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F.J. Lovicu, J. Boros, Q. Wang, L.W. Reneker, J.W. McAvoy; A Role for Growth Factor Antagonists, Sprouty and Sef, in Regulating Lens Development . Invest. Ophthalmol. Vis. Sci. 2005;46(13):2407.
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© ARVO (1962-2015); The Authors (2016-present)
Purpose: Growth factors play important roles in regulating lens epithelial cell proliferation and fiber differentiation. Recent studies have identified Sef and Sprouty (Spry) as antagonists of growth factor signaling, with Sef more specific for FGF signaling. As growth factors such as FGFs play an important role in lens biology, we initially set out to examine the expression of Sef and Spry in the lens. In addition, we employed in vitro and transgenic mouse strategies to identify the role these antagonists play in regulating lens cell behaviour. Methods: RT–PCR, in situ hybridisation and immunofluorescence were used to determine the expression patterns of Spry and Sef during lens morphogenesis and lens growth. For our functional studies, we overexpressed Sprouty or Sef specifically in cells of transfected lens explants and/or lenses of transgenic mice. Results: RT–PCR on postnatal rodent lenses demonstrated the presence of Sef, Spry1 and Spry2 in the lens epithelium and fiber cells. This was confirmed using in situ hybridisation, with stronger labeling in the lens epithelium compared to fibers, in particular for Sef. During lens morphogenesis, Spry appears to be ubiquitously expressed early in lens morphogenesis, however, with further lens development, labeling for both Spry and Sef becomes more restricted to the lens epithelium. FGF–induced fiber differentiation is blocked in lens cells overexpressing Sprouty and transgenic mice overexpressing Sef specially in the lens, demonstrate impaired lens, and consequently eye development. Conclusions: The expression patterns of Sef and Spry in the lens are consistent with a role for these molecules as regulators of growth factor signaling, potentially contributing to the establishment and maintenance of the lens epithelium. Any disruption to the normal expression of these genes, such as overexpression in the present study, may alter the responsiveness of lens cells to growth factors such as FGF, leading to aberrant cell proliferation and/or fiber differentiation. In conclusion, tight regulation of growth factors in the eye is essential for maintenance of the distinctive lens architecture, and it may be specific growth factor antagonists, such as Sef and Spry, that contribute to this regulation.
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