{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,25]],"date-time":"2026-07-25T05:34:24Z","timestamp":1784957664216,"version":"3.55.0"},"reference-count":83,"publisher":"The Company of Biologists","issue":"15","license":[{"start":{"date-parts":[[2024,8,12]],"date-time":"2024-08-12T00:00:00Z","timestamp":1723420800000},"content-version":"vor","delay-in-days":11,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"crossref","award":["EY032790-01"],"award-info":[{"award-number":["EY032790-01"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"crossref","award":["T32-GM133369"],"award-info":[{"award-number":["T32-GM133369"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"crossref","award":["P20GM144230"],"award-info":[{"award-number":["P20GM144230"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"crossref","award":["R01EY026580"],"award-info":[{"award-number":["R01EY026580"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"crossref","award":["P30EY001765-45"],"award-info":[{"award-number":["P30EY001765-45"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"crossref","award":["T32-GM136577"],"award-info":[{"award-number":["T32-GM136577"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"crossref","award":["T32EY007143-24"],"award-info":[{"award-number":["T32EY007143-24"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100006312","name":"Brightfocus Foundation","doi-asserted-by":"crossref","award":["G2020315"],"award-info":[{"award-number":["G2020315"]}],"id":[{"id":"10.13039\/100006312","id-type":"DOI","asserted-by":"crossref"}]},{"name":"National Science Foundation","award":["OIA-2242771"],"award-info":[{"award-number":["OIA-2242771"]}]},{"DOI":"10.13039\/100012304","name":"Johns Hopkins University School of Medicine","doi-asserted-by":"crossref","id":[{"id":"10.13039\/100012304","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2024,8,1]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n               <jats:p>Many genes are known to regulate retinal regeneration after widespread tissue damage. Conversely, genes controlling regeneration after limited cell loss, as per degenerative diseases, are undefined. As stem\/progenitor cell responses scale to injury levels, understanding how the extent and specificity of cell loss impact regenerative processes is important. Here, transgenic zebrafish enabling selective retinal ganglion cell (RGC) ablation were used to identify genes that regulate RGC regeneration. A single cell multiomics-informed screen of 100 genes identified seven knockouts that inhibited and 11 that promoted RGC regeneration. Surprisingly, 35 out of 36 genes known and\/or implicated as being required for regeneration after widespread retinal damage were not required for RGC regeneration. The loss of seven even enhanced regeneration kinetics, including the proneural factors neurog1, olig2 and ascl1a. Mechanistic analyses revealed that ascl1a disruption increased the propensity of progenitor cells to produce RGCs, i.e. increased \u2018fate bias\u2019. These data demonstrate plasticity in the mechanism through which M\u00fcller glia convert to a stem-like state and context specificity in how genes function during regeneration. Increased understanding of how the regeneration of disease-relevant cell types is specifically controlled will support the development of disease-tailored regenerative therapeutics.<\/jats:p>","DOI":"10.1242\/dev.202754","type":"journal-article","created":{"date-parts":[[2024,7,15]],"date-time":"2024-07-15T10:57:40Z","timestamp":1721041060000},"source":"Crossref","is-referenced-by-count":13,"title":["A large-scale CRISPR screen reveals context-specific genetic regulation of retinal ganglion cell regeneration"],"prefix":"10.1242","volume":"151","author":[{"given":"Kevin","family":"Emmerich","sequence":"first","affiliation":[{"name":"Wilmer Eye Institute 1 and the Department of Ophthalmology , , Baltimore, MD 21287 , USA"},{"name":"Johns Hopkins University School of Medicine 1 and the Department of Ophthalmology , , Baltimore, MD 21287 , USA"},{"name":"McKusick-Nathans Institute 2 and the Department of Genetic Medicine , , Baltimore, MD 21287 , USA"},{"name":"Johns Hopkins University School of Medicine 2 and the Department of