Purchase this article with an account.
L. W. Reneker; ERK1/2-Signaling Is Required for Epithelial-to-Fiber Differentiation in Lens Development. Invest. Ophthalmol. Vis. Sci. 2008;49(13):1135.
Download citation file:
© ARVO (1962-2015); The Authors (2016-present)
Both ERK1 and ERK2 activity are present in mouse lens during normal development. Our previous studies showed that absence of either ERK1 or ERK2 in mouse lens did not result in any morphological changes in the lens, but deletion of both ERK1/2 led to lens degeneration and microphthalmia. The developmental changes in the ERK1/2-deficient mouse lens were examined in detail in this study.
To delete both ERK1 and ERK2 in the lens, three different types of mice were used: ERK1 null, ERK2-flox conditional mutation mice, and transgenic mice (MLR10) expressing Cre in the lens. Wild type and ERK1/2-deficient lenses were isolated at different developmental stages and analyzed by histology and immunohistochemistry.
The mouse lenses in ERK1-/-, ERK2flox/flox and MLR10 Cre mice looked morphologically identical to the wild type lenses before embryonic day 15.5 (E15.5). After E15.5, the epithelial layer began to extend toward the posterior pole in the ERK1/2-deficient lens. By birth, the mutant lens completely lost its polarity with a monolayer of epithelial cells circling the entire lens. These results indicated that epithelial-to-fiber differentiation was disrupted in the ERK1/2-deficient lens. In addition to failure of fiber differentiation, cell proliferation in the ERK1/2-deficient lens was also severely inhibited by not totally blocked, as shown by the presence of cell proliferation maker, Ki67, in a few lens epithelial cells.
ERK1/2-signaling is required for epithelial-to-fiber differentiation in mouse lens older than E15. ERK1/2-signaling also plays a major role in cell proliferation during lens development. Future studies are focused on identifying the downstream target genes and proteins affected in the ERK1/2-deficient mouse lens.
This PDF is available to Subscribers Only