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G.F. Pontoriero, R. Ashery–Padan, T. Williams, J.A. West–Mays; An Essential Role for Cellular Adhesion in AP–2–Induced Lens Vesicle Separation . Invest. Ophthalmol. Vis. Sci. 2006;47(13):2939.
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© ARVO (1962-2015); The Authors (2016-present)
The molecular mechanisms governing lens vesicle separation from the surface ectoderm are not well understood. Changes in cellular adhesion have been hypothesized as being an important aspect of this developmental process. Evidence to support this theory arises from our previous work, in which a lens–specific knockout of AP–2α (Le–AP–2α) in mice, results in a failure of the lens to separate from the surface ectoderm coincident with decreased E–cadherin expression.
To more critically analyze the nature of the altered cell adhesion defect observed in Le–AP–2α animals, we undertook a detailed adhesion molecule expression analysis throughout lens morphogenesis. This included immunofluorescent labelling of ß–catenin, E–cadherin, N–cadherin and P–cadherin in Le–AP–2α lenses and that of wildtype littermates at numerous embryonic stages.
During early embryonic development (E9.5–E10.5), expression of all adhesion molecules analyzed was observed in both the lens placode and lens pit in the Le–AP–2α and wildtype mice. As the lens vesicle pinched away from the surface ectoderm in the wildtype lens, expression of P–cadherin was lost while expression of E–cadherin, N–cadherin and ß–catenin was maintained. In contrast, persistent formation of a lens stalk in the Le–AP–2α mouse (E11.5) was correlated with a lack of expression of E–cadherin within the lens stalk cells, while expression of E–cadherin in the rest of the lens vesicle was detected albeit reduced. As development further progressed (E13.5–P0) in the Le–AP–2α lens, a substantial loss of E–cadherin expression was observed throughout the lens epithelium while the expression of the other adhesion molecules analyzed was normal as compared to wildtype mice.
Cellular adhesion is an essential component of lens development and the creation of the Le–AP–2α mouse has allowed us to more critically analyze its role. While AP–2α has been shown to regulate E–cadherin in other systems, our future work will consist of confirming that E–cadherin is a direct target of AP–2α in the lens through the used of chromatin immunoprecipitation.
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