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Abstract #50592 Published in IGR 14-2
Ocular Anterior Segment Dysgenesis upon Ablation of p120 Catenin in Neural Crest Cells
Tian H; Sanders E; Reynolds A; van Roy F; van Hengel JInvestigative Ophthalmology and Visual Science 2012; 53: 5139-5153
PURPOSE: 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. METHODS: The authors 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. RESULTS: 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 about three weeks after birth, but histological defects were obvious at E18.5. Neither migration of NCC nor expression of key transcription factors appeared to be affected. In contrast, the N-cadherin expression pattern was significantly changed 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. CONCLUSIONS: p120ctn plays 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.
Department for Molecular Biomedical Research, VIB & Ghent University, Molecular Cell Biology Unit, Ghent, B-9052, Belgium.
Full articleClassification:
5.1 Rodent (Part of: 5 Experimental glaucoma; animal models)
3.4.2 Gene studies (Part of: 3 Laboratory methods > 3.4 Molecular genetics)
