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Here, we applied whole-exome sequencing to 140 probands of FEVR families and identified 3 candidate variants in the human\n                    <jats:italic>CTNND1<\/jats:italic>\n                    gene. We performed inducible deletion of\n                    <jats:italic>Ctnnd1<\/jats:italic>\n                    in the postnatal mouse endothelial cells (ECs) and observed typical phenotypes of FEVR with reactive gliosis. Using unbiased proteomics analysis combined with experimental approaches, we conclude that p120 is critical for the integrity of adherens junctions (AJs) and that p120 activates Wnt signaling activity by protecting \u03b2-catenin from glycogen synthase kinase 3 beta\u2013ubiqutin\u2013guided (Gsk3\u03b2-ubiquitin\u2013guided) degradation. Treatment of\n                    <jats:italic>CTNND1<\/jats:italic>\n                    -depleted human retinal microvascular ECs with Gsk3\u03b2 inhibitors LiCl or CHIR-99021 enhanced cell proliferation. Moreover, LiCl treatment increased vessel density in\n                    <jats:italic>Ctnnd1<\/jats:italic>\n                    -deficient mouse retinas. Variants in\n                    <jats:italic>CTNND1<\/jats:italic>\n                    caused FEVR by compromising the expression of AJs and Wnt signaling activity. Genetic interactions between p120 and \u03b2-catenin or \u03b1-catenin revealed by double-heterozygous deletion in mice showed that p120 regulates vascular development through the Wnt\/cadherin axis. In conclusion, variants in\n                    <jats:italic>CTNND1<\/jats:italic>\n                    can cause FEVR through the Wnt\/cadherin axis.\n                  <\/jats:p>","DOI":"10.1172\/jci.insight.158428","type":"journal-article","created":{"date-parts":[[2022,6,14]],"date-time":"2022-06-14T12:41:18Z","timestamp":1655210478000},"source":"Crossref","is-referenced-by-count":43,"title":["CTNND1 variants cause familial exudative vitreoretinopathy through the Wnt\/cadherin axis"],"prefix":"10.1172","volume":"7","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-6001-6827","authenticated-orcid":true,"given":"Mu","family":"Yang","sequence":"first","affiliation":[{"name":"Sichuan Provincial Key Laboratory for Human Disease Gene Study, Center for Medical Genetics, Sichuan Provincial People\u2019s Hospital, University of Electronic Science and Technology of China, Chengdu, China."},{"name":"Research Unit for Blindness Prevention of the Chinese Academy of Medical Sciences 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