# Histological study on the postnatal development of the nerve network in the rat ileal mucosa and submucosa

## TL;DR

This study investigates how nerve networks in the rat ileum develop after birth, focusing on differences between the mesenteric and antimesenteric sides.

## Contribution

The study reveals that nerve network and submucosal ganglion development in rat ileum occurs preferentially on the mesenteric side during the weaning period.

## Key findings

- Tuj1-immunopositive nerve fibers are more abundant in the lamina propria at 2 weeks old on the mesenteric side.
- SM-neurons and SMG are more frequently localized on the mesenteric side at P0 and 2 weeks old.
- Sox10 and S100β markers show homogeneous distribution in the submucosa across all ages and sides.

## Abstract

We have previously reported detailed structures of the mucosal nerve network in the rat ileum, but the mechanisms underlying the development of this nerve network remain unclear. Therefore, we aimed to clarify the developmental process of the mucosal nerve network and submucosal neurons (SM-neurons) or ganglia (SMG), which are the main source of nerve fibers projected to the mucosa, in the rat ileum during the postnatal period. Immunohistochemistry against tubulin beta III (Tuj1) revealed that Tuj1-immunopositivities were more abundant in the lamina propria at 2 weeks old (2wk; pre-weaning) than at postnatal day 0 (P0) or 4 weeks old (4wk; post-weaning) and more frequent on the mesenteric side than on the antimesenteric side at 2wk. Hu antigen D (HuD)-immunopositive SM-neurons and SMG were also more abundantly localized on the mesenteric side than the antimesenteric side at P0 and 2wk. On the other hand, cells immunopositive for SRY-related HMG-box 10 (Sox10), which is the marker for enteric nervous system progenitor cells and enteric glial cells, were homogenously scattered in the submucosa throughout the entire circumference at all ages. Glial cell marker S100 calcium-binding protein B (S100β) in the submucosa was detected at all ages without any significant difference between the mesenteric and antimesenteric sides. These findings indicate that SMG formation and associated neurite extension into the mucosa in the rat ileum might occur preferentially on the mesenteric side by the weaning period, leading us to hypothesize that the mechanism by which the mucosal nerve network and SMG develop differs along the mesenteric–antimesenteric side axis.

The online version contains supplementary material available at 10.1007/s00441-025-03949-3.