{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,7]],"date-time":"2026-10-07T23:29:22Z","timestamp":1791415762108,"version":"4.3.3"},"reference-count":39,"publisher":"The Company of Biologists","license":[{"start":{"date-parts":[[2020,9,5]],"date-time":"2020-09-05T00:00:00Z","timestamp":1599264000000},"content-version":"vor","delay-in-days":2074,"URL":"http:\/\/creativecommons.org\/licenses\/by\/3.0"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2015,1,1]]},"abstract":"<jats:p>During ocular morphogenesis the retinal pigment epithelium (RPE) and neural retina segregate fates from a bi-potential progenitor pool of cells comprising the optic vesicle. Several transcription factors and signaling pathways have been shown to be important for RPE maintenance and differentiation, but an understanding of the initial fate specification and determination of this ocular cell type is lacking. We show that Yap\/Taz-Tead activity is necessary and sufficient for optic vesicle progenitors to adopt RPE identity in zebrafish. In support, a Tead responsive transgene expresses within the domain of the optic cup from which RPE arises and Yap immunoreactivity localizes to nuclei of prospective RPE cells. yap mutants lack a subset of RPE cells and\/or exhibit coloboma. Loss of RPE in yap mutants is exacerbated in combination with taz mutant alleles such that when Yap and Taz are both absent, optic vesicle progenitor cells completely lose their ability to form RPE. The mechanism of Yap dependent RPE cell-type determination is reliant on both nuclear localization of Yap and interaction with a Tead co-factor. In contrast to loss of Yap and Taz, overexpression of either protein within optic vesicle progenitors leads to ectopic pigmentation in a dosage-dependent manner. Overall, this study identifies Yap and Taz as key early regulators of RPE genesis and provides a mechanistic framework for understanding the congenital ocular defects of Sveinsson's chorioretinal atrophy and congenital retinal coloboma.<\/jats:p>","DOI":"10.1242\/dev.119008","type":"journal-article","created":{"date-parts":[[2015,7,24]],"date-time":"2015-07-24T22:44:43Z","timestamp":1437777883000},"source":"Crossref","is-referenced-by-count":108,"title":["Yap and Taz regulate retinal pigment epithelial cell fate"],"prefix":"10.1242","author":[{"given":"Joel B.","family":"Miesfeld","sequence":"first","affiliation":[{"name":"Department of Cell Biology, Neurobiology and Anatomy, Medical College of Wisconsin, Milwaukee, WI, 53226, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gaia","family":"Gestri","sequence":"additional","affiliation":[{"name":"Department of Cell and Developmental Biology, UCL, London WC1E 6BT, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Brian S.","family":"Clark","sequence":"additional","affiliation":[{"name":"Department of Cell Biology, Neurobiology and Anatomy, Medical College of Wisconsin, Milwaukee, WI, 53226, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael A.","family":"Flinn","sequence":"additional","affiliation":[{"name":"Department of Cell Biology, Neurobiology and Anatomy, Medical College of Wisconsin, Milwaukee, WI, 53226, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Richard J.","family":"Poole","sequence":"additional","affiliation":[{"name":"Department of Cell and Developmental Biology, UCL, London WC1E 6BT, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jason R.","family":"Bader","sequence":"additional","affiliation":[{"name":"Department of Cell Biology, Neurobiology and Anatomy, Medical College of Wisconsin, Milwaukee, WI, 53226, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joseph C.","family":"Besharse","sequence":"additional","affiliation":[{"name":"Department of Cell Biology, Neurobiology and Anatomy, Medical College of Wisconsin, Milwaukee, WI, 53226, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stephen W.","family":"Wilson","sequence":"additional","affiliation":[{"name":"Department of Cell and Developmental Biology, UCL, London WC1E 6BT, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Brian A.","family":"Link","sequence":"additional","affiliation":[{"name":"Department of Cell Biology, Neurobiology and Anatomy, Medical College of Wisconsin, Milwaukee, WI, 53226, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"237","reference":[{"key":"2021042608080728900_DEV119008C1","doi-asserted-by":"publisher","first-page":"1443","DOI":"10.1016\/j.cell.2012.11.027","article-title":"Role of TAZ as mediator of Wnt signaling","volume":"151","author":"Azzolin","year":"2012","journal-title":"Cell"},{"key":"2021042608080728900_DEV119008C2","doi-asserted-by":"publisher","first-page":"3320","DOI":"10.1101\/gad.1726608","article-title":"YAP regulates neural progenitor cell number via the TEA domain transcription factor","volume":"22","author":"Cao","year":"2008","journal-title":"Genes Dev."