PUBLICATION

UXT potentiates angiogenesis by attenuating Notch signaling

Authors
Zhou, Y., Ge, R., Wang, R., Liu, F., Huang, Y., Liu, H., Hao, Y., Zhou, Q., Wang, C.
ID
ZDB-PUB-150127-13
Date
2015
Source
Development (Cambridge, England)   142(4): 774-86 (Journal)
Registered Authors
Liu, Feng, Zhou, Yi
Keywords
none
MeSH Terms
  • Cell Movement/genetics
  • Cell Movement/physiology
  • Humans
  • Neovascularization, Physiologic/genetics
  • Neovascularization, Physiologic/physiology*
  • Cell Division/genetics
  • Cell Division/physiology
  • Receptors, Notch/genetics
  • Receptors, Notch/metabolism*
  • Animals
  • Zebrafish Proteins/genetics
  • Zebrafish Proteins/metabolism*
  • Human Umbilical Vein Endothelial Cells
  • Zebrafish/embryology*
  • Zebrafish/genetics
  • Zebrafish/metabolism*
  • Immunoglobulin J Recombination Signal Sequence-Binding Protein/genetics
  • Immunoglobulin J Recombination Signal Sequence-Binding Protein/metabolism
(all 18)
PubMed
25617435 Full text @ Development
Abstract
Angiogenesis is spatially and temporally orchestrated by a myriad of signaling pathways, including the Notch signaling pathway. Here, we identified UXT as an evolutionarily conserved and developmentally expressed protein, indispensable for intersegmental vessel (ISV) formation in zebrafish. Deficiency of UXT in zebrafish embryos results in shorter ISVs, loss of tip cell behavior, and impairment of endothelial cell migration and division. Significantly, UXT attenuates the expression of the Notch-responsive genes in vitro and in vivo. Mechanistically, UXT binds to the promoters of the Notch signaling target genes and specifically interacts with the transactivation region domain of the Notch intracellular domain (NICD), impairing the interaction between NICD and the transcription factor RBP-Jκ endogenously. This prevents RBP-Jκ/CSL from activation and thus inhibits the consequent gene inductions. Furthermore, blockade of Notch signaling rescues the angiogenesis defect caused by UXT knockdown both in vitro and in vivo. Taken together, the data presented in this study characterize UXT as a novel repressor of Notch signaling, shedding new light on the molecular regulation of angiogenesis.
Genes / Markers
Marker Marker Type Name
angpt1GENEangiopoietin 1
aplnraGENEapelin receptor a
cdx4GENEcaudal type homeobox 4
dll4GENEdelta-like 4 (Drosophila)
efnb2aGENEephrin-B2a
flt1GENEfms related receptor tyrosine kinase 1
flt4GENEfms related receptor tyrosine kinase 4
gapdhGENEglyceraldehyde-3-phosphate dehydrogenase
her6GENEhairy-related 6
hey1GENEhes-related family bHLH transcription factor with YRPW motif 1
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Figures
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Expression
Phenotype
Mutations / Transgenics
Allele Construct Type Affected Genomic Region
jh11TgTransgenic Insertion
    s843TgTransgenic Insertion
      y1TgTransgenic Insertion
        y7TgTransgenic Insertion
          1 - 4 of 4
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          Human Disease / Model
          No data available
          Sequence Targeting Reagents
          Target Reagent Reagent Type
          dll4MO1-dll4MRPHLNO
          notch1bMO2-notch1bMRPHLNO
          rbpjaMO4-rbpja,rbpjbMRPHLNO
          rbpjbMO4-rbpja,rbpjbMRPHLNO
          uxtMO1-uxtMRPHLNO
          uxtMO2-uxtMRPHLNO
          uxtMO3-uxtMRPHLNO
          1 - 7 of 7
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          Fish
          Antibodies
          Name Type Antigen Genes Isotypes Host Organism
          Ab1-uxtmonoclonalMouse
          1 - 1 of 1
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          Orthology
          Gene Orthology
          uxt
          1 - 1 of 1
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          Engineered Foreign Genes
          Marker Marker Type Name
          EGFPEFGEGFP
          mCherryEFGmCherry
          1 - 2 of 2
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          Mapping
          No data available