PMID- 33195213 OWN - NLM STAT- PubMed-not-MEDLINE LR - 20240330 IS - 2296-634X (Print) IS - 2296-634X (Electronic) IS - 2296-634X (Linking) VI - 8 DP - 2020 TI - The Planar Polarity Component VANGL2 Is a Key Regulator of Mechanosignaling. PG - 577201 LID - 10.3389/fcell.2020.577201 [doi] LID - 577201 AB - 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. CI - Copyright (c) 2020 Cheong, Akram, Matellan, Kim, Gaboriau, Hind, del Rio Hernandez, Griffiths and Dean. FAU - Cheong, Sek-Shir AU - Cheong SS AD - National Heart and Lung Institute, Imperial College London, London, United Kingdom. FAU - Akram, Khondoker M AU - Akram KM AD - National Heart and Lung Institute, Imperial College London, London, United Kingdom. FAU - Matellan, Carlos AU - Matellan C AD - Cellular and Molecular Biomechanics Laboratory, Department of Bioengineering, Imperial College London, London, United Kingdom. FAU - Kim, Sally Yunsun AU - Kim SY AD - National Heart and Lung Institute, Imperial College London, London, United Kingdom. FAU - Gaboriau, David C A AU - Gaboriau DCA AD - Facility for Imaging by Light Microscopy, National Heart and Lung Institute, Faculty of Medicine, Imperial College London, London, United Kingdom. FAU - Hind, Matthew AU - Hind M AD - National Heart and Lung Institute, Imperial College London, London, United Kingdom. AD - National Institute for Health Research, Respiratory Biomedical Research Unit, Royal Brompton & Harefield NHS Foundation Trust, London, United Kingdom. FAU - Del Rio Hernandez, Armando E AU - Del Rio Hernandez AE AD - Cellular and Molecular Biomechanics Laboratory, Department of Bioengineering, Imperial College London, London, United Kingdom. FAU - Griffiths, Mark AU - Griffiths M AD - National Heart and Lung Institute, Imperial College London, London, United Kingdom. AD - Peri-Operative Medicine Department, St Bartholomew's Hospital, London, United Kingdom. FAU - Dean, Charlotte H AU - Dean CH AD - National Heart and Lung Institute, Imperial College London, London, United Kingdom. AD - MRC Harwell Institute, Harwell Campus, Oxfordshire, United Kingdom. LA - eng GR - WT_/Wellcome Trust/United Kingdom PT - Journal Article DEP - 20201029 PL - Switzerland TA - Front Cell Dev Biol JT - Frontiers in cell and developmental biology JID - 101630250 PMC - PMC7658195 OTO - NOTNLM OT - RhoA OT - VANGL2 OT - YAP signaling OT - cell migration OT - focal adhesion OT - mechanosignaling OT - planar cell polarity OT - traction force EDAT- 2020/11/17 06:00 MHDA- 2020/11/17 06:01 PMCR- 2020/01/01 CRDT- 2020/11/16 08:54 PHST- 2020/06/28 00:00 [received] PHST- 2020/10/08 00:00 [accepted] PHST- 2020/11/16 08:54 [entrez] PHST- 2020/11/17 06:00 [pubmed] PHST- 2020/11/17 06:01 [medline] PHST- 2020/01/01 00:00 [pmc-release] AID - 10.3389/fcell.2020.577201 [doi] PST - epublish SO - Front Cell Dev Biol. 2020 Oct 29;8:577201. doi: 10.3389/fcell.2020.577201. eCollection 2020.