TY - JOUR T1 - Intercellular calcium waves are controlled by morphogen signaling during organ development JF - bioRxiv DO - 10.1101/104745 SP - 104745 AU - Qinfeng Wu AU - Pavel A. Brodskiy AU - Cody Narciso AU - Megan Levis AU - Jianxu Chen AU - Peixian Liang AU - Ninfamaria Arredondo-Walsh AU - Danny Z. Chen AU - Jeremiah J. Zartman Y1 - 2017/01/01 UR - http://biorxiv.org/content/early/2017/03/29/104745.abstract N2 - Spontaneous and dramatic intercellular calcium waves are frequently observed during organ development, but are poorly understood. Calcium ions are ubiquitous second messengers that carry out a wide-range of functions, including the regulation of cell proliferation, metabolism and death. Consequently, regulation of calcium signaling encodes a significant portion of the cellular decision making state of cells through both amplitude and frequency-dependent regulation of transcription factors and key regulatory enzymes. Here we report that intercellular calcium waves exhibit spatiotemporal patterns at the organ-level using a quantitative image analysis pipeline. Intercellular calcium waves in the Drosophila wing disc require a specific phospholipase C, Plc21C. Further, we demonstrate that the morphogen signaling pathway, Hedgehog, controls frequencies of calcium oscillations uniformly in the tissue and is required for non-uniform spatial patterning of oscillation amplitudes. Thus, the dynamics of spontaneous intercellular calcium waves are regulated by morphogenetic signaling. Intercellular calcium waves propagate information at the organ-scale that reflects the differentiation state of the developing wing disc.Significance Statement Both calcium signaling and the Hedgehog pathway are essential in directing tissue and organ development in many organisms. This paper reports the first observation that the Hedgehog pathway, which patterns the anterior-posterior orientation of many tissues, spatially patterns intercellular calcium waves in the developing limb of fruit flies. Using image analysis, we show that calcium wave amplitude is higher in the posterior of the tissue, that wave activity decreases during development, and that perturbing the Hedgehog pathway abolishes the amplitude patterning and uniformly changes the frequency. Consequently, morphogenetic signaling results in a secondary level of pattern formation that emerges in calcium waves. Understanding how calcium dynamics encode morphogenetic information at the tissue scale will provide insights into development and cancer. ER -