Neovascularization of the Xenopus embryo.
The receptor tyrosine kinase, Flk-1 or VEGFR-2, and its ligand, vascular endothelial growth factor (VEGF) are required for the development of the embryonic vasculature. Targeted disruption of either gene in mice results in the failure of vascular system formation. The Xenopus homologues of flk-1 and VEGF have been cloned and their expression has been examined throughout early embryonic development. These studies indicate that flk-1 is expressed in groups of endothelial precursor cells which will form the major blood vessels of the embryo, including the posterior cardinal veins, the dorsal aorta, the vitelline veins, and the endocardium. VEGF expression is found in tissues adjacent to the mesenchyme containing the flk-1-expressing endothelial precursors. Expression of both flk-1 and VEGF is transient, appearing as the primary vascular plexus is forming and declining steadily after the onset of functional embryonic circulation. After establishment of the primary vascular structures, flk-1 expression is also observed in the intersegmental veins which form by an angiogenic mechanism. Overall, these results support a role for VEGF/flk-1 signaling in both vasculogenesis and angiogenesis in the Xenopus embryo. When VEGF is expressed ectopically in Xenopus embryos by microinjection of either plasmid DNA or synthetic mRNA, large, disorganized vascular structures are produced. This result indicates that ectopic VEGF is capable of altering the architecture of the developing vascular network.
Cleaver
O
O
Institute for Cellular and Molecular Biology, University of Texas at Austin 78712, USA.
Tonissen
K F
KF
Saha
M S
MS
Krieg
P A
PA
D000595:Amino Acid Sequence; D000818:Animals; D003001:Cloning, Molecular; D016228:Endothelial Growth Factors / Q000235:genetics*; D004730:Endothelium, Vascular / Q000166:cytology / Q000378:metabolism; D018507:Gene Expression Regulation, Developmental; D005796:Genes; D017403:In Situ Hybridization; D008222:Lymphokines / Q000235:genetics*; D008969:Molecular Sequence Data; D018919:Neovascularization, Physiologic; D012333:RNA, Messenger / Q000235:genetics; D020794:Receptor Protein-Tyrosine Kinases / Q000235:genetics*; D017978:Receptors, Growth Factor / Q000235:genetics*; D040262:Receptors, Vascular Endothelial Growth Factor; D016415:Sequence Alignment; D017386:Sequence Homology, Amino Acid; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors; D014982:Xenopus laevis / Q000196:embryology* / Q000235:genetics
D016228:Endothelial Growth Factors; D008222:Lymphokines; D012333:RNA, Messenger; D017978:Receptors, Growth Factor; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors; D020794:Receptor Protein-Tyrosine Kinases; D040262:Receptors, Vascular Endothelial Growth Factor