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Sensory neurons of the vagus nerve monitor distention, stretch and nutrients in the gastrointestinal tract, and major efforts are underway to assign physiological functions to the many distinct subtypes of vagal sensory neurons. Here, we used genetically guided anatomical tracing, optogenetics and electrophysiology to identify and characterize three vagal sensory neuronal subtypes expressing Prox2 and Runx3 in mice. We show that these neuronal subtypes function as putative mechanoreceptors. They innervate the esophagus and stomach where they display regionalized innervation patterns, as well as other organs. The electrophysiological analysis of Prox2/Runx3 neurons innervating the esophagus showed that they are all low threshold mechanoreceptors, but possess different adaptation properties. Lastly, genetic ablation of Prox2 and Runx3 neurons demonstrated their essential roles for esophageal …