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Originally published as MBC in Press, 10.1091/mbc.E08-02-0124 on April 9, 2008

Vol. 19, Issue 6, 2631-2641, June 2008

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Cross-Talk between Fibroblast Growth Factor and Bone Morphogenetic Proteins Regulates Gap Junction-mediated Intercellular Communication in Lens Cells

Bruce A. Boswell*, Pamela J. Lein{dagger}, and Linda S. Musil*

*Department of Biochemistry and Molecular Biology and {dagger}Center for Research on Occupational and Environmental Toxicology, Oregon Health & Science University, Portland, OR 97239

Submitted February 6, 2008; Revised March 19, 2008; Accepted April 2, 2008
Monitoring Editor: Asma Nusrat

Homeostasis in the lens is dependent on an extensive network of cell-to-cell gap junctional channels. Gap junction-mediated intercellular coupling (GJIC) is higher in the equatorial region of the lens than at either pole, an asymmetry believed essential for lens transparency. Primary cultures of embryonic chick lens epithelial cells up-regulate GJIC in response to purified fibroblast growth factor (FGF)1/2 or to medium conditioned by vitreous bodies, the major reservoir of factors (including FGF) for the lens equator. We show that purified bone morphogenetic protein (BMP)2, -4, and -7 also up-regulate GJIC in these cultures. BMP2, -4, or both are present in vitreous body conditioned medium, and BMP4 and -7 are endogenously expressed by lens cells. Remarkably, lens-derived BMP signaling is required for up-regulation of GJIC by purified FGF, and sufficient for up-regulation by vitreous humor. This is the first demonstration of an obligatory interaction between FGF and BMPs in postplacode lens cells, and of a role for FGF/BMP cross-talk in regulating GJIC in any cell type. Our results support a model in which the angular gradient in GJIC in the lens, and thus proper lens function, is dependent on signaling between the FGF and BMP pathways.

This was published online ahead of print in MBC in Press (http://www.molbiolcell.org/cgi/doi/10.1091/mbc.E08-02-0124) on April 9, 2008.

Address correspondence to: Linda S. Musil (musill{at}ohsu.edu)

Abbreviations used: DCDML, dissociated cell–derived monolayer culture; ERK, extracellular signal–regulated kinase; GJIC, gap junction–mediated intercellular coupling; VBCM, vitreous body conditioned medium.




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