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Keywords:

  • esophagus;
  • neurotrophic factors;
  • neurotrophins;
  • nociceptor;
  • vagus nerve;
  • visceral

Abstract

Background  The mouse is an invaluable model for mechanistic studies of esophageal nerves, but the afferent innervation of the mouse esophagus is incompletely understood. Vagal afferent neurons are derived from two embryonic sources: neural crest and epibranchial placodes. We hypothesized that both neural crest and placodes contribute to the TRPV1-positive (potentially nociceptive) vagal innervation of the mouse esophagus.

Methods  Vagal jugular/nodose ganglion (JNG) and spinal dorsal root ganglia (DRG) neurons were retrogradely labeled from the cervical esophagus. Single cell RT-PCR was performed on the labeled neurons.

Key Results  In the Wnt1Cre/R26R mice expressing a reporter in the neural crest-derived cells we found that both the neural crest- and the placodes-derived vagal JNG neurons innervate the mouse esophagus. In the wild-type mouse the esophageal vagal JNG TRPV1-positive neurons segregated into two subsets: putative neural crest-derived purinergic receptor P2X2-negative/preprotachykinin-A (PPT-A)-positive subset and putative placodes-derived P2X2-positive/PPTA-negative subset. These subsets also segregated by the expression of TrkA and GFRα3 in the putative neural crest-derived subset, and TrkB in the putative placodes-derived subset. The TRPV1-positive esophageal DRG neurons had the phenotype similar to the vagal putative neural crest-derived subset.

Conclusions & Inferences  The TRPV1-positive (potentially nociceptive) vagal afferent neurons innervating the mouse esophagus originate from both neural crest and placodes. The expression profile of the receptors for neurotrophic factors is similar between the neural crest-derived vagal and spinal nociceptors, but distinct from the vagal placodes-derived nociceptors.