},{"key":"2021042608080728900_DEV119008C3","doi-asserted-by":"publisher","first-page":"290","DOI":"10.1101\/gad.1865310","article-title":"Structural basis of YAP recognition by TEAD4 in the hippo pathway","volume":"24","author":"Chen","year":"2010","journal-title":"Genes Dev."},{"key":"2021042608080728900_DEV119008C4","doi-asserted-by":"publisher","first-page":"2452","DOI":"10.1002\/dvdy.22758","article-title":"Generation of Rab-based transgenic lines for in vivo studies of endosome biology in zebrafish","volume":"240","author":"Clark","year":"2011","journal-title":"Dev. Dyn."},{"key":"2021042608080728900_DEV119008C5","doi-asserted-by":"publisher","first-page":"975","DOI":"10.1093\/hmg\/ddh106","article-title":"A novel TEAD1 mutation is the causative allele in Sveinsson's chorioretinal atrophy (helicoid peripapillary chorioretinal degeneration)","volume":"13","author":"Fossdal","year":"2004","journal-title":"Hum. Mol. Genet."},{"key":"2021042608080728900_DEV119008C6","doi-asserted-by":"publisher","first-page":"141","DOI":"10.1016\/j.exer.2013.09.003","article-title":"Retinal pigment epithelium development, plasticity, and tissue homeostasis","volume":"123","author":"Fuhrmann","year":"2014","journal-title":"Exp. Eye Res."},{"key":"2021042608080728900_DEV119008C7","doi-asserted-by":"publisher","first-page":"e05216","DOI":"10.7554\/eLife.05216","article-title":"Eye morphogenesis driven by epithelial flow into the optic cup facilitated by modulation of bone morphogenetic protein","volume":"4","author":"Heermann","year":"2015","journal-title":"eLife"},{"key":"2021042608080728900_DEV119008C8","doi-asserted-by":"publisher","first-page":"1541","DOI":"10.1016\/j.ophtha.2006.11.016","article-title":"Sveinsson chorioretinal atrophy\/helicoid peripapillary chorioretinal degeneration: first histopathology report","volume":"114","author":"Jonasson","year":"2007","journal-title":"Ophthalmology"},{"key":"2021042608080728900_DEV119008C9","doi-asserted-by":"publisher","first-page":"6009","DOI":"10.1242\/jcs.109546","article-title":"The Hippo pathway member Yap plays a key role in influencing fate decisions in muscle satellite cells","volume":"125","author":"Judson","year":"2013","journal-title":"J. Cell Sci."},{"key":"2021042608080728900_DEV119008C10","doi-asserted-by":"publisher","first-page":"244","DOI":"10.1002\/dvdy.20516","article-title":"Transposon tools and methods in zebrafish","volume":"234","author":"Kawakami","year":"2005","journal-title":"Dev. Dyn."},{"key":"2021042608080728900_DEV119008C11","doi-asserted-by":"publisher","first-page":"e1394","DOI":"10.3791\/1394","article-title":"Generating chimeric zebrafish embryos by transplantation","volume":"29","author":"Kemp","year":"2009","journal-title":"J. Vis. Exp."},{"key":"2021042608080728900_DEV119008C12","doi-asserted-by":"publisher","first-page":"1022","DOI":"10.1016\/j.bbrc.2007.07.129","article-title":"A Sveinsson's chorioretinal atrophy-associated missense mutation in mouse Tead1 affects its interaction with the co-factors YAP and TAZ","volume":"361","author":"Kitagawa","year":"2007","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"2021042608080728900_DEV119008C13","doi-asserted-by":"publisher","first-page":"3088","DOI":"10.1002\/dvdy.21343","article-title":"The Tol2kit: a multisite gateway-based construction kit for Tol2 transposon transgenesis constructs","volume":"236","author":"Kwan","year":"2007","journal-title":"Dev. Dyn."},{"key":"2021042608080728900_DEV119008C14","doi-asserted-by":"publisher","first-page":"359","DOI":"10.1242\/dev.071407","article-title":"A complex choreography of cell movements shapes the vertebrate eye","volume":"139","author":"Kwan","year":"2012","journal-title":"Development"},{"key":"2021042608080728900_DEV119008C15","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1186\/1471-213X-6-1","article-title":"Proteomics of early zebrafish embryos","volume":"6","author":"Link","year":"2006","journal-title":"BMC Dev. Biol."