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Sphingosine 1-Phosp...
Sphingosine 1-Phosphate Receptor Signaling Establishes AP-1 Gradients to Allow for Retinal Endothelial Cell Specialization
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- Yanagida, Keisuke (author)
- Harvard Med Sch, Boston Childrens Hosp, Dept Surg, Vasc Biol Program, Boston, MA 02115 USA.
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- Engelbrecht, Eric (author)
- Harvard Med Sch, Boston Childrens Hosp, Dept Surg, Vasc Biol Program, Boston, MA 02115 USA.
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- Niaudet, Colin (author)
- Harvard Med Sch, Boston Childrens Hosp, Dept Surg, Vasc Biol Program, Boston, MA 02115 USA.
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- Jung, Bongnam (author)
- Harvard Med Sch, Boston Childrens Hosp, Dept Surg, Vasc Biol Program, Boston, MA 02115 USA.
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- Gängel, Konstantin (author)
- Uppsala universitet,Vaskulärbiologi
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- Holton, Kristina (author)
- Harvard Med Sch Res Comp, Boston, MA USA.
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- Swendeman, Steven (author)
- Harvard Med Sch, Boston Childrens Hosp, Dept Surg, Vasc Biol Program, Boston, MA 02115 USA.
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- Liu, Catherine H. (author)
- Weill Cornell Med, Dept Med, New York, NY USA.
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- Levesque, Michel, V (author)
- Harvard Med Sch, Boston Childrens Hosp, Dept Surg, Vasc Biol Program, Boston, MA 02115 USA.
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- Kuo, Andrew (author)
- Harvard Med Sch, Boston Childrens Hosp, Dept Surg, Vasc Biol Program, Boston, MA 02115 USA.
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- Fu, Zhongjie (author)
- Harvard Med Sch, Boston Childrens Hosp, Dept Ophthalmol, Boston, MA 02115 USA.
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- Smith, Lois E. H. (author)
- Harvard Med Sch, Boston Childrens Hosp, Dept Ophthalmol, Boston, MA 02115 USA.
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- Betsholtz, Christer (author)
- Uppsala universitet,Vaskulärbiologi,Karolinska Inst, ICMC, Novum, Huddinge, Sweden.
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- Hla, Timothy (author)
- Harvard Med Sch, Boston Childrens Hosp, Dept Surg, Vasc Biol Program, Boston, MA 02115 USA.;Broad Inst MIT & Harvard, Cambridge, MA 02142 USA.;Dana Farber Canc Inst, Boston, MA 02115 USA.
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Harvard Med Sch, Boston Childrens Hosp, Dept Surg, Vasc Biol Program, Boston, MA 02115 USA Vaskulärbiologi (creator_code:org_t)
- Elsevier BV, 2020
- 2020
- English.
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In: Developmental Cell. - : Elsevier BV. - 1534-5807 .- 1878-1551. ; 52:6, s. 779-
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Abstract
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- Transcriptional mechanisms that drive angiogenesis and organotypic vascular endothelial cell specialization are poorly understood. Here, we show that retinal endothelial sphingosine 1-phosphate receptors (S1PRs), which restrain vascular endothelial growth factor (VEGF)-induced angiogenesis, spatially restrict expression of JunB, a member of the activator protein 1 (AP-1) family of transcription factors (TFs). Mechanistically, VEGF induces JunB expression at the sprouting vascular front while S1PR-dependent vascular endothelial (VE)-cadherin assembly suppresses JunB expression in the nascent vascular network, thus creating a gradient of this TF. Endothelial-specific JunB knockout mice showed diminished expression of neurovascular guidance genes and attenuated retinal vascular network progression. In addition, endothelial S1PR signaling is required for normal expression of b-catenin-dependent genes such as TCF/LEF1 and ZIC3 TFs, transporters, and junctional proteins. These results show that S1PR signaling restricts JunB function to the expanding vascular front, thus creating an AP-1 gradient and enabling organotypic endothelial cell specialization of the vascular network.
Subject headings
- MEDICIN OCH HÄLSOVETENSKAP -- Medicinska och farmaceutiska grundvetenskaper -- Cell- och molekylärbiologi (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Basic Medicine -- Cell and Molecular Biology (hsv//eng)
Publication and Content Type
- ref (subject category)
- art (subject category)
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- By the author/editor
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Yanagida, Keisuk ...
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Engelbrecht, Eri ...
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Niaudet, Colin
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Jung, Bongnam
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Gängel, Konstant ...
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Holton, Kristina
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show more...
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Swendeman, Steve ...
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Liu, Catherine H ...
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Levesque, Michel ...
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Kuo, Andrew
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Fu, Zhongjie
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Smith, Lois E. H ...
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Betsholtz, Chris ...
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Hla, Timothy
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- About the subject
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- MEDICAL AND HEALTH SCIENCES
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MEDICAL AND HEAL ...
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and Basic Medicine
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and Cell and Molecul ...
- Articles in the publication
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Developmental Ce ...
- By the university
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Uppsala University
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Karolinska Institutet