Conditions affecting the arterial vasculature present pressing challenges in global health. Yet, the complex mechanisms underlying artery formation remain elusive, impeding the development of novel treatments. A team of researchers from the Max Planck Institute for Molecular Biomedicine, led by Mara Pitulescu and Ralf Adams, have uncovered new insights into how arteries form. Building on their earlier discovery how Notch-signaling directs „tip“ cells to become arteries, their latest study published in Nature Communications reveals the crucial role of EphB4 and ephrin-B2 in shaping the fate of tip cells.