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Mark J. Murphy, Bozena K. Polok, Daniel F. Schorderet, Michael L. Cleary; Essential Role for Pbx1 in Corneal Morphogenesis. Invest. Ophthalmol. Vis. Sci. 2010;51(2):795-803. doi: 10.1167/iovs.08-3327.
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The Pbx TALE (three-amino-acid loop extension) homeodomain proteins interact with class 1 Hox proteins, which are master regulators of cell fate decisions. This study was performed to elucidate the role of the Pbx1 TALE protein in the corneal epithelium of mice.
Pbx1f/f mice were crossed with mice containing Cre recombinase under the control of the K14 promoter. Subsequently, the eyes of these mice were dissected and prepared for histologic or molecular analysis.
Tissue-specific deletion of Pbx1 in the corneal epithelium of mice resulted in corneal dystrophy and clouding that was apparent in newborns and progressively worsened with age. Thickening of the cornea epithelium was accompanied by stromal infiltration with atypical basal cells, severe disorganization of stromal collagen matrix, and loss of corneal barrier function. High epithelial cell turnover was associated with perturbed expression of developmental regulators and aberrant differentiation, suggesting an important function for Pbx1 in determining corneal identity.
These studies establish an essential role of the Pbx1 proto-oncogene in corneal morphogenesis.
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