{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,9]],"date-time":"2026-11-09T21:05:18Z","timestamp":1794258318881,"version":"4.9.0"},"reference-count":88,"publisher":"Wiley","issue":"8","license":[{"start":{"date-parts":[[2019,5,15]],"date-time":"2019-05-15T00:00:00Z","timestamp":1557878400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000062","name":"National Institute of Diabetes and Digestive and Kidney Diseases","doi-asserted-by":"publisher","award":["DK056350"],"award-info":[{"award-number":["DK056350"]}],"id":[{"id":"10.13039\/100000062","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000062","name":"National Institute of Diabetes and Digestive and Kidney Diseases","doi-asserted-by":"publisher","award":["DK115380"],"award-info":[{"award-number":["DK115380"]}],"id":[{"id":"10.13039\/100000062","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100008615","name":"Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100008615","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["faseb.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["The FASEB Journal"],"published-print":{"date-parts":[[2019,8]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    Adequate supply of choline, an essential nutrient, is necessary to support proper brain development. Whether prenatal choline availability plays a role in development of the visual system is currently unknown. In this study, we addressed the role of\n                    <jats:italic>in utero<\/jats:italic>\n                    choline supply for the development and later function of the retina in a mouse model. We lowered choline availability in the maternal diet during pregnancy and assessed proliferative and differentiation properties of retinal progenitor cells (RPCs) in the developing prenatal retina, as well as visual function in adult offspring. We report that low choline availability during retinogenesis leads to persistent retinal cytoarchitectural defects, ranging from focal lesions with displacement of retinal neurons into subretinal space to severe hypocellularity and ultrastructural defects in photoreceptor organization. We further show that low choline availability impairs timely differentiation of retinal neuronal cells, such that the densities of early\u2010born retinal ganglion cells, amacrine and horizontal cells, as well as cone photoreceptor precursors, are reduced in low choline embryonic d 17.5 retinas. Maintenance of higher proportions of RPCs that fail to exit the cell cycle underlies aberrant neuronal differentiation in low choline embryos. Increased RPC cell cycle length, and associated reduction in neurofibromin 2\/Merlin protein, an upstream regulator of the Hippo signaling pathway, at least in part, explain aberrant neurogenesis in low choline retinas. Furthermore, we find that animals exposed to low choline diet\n                    <jats:italic>in utero<\/jats:italic>\n                    exhibit a significant degree of intraindividual variation in vision, characterized by marked functional discrepancy between the 2 eyes in individual animals. Together, our findings demonstrate, for the first time, that choline availability plays an essential role in the regulation of temporal progression of retinogenesis and provide evidence for the importance of adequate supply of choline for proper development of the visual system.\u2014Trujillo\u2010Gonzalez, I., Friday, W. B., Munson, C. A., Bachleda, A., Weiss, E. R., Alam, N. M., Sha, W., Zeisel, S. H., Surzenko, N. Low availability of choline\n                    <jats:italic>in utero<\/jats:italic>\n                    disrupts development and function of the retina. FASEB J. 33, 9194\u20139209 (2019).