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R. Kucerova, J. Lachova, Z. Kozmik; Role of Polycomb Gene Ezh2 in Lens Fibers Differentiation. Invest. Ophthalmol. Vis. Sci. 2010;51(13):2356.
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© ARVO (1962-2015); The Authors (2016-present)
To investigate the role of Ezh2 in early lens development and during lens fibers differentiation.
Cre/loxP system was employed to overcome embryonic lethality of Ezh2 KO mice. Lens-Cre mice were crossed with Ezh2fl/fl mice to achieve conditional inactvation of Ezh2 gene in lens as well as surface ectoderm. Histology and immunohistochemistry was employed to characterise the phenotype of Ezh2 mutant mice.
Epigenetic modification has been shown to play a fundamental role in tissue development and maintenance. Increasing evidence revealed the importance of polycomb group proteins in processes of tissue differentiation but it remains unclear how the polycomb repressor complexes (PRCs) control the fate of progenitor cells in developing tissue. We show that Ezh2 (the essential component of PRC2) is strongly expressed in lens epithelial cells and diminishes with differentiation into the lens fibers. Our data suggest that Ezh2 is not required for the early steps of lens induction but it is essential during fiber cell differentiation. More specifically, Lens-Cre mediated KO of Ezh2 leads to a complete inhibition of histone H3 K27 trimethylation mark in lens tissue and premature cell cycle exit as revealed by BrdU labeling as well as p27 staining. Such an increase in the developmental rate of differentiation causes the decrease in progenitor cell pool which corresponds to a smaller lens already detected at stage E12.5 of mouse development. Subsequently, the lens epithelium disappears at stage E16.5 leading to a complete lens deterioration by postnatal day 1. Abnormal lens fiber cell differentiation is confirmed by immunohistochemical visualization using various lens markers.
We suggest that histone H3 K27 trimethylation mediated by Ezh2 is required for maintaining the proliferative potential of lens epithelial cells and control the correct rate of lens fiber differentiation.
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