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J. Cardiovasc. Dev. Dis. 2015, 2(4), 282-298; doi:10.3390/jcdd2040282

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

1,* , 1,2,3
Department of Cell and Molecular Biology, Tulane University, New Orleans, LA 70118, USA
Southern Center for Biomedical Research, Fujian Normal University, Fuzhou 350108, China
Fujian Key Laboratory of Developmental and Neural Biology, College of Life Science, Fujian Normal University, Fuzhou 350108, China
Authors to whom correspondence should be addressed.
Academic Editors: Robert E. Poelmann and Monique R.M. Jongbloed
Received: 28 October 2015 / Revised: 22 November 2015 / Accepted: 24 November 2015 / Published: 30 November 2015
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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. View Full-Text
Keywords: pacemaker development; venous pole; atrial fibrillation; SAN; pulmonary vein pacemaker development; venous pole; atrial fibrillation; SAN; pulmonary vein

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This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. (CC BY 4.0).

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MDPI and ACS Style

Ye, W.; Song, Y.; Huang, Z.; Zhang, Y.; Chen, Y. Genetic Regulation of Sinoatrial Node Development and Pacemaker Program in the Venous Pole. J. Cardiovasc. Dev. Dis. 2015, 2, 282-298.

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