{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,18]],"date-time":"2026-10-18T00:29:04Z","timestamp":1792283344685,"version":"4.4.0"},"reference-count":93,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2021,1,11]],"date-time":"2021-01-11T00:00:00Z","timestamp":1610323200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100014013","name":"UK Research and Innovation","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100014013","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Cell Dev. Biol."],"abstract":"<jats:p>A key embryonic process that occurs early in ocular development is optic fissure closure (OFC). This fusion process closes the ventral optic fissure and completes the circumferential continuity of the 3-dimensional eye. It is defined by the coming together and fusion of opposing neuroepithelia along the entire proximal-distal axis of the ventral optic cup, involving future neural retina, retinal pigment epithelium (RPE), optic nerve, ciliary body, and iris. Once these have occurred, cells within the fused seam differentiate into components of the functioning visual system. Correct development and progression of OFC, and the continued integrity of the fused margin along this axis, are important for the overall structure of the eye. Failure of OFC results in ocular coloboma\u2014a significant cause of childhood visual impairment that can be associated with several complex ocular phenotypes including microphthalmia and anterior segment dysgenesis. Despite a large number of genes identified, the exact pathways that definitively mediate fusion have not yet been found, reflecting both the biological complexity and genetic heterogeneity of the process. This review will highlight how recent developmental studies have become focused specifically on the epithelial fusion aspects of OFC, applying a range of model organisms (spanning fish, avian, and mammalian species) and utilizing emerging high-resolution live-imaging technologies, transgenic fluorescent models, and unbiased transcriptomic analyses of segmentally-dissected fissure tissue. Key aspects of the fusion process are discussed, including basement membrane dynamics, unique cell behaviors, and the identities and fates of the cells that mediate fusion. These will be set in the context of what is now known, and how these point the way to new avenues of research.<\/jats:p>","DOI":"10.3389\/fcell.2020.620774","type":"journal-article","created":{"date-parts":[[2021,1,12]],"date-time":"2021-01-12T23:48:33Z","timestamp":1610495313000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":29,"title":["Closing the Gap: Mechanisms of Epithelial Fusion During Optic Fissure Closure"],"prefix":"10.3389","volume":"8","author":[{"given":"Brian Ho Ching","family":"Chan","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mariya","family":"Moosajee","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joe","family":"Rainger","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2021,1,11]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"92","DOI":"10.1016\/j.ajhg.2010.12.002","article-title":"Mutations in the SPARC-related modular calcium-binding protein 1 gene, SMOC1, cause waardenburg anophthalmia syndrome.","volume":"88","author":"Abouzeid","year":"2011","journal-title":"Am. J. Hum. Genet."},{"key":"B2","doi-asserted-by":"publisher","first-page":"865","DOI":"10.1007\/s00439-019-02019-3","article-title":"An update on the genetics of ocular coloboma.","volume":"138","author":"ALSomiry","year":"2019","journal-title":"Hum. Genet."