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

Abstract

Interstitial cells of Cajal (ICC) and PDGFRα⁺ cells regulate smooth muscle motility in the gastrointestinal (GI) tract. However, their role(s) in esophageal motility are still unclear. The mouse esophagus has traditionally been described as almost entirely skeletal muscle in nature though ICC have been identified along its entire length. The current study evaluated the distribution of skeletal and smooth muscle within the esophagus using a mouse selectively expressing eGFP in smooth muscle cells (SMCs). The relationship of SMCs to ICC and PDGFRα⁺ cells was also examined. SMCs declined in density in the oral direction however SMCs represented ~ 25% of the area in the distal esophagus suggesting a likeness to the transition zone observed in humans. ANO1⁺ intramuscular ICC (ICC-IM) were distributed along the length of the esophagus though like SMCs, declined proximally. ICC-IM were closely associated with SMCs but were also found in regions devoid of SMCs. Intramuscular and submucosal PDGFRα⁺ cells were densely distributed throughout the esophagus though only intramuscular PDGFRα⁺ cells within the LES and distal esophagus highly expressed SK3. ICC-IM and PDGFRα⁺ cells were closely associated with nNOS⁺, VIP⁺, VAChT⁺ and TH⁺ neurons throughout the LES and distal esophagus. GFAP⁺ cells resembling intramuscular enteric glia were observed within the muscle and were closely associated with ICC-IM and PDGFRα⁺ cells, occupying a similar location to motor nerve fibers. These data suggest that the mouse esophagus is more similar to the human than thought previously and thus set the foundation for future functional and molecular studies using transgenic mice.