{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,20]],"date-time":"2026-10-20T11:43:35Z","timestamp":1792496615364,"version":"4.5.0"},"reference-count":49,"publisher":"Elsevier BV","issue":"11","license":[{"start":{"date-parts":[[2019,11,1]],"date-time":"2019-11-01T00:00:00Z","timestamp":1572566400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/tdm\/userlicense\/1.0\/"},{"start":{"date-parts":[[2019,11,1]],"date-time":"2019-11-01T00:00:00Z","timestamp":1572566400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/legal\/tdmrep-license"},{"start":{"date-parts":[[2023,1,5]],"date-time":"2023-01-05T00:00:00Z","timestamp":1672876800000},"content-version":"vor","delay-in-days":1161,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81371003"],"award-info":[{"award-number":["81371003"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100002858","name":"China Postdoctoral Science Foundation","doi-asserted-by":"publisher","award":["81870646"],"award-info":[{"award-number":["81870646"]}],"id":[{"id":"10.13039\/501100002858","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100002858","name":"China Postdoctoral Science Foundation","doi-asserted-by":"publisher","award":["2015M570517"],"award-info":[{"award-number":["2015M570517"]}],"id":[{"id":"10.13039\/501100002858","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["li.uscap.org","elsevier.com","sciencedirect.com"],"crossmark-restriction":true},"short-container-title":["Laboratory Investigation"],"published-print":{"date-parts":[[2019,11]]},"DOI":"10.1038\/s41374-018-0180-y","type":"journal-article","created":{"date-parts":[[2019,1,25]],"date-time":"2019-01-25T11:02:40Z","timestamp":1548414160000},"page":"1714-1727","update-policy":"https:\/\/doi.org\/10.1016\/elsevier_cm_policy","source":"Crossref","is-referenced-by-count":4,"title":["Lens-specific conditional knockout of Msx2 in mice leads to ocular anterior segment dysgenesis via activation of a calcium signaling pathway"],"prefix":"10.1016","volume":"99","author":[{"given":"Wenting","family":"Yu","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ziyan","family":"Yu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Danhong","family":"Wu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiao","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ying","family":"Zhu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yang","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hong","family":"Ning","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mingwu","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jinsong","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiangyue","family":"Zhao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"78","reference":[{"key":"10.1038\/s41374-018-0180-y_bib1","doi-asserted-by":"crossref","first-page":"13","DOI":"10.1111\/ceo.12152","article-title":"Genomics and anterior segment dysgenesis: a review","volume":"42","author":"Ito","year":"2014","journal-title":"Clin Exp Ophthalmol"},{"key":"10.1038\/s41374-018-0180-y_bib2","doi-asserted-by":"crossref","first-page":"1185","DOI":"10.1093\/hmg\/11.10.1185","article-title":"Anterior segment dysgenesis and the developmental glaucomas are complex traits","volume":"11","author":"Gould","year":"2002","journal-title":"Hum Mol Genet"},{"key":"10.1038\/s41374-018-0180-y_bib3","doi-asserted-by":"crossref","first-page":"314","DOI":"10.1097\/ICU.0b013e328349412b","article-title":"Genetics of anterior segment dysgenesis disorders","volume":"22","author":"Reis","year":"2011","journal-title":"Curr Opin Ophthalmol"},{"key":"10.1038\/s41374-018-0180-y_bib4","doi-asserted-by":"crossref","first-page":"1310","DOI":"10.1038\/sj.eye.6702852","article-title":"Molecular and developmental mechanisms of anterior segment dysgenesis","volume":"21","author":"Sowden","year":"2007","journal-title":"Eye"},{"key":"10.1038\/s41374-018-0180-y_bib5","doi-asserted-by":"crossref","first-page":"2569","DOI":"10.1242\/dev.121.8.2569","article-title":"Cranial