Induction of Purkinje fiber differentiation by coronary arterialization

A synchronized heart beat is controlled by pacemaking impulses conducted th rough Purkinje fibers. In chicks, these impulse-conducting cells are recrui ted during embryogenesis from myocytes in direct association with developin g coronary arteries. In culture, the vascular cytokine endothelin converts embryonic myocytes to Purkinje cells, implying that selection of conduction phenotype may be mediated by an instructive cue from arteries. To investig ate this hypothesis, coronary arterial development in the chicken embryo wa s either inhibited by neural crest ablation or activated by ectopic express ion of fibroblast growth factor (FGF), Ablation of cardiac neural crest res ulted in approximate to 70% reductions (P < 0.01) in the density of intramu ral coronary arteries and associated Purkinje fibers. Activation of coronar y arterial branching was induced by retrovirus-mediated overexpression of F GF. At sites of FGF-induced hypervascularization, ectopic Purkinje fibers d ifferentiated adjacent to newly induced coronary arteries. Our data indicat e the necessity and sufficiency of developing arterial bed for converting a juxtaposed myocyte into a Purkinje fiber cell and provide evidence for an inductive function for arteriogenesis in heart development distinct from it s role in establishing coronary blood circulation.