Ephrin-B1 forward and reverse signaling are required during mouse development.
Eph receptors and ephrin ligands are key players in many developmental processes including embryo patterning, angiogenesis, and axon guidance. Eph/ephrin interactions lead to the generation of a bidirectional signal, in which both the Eph receptors and the ephrins activate downstream signaling cascades simultaneously. To understand the role of ephrin-B1 and the importance of ephrin-B1-induced reverse signaling during embryonic development, we have generated mouse lines carrying mutations in the efnb1 gene. Complete ablation of ephrin-B1 resulted in perinatal lethality associated with a range of phenotypes, including defects in neural crest cell (NCC)-derived tissues, incomplete body wall closure, and abnormal skeletal patterning. Conditional deletion of ephrin-B1 demonstrated that ephrin-B1 acts autonomously in NCCs, and controls their migration. Last, a mutation in the PDZ binding domain indicated that ephrin-B1-induced reverse signaling is required in NCCs. Our results demonstrate that ephrin-B1 acts both as a ligand and as a receptor in a tissue-specific manner during embryogenesis.
Davy
Alice
A
Program in Developmental Biology, Division of Basic Sciences, Fred Hutchinson Cancer Research Center, Seattle, Washington 98109, USA.
Aubin
Josée
J
Soriano
Philippe
P
D000818:Animals; D001846:Bone Development / Q000235:genetics; D002352:Carrier Proteins / Q000235:genetics / Q000502:physiology*; D005314:Embryonic and Fetal Development / Q000235:genetics*; D036387:Ephrin-B1; D005121:Extremities / Q000196:embryology / Q000254:growth & development; D005260:Female; D006579:Heterozygote; D051379:Mice; D018345:Mice, Knockout; D009432:Neural Crest / Q000254:growth & development / Q000473:pathology; D010641:Phenotype; D017689:Polydactyly / Q000209:etiology / Q000235:genetics; D011956:Receptors, Cell Surface / Q000235:genetics / Q000502:physiology*; D015398:Signal Transduction; D012886:Skull / Q000254:growth & development
D002352:Carrier Proteins; C092571:Efnb1 protein, mouse; D036387:Ephrin-B1; D011956:Receptors, Cell Surface