Control of endothelial sprouting by a Tel-CtBP complex
The conserved vertebrate transcriptional repressor Tel regulates angiogenesis by directly controlling endothelial sprouting through modulation of Notch ligand Dll4 and vessel branching through other angiogenesis factors such as sprouty and VE-cadherin We show that the transcriptional repressor Tel p...
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| Veröffentlicht in: | Nature cell biology 2010-10, Vol.12 (10), p.933-942 |
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| creator | Peterson-Maduro, Josi van Dam, Hans Alloul-Ramdhani, Mariam Baan, Bart Kobayashi, Kazuki Baker, David A Roukens, M. Guy Schulte-Merker, Stefan |
| description | The conserved vertebrate transcriptional repressor Tel regulates angiogenesis by directly controlling endothelial sprouting through modulation of Notch ligand Dll4 and vessel branching through other angiogenesis factors such as sprouty and VE-cadherin
We show that the transcriptional repressor Tel plays an evolutionarily conserved role in angiogenesis: it is indispensable for the sprouting of human endothelial cells and for normal development of the
Danio rerio
blood circulatory system. Tel orchestrates endothelial sprouting by binding to the generic co-repressor, CtBP. The Tel–CtBP complex temporally restricts a VEGF (vascular endothelial growth factor)-mediated pulse of
dll4
expression and thereby directly links VEGF receptor intracellular signalling and intercellular Notch–Dll4 signalling. It further controls branching by regulating expression of other factors that constrain angiogenesis such as
sprouty
family members and
ve-cadherin
. Thus, the Tel–CtBP complex conditions endothelial cells for angiogenesis by controlling the balance between stimulatory and antagonistic sprouting cues. Tel control of branching seems to be a refinement of invertebrate tracheae morphogenesis that requires Yan, the invertebrate orthologue of Tel. This work highlights Tel and its associated networks as potential targets for the development of therapeutic strategies to inhibit pathological angiogenesis. |
| doi_str_mv | 10.1038/ncb2096 |
| format | Article |
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We show that the transcriptional repressor Tel plays an evolutionarily conserved role in angiogenesis: it is indispensable for the sprouting of human endothelial cells and for normal development of the
Danio rerio
blood circulatory system. Tel orchestrates endothelial sprouting by binding to the generic co-repressor, CtBP. The Tel–CtBP complex temporally restricts a VEGF (vascular endothelial growth factor)-mediated pulse of
dll4
expression and thereby directly links VEGF receptor intracellular signalling and intercellular Notch–Dll4 signalling. It further controls branching by regulating expression of other factors that constrain angiogenesis such as
sprouty
family members and
ve-cadherin
. Thus, the Tel–CtBP complex conditions endothelial cells for angiogenesis by controlling the balance between stimulatory and antagonistic sprouting cues. Tel control of branching seems to be a refinement of invertebrate tracheae morphogenesis that requires Yan, the invertebrate orthologue of Tel. This work highlights Tel and its associated networks as potential targets for the development of therapeutic strategies to inhibit pathological angiogenesis.</description><identifier>ISSN: 1465-7392</identifier><identifier>EISSN: 1476-4679</identifier><identifier>DOI: 10.1038/ncb2096</identifier><identifier>PMID: 20835243</identifier><language>eng</language><publisher>London: Nature Publishing Group UK</publisher><subject>631/136/16 ; 631/80/86 ; Alcohol Oxidoreductases - metabolism ; Amino Acid Motifs ; Amino Acid Sequence ; Analysis ; Angiogenesis ; Animals ; Biology ; Biomedical and Life Sciences ; Blood ; Cancer Research ; Cell Biology ; Cells, Cultured ; Consensus Sequence ; Danio rerio ; Developmental Biology ; DNA-Binding Proteins - metabolism ; Embryonic development ; Endothelial Cells - cytology ; Endothelial Cells - metabolism ; Endothelium ; ETS Translocation Variant 6 Protein ; Eye Proteins ; Freshwater ; Genetic aspects ; Humans ; Invertebrates ; Kinases ; Life Sciences ; Molecular Sequence Data ; NAD - metabolism ; Neovascularization, Physiologic - physiology ; Physiological aspects ; Protein Binding ; Proto-Oncogene Proteins c-ets - metabolism ; Repressor Proteins - genetics ; Repressor Proteins - metabolism ; Signal transduction ; Stem Cells ; Transcription Factors - genetics ; Transcription Factors - metabolism ; Vascular endothelial growth factor ; Vascular Endothelial Growth Factor A - metabolism ; Vertebrates ; Zebrafish - embryology ; Zebrafish Proteins - genetics ; Zebrafish Proteins - metabolism</subject><ispartof>Nature cell biology, 2010-10, Vol.12 (10), p.933-942</ispartof><rights>Springer Nature Limited 2010</rights><rights>COPYRIGHT 2010 Nature Publishing Group</rights><rights>Copyright Nature Publishing Group Oct 2010</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c561t-3418b92a6104535de8c9fd08a0b5c961fc3d715c75aac8472b764a10fc28c8623</citedby><cites>FETCH-LOGICAL-c561t-3418b92a6104535de8c9fd08a0b5c961fc3d715c75aac8472b764a10fc28c8623</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,780,784,2727,27924,27925</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/20835243$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Peterson-Maduro, Josi</creatorcontrib><creatorcontrib>van Dam, Hans</creatorcontrib><creatorcontrib>Alloul-Ramdhani, Mariam</creatorcontrib><creatorcontrib>Baan, Bart</creatorcontrib><creatorcontrib>Kobayashi, Kazuki</creatorcontrib><creatorcontrib>Baker, David A</creatorcontrib><creatorcontrib>Roukens, M. Guy</creatorcontrib><creatorcontrib>Schulte-Merker, Stefan</creatorcontrib><title>Control of endothelial sprouting by a Tel-CtBP complex</title><title>Nature cell biology</title><addtitle>Nat Cell Biol</addtitle><addtitle>Nat Cell Biol</addtitle><description>The conserved vertebrate transcriptional repressor Tel regulates angiogenesis by directly controlling endothelial sprouting through modulation of Notch ligand Dll4 and vessel branching through other angiogenesis factors such as sprouty and VE-cadherin
We show that the transcriptional repressor Tel plays an evolutionarily conserved role in angiogenesis: it is indispensable for the sprouting of human endothelial cells and for normal development of the
Danio rerio
blood circulatory system. Tel orchestrates endothelial sprouting by binding to the generic co-repressor, CtBP. The Tel–CtBP complex temporally restricts a VEGF (vascular endothelial growth factor)-mediated pulse of
dll4
expression and thereby directly links VEGF receptor intracellular signalling and intercellular Notch–Dll4 signalling. It further controls branching by regulating expression of other factors that constrain angiogenesis such as
sprouty
family members and
ve-cadherin
. Thus, the Tel–CtBP complex conditions endothelial cells for angiogenesis by controlling the balance between stimulatory and antagonistic sprouting cues. Tel control of branching seems to be a refinement of invertebrate tracheae morphogenesis that requires Yan, the invertebrate orthologue of Tel. This work highlights Tel and its associated networks as potential targets for the development of therapeutic strategies to inhibit pathological angiogenesis.</description><subject>631/136/16</subject><subject>631/80/86</subject><subject>Alcohol Oxidoreductases - metabolism</subject><subject>Amino Acid Motifs</subject><subject>Amino Acid Sequence</subject><subject>Analysis</subject><subject>Angiogenesis</subject><subject>Animals</subject><subject>Biology</subject><subject>Biomedical and Life Sciences</subject><subject>Blood</subject><subject>Cancer Research</subject><subject>Cell Biology</subject><subject>Cells, Cultured</subject><subject>Consensus Sequence</subject><subject>Danio rerio</subject><subject>Developmental Biology</subject><subject>DNA-Binding Proteins - metabolism</subject><subject>Embryonic development</subject><subject>Endothelial Cells - cytology</subject><subject>Endothelial Cells - metabolism</subject><subject>Endothelium</subject><subject>ETS Translocation Variant 6 Protein</subject><subject>Eye Proteins</subject><subject>Freshwater</subject><subject>Genetic aspects</subject><subject>Humans</subject><subject>Invertebrates</subject><subject>Kinases</subject><subject>Life Sciences</subject><subject>Molecular Sequence Data</subject><subject>NAD - metabolism</subject><subject>Neovascularization, Physiologic - physiology</subject><subject>Physiological aspects</subject><subject>Protein Binding</subject><subject>Proto-Oncogene Proteins c-ets - metabolism</subject><subject>Repressor Proteins - genetics</subject><subject>Repressor Proteins - metabolism</subject><subject>Signal transduction</subject><subject>Stem Cells</subject><subject>Transcription Factors - genetics</subject><subject>Transcription Factors - metabolism</subject><subject>Vascular endothelial growth factor</subject><subject>Vascular Endothelial Growth Factor A - metabolism</subject><subject>Vertebrates</subject><subject>Zebrafish - embryology</subject><subject>Zebrafish Proteins - genetics</subject><subject>Zebrafish Proteins - metabolism</subject><issn>1465-7392</issn><issn>1476-4679</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2010</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>ABUWG</sourceid><sourceid>AFKRA</sourceid><sourceid>AZQEC</sourceid><sourceid>BENPR</sourceid><sourceid>CCPQU</sourceid><sourceid>DWQXO</sourceid><sourceid>GNUQQ</sourceid><recordid>eNqF0V1rFDEUBuAgiq2t-AuUQS_Ui6n5_risi9VCoaWt1yGTyaxTMsmaZKD992bZbcuqUHKRkDznkMMLwBsEjxAk8kuwHYaKPwP7iAreUi7U8_WZs1YQhffAq5xvIESUQvES7GEoCcOU7AO-iKGk6Js4NC70sfxyfjS-yasU5zKGZdPdNaa5dr5dlK8XjY3TyrvbQ_BiMD6719v9APw8-Xa9-NGenX8_XRyftZZxVFpCkewUNhxBygjrnbRq6KE0sGNWcTRY0gvErGDGWEkF7gSnBsHBYmklx-QAfNz0rd_5Pbtc9DRm67w3wcU5a8m4YJxw9qSsjHPEFany_V_yJs4p1DHWCComlKjowwYtjXd6DEMsydh1S32MiYJSEaiqOvqPqqt302hjcMNY73cKPu8UVFPcbVmaOWd9enW5a7cT2RRzTm7QqzROJt1pBPU6db1Nvcp324nmbnL9g7uPuYJPG1BjrZm69Djyv73ebmgwZU7uodf9-x--OLmN</recordid><startdate>20101001</startdate><enddate>20101001</enddate><creator>Peterson-Maduro, Josi</creator><creator>van Dam, Hans</creator><creator>Alloul-Ramdhani, Mariam</creator><creator>Baan, Bart</creator><creator>Kobayashi, Kazuki</creator><creator>Baker, David A</creator><creator>Roukens, M. 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Guy</au><au>Schulte-Merker, Stefan</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Control of endothelial sprouting by a Tel-CtBP complex</atitle><jtitle>Nature cell biology</jtitle><stitle>Nat Cell Biol</stitle><addtitle>Nat Cell Biol</addtitle><date>2010-10-01</date><risdate>2010</risdate><volume>12</volume><issue>10</issue><spage>933</spage><epage>942</epage><pages>933-942</pages><issn>1465-7392</issn><eissn>1476-4679</eissn><abstract>The conserved vertebrate transcriptional repressor Tel regulates angiogenesis by directly controlling endothelial sprouting through modulation of Notch ligand Dll4 and vessel branching through other angiogenesis factors such as sprouty and VE-cadherin
We show that the transcriptional repressor Tel plays an evolutionarily conserved role in angiogenesis: it is indispensable for the sprouting of human endothelial cells and for normal development of the
Danio rerio
blood circulatory system. Tel orchestrates endothelial sprouting by binding to the generic co-repressor, CtBP. The Tel–CtBP complex temporally restricts a VEGF (vascular endothelial growth factor)-mediated pulse of
dll4
expression and thereby directly links VEGF receptor intracellular signalling and intercellular Notch–Dll4 signalling. It further controls branching by regulating expression of other factors that constrain angiogenesis such as
sprouty
family members and
ve-cadherin
. Thus, the Tel–CtBP complex conditions endothelial cells for angiogenesis by controlling the balance between stimulatory and antagonistic sprouting cues. Tel control of branching seems to be a refinement of invertebrate tracheae morphogenesis that requires Yan, the invertebrate orthologue of Tel. This work highlights Tel and its associated networks as potential targets for the development of therapeutic strategies to inhibit pathological angiogenesis.</abstract><cop>London</cop><pub>Nature Publishing Group UK</pub><pmid>20835243</pmid><doi>10.1038/ncb2096</doi><tpages>10</tpages></addata></record> |
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| subjects | 631/136/16 631/80/86 Alcohol Oxidoreductases - metabolism Amino Acid Motifs Amino Acid Sequence Analysis Angiogenesis Animals Biology Biomedical and Life Sciences Blood Cancer Research Cell Biology Cells, Cultured Consensus Sequence Danio rerio Developmental Biology DNA-Binding Proteins - metabolism Embryonic development Endothelial Cells - cytology Endothelial Cells - metabolism Endothelium ETS Translocation Variant 6 Protein Eye Proteins Freshwater Genetic aspects Humans Invertebrates Kinases Life Sciences Molecular Sequence Data NAD - metabolism Neovascularization, Physiologic - physiology Physiological aspects Protein Binding Proto-Oncogene Proteins c-ets - metabolism Repressor Proteins - genetics Repressor Proteins - metabolism Signal transduction Stem Cells Transcription Factors - genetics Transcription Factors - metabolism Vascular endothelial growth factor Vascular Endothelial Growth Factor A - metabolism Vertebrates Zebrafish - embryology Zebrafish Proteins - genetics Zebrafish Proteins - metabolism |
| title | Control of endothelial sprouting by a Tel-CtBP complex |
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