During limb development, dorsal and ventral muscles progressively separate to form individual muscles in a process called muscle splitting. In their study on p. 2579,Duprez and colleagues reveal that blood vessels regulate this process. They report that the location of endothelial cells, which are present in the developing chick limb before muscle, determines the site of future zones of muscle cleavage. By overexpressing VEGFA (a key growth factor in blood vessel development) in chick wing buds prior to muscle splitting, the researchers induced both blood vessel and connective tissue formation, while inhibiting muscle formation. Conversely, blocking blood vessel formation with a soluble VEGFR1 in chick wing buds caused muscle fusion. The authors propose that PDGFB(platelet-derived growth factor B), which is expressed in endothelial cells,is the molecular signal that regulates this process, perhaps by promoting the production of the extracellular matrix and attracting connective tissue cells to future sites of muscle splitting.