PUBLICATION

Sphingosine-1-Phosphate Receptors S1pr1 and S1pr2 Cooperatively Regulate Embryonic Vascular Development

Authors
Mendelson, K., Zygmunt, T., Torres-Vazquez, J., Evans, T., and Hla, T.
ID
ZDB-PUB-121220-12
Date
2013
Source
The Journal of biological chemistry   288(4): 2143-2156 (Journal)
Registered Authors
Evans, Todd, Torres-Vázquez, Jesús, Zygmunt, Tomasz
Keywords
angiogenesis, development, sphingolipid, sphingosine-1-phosphate, vascular biology, zebrafish
MeSH Terms
  • Cloning, Molecular
  • Zebrafish
  • Genome
  • Microscopy, Fluorescence/methods
  • Endothelium, Vascular/embryology*
  • Cell Proliferation
  • Biological Transport
  • Sphingolipids/metabolism
  • Neovascularization, Physiologic
  • Animals
  • Signal Transduction
  • Tissue Distribution
  • Models, Biological
  • Phenotype
  • Neovascularization, Pathologic
  • In Situ Hybridization
  • Receptors, Lysosphingolipid/metabolism*
  • Body Patterning
  • Gene Expression Regulation, Developmental*
(all 19)
PubMed
23229546 Full text @ J. Biol. Chem.
Abstract

Sphingosine-1-phosphate (S1P) binds G-protein coupled S1pr1-5 receptors to regulate a multitude of physiological effects, especially those in the vascular and immune systems. S1P receptors in the vascular system have been characterized primarily in mammals. Here we report that the S1P receptors and metabolic enzymes are conserved in the genome of zebrafish Danio rerio. Bioinformatic analysis identified seven S1P receptor-like sequences in the zebrafish genome, including duplicated orthologs of receptors 3 and 5. Sphingolipidomic analysis detected erythrocyte and plasma S1P as well as high plasma ceramides and sphingosine. Morpholino-mediated knockdown of s1pr1 causes global and pericardial edema, loss of blood circulation, and vascular defects characterized by both reduced vascularization in intersegmental vessels, decreased proliferation of intersegmental and axial vessels, and hypersprouting in the caudal vein plexus. The s1pr2 gene was previously characterized as a regulator of cell migration and heart development but its role in angiogenesis is not known. However, when expression of both s1pr1 and s1pr2 is suppressed, severely reduced vascular development of the intersegmental vessels was observed with doses of the s1pr1 morpholino that alone did not cause any discernible vascular defects, suggesting that s1pr1 and s1pr2 function cooperatively to regulate vascular development in zebrafish. Similarly, the S1P transporter, spns2, also cooperated with s1pr1. We propose that extracellular S1P acts through vascular S1P receptors to regulate vascular development.

Genes / Markers
Figures
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Expression
Phenotype
Mutations / Transgenics
Allele Construct Type Affected Genomic Region
s896TgTransgenic Insertion
    sd2TgTransgenic Insertion
      ubs1TgTransgenic Insertion
        y1TgTransgenic Insertion
          1 - 4 of 4
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          Human Disease / Model
          No data available
          Sequence Targeting Reagents
          Target Reagent Reagent Type
          s1pr1MO2-s1pr1MRPHLNO
          s1pr1MO3-s1pr1MRPHLNO
          s1pr2MO1-s1pr2MRPHLNO
          s1pr2MO3-s1pr2MRPHLNO
          spns2MO2-spns2MRPHLNO
          tp53MO4-tp53MRPHLNO
          1 - 6 of 6
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          Fish
          Antibodies
          No data available
          Orthology
          Engineered Foreign Genes
          Marker Marker Type Name
          DsRedEFGDsRed
          EGFPEFGEGFP
          mCherryEFGmCherry
          1 - 3 of 3
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          Mapping
          No data available