Gα

The G protein alpha subunit, Gαq, transduces extracellular signals from G-protein-coupled receptors (GPCRs) into the cell, playing essential roles in developmental processes such as organ size control, wound healing, and disease. Hyperactivating mutations in the Gαq are associated with Sturge-Weber syndrome and uveal melanoma, and thus, it serves as an important candidate drug target. However, the downstream mechanisms of Gαq signaling remain poorly defined, creating a bottleneck for designing more effective and targeted therapeutics. Here, we used Drosophila melanogaster wing discs to investigate the cellular and transcriptional consequences of Gαq dysregulation in a model epithelial system. We found that overexpression of Gαq in the wing discs reduces adult wing size and induces systemic developmental delay. Additional notable phenotypes include decreased apoptosis and reduced proliferation. Transcriptomic profiling reveals that the JAK/STAT signaling pathway is specifically upregulated in Gαq overexpression, but not in Gαq knockdown. Furthermore, perturbing Gαq impacts the cytoskeleton, confirmed by altered localization of phosphorylated Myosin II. Gαq overexpression in the wing disc upregulates stress-response pathways and triggers secretion of Drosophila insulin-like peptide 8 (Dilp8), a hormone that coordinates growth and developmental timing. Functional experiments confirmed that IP₃ receptor (IP₃R)-dependent calcium signaling mediates this delay and that the delay is rescued by the knockdown of Dilp8. In sum, Gαq acts as a critical regulator of epithelial growth and developmental timing via Ca