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Edg-1, the G protein-coupled receptor for sphingosine-1-phosphate, is essential for vascular maturation.

Sphingolipid signaling pathways have been implicated in many critical cellular events. Sphingosine-1-phosphate (SPP), a sphingolipid metabolite found in high concentrations in platelets and blood, stimulates members of the endothelial differentiation gene (Edg) family of G protein-coupled receptors and triggers diverse effects, including cell growth, survival, migration, and morphogenesis. To determine the in vivo functions of the SPP/Edg signaling pathway, we disrupted the Edg1 gene in mice. Edg1(-/-) mice exhibited embryonic hemorrhage leading to intrauterine death between E12.5 and E14.5. Vasculogenesis and angiogenesis appeared normal in the mutant embryos. However, vascular maturation was incomplete due to a deficiency of vascular smooth muscle cells/pericytes. We also show that Edg-1 mediates an SPP-induced migration response that is defective in mutant cells due to an inability to activate the small GTPase, Rac. Our data reveal Edg-1 to be the first G protein-coupled receptor required for blood vessel formation and show that sphingolipid signaling is essential during mammalian development.

Pubmed ID: 11032855


  • Liu Y
  • Wada R
  • Yamashita T
  • Mi Y
  • Deng CX
  • Hobson JP
  • Rosenfeldt HM
  • Nava VE
  • Chae SS
  • Lee MJ
  • Liu CH
  • Hla T
  • Spiegel S
  • Proia RL


The Journal of clinical investigation

Publication Data

October 15, 2000

Associated Grants


Mesh Terms

  • Animals
  • Blood Vessels
  • Cardiovascular System
  • Cell Movement
  • Fibroblasts
  • GTP-Binding Proteins
  • Heart
  • Homozygote
  • Immediate-Early Proteins
  • Lysophospholipids
  • Mice
  • Mice, Knockout
  • Muscle, Smooth, Vascular
  • Phenotype
  • Receptors, Cell Surface
  • Receptors, G-Protein-Coupled
  • Receptors, Lysophospholipid
  • Signal Transduction
  • Sphingosine