Fibre differentiation and polarity in the mammalian lens: a key role for FGF

Abstract

Abstract The mammalian lens exhibits characteristic antero-posterior patterns of cellular proliferation, movement and fibre differentiation. Based on our findings that fibroblast growth factor (FGF) induces proliferation, migration and differentiation in a similar sequence as its concentration is increased, we put forward the hypothesis that normal lens morphology with its antero-posterior patterns of cellular behaviour is determined by an antero-posterior gradient of FGF stimulation. Support for this hypothesis is now available from a wide range of studies, including: 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 altered patterns of FGF expression, which exhibit abnormal patterns of differentiation. Furthermore, gross abnormalities in lenses of transgenic mice that express a dominant-negative FGF receptor provide strong evidence that FGF is involved in the differentiation and maintenance of lens fibre cells in situ. Other biological molecules that may modulate the effects of FGF on lens cells in the normal lens have also been investigated, including capsule heparan sulphate proteoglycans, insulin and IGF and TGFβ. In addition, a potential role for TGFβ in the aetiology of cataracts has been identified. It is now clear that there are many possible mechanisms by which the behaviour of lens cells may be regulated to ensure normal growth and maintenance of polarity in the mammalian lens. Although several growth factors are probably involved, a key role for FGF has emerged.