| First Author | Cheong SS | Year | 2020 |
| Journal | Front Cell Dev Biol | Volume | 8 |
| Pages | 577201 | PubMed ID | 33195213 |
| Mgi Jnum | J:308788 | Mgi Id | MGI:6741784 |
| Doi | 10.3389/fcell.2020.577201 | Citation | Cheong SS, et al. (2020) The Planar Polarity Component VANGL2 Is a Key Regulator of Mechanosignaling. Front Cell Dev Biol 8:577201 |
| abstractText | VANGL2 is a component of the planar cell polarity (PCP) pathway, which regulates tissue polarity and patterning. The Vangl2 (Lp) 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 Vangl2 (Lp/+) mice to determine that alveologenesis is attenuated as a result of impaired epithelial cell migration. Vangl2 (Lp/+) 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 Vangl2 (Lp/+) TECs. YAP signaling in Vangl2 (Lp) airway epithelium was reduced, consistent with a role for VANGL2 in mechanotransduction. Furthermore, activation of RhoA signaling restored actomyosin organization in Vangl2 (Lp/+) , 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. |
