{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,28]],"date-time":"2026-10-28T23:16:26Z","timestamp":1793229386171,"version":"4.5.0"},"reference-count":94,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2004,3,26]],"date-time":"2004-03-26T00:00:00Z","timestamp":1080259200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["BioEssays"],"published-print":{"date-parts":[[2004,4]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>During development of the anterior eye segment, cells that originate from the surface epithelium or the neuroepithelium need to interact with mesenchymal cells, which predominantly originate from the neural crest. Failures of proper interaction result in a complex of developmental disorders such Peters' anomaly, Axenfeld\u2013Rieger's syndrome or <jats:italic>aniridia<\/jats:italic>. Here we review the role of transcription factors that have been identified to be involved in the coordination of anterior eye development. Among these factors is PAX6, which is active in both epithelial and mesenchymal cells during ocular development, albeit at different doses and times. We propose that PAX6 is a key element that synchronizes the complex interaction of cell types of different origin, which are all needed for proper morphogenesis of the anterior eye. We discuss several molecular mechanisms that might explain the effects of haploinsufficiency of PAX6 and other transcription factors, and the broad variation of the resulting phenotypes. BioEssays 26:374\u2013386, 2004. \u00a9 2004 Wiley Periodicals, Inc.<\/jats:p>","DOI":"10.1002\/bies.20009","type":"journal-article","created":{"date-parts":[[2004,3,26]],"date-time":"2004-03-26T19:02:48Z","timestamp":1080327768000},"page":"374-386","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":272,"title":["Anterior eye development and ocular mesenchyme: new insights from mouse models and human diseases"],"prefix":"10.1002","volume":"26","author":[{"given":"Ale\u0161","family":"Cvekl","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ernst R.","family":"Tamm","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2004,3,26]]},"reference":[{"key":"e_1_2_1_2_2","volume-title":"Normal and Abnormal Development. Part 1. Embryology","author":"Duke\u2010Elder S","year":"1963"},{"key":"e_1_2_1_3_2","doi-asserted-by":"publisher","DOI":"10.1007\/BF00315823"},{"key":"e_1_2_1_4_2","doi-asserted-by":"publisher","DOI":"10.1002\/ar.1091680109"},{"key":"e_1_2_1_5_2","first-page":"381","article-title":"Comparative embryologic studies of the early development of the cornea and the pupillary membrane in reptiles, birds and mammals","volume":"76","author":"D\u00fcblin I","year":"1970","journal-title":"Acta Anat (Basel)"},{"key":"e_1_2_1_6_2","doi-asserted-by":"publisher","DOI":"10.1006\/dbio.1999.9314"},{"key":"e_1_2_1_7_2","doi-asserted-by":"crossref","first-page":"533","DOI":"10.1242\/dev.127.3.533","article-title":"Formation of corneal endothelium is essential for anterior segment development","volume":"127","author":"Reneker LW","year":"2000","journal-title":"Development"},{"key":"e_1_2_1_8_2","doi-asserted-by":"publisher","DOI":"10.1002\/dvdy.10144"},{"key":"e_1_2_1_9_2","first-page":"623","volume-title":"Handbuch der mikroskopischen Anatomie des Menschen, Haut und Siinesorgane. 