Angiogenesis, the formation of new blood vessels from preexisting vessels, is critical to most physiological processes and many pathological conditions. During zebrafish development, angiogenesis expands the axial vessels into a complex vascular network that is necessary for efficient oxygen delivery. Although the dorsal aorta (DA) and the axial vein (AV) are spatially juxtaposed, the initial angiogenic sprouts from these vessels extend in opposite directions, suggesting that distinct cues may regulate angiogenesis of the axial vessels. In this report, we found that angiogenic sprouts from the DA are dependent on Vegf-A signaling, and do not respond to Bmp signals. In contrast, sprouts from the AV are regulated by Bmp signaling independent of Vegf-A signals, suggesting that Bmp is a vein-specific angiogenic cue during early vascular development. Our results support a paradigm, whereby different signals regulate distinct programs of sprouting angiogenesis from the AV and DA, and suggest that signaling heterogeneity contributes to the complexity of vascular networks
