Otx2 is involved in the regional specification of the developing retinal pigment epithelium by preventing the expression of sox2 and fgf8, factors that induce neural retina differentiation
The retinal pigment epithelium (RPE) shares its developmental origin with the neural retina (NR). When RPE development is disrupted, cells in the presumptive RPE region abnormally differentiate into NR-like cells. Therefore, the prevention of NR differentiation in the presumptive RPE area seems to b...
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| creator | Nishihara, Daisuke Yajima, Ichiro Tabata, Hiromasa Nakai, Masato Tsukiji, Nagaharu Katahira, Tatsuya Takeda, Kazuhisa Shibahara, Shigeki Nakamura, Harukazu Yamamoto, Hiroaki |
| description | The retinal pigment epithelium (RPE) shares its developmental origin with the neural retina (NR). When RPE development is disrupted, cells in the presumptive RPE region abnormally differentiate into NR-like cells. Therefore, the prevention of NR differentiation in the presumptive RPE area seems to be essential for regionalizing the RPE during eye development. However, its molecular mechanisms are not fully understood. In this study, we conducted a functional inhibition of a transcription factor Otx2, which is required for RPE development, using early chick embryos. The functional inhibition of Otx2 in chick eyes, using a recombinant gene encoding a dominant negative form of Otx2, caused the outer layer of the optic cup (the region forming the RPE, when embryos normally develop) to abnormally form an ectopic NR. In that ectopic NR, the characteristics of the RPE did not appear and NR markers were ectopically expressed. Intriguingly, the repression of Otx2 function also caused the ectopic expression of Fgf8 and Sox2 in the outer layer of the optic cup (the presumptive RPE region of normally developing eyes). These two factors are known to be capable of inducing NR cell differentiation in the presumptive RPE region, and are not expressed in the normally developing RPE region. Here, we suggest that Otx2 prevents the presumptive RPE region from forming the NR by repressing the expression of both Fgf8 and Sox2 which induce the NR cell fate. |
| doi_str_mv | 10.1371/journal.pone.0048879 |
| format | Article |
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When RPE development is disrupted, cells in the presumptive RPE region abnormally differentiate into NR-like cells. Therefore, the prevention of NR differentiation in the presumptive RPE area seems to be essential for regionalizing the RPE during eye development. However, its molecular mechanisms are not fully understood. In this study, we conducted a functional inhibition of a transcription factor Otx2, which is required for RPE development, using early chick embryos. The functional inhibition of Otx2 in chick eyes, using a recombinant gene encoding a dominant negative form of Otx2, caused the outer layer of the optic cup (the region forming the RPE, when embryos normally develop) to abnormally form an ectopic NR. In that ectopic NR, the characteristics of the RPE did not appear and NR markers were ectopically expressed. Intriguingly, the repression of Otx2 function also caused the ectopic expression of Fgf8 and Sox2 in the outer layer of the optic cup (the presumptive RPE region of normally developing eyes). These two factors are known to be capable of inducing NR cell differentiation in the presumptive RPE region, and are not expressed in the normally developing RPE region. Here, we suggest that Otx2 prevents the presumptive RPE region from forming the NR by repressing the expression of both Fgf8 and Sox2 which induce the NR cell fate.</description><identifier>ISSN: 1932-6203</identifier><identifier>EISSN: 1932-6203</identifier><identifier>DOI: 10.1371/journal.pone.0048879</identifier><identifier>PMID: 23145006</identifier><language>eng</language><publisher>United States: Public Library of Science</publisher><subject>Animals ; Apoptosis - genetics ; Avian Proteins - metabolism ; Biology ; Cell Differentiation ; Cell fate ; Cell Proliferation ; Chick Embryo ; Developmental biology ; Differentiation (biology) ; Ectopic expression ; Embryonic development ; Embryos ; Epithelium ; Eye ; Eye (anatomy) ; Eye - embryology ; Eye - metabolism ; Eye - pathology ; Fibroblast growth factor 8 ; Fibroblast growth factors ; Fibroblast Growth Factors - metabolism ; Fibroblasts ; Forming ; Gene Expression Regulation, Developmental ; Genes ; Growth factors ; Health sciences ; Inhibition ; Life sciences ; Molecular biology ; Molecular modelling ; Morphogenesis ; Neurobiology ; Neurosciences ; Otx Transcription Factors - antagonists & inhibitors ; Otx Transcription Factors - physiology ; Otx2 protein ; Physiology ; Recombinant Fusion Proteins - metabolism ; Regional development ; Repressing ; Retina ; Retinal pigment epithelium ; Retinal Pigment Epithelium - embryology ; Retinal Pigment Epithelium - metabolism ; Retinal Pigment Epithelium - pathology ; SOXB1 Transcription Factors - metabolism ; Telencephalon - embryology ; Transfection</subject><ispartof>PloS one, 2012-11, Vol.7 (11), p.e48879-e48879</ispartof><rights>COPYRIGHT 2012 Public Library of Science</rights><rights>2012 Nishihara et al. 