Genetic Regulation of Sinoatrial Node Development and Pacemaker Program in the Venous Pole

Journal of Cardiovascular Development and Disease

Wenduo Ye³  Yingnan Song³  Zhen Huang³  Yanding Zhang²  Yiping Chen³  Robert E. Poelmann¹ 

[1] Department of Cell and Molecular Biology, Tulane University, New Orleans, LA 70118, USA;;Southern Center for Biomedical Research, Fujian Normal University, Fuzhou 350108, China; E-Mail:;Department of Cell and Molecular Biology, Tulane University, New Orleans, LA 70118, USA; E-Mails:

关键词: pacemaker development;    venous pole;    atrial fibrillation;    SAN;    pulmonary vein;   

DOI  :  10.3390/jcdd2040282

来源: mdpi

【 摘 要 】

The definitive sinoatrial node (SAN), the primary pacemaker of the mammalian heart, develops from part of pro-pacemaking embryonic venous pole that expresses both Hcn4 and the transcriptional factor Shox2. It is noted that ectopic pacemaking activities originated from the myocardial sleeves of the pulmonary vein and systemic venous return, both derived from the Shox2⁺ pro-pacemaking cells in the venous pole, cause atrial fibrillation. However, the developmental link between the pacemaker properties in the embryonic venous pole cells and the SAN remains largely uncharacterized. Furthermore, the genetic program for the development of heterogeneous populations of the SAN is also under-appreciated. Here, we review the literature for a better understanding of the heterogeneous development of the SAN in relation to that of the sinus venosus myocardium and pulmonary vein myocardium. We also attempt to revisit genetic models pertinent to the development of pacemaker activities in the perspective of a Shox2-Nkx2-5 epistatic antagonism. Finally, we describe recent efforts in deciphering the regulatory networks for pacemaker development by genome-wide approaches.

【 授权许可】

CC BY   
© 2015 by the authors; licensee MDPI, Basel, Switzerland.