paraxial mesoderm and neural crest cells of the mouse embryo: co-distribution in the craniofacial mesenchyme but distinct segregation in branchial arches","volume":"121","author":"Trainor","year":"1995","journal-title":"Development"},{"key":"10.1038\/s41374-018-0180-y_bib6","doi-asserted-by":"crossref","first-page":"4200","DOI":"10.1167\/iovs.05-0691","article-title":"Fate maps of neural crest and mesoderm in the mammalian eye","volume":"46","author":"Gage","year":"2005","journal-title":"Invest Ophthalmol Vis Sci"},{"key":"10.1038\/s41374-018-0180-y_bib7","doi-asserted-by":"crossref","first-page":"405","DOI":"10.1016\/S0168-9525(00)89124-6","article-title":"The function and evolution of Msx genes: pointers and paradoxes","volume":"11","author":"Davidson","year":"1995","journal-title":"Trends Genet"},{"key":"10.1038\/s41374-018-0180-y_bib8","doi-asserted-by":"crossref","first-page":"387","DOI":"10.1038\/74224","article-title":"Functional haploinsufficiency of the human homeobox gene MSX2 causes defects in skull ossification","volume":"24","author":"Elanko","year":"2000","journal-title":"Nat Genet"},{"key":"10.1038\/s41374-018-0180-y_bib9","doi-asserted-by":"crossref","first-page":"203","DOI":"10.1016\/j.jdermsci.2013.04.019","article-title":"Hairless down-regulates expression of Msx2 and its related target genes in hair follicles","volume":"71","author":"Kim","year":"2013","journal-title":"J Dermatol Sci"},{"key":"10.1038\/s41374-018-0180-y_bib10","doi-asserted-by":"crossref","first-page":"624","DOI":"10.1016\/j.tig.2005.09.001","article-title":"msh\/Msx gene family in neural development","volume":"21","author":"Ramos","year":"2005","journal-title":"Trends Genet"},{"key":"10.1038\/s41374-018-0180-y_bib11","first-page":"510","article-title":"MSX2 in ameloblast cell fate and activity","volume":"5","author":"Babajko","year":"2014","journal-title":"Front Physiol"},{"key":"10.1038\/s41374-018-0180-y_bib12","doi-asserted-by":"crossref","first-page":"421","DOI":"10.1016\/j.ydbio.2007.05.037","article-title":"Msx1 and Msx2 regulate survival of secondary heart field precursors and post-migratory proliferation of cardiac neural crest in the outflow tract","volume":"308","author":"Chen","year":"2007","journal-title":"Dev Biol"},{"key":"10.1038\/s41374-018-0180-y_bib13","doi-asserted-by":"crossref","first-page":"2404","DOI":"10.1167\/iovs.02-0317","article-title":"Microphthalmia resulting fromMsx2-induced apoptosis in the optic vesicle","volume":"44","author":"Wu","year":"2003","journal-title":"Invest Opthalmol Vis Sci"},{"key":"10.1038\/s41374-018-0180-y_bib14","doi-asserted-by":"crossref","first-page":"2230","DOI":"10.1016\/j.ajpath.2012.02.017","article-title":"Loss of Msx2 function down-regulates the FoxE3 expression and results in anterior segment dysgenesis resembling Peters anomaly","volume":"180","author":"Zhao","year":"2012","journal-title":"Am J Pathol"},{"key":"10.1038\/s41374-018-0180-y_bib15","doi-asserted-by":"crossref","first-page":"2843","DOI":"10.1177\/0300060518774687","article-title":"Lens-specific deletion of the Msx2 gene increased apoptosis by enhancing the caspase-3\/caspase-8 signaling pathway","volume":"46","author":"Yu","year":"2018","journal-title":"J Int Med Res"},{"key":"10.1038\/s41374-018-0180-y_bib16","doi-asserted-by":"crossref","first-page":"276","DOI":"10.1002\/dvg.20390","article-title":"Generation of an Msx2-GFP conditional null allele","volume":"46","author":"Bensoussan","year":"2008","journal-title":"Genesis"},{"issue":"10","key":"10.1038\/s41374-018-0180-y_bib17","doi-asserted-by":"crossref","first-page":"e109193","DOI":"10.1371\/journal.pone.0109193","article-title":"Hemizygous Le-Cre transgenic mice have severe eye abnormalities on some genetic backgrounds in the absence of LoxP sites","volume":"9","author":"Dor\u00e0","year":"2014","journal-title":"PLoS One"},{"key":"10.1038\/s41374-018-0180-y_bib18","doi-asserted-by":"crossref","first-page":"2701","DOI":"10.1101\/gad.184000","article-title":"Pax6 