4.7 Article

Embryonic Tbx3+ cardiomyocytes form the mature cardiac conduction system by progressive fate restriction

Journal

DEVELOPMENT
Volume 145, Issue 17, Pages -

Publisher

COMPANY BIOLOGISTS LTD
DOI: 10.1242/dev.167361

Keywords

Genetic inducible fate mapping; Cardiac conduction system; Sinus node; Atrioventricular node; Atrioventricular bundle; T-box; Tbx3

Funding

  1. Hartstichting [2010B205, 2016T047, 2014T065]
  2. Fondation Leducq
  3. Nederlandse Organisatie voor Wetenschappelijk Onderzoek [ZonMw Veni 016.156.162]
  4. European Research Council (ERC Starting Grant) [714866]
  5. European Research Council (ERC) [714866] Funding Source: European Research Council (ERC)

Ask authors/readers for more resources

A small network of spontaneously active Tbx3(+) cardiomyocytes forms the cardiac conduction system (CCS) in adults. Understanding the origin and mechanism of development of the CCS network are important steps towards disease modeling and the development of biological pacemakers to treat arrhythmias. We found that Tbx3 expression in the embryonic mouse heart is associated with automaticity. Genetic inducible fate mapping revealed that Tbx3(+) cells in the early heart tube are fated to form the definitive CCS components, except the Purkinje fiber network. At mid-fetal stages, contribution of Tbx3(+) cells was restricted to the definitive CCS. We identified a Tbx3(+) population in the outflow tract of the early heart tube that formed the atrioventricular bundle. Whereas Tbx3(+) cardiomyocytes also contributed to the adjacent Gja5(+) atrial and ventricular chamber myocardium, embryonic Gja5(+) chamber cardiomyocytes did not contribute to the Tbx3(+) sinus node or to atrioventricular ring bundles. In conclusion, the CCS is established by progressive fate restriction of a Tbx3(+) cell population in the early developing heart, which implicates Tbx3 as a useful tool for developing strategies to study and treat CCS diseases.

Authors

I am an author on this paper
Click your name to claim this paper and add it to your profile.

Reviews

Primary Rating

4.7
Not enough ratings

Secondary Ratings

Novelty
-
Significance
-
Scientific rigor
-
Rate this paper

Recommended

No Data Available
No Data Available