E-cadherin and LGN align epithelial cell divisions with tissue tension independently of cell shape

• Published in: Proceedings of the National Academy of Sciences - PNAS 2017-07, Vol.114 (29), p.E5845-E5853
• Main Authors: Hart, Kevin C., Tan, Jiongyi, Siemers, Kathleen A., Sim, Joo Yong, Pruitt, Beth L., Nelson, W. James, Gloerich, Martijn
• Format: Article
• Language: English
• Subjects: Biological Sciences; Cell adhesion & migration; Cell division; Cell size; E-cadherin; Epithelial cells; Low level; Machinery and equipment; Mechanical stimuli; Mechanotransduction; Monolayers; Morphogenesis; Orientation; PNAS Plus; Recruitment; Tension; Tissues
• ISSN: 0027-8424; 1091-6490
• DOI: 10.1073/pnas.1701703114

Tissue morphogenesis requires the coordinated regulation of cellular behavior, which includes the orientation of cell division that defines the position of daughter cells in the tissue. Cell division orientation is instructed by biochemical and mechanical signals from the local tissue environment, but how those signals control mitotic spindle orientation is not fully understood. Here, we tested how mechanical tension across an epithelial monolayer is sensed to orient cell divisions. Tension across Madin–Darby canine kidney cell monolayers was increased by a low level of uniaxial stretch, which oriented cell divisions with the stretch axis irrespective of the orientation of the cell long axis. We demonstrate that stretch-induced division orientation required mechanotransduction through E-cadherin cell–cell adhesions. Increased tension on the E-cadherin complex promoted the junctional recruitment of the protein LGN, a core component of the spindle orientation machinery that binds the cytosolic tail of E-cadherin. Consequently, uniaxial stretch triggered a polarized cortical distribution of LGN. Selective disruption of trans engagement of E-cadherin in an otherwise cohesive cell monolayer, or loss of LGN expression, resulted in randomly oriented cell divisions in the presence of uniaxial stretch. Our findings indicate that E-cadherin plays a key role in sensing polarized tensile forces across the tissue and transducing this information to the spindle orientation machinery to align cell divisions.