2","author":"Kolmer W","year":"1936"},{"key":"e_1_2_1_10_2","doi-asserted-by":"publisher","DOI":"10.1002\/jmor.1051530207"},{"key":"e_1_2_1_11_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0074-7696(08)61760-X"},{"key":"e_1_2_1_12_2","first-page":"269","article-title":"The development of the productive and draining system of the aqueous humor in the human eye","volume":"26","author":"Wulle KG","year":"1972","journal-title":"Adv Ophthalmol"},{"key":"e_1_2_1_13_2","doi-asserted-by":"publisher","DOI":"10.1186\/1471-213X-1-3"},{"key":"e_1_2_1_14_2","doi-asserted-by":"publisher","DOI":"10.1007\/BF00143888"},{"key":"e_1_2_1_15_2","doi-asserted-by":"publisher","DOI":"10.1016\/0014-4835(79)90164-7"},{"key":"e_1_2_1_16_2","doi-asserted-by":"publisher","DOI":"10.1242\/dev.121.8.2569"},{"key":"e_1_2_1_17_2","doi-asserted-by":"publisher","DOI":"10.1002\/jez.1401560104"},{"key":"e_1_2_1_18_2","doi-asserted-by":"publisher","DOI":"10.1038\/210209a0"},{"key":"e_1_2_1_19_2","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/11.1.33"},{"key":"e_1_2_1_20_2","doi-asserted-by":"publisher","DOI":"10.1242\/dev.127.2.307"},{"key":"e_1_2_1_21_2","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/10.3.231"},{"key":"e_1_2_1_22_2","first-page":"1350","article-title":"Foxe3 haploinsufficiency in mice: a model for Peters' anomaly","volume":"43","author":"Ormestad M","year":"2002","journal-title":"Invest Ophthalmol Vis Sci"},{"key":"e_1_2_1_23_2","doi-asserted-by":"publisher","DOI":"10.1101\/gad.14.2.245"},{"key":"e_1_2_1_24_2","doi-asserted-by":"publisher","DOI":"10.1002\/1526-968X(200006)27:2<81::AID-GENE50>3.0.CO;2-N"},{"key":"e_1_2_1_25_2","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/9.11.1575"},{"key":"e_1_2_1_26_2","doi-asserted-by":"publisher","DOI":"10.1006\/geno.2000.6464"},{"key":"e_1_2_1_27_2","doi-asserted-by":"publisher","DOI":"10.1093\/oxfordjournals.jhered.a107667"},{"key":"e_1_2_1_28_2","doi-asserted-by":"publisher","DOI":"10.1038\/527"},{"key":"e_1_2_1_29_2","first-page":"887","volume-title":"The glaucomas","author":"Schottenstein EM","year":"1996"},{"key":"e_1_2_1_30_2","doi-asserted-by":"publisher","DOI":"10.1038\/45797"},{"key":"e_1_2_1_31_2","doi-asserted-by":"publisher","DOI":"10.1038\/45803"},{"key":"e_1_2_1_32_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0092-8674(00)81204-0"},{"key":"e_1_2_1_33_2","doi-asserted-by":"publisher","DOI":"10.1086\/302109"},{"key":"e_1_2_1_34_2","first-page":"2456","article-title":"Phenotypic variability and asymmetry of Rieger syndrome associated with PITX2 mutations","volume":"41","author":"Perveen R","year":"2000","journal-title":"Invest Ophthalmol Vis Sci"},{"key":"e_1_2_1_35_2","doi-asserted-by":"crossref","first-page":"152","DOI":"10.1136\/jmg.36.2.152","article-title":"A mutation in the RIEG1 gene associated with Peters' anomaly","volume":"36","author":"Doward W","year":"1999","journal-title":"J Med Genet"},{"key":"e_1_2_1_36_2","doi-asserted-by":"publisher","DOI":"10.1038\/493"},{"key":"e_1_2_1_37_2","doi-asserted-by":"publisher","DOI":"10.1038\/ng1296-392"},{"key":"e_1_2_1_38_2","doi-asserted-by":"publisher","DOI":"10.1086\/318183"},{"key":"e_1_2_1_39_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0002-9394(00)00525-0"},{"key":"e_1_2_1_40_2","doi-asserted-by":"publisher","DOI":"10.1016\/0039-6257(75)90034-X"},{"key":"e_1_2_1_41_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0002-9394(02)02061-5"},{"key":"e_1_2_1_42_2","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/11.10.1185"},{"key":"e_1_2_1_43_2","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/9.7.1021"},{"key":"e_1_2_1_44_2","doi-asserted-by":"publisher","DOI":"10.1242\/dev.126.20.4643"},{"key":"e_1_2_1_45_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0955-0674(00)00274-X"},{"key":"e_1_2_1_46_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0168-9525(99)01776-X"},{"key":"e_1_2_1_47_2","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.cellbio.17.1.255"},{"key":"e_1_2_1_48_2","doi-asserted-by":"publisher","DOI":"10.1016\/0092-8674(91)90284-6"},{"key":"e_1_2_1_49_2","doi-asserted-by":"publisher","DOI":"10.1038\/ng0892-328"},{"key":"e_1_2_1_50_2","doi-asserted-by":"publisher","DOI":"10.1038\/ng1192-232"},{"key":"e_1_2_1_51_2","first-page":"859","volume-title":"The