\n                    <jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" xlink:href=\"http:\/\/www.fasebj.org\">www.fasebj.org<\/jats:ext-link>\n                  <\/jats:p>","DOI":"10.1096\/fj.201900444r","type":"journal-article","created":{"date-parts":[[2019,5,15]],"date-time":"2019-05-15T21:34:58Z","timestamp":1557956098000},"page":"9194-9209","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":28,"title":["Low availability of choline\n                    <i>in utero<\/i>\n                    disrupts development and function of the retina"],"prefix":"10.1096","volume":"33","author":[{"given":"Isis","family":"Trujillo\u2010Gonzalez","sequence":"first","affiliation":[{"name":"Nutrition Research Institute University of North Carolina\u2013Chapel Hill  Kannapolis North Carolina USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Walter B.","family":"Friday","sequence":"additional","affiliation":[{"name":"Nutrition Research Institute University of North Carolina\u2013Chapel Hill  Kannapolis North Carolina USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carolyn A.","family":"Munson","sequence":"additional","affiliation":[{"name":"Nutrition Research Institute University of North Carolina\u2013Chapel Hill  Kannapolis North Carolina USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amelia","family":"Bachleda","sequence":"additional","affiliation":[{"name":"Department of Cell Biology and Physiology University of North Carolina\u2010Chapel Hill  Chapel Hill North Carolina USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ellen R.","family":"Weiss","sequence":"additional","affiliation":[{"name":"Department of Cell Biology and Physiology University of North Carolina\u2010Chapel Hill  Chapel Hill North Carolina USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nazia M.","family":"Alam","sequence":"additional","affiliation":[{"name":"Department of Physiology and Biophysics Weill Cornell Medical College  New York New York USA"},{"name":"Center for Visual Restoration Burke Neurological Institute  White Plains New York USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wei","family":"Sha","sequence":"additional","affiliation":[{"name":"Bioinformatics Services Division University of North Carolina\u2013Charlotte  Kannapolis North Carolina USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Steven H.","family":"Zeisel","sequence":"additional","affiliation":[{"name":"Nutrition Research Institute University of North Carolina\u2013Chapel Hill  Kannapolis North Carolina USA"},{"name":"Department of Nutrition Gillings School of Global Public Health University of North Carolina\u2010Chapel Hill  Chapel Hill North Carolina USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Natalia","family":"Surzenko","sequence":"additional","affiliation":[{"name":"Nutrition Research Institute University of North Carolina\u2013Chapel Hill  Kannapolis North Carolina USA"},{"name":"Department of Nutrition Gillings School of Global Public Health University of North Carolina\u2010Chapel Hill  Chapel Hill North Carolina USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2019,5,15]]},"reference":[{"key":"e_1_2_7_2_1","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.nutr.26.061505.111156"},{"key":"e_1_2_7_3_1","doi-asserted-by":"publisher","DOI":"10.2174\/0929867322666151029104152"},{"key":"e_1_2_7_4_1","doi-asserted-by":"publisher","DOI":"10.2174\/092986708783503203"},{"key":"e_1_2_7_5_1","doi-asserted-by":"publisher","DOI":"10.3390\/nu9050445"},{"key":"e_1_2_7_6_1","doi-asserted-by":"publisher","DOI":"10.1093\/aje\/kws395"},{"key":"e_1_2_7_7_1","doi-asserted-by":"publisher","DOI":"10.1080\/07315724.2013.846806"},{"key":"e_1_2_7_8_1","doi-asserted-by":"publisher","DOI":"10.3945\/ajcn.112.048462"},{"key":"e_1_2_7_9_1","doi-asserted-by":"publisher","DOI":"10.1097\/01.ede.0000208348.30012.35"},{"key":"e_1_2_7_10_1","doi-asserted-by":"publisher","DOI":"10.1590\/S0043-31442005000600002"},{"key":"e_1_2_7_11_1","doi-asserted-by":"publisher","DOI":"10.1093\/ajcn\/85.5.1275"},{"key":"e_1_2_7_12_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M110.106922"},{"key":"e_1_2_7_13_1","doi-asserted-by":"publisher","DOI":"10.1096\/fj.15-282426"},{"key":"e_1_2_7_14_1","doi-asserted-by":"publisher","DOI":"10.1093\/jn\/133.11.3614"},{"key":"e_1_2_7_15_1","doi-asserted-by":"publisher","DOI":"10.1096\/fj.201801094RR"},{"key":"e_1_2_7_16_1","doi-asserted-by":"publisher","DOI":"10.1097\/00001756-199709290-00010"},{"key":"e_1_2_7_17_1","doi-asserted-by":"publisher","DOI":"10.1002\/dev.420210405"},{"key":"e_1_2_7_18_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0149-7634(03)00069-1"},{"key":"e_1_2_7_19_1","doi-asserted-by":"publisher","DOI":"10.3389\/neuro.07.007.2007"},{"key":"e_1_2_7_20_1","doi-asserted-by":"publisher","DOI":"10.1096\/fj.201700692RR"},{"key":"e_1_2_7_21_1","doi-asserted-by":"publisher","DOI":"10.1016\/B978-0-12-385044-7.00003-5"},{"key":"e_1_2_7_22_1","doi-asserted-by":"publisher","DOI":"10.1002\/bies.10356"},{"key":"e_1_2_7_23_1","doi-asserted-by":"crossref","first-page":"105","DOI":"10.3389\/fncir.2017.00105","article-title":"Temporal