{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,3]],"date-time":"2026-02-03T16:08:02Z","timestamp":1770134882599,"version":"3.49.0"},"reference-count":41,"publisher":"Wiley","issue":"12","license":[{"start":{"date-parts":[[2019,10,21]],"date-time":"2019-10-21T00:00:00Z","timestamp":1571616000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100000030","name":"Institute of Genetics","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100000030","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["anatomypubs.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Developmental Dynamics"],"published-print":{"date-parts":[[2019,12]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>Familial exudative vitreoretinopathy (FEVR) is a rare congenital disorder characterized by a lack of blood vessel growth to the periphery of the retina with secondary fibrovascular proliferation at the vascular\u2010avascular junction. These structurally abnormal vessels cause leakage and hemorrhage, while the fibroproliferative scarring results in retinal dragging, detachment and blindness. Mutations in the <jats:italic>FZD4<\/jats:italic> gene represent one of the most common causes of FEVR.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>A loss of function mutation resulting from a 10\u2010nucleotide insertion into exon 1 of the zebrafish <jats:italic>fzd4<\/jats:italic> gene was generated using transcription activator\u2010like effector nucleases (TALENs). Structural and functional integrity of the retinal vasculature was examined by fluorescent microscopy and optokinetic responses.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Zebrafish retinal vasculature is asymmetrically distributed along the dorsoventral axis, with active vascular remodeling on the ventral surface of the retina throughout development. <jats:italic>fzd4<\/jats:italic> mutants exhibit disorganized ventral retinal vasculature with discernable tubular fusion by week 8 of development. Furthermore, <jats:italic>fzd4<\/jats:italic> mutants have impaired optokinetic responses requiring increased illumination.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>We have generated a visually impaired zebrafish FEVR model exhibiting abnormal retinal vasculature. These fish provide a tractable system for studying vascular biology in retinovascular disorders, and demonstrate the feasibility of using zebrafish for evaluating future FEVR genes identified in humans.<\/jats:p><\/jats:sec>","DOI":"10.1002\/dvdy.117","type":"journal-article","created":{"date-parts":[[2019,10,1]],"date-time":"2019-10-01T00:40:49Z","timestamp":1569890449000},"page":"1243-1256","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":13,"title":["<i>Frizzled 4<\/i> regulates ventral blood vessel remodeling in the zebrafish retina"],"prefix":"10.1002","volume":"248","author":[{"given":"Lucia","family":"Caceres","sequence":"first","affiliation":[{"name":"Department of Pediatrics IWK Health Centre\/Dalhousie University  Halifax Nova Scotia Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sergey V.","family":"Prykhozhij","sequence":"additional","affiliation":[{"name":"Department of Pediatrics IWK 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