RT Journal Article
SR Electronic
T1 Nkx2-5 defines distinct scaffold and recruitment phases during formation of the cardiac Purkinje fiber network
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 2020.03.23.003764
DO 10.1101/2020.03.23.003764
A1 Caroline Choquet
A1 Robert G. Kelly
A1 Lucile Miquerol
YR 2020
UL http://biorxiv.org/content/early/2020/09/09/2020.03.23.003764.abstract
AB 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. 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.Competing Interest StatementThe authors have declared no competing interest.