},{"key":"B3","doi-asserted-by":"publisher","first-page":"10729","DOI":"10.1073\/pnas.96.19.10729","article-title":"A homeobox gene, vax2, controls the patterning of the eye dorsoventral axis.","volume":"96","author":"Barbieri","year":"1999","journal-title":"Proc. Natl. Acad. Sci. U. S. A."},{"key":"B4","doi-asserted-by":"publisher","first-page":"137","DOI":"10.1016\/j.ydbio.2018.05.010","article-title":"The cellular bases of choroid fissure formation and closure.","volume":"440","author":"Bernstein","year":"2018","journal-title":"Dev. Biol."},{"key":"B5","doi-asserted-by":"publisher","first-page":"421","DOI":"10.1078\/0171-9335-00328","article-title":"Role of apoptosis and mitosis during human eye development.","volume":"82","author":"Bo\u017eani\u0107","year":"2003","journal-title":"Eur. J. Cell Biol."},{"key":"B6","doi-asserted-by":"publisher","first-page":"1462","DOI":"10.1073\/pnas.0812017106","article-title":"Expression profiling during ocular development identifies 2 Nlz genes with a critical role in optic fissure closure.","volume":"106","author":"Brown","year":"2009","journal-title":"Proc. Natl. Acad. Sci. U. S. A."},{"key":"B7","doi-asserted-by":"publisher","first-page":"231","DOI":"10.1242\/dev.079152","article-title":"Palatogenesis: morphogenetic and molecular mechanisms of secondary palate development.","volume":"139","author":"Bush","year":"2012","journal-title":"Development"},{"key":"B8","doi-asserted-by":"publisher","first-page":"2711","DOI":"10.1242\/dev.089987","article-title":"Deficient FGF signaling causes optic nerve dysgenesis and ocular coloboma.","volume":"140","author":"Cai","year":"2013","journal-title":"Development"},{"key":"B9","doi-asserted-by":"publisher","first-page":"1167","DOI":"10.1167\/iovs.17-22827","article-title":"Metalloproteinase adamts16 is required for proper closure of the optic fissure.","volume":"59","author":"Cao","year":"2018","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"B10","doi-asserted-by":"publisher","first-page":"43","DOI":"10.1016\/j.ydbio.2019.04.012","article-title":"Temporal characterization of optic fissure basement membrane composition suggests nidogen may be an initial target of remodeling.","volume":"452","author":"Carrara","year":"2019","journal-title":"Dev. Biol."},{"key":"B11","doi-asserted-by":"publisher","first-page":"447","DOI":"10.1097\/01.icu.0000243020.82380.f6","article-title":"Uveal coloboma: clinical and basic science update.","volume":"17","author":"Chang","year":"2006","journal-title":"Curr. Opin. Ophthalmol."},{"key":"B12","doi-asserted-by":"publisher","first-page":"254","DOI":"10.1038\/cr.2012.150","article-title":"Defective FGF signaling causes coloboma formation and disrupts retinal neurogenesis.","volume":"23","author":"Chen","year":"2012","journal-title":"Cell Res."},{"key":"B13","doi-asserted-by":"publisher","first-page":"255","DOI":"10.1146\/annurev.cellbio.17.1.255","article-title":"Early eye development in vertebrates.","volume":"17","author":"Chow","year":"2001","journal-title":"Annu. Rev. Cell Dev. Biol."},{"key":"B14","doi-asserted-by":"publisher","first-page":"257","DOI":"10.1387\/ijdb.170323mm","article-title":"Illuminating the chicken model through genetic modification.","volume":"62","author":"Davey","year":"2018","journal-title":"Int. J. Dev. Biol."},{"key":"B15","doi-asserted-by":"publisher","first-page":"298","DOI":"10.1016\/j.ydbio.2006.05.030","article-title":"Epithelial and ectomesenchymal role of the type I TGF-\u03b2 receptor ALK5 during facial morphogenesis and palatal fusion.","volume":"296","author":"Dudas","year":"2006","journal-title":"Dev. Biol."