Fibroblast growth factor interactions in the developing lung

Cellular activities that lead to organogenesis are mediated by epithelial-m esenchymal interactions, which ultimately result from local activation of c omplex gene networks. Fibroblast growth factor (FGF) signaling is an essent ial component of the regulatory network present in the embryonic lung, cont rolling proliferation, differentiation and pattern formation. However, litt le is known about how FGFs interact with other signaling molecules in these processes. By using cell and organ culture systems, we provide evidence th at FGFs, Sonic hedgehog (Shh), bone morphogenetic protein 4 (BMP-4), and TG F beta-1 form a regulatory circuit that is likely relevant for lung develop ment in vivo. Our data show that FGF-10 and FGF-7, important for patterning and growth of the lung bud, are differentially regulated by FGF-1, -2 and Shh. In addition, we show that FGFs regulate expression of Shh, BMP-4 and o ther FGF family members. Our data support a model in which Shh, TGF beta-1 and BMP-4 counteract the bud promoting effects of FGF-10, and where FGF lev els are maintained throughout lung development by other FGFs and Shh. (C) 1 999 Elsevier Science Ireland Ltd. All rights reserved.