title: TGF beta 1 inhibits branching morphogenesis and N-myc expression in lung bud organ cultures.
abstract: Lung buds isolated from 11.5 days post coitum mouse embryos survive and undergo branching morphogenesis in culture. This organ culture system was used to examine the role of TGF beta 1 and N-myc expression in lung branching morphogenesis. By 24 hours, TGF beta 1 reversibly inhibited branching morphogenesis in a concentration-dependent manner. N-myc is known to be expressed during embryonic development in epithelial cells involved in branching morphogenesis and homozygous null N-myc mice have defects in lung development. In the present study, TGF beta 1 was shown to inhibit the steady-state level of N-myc RNA 3- to 4-fold at 14 and 48 hours of treatment as measured by northern blot and RNase protection analysis. Suppression of N-myc expression in epithelium was confirmed by in situ hybridization. Since inhibition of N-myc occurred prior to the observed changes in morphology and previous genetic studies have demonstrated and important role for N-myc in lung development, a model is proposed in which TGF beta 1 inhibits tracheobronchial development by inhibiting expression of N-myc.
authors.affiliation: Department of Cell Biology, Vanderbilt University School of Medicine, Nashville, Tennessee 37232-2175.
authors.forename: R
authors.initials: R
authors.lastname: Serra
authors.forename: R W
authors.initials: RW
authors.lastname: Pelton
authors.forename: H L
authors.initials: HL
authors.lastname: Moses
mesh_terms: D000818:Animals; D015152:Blotting, Northern; D004305:Dose-Response Relationship, Drug; D004848:Epithelium / Q000196:embryology; D015870:Gene Expression / Q000187:drug effects; D005821:Genetic Techniques; D017403:In Situ Hybridization; D008168:Lung / Q000196:embryology*; D051379:Mice; D008810:Mice, Inbred C57BL; D008813:Mice, Inbred ICR; D008954:Models, Biological; D009024:Morphogenesis / Q000187:drug effects; D009924:Organ Culture Techniques; D016271:Proto-Oncogene Proteins c-myc / Q000235:genetics*; D012313:RNA / Q000032:analysis; D016212:Transforming Growth Factor beta / Q000494:pharmacology*
chemical_list: D016271:Proto-Oncogene Proteins c-myc; D016212:Transforming Growth Factor beta; D012313:RNA