FIGURE 3. Vascular development along the mammalian body axis.

Formation of the dorsal aorta and cardinal veins occurs by de novo aggregation of angioblasts along the anterior/posterior body axis in response to VEGF from the endoderm. Somites, in response to hedgehog from the notochord, might also produce VEGF required for development of these axial vessels. Bone morphogenetic protein (BMP) inhibitors, noggin and chordin, produced by the notochord establish an avascular midline zone. Intersomitic vessels sprout from the dorsal aorta and cardinal vein (not shown) in a VEGF-dependent manner, and are then guided between the somites by repulsive cues, such as ephrinB2, semaphorin3A (sema3A) and sema3E in the somite boundary. Intersomitic arteries bifurcate once they reach the medial edge of the somite, fusing with adjacent intersomitic arteries to form the vertebral artery. The perineural vascular plexus surrounds the neural tube and is formed by angioblasts migrating from the somites in response to VEGF from the neural tube (green band). Once specified by VEGF from the endoderm, the dorsal aorta signals back to the endoderm to induce pancreatic bud formation by means of an unknown signal (blue arrow). Endothelial cells surrounding the prospective hepatic endoderm also provide an unknown signal (blue arrows) to induce hepatic bud development.