{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,20]],"date-time":"2026-03-20T20:16:11Z","timestamp":1774037771988,"version":"3.50.1"},"reference-count":36,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2023,1,10]],"date-time":"2023-01-10T00:00:00Z","timestamp":1673308800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000053","name":"National Eye Institute","doi-asserted-by":"publisher","award":["Intramural program"],"award-info":[{"award-number":["Intramural program"]}],"id":[{"id":"10.13039\/100000053","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":[[2023,4]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p><jats:italic>RERE<\/jats:italic> is a highly conserved transcriptional co\u2010regulator that is associated with a human neurodevelopmental disorder with or without anomalies of the brain, eye, or heart (NEDBEH, OMIM: 616975).<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>We show that the zebrafish <jats:italic>rerea<\/jats:italic> mutant (<jats:italic>babyface<\/jats:italic>) robustly recapitulates optic fissure closure defects resulting from loss of RERE function, as observed in humans. These defects result from expansion of proximal retinal optic stalk (OS) and reduced expression of some of the ventral retinal fate genes due to deregulated <jats:italic>protein<\/jats:italic> signaling. Using zebrafish and cell\u2010based assays, we determined that NEDBEH\u2010associated human RERE variants function as hypomorphs in their ability to repress shh signaling and some exhibit abnormal nuclear localization. Inhibiting <jats:italic>shh<\/jats:italic> signaling by the <jats:italic>protein<\/jats:italic> inhibitor HPI\u20101 rescues coloboma, confirming our observation that coloboma in <jats:italic>rerea<\/jats:italic> mutants is indeed due to deregulation of <jats:italic>shh<\/jats:italic> signaling.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>Zebrafish <jats:italic>rerea<\/jats:italic> mutants exhibit OS and optic fissure closure defects. The optic fissure closure defect was rescued by an <jats:italic>shh<\/jats:italic> signaling inhibitor, suggesting that this defect could arise due to deregulated <jats:italic>shh<\/jats:italic> signaling.<\/jats:p><\/jats:sec>","DOI":"10.1002\/dvdy.561","type":"journal-article","created":{"date-parts":[[2022,12,28]],"date-time":"2022-12-28T10:44:51Z","timestamp":1672224291000},"page":"495-509","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Zebrafish model of <scp>RERE<\/scp> syndrome recapitulates key ophthalmic defects that are rescued by small molecule inhibitor of shh signaling"],"prefix":"10.1002","volume":"252","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4315-7617","authenticated-orcid":false,"given":"Aman","family":"George","sequence":"first","affiliation":[{"name":"Pediatric Developmental &amp; Genetic Ophthalmology Section, Ophthalmic Genetics and Visual Function Branch National Eye Institute, National Institutes of Health  Bethesda Maryland USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jerry","family":"Lee","sequence":"additional","affiliation":[{"name":"Pediatric Developmental &amp; Genetic Ophthalmology Section, Ophthalmic Genetics and Visual Function Branch National Eye Institute, National Institutes of Health  Bethesda Maryland USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"James","family":"Liu","sequence":"additional","affiliation":[{"name":"Pediatric Developmental &amp; Genetic Ophthalmology Section, Ophthalmic Genetics and Visual Function Branch National Eye Institute, National Institutes of Health  Bethesda Maryland USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Suzie","family":"Kim","sequence":"additional","affiliation":[{"name":"Pediatric Developmental &amp; Genetic Ophthalmology Section, Ophthalmic Genetics and Visual Function Branch National Eye Institute, National Institutes of Health  Bethesda Maryland USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1916-7551","authenticated-orcid":false,"given":"Brian P.","family":"Brooks","sequence":"additional","affiliation":[{"name":"Pediatric Developmental &amp; Genetic Ophthalmology Section, Ophthalmic Genetics and Visual Function Branch National Eye Institute, National Institutes of Health  Bethesda Maryland 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