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L. Musil, B. Boswell; Cross-Talk Between FGF and BMP Signaling in Lens Cell Differentiation and Function. Invest. Ophthalmol. Vis. Sci. 2007;48(13):1118. doi: https://doi.org/.
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© ARVO (1962-2015); The Authors (2016-present)
Primary cultures of embryonic chick lens epithelial cells (chDCDML) upregulate gap junction-mediated intercellular coupling (GJIC) in response to either recombinant FGF (-1 or 2) or to medium conditioned by intact vitreous bodies, the major reservoir of diffusible factors (including FGF) for the lens equator in vivo (Le and Musil 2001 J. Cell Biol.). FGF and vitreous body conditioned medium also enhance the expression of the fiber differentiation markers delta crystallin and CP49 (Le and Musil 2001 Dev. Biol.). More recently, we have reported that delta crystallin and CP49 synthesis, as well as GJIC, are also upregulated in our lens cultures by recombinant BMP -2, 4, or 7, and that vitreous contains diffusible BMP bioactivity. Remarkably, the ability of recombinant FGF to enhance GJIC and fiber marker expression is dependent on the activity of noggin-sensitive BMPs endogenously produced by the lens cells (ICER 2006). Lens epithelial cells have been reported to synthesize FGF1 and FGF2. In some extralenticular tissues, FGF signaling promotes the ability of the cells to respond to exogenous BMP. The goal of this study was to investigate whether this is also the case for lens cultures.
chDCDMLs were cultured with recombinant BMP 2,4, or 7 with or without SU5402, an inhibitor of FGF receptor-mediated signaling. GJIC was measured using the scrape-loading/dye transfer assay, and fiber marker expression by either metabolic radiolabeling (for delta crystallin) or quantitative Western blotting (CP49).
As expected, the ability of FGF to upregulate ERK and p38 activation, GJIC, and fiber marker expression in cultured lens cells was blocked by SU5402. In contrast, SU5402 had little effect on signaling by IGF-1. Although all effects induced by exogenous BMP were potently blocked by specific inhibitors of BMP signaling (noggin and function-blocking anti-BMP antibodies), none of these process were inhibited by SU5402.
Although upregulation of GJIC and fiber marker expression in response to exogenous FGF requires endogenous BMP activity, the ability of higher concentrations of exogenous BMP to induce the same processes is independent of lens-derived FGF signaling. The obligatory interaction between BMP and FGF in regulating GJIC and fiber marker expression in chDCDMLs is therefore not due to a requirement for FGF signaling to maintain cells in a BMP-responsive state. Furthermore, endogenous FGF does not act as an obligatory survival factor in this system.
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