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When RPE development is disrupted, cells in the presumptive RPE region abnormally differentiate into NR-like cells. Therefore, the prevention of NR differentiation in the presumptive RPE area seems to be essential for regionalizing the RPE during eye development. However, its molecular mechanisms are not fully understood. In this study, we conducted a functional inhibition of a transcription factor Otx2, which is required for RPE development, using early chick embryos. The functional inhibition of Otx2 in chick eyes, using a recombinant gene encoding a dominant negative form of Otx2, caused the outer layer of the optic cup (the region forming the RPE, when embryos normally develop) to abnormally form an ectopic NR. In that ectopic NR, the characteristics of the RPE did not appear and NR markers were ectopically expressed. 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Academic</collection><collection>PubMed Central (Full Participant titles)</collection><collection>DOAJ Directory of Open Access Journals</collection><jtitle>PloS one</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Nishihara, Daisuke</au><au>Yajima, Ichiro</au><au>Tabata, Hiromasa</au><au>Nakai, Masato</au><au>Tsukiji, Nagaharu</au><au>Katahira, Tatsuya</au><au>Takeda, Kazuhisa</au><au>Shibahara, Shigeki</au><au>Nakamura, Harukazu</au><au>Yamamoto, Hiroaki</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Otx2 is involved in the regional specification of the developing retinal pigment epithelium by preventing the expression of sox2 and fgf8, factors that induce neural retina differentiation</atitle><jtitle>PloS one</jtitle><addtitle>PLoS One</addtitle><date>2012-11-08</date><risdate>2012</risdate><volume>7</volume><issue>11</issue><spage>e48879</spage><epage>e48879</epage><pages>e48879-e48879</pages><issn>1932-6203</issn><eissn>1932-6203</eissn><abstract>The retinal pigment epithelium (RPE) shares its developmental origin with the neural retina (NR). When RPE development is disrupted, cells in the presumptive RPE region abnormally differentiate into NR-like cells. Therefore, the prevention of NR differentiation in the presumptive RPE area seems to be essential for regionalizing the RPE during eye development. However, its molecular mechanisms are not fully understood. In this study, we conducted a functional inhibition of a transcription factor Otx2, which is required for RPE development, using early chick embryos. The functional inhibition of Otx2 in chick eyes, using a recombinant gene encoding a dominant negative form of Otx2, caused the outer layer of the optic cup (the region forming the RPE, when embryos normally develop) to abnormally form an ectopic NR. In that ectopic NR, the characteristics of the RPE did not appear and NR markers were ectopically expressed. Intriguingly, the repression of Otx2 function also caused the ectopic expression of Fgf8 and Sox2 in the outer layer of the optic cup (the presumptive RPE region of normally developing eyes). These two factors are known to be capable of inducing NR cell differentiation in the presumptive RPE region, and are not expressed in the normally developing RPE region. Here, we suggest that Otx2 prevents the presumptive RPE region from forming the NR by repressing the expression of both Fgf8 and Sox2 which induce the NR cell fate.</abstract><cop>United States</cop><pub>Public Library of Science</pub><pmid>23145006</pmid><doi>10.1371/journal.pone.0048879</doi><tpages>e48879</tpages><oa>free_for_read</oa></addata></record> |
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| recordid | cdi_plos_journals_1326733422 |
| source | Public Library of Science (PLoS) Journals Open Access; MEDLINE; DOAJ Directory of Open Access Journals; Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals; PubMed Central; Free Full-Text Journals in Chemistry |
| subjects | Animals Apoptosis - genetics Avian Proteins - metabolism Biology Cell Differentiation Cell fate Cell Proliferation Chick Embryo Developmental biology Differentiation (biology) Ectopic expression Embryonic development Embryos Epithelium Eye Eye (anatomy) Eye - embryology Eye - metabolism Eye - pathology Fibroblast growth factor 8 Fibroblast growth factors Fibroblast Growth Factors - metabolism Fibroblasts Forming Gene Expression Regulation, Developmental Genes Growth factors Health sciences Inhibition Life sciences Molecular biology Molecular modelling Morphogenesis Neurobiology Neurosciences Otx Transcription Factors - antagonists & inhibitors Otx Transcription Factors - physiology Otx2 protein Physiology Recombinant Fusion Proteins - metabolism Regional development Repressing Retina Retinal pigment epithelium Retinal Pigment Epithelium - embryology Retinal Pigment Epithelium - metabolism Retinal Pigment Epithelium - pathology SOXB1 Transcription Factors - metabolism Telencephalon - embryology Transfection |
| title | Otx2 is involved in the regional specification of the developing retinal pigment epithelium by preventing the expression of sox2 and fgf8, factors that induce neural retina differentiation |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-02-21T23%3A24%3A00IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-gale_plos_&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=Otx2%20is%20involved%20in%20the%20regional%20specification%20of%20the%20developing%20retinal%20pigment%20epithelium%20by%20preventing%20the%20expression%20of%20sox2%20and%20fgf8,%20factors%20that%20induce%20neural%20retina%20differentiation&rft.jtitle=PloS%20one&rft.au=Nishihara,%20Daisuke&rft.date=2012-11-08&rft.volume=7&rft.issue=11&rft.spage=e48879&rft.epage=e48879&rft.pages=e48879-e48879&rft.issn=1932-6203&rft.eissn=1932-6203&rft_id=info:doi/10.1371/journal.pone.0048879&rft_dat=%3Cgale_plos_%3EA477091616%3C/gale_plos_%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_pqid=1326733422&rft_id=info:pmid/23145006&rft_galeid=A477091616&rft_doaj_id=oai_doaj_org_article_b539f969ef2f410ca9612760506d461e&rfr_iscdi=true |