Regulation of feeding and defecation in Drosophila by trpγ, piezo, and DH44R2

Normal gastrointestinal (GI) motility, including defecation, is crucial for nutrient absorption, energy balance, and overall health in species ranging from insects to humans. Disruptions in GI motility can lead to conditions like constipation or severe diseases. Mechanosensors, including TRP channels and Piezo, are known to play key roles in regulating gut physiology in Drosophila melanogaster, but their precise involvement in defecation is not fully understood. Additionally, neuropeptides like DH44 have been implicated in gut regulation. This study explores the roles of Trpγ, Diuretic hormone 44 Receptor 2 (DH44R2), and Piezo in controlling feeding amount, gut motility, and defecation using genetic mutants and RNAi techniques. Mutants for these genes exhibited increased excreta production and size, whereas Dh44 and Dh44R1 mutants had a reduced number of excreta, but with increased size. Co-expression and rescue experiments further confirmed the critical roles of these genes in the same gut cells. The findings reveal that local gut-specific mechanisms are the primary drivers of defecation. The results highlight the collaboration between Trpγ, Piezo, and DH44R2 in regulating gut motility and defecation. By uncovering how these mechanosensory proteins and cells work together, this research may offer insights into human GI disorders like Irritable Bowel Syndrome (IBS) and Hirschsprung's disease, shedding light on the complex regulatory network underlying defecation.