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 Ca2+-dependent Dilp8 signaling. These findings establish mechanistic links between GPCR signaling, tissue regeneration, and systemic developmental coordination, with broader implications for understanding Gαq-related pathologies in humans.
Keywords: Ca2+; Calcium signaling; Dilp8; G alpha q; Insulin-like peptide 8.
This study explores how a protein called Gαq helps organs grow to the optimal size and shape during development, using fruit flies as a model. Gαq is part of a signaling system that controls how cells communicate and respond to their environment.We found that Gαq helps produce waves of calcium activity in developing wing tissue. When we altered Gαq levels during larval development, the adult wings became smaller. This was due to fewer cells dividing and, unexpectedly, fewer cells dying. These effects may relate to how Gαq functions in human diseases like cancer, though more research is needed.Gαq also slowed overall development. This delay was linked to the release of a signal called Dilp8, which tells the body to slow down growth so tissues can catch up. We showed that blocking Dilp8, or interfering with calcium signaling, could restore normal development speed. This means Gαq plays a role in managing developmental timing through a hormone system that coordinates growth across the body.Further genetic analysis revealed that Gαq activates several important pathways involved in immunity, growth, and cell structure. It also affects how cells connect physically and multiply, which are crucial for shaping tissues.In summary, Gαq is a key regulator of growth and timing during development. By influencing both local cell behavior and whole-body signals, it ensures that organs form correctly and in sync with the rest of the organism.
© 2025. The Author(s).