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Factors involved in the development of lens fiber cells are largely unknown in vertebrates. In this study, we reported that GATA2 is essential for lens morphogenesis in Nile tilapia (Oreochromis\u00a0niloticus). In this study, Gata2a was detected in the primary and secondary lens fiber cells, with the highest expression in primary fiber cells. gata2a homozygous mutants of tilapia were obtained using CRISPR\/Cas9. Different from fetal lethality caused by Gata2\/gata2a mutation in mice and zebrafish, some gata2a homozygous mutants of tilapia are viable, which provides a good model for studying the role of gata2 in non-hematopoietic organs. Our data showed that gata2a mutation caused extensive degeneration and apoptosis of primary lens fiber cells. The mutants exhibited progressive microphthalmia and blindness in adulthood. Transcriptome analysis of the eyes showed that the expression levels of almost all genes encoding crystallin were significantly down-regulated, while the expression levels of genes involved in visual perception and metal ion binding were significantly up-regulated after gata2a mutation. Altogether, our findings indicate that gata2a is required for the survival of lens fiber cells and provide insights into transcriptional regulation underlying lens morphogenesis in teleost fish.<\/jats:p>","DOI":"10.3390\/ijms24043567","type":"journal-article","created":{"date-parts":[[2023,2,10]],"date-time":"2023-02-10T04:48:03Z","timestamp":1676004483000},"page":"3567","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Gata2a Mutation Causes Progressive Microphthalmia and Blindness in Nile Tilapia"],"prefix":"10.3390","volume":"24","author":[{"given":"Xingyong","family":"Liu","sequence":"first","affiliation":[{"name":"Integrative Science Center of Germplasm Creation in Western China (CHONGQING) Science City, Key Laboratory of Freshwater Fish Reproduction and Development (Ministry of Education), Key Laboratory of Aquatic Science of Chongqing, School of Life Sciences, Southwest University, Chongqing 400715, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Li","family":"Zhou","sequence":"additional","affiliation":[{"name":"Integrative Science Center of Germplasm Creation in Western China (CHONGQING) Science City, Key Laboratory of Freshwater Fish Reproduction and Development (Ministry of Education), Key Laboratory of Aquatic Science of Chongqing, School of Life Sciences, Southwest University, Chongqing 400715, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Wenbo","family":"Li","sequence":"additional","affiliation":[{"name":"Integrative Science Center of Germplasm Creation in Western China (CHONGQING) Science City, Key Laboratory of Freshwater Fish Reproduction and Development (Ministry of Education), Key Laboratory of Aquatic Science of Chongqing, School of Life Sciences, Southwest University, Chongqing 400715, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jiahong","family":"Wu","sequence":"additional","affiliation":[{"name":"Integrative Science Center of Germplasm Creation in Western China (CHONGQING) Science City, Key Laboratory of Freshwater Fish Reproduction and Development (Ministry of Education), Key Laboratory of Aquatic Science of Chongqing, School of Life Sciences, Southwest University, Chongqing 400715, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4967-524X","authenticated-orcid":false,"given":"Deshou","family":"Wang","sequence":"additional","affiliation":[{"name":"Integrative Science Center of Germplasm Creation in Western China (CHONGQING) Science City, Key Laboratory of Freshwater Fish Reproduction and Development (Ministry of Education), Key Laboratory of Aquatic Science of Chongqing, School of Life Sciences, Southwest University, Chongqing 400715, China"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2023,2,10]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"4432","DOI":"10.1242\/dev.107953","article-title":"The cellular and molecular mechanisms of vertebrate lens development","volume":"141","author":"Cvekl","year":"2014","journal-title":"Development"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"e1790","DOI":"10.7717\/peerj.1790","article-title":"Origin and evolution of GATA2a and GATA2b in teleosts: Insights from tongue sole, Cynoglossus semilaevis","volume":"4","author":"Liu","year":"2016","journal-title":"PeerJ"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"351","DOI":"10.1016\/bs.ctdb.2018.12.008","article-title":"Eye organogenesis: A hierarchical view of ocular development","volume":"132","author":"Miesfeld","year":"2019","journal-title":"Curr. Top Dev. Biol."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"1007","DOI":"10.1007\/s00439-019-01995-w","article-title":"Mouse models for microphthalmia, anophthalmia and cataracts","volume":"138","author":"Graw","year":"2019","journal-title":"Hum. Genet."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"119","DOI":"10.1016\/bs.pmbts.2015.04.006","article-title":"Overview of the Lens","volume":"134","author":"Hejtmancik","year":"2015","journal-title":"Prog. Mol. Biol. Transl. Sci."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"333","DOI":"10.1186\/s13023-020-01613-3","article-title":"The genetic landscape of crystallins in congenital cataract","volume":"15","author":"Berry","year":"2020","journal-title":"Orphanet J. Rare Dis."