The Cytoplasmic Domain of the Ligand EphrinB2 Is Required for Vascular Morphogenesis but Not Cranial Neural Crest Migration

The transmembrane ligand ephrinB2 and its cognate Eph receptor tyrosine kinases are important regulators of vascular morphogenesis. EphrinB2 may have an active signaling role, resulting in bi-directional signal transduction downstream of both ephrinB2 and Eph receptors. To separate the ligand and receptor-like functions of ephrinB2 in mice, we replaced the endogenous gene by cDNAs encoding either carboxyterminally truncated (ephrinB2 ΔC) or, as a control, full-length ligand (ephrinB2 WT). While homozygous ephrinB2 WT/WT animals were viable and fertile, loss of the ephrinB2 cytoplasmic domain resulted in midgestation lethality similar to ephrinB2 null mutants (ephrinB2 KO). The truncated ligand was sufficient to restore guidance of migrating cranial neural crest cells, but ephrinB2 ΔC/ΔC embryos showed defects in vasculogenesis and angiogenesis very similar to those observed in ephrinB2 KO/KO animals. Our results indicate distinct requirements of functions mediated by the ephrinB carboxyterminus for developmental processes in the vertebrate embryo.