VEGF MEDIATES ANGIOBLAST MIGRATION DURING DEVELOPMENT OF THE DORSAL AORTA IN XENOPUS

Angioblasts are precursor cells of the vascular endothelium which orga nize into the primitive blood vessels during embryogenesis. The molecu lar mechanisms underlying patterning of the embryonic vasculature rema in unclear Mutational analyses of the receptor tyrosine kinase flk-1 a nd its ligand vascular endothelial growth factor, VEGF, indicate that these molecules are critical for vascular development, Targeted ablati on of the flk-1 gene results in complete failure of blood and vascular development (F, Shalaby et al, (1995) Nature 376, 62-66), while targe ted ablation of the VEGF gene results in gross abnormalities in vascul ar patterning (P, Carmeliet et al, (1996) Nature 380, 435-439; N, Ferr ara et al, (1996) Nature 380, 439-442), Here we report a role for VEGF in patterning the dorsal aorta of the Xenopus embryo. We show that th e diffusible form of VEGF is expressed by the hypochord, which lies at the embryonic midline immediately dorsal to the location of the futur e dorsal aorta. We find that, initially, no flk-1-expressing angioblas ts are present at this location, but that during subsequent developmen t, angioblasts migrate from the lateral plate mesoderm to the midline where they form a single dorsal aorta. We have demonstrated that VEGF can act as a chemoattractant for angioblasts by ectopic expression of VEGF in the embryo. These results strongly suggest that localized sour ces of VEGF play a role in patterning the embryonic vasculature.