},{"key":"B16","doi-asserted-by":"publisher","DOI":"10.3390\/ijms21082760","article-title":"In vivo analysis of optic fissure fusion in zebrafish: pioneer cells, basal lamina, hyaloid vessels, and how fissure fusion is affected by BMP.","volume":"21","author":"Eckert","year":"2020","journal-title":"Int. J. Mol. Sci."},{"key":"B17","doi-asserted-by":"crossref","first-page":"2451","DOI":"10.1242\/dev.124.12.2451","article-title":"Involvement of programmed cell death in morphogenesis of the vertebrate inner ear.","volume":"124","author":"Fekete","year":"1997","journal-title":"Development"},{"key":"B18","doi-asserted-by":"crossref","first-page":"585","DOI":"10.1242\/dev.109.3.585","article-title":"Differential expression of TGF beta isoforms in murine palatogenesis.","volume":"109","author":"Fitzpatrick","year":"1990","journal-title":"Development"},{"key":"B19","doi-asserted-by":"publisher","first-page":"61","DOI":"10.1016\/B978-0-12-385044-7.00003-5.Eye","article-title":"Eye morphogenesis and patterning of the optic vesicle.","volume":"93","author":"Fuhrmann","year":"2010","journal-title":"Curr. Top Dev. Biol."},{"key":"B20","doi-asserted-by":"publisher","first-page":"393","DOI":"10.1016\/S0012-1606(02)90792-X","article-title":"TGF-\u03b23-induced chondroitin sulphate proteoglycan mediates palatal shelf adhesion.","volume":"250","author":"Gato","year":"2002","journal-title":"Dev. Biol."},{"key":"B21","doi-asserted-by":"publisher","DOI":"10.1016\/j.exer.2020.107940","article-title":"Genetics of syndromic ocular coloboma: CHARGE and COACH syndromes.","volume":"193","author":"George","year":"2020","journal-title":"Exp. Eye Res."},{"key":"B22","doi-asserted-by":"publisher","DOI":"10.3389\/fncel.2018.00042","article-title":"Cell behaviors during closure of the choroid fissure in the developing eye.","volume":"12","author":"Gestri","year":"2018","journal-title":"Front. Cell. Neurosci."},{"key":"B23","doi-asserted-by":"publisher","first-page":"2482","DOI":"10.1093\/hmg\/ddm204","article-title":"SNP genome scanning localizes oto-dental syndrome to chromosome 11q13 and microdeletions at this locus implicate FGF3 in dental and inner-ear disease and FADD in ocular coloboma.","volume":"16","author":"Gregory-Evans","year":"2007","journal-title":"Hum. Mol. Genet."},{"key":"B24","doi-asserted-by":"publisher","first-page":"881","DOI":"10.1136\/jmg.2004.025494","article-title":"Ocular coloboma: a reassessment in the age of molecular neuroscience.","volume":"41","author":"Gregory-Evans","year":"2004","journal-title":"J. Med. Genet."},{"key":"B25","doi-asserted-by":"publisher","first-page":"129","DOI":"10.1016\/0301-2115(95)02261-9","article-title":"Apoptosis: programmed cell death in fetal development.","volume":"64","author":"Haanen","year":"1996","journal-title":"Eur. J. Obstet. Gynecol. Reprod. Biol."},{"key":"B26","doi-asserted-by":"publisher","first-page":"903","DOI":"10.1083\/jcb.201301091","article-title":"The netrin receptor DCC focuses invadopodia-driven basement membrane transmigration in vivo.","volume":"201","author":"Hagedorn","year":"2013","journal-title":"J. Cell Biol."},{"key":"B27","doi-asserted-by":"publisher","first-page":"591","DOI":"10.1038\/nrm3416","article-title":"Transduction of mechanical and cytoskeletal cues by YAP and TAZ.","volume":"13","author":"Halder","year":"2012","journal-title":"Nat. Rev. Mol. Cell Biol."},{"key":"B28","doi-asserted-by":"publisher","DOI":"10.7554\/eLife.43877","article-title":"Detailed analysis of chick optic fissure closure reveals Netrin-1 as an essential mediator of epithelial fusion.","volume":"8","author":"Hardy","year":"2019","journal-title":"Elife"},{"key":"B29","doi-asserted-by":"publisher","first-page":"229","DOI":"10.1016\/0014-4835(89)90093-6","article-title":"The optic fissure in the normal and microphthalmic mouse.","volume":"49","author":"Hero","year":"1989","journal-title":"Exp. Eye Res."