Symmetrical mutant phenotypes of the receptor EphB4 and its specific transmembrane ligand ephrin-B2 in cardiovascular development.
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.
Gerety
S S
SS
Division of Biology, Howard Hughes Medical Institute, California Institute of Technology, Pasadena 91125, USA.
Wang
H U
HU
Chen
Z F
ZF
Anderson
D J
DJ
D000818:Animals; D001158:Arteries / Q000737:chemistry / Q000196:embryology; D001775:Blood Circulation; D002319:Cardiovascular System / Q000196:embryology*; D004730:Endothelium, Vascular / Q000737:chemistry; D036388:Ephrin-B2; D005838:Genotype; D006257:Head / Q000098:blood supply; D006321:Heart / Q000196:embryology; D006579:Heterozygote; D008024:Ligands; D008565:Membrane Proteins / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D008817:Mice, Mutant Strains; D009024:Morphogenesis; D016297:Mutagenesis, Site-Directed; D009200:Myocardial Contraction; D018919:Neovascularization, Physiologic; D010641:Phenotype; D020794:Receptor Protein-Tyrosine Kinases / Q000235:genetics / Q000302:isolation & purification / Q000378:metabolism*; D036183:Receptor, EphB2; D015183:Restriction Mapping; D014018:Tissue Distribution; D014680:Veins / Q000737:chemistry / Q000196:embryology; D015017:Yolk Sac / Q000098:blood supply
D036388:Ephrin-B2; D008024:Ligands; D008565:Membrane Proteins; D020794:Receptor Protein-Tyrosine Kinases; D036183:Receptor, EphB2