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"43","DOI":"10.3389\/fphar.2013.00043","article-title":"Connexin mutants and cataracts","volume":"4","author":"Beyer","year":"2013","journal-title":"Front. Pharmacol."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"1512","DOI":"10.18240\/ijo.2020.10.02","article-title":"A novel mutation of LIM2 causes autosomal dominant membranous cataract in a Chinese family","volume":"13","author":"Pei","year":"2020","journal-title":"Int. J. Ophthalmol."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"471","DOI":"10.1002\/humu.23395","article-title":"Mutation update of transcription factor genes FOXE3, HSF4, MAF, and PITX3 causing cataracts and other developmental ocular defects","volume":"39","author":"Anand","year":"2018","journal-title":"Human Mutat."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"1837","DOI":"10.1172\/JCI38277","article-title":"Functions of the intermediate filament cytoskeleton in the eye lens","volume":"119","author":"Song","year":"2009","journal-title":"J. Clin. Investig."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"1540","DOI":"10.1167\/iovs.09-4388","article-title":"Cell fate and differentiation of the developing ocular lens","volume":"51","author":"Greiling","year":"2010","journal-title":"Invest. Ophthalmol. Vis. Sci."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"133","DOI":"10.1016\/j.exer.2008.08.017","article-title":"On the mechanism of organelle degradation in the vertebrate lens","volume":"88","author":"Bassnett","year":"2009","journal-title":"Exp. Eye Res."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"1190","DOI":"10.1098\/rstb.2010.0377","article-title":"The ocular lens: A classic model for development, physiology and disease","volume":"366","author":"Wormstone","year":"2011","journal-title":"Philos. Trans. R Soc. Lond. B Biol. Sci."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"169","DOI":"10.1016\/bs.pmbts.2015.04.007","article-title":"Lens Biology and Biochemistry","volume":"134","author":"Hejtmancik","year":"2015","journal-title":"Prog. Mol. Biol. Transl. Sci."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"74","DOI":"10.1016\/j.exer.2007.02.015","article-title":"Development and adult morphology of the eye lens in the zebrafish","volume":"85","author":"Dahm","year":"2007","journal-title":"Exp. Eye Res."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"41","DOI":"10.1016\/j.exer.2016.03.016","article-title":"The molecular mechanisms underlying lens fiber elongation","volume":"156","author":"Audette","year":"2017","journal-title":"Exp. Eye Res."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"2869","DOI":"10.1167\/iovs.18-24044","article-title":"Aqp0a Regulates Suture Stability in the Zebrafish Lens","volume":"59","author":"Vorontsova","year":"2018","journal-title":"Invest. Ophthalmol. Vis. Sci."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"1219","DOI":"10.1098\/rstb.2010.0324","article-title":"Lens fibre cell differentiation and organelle loss: Many paths lead to clarity","volume":"366","author":"Wride","year":"2011","journal-title":"Philos. Trans. R Soc. Lond. B Biol. Sci."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"141","DOI":"10.1016\/j.exer.2013.08.017","article-title":"Autophagy and mitophagy participate in ocular lens organelle degradation","volume":"116","author":"Costello","year":"2013","journal-title":"Exp. Eye Res."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"1273","DOI":"10.1007\/s12038-007-0136-7","article-title":"GATA family of transcription factors of vertebrates: Phylogenetics and chromosomal synteny","volume":"32","author":"He","year":"2007","journal-title":"J. Biosci."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"1366","DOI":"10.1210\/me.2005-0378","article-title":"Pituitary-specific Gata2 knockout: Effects on gonadotrope and thyrotrope function","volume":"20","author":"Charles","year":"2006","journal-title":"Mol. Endocrinol."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"569","DOI":"10.1111\/j.1365-2443.2009.01289.x","article-title":"GATA2-dependent and region-specific regulation of Gata2 transcription in the mouse midbrain","volume":"14","author":"Nozawa","year":"2009","journal-title":"Genes Cells"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"104","DOI":"10.1097\/ACI.0000000000000126","article-title":"GATA2 deficiency","volume":"15","author":"Hsu","year":"2015","journal-title":"Curr. Opin. Allergy Clin. Immunol."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"1519","DOI":"10.1182\/blood-2009-03-208629","article-title":"Autosomal dominant and sporadic monocytopenia with susceptibility to mycobacteria, fungi, papillomaviruses, and myelodysplasia","volume":"115","author":"Vinh","year":"2009","journal-title":"Blood"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"1081","DOI":"10.3324\/haematol.2011.048355","article-title":"Dendritic cell, monocyte, B and NK lymphoid deficiency defines the lost lineages of a new GATA-2 dependent myelodysplastic syndrome","volume":"96","author":"Bigley","year":"2011","journal-title":"Haematologica"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"1012","DOI":"10.1038\/ng.913","article-title":"Heritable GATA2 mutations associated with familial myelodysplastic syndrome and acute myeloid leukemia","volume":"43","author":"Hahn","year":"2011","journal-title":"Nat. Genet."