Genetic Medicine , , Baltimore, MD 21287 , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John","family":"Hageter","sequence":"additional","affiliation":[{"name":"West Virginia University 3 Department of Biology , , Morgantown, WV 26505 , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thanh","family":"Hoang","sequence":"additional","affiliation":[{"name":"Wilmer Eye Institute 1 and the Department of Ophthalmology , , Baltimore, MD 21287 , USA"},{"name":"Johns Hopkins University School of Medicine 1 and the Department of Ophthalmology , , Baltimore, MD 21287 , USA"},{"name":"University of Michigan School of Medicine 4 Department of Ophthalmology and Visual Sciences , , Ann Arbor, MI 48105 , USA"},{"name":"University of Michigan School of Medicine 5 Department of Cell and Developmental Biology , , Ann Arbor, MI 48105 , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pin","family":"Lyu","sequence":"additional","affiliation":[{"name":"Wilmer Eye Institute 1 and the Department of Ophthalmology , , Baltimore, MD 21287 , USA"},{"name":"Johns Hopkins University School of Medicine 1 and the Department of Ophthalmology , , Baltimore, MD 21287 , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Abigail V.","family":"Sharrock","sequence":"additional","affiliation":[{"name":"School of Biological Sciences, Victoria University of Wellington 6 , Wellington 6012 , New Zealand"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anneliese","family":"Ceisel","sequence":"additional","affiliation":[{"name":"Wilmer Eye Institute 1 and the Department of Ophthalmology , , Baltimore, MD 21287 , USA"},{"name":"Johns Hopkins University School of Medicine 1 and the Department of Ophthalmology , , Baltimore, MD 21287 , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"James","family":"Thierer","sequence":"additional","affiliation":[{"name":"Wilmer Eye Institute 1 and the Department of Ophthalmology , , Baltimore, MD 21287 , USA"},{"name":"Johns Hopkins University School of Medicine 1 and the Department of Ophthalmology , , Baltimore, MD 21287 , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zeeshaan","family":"Chunawala","sequence":"additional","affiliation":[{"name":"Wilmer Eye Institute 1 and the Department of Ophthalmology , , Baltimore, MD 21287 , USA"},{"name":"Johns Hopkins University School of Medicine 1 and the Department of Ophthalmology , , Baltimore, MD 21287 , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Saumya","family":"Nimmagadda","sequence":"additional","affiliation":[{"name":"Wilmer Eye Institute 1 and the Department of Ophthalmology , , Baltimore, MD 21287 , USA"},{"name":"Johns Hopkins University School of Medicine 1 and the Department of Ophthalmology , , Baltimore, MD 21287 , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Isabella","family":"Palazzo","sequence":"additional","affiliation":[{"name":"Institute for Cell Engineering, Johns Hopkins University School of Medicine 7 , Baltimore, MD 21287 , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Frazer","family":"Matthews","sequence":"additional","affiliation":[{"name":"Wilmer Eye Institute 1 and the Department of Ophthalmology , , Baltimore, MD 21287 , USA"},{"name":"Johns Hopkins University School of Medicine 1 and the Department of Ophthalmology , , Baltimore, MD 21287 , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Liyun","family":"Zhang","sequence":"additional","affiliation":[{"name":"Wilmer Eye Institute 1 and the Department of Ophthalmology , , Baltimore, MD 21287 , USA"},{"name":"Johns Hopkins University School of Medicine 1 and the Department of Ophthalmology , , Baltimore, MD 21287 , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David T.","family":"White","sequence":"additional","affiliation":[{"name":"Wilmer Eye Institute 1 and the Department of Ophthalmology , , Baltimore, MD 21287 , USA"},{"name":"Johns Hopkins University School of Medicine 1 and the Department of Ophthalmology , , Baltimore, MD 21287 , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Catalina","family":"Rodriguez","sequence":"additional","affiliation":[{"name":"Wilmer Eye Institute 1 and the Department of Ophthalmology , , Baltimore, MD 21287 , USA"},{"name":"Johns Hopkins University School of Medicine 1 and the