},{"key":"B30","first-page":"197","article-title":"Optic fissure closure in the normal cinnamon mouse: an ultrastructural study.","volume":"31","author":"Hero","year":"1990","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"B31","doi-asserted-by":"publisher","first-page":"641","DOI":"10.1038\/ncb2233","article-title":"Basement membrane sliding and targeted adhesion remodels tissue boundaries during uterine-vulval attachment in Caenorhabditis elegans.","volume":"13","author":"Ihara","year":"2011","journal-title":"Nat. Cell Biol."},{"key":"B32","doi-asserted-by":"publisher","first-page":"733","DOI":"10.1111\/j.1601-0825.2011.01806.x","article-title":"The mechanism of TGF-\u03b2 signaling during palate development.","volume":"17","author":"Iwata","year":"2011","journal-title":"Oral. Dis."},{"key":"B33","doi-asserted-by":"publisher","first-page":"578","DOI":"10.1002\/ajmg.c.31837","article-title":"Molecular diagnostic challenges for non-retinal developmental eye disorders in the United Kingdom.","volume":"184","author":"Jackson","year":"2020","journal-title":"Am. J. Med. Genet. Part C Semin. Med. Genet."},{"key":"B34","doi-asserted-by":"publisher","first-page":"262","DOI":"10.1016\/j.ydbio.2016.09.008","article-title":"The hyaloid vasculature facilitates basement membrane breakdown during choroid fissure closure in the zebrafish eye.","volume":"419","author":"James","year":"2016","journal-title":"Dev. Biol."},{"key":"B35","doi-asserted-by":"publisher","first-page":"291","DOI":"10.1083\/jcb.201311112","article-title":"Traversing the basement membrane in vivo: a diversity of strategies.","volume":"204","author":"Kelley","year":"2014","journal-title":"J. Cell Biol."},{"key":"B36","doi-asserted-by":"publisher","first-page":"1","DOI":"10.4137\/JCD.S23844","article-title":"Inhibition of apoptosis and efficacy of pan caspase inhibitor, Q-VD-OPh, in models of human disease.","volume":"8","author":"Keoni","year":"2015","journal-title":"J. Cell Death"},{"key":"B37","doi-asserted-by":"publisher","DOI":"10.1098\/rsob.170134","article-title":"TGFb-facilitated optic fissure fusion and the role of bone morphogenetic protein antagonism.","volume":"8","author":"Knickmeyer","year":"2018","journal-title":"Open Biol."},{"key":"B38","doi-asserted-by":"publisher","DOI":"10.1002\/prca.201800045","article-title":"MALDI imaging for proteomic painting of heterogeneous tissue structures.","volume":"13","author":"Kriegsmann","year":"2019","journal-title":"Proteomics Clin. Appl."},{"key":"B39","doi-asserted-by":"publisher","first-page":"437","DOI":"10.1002\/pmic.201500345","article-title":"In situ detection of histone variants and modifications in mouse brain using imaging mass spectrometry.","volume":"16","author":"Lahiri","year":"2016","journal-title":"Proteomics"},{"key":"B40","doi-asserted-by":"publisher","first-page":"178","DOI":"10.1038\/nrm3758.Molecular","article-title":"Molecular mechanisms of epithelial\u2013mesenchymal transition.","volume":"15","author":"Lamouille","year":"2014","journal-title":"Nat. Rev. Mol. Cell Biol."},{"key":"B41","doi-asserted-by":"publisher","first-page":"2483","DOI":"10.1167\/iovs.06-1211","article-title":"Laminin \u03b21 and \u03b31 containing laminins are essential for basement membrane integrity in the zebrafish eye.","volume":"48","author":"Lee","year":"2007","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"B42","doi-asserted-by":"publisher","first-page":"3568","DOI":"10.1093\/hmg\/ddt211","article-title":"Bcl6a function is required during optic cup formation to prevent p53-dependent apoptosis and colobomata.","volume":"22","author":"Lee","year":"2013","journal-title":"Hum. Mol. Genet."