Credit to the Fruit Fly: How the Tiny Insect Lights Up Our Understanding of Human Disease

Drosophila melanogaster, widely known as the fruit fly, has emerged as a pivotal model organism for studying development and signaling transduction. Its fully sequenced genome, short generation time, and powerful genetic toolkit-including the Gal4/UAS system, RNA interference, and CRISPR-Cas9-enable precise, tissue-specific manipulation and high-throughput functional analyses. Despite differences in anatomy, the internal organ systems of Drosophila melanogaster, including the nervous system, heart, fat body, oenocytes, and nephrocytes, exhibit conserved molecular pathways and physiological functions comparable to those of humans. The morphological differences between invertebrates and vertebrates have long led researchers to undervalue the studies of insects in underlying the pathogenesis of human diseases. Over the past decades, the fruit fly has been widely validated for modeling the pathogenesis of neurodegenerative, cardiovascular, metabolic, renal, and muscular disorders. In this review, we systematically summarize the conserved molecular pathways and organ functions between the fruit fly and human, and provide examples of recent studies that use the fruit fly as a model system to answer questions associated with human diseases. We also discuss how Drosophila help researchers to fulfill the gap from mechanistic study toward translational research, and provide methodological considerations regarding the utility of Drosophila models in drug screening.