Immunohistochemical characterization of interstitial cells and their spatial relationship to motor neurons within the mouse esophagus.

Interstitial cells of Cajal (ICC) and PDGFRα⁺ cells regulate smooth muscle motility in the gastrointestinal (GI) tract, yet their function in the esophagus remains unknown. The mouse esophagus has been described as primarily skeletal muscle; however, ICC  have been identified in this region. This study characterizes the distribution of skeletal and smooth muscle cells (SMCs) and their spatial relationship to ICC, PDGFRα⁺ cells, and intramuscular motor neurons in the mouse esophagus. SMCs occupied approximately 30% of the distal esophagus, but their density declined in more proximal regions. Similarly, ANO1⁺ intramuscular ICC (ICC-IM) were distributed along the esophagus, with density decreasing proximally. While ICC-IM were closely associated with SMCs, they were also present in regions of skeletal muscle. Intramuscular, submucosal, and myenteric PDGFRα⁺ cells were densely distributed throughout the esophagus, yet only intramuscular PDGFRα⁺ cells in the lower esophageal sphincter (LES) and distal esophagus expressed SK3. ICC-IM and PDGFRα⁺ cells were closely associated with intramuscular nNOS⁺, VIP⁺, VAChT⁺, and TH⁺ neurons and GFAP⁺ cells resembling intramuscular enteric glia. These findings suggest that ICC-IM and PDGFRα⁺ cells may have roles in regulating esophageal motility due to their close proximity to each other and to skeletal muscle and SMCs, although further functional studies are needed to explore their role in this region. The mixed muscular composition and presence of interstitial cells in the mouse distal esophagus is anatomically similar to the transitional zone found in the human esophagus, and therefore, motility studies in the mouse may be translatable to humans.