},{"key":"B43","doi-asserted-by":"publisher","first-page":"8698","DOI":"10.1073\/pnas.1103802108","article-title":"Retinoic acid receptor signaling regulates choroid fissure closure through independent mechanisms in the ventral optic cup and periocular mesenchyme.","volume":"108","author":"Lupo","year":"2011","journal-title":"Proc. Natl. Acad. Sci. U. S. A."},{"key":"B44","doi-asserted-by":"publisher","first-page":"453","DOI":"10.1007\/s00418-014-1303-1","article-title":"High-resolution MALDI mass spectrometric imaging of lipids in the mammalian retina.","volume":"143","author":"Ly","year":"2015","journal-title":"Histochem. Cell Biol."},{"key":"B45","doi-asserted-by":"crossref","first-page":"2397","DOI":"10.1242\/dev.124.12.2397","article-title":"The Pax protein Noi is required for commissural axon pathway formation in the rostral forebrain.","volume":"124","author":"Macdonald","year":"1997","journal-title":"Development"},{"key":"B46","doi-asserted-by":"publisher","first-page":"135","DOI":"10.18926\/AMO\/56649","article-title":"Collagen XVIII deposition in the basement membrane zone beneath the newly forming epidermis during wound healing in mice.","volume":"73","author":"Maeba","year":"2019","journal-title":"Acta Med. Okayama"},{"key":"B47","author":"Mann","year":"1964","journal-title":"The Development of the Human Eye"},{"key":"B48","doi-asserted-by":"publisher","first-page":"4292","DOI":"10.1016\/j.celrep.2020.03.024","article-title":"BMP signaling gradient scaling in the zebrafish pectoral fin.","volume":"30","author":"Mateus","year":"2020","journal-title":"Cell Rep."},{"key":"B49","doi-asserted-by":"publisher","first-page":"3021","DOI":"10.1242\/dev.119008","article-title":"Yap and Taz regulate retinal pigment epithelial cell fate.","volume":"142","author":"Miesfeld","year":"2015","journal-title":"Development"},{"key":"B50","doi-asserted-by":"publisher","first-page":"321","DOI":"10.1016\/j.devcel.2020.01.012","article-title":"Integrin-Mediated focal anchorage drives epithelial zippering during mouse neural tube closure.","volume":"52","author":"Mol\u00e8","year":"2020","journal-title":"Dev. Cell"},{"key":"B51","doi-asserted-by":"publisher","first-page":"209","DOI":"10.1586\/17469899.1.2.209","article-title":"Advances in the molecular genetics of ocular coloboma.","volume":"1","author":"Moosajee","year":"2006","journal-title":"Expert Rev. Ophthalmol."},{"key":"B52","doi-asserted-by":"publisher","first-page":"16","DOI":"10.1136\/jmg.39.1.16","article-title":"National study of microphthalmia, anophthalmia, and coloboma (MAC) in Scotland: investigation of genetic aetiology.","volume":"39","author":"Morrison","year":"2002","journal-title":"J. Med. Genet."},{"key":"B53","doi-asserted-by":"publisher","first-page":"1249","DOI":"10.1101\/gad.1276605","article-title":"Vax genes ventralize the embryonic eye.","volume":"19","author":"Mui","year":"2005","journal-title":"Genes Dev."},{"key":"B54","doi-asserted-by":"publisher","first-page":"411","DOI":"10.1038\/ng1321","article-title":"Oculofaciocardiodental and Lenz microphthalmia syndromes result from distinct classes of mutations in BCOR.","volume":"36","author":"Ng","year":"2004","journal-title":"Nat. Genet."