Development of the cardiac conduction system involves recruitment within amultipotent cardiomyogenic lineage

The cardiac pacemaking and conduction system sets and maintains the rhythmi c pumping action of the heart. Previously, we have shown that peripheral ce lls of the conduction network in chick (periarterial Purkinje fibers) are s elected within a cardiomyogenic lineage and that this recruitment occurs as a result of paracrine cues from coronary arteries. At present, the cellula r derivation of other elements of this specialized system (e,g, the nodes a nd bundles of the central conduction system) are controversial, with some p roposing that the evidence supports a neurogenic and others a myogenic orig in for these tissues, While such ontological questions remain, it is unlike ly that progress can be made on the molecular mechanisms governing patterni ng and induction of the central conduction system, Here, we have undertaken lineage-tracing strategies based on the distinct properties of replication -incompetent adenoviral and retroviral lacZ-expressing constructs. Using th ese complementary approaches, it is shown that cells constituting both peri pheral and central conduction tissues originate from cardiomyogenic progeni tors present in the looped, tubular heart with no detectable contribution b y migratory neuroectoderm-derived populations. Moreover, clonal analyses of retrovirally infected cells incorporated within any part of the conduction system suggest that such cells share closer lineage relationships with nea rby contractive myocytes than with other, more distal elements of the condu ction system. Differentiation birthdating by label dilution using [H-3]thym idine also demonstrates the occurrence of ongoing myocyte conscription to c onductive specialization and provides a time course for this active and loc alized selection process in different parts of the system, Together, these data suggest that the cardiac conduction system does not develop by outgrow th from a prespecified pool of 'primary' myogenic progenitors. Rather, its assembly and elaboration occur via processes that include progressive and l ocalized recruitment of multipotent cardiomyogenic cells to the developing network of specialized cardiac tissues.