GROWTH-FACTOR CONTROL OF GROWTH AND EPITHELIAL DIFFERENTIATION IN EMBRYONIC LUNGS

Branching morphogenesis and epithelial differentiation occur simultane ously during lung development, hence controlling factors may affect bo th aspects of development simultaneously. We hypothesized that in the embryonic lung EGF and TGF beta 1 alter both epithelial differentiatio n and developmental morphogenesis. Day 10 1/2 embryonic lung cultures were exposed to either EGF (10 ng/ml) or TGF beta 1 (2 ng/ml) for 72 h , and branching morphogenesis, cell proliferation, and epithelial diff erentiation (the expression of DSPC synthesis and of surfactant protei n C (SP-C) mRNA) were studied. EGF treatment stimulated branching morp hogenesis (measured as the number of terminal left lung buds), epithel ial differentiation, and cell proliferation. Branching morphogenesis w as increased compared to controls after 48 h of culture by 47% and aft er 72 h by 34% (P < 0.0005). Choline incorporation into DSPC was stimu lated by 343% (P = 0.05). SP-C expression was increased sixfold. Thymi dine incorporation was stimulated by 49% (P < 0.05). The effects of EG F on thymidine labeling were distributed among epithelial cells of the airway walls and of the branching tips, and also the mesenchyme (P < 0.01 for each area compared to controls). In contrast, TGF beta 1 did not alter the number of terminal left lung buds, inhibited choline inc orporation into DSPC by 35% (P < 0.05), and had no effect on thymidine incorporation (87% of control). There was increased thymidine labelin g at the branching tips (P < 0.01), while other areas were not differe nt from controls. We conclude that both EGF and TGF beta 1 affect the development of branching morphogenesis and of epithelial differentiati on in the embryonic lung. (C) 1997 Academic Press.