},{"key":"B55","doi-asserted-by":"publisher","first-page":"3349","DOI":"10.1242\/dev.144519","article-title":"Distinct functions for netrin 1 in chicken and murine semicircular canal morphogenesis.","volume":"144","author":"Nishitani","year":"2017","journal-title":"Development"},{"key":"B56","doi-asserted-by":"publisher","first-page":"461","DOI":"10.1242\/dev.129478","article-title":"Proper closure of the optic fissure requires ephrin A5-EphB2-JNK signaling.","volume":"143","author":"Noh","year":"2016","journal-title":"Development"},{"key":"B57","doi-asserted-by":"publisher","first-page":"30","DOI":"10.1016\/j.ajhg.2010.11.012","article-title":"SMOC1 is essential for ocular and limb development in humans and mice.","volume":"88","author":"Okada","year":"2011","journal-title":"Am. J. Hum. Genet."},{"key":"B58","first-page":"1","article-title":"The early development of the eye in staged human embryos.","volume":"625","author":"O\u2019Rahilly","year":"1966","journal-title":"Carnegie Instn Wash Publ."},{"key":"B59","doi-asserted-by":"publisher","first-page":"367","DOI":"10.1076\/0271-3683(200005)2051-1FT367","article-title":"Apoptosis is associated with formation and persistence of the embryonic fissure.","volume":"20","author":"Ozeki","year":"2000","journal-title":"Curr. Eye Res."},{"key":"B60","first-page":"57","article-title":"Epithelial tube fusion as a mechanism for the development of complex lumen-containing organs.","volume":"10","author":"Palmer","year":"2017","journal-title":"Trends Dev. Biol."},{"key":"B61","doi-asserted-by":"publisher","first-page":"1318","DOI":"10.1002\/dvdy.215","article-title":"Fusion of airways during avian lung development constitutes a novel mechanism for the formation of continuous lumena in multicellular epithelia.","volume":"249","author":"Palmer","year":"2020","journal-title":"Dev. Dyn."},{"key":"B62","doi-asserted-by":"publisher","first-page":"55","DOI":"10.1016\/j.semcdb.2017.10.010","article-title":"Genes and pathways in optic fissure closure.","volume":"91","author":"Patel","year":"2017","journal-title":"Semin. Cell Dev. Biol."},{"key":"B63","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pgen.1002114","article-title":"Loss of the BMP antagonist, SMOC-1, causes Ophthalmo-acromelic (Waardenburg Anophthalmia) syndrome in humans and mice.","volume":"7","author":"Rainger","year":"2011","journal-title":"PLoS Genet."},{"key":"B64","doi-asserted-by":"publisher","first-page":"942","DOI":"10.1002\/humu.23246","article-title":"A recurrent de novo mutation in ACTG1 causes isolated ocular coloboma.","volume":"38","author":"Rainger","year":"2017","journal-title":"Hum. Mutat."},{"key":"B65","doi-asserted-by":"publisher","first-page":"1701","DOI":"10.1242\/dev.068338","article-title":"Mechanisms of tissue fusion during development.","volume":"139","author":"Ray","year":"2012","journal-title":"Development"},{"key":"B66","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-018-38379-5","article-title":"Transcriptome profiling of zebrafish optic fissure fusion.","volume":"9","author":"Richardson","year":"2019","journal-title":"Sci. Rep."},{"key":"B67","doi-asserted-by":"publisher","first-page":"S1","DOI":"10.1038\/ng.1091","article-title":"De novo mutations in the actin genes ACTB and ACTG1 cause Baraitser-Winter syndrome.","volume":"44","author":"Rivi\u00e8re","year":"2012","journal-title":"Nat. Genet."},{"key":"B68","doi-asserted-by":"publisher","DOI":"10.7554\/eLife.13273","article-title":"Regulation of cell protrusions by small GTPases during fusion of the neural folds.","volume":"5","author":"Rolo","year":"2016","journal-title":"Elife"},{"key":"B69","doi-asserted-by":"publisher","first-page":"209","DOI":"10.1053\/j.sempedsurg.2010.03.006","article-title":"The embryologic origin of ventral body wall defects.","volume":"19","author":"Sadler","year":"2010","journal-title":"Semin. Pediatr. Surg."