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Y. Sugiyama, K. Akimoto, S. Ohno, M.L. Robinson, A.R. Prescott, R.A. Quinlan; Cell Polarity and Apical Junctional Complex Regulated by aPKC During Lens Formation . Invest. Ophthalmol. Vis. Sci. 2006;47(13):1996.
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© ARVO (1962-2015); The Authors (2016-present)
aPKC/Par cassette is evolutionally conserved and essential to asymmetric cell division and cell polarity formation in various cell types. In epithelial cells, aPKC/Par is required for cell polarity and the formation of the apical junctional complex (AJC), which comprises both belt–like adherens junctions and tight junctions. The eye lens is derived from the surface ectoderm of the embryo and lens cells maintain this cell polarity and the formation of the AJC. We speculate that the aPKC/Par machinery is required for lens formation. To determine the roles of this cell polarity complex in this process, we have developed aPKC knockout lenses and examined the impact of aPKC depletion.
aPKC/Par protein localisation was determined by confocal immunofluorescence microscopy of adult bovine lens cryosections. aPKC knockout lenses were generated by crossing the aPKC lambda flox mice (K Akimoto et al) with the MLR10 transgenic mice, which express Cre recombinase both in lens epithelial and fibre cells from E10.5 (ML Robinson et al).
aPKC, Par3 and Par6 are colocalising with ZO–1 and N–cadherin at the AJC in bovine lens epithelial cells. We found aPKC depletion in the mouse lens causes both microphthalmia and cataract formation. Further examination indicated that the lens epithelial cells lost their cuboidal cell shape and became multilayered. No newly formed secondary fibre cells were found in lenses of weaned mice, which could account for the microphthalmia. The fibre cell alignment is distorted and abnormal spaces/vacuoles were detected in the lenses of these aPKC knockout mice. Incomplete elongation and detachment from anterior epithelium of fibre cells were evident. Disorganisation of these secondary lens fibre cells is a likely cause of the resulting cataract.
aPKC has critical roles not only for lens epithelial cells, but also for secondary fibre cell organization in the lens. aPKC is required for maintenance of lens epithelial cells as same as for typical epithelial cells, and it is also required for lens epithelial cells to maintain their capacity to differentiate into fibre cells. We are currently exploring the mechanism(s) of this disruption to fibre cell organization and to the formation and integrity of the AJC in the aPKC knockout mice.
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