title: Resolving cell lineage contributions to the ventricular conduction system with a Cx40-GFP allele: a dual contribution of the first and second heart fields.
abstract: 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.
authors.affiliation: Aix-Marseille University, CNRS UMR 7288, Developmental Biology Institute of Marseille, Marseille, France. lucile.miquerol@univ-amu.fr
authors.forename: Lucile
authors.initials: L
authors.lastname: Miquerol
authors.forename: Anaïs
authors.initials: A
authors.lastname: Bellon
authors.forename: Natividad
authors.initials: N
authors.lastname: Moreno
authors.forename: Sabrina
authors.initials: S
authors.lastname: Beyer
authors.forename: Sigolène M
authors.initials: SM
authors.lastname: Meilhac
authors.forename: Margaret
authors.initials: M
authors.lastname: Buckingham
authors.forename: Diego
authors.initials: D
authors.lastname: Franco
authors.forename: Robert G
authors.initials: RG
authors.lastname: Kelly
mesh_terms: D000483:Alleles; D000818:Animals; D002036:Bundle of His / Q000378:metabolism; D019070:Cell Lineage; D017630:Connexins / Q000235:genetics* / Q000502:physiology; D005260:Female; D049452:Green Fluorescent Proteins / Q000378:metabolism; D006329:Heart Conduction System / Q000196:embryology*; D006352:Heart Ventricles / Q000196:embryology*; D008297:Male; D051379:Mice; D008856:Microscopy, Fluorescence; D009206:Myocardium / Q000166:cytology; D032383:Myocytes, Cardiac / Q000166:cytology; D013234:Stem Cells / Q000166:cytology*; D013997:Time Factors; D014158:Transcription, Genetic; D019076:Transgenes; D000097003:Gap Junction alpha-5 Protein
chemical_list: D017630:Connexins; D049452:Green Fluorescent Proteins; D000097003:Gap Junction alpha-5 Protein