OVERLAPPING EFFECTS OF DIFFERENT MEMBERS OF THE FGF FAMILY ON LENS FIBER DIFFERENTIATION IN TRANSGENIC MICE

Fibroblast growth factors (FGFs), such as FGF-1, have been shown to in duce differentiation of lens epithelial cells both in tissue culture a nd in transgenic mice. In the present study, using the alpha A-crystal lin promoter, we generated transgenic mice that express different FGFs (FGF-4, FGF-7, FGF-8, FGF-9) specifically in the lens, All four FGFs induced changes in ocular development. Microphthalmic eyes were eviden t in transgenic mice expressing FGF-8, FGF-9 and some lines expressing FGF-4, A developmental study of the microphthalmic eyes revealed that , by embryonic day 15, expression of these FGFs induced lens epithelia l cells to undergo premature fiber differentiation. In less severely a ffected lines expressing FGF-4 or FGF-7, the lens epithelial cells exh ibited a premature exit from the cell cycle and underwent a fiber diff erentiation response later in development, leading to cataract formati on. The responsiveness of lens cells to different FGFs indicates that these proteins stimulate the same or overlapping downstream signalling pathway(s). These overlapping effects of different FGFs on a common c ell type indicate that the normal developmental roles for these genes are determined by the temporal and spatial regulation of their express ion patterns. The fact that any of these FGFs can induce ocular defect s and loss of lens transparency implies that it is essential for the n ormal eye to maintain very specific spatial control over FGF expressio n in order to prevent cataract induction.