Peripheral nerves and blood vessels lie close together and have similar branching patterns in many tissues, which suggests that their development might be coordinated. Previously, Yoh-suke Mukouyama and co-workers reported that signals secreted by sensory nerves determine vascular patterning in the skin. Here (), the researchers show that there is an anatomical congruence between sympathetic nerves and coronary veins in the developing mouse heart. In contrast to the situation in skin, this neurovascular association is not important for vascular patterning, but is instead required for the functional sympathetic innervation of the heart. Vascular smooth muscle cells (VSMCs) associate with coronary veins during angiogenic remodelling, they report, and mediate the extension of sympathetic axons within the subepicardium by secreting nerve growth factor (NGF). Subsequently, venous VSMCs downregulate NGF expression and arterial VSMCs begin to secrete NGF, which stimulates the axons to innervate coronary arteries in the myocardium. Thus, sequential expression of NGF in subepicardial venous VSMCs and myocardial arterial VSMCs determines the heart’s stereotypical pattern of sympathetic innervation.
