title: Diaphragm defects occur in a CDH hernia model independently of myogenesis and lung formation.
abstract: Congenital diaphragmatic hernia (CDH) is a significant clinical problem in which a portion of the diaphragmatic musculature fails to form, resulting in a hole in the diaphragm. Here we use animal models of CDH to test two hypotheses regarding the pathogenesis. First, the origin of the defect results from the malformation of the amuscular mesenchymal component of the primordial diaphragm rather than with the process of myogenesis. Second, the defect in the primordial diaphragmatic tissue is not secondary to defects in the developing lung. In c-met(-/-) mouse embryos, in which diaphragm muscle fibers do not form because of a defect in muscle precursor migration, the amuscular substratum forms fully. We show that a defect characteristic of CDH can be induced in the amuscular membrane. In Fgf10(-/-) mouse embryos that have lung agenesis we show that the primordial diaphragm does not depend on signals from lung tissue for proper development and that diaphragmatic malformation is a primary defect in CDH. These data suggest that the pathogenesis of CDH involves mechanisms fundamentally different from previously proposed hypotheses.
authors.affiliation: Department of Physiology, Perinatal Research Centre, 513 Heritage Medical Research Centre, University of Alberta, Edmonton, Alberta, Canada T6G 2S2.
authors.forename: Randal P
authors.initials: RP
authors.lastname: Babiuk
authors.forename: John J
authors.initials: JJ
authors.lastname: Greer
mesh_terms: D000818:Animals; D003964:Diaphragm / Q000196:embryology*; D005314:Embryonic and Fetal Development; D051526:Fibroblast Growth Factor 10; D005346:Fibroblast Growth Factors / Q000172:deficiency / Q000235:genetics; D006548:Hernia, Diaphragmatic / Q000196:embryology* / Q000235:genetics; D008168:Lung / Q000196:embryology*; D051379:Mice; D018345:Mice, Knockout / Q000235:genetics; D024510:Muscle Development; D019859:Proto-Oncogene Proteins c-met / Q000172:deficiency / Q000235:genetics
chemical_list: C496464:Fgf10 protein, mouse; D051526:Fibroblast Growth Factor 10; D005346:Fibroblast Growth Factors; D019859:Proto-Oncogene Proteins c-met