},{"key":"2021042608080728900_DEV119008C16","doi-asserted-by":"publisher","first-page":"2529","DOI":"10.1002\/dvdy.22743","article-title":"Embryonic expression of zebrafish MiT family genes tfe3b, tfeb, and tfec","volume":"240","author":"Lister","year":"2011","journal-title":"Dev. Dyn."},{"key":"2021042608080728900_DEV119008C17","doi-asserted-by":"publisher","first-page":"37159","DOI":"10.1074\/jbc.M110.152942","article-title":"The hippo tumor pathway promotes TAZ degradation by phosphorylating a phosphodegron and recruiting the SCF{beta}-TrCP E3 ligase","volume":"285","author":"Liu","year":"2010","journal-title":"J. Biol. Chem."},{"key":"2021042608080728900_DEV119008C18","doi-asserted-by":"publisher","first-page":"827","DOI":"10.1016\/j.modgep.2007.08.001","article-title":"Vestigial-like-2b (VITO-1b) and Tead-3a (Tef-5a) expression in zebrafish skeletal muscle, brain and notochord","volume":"7","author":"Mann","year":"2007","journal-title":"Gene Expr. Patterns"},{"key":"2021042608080728900_DEV119008C19","doi-asserted-by":"publisher","first-page":"177","DOI":"10.1016\/j.mod.2014.02.003","article-title":"Establishment of transgenic lines to monitor and manipulate Yap\/Taz-Tead activity in zebrafish reveals both evolutionarily conserved and divergent functions of the Hippo pathway","volume":"133","author":"Miesfeld","year":"2014","journal-title":"Mech. Dev."},{"key":"2021042608080728900_DEV119008C20","doi-asserted-by":"publisher","first-page":"745","DOI":"10.1387\/ijdb.072375fn","article-title":"Differential expression of two TEF-1 (TEAD) genes during Xenopus laevis development and in response to inducing factors","volume":"51","author":"Naye","year":"2007","journal-title":"Int. J. Dev. Biol."},{"key":"2021042608080728900_DEV119008C21","doi-asserted-by":"publisher","first-page":"398","DOI":"10.1016\/j.devcel.2009.02.003","article-title":"The Hippo signaling pathway components Lats and Yap pattern Tead4 activity to distinguish mouse trophectoderm from inner cell mass","volume":"16","author":"Nishioka","year":"2009","journal-title":"Dev. Cell"},{"key":"2021042608080728900_DEV119008C22","doi-asserted-by":"publisher","first-page":"e1000214","DOI":"10.1371\/journal.pbio.1000214","article-title":"Dynamic coupling of pattern formation and morphogenesis in the developing vertebrate retina","volume":"7","author":"Picker","year":"2009","journal-title":"PLoS Biol."},{"key":"2021042608080728900_DEV119008C23","doi-asserted-by":"publisher","first-page":"217","DOI":"10.1038\/nature14215","article-title":"YAP is essential for tissue tension to ensure vertebrate 3D body shape","volume":"521","author":"Porazinski","year":"2015","journal-title":"Nature"},{"key":"2021042608080728900_DEV119008C24","doi-asserted-by":"publisher","first-page":"e78","DOI":"10.1371\/journal.pgen.0030078","article-title":"p53 activation by knockdown technologies","volume":"3","author":"Robu","year":"2007","journal-title":"PLoS Genet."},{"key":"2021042608080728900_DEV119008C25","doi-asserted-by":"publisher","first-page":"509","DOI":"10.1016\/S0140-6736(14)61376-3","article-title":"Human embryonic stem cell-derived retinal pigment epithelium in patients with age-related macular degeneration and Stargardt's macular dystrophy: follow-up of two open-label phase 1\/2 studies","volume":"385","author":"Schwartz","year":"2015","journal-title":"Lancet"},{"key":"2021042608080728900_DEV119008C26","doi-asserted-by":"publisher","first-page":"864","DOI":"10.1016\/j.cell.2008.03.037","article-title":"Chk1 suppresses a caspase-2 apoptotic response to DNA damage that bypasses p53, Bcl-2, and caspase-3","volume":"133","author":"Sidi","year":"2008","journal-title":"Cell"},{"key":"2021042608080728900_DEV119008C27","doi-asserted-by":"publisher","first-page":"347","DOI":"10.1016\/j.mod.2013.05.001","article-title":"An eye on eye development","volume":"130","author":"Sinn","year":"2013","journal-title":"Mech. Dev."