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We performed VSX2 ChIP-seq and ChIP-PCR assays on early stage optic vesicle-like structures (OVs) derived from human iPS cells (hiPSCs), which highlighted WNT pathway genes as direct regulatory targets of VSX2. Examination of early NR patterning in hiPSC-OVs from a patient with a functional null mutation in VSX2 revealed mis-expression and upregulation of WNT pathway components and retinal pigmented epithelium (RPE) markers in comparison to control hiPSC-OVs. Furthermore, pharmacological inhibition of WNT signaling rescued the early mutant phenotype, whereas augmentation of WNT signaling in control hiPSC-OVs phenocopied the mutant. These findings reveal an important role for VSX2 as a regulator of WNT signaling and suggest that VSX2 may act to maintain NR identity at the expense of RPE in part by direct repression of WNT pathway constituents.<\/jats:p>","DOI":"10.1002\/stem.2414","type":"journal-article","created":{"date-parts":[[2016,6,14]],"date-time":"2016-06-14T16:00:31Z","timestamp":1465920031000},"page":"2625-2634","source":"Crossref","is-referenced-by-count":47,"title":["Regulation of WNT Signaling by VSX2 During Optic Vesicle Patterning in Human Induced Pluripotent Stem Cells"],"prefix":"10.1093","volume":"34","author":[{"given":"Elizabeth E.","family":"Capowski","sequence":"first","affiliation":[{"name":"Waisman Center, University of Wisconsin-Madison, Madison, WI, 53705, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lynda S.","family":"Wright","sequence":"additional","affiliation":[{"name":"Waisman Center, University of Wisconsin-Madison, Madison, WI, 53705, USA"},{"name":"McPherson Eye Research Institute, University of Wisconsin-Madison, Madison, WI, 53705, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kun","family":"Liang","sequence":"additional","affiliation":[{"name":"Statistics and Actuarial Science, University of Waterloo, Waterloo, ON, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M. Joseph","family":"Phillips","sequence":"additional","affiliation":[{"name":"Waisman Center, University of Wisconsin-Madison, Madison, WI, 53705, USA"},{"name":"McPherson Eye Research Institute, University of Wisconsin-Madison, Madison, WI, 53705, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kyle","family":"Wallace","sequence":"additional","affiliation":[{"name":"Waisman Center, University of Wisconsin-Madison, Madison, WI, 53705, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anna","family":"Petelinsek","sequence":"additional","affiliation":[{"name":"Waisman Center, University of Wisconsin-Madison, Madison, WI, 53705, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anna","family":"Hagstrom","sequence":"additional","affiliation":[{"name":"Waisman Center, University of Wisconsin-Madison, Madison, WI, 53705, 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