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Y. Li, J. Piatigorsky; Dicer and microRNAs Are Essential for Development of Lens and Cornea in Mice. Invest. Ophthalmol. Vis. Sci. 2009;50(13):4350.
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Although it is known that microRNAs (miRNAs) play important roles in regulating gene expression in many tissues, little is known of miRNA functions in eye development.
Processing of miRNAs requires the ribonuclease Dicer. We conditionally deleted Dicer in cornea and lens and characterized the phenotype of the conditional knockout mice.
We demonstrated specific reduction in Dicer and miRNA expressions in the developing lens by E12.5. Lens morphogenesis in the mutant mice progressed normally at E12.5 but started to degenerate at E14.5. Increased cell death and reduced cell proliferation were observed as early as E12.5 in lens epithelia. Expressions of key transcription factors for lens development, such as Pax-6 and Prox1, were not affected by conditional deletion of Dicer in the E12.5 lenses but later started to decrease due to lens degeneration. Except for much smaller size, the corneal epithelia in the mutant mice maintained normal morphology and Pax-6 expression even after birth. However, the corneal epithelial cells did not stratify two weeks after birth. Adult 8-week-old mice lacking Dicer in lens and cornea were severely microphthalmic.
These results reveal critical roles for Dicer and miRNAs in the control of cell growth and differentiation during the development of lens and cornea.
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