A novel role for FGF and extracellular signal-regulated kinase in gap junction-mediated intercellular communication in the lens

Gap junction-mediated intercellular coupling is higher in the equatorial re gion of the lens than at either pole, a property believed to be essential f or lens transparency. We show that fibroblast growth factor (FGF) upregulat es gap junctional intercellular dye transfer in primary cultures of embryon ic chick lens cells without detectably increasing either gap junction prote in (connexin) synthesis or assembly. Insulin and insulin-like growth factor 1, as potent as FGF in inducing lens cell differentiation, had no effect o n gap junctions. FGF induced sustained activation of extracellular signal-r egulated kinase (ERK) in lens cells, an event necessary and sufficient to i ncrease gap junctional coupling. We also identify vitreous humor as an in v ivo source of an FGF-like intercellular communication-promoting activity an d show that FGF-induced ERK activation in the intact lens is higher in the equatorial region than in polar and core fibers. These findings support a m odel in which regional differences in FGF signaling through the ERK pathway lead to the asymmetry in gap junctional coupling required for proper lens function. Our results also identity upregulation of intercellular communica tion as a new function for sustained ERK activation and change the current paradigm that ERKs only negatively regulate gap junction channel activity.