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(DeltaC)) 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(DeltaC/DeltaC) 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.
Adams
R H
RH
European Molecular Biology Laboratory, Meyerhofstrasse 1, D-69117 Heidelberg, Germany.
Diella
F
F
Hennig
S
S
Helmbacher
F
F
Deutsch
U
U
Klein
R
R
D042683:Angiopoietin-1; D000818:Animals; D001808:Blood Vessels / Q000737:chemistry / Q000166:cytology / Q000196:embryology; D001934:Branchial Region / Q000737:chemistry / Q000166:cytology / Q000196:embryology; D002465:Cell Movement / Q000502:physiology*; D003593:Cytoplasm / Q000737:chemistry; D005314:Embryonic and Fetal Development / Q000502:physiology; D036388:Ephrin-B2; D018507:Gene Expression Regulation, Developmental; D008024:Ligands; D008562:Membrane Glycoproteins / Q000235:genetics; D008565:Membrane Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D051379:Mice; D008817:Mice, Mutant Strains; D018919:Neovascularization, Physiologic / Q000502:physiology*; D009432:Neural Crest / Q000737:chemistry / Q000166:cytology* / Q000196:embryology; D009474:Neurons / Q000737:chemistry / Q000166:cytology; D017434:Protein Structure, Tertiary; D020794:Receptor Protein-Tyrosine Kinases / Q000235:genetics / Q000378:metabolism; D036224:Receptor, EphB4; D042787:Receptor, TIE-2; D036081:Receptors, Eph Family; D015398:Signal Transduction / Q000502:physiology
D042683:Angiopoietin-1; C467628:Angpt1 protein, mouse; D036388:Ephrin-B2; D008024:Ligands; D008562:Membrane Glycoproteins; D008565:Membrane Proteins; D020794:Receptor Protein-Tyrosine Kinases; D036224:Receptor, EphB4; D042787:Receptor, TIE-2; D036081:Receptors, Eph Family