progression of retinal progenitor cell identity: implications in cell replacement therapies","volume":"11","author":"Javed A.","year":"2017","journal-title":"Front. Neural Circuits"},{"key":"e_1_2_7_24_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0959-4388(99)80005-1"},{"key":"e_1_2_7_25_1","doi-asserted-by":"crossref","first-page":"e1125409","DOI":"10.1080\/23262133.2015.1125409","article-title":"Mechanisms of temporal identity regulation in mouse retinal progenitor cells","volume":"2","author":"Mattar P.","year":"2015","journal-title":"Neurogenesis (Austin)"},{"key":"e_1_2_7_26_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0601992103"},{"key":"e_1_2_7_27_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.3812-07.2007"},{"key":"e_1_2_7_28_1","doi-asserted-by":"publisher","DOI":"10.1038\/nn.2467"},{"key":"e_1_2_7_29_1","doi-asserted-by":"publisher","DOI":"10.1167\/iovs.07-1012"},{"key":"e_1_2_7_30_1","doi-asserted-by":"publisher","DOI":"10.1167\/iovs.15-17994"},{"key":"e_1_2_7_31_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ymthe.2016.12.016"},{"key":"e_1_2_7_32_1","doi-asserted-by":"publisher","DOI":"10.1167\/iovs.04-0541"},{"key":"e_1_2_7_33_1","doi-asserted-by":"publisher","DOI":"10.1017\/S0952523805225166"},{"key":"e_1_2_7_34_1","doi-asserted-by":"publisher","DOI":"10.1186\/1749-8104-9-27"},{"key":"e_1_2_7_35_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ydbio.2005.04.005"},{"key":"e_1_2_7_36_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.2517-6161.1995.tb02031.x"},{"key":"e_1_2_7_37_1","first-page":"1","volume-title":"Webvision: The Organization of the Retina and Visual System","author":"Kolb H.","year":"1995"},{"key":"e_1_2_7_38_1","first-page":"98","volume-title":"Webvision: The Organization of the Retina and Visual System","author":"Kolb H.","year":"1995"},{"key":"e_1_2_7_39_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1203138109"},{"key":"e_1_2_7_40_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.89.2.693"},{"key":"e_1_2_7_41_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.brainres.2007.05.021"},{"key":"e_1_2_7_42_1","doi-asserted-by":"publisher","DOI":"10.1101\/gad.1909210"},{"key":"e_1_2_7_43_1","doi-asserted-by":"publisher","DOI":"10.1002\/dvdy.24628"},{"key":"e_1_2_7_44_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.preteyeres.2013.12.003"},{"key":"e_1_2_7_45_1","doi-asserted-by":"publisher","DOI":"10.1113\/jphysiol.2008.159327"},{"key":"e_1_2_7_46_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1350-9462(03)00036-3"},{"key":"e_1_2_7_47_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.preteyeres.2011.01.001"},{"key":"e_1_2_7_48_1","first-page":"183","article-title":"The outer limiting membrane (OLM) revisited: clinical implications","volume":"4","author":"Omri S.","year":"2010","journal-title":"Clin. Ophthalmol."},{"key":"e_1_2_7_49_1","doi-asserted-by":"publisher","DOI":"10.1242\/dev.071878"},{"key":"e_1_2_7_50_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.exer.2007.08.004"},{"key":"e_1_2_7_51_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.exer.2008.02.005"},{"key":"e_1_2_7_52_1","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/ddg232"},{"key":"e_1_2_7_53_1","doi-asserted-by":"publisher","DOI":"10.1167\/iovs.12-9662"},{"key":"e_1_2_7_54_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.febslet.2014.04.001"},{"key":"e_1_2_7_55_1","doi-asserted-by":"publisher","DOI":"10.1038\/sj.bjc.6604002"},{"key":"e_1_2_7_56_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0700044104"},{"key":"e_1_2_7_57_1","doi-asserted-by":"publisher","DOI":"10.1038\/nn.3348"},{"key":"e_1_2_7_58_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(09)60259-2"},{"key":"e_1_2_7_59_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1750-3639.2007.00086.x"},{"key":"e_1_2_7_60_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrn2880"},{"key":"e_1_2_7_61_1","doi-asserted-by":"publisher","DOI":"10.4161\/org.26710"},{"key":"e_1_2_7_62_