Fibroblast growth factor receptor 1 (Fgfr1) is not essential for lens fiber differentiation in mice.
OBJECTIVE
The developing lens expresses at least three different FGF receptor genes (Fgfr1, Fgfr2, Fgfr3). Furthermore, FGFs have been shown to induce lens epithelial cells to differentiate into fiber cells both in vitro and in vivo. While the loss of Fgfr2 alone does not prevent fiber differentiation and the loss of Fgfr3 alone does not appear to affect lens development, the independent role of Fgfr1 in lens development has not been reported. These experiments were conducted to determine if Fgfr1 plays an independent, essential role in lens development.


METHODS
To address this question, we took two complementary approaches. First, we employed the aphakia (ak) lens complementation system to show that Fgfr1 deficient embryonic stem (ES) cells were able to form a normal embryonic lens that maintains a normal pattern of crystallin gene expression. Second, we employed the Cre-loxP system to achieve lens-specific inactivation of Fgfr1.


RESULTS
Fgfr1 null embryonic stem cells were able to rescue normal embryonic lens development in chimeric combination with aphakia mutant embryos. In addition, conditional deletion of Fgfr1 does not compromise lens development either before or after birth.


CONCLUSIONS
The results of both approaches suggest that lens epithelial cell integrity, cell cycle regulation and lens fiber differentiation are intact in the Fgfr1 deficient lens. Overall, our results demonstrate that Fgfr1 is not cell autonomously essential for lens development and suggests functional redundancy among different FGF receptor genes with respect to lens fiber differentiation.
Zhao
Haotian
H
Center for Human and Molecular Genetics, Columbus Children's Research Institute, Columbus, OH, USA. Haotian.Zhao@stjude.org
Yang
Ying
Y
Partanen
Juha
J
Ciruna
Brian G
BG
Rossant
Janet
J
Robinson
Michael L
ML
D000483:Alleles; D000818:Animals; D000831:Animals, Newborn; D001035:Aphakia / Q000235:genetics; D002678:Chimera; D047108:Embryonic Development / Q000502:physiology; D005455:Fluorescent Antibody Technique; D005838:Genotype; D017403:In Situ Hybridization; D007908:Lens, Crystalline / Q000196:embryology* / Q000254:growth & development* / Q000378:metabolism / Q000473:pathology; D051379:Mice; D008817:Mice, Mutant Strains; D008822:Mice, Transgenic; D009154:Mutation; D051496:Receptor, Fibroblast Growth Factor, Type 1 / Q000235:genetics / Q000378:metabolism*
C496349:Fgfr1 protein, mouse; D051496:Receptor, Fibroblast Growth Factor, Type 1