title: CFTR and Wnt/beta-catenin signaling in lung development.
abstract: BACKGROUND
  Cystic fibrosis transmembrane conductance regulator (CFTR) was shown previously to modify stretch induced differentiation in the lung. The mechanism for CFTR modulation of lung development was examined by in utero gene transfer of either a sense or antisense construct to alter CFTR expression levels. The BAT-gal transgenic reporter mouse line, expressing beta-galactosidase under a canonical Wnt/beta-catenin-responsive promoter, was used to assess the relative roles of CFTR, Wnt, and parathyroid hormone-related peptide (PTHrP) in lung organogenesis. Adenoviruses containing full-length CFTR, a short anti-sense CFTR gene fragment, or a reporter gene as control were used in an intra-amniotic gene therapy procedure to transiently modify CFTR expression in the fetal lung.
  
  
  RESULTS
  A direct correlation between CFTR expression levels and PTHrP levels was found. An inverse correlation between CFTR and Wnt signaling activities was demonstrated.
  
  
  CONCLUSIONS
  These data are consistent with CFTR participating in the mechanicosensory process essential to regulate Wnt/beta-Catenin signaling required for lung organogenesis.
authors.affiliation: The Brady Laboratory, Section of Neonatology, Department of Pediatrics, Stony Brook University, School of Medicine, Stony Brook, New York, USA. jcraig.cohen@stonybrook.edu
authors.forename: J Craig
authors.initials: JC
authors.lastname: Cohen
authors.forename: Janet E
authors.initials: JE
authors.lastname: Larson
authors.forename: Erin
authors.initials: E
authors.lastname: Killeen
authors.forename: Damon
authors.initials: D
authors.lastname: Love
authors.forename: Ken-Ichi
authors.initials: K
authors.lastname: Takemaru
mesh_terms: D000818:Animals; D019005:Cystic Fibrosis Transmembrane Conductance Regulator / Q000235:genetics / Q000502:physiology*; D004622:Embryo, Mammalian; D005786:Gene Expression Regulation / Q000502:physiology; D008168:Lung / Q000254:growth & development*; D051379:Mice; D038081:Organogenesis; D044162:Parathyroid Hormone-Related Protein / Q000235:genetics*; D015398:Signal Transduction; D014162:Transfection; D051153:Wnt Proteins / Q000378:metabolism*; D051176:beta Catenin / Q000378:metabolism*
chemical_list: D044162:Parathyroid Hormone-Related Protein; D051153:Wnt Proteins; D051176:beta Catenin; D019005:Cystic Fibrosis Transmembrane Conductance Regulator