Temporal requirement of Nkx2-5 during cardiac conduction system development

The cardiac conduction system (CCS) encompasses a complex system responsible for the coordinated contraction of the heart. In the developing heart, as well as in the adult heart, tissues of the (putative) CCS are characterized by different properties than the surrounding working myocardium, which can be observed on a histological level, as well as by the expression patterns of several immunohistological and molecular markers. In recent years, many markers have been studied that have helped to elucidate the processes involved in CCS development. It has become clear that multiple genes, cells and their interactions are involved in this complex process. In this article, an overview of the current knowledge of CCS development is supplied. Furthermore, several controversies regarding conduction system development are discussed, as well as the possible significance of embryologic development of the CCS for the development of arrhythmias later in life.

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Distinct roles of HF-1b/Sp4 in ventricular and neural crest cells lineages affect cardiac conduction system development

Developmental Biology ◽

10.1016/j.ydbio.2005.10.018 ◽

2006 ◽

Vol 291 (2) ◽

pp. 208-217 ◽

Cited By ~ 23

Author(s):

Tara R. St. Amand ◽

Jonathan T. Lu ◽

Monica Zamora ◽

Yusu Gu ◽

Janelle Stricker ◽

...

Keyword(s):

Neural Crest ◽

System Development ◽

Neural Crest Cells ◽

Conduction System ◽

Cardiac Conduction ◽

Cardiac Conduction System

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Transcriptional regulation of cardiac conduction system development: 2004 FASEB cardiac conduction system minimeeting, Washington, DC

The Anatomical Record ◽

10.1002/ar.a.20101 ◽

2004 ◽

Vol 280A (2) ◽

pp. 1036-1045 ◽

Cited By ~ 9

Author(s):

Brett S. Harris ◽

Patrick Y. Jay ◽

Mary S. Rackley ◽

Seigo Izumo ◽

Terrence X. O'Brien ◽

...

Keyword(s):

Transcriptional Regulation ◽

System Development ◽

Conduction System ◽

Cardiac Conduction ◽

Cardiac Conduction System ◽

Washington Dc

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Mouse Models for Cardiac Conduction System Development

Novartis Foundation Symposia - Development of the Cardiac Conduction System ◽

10.1002/0470868066.ch4 ◽

2008 ◽

pp. 44-67 ◽

Cited By ~ 8

Author(s):

Andy Wessels ◽

Aimee Phelps ◽

Thomas C. Trusk ◽

Dorene L. Davis ◽

Angela V. Edwards ◽

...

Keyword(s):

Mouse Models ◽

System Development ◽

Conduction System ◽

Cardiac Conduction ◽

Cardiac Conduction System

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Tbx3-Mediated Regulation of Cardiac Conduction System Development and Function: Potential Contributions of Alternative RNA Processing

Pediatric Cardiology ◽

10.1007/s00246-019-02166-4 ◽

2019 ◽

Vol 40 (7) ◽

pp. 1388-1400

Author(s):

Brian P. Delisle ◽

Yao Yu ◽

Pavan Puvvula ◽

Allison R. Hall ◽

Chad Huff ◽

...

Keyword(s):

Rna Processing ◽

System Development ◽

Conduction System ◽

Cardiac Conduction ◽

Cardiac Conduction System ◽

And Function ◽

Function Potential

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Visualization and functional characterization of the developing murine cardiac conduction system

Development ◽

10.1242/dev.128.10.1785 ◽

2001 ◽

Vol 128 (10) ◽

pp. 1785-1792 ◽

Cited By ~ 8

Author(s):

S. Rentschler ◽

D.M. Vaidya ◽

H. Tamaddon ◽

K. Degenhardt ◽

D. Sassoon ◽

...

Keyword(s):

Transgenic Mice ◽

Optical Mapping ◽

System Development ◽

Conduction System ◽

Cardiac Conduction ◽

Cardiac Conduction System ◽

Conductive Network ◽

Lacz Reporter ◽

Lacz Expression ◽

Lacz Reporter Gene

The cardiac conduction system is a complex network of cells that together orchestrate the rhythmic and coordinated depolarization of the heart. The molecular mechanisms regulating the specification and patterning of cells that form this conductive network are largely unknown. Studies in avian models have suggested that components of the cardiac conduction system arise from progressive recruitment of cardiomyogenic progenitors, potentially influenced by inductive effects from the neighboring coronary vasculature. However, relatively little is known about the process of conduction system development in mammalian species, especially in the mouse, where even the histological identification of the conductive network remains problematic. We have identified a line of transgenic mice where lacZ reporter gene expression delineates the developing and mature murine cardiac conduction system, extending proximally from the sinoatrial node to the distal Purkinje fibers. Optical mapping of cardiac electrical activity using a voltage-sensitive dye confirms that cells identified by the lacZ reporter gene are indeed components of the specialized conduction system. Analysis of lacZ expression during sequential stages of cardiogenesis provides a detailed view of the maturation of the conductive network and demonstrates that patterning occurs surprisingly early in embryogenesis. Moreover, optical mapping studies of embryonic hearts demonstrate that a murine His-Purkinje system is functioning well before septation has completed. Thus, these studies describe a novel marker of the murine cardiac conduction system that identifies this specialized network of cells throughout cardiac development. Analysis of lacZ expression and optical mapping data highlight important differences between murine and avian conduction system development. Finally, this line of transgenic mice provides a novel tool for exploring the molecular circuitry controlling mammalian conduction system development and should be invaluable in studies of developmental mutants with potential structural or functional conduction system defects.

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