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 (tF GERs) in different regions of the developing lens. Two sets of transgenic m ice were generated, one expressing tFGFRs from the alpha A-crystallin promo ter (alpha A-tFGFR), which expresses linked genes in fiber cells throughout their differentiation program, and the other expressing tFGFRs from the ga mma F-crystallin promoter (gamma F-tFGFR), which expresses linked genes beg inning later during their differentiation. Histological and TUNEL analyses of lenses from alpha A-tFGFR and gamma F-tFGFR transgenic mice suggest that FGFR signaling is required for both early and late fiber cell differentiat ion and/or survival of the terminally differentiated cells. Additionally, m ultilayering and increased levels of apoptosis were observed in the anterio r epithelium after the onset of fiber cell abnormalities. In situ hybridiza tions suggest that tFGFR transgenes were not expressed at significant level s in the epithelium. Combined with TUNEL and X-gal analyses on the lens epi thelium from gamma F-tFGFR/Rosa beta-geo26 and nontransgenic/Rosa beta-geo2 6 chimeras, these results suggest that the organization and survival of the epithelial cells depend on appropriate structure and/or function of the di fferentiated fiber cells. (C) 2000 Academic Press.