TGF beta 1 inhibits branching morphogenesis and N-myc expression in lung bud organ cultures.

Serra R, Pelton RW, Moses HL
Development. 1994 120 (8): 2153-61

PMID: 7523056

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.

MeSH Terms (17)

Animals Blotting, Northern Dose-Response Relationship, Drug Epithelium Gene Expression Genetic Techniques In Situ Hybridization Lung Mice Mice, Inbred C57BL Mice, Inbred ICR Models, Biological Morphogenesis Organ Culture Techniques Proto-Oncogene Proteins c-myc RNA Transforming Growth Factor beta

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