| dc.description.abstract | Epithelial wound healing is a vital biological process that involves the coordination of cells across a wounded tissue. Cells must be able to integrate both physical and chemical signals resulting from a wound in order to identify its presence and heal it properly. Calcium signaling has shown to be required for proper epithelial wound healing across a variety of systems, yet the particular mechanisms that give rise to calcium signaling around wounds were not fully understood. Here, laser-induced wounds in Drosophila are used to investigate calcium signals around epithelial wounds. It is found that multiple mechanisms, both physical and chemical, lead to distinct calcium signaling events, and that a complex signaling cascade involving proteolytic activation of growth-blocking peptides is what drives a delayed and distal calcium response. Due to the complexity of the resulting damage signals as well as the calcium signaling dynamics, mathematical modeling done in parallel with experiments is necessary for a complete understanding of the wound signaling system. Here, a reaction-diffusion model is developed for the protease-initiated signal cascade, and this is then implemented across a tissue-level model made up of thousands of coupled cells that replicates, explains, and predicts properties of calcium signals around epithelial wounds. The mathematical modeling presented here shows that gradual protease release from lysed cells near the wound, cell-cell variability, and intercellular transfer of both calcium and IP¬3 are all necessary to produce observed wound-induced calcium signals. Furthermore, the models presented here serve as an essential framework for future studies of both wound signaling and calcium signaling in the Drosophila system and beyond. | |
