Fig. 8.

A two-step process is responsible for sympathetic innervation of the developing heart. Model for sympathetic axon innervation of the developing mouse heart. At E13.5, coronary veins undergo angiogenic remodeling in the subepicardium. Venous VSMCs transiently secrete NGF as they associate with remodeled veins. Sympathetic axons start to extend into the subepicardium. By E15.5, NGF expression in venous VSMCs proceeds distally in parallel with vascular remodeling, and axons extend along newly formed veins. Some arterial VSMCs begin to express NGF in the myocardium. By E17.5, which is the stage when sympathetic innervation penetrates the myocardium, NGF expression is detected only in arterial VSMCs.