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1399-0004.2009.01240.x"},{"key":"e_1_2_7_63_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.preteyeres.2017.11.001"},{"key":"e_1_2_7_64_1","doi-asserted-by":"publisher","DOI":"10.1096\/fj.09-140145"},{"key":"e_1_2_7_65_1","doi-asserted-by":"publisher","DOI":"10.1096\/fj.05-4707com"},{"key":"e_1_2_7_66_1","doi-asserted-by":"publisher","DOI":"10.2174\/187152412800792706"},{"key":"e_1_2_7_67_1","doi-asserted-by":"publisher","DOI":"10.1194\/jlr.M044990"},{"key":"e_1_2_7_68_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.preteyeres.2016.05.003"},{"key":"e_1_2_7_69_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.77.3.1671"},{"key":"e_1_2_7_70_1","first-page":"288","article-title":"Alteration of retinal choline metabolism in an experimental model for photoreceptor cell degeneration","volume":"24","author":"Pu G. A.","year":"1983","journal-title":"Invest. Ophthalmol. Vis. Sci."},{"key":"e_1_2_7_71_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0896-6273(00)80937-X"},{"key":"e_1_2_7_72_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuron.2005.01.045"},{"key":"e_1_2_7_73_1","doi-asserted-by":"publisher","DOI":"10.1006\/mcne.1997.0659"},{"key":"e_1_2_7_74_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.devcel.2017.11.011"},{"key":"e_1_2_7_75_1","doi-asserted-by":"publisher","DOI":"10.1101\/gad.1726608"},{"key":"e_1_2_7_76_1","doi-asserted-by":"publisher","DOI":"10.1242\/dev.096537"},{"key":"e_1_2_7_77_1","doi-asserted-by":"publisher","DOI":"10.7554\/eLife.08488"},{"key":"e_1_2_7_78_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1097-2765(03)00382-4"},{"key":"e_1_2_7_79_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13041-015-0124-z"},{"key":"e_1_2_7_80_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00018-013-1347-8"},{"key":"e_1_2_7_81_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.exer.2018.03.017"},{"key":"e_1_2_7_82_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.3396-06.2006"},{"key":"e_1_2_7_83_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0002055"},{"key":"e_1_2_7_84_1","doi-asserted-by":"publisher","DOI":"10.3389\/fncir.2014.00082"},{"key":"e_1_2_7_85_1","first-page":"877","article-title":"Prevalence and causes of functional low vision in school\u2010age children: results from standardized population surveys in Asia","volume":"49","author":"Gilbert C. E.","year":"2008","journal-title":"Africa, and Latin America. Invest. Ophthalmol. Vis. Sci."},{"key":"e_1_2_7_86_1","doi-asserted-by":"crossref","first-page":"209","DOI":"10.1186\/s12886-017-0609-x","article-title":"Retrospective data on causes of childhood vision impairment in Eritrea","volume":"17","author":"Gyawali R.","year":"2017","journal-title":"BMC Ophthalmol."},{"key":"e_1_2_7_87_1","doi-asserted-by":"publisher","DOI":"10.1097\/01.icu.0000397180.37316.5d"},{"key":"e_1_2_7_88_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.brainres.2007.07.005"},{"key":"e_1_2_7_89_1","doi-asserted-by":"publisher","DOI":"10.1080\/07315724.2015.1080127"}],"container-title":["The FASEB Journal"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1096\/fj.201900444R","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1096\/fj.201900444R","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/faseb.onlinelibrary.wiley.com\/doi\/pdf\/10.1096\/fj.201900444R","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,28]],"date-time":"2025-10-28T16:23:48Z","timestamp":1761668628000},"score":1,"resource":{"primary":{"URL":"https:\/\/faseb.onlinelibrary.wiley.com\/doi\/10.1096\/fj.201900444R"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2019,5,15]]},"references-count":88,"journal-issue":{"issue":"8","published-print":{"date-parts":[[2019,8]]}},"alternative-id":["10.1096\/fj.201900444R"],"URL":"https:\/\/doi.org\/10.1096\/fj.201900444r","archive":["Portico"],"relation":{},"ISSN":["0892-6638","1530-6860"],"issn-type":[{"value":"0892-6638","type":"print"},{"value":"1530-6860","type":"electronic"}],"subject":[],"published":{"date-parts":[[2019,5,15]]},"assertion":[{"value":"2019-02-15","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2019-04-15","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2019-05-15","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}