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Z. Yu, X. Xu, Sr., B. Andersen; Co-Factors of Lim Domains (clims/ldb/nli) Control Corneal Epithelial Cell Fate. Invest. Ophthalmol. Vis. Sci. 2008;49(13):4309.
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The corneal epithelium is maintained by corneal epithelial stem cells that differentiate into a stratified and nonkeratinized epithelium, which is essential for a transparent cornea. We have previously shown that corneal epithelial expression of a dominant-negative Co-factor of LIM domains (DN-Clim) leads to transdifferentiation of corneal epithelial cells to epidermis-like epithelium and blindness. Our purpose is to elucidate the molecular mechanism underlying corneal cell fate maintenance by Clims.
We established Keratin 14-DN-Clim transgenic mice, and used immunostaining to investigate key signaling pathways that are involved in corneal epithelial cell fate.
We found that interfering with binding of Clim co-factors to transcription factors causes corneal epithelial cell switch to epidermis like cells. Furthermore, Pax 6, an important transcriptional factor for corneal cell fate maintenance, is strikingly downregulated in the highly hyperplastic corneal epithelium. We also found that beta-catenin is upregulated in the corneas of keratin14-DN-Clims transgenic mice.
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