Abstract
The aganglionic bowel in short segment Hirschsprung’s disease is characterised both by the absence of enteric ganglia and the presence of extrinsic thickened nerve bundles (TNBs). The relationship between the TNBs and the loss of enteric ganglia is unknown. Previous studies have described decreasing numbers of ganglia with increasing density of TNBs within the transition zone (TZ) between ganglionic and aganglionic gut, and there is some evidence of spatial contact between them in this region. To determine the cellular interactions involved, we have analysed the expression of perineurial markers of TNBs and enteric ganglionic markers for both neural cells and their ensheathing telocytes across four cranio-caudal segments consisting of most proximal ganglionic to most distal aganglionic from pull-through resected colon. We show that in the TZ, enteric ganglia are abnormal, being surrounded by perineurium cells characteristic of TNBs. Furthermore, short processes of ganglionic neurons extend caudally towards the aganglionic region, where telocytes in the TNB are located between the perineurium and nerve fibres into which they project telopodes. Thus, enteric ganglia within the TZ have abnormal structural characteristics, the cellular relationships of which are shared by the TNBs. These findings will help towards elucidation of the cellular mechanisms involved in the aetiology of Hirschsprung’s disease.
Competing Interest Statement
The authors have declared no competing interest.
Funding Statement
We received funding from the Bowel and Cancer Research Charity (now Bowel Research UK) and the Institute of Integrative, Systems and Molecular Biology (University of Liverpool), a project grant from the Childrens Research Fund, as well as from the Medical Research Council for a clinical research training fellowship MR/R002/42/1.
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UK North West 3 Research Ethics Committee gave ethical approval for this work.
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Footnotes
Revisions to this document include a change in the order in which Figures 2-4 are presented and additional comments in line with peer reviewed comments.
Data Availability
All data produced in the present study are available upon reasonable request to the authors