},{"key":"2021042608080728900_DEV119008C28","doi-asserted-by":"crossref","first-page":"311","DOI":"10.1093\/genetics\/112.2.311","article-title":"Segregation analyses and gene-centromere distances in zebrafish","volume":"112","author":"Streisinger","year":"1986","journal-title":"Genetics"},{"key":"2021042608080728900_DEV119008C29","article-title":"High throughput expression analysis in zebrafish","author":"Thisse","year":"2004"},{"key":"2021042608080728900_DEV119008C30","doi-asserted-by":"publisher","first-page":"e47398","DOI":"10.1371\/journal.pone.0047398","article-title":"Functional assessment of human coding mutations affecting skin pigmentation using zebrafish","volume":"7","author":"Tsetskhladze","year":"2012","journal-title":"PLoS ONE"},{"key":"2021042608080728900_DEV119008C39","doi-asserted-by":"publisher","first-page":"280","DOI":"10.1016\/j.ydbio.2012.08.032","article-title":"Id2a functions to limit Notch pathway activity and thereby influence the transition from proliferation to differentiation of retinoblasts during zebrafish retinogenesis","volume":"371","author":"Uribe","year":"2012","journal-title":"Dev. Biol."},{"key":"2021042608080728900_DEV119008C31","doi-asserted-by":"publisher","first-page":"3931","DOI":"10.1242\/dev.062695","article-title":"Lef1-dependent Wnt\/beta-catenin signalling drives the proliferative engine that maintains tissue homeostasis during lateral line development","volume":"138","author":"Valdivia","year":"2011","journal-title":"Development"},{"key":"2021042608080728900_DEV119008C32","doi-asserted-by":"publisher","first-page":"1614","DOI":"10.1242\/dev.102376","article-title":"The Hippo pathway effectors TAZ and YAP in development, homeostasis and disease","volume":"141","author":"Varelas","year":"2014","journal-title":"Development"},{"key":"2021042608080728900_DEV119008C33","doi-asserted-by":"publisher","first-page":"831","DOI":"10.1016\/j.devcel.2010.11.012","article-title":"The Crumbs complex couples cell density sensing to Hippo-dependent control of the TGF-beta-SMAD pathway","volume":"19","author":"Varelas","year":"2010","journal-title":"Dev. Cell"},{"key":"2021042608080728900_DEV119008C34","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":"2021042608080728900_DEV119008C35","doi-asserted-by":"publisher","first-page":"13839","DOI":"10.1073\/pnas.1313192110","article-title":"Hippo pathway effector Yap promotes cardiac regeneration","volume":"110","author":"Xin","year":"2013","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"2021042608080728900_DEV119008C36","doi-asserted-by":"publisher","first-page":"1324","DOI":"10.1016\/j.cell.2014.03.060","article-title":"Hippo pathway activity influences liver cell fate","volume":"157","author":"Yimlamai","year":"2014","journal-title":"Cell"},{"key":"2021042608080728900_DEV119008C37","doi-asserted-by":"publisher","first-page":"e22278","DOI":"10.1371\/journal.pone.0022278","article-title":"Yki\/YAP, Sd\/TEAD and Hth\/MEIS control tissue specification in the Drosophila eye disc epithelium","volume":"6","author":"Zhang","year":"2011","journal-title":"PLoS ONE"},{"key":"2021042608080728900_DEV119008C38","doi-asserted-by":"publisher","first-page":"1962","DOI":"10.1101\/gad.1664408","article-title":"TEAD mediates YAP-dependent gene induction and growth control","volume":"22","author":"Zhao","year":"2008","journal-title":"Genes Dev."}],"container-title":["Development"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/journals.biologists.com\/dev\/article-pdf\/142\/17\/3021\/1838723\/dev119008.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"http:\/\/journals.biologists.com\/dev\/article-pdf\/doi\/10.1242\/dev.119008\/2003676\/dev_119008v1.pdf","content-type":"application\/pdf","content-version":"am","intended-application":"syndication"},{"URL":"http:\/\/journals.biologists.com\/dev\/article-pdf\/doi\/10.1242\/dev.119008\/2003676\/dev_119008v1.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2021,5,18]],"date-time":"2021-05-18T17:29:00Z","timestamp":1621358940000},"score":1,"resource":{"primary":{"URL":"https:\/\/journals.biologists.com\/dev\/article\/doi\/10.1242\/dev.119008\/258633\/Yap-and-Taz-regulate-retinal-pigment-epithelial"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2015,1,1]]},"references-count":39,"URL":"https:\/\/doi.org\/10.1242\/dev.119008","relation":{"has-review":[{"id-type":"doi","id":"10.3410\/f.725671012.793508843","asserted-by":"object"}]},"ISSN":["1477-9129","0950-1991"],"issn-type":[{"value":"1477-9129","type":"electronic"},{"value":"0950-1991","type":"print"}],"subject":[],"published":{"date-parts":[[2015,1,1]]},"article-number":"dev.119008"}}