glaucomas","author":"Mintz\u2010Hittner HA","year":"1996"},{"key":"e_1_2_1_52_2","doi-asserted-by":"publisher","DOI":"10.1016\/0039-6257(84)90184-X"},{"key":"e_1_2_1_53_2","doi-asserted-by":"publisher","DOI":"10.1002\/(SICI)1098-1004(1998)11:2<93::AID-HUMU1>3.0.CO;2-M"},{"key":"e_1_2_1_54_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0925-4773(02)00260-5"},{"key":"e_1_2_1_55_2","doi-asserted-by":"crossref","first-page":"115","DOI":"10.1242\/dev.103.Supplement.115","article-title":"Small eye (Sey): a mouse model for the genetic analysis of craniofacial abnormalities","volume":"103","author":"Hogan BL","year":"1988","journal-title":"Development"},{"key":"e_1_2_1_56_2","doi-asserted-by":"publisher","DOI":"10.1167\/iovs.02-0576"},{"key":"e_1_2_1_57_2","doi-asserted-by":"publisher","DOI":"10.1242\/jcs.00441"},{"key":"e_1_2_1_58_2","doi-asserted-by":"publisher","DOI":"10.1242\/dev.113.4.1435"},{"key":"e_1_2_1_59_2","doi-asserted-by":"publisher","DOI":"10.1242\/dev.121.5.1433"},{"key":"e_1_2_1_60_2","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.16-16-05082.1996"},{"key":"e_1_2_1_61_2","first-page":"108","article-title":"The Pax\u20106 homeobox gene is expressed throughout the corneal and conjunctival epithelia","volume":"38","author":"Koroma BM","year":"1997","journal-title":"Invest Ophthalmol Vis Sci"},{"key":"e_1_2_1_62_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0012-1606(02)00095-7"},{"key":"e_1_2_1_63_2","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/29.5.1228"},{"key":"e_1_2_1_64_2","doi-asserted-by":"publisher","DOI":"10.1101\/gad.184000"},{"key":"e_1_2_1_65_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0925-4773(02)00137-5"},{"key":"e_1_2_1_66_2","doi-asserted-by":"publisher","DOI":"10.1128\/MCB.14.11.7363"},{"key":"e_1_2_1_67_2","doi-asserted-by":"publisher","DOI":"10.1242\/dev.127.24.5439"},{"key":"e_1_2_1_68_2","doi-asserted-by":"crossref","first-page":"3173","DOI":"10.1242\/jcs.113.18.3173","article-title":"Overexpression of PAX6(5a) in lens fiber cells results in cataract and upregulation of (alpha)5(beta)1 integrin expression","volume":"113","author":"Duncan MK","year":"2000","journal-title":"J Cell Sci"},{"key":"e_1_2_1_69_2","doi-asserted-by":"publisher","DOI":"10.1046\/j.1365-2443.2002.00602.x"},{"key":"e_1_2_1_70_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.161144098"},{"key":"e_1_2_1_71_2","doi-asserted-by":"publisher","DOI":"10.1186\/1471-2156-2-18"},{"key":"e_1_2_1_72_2","doi-asserted-by":"crossref","first-page":"2659","DOI":"10.1242\/dev.124.13.2659","article-title":"TGFbeta2 knockout mice have multiple developmental defects that are non\u2010 overlapping with other TGFbeta knockout phenotypes","volume":"124","author":"Sanford