Tension Regulates Actomyosin Dynamics during Drosophila Embryonic Wound Repair
Kobb, Anna 1, 2 ; Fernandez-Gonzalez, Rodrigo 1, 2, 3, 4
1. Institute of Biomaterials and Biomedical Engineering, University of Toronto; 2. Ted Rogers Centre for Heart Research, University of Toronto; 3. Department of Cell and Systems Biology, University of Toronto; 4. Developmental and Stem Cell Biology Program, The Hospital for Sick Children
Coordinated cell behaviours are critical for embryonic development and tissue repair. Cell behaviours are often coordinated through the assembly of supracellular cytoskeletal networks formed by actin and the motor protein non-muscle myosin II. Embryonic wound repair is driven by the collective migration of the cells around the wound. During embryonic wound repair, actin and myosin are polarized in the cells adjacent to the wound, accumulating at the interface with the wounded cells where they form a contractile, supracellular cable that acts as a purse string to coordinate cell movements and drive rapid wound closure. Using fluorescence recovery after photobleaching (FRAP), we found that myosin turns over as the purse string contracts in wounded Drosophila embryos. Myosin turnover at the purse string was significantly slower than in non-contractile cytoskeletal networks. Mathematical modelling revealed that the rates of myosin assembly and disassembly were both reduced by tension at the wound edge. Using laser ablation, we showed that tension at the purse string increased as wound closure progressed, and the increase in tension was associated with slower myosin turnover. Reducing tension by laser-severing the purse string resulted in destabilization and loss of myosin from the wound edge. Genetic and pharmacological manipulations demonstrated that myosin motor activity is necessary for tension-based myosin stabilization around wounds. Together, our results demonstrate that mechanical forces regulate myosin dynamics during the collective cell movements that drive embryonic wound repair. We are currently investigating whether tension affects myosin directly or indirectly through effects on actin or regulators thereof.