From spikes to intercellular waves: tuning the strength of calcium stimulation modulates organ size control

Calcium (Ca 2+ ) signaling is a fundamental molecular communication mechanism for the propagation of information in eukaryotic cells. Cytosolic calcium ions integrate a broad range of hormonal, mechanical and electrical stimuli within cells to modulate downstream cellular processes involved in organ development. However, how the spatiotemporal dynamics of calcium signaling are controlled at the organ level remains poorly understood. Here, we show that the spatiotemporal extent of calcium signaling within an epithelial system is determined by the class and level of hormonal stimulation and by the subdivision of the cell population into a small fraction of initiator cells surrounded by a larger fraction of standby cells connected through gap junction communication. To do so, we built a geometrically accurate computational model of intercellular Ca 2+ signaling that spontaneously occurs within developing Drosophila wing imaginal discs. The multi-scale computational model predicts the regulation of the main classes of Ca 2+ signaling dynamics observed in vivo: single cell Ca 2+ spikes, intercellular transient bursts, intercellular waves and global fluttering. We show that the tuning of the spatial extent of Ca 2+ dynamics from single cells to global waves emerges naturally as a function of global hormonal stimulation strength. Further, this model provides insight into how emergent properties of intercellular calcium signaling dynamics modulates cell growth within the tissue context. It provides a framework for analyzing second messenger dynamics in multicellular systems.