Overlapping effects of different members of the FGF family on lens fiber differentiation in transgenic mice.
Fibroblast growth factors (FGFs), such as FGF-1, have been shown to induce differentiation of lens epithelial cells both in tissue culture and in transgenic mice. In the present study, using the alpha A-crystallin promoter, we generated transgenic mice that express different FGFs (FGF-4, FGF-7, FGF-8, FGF-9) specifically in the lens. All four FGFs induced changes in ocular development. Microphthalmic eyes were evident in transgenic mice expressing FGF-8, FGF-9 and some lines expressing FGF-4. A developmental study of the microphthalmic eyes revealed that, by embryonic day 15, expression of these FGFs induced lens epithelial cells to undergo premature fiber differentiation. In less severely affected lines expressing FGF-4 or FGF-7, the lens epithelial cells exhibited a premature exit from the cell cycle and underwent a fiber differentiation response later in development, leading to cataract formation. The responsiveness of lens cells to different FGFs indicates that these proteins stimulate the same or overlapping downstream signalling pathway(s). These overlapping effects of different FGFs on a common cell type indicate that the normal developmental roles for these genes are determined by the temporal and spatial regulation of their expression patterns. The fact that any of these FGFs can induce ocular defects and loss of lens transparency implies that it is essential for the normal eye to maintain very specific spatial control over FGF expression in order to prevent cataract induction.
Department of Cell Biology, Baylor College of Medicine, One Baylor Plaza, Houston, Texas, TX 77030, USA.
F J
FJ
Lovicu
P A
PA
Overbeek
D000818:Animals; D001483:Base Sequence; D002386:Cataract / Q000196:embryology / Q000209:etiology / Q000235:genetics; D002454:Cell Differentiation; D017931:DNA Primers / Q000235:genetics; D004847:Epithelial Cells / Q000166:cytology; D005260:Female; D051526:Fibroblast Growth Factor 10; D051519:Fibroblast Growth Factor 4; D051523:Fibroblast Growth Factor 7; D051524:Fibroblast Growth Factor 8; D051525:Fibroblast Growth Factor 9; D005346:Fibroblast Growth Factors / Q000235:genetics / Q000502:physiology*; D018507:Gene Expression Regulation, Developmental; D005865:Gestational Age; D006133:Growth Substances / Q000235:genetics / Q000502:physiology; D017403:In Situ Hybridization; D007908:Lens, Crystalline / Q000166:cytology / Q000196:embryology* / Q000378:metabolism; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D008850:Microphthalmos / Q000196:embryology / Q000209:etiology / Q000235:genetics; D016133:Polymerase Chain Reaction; D011247:Pregnancy; D011518:Proto-Oncogene Proteins / Q000235:genetics / Q000502:physiology
D017931:DNA Primers; C496446:Fgf4 protein, mouse; C496454:Fgf7 protein, mouse; C496457:Fgf8 protein, mouse; C496460:Fgf9 protein, mouse; D051526:Fibroblast Growth Factor 10; D051519:Fibroblast Growth Factor 4; D051525:Fibroblast Growth Factor 9; D006133:Growth Substances; D011518:Proto-Oncogene Proteins; D051523:Fibroblast Growth Factor 7; D051524:Fibroblast Growth Factor 8; D005346:Fibroblast Growth Factors