The rhythmic excitation of the mature heart depends upon the integrated function of the heterogeneous network of cells that together comprise the specialized cardiac conduction system

The rhythmic excitation of the mature heart depends upon the integrated function of the heterogeneous network of cells that together comprise the specialized cardiac conduction system (CCS). While substantial progress has been made in clarifying the molecular pathways regulating many aspects of cardiogenesis (reviewed in Srivastava and Olson, 2000), a detailed understanding of the specification, differentiation and patterning of the conduction system itself is lacking. As the number of identifiable inherited human syndromes and induced mouse mutants with defects in cardiac conduction has increased, the impetus to unravel the molecular pathways governing formation and function of this cellular network has grown. Several fundamental questions in CCS development have been the subject of recent investigation. Perhaps foremost has been the origin of conductive cells. While conductive cells from a number of species express several genes in common with neuronal cells, an elegant series of experiments using retroviral lineage-tracing techniques has provided strong evidence that in the chick, components of the conduction system derive from bipotential cardiomyogenic cells, rather than through transdifferentiation of neural crest derivatives (Gourdie et al., 1995; Cheng et al., 1999). Indirect evidence using Cre/lox technology to mark neural crest derivatives in the developing mouse also argues against a contribution of this lineage to the CCS (Jiang et al., 2000). Prompted by the observation that a subset of the distal elements of the avian CCS, specifically the intramural Purkinje 1785 Development 128, 1785-1792 (2001) Printed in Great Britain © The Company of Biologists Limited 2001 DEV3297