%0 Journal Article %T Biphasic development of the mammalian ventricular conduction system. %+ Institut de Biologie du Développement de Marseille (IBDM) %+ Université de la Méditerranée - Aix-Marseille 2 %+ Universidad de Jaén (UJA) %+ Biologie du Développement %+ National Institute for Medical Research (NIMR) %A Miquerol, Lucile %A Moreno-Rascon, Natividad %A Beyer, Sabrina %A Dupays, Laurent %A Meilhac, Sigolène M %A Buckingham, Margaret E %A Franco, Diego %A Kelly, Robert G %Z This work was supported by the CNRS (to R.G.K. and M.E.B.); the Association Française contre les Myopathies (to L.M.); the Institut Pasteur (to M.E.B.); the Junta de Andalusia CTS 446, CTS 1614 (to D.F.); and the European Community’s FP6 contract (HeartRepair) LSHM-CT-2005-018630 (to R.G.K., D.F., and M.E.B.) and FP7 CardioGeNet project (grant HEALTH-2007-B-223463). S.M. is an INSERM research fellow. %< avec comité de lecture %@ 0009-7330 %J Circulation Research %I American Heart Association %V 107 %N 1 %P 153-61 %8 2010-07-09 %D 2010 %R 10.1161/CIRCRESAHA.110.218156 %M 20466980 %K conduction system %K cell lineage %K clonal analysis %K nlaacZ %K Purkinje fibers %K conduction system %Z Life Sciences [q-bio]/Development Biology/MorphogenesisJournal articles %X RATIONALE:The ventricular conduction system controls the propagation of electric activity through the heart to coordinate cardiac contraction. This system is composed of specialized cardiomyocytes organized in defined structures including central components and a peripheral Purkinje fiber network. How the mammalian ventricular conduction system is established during development remains controversial. %X OBJECTIVE:To define the lineage relationship between cells of the murine ventricular conduction system and surrounding working myocytes. %X METHODS AND RESULTS:A retrospective clonal analysis using the alpha-cardiac actin(nlaacZ/+) mouse line was carried out in three week old hearts. Clusters of clonally related myocytes were screened for conductive cells using connexin40-driven enhanced green fluorescent protein expression. Two classes of clusters containing conductive cells were obtained. Mixed clusters, composed of conductive and working myocytes, reveal that both cell types develop from common progenitor cells, whereas smaller unmixed clusters, composed exclusively of conductive cells, show that proliferation continues after lineage restriction to the conduction system lineage. Differences in the working component of mixed clusters between the right and left ventricles reveal distinct progenitor cell histories in these cardiac compartments. These results are supported by genetic fate mapping using Cre recombinase revealing progressive restriction of connexin40-positive myocytes to a conductive fate. %X CONCLUSIONS:A biphasic mode of development, lineage restriction followed by limited outgrowth, underlies establishment of the mammalian ventricular conduction system. %G English %Z We thank Jean-François Nicolas and Elena Tzouanacou for extensive discussions and careful reading of the manuscript and Rachel Sturny for technical assistance. We thank IGBMC and Dr Roger Y. Tsien for giving us permission to use the sequences CreERT2 and mRFP-1. %2 https://pasteur.hal.science/pasteur-01572048/document %2 https://pasteur.hal.science/pasteur-01572048/file/Biphasic%20development%20of%20the%20mammalian%20ventricular%20conduction%20system.pdf %L pasteur-01572048 %U https://pasteur.hal.science/pasteur-01572048 %~ PASTEUR %~ CNRS %~ UNIV-AMU %~ OPENAIRE %~ IBDM