CONSERVATION OF FIBROBLAST GROWTH-FACTOR FUNCTION IN LENS REGENERATION

In urodele amphibians, lens induction during development and regenerat ion occurs through different pathways. During development, the lens is induced from the mutual interaction of the ectoderm and the optic ves icle, whereas after lentectomy the lens is regenerated through the tra nsdifferentiation of the iris-pigmented epithelial cells. Given the kn own role of fibroblast growth factors (FGFs) during lens development, we examined whether or not the expression and the effects of exogenous FGF during urodele lens regeneration were conserved. In this paper, w e describe expression of FGF-1 and its receptors, FGFR-2 (KGFR and bek variants) and FGFR-3, in newts during lens regeneration. Expression o f these genes was readily observed in the dedifferentiating pigmented epithelial cells, and the levels of expression were high in the lens e pithelium and the differentiating fibers and lower in the retina. Thes e patterns of expression implied involvement of FGFs in lens regenerat ion. To further elucidate this function, we examined the effects of ex ogenous FGF-1 and FGF-4 during lens regeneration. FGF-I or FGF-4 treat ment in lentectomized eyes resulted in the induction of abnormalities reminiscent to the ones induced during lens development in transgenic mice. Effects included transformation of epithelial cells to fiber cel ls, double lens regeneration, and lenses with abnormal polarity. These results establish that FGF molecules are key factors in fiber differe ntiation, polarity, and morphogenesis of the lens during regeneration even though the regenerating lens is induced by a different mechanism than in lens development. In this sense, FGF function in lens regenera tion and development should be regarded as conserved. Such conservatio n should help elucidate the mechanisms of lens regeneration in urodele s and its absence in higher vertebrates.