A. , Hind Matthew , del Río Hernández Armando E. , Griffiths Mark , Dean Charlotte H.
TITLE=The Planar Polarity Component VANGL2 Is a Key Regulator of Mechanosignaling
JOURNAL=Frontiers in Cell and Developmental Biology
VOLUME=8
YEAR=2020
URL=https://www.frontiersin.org/journals/cell-and-developmental-biology/articles/10.3389/fcell.2020.577201
DOI=10.3389/fcell.2020.577201
ISSN=2296-634X
ABSTRACT=
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.