Key result
Genetic tracing and clonal analysis in Connexin40-GFP mice revealed that the mammalian ventricular conduction system is comprised of cells derived from first and second heart field progenitor lineages.
The study demonstrates that the mammalian ventricular conduction system derives from two distinct lineages originating from the first and second heart fields.
May inform congenital conduction disorder mechanisms; leaves open whether dual heart field origins apply in humans.
BACKGROUND: The ventricular conduction system (VCS) coordinates the heartbeat and is composed of central components (the atrioventricular node, bundle, and right and left bundle branches) and a peripheral Purkinje fiber network. Conductive myocytes develop from common progenitor cells with working myocytes in a bimodal process of lineage restriction followed by limited outgrowth. The lineage relationship between progenitor cells giving rise to different components of the VCS is unclear. RESULTS: Cell lineage contributions to different components of the VCS were analysed by a combination of retrospective clonal analysis, regionalized transgene expression studies, and genetic tracing experiments using Connexin40-GFP mice that precisely delineate the VCS. Analysis of a library of hearts containing rare large clusters of clonally related myocytes identifies two VCS lineages encompassing either the right Purkinje fiber network or left bundle branch. Both lineages contribute to the atrioventricular bundle and right bundle branch that segregate early from working myocytes. Right and left VCS lineages share the transcriptional program of the respective ventricular working myocytes and genetic tracing experiments discount alternate progenitor cell contributions to the VCS. CONCLUSIONS: The mammalian VCS is comprised of cells derived from two lineages, supporting a dual contribution of first and second heart field progenitor cells.
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Miquerol et al. (2013) studied Ventricular conduction system development. Genetic tracing and clonal analysis was evaluated on Cell lineage contributions to the ventricular conduction system. Genetic tracing and clonal analysis in Connexin40-GFP mice revealed that the mammalian ventricular conduction system is comprised of cells derived from first and second heart field progenitor lineages.
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