Cell and Tissue Research

, Volume 366, Issue 1, pp 13–22 | Cite as

Extrinsic innervation of ileum and pelvic flexure of foals with ileocolonic aganglionosis

  • F. Giancola
  • F. Gentilini
  • N. Romagnoli
  • A. Spadari
  • M. E. Turba
  • M. Giunta
  • J. Sadeghinezhad
  • C. Sorteni
  • R. ChiocchettiEmail author
Regular article


Equine ileocolonic aganglionosis, which is also called lethal white foal syndrome (LWFS), is a severe congenital condition characterized by the unsuccessful colonization of neural crest progenitors in the caudal part of the small intestine and the entire large intestine. LWFS, which is attributable to a mutation in the endothelin receptor B gene, is the horse equivalent of Hirschsprung’s disease in humans. Affected foals suffer from aganglionosis or hypoganglionosis of the enteric ganglia resulting in intestinal akinesia and colic. In other species with aganglionosis, fibers of extrinsic origin show an abnormal distribution pattern within the gut wall, but we have no information to date regarding this occurrence in horses. Our present aim is to investigate the distribution of extrinsic sympathetic and sensory neural fibers in LWFS, focusing on ileum and the pelvic flexure of the colon of two LWFS foals compared with a control subject. The sympathetic fibers were immunohistochemically identified with the markers tyrosine hydroxylase and dopamine beta-hydroxylase. The extrinsic sensory fibers were identified with the markers Substance P (SP) and calcitonin gene-related peptide (CGRP). Since SP and CGRP are also synthesized by subclasses of horse intramural neurons, LWFS represents a good model for the selective study of extrinsic fiber distribution. Affected foals showed large bundles of extrinsic fibers, compared with the control, as observed in Hirschsprung’s disease. Furthermore, altered adrenergic pathways were observed, prominently in the pelvic flexure. The numbers of SP- and CGRP-immunoreactive fibers in the muscle, a target of enteric neurons, were dramatically reduced, whereas fibers deduced to be extrinsic sensory axons persisted around submucosal blood vessels. Fiber numbers in the mucosa were reduced. Thus, extrinsic innervation, contributing to modulate enteric functions, might also be affected during LWFS.


Enteric nervous system Immunohistochemistry Hirschsprung’s disease Lethal white foal syndrome Overo coat pattern 



The excellent technical assistance of Dr. Riccardo Rinnovati is gratefully acknowledged.

Compliance with ethical standards


This research was supported by no specific grant from any funding agency in the public, commercial, or not-for-profit sector.

Conflict of interest

The authors declare that they have no conflict of interest.

Supplementary material

441_2016_2422_MOESM1_ESM.pdf (777 kb)
ESM 1 (PDF 776 kb)


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Copyright information

© Springer-Verlag Berlin Heidelberg 2016

Authors and Affiliations

  • F. Giancola
    • 1
  • F. Gentilini
    • 1
  • N. Romagnoli
    • 1
  • A. Spadari
    • 1
  • M. E. Turba
    • 1
  • M. Giunta
    • 1
  • J. Sadeghinezhad
    • 2
  • C. Sorteni
    • 1
  • R. Chiocchetti
    • 1
    Email author
  1. 1.Department of Veterinary Medical Sciences (UNI EN ISO 9001:2008)University of BolognaOzzano dell’EmiliaItaly
  2. 2.Department of Basic Sciences, Faculty of Veterinary MedicineUniversity of TehranTehranIran

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