Purchase this article with an account.
Lixing W Reneker, Jinglin Zhang, dinesh upadhya, Lin Lu; Fibroblast Growth Factor Receptor 2 (FGFR2) is Required for Corneal Epithelial Cell Proliferation and Differentiation During Embryonic Eye Development. Invest. Ophthalmol. Vis. Sci. 2015;56(7 ):5830.
Download citation file:
© ARVO (1962-2015); The Authors (2016-present)
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.
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.
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.
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.
This PDF is available to Subscribers Only