scholarly journals H019 Clonal analysis of the origin of the ventricular conduction system

2009 ◽  
Vol 102 ◽  
pp. S78
Author(s):  
L. Miquerol ◽  
N. Moreno ◽  
L. Dupays ◽  
S. Meilhac ◽  
M. Buckingham ◽  
...  
2020 ◽  
Vol 11 (1) ◽  
Author(s):  
Caroline Choquet ◽  
Robert G. Kelly ◽  
Lucile Miquerol

Abstract The ventricular conduction system coordinates heartbeats by rapid propagation of electrical activity through the Purkinje fiber (PF) network. PFs share common progenitors with contractile cardiomyocytes, yet the mechanisms of segregation and network morphogenesis are poorly understood. Here, we apply genetic fate mapping and temporal clonal analysis to identify murine cardiomyocytes committed to the PF lineage as early as E7.5. We find that a polyclonal PF network emerges by progressive recruitment of conductive precursors to this scaffold from a pool of bipotent progenitors. At late fetal stages, the segregation of conductive cells increases during a phase of rapid recruitment to build the definitive PF network through a non-cell autonomous mechanism. We also show that PF differentiation is impaired in Nkx2-5 haploinsufficient embryos leading to failure to extend the scaffold. In particular, late fetal recruitment fails, resulting in PF hypoplasia and persistence of bipotent progenitors. Our results identify how transcription factor dosage regulates cell fate divergence during distinct phases of PF network morphogenesis.


2020 ◽  
Author(s):  
Caroline Choquet ◽  
Robert G. Kelly ◽  
Lucile Miquerol

AbstractThe ventricular conduction system coordinates heartbeats by rapid propagation of electrical activity through the Purkinje fiber (PF) network. PFs share common progenitors with contractile cardiomyocytes, yet the mechanisms of segregation and network morphogenesis are poorly understood. In this study, we apply genetic fate mapping and temporal clonal analysis to identify cardiomyocytes committed to the PF lineage as early as E7.5. We find that a polyclonal PF network emerges by progressive recruitment of conductive precursors to this scaffold from a pool of bipotent progenitors. At late fetal stages, the segregation of conductive cells increases during a phase of rapid recruitment to build the definitive PF network through a non-cell autonomous mechanism. We also show that PF differentiation is impaired in Nkx2-5 haploinsufficient embryos leading to failure to extend the scaffold. In particular, late fetal recruitment fails, resulting in PF hypoplasia and persistence of bipotent progenitors. Our results identify how transcription factor dosage regulates cell fate divergence during distinct phases of PF network morphogenesis.


2016 ◽  
Vol 6 (1) ◽  
Author(s):  
Kyoung-Han Kim ◽  
Anna Rosen ◽  
Samer M. I. Hussein ◽  
Vijitha Puviindran ◽  
Adam S. Korogyi ◽  
...  

2012 ◽  
Vol 95 (4) ◽  
pp. 469-479 ◽  
Author(s):  
Barbora Sankova ◽  
Jiri Benes ◽  
Eliska Krejci ◽  
Laurent Dupays ◽  
Magali Theveniau-Ruissy ◽  
...  

1984 ◽  
Vol 4 (1) ◽  
pp. 25-33
Author(s):  
Takashi Hiraga ◽  
Yutaka Nakaya ◽  
Toshiharu Niki ◽  
Hiroyoshi Mori ◽  
Kazuo Hizawa

2015 ◽  
Vol 29 (S1) ◽  
Author(s):  
Alena Kvasilova ◽  
Bjarke Jensen ◽  
Vincent Christoffels ◽  
David Sedmera

eLife ◽  
2018 ◽  
Vol 7 ◽  
Author(s):  
Bjarke Jensen ◽  
Bastiaan J Boukens ◽  
Dane A Crossley ◽  
Justin Conner ◽  
Rajiv A Mohan ◽  
...  

Mammals and birds have a specialized cardiac atrioventricular conduction system enabling rapid activation of both ventricles. This system may have evolved together with high heart rates to support their endothermic state (warm-bloodedness) and is seemingly lacking in ectothermic vertebrates from which first mammals then birds independently evolved. Here, we studied the conduction system in crocodiles (Alligator mississippiensis), the only ectothermic vertebrates with a full ventricular septum. We identified homologues of mammalian conduction system markers (Tbx3-Tbx5, Scn5a, Gja5, Nppa-Nppb) and show the presence of a functional atrioventricular bundle. The ventricular Purkinje network, however, was absent and slow ventricular conduction relied on trabecular myocardium, as it does in other ectothermic vertebrates. We propose the evolution of the atrioventricular bundle followed full ventricular septum formation prior to the development of high heart rates and endothermy. In contrast, the evolution of the ventricular Purkinje network is strongly associated with high heart rates and endothermy.


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