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

**Authors:** Emer Ni Bhraonain, Jack Turner, Karen Hannigan, Kenton Sanders, Caroline Cobine

PMC · DOI: 10.21203/rs.3.rs-4474290/v1 · 2024-06-11

## TL;DR

This study explores the distribution and relationships of interstitial cells and motor neurons in the mouse esophagus, revealing similarities to human anatomy.

## Contribution

The study provides new insights into the cellular composition and organization of the mouse esophagus, highlighting its similarity to the human esophagus.

## Key findings

- Smooth muscle cells (SMCs) decrease in density toward the oral direction but remain significant in the distal esophagus.
- ICC-IM and PDGFRα+ cells are closely associated with motor neurons and glial cells in the distal esophagus and LES.
- The mouse esophagus shows structural similarities to the human esophagus, particularly in the transition zone.

## 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 c. 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.

## Linked entities

- **Proteins:** PDGFRA (platelet derived growth factor receptor alpha), ANO1 (anoctamin 1), KCNN3 (potassium calcium-activated channel subfamily N member 3), NOS1 (nitric oxide synthase 1), VIP (vasoactive intestinal peptide), SLC18A3 (solute carrier family 18 member A3), TH (tyrosine hydroxylase), GFAP (glial fibrillary acidic protein)
- **Species:** Mus musculus (taxon 10090)

## Full-text entities

- **Genes:** Ano1 (anoctamin 1, calcium activated chloride channel) [NCBI Gene 101772] {aka Tmem16a}, Gfap (glial fibrillary acidic protein) [NCBI Gene 14580], Pdgfra (platelet derived growth factor receptor, alpha polypeptide) [NCBI Gene 18595] {aka CD140a, Pdgfr-2}, VIP (vasoactive intestinal peptide) [NCBI Gene 7432] {aka PHM27}, NOS1 (nitric oxide synthase 1) [NCBI Gene 4842] {aka IHPS1, N-NOS, NC-NOS, NOS, bNOS, nNOS}, PDGFRA (platelet derived growth factor receptor alpha) [NCBI Gene 5156] {aka CD140A, PDGFR-2, PDGFR2}, KCNN3 (potassium calcium-activated channel subfamily N member 3) [NCBI Gene 3782] {aka KCa2.3, SK3, SKCA3, ZLS3, hSK3}, SLC18A3 (solute carrier family 18 member A3) [NCBI Gene 6572] {aka CMS21, VACHT}
- **Diseases:** ICC-IM (MESH:D007984)
- **Species:** Homo sapiens (human, species) [taxon 9606], Mus musculus (house mouse, species) [taxon 10090]

## Figures

9 figures with captions in the complete paper: https://tomesphere.com/paper/PMC11213231/full.md

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Source: https://tomesphere.com/paper/PMC11213231