title: The expression pattern of laminin isoforms in Hirschsprung disease reveals a distal peripheral nerve differentiation.
abstract: Hirschsprung disease (HD), a developmental disorder, is associated with failure of enteric ganglia formation. Signaling molecules, including secreted basement membrane molecules, derived from the mesenchyme of the gut wall play an important role in the colonization and/or differentiation of the enteric nervous system. The current study aims to define the possible alterations of laminins involved in the pathogenesis of HD. Expression of the various laminin alpha, beta, and gamma chains, was assessed in the aganglionic, transitional, and ganglionic bowel segments of patients with HD or with other motor disorders. Cytoskeletal, neuronal, and glial markers were also included in this study. The major finding highlighted by the present work concerns the clear identification and location of myenteric aganglionic plexuses in HD with some of the laminin antibodies, which reveal a peripheral nerve type of differentiation. Furthermore, we could show an increase of laminin alpha5 chain immunostaining in the dilated muscle of the ganglionic bowel upstream the distal aganglionic region in a subgroup of patients with HD, as well as a relocalization of laminin alpha2 chain in the subepithelial basement membrane. Overall, these basement membrane molecules could provide useful markers for diagnosis of aganglionosis or hypoganglionosis.
authors.affiliation: Inserm U682, Univ Louis Pasteur, F-67200 Strasbourg, France.
authors.forename: Fabien
authors.initials: F
authors.lastname: Alpy
authors.forename: Léa
authors.initials: L
authors.lastname: Ritié
authors.forename: Francis
authors.initials: F
authors.lastname: Jaubert
authors.forename: François
authors.initials: F
authors.lastname: Becmeur
authors.forename: Agnès
authors.initials: A
authors.lastname: Méchine-Neuville
authors.forename: Olivier
authors.initials: O
authors.lastname: Lefebvre
authors.forename: Christiane
authors.initials: C
authors.lastname: Arnold
authors.forename: Lydia
authors.initials: L
authors.lastname: Sorokin
authors.forename: Michèle
authors.initials: M
authors.lastname: Kedinger
authors.forename: Patricia
authors.initials: P
authors.lastname: Simon-Assmann
mesh_terms: D001485:Basement Membrane / Q000378:metabolism; D015415:Biomarkers / Q000378:metabolism; D002454:Cell Differentiation; D002675:Child, Preschool; D017615:Enteric Nervous System / Q000378:metabolism / Q000473:pathology; D019084:Fluorescent Antibody Technique, Indirect; D018507:Gene Expression Regulation, Developmental; D006627:Hirschsprung Disease / Q000209:etiology* / Q000235:genetics / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D006801:Humans; D007150:Immunohistochemistry; D007223:Infant; D007231:Infant, Newborn; D007797:Laminin / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D008954:Models, Biological; D010525:Peripheral Nerves / Q000473:pathology*; D020033:Protein Isoforms / Q000235:genetics / Q000276:immunology / Q000378:metabolism
chemical_list: D015415:Biomarkers; D007797:Laminin; D020033:Protein Isoforms; C097043:laminin alpha5