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. © 1993 by Academic Press, Inc.