Department of Ophthalmology , , Baltimore, MD 21287 , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gianna","family":"Graziano","sequence":"additional","affiliation":[{"name":"Wilmer Eye Institute 1 and the Department of Ophthalmology , , Baltimore, MD 21287 , USA"},{"name":"Johns Hopkins University School of Medicine 1 and the Department of Ophthalmology , , Baltimore, MD 21287 , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Patrick","family":"Marcos","sequence":"additional","affiliation":[{"name":"Wilmer Eye Institute 1 and the Department of Ophthalmology , , Baltimore, MD 21287 , USA"},{"name":"Johns Hopkins University School of Medicine 1 and the Department of Ophthalmology , , Baltimore, MD 21287 , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Adam","family":"May","sequence":"additional","affiliation":[{"name":"Wilmer Eye Institute 1 and the Department of Ophthalmology , , Baltimore, MD 21287 , USA"},{"name":"Johns Hopkins University School of Medicine 1 and the Department of Ophthalmology , , Baltimore, MD 21287 , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tim","family":"Mulligan","sequence":"additional","affiliation":[{"name":"Wilmer Eye Institute 1 and the Department of Ophthalmology , , Baltimore, MD 21287 , USA"},{"name":"Johns Hopkins University School of Medicine 1 and the Department of Ophthalmology , , Baltimore, MD 21287 , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Barak","family":"Reibman","sequence":"additional","affiliation":[{"name":"Wilmer Eye Institute 1 and the Department of Ophthalmology , , Baltimore, MD 21287 , USA"},{"name":"Johns Hopkins University School of Medicine 1 and the Department of Ophthalmology , , Baltimore, MD 21287 , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Meera T.","family":"Saxena","sequence":"additional","affiliation":[{"name":"Wilmer Eye Institute 1 and the Department of Ophthalmology , , Baltimore, MD 21287 , USA"},{"name":"Johns Hopkins University School of Medicine 1 and the Department of Ophthalmology , , Baltimore, MD 21287 , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David F.","family":"Ackerley","sequence":"additional","affiliation":[{"name":"School of Biological 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and the Department of Ophthalmology , , Baltimore, MD 21287 , USA"},{"name":"Johns Hopkins University School of Medicine 1 and the Department of Ophthalmology , , Baltimore, MD 21287 , USA"},{"name":"McKusick-Nathans Institute 2 and the Department of Genetic Medicine , , Baltimore, MD 21287 , USA"},{"name":"Johns Hopkins University School of Medicine 2 and the Department of Genetic Medicine , , Baltimore, MD 21287 , USA"},{"name":"Johns Hopkins University School of Medicine 9 Department of Neuroscience , , Baltimore, MD 21287 , USA"},{"name":"Center for Nanomedicine, Johns Hopkins University School of Medicine 11 , Baltimore, MD 21287 , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"237","published-online":{"date-parts":[[2024,8,12]]},"reference":[{"key":"2024081214455297200_DEV202754C1","doi-asserted-by":"publisher","first-page":"1083","DOI":"10.1038\/nmeth.4463","article-title":"SCENIC: single-cell regulatory network inference and 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Neurosci."},{"key":"2024081214455297200_DEV202754C4","doi-asserted-by":"publisher","first-page":"3519","DOI":"10.1242\/dev.064006","article-title":"Ascl1 expression defines a subpopulation of lineage-restricted progenitors in the mammalian retina","volume":"138","author":"Brzezinski","year":"2011","journal-title":"Development"},{"key":"2024081214455297200_DEV202754C5","doi-asserted-by":"publisher","first-page":"1048","DOI":"10.4103\/1673-5374.211178","article-title":"SoxC transcription factors in retinal development and regeneration","volume":"12","author":"Chang","year":"2017","journal-title":"Neural Regen. Res."},{"key":"2024081214455297200_DEV202754C6","doi-asserted-by":"publisher","first-page":"4967","DOI":"10.1523\/JNEUROSCI.3430-13.2017","article-title":"Novel regulatory mechanisms for the SoxC transcriptional network required for visual pathway development","volume":"37","author":"Chang","year":"2017","journal-title":"J. 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