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"221","DOI":"10.1038\/371221a0","article-title":"An early haematopoietic defect in mice lacking the transcription factor GATA-2","volume":"371","author":"Tsai","year":"1994","journal-title":"Nature"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"708113","DOI":"10.3389\/fcell.2021.708113","article-title":"Differential Requirement of Gata2a and Gata2b for Primitive and Definitive Myeloid Development in Zebrafish","volume":"9","author":"Lubin","year":"2021","journal-title":"Front. Cell. Dev. Biol."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"2687","DOI":"10.1182\/bloodadvances.2020002993","article-title":"Essential role for Gata2 in modulating lineage output from hematopoietic stem cells in zebrafish","volume":"5","author":"Gioacchino","year":"2021","journal-title":"Blood Adv."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"519","DOI":"10.1242\/dev.119.2.519","article-title":"Expression of the chicken GATA factor family during early erythroid development and differentiation","volume":"119","author":"Leonard","year":"1993","journal-title":"Development"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"2280","DOI":"10.1002\/dvdy.22035","article-title":"Transcription factor GATA-3 is essential for lens development","volume":"238","author":"Maeda","year":"2009","journal-title":"Dev. Dyn."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"2155","DOI":"10.1242\/dev.02377","article-title":"The GATA2 transcription factor negatively regulates the proliferation of neuronal progenitors","volume":"133","author":"Francius","year":"2006","journal-title":"Development"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"137","DOI":"10.1016\/j.semcdb.2004.11.002","article-title":"GATA1 in normal and malignant hematopoiesis","volume":"16","author":"Crispino","year":"2005","journal-title":"Semin. Cell Dev. Biol."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"53","DOI":"10.1242\/dev.02184","article-title":"Pax 2\/8-regulated Gata3 expression is necessary for morphogenesis and guidance of the nephric duct in the developing kidney","volume":"133","author":"Grote","year":"2006","journal-title":"Development"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"439","DOI":"10.1007\/978-3-030-28151-9_14","article-title":"Crystallins and Their Complexes","volume":"93","author":"Ghosh","year":"2019","journal-title":"Subcell Biochem."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"52","DOI":"10.1016\/j.pbiomolbio.2014.02.006","article-title":"Functions of crystallins in and out of lens: Roles in elongated and post-mitotic cells","volume":"115","author":"Slingsby","year":"2014","journal-title":"Prog. Biophys Mol. Biol."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"1105","DOI":"10.1007\/s00775-018-1607-z","article-title":"Mercury-induced aggregation of human lens \u03b3-crystallins reveals a potential role in cataract disease","volume":"23","author":"Serebryany","year":"2018","journal-title":"J. Biol. Inorg. Chem."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"698","DOI":"10.1016\/j.semcdb.2006.10.011","article-title":"The role of the lens actin cytoskeleton in fiber cell elongation and differentiation","volume":"17","author":"Rao","year":"2006","journal-title":"Semin. Cell Dev. Biol."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"143","DOI":"10.1146\/annurev-physchem-090419-121428","article-title":"\u03b1-Crystallins in the Vertebrate Eye Lens: Complex Oligomers and Molecular Chaperones","volume":"72","author":"Rocha","year":"2021","journal-title":"Annu. Rev. Phys. Chem."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"776","DOI":"10.1101\/gad.12.6.776","article-title":"Sox1 directly regulates the gamma-crystallin genes and is essential for lens development in mice","volume":"12","author":"Nishiguchi","year":"1998","journal-title":"Genes Dev."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"785","DOI":"10.1016\/0014-4835(92)90034-P","article-title":"Temporal regulation of six crystallin transcripts during mouse lens development","volume":"54","author":"Goring","year":"1992","journal-title":"Exp. Eye Res."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"307","DOI":"10.1242\/dev.127.2.307","article-title":"Regulation of mouse lens fiber cell development and differentiation by the Maf gene","volume":"127","author":"Ring","year":"2000","journal-title":"Development"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"417","DOI":"10.1006\/exer.1997.0344","article-title":"Determinations of some trace and heavy metals in rat lenses after tobacco smoke exposure and their relationships to lens injury","volume":"65","author":"Avunduk","year":"1997","journal-title":"Exp. Eye Res."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"591","DOI":"10.1534\/genetics.114.163667","article-title":"Efficient and heritable gene targeting in tilapia by CRISPR\/Cas9","volume":"197","author":"Li","year":"2014","journal-title":"Genetics"}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/24\/4\/3567\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T18:30:08Z","timestamp":1760121008000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/24\/4\/3567"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,2,10]]},"references-count":44,"journal-issue":{"issue":"4","published-online":{"date-parts":[[2023,2]]}},"alternative-id":["ijms24043567"],"URL":"https:\/\/doi.org\/10.3390\/ijms24043567","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,2,10]]}}}