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Huiyu Tian, Ellen Sanders, Albert Reynolds, Frans van Roy, Jolanda van Hengel; Ocular Anterior Segment Dysgenesis upon Ablation of p120 Catenin in Neural Crest Cells. Invest. Ophthalmol. Vis. Sci. 2012;53(9):5139-5153. doi: https://doi.org/10.1167/iovs.12-9472.
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Development of the ocular anterior segment depends largely on periocular mesenchyme cells, which are derived predominantly from neural crest cells (NCC). Specific and differential cell adhesion is expected to be instrumental in induction, migration, and differentiation of NCC. As p120 catenin (ctn) is an important component of cadherin–catenin cell adhesion complexes, we assessed its role in development of the anterior segment structure.
We generated conditional p120ctnfl/fl;Wnt1Cre knockout mice and studied the effect of this gene ablation on eye development in vivo. In addition, p120ctn was knocked down in vitro.
Wnt1Cre-mediated deletion of floxed p120ctn alleles in NCC resulted in serious ocular anterior segment dysgenesis (ASD), including iridocorneal angle closure, complete anterior chamber obliteration, iris and ciliary body hypoplasia, corneal malformation and opacity, and glaucoma-like defects. A completely penetrant phenotype was visible approximately three weeks after birth, but histologic defects were obvious at embryonal day 18.5 (E18.5). Neither migration of NCC nor expression of key transcription factors appeared to be affected. In contrast, the N-cadherin expression pattern was changed significantly in iridocorneal angle cells and corneal endothelium. A human trabecular meshwork cell line in which p120ctn was knocked down also showed decreased expression levels of N-cadherin and β-catenin at the plasma membrane, but no defect in cell migration.
p120ctn has a critical role in ocular mesenchyme development. Loss of p120ctn and the associated N-cadherin downregulation in NCC leads to ASD without affecting cell migration. p120ctn abnormalities might have a role in the pathophysiology of mammalian eye development.
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