Cofilin promotes actin turnover and flexibility to drive coordinated cell movements in vivo

Embryos display a striking ability to repair wounds rapidly, with no inflammation or scarring. Embryonic wound healing is driven by the collective movement of the cells adjacent to the wound. The cells at the wound edge polarize actin and the molecular motor non-muscle myosin II, forming a supracellular cable around the wound that generates force and coordinates cell movements to close the lesion. Actin network contraction has been associated with the disassembly of the actin filaments that form the network. We found that the actin-severing protein cofilin and its co-factor Aip1 accumulated at the edge of epidermal wounds in Drosophila embryos. Reducing cofilin activity slowed down wound closure by 26%, indicating that cofilin is necessary for rapid wound healing. Using quantitative microscopy, we showed that cofilin controls F-actin turnover at the wound edge, but not F-actin polarity or contractile force generation. Combining genetic and pharmacological manipulations, we found that F-actin turnover at the wound edge must be tightly regulated for wounds to close rapidly. Computational modelling suggested that cofilin may contribute to rapid wound repair by maintaining a flexible actin network at the wound edge. Consistent with this model, fluorescence fluctuation analysis revealed that F-actin networks at the wound edge were significantly more rigid when we reduced cofilin activity. Together, our results indicate that cofilin promotes F-actin turnover at the wound edge to maintain a flexible actin network and facilitate rapid contraction and wound healing.