Extracellular vesicles (EVs) are fundamental mediators of intercellular communication, transporting proteins, lipids, and nucleic acids between cells to regulate a wide range of physiological and pathological processes. Although EV research has expanded rapidly in recent years, defining their biogenesis, molecular regulation, and in vivo functions remains challenging because of the complexity and heterogeneity of EV populations.
A new review published in EXO – Beyond the Cell examines how the genetic model organism Drosophila melanogaster has become an important experimental system for investigating conserved mechanisms of EV biology. The review argues that the complementary strengths of Drosophila and mammalian models can help advance mechanistic studies of EV-mediated intercellular communication across species.
Written by Kyosuke Yanagawa and Norbert Perrimon of Harvard Medical School, the review provides a comprehensive overview of current knowledge on EV nomenclature, biogenesis, cargo sorting, and biological functions in both mammals and Drosophila. The authors also discuss recent efforts to establish standardized EV classification and emphasize the importance of defining EV populations according to experimentally supported biogenesis rather than relying solely on size or molecular markers.
The review summarizes conserved molecular pathways that regulate EV formation, including ESCRT-dependent and ESCRT-independent mechanisms, Rab GTPase-mediated membrane trafficking, lipid remodeling, and endosomal transport. Studies in Drosophila have revealed genetically tractable systems for investigating these pathways in vivo, including tissue-specific mechanisms controlling EV biogenesis and cargo trafficking at the neuromuscular junction, imaginal discs, glial cells, and male accessory glands.
Beyond EV biogenesis, the authors highlight diverse physiological functions of EVs across species. In mammals, EVs participate in development, metabolism, immunity, and cancer progression, whereas studies in Drosophila have demonstrated important roles for EVs in synaptic communication, long-distance signaling, and systemic antiviral defense. Together, these findings underscore the evolutionary conservation of EV-mediated intercellular communication while illustrating how Drosophila genetics can facilitate functional studies that are difficult to perform in mammalian systems alone.
The review concludes that Drosophila should be viewed not as a replacement for mammalian models, but as a complementary genetic system for dissecting the causal mechanisms underlying EV biology. Integrating discoveries from both experimental systems is expected to deepen our understanding of EV function and support future studies of intercellular communication in development and disease.
