Abstract
Purpose:
During eye development, the lens and corneal epithelium are derived from the same surface ectodermal tissue. FGFR-signaling is known to be required for lens development. In study, the role of FGFR2 in corneal development was investigated.
Methods:
Fgfr2 conditional knockout mice was created by crossing the Fgfr2flox mice with Le-Cre transgenic mice in which Cre is activated at lens induction stage by Pax6 P0 promoter. The cornea in Le-Cre;Fgfr2flox/flox mice (referred as Fgfr2CKO) was analyzed to assess changes in cell proliferation, differentiation and survival.
Results:
We found that Fgfr2CKO cornea was much thinner in epithelial and stromal layer when compared to WT cornea. At embryonic day 12.5-13.5 (E12.5-13.5) shortly after the lens vesicle detaches from the overlying surface ectoderm, cell proliferation (judged by labeling indices of Ki-67, BrdU and phospho-histone H3) was significantly reduced in corneal epithelium in Fgfr2CKO mice. At later stage, cell differentiation markers for corneal epithelium and underlying stromal mesenchyme, keratin-12 and keratocan respectively, were not expressed in Fgfr2CKO cornea. Furthermore, Pax6, a transcription factor essential for eye development, was not present in the Fgfr2CKO mutant corneal epithelial at E16.5 but was expressed normally at E12.5, suggesting that FGFR2-signaling is required for maintaining Pax6 expression in this tissue. Interestingly, the role of FGFR2 in corneal epithelial development is independent of ERK1/2-signaling. In contrast to the lens, FGFR2 is not required for cell survival in cornea.
Conclusions:
This study demonstrated for the first time that FGFR2 plays an essential role in controlling cell proliferation and differentiation, and maintaining Pax6 levels in corneal epithelium via ERK-independent pathways during embryonic eye development.