Role of epidermal growth factor expression in early mouse embryo lung branching morphogenesis in culture: antisense oligodeoxynucleotide inhibitory strategy.
Epidermal growth factor (EGF) expression and branching morphogenesis were inhibited using a 5' 15-mer antisense oligodeoxynucleotide (ODN) directed against EGF precursor mRNA in embryonic mouse lung in culture under chemically defined, serumless conditions. Antisense EGF ODN resulted in > 90% inhibition of EGF immunoreactive peptide synthesis, 75% reduction in branching morphogenesis, 73% decrease in DNA content, 64% decrease in RNA content, 73% decrease in protein synthesis, and 65% decrease in [3H]thymidine incorporation into DNA compared to Embryonic Day 11 controls in culture for 4 days. Sense ODN results were similar to control. Supplementing antisense ODN with EGF partially reversed antisense effects. The results further support a role for EGF in pulmonary organogenesis.
Seth
R
R
Developmental Lung Cell & Molecular Biology Center, Childrens Hospital of Los Angeles, University of Southern California School of Medicine 90027.
Shum
L
L
Wu
F
F
Wuenschell
C
C
Hall
F L
FL
Slavkin
H C
HC
Warburton
D
D
D000818:Animals; D001483:Base Sequence; D004815:Epidermal Growth Factor / Q000032:analysis / Q000235:genetics / Q000502:physiology*; D008168:Lung / Q000196:embryology* / Q000378:metabolism; D051379:Mice; D009024:Morphogenesis; D016376:Oligonucleotides, Antisense / Q000494:pharmacology*; D009924:Organ Culture Techniques; D012322:RNA Precursors / Q000378:metabolism
D016376:Oligonucleotides, Antisense; D012322:RNA Precursors; D004815:Epidermal Growth Factor