LP","year":"1997","journal-title":"Development"},{"key":"e_1_2_1_73_2","doi-asserted-by":"publisher","DOI":"10.1006\/dbio.2001.0480"},{"key":"e_1_2_1_74_2","doi-asserted-by":"publisher","DOI":"10.1006\/geno.2002.6860"},{"key":"e_1_2_1_75_2","doi-asserted-by":"publisher","DOI":"10.1128\/MCB.15.5.2858"},{"key":"e_1_2_1_76_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.132195699"},{"key":"e_1_2_1_77_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M104523200"},{"key":"e_1_2_1_78_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M008882200"},{"key":"e_1_2_1_79_2","first-page":"1041","article-title":"Quail Pax\u20106 (Pax\u2010QNR) encodes a transcription factor able to bind and trans\u2010activate its own promoter","volume":"4","author":"Plaza S","year":"1993","journal-title":"Cell Growth Differ"},{"key":"e_1_2_1_80_2","doi-asserted-by":"publisher","DOI":"10.1128\/MCB.15.2.892"},{"key":"e_1_2_1_81_2","doi-asserted-by":"publisher","DOI":"10.1101\/gad.13.10.1263"},{"key":"e_1_2_1_82_2","doi-asserted-by":"publisher","DOI":"10.1167\/iovs.03-0968"},{"key":"e_1_2_1_83_2","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/2.12.2093"},{"key":"e_1_2_1_84_2","doi-asserted-by":"publisher","DOI":"10.1038\/ng0894-463"},{"key":"e_1_2_1_85_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.273.34.21531"},{"key":"e_1_2_1_86_2","first-page":"1343","article-title":"Pax\u20106 interactions with TATA\u2010box\u2010binding protein and retinoblastoma protein","volume":"40","author":"Cvekl A","year":"1999","journal-title":"Invest Ophthalmol Vis Sci"},{"key":"e_1_2_1_87_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0092-8674(00)80078-1"},{"key":"e_1_2_1_88_2","doi-asserted-by":"publisher","DOI":"10.1038\/ng0294-168"},{"key":"e_1_2_1_89_2","doi-asserted-by":"publisher","DOI":"10.1002\/(SICI)1098-1004(1998)12:5<304::AID-HUMU3>3.0.CO;2-D"},{"key":"e_1_2_1_90_2","doi-asserted-by":"crossref","first-page":"1689","DOI":"10.1093\/genetics\/159.4.1689","article-title":"Molecular characterization of Pax6(2Neu) through Pax6(10Neu): an extension of the Pax6 allelic series and the identification of two possible hypomorph alleles in the mouse Mus musculus","volume":"159","author":"Favor J","year":"2001","journal-title":"Genetics"},{"key":"e_1_2_1_91_2","doi-asserted-by":"crossref","first-page":"9873","DOI":"10.1523\/JNEUROSCI.23-30-09873.2003","article-title":"R\u2010cadherin is a Pax6\u2010regulated, growth\u2010promoting cue for pioneer axons","volume":"23","author":"Andrews GL","year":"2003","journal-title":"J Neurosci"},{"key":"e_1_2_1_92_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M110531200"},{"key":"e_1_2_1_93_2","doi-asserted-by":"publisher","DOI":"10.1038\/ng0493-299"},{"key":"e_1_2_1_94_2","doi-asserted-by":"publisher","DOI":"10.1006\/dbio.2000.9652"},{"key":"e_1_2_1_95_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0437920100"}],"container-title":["BioEssays"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1002%2Fbies.20009","content-type":"unspecified","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/bies.20009","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,9,28]],"date-time":"2023-09-28T21:21:54Z","timestamp":1695936114000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/bies.20009"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2004,3,26]]},"references-count":94,"journal-issue":{"issue":"4","published-print":{"date-parts":[[2004,4]]}},"alternative-id":["10.1002\/bies.20009"],"URL":"https:\/\/doi.org\/10.1002\/bies.20009","archive":["Portico"],"relation":{},"ISSN":["0265-9247","1521-1878"],"issn-type":[{"value":"0265-9247","type":"print"},{"value":"1521-1878","type":"electronic"}],"subject":[],"published":{"date-parts":[[2004,3,26]]},"assertion":[{"value":"2004-03-26","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}