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Timothy F Plageman, Albert Reynolds, Richard A Lang; Junctional p120-catenin Recruitment of Shroom3 Facilitates Apical Constriction During Lens Pit Morphogenesis. Invest. Ophthalmol. Vis. Sci. 2014;55(13):4464.
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© ARVO (1962-2015); The Authors (2016-present)
Apical constriction is an important epithelial cell behavior characterized by the conversion of a cylindrical to wedge-like shape that is necessary for normal embryonic morphogenesis of the eye. During lens pit invagination cells undergo apical constriction under the direction of the cytoskeletal protein Shroom3. Invertebrate epithelial cells undergoing apical constriction depend on the contraction of apical cortex spanning actomyosin filaments that generate force on the apical junctions and pull them toward the middle of the cell, effectively reducing the apical circumference. A current challenge is to determine whether these mechanisms are conserved in the vertebrate lens during invagination and to identify the molecules responsible for linking apical junctions with the Shroom3-dependent apical constriction machinery. This study tests the hypothesis that p120-catenin is required for apical constriction through the recruitment of Shroom3 to adherens junctions.
Utilizing the developing mouse eye as a model system, the embryonic lens placode and lens pits of wild-type and mutant embryos were analyzed by immunofluorescent labeling of whole-mount and histologically sectioned embryos. A genetic interaction screen utilizing Shroom3 and conditional adherens junction alleles was also performed to determine which junctional proteins function with Shroom3. Cultured epithelial cells expressing Shroom3 to model apical constriction and test junctional localization were also utilized.
Contractile actomyosin filaments spanning the apical cortex are circumferentially positioned in the invaginating lens pit. Among several junctional components, it was determined that p120-catenin strongly genetically interacts with Shroom3 becoming a candidate molecule for functionally linking the apical constriction machinery with epithelial junctions. Further analysis revealed that like Shroom3, p120-catenin is required for apical constriction of lens pit cells. Finally, we determined that p120-catenin functions by recruiting Shroom3 to adherens junctions.
These data demonstrate the existence of contractile, apical cortex spanning actomyosin filaments that require linkage to the Shroom3-dependent apical constriction machinery via p120-catenin during lens pit invagination.
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