Visceral Mechano-sensing Neurons Control Drosophila Feeding by Using Piezo as a Sensor

Animal feeding is controlled by external sensory cues and internal metabolic states. Does it also depend on enteric neurons that sense mechanical cues to signal fullness of the digestive tract? Here, we identify a group of piezo-expressing neurons innervating the Drosophila crop (the fly equivalent of the stomach) that monitor crop volume to avoid food overconsumption. These neurons reside in the pars intercerebralis (PI), a neuro-secretory center in the brain involved in homeostatic control, and express insulin-like peptides with well-established roles in regulating food intake and metabolism. Piezo knockdown in these neurons of wild-type flies phenocopies the food overconsumption phenotype of piezo-null mutant flies. Conversely, expression of either fly Piezo or mammalian Piezo1 in these neurons of piezo-null mutants suppresses the overconsumption phenotype. Importantly, Piezo⁺ neurons at the PI are activated directly by crop distension, thus conveying a rapid satiety signal along the "brain-gut axis" to control feeding.