activity in the lens primordium is required for lens formation and for correct placement of a single retina in the eye","volume":"14","author":"Ashery-Padan","year":"2000","journal-title":"Genes Dev"},{"key":"10.1038\/s41374-018-0180-y_bib19","first-page":"Unit14 19","article-title":"Whole-mount in situ hybridization and detection of RNAs in vertebrate embryos and isolated organs","volume":"Chapter 14","author":"Pizard","year":"2004","journal-title":"Curr Protoc Mol Biol"},{"key":"10.1038\/s41374-018-0180-y_bib20","doi-asserted-by":"crossref","first-page":"1182","DOI":"10.1016\/j.bbadis.2011.04.006","article-title":"Assessment of newly synthesized mitochondrial DNA using BrdU labeling in primary neurons from Alzheimer's disease mice: Implications for impaired mitochondrial biogenesis and synaptic damage","volume":"1812","author":"Calkins","year":"2011","journal-title":"Biochim Biophys Acta"},{"issue":"1","key":"10.1038\/s41374-018-0180-y_bib21","doi-asserted-by":"crossref","first-page":"e0190817","DOI":"10.1371\/journal.pone.0190817","article-title":"Probing the changes in gene expression due to \u03b1-crystallin mutations in mouse models of hereditary human cataract","volume":"13","author":"Andley","year":"2018","journal-title":"PLoS One"},{"key":"10.1038\/s41374-018-0180-y_bib22","first-page":"1491","article-title":"Comparative transcriptome analysis of epithelial and fiber cells in newborn mouse lenses with RNA sequencing","volume":"20","author":"Hoang","year":"2014","journal-title":"Mol Vis"},{"issue":"12","key":"10.1038\/s41374-018-0180-y_bib23","doi-asserted-by":"crossref","first-page":"e0143781","DOI":"10.1371\/journal.pone.0143781","article-title":"The analysis of intracellular and intercellular calcium signaling in human anterior lens capsule epithelial cells with regard to different types and stages of the cataract","volume":"10","author":"Marko","year":"2015","journal-title":"PLoS One"},{"key":"10.1038\/s41374-018-0180-y_bib24","doi-asserted-by":"crossref","first-page":"443","DOI":"10.1016\/0092-8674(93)90379-5","article-title":"A mutation in the homeodomain of the human MSX2 gene in a family affected with autosomal dominant craniosynostosis","volume":"75","author":"Jabs","year":"1993","journal-title":"Cell"},{"key":"10.1038\/s41374-018-0180-y_bib25","doi-asserted-by":"crossref","first-page":"6137","DOI":"10.1073\/pnas.92.13.6137","article-title":"Premature suture closure and ectopic cranial bone in mice expressing Msx2 transgenes in the developing skull","volume":"92","author":"Liu","year":"1995","journal-title":"Proc Natl Acad Sci"},{"key":"10.1038\/s41374-018-0180-y_bib26","doi-asserted-by":"crossref","first-page":"48","DOI":"10.1111\/j.1749-6632.1996.tb56243.x","article-title":"Function of the Msx2 gene in the morphogenesis of the skulla","volume":"785","author":"Liu","year":"1996","journal-title":"Ann N Y Acad Sci"},{"issue":"2","key":"10.1038\/s41374-018-0180-y_bib27","doi-asserted-by":"crossref","first-page":"260","DOI":"10.1006\/dbio.1998.9114","article-title":"Msx2 gene dosage influences the number of proliferative osteogenic cells in growth centers of the developing murine skull: a possible mechanism for Msx2 -mediated craniosynostosis in humans","volume":"205","author":"Liu","year":"1999","journal-title":"Dev Biol"},{"key":"10.1038\/s41374-018-0180-y_bib28","doi-asserted-by":"crossref","first-page":"230","DOI":"10.1046\/j.1523-1747.1999.00680.x","article-title":"Epidermal dysplasia and abnormal hair follicles in transgenic mice overexpressing homeobox gene MSX-2","volume":"113","author":"Jiang","year":"1999","journal-title":"J Invest Dermatol"},{"key":"10.1038\/s41374-018-0180-y_bib29","doi-asserted-by":"crossref","first-page":"391","DOI":"10.1038\/74231","article-title":"Msx2 deficiency in mice causes pleiotropic defects in bone growth and ectodermal organ formation","volume":"24","author":"Satokata","year":"2000","journal-title":"Nat