FGF RECEPTOR-1 (FLG) EXPRESSION IS CORRELATED WITH FIBER DIFFERENTIATION DURING RAT LENS MORPHOGENESIS AND GROWTH

Our previous studies indicate an important role for fibroblast growth factor (FGF) in lens development. Here we study the expression of the flg variant of FGF receptor 1 (FGFR1) during lens development by immun ohistochemistry and in situ hybridisation. FGFR1 was expressed through out lens development. Prominent FGFR1 immunoreactivity was associated with cell nuclei, particularly in differentiating lens fibres, suggest ing internalisation and nuclear translocation of the receptor. FGFR1 i mmunoreactivity was also associated with basolateral membranes of cell s in the equatorial region and at lens sutures. FGFR1 mRNA was only we akly expressed during early lens morphogenesis but expression increase d with the onset of lens fibre differentiation. Once the lens acquired its distinct polarity, an anteroposterior gradient in both protein re activity and mRNA signal was evident. Anteriorly, central epithelial c ells showed weak expression for FGFR1, whereas more posteriorly, in th e germinative and transitional zones of the lens where cells maximally proliferate and undergo early stages of fibre differentiation, respec tively, expression was significantly stronger. The anteroposterior gra dient of increased expression of FGFR1 in the lens coincides with the previously documented anteroposterior gradient of FGF stimulation. In lens epithelial explants, FGF stimulation was found to upregulate FGFR 1 expression. Such upregulation may be an important mechanism for gene rating a high level of FGF stimulation and ensuring a fibre differenti ation response. In postnatal rat lenses, there was a significant age-r elated decline in FGFR1 expression; this correlates with the reduced r ate of lens fibre differentiation with age. Overall, these studies sup port the hypothesis that FGF and FGFR1 are important for regulation of lens fibre differentiation throughout lens development. (C) 1996 Wile y-Liss, Inc.