Overexpression of FGF-2 modulates fiber cell differentiation and survival in the mouse lens.
During mammalian embryogenesis, the ocular lens forms through a temporally and spatially regulated pattern of differentiation which is thought to be coordinated at least in part by the FGF-1 and FGF-2 members of the fibroblast growth factor (FGF) family. Previous transgenic experiments in which FGF-1 or dominant negative FGF receptors were overexpressed in the lens indicated that FGF-1 could induce differentiation while differentiated lens cells rely upon FGF signaling for their survival. In this study, we asked if the 17.5 kDa FGF-2 protein was capable of inducing differentiation of lens cells in transgenic mice. Unexpectedly, differentiation was inhibited by lens-specific expression of a transgene encoding a secreted form of the 17.5 kDa bovine FGF-2 protein under the transcriptional control of the murine alphaA-crystallin promoter (alphaAIgFGF-2 transgenic mice). To address the possibility that FGF-2 functions as a modulator of fiber cell survival, alphaAIgFGF-2 transgenic mice were crossed to transgenic mice exhibiting extensive apoptosis in the lens due to the functional inactivation of the retinoblastoma protein (alphaAE7 transgenic mice). The level of apoptosis in the lenses of double transgenic mice was substantially reduced as compared to the level in lenses from alphaAE7 only mice. These studies indicate that FGF-2 can act as a modulator of the later stages of differentiation including fiber cell survival. Additionally, they imply that control of lens development by FGFs is a complex process in which FGF-1 and FGF-2 play distinct roles.
Stolen
C M
CM
Department of Anatomy, University of Wisconsin Medical School, Madison 53706, USA.
Jackson
M W
MW
Griep
A E
AE
D000818:Animals; D002417:Cattle; D002454:Cell Differentiation / Q000235:genetics; D002470:Cell Survival / Q000235:genetics; D016222:Fibroblast Growth Factor 2 / Q000235:genetics*; D018507:Gene Expression Regulation, Developmental; D018014:Gene Transfer Techniques; D007908:Lens, Crystalline / Q000166:cytology* / Q000196:embryology / Q000502:physiology*; D051379:Mice; D008822:Mice, Transgenic
D016222:Fibroblast Growth Factor 2