Cell Size Patterns Wound-Induced Intercellular Ca2+ Flashes in a Developing Epithelium

The propagation of Ca²⁺ through neighboring cells has been observed in a variety of cell types, including epithelial, glial, cardiac and muscle cells, and is mediated by many different stimuli. For example, Ca²⁺ flashes have been shown to provide the immediate initial response after wounding. To develop a quantitative understanding of the propagation of wound-induced Ca²⁺ flashes, we compare live-imaging of Ca²⁺ flashes in a genetic model of a developing epithelial organ with an in silico model that extends known conserved, general features of intracellular Ca²⁺ regulation. We consider the spatiotemporal dynamics of intercellular Ca²⁺ flashes in the Drosophila wing disc pouch, the primordium of the fly wing. We start with a well-established two-pool model of intracellular Ca²⁺ dynamics, and extend it to the full wing disc tissue by incorporating the effects of Ca²⁺ transport between cells via gap junctions. The computational model is refined iteratively to capture the observed dynamics of laser-induced flashes, namely a spatiotemporal asymmetric wedge that points toward the center of the disc.  By segmenting wing disc images we are able to simulate our model on a biologically realistic geometry, and hence understand how boundary shape influences flash propagation. Further, we demonstrate that variability in cell sizes across the disc plays a key role in explaining the spatiotemporal characteristics of Ca²⁺ flashes.