FGF-1 AND FGF-7 INDUCE DISTINCT PATTERNS OF GROWTH AND DIFFERENTIATION IN EMBRYONIC LUNG EPITHELIUM

Fibroblast growth factors (FGFs) and receptors (FGFRs) are expressed i n the developing lung and appear to be major regulators of lung growth and differentiation. By using mesenchyme-free lung epithelial culture s we show that FGF-1 (aFGF) and FGF-7 (KGF) produce different effects in the developing lung, FGF-1 stimulates epithelial proliferation that results in bud formation (branching), while FGF-7 promotes epithelial proliferation that leads to formation of cyst-like structures, In add ition, FGF-7 stimulates epithelial differentiation, stimulating expres sion of SP-A and SP-B mRNA throughout the explant, and inducing format ion of focal areas of highly differentiated cells, The FGF-1 effects o n differentiation are limited to induction of surfactant protein SP-B mRNA at the tips of the explant, The FGF-induced patterns of growth ap pear to correlate with the distribution of epithelial FGFRs mRNAs; FGF R-2 IIIb (KGFR) is diffusely expressed in the day 11 lung epithelium, while FGFR-4 appears in distal but not in proximal sites, We propose t hat cyst-like structures may result from FGF-7 binding to the uniforml y distributed FGFR-2-IIIb, Lung bud formation may be regulated by FGF- 1 and/or other ligands binding to FGFR-2 and a distally located FGFR, such as FGFR-4, leading to an increasing binding and activation of FGF Rs at the tips of the explant, Thus, in the embryonic lung epithelium, growth effects of FGFs appear to be dependent on location of FGFRs, w hile effects on differentiation are ligand-dependent. (C) 1997 Wiley-L iss, Inc.