FIBER DIFFERENTIATION AND POLARITY IN THE MAMMALIAN LENS - A KEY ROLEFOR FGF

The mammalian lens exhibits characteristic antero-posterior patterns o f cellular proliferation, movement and fibre differentiation. Based on our findings that fibroblast growth factor (FGF) induces proliferatio n, migration and differentiation in a similar sequence as its concentr ation is increased, we put forward the hypothesis that normal lens mor phology with its antero-posterior patterns of cellular behaviour is de termined by an antero-posterior gradient of FGF stimulation. Support f or this hypothesis is now available from a wide range of studies, incl uding: studies of the distribution of FGF and its mRNA in the eye and FGF activity in ocular media and the lens; studies of FGF receptor and mRNA expression in the lens; and studies of transgenic mice with alte red patterns of FGF expression, which exhibit abnormal patterns of dif ferentiation. Furthermore, gross abnormalities in lenses of transgenic mice that express a dominant-negative FGF receptor provide strong evi dence that FGF is involved in the differentiation and maintenance of l ens fibre cells in situ. Other biological molecules that may modulate the effects of FGF on lens cells in the normal lens have also been inv estigated, including capsule heparan sulphate proteoglycans, insulin a nd IGF and TGF beta. In addition, a potential role for TGF beta in the aetiology of cataracts has been identified. It is now clear that ther e are many possible mechanisms by which the behaviour of lens cells ma y be regulated to ensure normal growth and maintenance of polarity in the mammalian lens. Although several growth factors are probably invol ved, a key role for FGF has emerged. (C) 1997 Elsevier Science Ltd.