Genet"},{"key":"10.1038\/s41374-018-0180-y_bib30","doi-asserted-by":"crossref","first-page":"223","DOI":"10.1016\/0014-4835(75)90136-0","article-title":"Ion analyses of human cataractous lenses","volume":"20","author":"Duncan","year":"1975","journal-title":"Exp Eye Res"},{"key":"10.1038\/s41374-018-0180-y_bib31","doi-asserted-by":"crossref","unstructured":"Duncan G, Jacob TJC. Calcium and the physiology of cataract. Ciba Foundation Symposium 106\u2013Human Cataract Formation. John Wiley & Sons, Ltd., UK: Cardiff University; 2008. p. 132\u201362.","DOI":"10.1002\/9780470720875.ch8"},{"key":"10.1038\/s41374-018-0180-y_bib32","first-page":"2835","article-title":"Calcium regulation in tissue-cultured human and bovine lens epithelial cells","volume":"34","author":"Duncan","year":"1993","journal-title":"Invest Ophthalmol Vis Sci"},{"key":"10.1038\/s41374-018-0180-y_bib33","doi-asserted-by":"crossref","first-page":"851","DOI":"10.2174\/156652410793937750","article-title":"Gap junctions or hemichannel-dependent and independent roles of connexins in cataractogenesis and lens development","volume":"10","author":"Jiang","year":"2010","journal-title":"Curr Mol Med"},{"key":"10.1038\/s41374-018-0180-y_bib34","doi-asserted-by":"crossref","first-page":"9","DOI":"10.1007\/s00232-007-9033-0","article-title":"Connexins in lens development and cataractogenesis","volume":"218","author":"Gong","year":"2007","journal-title":"J Membr Biol"},{"key":"10.1038\/s41374-018-0180-y_bib35","doi-asserted-by":"crossref","first-page":"289","DOI":"10.1085\/jgp.200409121","article-title":"Connections between connexins, calcium, and cataracts in the lens","volume":"124","author":"Gao","year":"2004","journal-title":"J Gen Physiol"},{"key":"10.1038\/s41374-018-0180-y_bib36","doi-asserted-by":"crossref","first-page":"1077","DOI":"10.1083\/jcb.115.4.1077","article-title":"Connexin46, a novel lens gap junction protein, induces voltage-gated currents in nonjunctional plasma membrane of Xenopus oocytes","volume":"115","author":"Paul","year":"1991","journal-title":"J Cell Biol"},{"key":"10.1038\/s41374-018-0180-y_bib37","doi-asserted-by":"crossref","first-page":"711","DOI":"10.1091\/mbc.3.7.711","article-title":"Mouse Cx50, a functional member of the connexin family of gap junction proteins, is the lens fiber protein MP70","volume":"3","author":"White","year":"1992","journal-title":"Mol Biol Cell"},{"key":"10.1038\/s41374-018-0180-y_bib38","doi-asserted-by":"crossref","first-page":"7614","DOI":"10.1167\/iovs.13-13188","article-title":"Connexin50D47A decreases levels of fiber cell connexins and impairs lens fiber cell differentiation","volume":"54","author":"Berthoud","year":"2013","journal-title":"Invest Ophthalmol Vis Sci"},{"key":"10.1038\/s41374-018-0180-y_bib39","first-page":"1585","article-title":"A novel mutation in Gja8 causing congenital cataract-microcornea syndrome in a Chinese pedigree","volume":"16","author":"Hu","year":"2010","journal-title":"Mol Vis"},{"key":"10.1038\/s41374-018-0180-y_bib40","first-page":"418","article-title":"A novel connexin 50 (GJA8) mutation in a Chinese family with a dominant congenital pulverulent nuclear cataract","volume":"14","author":"Ming","year":"2008","journal-title":"Mol Vis"},{"key":"10.1038\/s41374-018-0180-y_bib41","doi-asserted-by":"crossref","first-page":"204","DOI":"10.1016\/0006-291X(83)90401-1","article-title":"Lens calcium activated proteinase: degradation of vimentin","volume":"116","author":"Roy","year":"1983","journal-title":"Biochem Biophys Res Commun"},{"key":"10.1038\/s41374-018-0180-y_bib42","doi-asserted-by":"crossref","first-page":"893","DOI":"10.1006\/bbrc.1996.0159","article-title":"Calcium ionophore induced proteolysis and cataract: inhibition by cell permeable calpain antagonists","volume":"218","author":"Sanderson","year":"1996","journal-title":"Biochem Biophys Res Commun"},{"key":"10.1038\/s41374-018-0180-y_bib43","doi-asserted-by":"crossref","first-page":"78","DOI":"10.1016\/j.molmed.2003.12.007","article-title":"Calpains: