title: A key role for E-cadherin in intestinal homeostasis and Paneth cell maturation.
abstract: BACKGROUND
  E-cadherin is a major component of adherens junctions. Impaired expression of E-cadherin in the small intestine and colon has been linked to a disturbed intestinal homeostasis and barrier function. Down-regulation of E-cadherin is associated with the pathogenesis of infections with enteropathogenic bacteria and Crohn's disease.
  
  
  RESULTS
  To genetically clarify the function of E-cadherin in intestinal homeostasis and maintenance of the epithelial defense line, the Cdh1 gene was conditionally inactivated in the mouse intestinal epithelium. Inactivation of the Cdh1 gene in the small intestine and colon resulted in bloody diarrhea associated with enhanced apoptosis and cell shedding, causing life-threatening disease within 6 days. Loss of E-cadherin led cells migrate faster along the crypt-villus axis and perturbed cellular differentiation. Maturation and positioning of goblet cells and Paneth cells, the main cell lineage of the intestinal innate immune system, was severely disturbed. The expression of anti-bacterial cryptidins was reduced and mice showed a deficiency in clearing enteropathogenic bacteria from the intestinal lumen.
  
  
  CONCLUSIONS
  These results highlight the central function of E-cadherin in the maintenance of two components of the intestinal epithelial defense: E-cadherin is required for the proper function of the intestinal epithelial lining by providing mechanical integrity and is a prerequisite for the proper maturation of Paneth and goblet cells.
authors.affiliation: Institute of Molecular Animal Breeding and Biotechnology, and Laboratory for Functional Genome Analysis (LAFUGA), Gene Center, University of Munich, Munich, Germany.
authors.forename: Marlon R
authors.initials: MR
authors.lastname: Schneider
authors.forename: Maik
authors.initials: M
authors.lastname: Dahlhoff
authors.forename: David
authors.initials: D
authors.lastname: Horst
authors.forename: Benjamin
authors.initials: B
authors.lastname: Hirschi
authors.forename: Konrad
authors.initials: K
authors.lastname: Trülzsch
authors.forename: Josef
authors.initials: J
authors.lastname: Müller-Höcker
authors.forename: Roger
authors.initials: R
authors.lastname: Vogelmann
authors.forename: Michael
authors.initials: M
authors.lastname: Allgäuer
authors.forename: Markus
authors.initials: M
authors.lastname: Gerhard
authors.forename: Sylvia
authors.initials: S
authors.lastname: Steininger
authors.forename: Eckhard
authors.initials: E
authors.lastname: Wolf
authors.forename: Frank T
authors.initials: FT
authors.lastname: Kolligs
mesh_terms: D000818:Animals; D015820:Cadherins / Q000096:biosynthesis / Q000502:physiology*; D064200:Cdh1 Proteins; D018797:Cell Cycle Proteins / Q000235:genetics* / Q000378:metabolism; D016923:Cell Death; D003106:Colon / Q000378:metabolism; D003424:Crohn Disease / Q000378:metabolism; D004847:Epithelial Cells / Q000378:metabolism; D005786:Gene Expression Regulation; D020397:Goblet Cells / Q000378:metabolism; D006706:Homeostasis; D006720:Homozygote; D007421:Intestine, Small / Q000378:metabolism; D051379:Mice; D008822:Mice, Transgenic; D019879:Paneth Cells / Q000166:cytology*
chemical_list: D015820:Cadherins; D064200:Cdh1 Proteins; D018797:Cell Cycle Proteins; C577585:Fzr1 protein, mouse