Calcium (Ca²⁺) is a crucial second messenger that coordinates cellular processes across tissues. However, direct control over Ca²⁺-mediated processes remains limited. Here, we use the optogenetic channelrhodopsin CsChrimson to investigate how Ca²⁺ signaling impacts epithelial growth and morphogenesis in Drosophila melanogaster. Optogenetic activation of CsChrimson modulates cytosolic Ca²⁺ levels, influencing proliferation, apoptosis, and integrin-mediated adhesion. We observed a biphasic Ca²⁺ response that optimally regulates organ size, while prolonged activation (>6 hours) increased apoptosis and caused severe morphological defects, including epithelial blistering. Mechanistically, Ca²⁺ elevation disrupted cytoskeletal organization, reducing integrin levels and adhesion strength. To further explore the interplay between Ca²⁺ signaling and tumorigenesis, we have developed a transgenic line that co-expresses CsChrimson with Ras-V12, to enable investigations into how Ca2+ directly impacts tumor growth and mechanics. These findings demonstrate that optogenetics enables precise control of Ca²⁺ dynamics to regulate cellular processes and mechanics, tissue integrity, and organ shape. Our work provides insights into Ca²⁺-mediated growth control and its potential applications in phenotypic drug screening and therapeutic innovations for human diseases, including cancer.
