Cross-talk between fibroblast growth factor and bone morphogenetic proteins regulates gap junction-mediated intercellular communication in lens cells.
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.
Boswell
Bruce A
BA
Department of Biochemistry and Molecular Biology, Oregon Health & Science University, Portland, OR 97239, USA.
Lein
Pamela J
PJ
Musil
Linda S
LS
D000818:Animals; D055396:Bone Morphogenetic Protein 2 / Q000494:pharmacology*; D055415:Bone Morphogenetic Protein 4 / Q000494:pharmacology*; D055419:Bone Morphogenetic Protein 7 / Q000378:metabolism; D002352:Carrier Proteins / Q000378:metabolism; D002450:Cell Communication / Q000187:drug effects*; D017077:Culture Media, Conditioned; D004789:Enzyme Activation / Q000187:drug effects; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D016222:Fibroblast Growth Factor 2 / Q000494:pharmacology*; D017629:Gap Junctions / Q000187:drug effects* / Q000378:metabolism*; D006801:Humans; D007908:Lens, Crystalline / Q000166:cytology* / Q000201:enzymology; D015398:Signal Transduction / Q000187:drug effects; D015854:Up-Regulation / Q000187:drug effects; D014822:Vitreous Body / Q000201:enzymology; D000099176:Noggin Protein
D055396:Bone Morphogenetic Protein 2; D055415:Bone Morphogenetic Protein 4; D055419:Bone Morphogenetic Protein 7; D002352:Carrier Proteins; D017077:Culture Media, Conditioned; D048049:Extracellular Signal-Regulated MAP Kinases; D016222:Fibroblast Growth Factor 2; D000099176:Noggin Protein