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

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.