Distribution of interstitial cells within the mouse esophagus and their spatial relationship to enteric neurons

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Background/Objectives: The esophagus is a conduit for the passage of ingested material into the stomach. In humans, it is divided into thirds; the proximal portion is composed of skeletal muscle, the distal is composed of smooth muscle and the middle is a transition zone between skeletal and smooth muscles. In other species such as the mouse, the esophagus has been described to consist entirely of skeletal muscle. Despite this, interstitial cells of Cajal (ICC), cells that regulate gastrointestinal (GI) smooth muscle contractility, have been identified throughout the mouse esophageal body (Rumessen et al., 2001; PMID:11683170). Additional studies in the human esophagus have identified another interstitial cell type, PDGFRa+ cells (Chen et al., 2013; PMID:23734090). However, the distribution of interstitial cells, motor and sensory neurons and their spatial relationship to one another have never been examined. Since interstitial cells modulate contractility of smooth muscle in other GI regions, the presence of these cells leads to the hypothesis that the mouse esophagus also contains smooth muscle cells (SMCs). Therefore, the aims of our study were to 1) determine if SMCs are found within the mouse esophagus, 2) characterize the distribution of ICC and PDGFRa+ cells, and 3) examine the relationship of interstitial cells to enteric motor and sensory neurons. Methods: Wildtype (C57Bl/6) and smooth muscle eGFP (smMHC-eGFP) mouse esophagus was used for dual labeling immunohistochemistry. ICC were labeled with antibodies against Kit or ANO1. PDGFRa+ cells were labeled with antibodies against PDGFRa or SK3. Extrinsic sympathetic neurons were labeled with tyrosine hydroxylase (TH). Motor neurons were labeled with antibodies against NOS, VIP (inhibitory) and vChAT (excitatory). Sensory neurons were labeled with CGRP. Images were taken with a Leica Stellaris 5 confocal microscope and processed using LasX software. Results: SMCs were found throughout the length of the esophagus, although their density declined proximally. Intramuscular ICC expressed ANO1 and were distributed throughout the length of the esophagus with the greatest density in the gastroesophageal junction (GEJ). Submucosal and intramuscular PDGFRa+ cells were distributed throughout the esophagus and GEJ. Intramuscular PDGFRa+ cells expressed SK3 though this expression declined proximally. SMCs, intramuscular ICC and PDGFRa+ cells were closely associated with one another as well as with neurons. Discussion/Conclusions: This study is the first to systematically characterize SMCs, ICC, PDGFRa+ cells and neurons in the mouse esophagus. These findings suggest that the mouse may represent a better translational model for studying esophageal motility than previously assumed. NIH DK129528 and P20GM130459. This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.