targets of cataract prevention?","volume":"10","author":"Biswas","year":"2004","journal-title":"Trends Mol Med"},{"key":"10.1038\/s41374-018-0180-y_bib44","doi-asserted-by":"crossref","first-page":"458","DOI":"10.1076\/ceyr.22.6.458.5483","article-title":"Proteolysis by m-calpain enhances in vitro light scattering by crystallins from human and bovine lenses","volume":"22","author":"Shih","year":"2001","journal-title":"Curr Eye Res"},{"key":"10.1038\/s41374-018-0180-y_bib45","doi-asserted-by":"crossref","first-page":"245","DOI":"10.1016\/S0014-5793(01)02565-0","article-title":"Transglutaminase\u2010mediated cross\u2010linking of \u03b1\u2010crystallin: structural and functional consequences","volume":"499","author":"Shridas","year":"2001","journal-title":"FEBS Lett"},{"key":"10.1038\/s41374-018-0180-y_bib46","doi-asserted-by":"crossref","first-page":"15032","DOI":"10.1074\/jbc.M308734200","article-title":"Cell type-specific activation of intracellular transglutaminase 2 by oxidative stress or ultraviolet irradiation: implications of transglutaminase 2 in age-related cataractogenesis","volume":"279","author":"Shin","year":"2004","journal-title":"J Biol Chem"},{"key":"10.1038\/s41374-018-0180-y_bib47","doi-asserted-by":"crossref","first-page":"15","DOI":"10.1002\/emmm.201100184","article-title":"AKAP2 anchors PKA with aquaporin-0 to support ocular lens transparency","volume":"4","author":"Gold","year":"2012","journal-title":"EMBO Mol Med"},{"key":"10.1038\/s41374-018-0180-y_bib48","doi-asserted-by":"crossref","first-page":"339","DOI":"10.1021\/bi701980t","article-title":"Aquaporin 0-calmodulin interaction and the effect of aquaporin 0 phosphorylation","volume":"47","author":"Rose","year":"2008","journal-title":"Biochemistry"},{"key":"10.1038\/s41374-018-0180-y_bib49","doi-asserted-by":"crossref","first-page":"e37637","DOI":"10.1371\/journal.pone.0037637","article-title":"The Arg233Lys AQP0 mutation disturbs aquaporin0-calmodulin interaction causing polymorphic congenital cataract","volume":"7","author":"Hu","year":"2012","journal-title":"PLoS One"}],"container-title":["Laboratory Investigation"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/www.nature.com\/articles\/s41374-018-0180-y.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"http:\/\/www.nature.com\/articles\/s41374-018-0180-y","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0023683722005694?httpAccept=text\/xml","content-type":"text\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0023683722005694?httpAccept=text\/plain","content-type":"text\/plain","content-version":"vor","intended-application":"text-mining"},{"URL":"http:\/\/www.nature.com\/articles\/s41374-018-0180-y.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,9,20]],"date-time":"2025-09-20T19:30:41Z","timestamp":1758396641000},"score":1,"resource":{"primary":{"URL":"https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S0023683722005694"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2019,11]]},"references-count":49,"journal-issue":{"issue":"11","published-print":{"date-parts":[[2019,11]]}},"alternative-id":["S0023683722005694"],"URL":"https:\/\/doi.org\/10.1038\/s41374-018-0180-y","relation":{},"ISSN":["0023-6837"],"issn-type":[{"value":"0023-6837","type":"print"}],"subject":[],"published":{"date-parts":[[2019,11]]},"assertion":[{"value":"Elsevier","name":"publisher","label":"This article is maintained by"},{"value":"Lens-specific conditional knockout of Msx2 in mice leads to ocular anterior segment dysgenesis via activation of a calcium signaling pathway","name":"articletitle","label":"Article Title"},{"value":"Laboratory Investigation","name":"journaltitle","label":"Journal Title"},{"value":"https:\/\/doi.org\/10.1038\/s41374-018-0180-y","name":"articlelink","label":"CrossRef DOI link to publisher maintained version"},{"value":"article","name":"content_type","label":"Content Type"},{"value":"\u00a9 2019 The Authors.","name":"copyright","label":"Copyright"}]}}