},{"key":"B70","doi-asserted-by":"crossref","first-page":"13","DOI":"10.1242\/dev.127.1.13","article-title":"Netrin 1 is required for semicircular canal formation in the mouse inner ear.","volume":"127","author":"Salminen","year":"2000","journal-title":"Development"},{"key":"B71","doi-asserted-by":"crossref","first-page":"2659","DOI":"10.1242\/dev.124.13.2659","article-title":"TGF\u03b22 knockout mice have multiple developmental defects that are non-overlapping with other TGF\u03b2 knockout phenotypes.","volume":"124","author":"Sanford","year":"1997","journal-title":"Development"},{"key":"B72","doi-asserted-by":"publisher","first-page":"23750","DOI":"10.1074\/jbc.M703137200","article-title":"Binding of netrin-4 to laminin short arms regulates basement membrane assembly.","volume":"282","author":"Schneiders","year":"2007","journal-title":"J. Biol. Chem."},{"key":"B73","doi-asserted-by":"publisher","first-page":"23","DOI":"10.1016\/j.ydbio.2008.03.041","article-title":"Ectopic Pax2 expression in chick ventral optic cup phenocopies loss of Pax2 expression.","volume":"319","author":"Sehgal","year":"2008","journal-title":"Dev. Biol."},{"key":"B74","doi-asserted-by":"publisher","first-page":"2051","DOI":"10.1093\/hmg\/9.13.2051","article-title":"Collagen XVIII, containing an endogenous inhibitor of angiogenesis and tumor growth, plays a critical role in the maintenance of retinal structure and in neural tube closure (Knobloch syndrome).","volume":"9","author":"Serti\u00e9","year":"2000","journal-title":"Hum. Mol. Genet."},{"key":"B75","doi-asserted-by":"publisher","first-page":"928","DOI":"10.1242\/dev.145367","article-title":"Efficient TALEN-mediated gene targeting of chicken primordial germ cells.","volume":"144","author":"Taylor","year":"2017","journal-title":"Development"},{"key":"B76","doi-asserted-by":"publisher","DOI":"10.7554\/eLife.17935","article-title":"SMOC can act as both an antagonist and an expander of BMP signaling.","volume":"6","author":"Thomas","year":"2017","journal-title":"Elife"},{"key":"B77","doi-asserted-by":"publisher","first-page":"172","DOI":"10.1002\/(SICI)1096-9926(200003)61:3<172::AID-TERA4<3.0.CO;2-B","article-title":"Normal development of the male anterior urethra.","volume":"61","author":"Van Der Werff","year":"2000","journal-title":"Teratology"},{"key":"B78","doi-asserted-by":"publisher","first-page":"228","DOI":"10.1038\/nature13585","article-title":"Inappropriate p53 activation during development induces features of CHARGE syndrome.","volume":"514","author":"Van Nostrand","year":"2014","journal-title":"Nature"},{"key":"B79","doi-asserted-by":"publisher","first-page":"805","DOI":"10.1042\/BJ20030532","article-title":"Characterization of SMOC-2, a modular extracellular calcium-binding protein.","volume":"373","author":"Vannahme","year":"2003","journal-title":"Biochem. J."},{"key":"B80","doi-asserted-by":"publisher","first-page":"37977","DOI":"10.1074\/jbc.M203830200","article-title":"Characterization of SMOC-1, a novel modular calcium-binding protein in basement membranes.","volume":"277","author":"Vannahme","year":"2002","journal-title":"J. Biol. Chem."},{"key":"B81","doi-asserted-by":"publisher","first-page":"2357","DOI":"10.1093\/hmg\/dds056","article-title":"Pax2 regulates a fadd-dependent molecular switch that drives tissue fusion during eye development.","volume":"21","author":"Viringipurampeer","year":"2012","journal-title":"Hum. Mol. Genet."},{"key":"B82","doi-asserted-by":"publisher","first-page":"611","DOI":"10.1038\/ncb2064","article-title":"Control of Dpp morphogen signalling by a secreted feedback regulator.","volume":"12","author":"Vuilleumier","year":"2010","journal-title":"Nat. Cell Biol."