Disruption of lens fiber cell differentiation and survival at multiple stages by region-specific expression of truncated FGF receptors.

To determine if fibroblast growth factor signaling mechanisms are required for terminal differentiation and survival of lens fiber cells, we evaluated the effects of expressing truncated fibroblast growth factor receptors (tFGFRs) in different regions of the developing lens. Two sets of transgenic mice were generated, one expressing tFGFRs from the alphaA-crystallin promoter (alphaA-tFGFR), which expresses linked genes in fiber cells throughout their differentiation program, and the other expressing tFGFRs from the gammaF-crystallin promoter (gammaF-tFGFR), which expresses linked genes beginning later during their differentiation. Histological and TUNEL analyses of lenses from alphaA-tFGFR and gammaF-tFGFR transgenic mice suggest that FGFR signaling is required for both early and late fiber cell differentiation and/or survival of the terminally differentiated cells. Additionally, multilayering and increased levels of apoptosis were observed in the anterior epithelium after the onset of fiber cell abnormalities. In situ hybridizations suggest that tFGFR transgenes were not expressed at significant levels in the epithelium. Combined with TUNEL and X-gal analyses on the lens epithelium from gammaF-tFGFR/Rosabeta-geo26 and nontransgenic/Rosabeta-geo26 chimeras, these results suggest that the organization and survival of the epithelial cells depend on appropriate structure and/or function of the differentiated fiber cells. Copyright 2000 Academic Press.