Symmetrical mutant phenotypes of the receptor EphB4 and its specific transmembrane ligand ephrin-B2 in cardiovascular development

Mol Cell. 1999 Sep;4(3):403-14. doi: 10.1016/s1097-2765(00)80342-1.


Ephrin-B2 is a transmembrane ligand that is specifically expressed on arteries but not veins and that is essential for cardiovascular development. However, ephrin-B2 is also expressed in nonvascular tissues and interacts with multiple EphB class receptors expressed in both endothelial and nonendothelial cell types. Thus, the identity of the relevant receptor for ephrin-B2 and the site(s) where these molecules interact to control angiogenesis were not clear. Here we show that EphB4, a specific receptor for ephrin-B2, is exclusively expressed by vascular endothelial cells in embryos and is preferentially expressed on veins. A targeted mutation in EphB4 essentially phenocopies the mutation in ephrin-B2. These data indicate that ephrin-B2-EphB4 interactions are intrinsically required in vascular endothelial cells and are consistent with the idea that they mediate bidirectional signaling essential for angiogenesis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Arteries / chemistry
  • Arteries / embryology
  • Blood Circulation
  • Cardiovascular System / embryology*
  • Endothelium, Vascular / chemistry
  • Ephrin-B2
  • Genotype
  • Head / blood supply
  • Heart / embryology
  • Heterozygote
  • Ligands
  • Membrane Proteins / metabolism*
  • Mice
  • Mice, Inbred C57BL
  • Mice, Mutant Strains
  • Morphogenesis
  • Mutagenesis, Site-Directed
  • Myocardial Contraction
  • Neovascularization, Physiologic*
  • Phenotype
  • Receptor Protein-Tyrosine Kinases / genetics
  • Receptor Protein-Tyrosine Kinases / isolation & purification
  • Receptor Protein-Tyrosine Kinases / metabolism*
  • Receptor, EphB2
  • Restriction Mapping
  • Tissue Distribution
  • Veins / chemistry
  • Veins / embryology
  • Yolk Sac / blood supply


  • Ephrin-B2
  • Ligands
  • Membrane Proteins
  • Receptor Protein-Tyrosine Kinases
  • Receptor, EphB2