Internal mechanosensory feedback modulates central pattern generation to coordinate ovulation in Drosophila

Successful reproduction requires precise coordination of muscle contractions during ovulation and has been well investigated in insects. However, the neural mechanisms of the central pattern generator (CPG) orchestrating this process remain poorly understood. Using Drosophila , we identify a novel pair of multidendritic mechanosensory neurons (mdn-LO) in the lateral oviducts that express the mechanosensitive channels TMC (transmembrane channel-like protein), PPK (pickpocket), and Piezo. We demonstrate that TMC is essential for ovulation coordination: tmc mutation or neuron-specific knockdown significantly increases egg-jamming at the junction between the lateral and the common oviduct, while ppk or Piezo single mutants reduce egg-laying without causing jamming. Calcium imaging reveals that mdn-LO neurons are rhythmically activated by oviduct contractions, and chemogenetic stimulation of these neurons triggers muscle contraction. Trans-Tango and GRASP (GFP Reconstitution Across Synaptic Partners) analyses show that mdn-LO neurons form synapses with efferent insulin-like peptide 7 (ILP7)-expressing motor neurons in the abdominal ganglion. Activating either mdn-LO or ILP7 neurons induces egg-jamming, indicating their roles within a CPG network. This circuit, including the TMC-expressing mdn-LO neurons and a set of ILP7 neurons, organizes an innate behavior by coupling strategic sensory information and a CPG to ensure bilateral coordination of oviduct contractions to prevent egg jamming during oviposition.