Development of the Cardiac Conduction System

Overview

Journal Adv Exp Med Biol

Specialties Biology
General Medicine

Date 2024 Jun 17

PMID 38884712

Authors

Lieve E van der Maarel

Vincent M Christoffels

Affiliations

Soon will be listed here.

Abstract

The electrical impulses that coordinate the sequential, rhythmic contractions of the atria and ventricles are initiated and tightly regulated by the specialized tissues of the cardiac conduction system. In the mature heart, these impulses are generated by the pacemaker cardiomyocytes of the sinoatrial node, propagated through the atria to the atrioventricular node where they are delayed and then rapidly propagated to the atrioventricular bundle, right and left bundle branches, and finally, the peripheral ventricular conduction system. Each of these specialized components arise by complex patterning events during embryonic development. This chapter addresses the origins and transcriptional networks and signaling pathways that drive the development and maintain the function of the cardiac conduction system.

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References

Cingolani E, Goldhaber J, Marban E . Next-generation pacemakers: from small devices to biological pacemakers. Nat Rev Cardiol. 2017; 15(3):139-150. PMC: 6261336. DOI: 10.1038/nrcardio.2017.165. View

Tyser R, Miranda A, Chen C, Davidson S, Srinivas S, Riley P . Calcium handling precedes cardiac differentiation to initiate the first heartbeat. Elife. 2016; 5. PMC: 5059139. DOI: 10.7554/eLife.17113. View

Meilhac S, Buckingham M . The deployment of cell lineages that form the mammalian heart. Nat Rev Cardiol. 2018; 15(11):705-724. DOI: 10.1038/s41569-018-0086-9. View

Miquerol L, Bellon A, Moreno N, Beyer S, Meilhac S, Buckingham M . Resolving cell lineage contributions to the ventricular conduction system with a Cx40-GFP allele: a dual contribution of the first and second heart fields. Dev Dyn. 2013; 242(6):665-77. DOI: 10.1002/dvdy.23964. View

Miquerol L, Moreno-Rascon N, Beyer S, Dupays L, Meilhac S, Buckingham M . Biphasic development of the mammalian ventricular conduction system. Circ Res. 2010; 107(1):153-61. DOI: 10.1161/CIRCRESAHA.110.218156. View

Liang D, Xue J, Geng L, Zhou L, Lv B, Zeng Q . Cellular and molecular landscape of mammalian sinoatrial node revealed by single-cell RNA sequencing. Nat Commun. 2021; 12(1):287. PMC: 7804277. DOI: 10.1038/s41467-020-20448-x. View

Linscheid N, Logantha S, Poulsen P, Zhang S, Schrolkamp M, Egerod K . Quantitative proteomics and single-nucleus transcriptomics of the sinus node elucidates the foundation of cardiac pacemaking. Nat Commun. 2019; 10(1):2889. PMC: 6599035. DOI: 10.1038/s41467-019-10709-9. View

Vedantham V, Galang G, Evangelista M, Deo R, Srivastava D . RNA sequencing of mouse sinoatrial node reveals an upstream regulatory role for Islet-1 in cardiac pacemaker cells. Circ Res. 2015; 116(5):797-803. PMC: 4344860. DOI: 10.1161/CIRCRESAHA.116.305913. View

Goodyer W, Beyersdorf B, Paik D, Tian L, Li G, Buikema J . Transcriptomic Profiling of the Developing Cardiac Conduction System at Single-Cell Resolution. Circ Res. 2019; 125(4):379-397. PMC: 6675655. DOI: 10.1161/CIRCRESAHA.118.314578. View

10.

VAN MIEROP L . Location of pacemaker in chick embryo heart at the time of initiation of heartbeat. Am J Physiol. 1967; 212(2):407-15. DOI: 10.1152/ajplegacy.1967.212.2.407. View

11.

Christoffels V, Smits G, Kispert A, Moorman A . Development of the pacemaker tissues of the heart. Circ Res. 2010; 106(2):240-54. DOI: 10.1161/CIRCRESAHA.109.205419. View

12.

Stieber J, Herrmann S, Feil S, Loster J, Feil R, Biel M . The hyperpolarization-activated channel HCN4 is required for the generation of pacemaker action potentials in the embryonic heart. Proc Natl Acad Sci U S A. 2003; 100(25):15235-40. PMC: 299971. DOI: 10.1073/pnas.2434235100. View

13.

Garcia-Frigola C, Shi Y, Evans S . Expression of the hyperpolarization-activated cyclic nucleotide-gated cation channel HCN4 during mouse heart development. Gene Expr Patterns. 2003; 3(6):777-83. PMC: 5576435. DOI: 10.1016/s1567-133x(03)00125-x. View

14.

Liang X, Wang G, Lin L, Lowe J, Zhang Q, Bu L . HCN4 dynamically marks the first heart field and conduction system precursors. Circ Res. 2013; 113(4):399-407. PMC: 4017870. DOI: 10.1161/CIRCRESAHA.113.301588. View

15.

Bressan M, Liu G, Mikawa T . Early mesodermal cues assign avian cardiac pacemaker fate potential in a tertiary heart field. Science. 2013; 340(6133):744-8. PMC: 3651765. DOI: 10.1126/science.1232877. View

16.

Yi T, Wong J, Feller E, Sink S, Taghli-Lamallem O, Wen J . Electrophysiological mapping of embryonic mouse hearts: mechanisms for developmental pacemaker switch and internodal conduction pathway. J Cardiovasc Electrophysiol. 2011; 23(3):309-18. PMC: 3749437. DOI: 10.1111/j.1540-8167.2011.02191.x. View

17.

Vicente-Steijn R, Kelder T, Tertoolen L, Wisse L, Pijnappels D, Poelmann R . RHOA-ROCK signalling is necessary for lateralization and differentiation of the developing sinoatrial node. Cardiovasc Res. 2017; 113(10):1186-1197. DOI: 10.1093/cvr/cvx104. View

18.

Mommersteeg M, Hoogaars W, Prall O, de Gier-de Vries C, Wiese C, Clout D . Molecular pathway for the localized formation of the sinoatrial node. Circ Res. 2007; 100(3):354-62. DOI: 10.1161/01.RES.0000258019.74591.b3. View

19.

Mommersteeg M, Dominguez J, Wiese C, Norden J, de Gier-de Vries C, Burch J . The sinus venosus progenitors separate and diversify from the first and second heart fields early in development. Cardiovasc Res. 2010; 87(1):92-101. DOI: 10.1093/cvr/cvq033. View

20.

Hoogaars W, Engel A, Brons J, Verkerk A, de Lange F, Wong L . Tbx3 controls the sinoatrial node gene program and imposes pacemaker function on the atria. Genes Dev. 2007; 21(9):1098-112. PMC: 1855235. DOI: 10.1101/gad.416007. View