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Christine L. Kerr, Michael L. Robinson, Judith A. West-Mays; AP-2α Required for Maintenance of Lens Cell Adhesion Subsequent to Lens Vesicle Separation. Invest. Ophthalmol. Vis. Sci. 2012;53(14):4146.
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The Activating Protein-2 (AP-2) transcription factors are a family of genes important in the development of a myriad of tissues, including the eye. Our lab has previously shown a requirement for AP-2α in early lens development, and its conditional deletion from the lens placode in Le-AP-2α mutants resulted in failed lens separation. We have also demonstrated a role for AP-2α in lens epithelial cell maintenance through ectopic AP-2α expression in lens fiber cells. In the current study, we investigated the role of AP-2α in later stages of lens development subsequent to lens vesicle separation, using a loss of function approach.
The MLR10 cre mouse line (in which cre-recombinase is expressed in the lens at E10.5 and later), was utilized to create a line of mice with AP-2α conditionally deleted from the lens epithelium following its separation from the overlying ectoderm. Eyes and lenses were examined at embryonic and postnatal stages using histological and immunofluorescent techniques.
Previous analyses of the MLR10/AP-2α mutants revealed a vacuolated lens with fragile cell-cell contact at the epithelial-fiber cell border beginning at postnatal day (P) 4. In the current study, we show that immunostaining with ZO-1, N-cadherin and β-catenin reveal cell adhesion defects in our mutants at P4. The tight junction protein ZO-1, normally expressed tightly at the apical aspect of the lens epithelium, showed disorganized expression in the mutant. At P4, its expression appeared discontinuous with an expanded expression domain in the apical membrane of the lens epithelium and this continued at P14. N-cadherin was expressed abnormally in the mutant lens beginning at P4, with expression observed to extend beyond the transition zone and continuing throughout the entire posterior fiber cell region. Expression was also observed at the epithelial-fiber cell border in the mutants. Similarly, β-catenin was observed throughout the fiber cell region of the mutant lens beginning at this stage. Interestingly, each of the cell adhesion molecules examined showed expression directly around the vacuoles present in the mutant lenses during postnatal development.
Our studies reveal a requirement for AP-2α in maintenance of normal lens cell adhesion during development subsequent to lens vesicle separation. The loss of AP-2α appears to result in an altered pattern of expression of cell adhesion molecules and we hypothesize that these defects contribute to the extreme vacuolization and fragile epithelial-fiber cell contact observed in our mutant lenses.
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