The Orphan Nuclear Receptor Tlx Regulates Pax2 and Is Essential for Vision
Although the development of the vertebrate eye is well described, the number of transcription factors known to be key to this process is still limited. The localized expression of the orphan nuclear receptor Tlx in the optic cup and discrete parts of the central nervous system suggested the possible...
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| Veröffentlicht in: | Proceedings of the National Academy of Sciences - PNAS 2000-03, Vol.97 (6), p.2621-2625 |
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| container_title | Proceedings of the National Academy of Sciences - PNAS |
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| creator | Yu, R T Chiang, M Y Tanabe, T Kobayashi, M Yasuda, K Evans, R M Umesono, K |
| description | Although the development of the vertebrate eye is well described, the number of transcription factors known to be key to this process is still limited. The localized expression of the orphan nuclear receptor Tlx in the optic cup and discrete parts of the central nervous system suggested the possible role of Tlx in the formation or function of these structures. Analyses of Tlx targeted mice revealed that, in addition to the central nervous system cortical defects, lack of Tlx function results in progressive retinal and optic nerve degeneration with associated blindness. An extensive screen of Tlx-positive and Tlx-negative P19 neural precursors identified Pax2 as a candidate target gene. This identification is significant, because Pax2 is known to be involved in retinal development in both the human and the mouse eye. We find that Pax2 is a direct target and that the Tlx binding site in its promoter is conserved between mouse and human. These studies show that Tlx is a key component of retinal development and vision and an upstream regulator of the Pax2 signaling cascade. |
| doi_str_mv | 10.1073/pnas.050566897 |
| format | Article |
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The localized expression of the orphan nuclear receptor Tlx in the optic cup and discrete parts of the central nervous system suggested the possible role of Tlx in the formation or function of these structures. Analyses of Tlx targeted mice revealed that, in addition to the central nervous system cortical defects, lack of Tlx function results in progressive retinal and optic nerve degeneration with associated blindness. An extensive screen of Tlx-positive and Tlx-negative P19 neural precursors identified Pax2 as a candidate target gene. This identification is significant, because Pax2 is known to be involved in retinal development in both the human and the mouse eye. We find that Pax2 is a direct target and that the Tlx binding site in its promoter is conserved between mouse and human. These studies show that Tlx is a key component of retinal development and vision and an upstream regulator of the Pax2 signaling cascade.</description><identifier>ISSN: 0027-8424</identifier><identifier>EISSN: 1091-6490</identifier><identifier>DOI: 10.1073/pnas.050566897</identifier><identifier>PMID: 10706625</identifier><language>eng</language><publisher>United States: National Academy of Sciences of the United States of America</publisher><subject>Animals ; Binding Sites ; Biological Sciences ; Chick Embryo ; Conserved Sequence ; DNA ; DNA-Binding Proteins - genetics ; DNA-Binding Proteins - metabolism ; Electroporation ; Embryos ; Eyes ; Gene Expression Regulation, Developmental ; Gene Library ; Genetic vectors ; In Situ Hybridization ; Mice ; Mice, Mutant Strains ; Neoplasms, Experimental ; Optic nerve ; Optics ; pax2 protein ; PAX2 Transcription Factor ; Plasmids ; Promoter Regions, Genetic ; Receptors, Cytoplasmic and Nuclear - genetics ; Receptors, Cytoplasmic and Nuclear - physiology ; Repression ; Retina ; Retina - metabolism ; Reverse transcriptase polymerase chain reaction ; Teratocarcinoma ; Tlx protein ; Transcription Factors - genetics ; Transcription Factors - metabolism ; Transfection ; Tumor Cells, Cultured ; Vision, Ocular - genetics ; Vision, Ocular - physiology</subject><ispartof>Proceedings of the National Academy of Sciences - PNAS, 2000-03, Vol.97 (6), p.2621-2625</ispartof><rights>Copyright 1993-2000 National Academy of Sciences of the United States of America</rights><rights>Copyright National Academy of Sciences Mar 14, 2000</rights><rights>Copyright © 2000, The National Academy of Sciences 2000</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c581t-b25a596f51f9235cfd4ba3425f0029ba50bdfd09bdf35a923c7672b884f966d03</citedby><cites>FETCH-LOGICAL-c581t-b25a596f51f9235cfd4ba3425f0029ba50bdfd09bdf35a923c7672b884f966d03</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Uhttp://www.pnas.org/content/97/6.cover.gif</thumbnail><linktopdf>$$Uhttps://www.jstor.org/stable/pdf/122212$$EPDF$$P50$$Gjstor$$H</linktopdf><linktohtml>$$Uhttps://www.jstor.org/stable/122212$$EHTML$$P50$$Gjstor$$H</linktohtml><link.rule.ids>230,314,727,780,784,803,885,27924,27925,53791,53793,58017,58250</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/10706625$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Yu, R T</creatorcontrib><creatorcontrib>Chiang, M Y</creatorcontrib><creatorcontrib>Tanabe, T</creatorcontrib><creatorcontrib>Kobayashi, M</creatorcontrib><creatorcontrib>Yasuda, K</creatorcontrib><creatorcontrib>Evans, R M</creatorcontrib><creatorcontrib>Umesono, K</creatorcontrib><title>The Orphan Nuclear Receptor Tlx Regulates Pax2 and Is Essential for Vision</title><title>Proceedings of the National Academy of Sciences - PNAS</title><addtitle>Proc Natl Acad Sci U S A</addtitle><description>Although the development of the vertebrate eye is well described, the number of transcription factors known to be key to this process is still limited. 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| subjects | Animals Binding Sites Biological Sciences Chick Embryo Conserved Sequence DNA DNA-Binding Proteins - genetics DNA-Binding Proteins - metabolism Electroporation Embryos Eyes Gene Expression Regulation, Developmental Gene Library Genetic vectors In Situ Hybridization Mice Mice, Mutant Strains Neoplasms, Experimental Optic nerve Optics pax2 protein PAX2 Transcription Factor Plasmids Promoter Regions, Genetic Receptors, Cytoplasmic and Nuclear - genetics Receptors, Cytoplasmic and Nuclear - physiology Repression Retina Retina - metabolism Reverse transcriptase polymerase chain reaction Teratocarcinoma Tlx protein Transcription Factors - genetics Transcription Factors - metabolism Transfection Tumor Cells, Cultured Vision, Ocular - genetics Vision, Ocular - physiology |
| title | The Orphan Nuclear Receptor Tlx Regulates Pax2 and Is Essential for Vision |
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