June 2015
Volume 56, Issue 7
Free
ARVO Annual Meeting Abstract  |   June 2015
Fibroblast Growth Factor Receptor 2 (FGFR2) is Required for Corneal Epithelial Cell Proliferation and Differentiation During Embryonic Eye Development
Author Affiliations & Notes
  • Lixing W Reneker
    Ophthalmology, University of Missouri-Columbia, Columbia, MO
  • Jinglin Zhang
    Zhongshan Ophthalmic Center, State Key Laboratory of Ophthalmology, Guangzhou, China
  • dinesh upadhya
    Ophthalmology, University of Missouri-Columbia, Columbia, MO
  • Lin Lu
    Zhongshan Ophthalmic Center, State Key Laboratory of Ophthalmology, Guangzhou, China
  • Footnotes
    Commercial Relationships Lixing Reneker, None; Jinglin Zhang, None; dinesh upadhya, None; Lin Lu, None
  • Footnotes
    Support None
Investigative Ophthalmology & Visual Science June 2015, Vol.56, 5830. doi:
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      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.

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      © ARVO (1962-2015); The Authors (2016-present)

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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.

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