title: Loss of Sonic hedgehog leads to alterations in intestinal secretory cell maturation and autophagy.
abstract: BACKGROUND
  Intestinal epithelial cells express the Sonic and Indian hedgehog ligands. Despite the strong interest in gut hedgehog signaling in GI diseases, no studies have specifically addressed the singular role of intestinal epithelial cell Sonic hedgehog signaling. The aim of this study was to investigate the specific role of Sonic hedgehog in adult ileal epithelial homeostasis.
  
  
  RESULTS
  A Sonic hedgehog intestinal epithelial conditional knockout mouse model was generated. Assessment of ileal histological abnormalities, crypt epithelial cell proliferation, epithelial cell fate, junctional proteins, signaling pathways, as well as ultrastructural analysis of intracellular organelles were performed in control and mutant mice. Mice lacking intestinal epithelial Sonic Hedgehog displayed decreased ileal crypt/villus length, decreased crypt proliferation as well as a decrease in the number of ileal mucin-secreting goblet cells and antimicrobial peptide-secreting Paneth cells during adult life. These secretory cells also exhibited disruption of their secretory products in mutant mice. Ultrastructural microscopy analysis revealed a dilated ER lumen in secretory cells. This phenotype was also associated with a decrease in autophagy.
  
  
  CONCLUSIONS
  Altogether, these findings indicate that the loss of Sonic hedgehog can lead to ileal secretory cell modifications indicative of endoplasmic reticulum stress, accompanied by a significant reduction in autophagy.
authors.affiliation: Département d'Anatomie et Biologie Cellulaire, Faculté de Médecine et des Sciences de la Santé, Université de Sherbrooke, Sherbrooke, QC, Canada.
authors.forename: Jessica
authors.initials: J
authors.lastname: Gagné-Sansfaçon
authors.affiliation: Département d'Anatomie et Biologie Cellulaire, Faculté de Médecine et des Sciences de la Santé, Université de Sherbrooke, Sherbrooke, QC, Canada.
authors.forename: Joannie M
authors.initials: JM
authors.lastname: Allaire
authors.affiliation: Département d'Anatomie et Biologie Cellulaire, Faculté de Médecine et des Sciences de la Santé, Université de Sherbrooke, Sherbrooke, QC, Canada.
authors.forename: Christine
authors.initials: C
authors.lastname: Jones
authors.affiliation: Département d'Anatomie et Biologie Cellulaire, Faculté de Médecine et des Sciences de la Santé, Université de Sherbrooke, Sherbrooke, QC, Canada.
authors.forename: François
authors.initials: F
authors.lastname: Boudreau
authors.affiliation: Département d'Anatomie et Biologie Cellulaire, Faculté de Médecine et des Sciences de la Santé, Université de Sherbrooke, Sherbrooke, QC, Canada.
authors.forename: Nathalie
authors.initials: N
authors.lastname: Perreault
mesh_terms: D000818:Animals; D001343:Autophagy; D015153:Blotting, Western; D053823:Hedgehog Proteins / Q000235:genetics / Q000378:metabolism*; D020287:In Situ Nick-End Labeling; D007421:Intestine, Small / Q000166:cytology*; D051379:Mice; D008810:Mice, Inbred C57BL; D008854:Microscopy, Electron; D015398:Signal Transduction
chemical_list: D053823:Hedgehog Proteins