},{"key":"B83","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-020-66451-6","article-title":"Hyaloid vasculature and mmp2 activity play a role during optic fissure fusion in zebrafish.","volume":"10","author":"Weaver","year":"2020","journal-title":"Sci. Rep."},{"key":"B84","doi-asserted-by":"publisher","first-page":"369","DOI":"10.1016\/j.ejmg.2014.05.002","article-title":"The genetic architecture of microphthalmia, anophthalmia and coloboma.","volume":"57","author":"Williamson","year":"2014","journal-title":"Eur. J. Med. Genet."},{"key":"B85","doi-asserted-by":"publisher","first-page":"1413","DOI":"10.1093\/hmg\/ddl064","article-title":"Mutations in SOX2 cause anophthalmia-esophageal-genital (AEG) syndrome.","volume":"15","author":"Williamson","year":"2006","journal-title":"Hum. Mol. Genet."},{"key":"B86","doi-asserted-by":"publisher","first-page":"295","DOI":"10.1016\/j.ajhg.2014.01.001","article-title":"Heterozygous loss-of-function mutations in YAP1 cause both isolated and syndromic optic fissure closure defects.","volume":"94","author":"Williamson","year":"2014","journal-title":"Am. J. Hum. Genet."},{"key":"B87","doi-asserted-by":"publisher","first-page":"315","DOI":"10.1007\/s00335-017-9701-z","article-title":"Gene editing in birds takes flight.","volume":"28","author":"Woodcock","year":"2017","journal-title":"Mamm. Genome"},{"key":"B88","doi-asserted-by":"publisher","DOI":"10.1167\/iovs.61.2.44","article-title":"Mutation in BMPR1B leads to optic disc coloboma and ventral retinal gliosis in mice.","volume":"61","author":"Yan","year":"2020","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"B89","doi-asserted-by":"publisher","first-page":"590","DOI":"10.1002\/ajmg.c.31831","article-title":"Ocular coloboma?: Genetic variants reveal a dynamic model of eye development.","volume":"184","author":"Yoon","year":"2020","journal-title":"Am. J. Med. Genet. Semin. Med. Genet. Part C"},{"key":"B90","doi-asserted-by":"publisher","first-page":"3686","DOI":"10.1242\/dev.128942","article-title":"Phenotypic analysis of mice completely lacking Netrin-1.","volume":"142","author":"Yung","year":"2015","journal-title":"Development"},{"key":"B91","doi-asserted-by":"publisher","first-page":"1577","DOI":"10.1096\/fasebj.4.6.2180767","article-title":"Molecular architecture of basement membranes.","volume":"4","author":"Yurchenco","year":"1990","journal-title":"FASEB J."},{"key":"B92","doi-asserted-by":"publisher","first-page":"572","DOI":"10.1016\/j.ceb.2004.07.013","article-title":"Assembly and tissue functions of early embryonic laminins and netrins.","volume":"16","author":"Yurchenco","year":"2004","journal-title":"Curr. Opin. Cell Biol."},{"key":"B93","doi-asserted-by":"publisher","first-page":"964","DOI":"10.1038\/nm888","article-title":"BMP-7 counteracts TGF-\u03b21-induced epithelial-to-mesenchymal transition and reverses chronic renal injury.","volume":"9","author":"Zeisberg","year":"2003","journal-title":"Nat. Med."}],"container-title":["Frontiers in Cell and Developmental Biology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fcell.2020.620774\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,12,11]],"date-time":"2022-12-11T10:09:18Z","timestamp":1670753358000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fcell.2020.620774\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,1,11]]},"references-count":93,"alternative-id":["10.3389\/fcell.2020.620774"],"URL":"https:\/\/doi.org\/10.3389\/fcell.2020.620774","relation":{},"ISSN":["2296-634X"],"issn-type":[{"value":"2296-634X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,1,11]]},"article-number":"620774"}}