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On the Evolution of the Cardiac Pacemaker

Hubrecht Institute-KNAW and University Medical Center Utrecht, 3584 CT Utrecht, The Netherlands
Department of Medical Biology, Academic Medical Center Amsterdam, 1105 AZ Amsterdam, The Netherlands
Department of Medical Physiology, Division of Heart and Lungs, University Medical Center Utrecht, 3584 CT Utrecht, The Netherlands
Author to whom correspondence should be addressed.
Academic Editors: Robert E. Poelmann and Monique R. M. Jongbloed
J. Cardiovasc. Dev. Dis. 2017, 4(2), 4;
Received: 24 March 2017 / Revised: 18 April 2017 / Accepted: 24 April 2017 / Published: 27 April 2017
The rhythmic contraction of the heart is initiated and controlled by an intrinsic pacemaker system. Cardiac contractions commence at very early embryonic stages and coordination remains crucial for survival. The underlying molecular mechanisms of pacemaker cell development and function are still not fully understood. Heart form and function show high evolutionary conservation. Even in simple contractile cardiac tubes in primitive invertebrates, cardiac function is controlled by intrinsic, autonomous pacemaker cells. Understanding the evolutionary origin and development of cardiac pacemaker cells will help us outline the important pathways and factors involved. Key patterning factors, such as the homeodomain transcription factors Nkx2.5 and Shox2, and the LIM-homeodomain transcription factor Islet-1, components of the T-box (Tbx), and bone morphogenic protein (Bmp) families are well conserved. Here we compare the dominant pacemaking systems in various organisms with respect to the underlying molecular regulation. Comparative analysis of the pathways involved in patterning the pacemaker domain in an evolutionary context might help us outline a common fundamental pacemaker cell gene programme. Special focus is given to pacemaker development in zebrafish, an extensively used model for vertebrate development. Finally, we conclude with a summary of highly conserved key factors in pacemaker cell development and function. View Full-Text
Keywords: pacemaker cell; heart evolution; sinoatrial node; zebrafish; heart development pacemaker cell; heart evolution; sinoatrial node; zebrafish; heart development
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Burkhard, S.; Van Eif, V.; Garric, L.; Christoffels, V.M.; Bakkers, J. On the Evolution of the Cardiac Pacemaker. J. Cardiovasc. Dev. Dis. 2017, 4, 4.

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