Visualization and functional characterization of the developing murine cardiac conduction system

S. Rentschler, Dhananjay Vaidya, H. Tamaddon, K. Degenhardt, D. Sassoon, G. E. Morley, J. Jalife, G. I. Fishman

Research output: Contribution to journalArticle

Abstract

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.

Original languageEnglish (US)
Pages (from-to)1785-1792
Number of pages8
JournalDevelopment
Volume128
Issue number10
StatePublished - 2001

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Lac Operon
Reporter Genes
Transgenic Mice
Gene Components
Purkinje Fibers
Sinoatrial Node
Embryonic Development
Coloring Agents
Gene Expression

Keywords

  • Conduction system
  • Heart development
  • Mouse
  • Optical mapping
  • Purkinje fiber

ASJC Scopus subject areas

  • Anatomy
  • Cell Biology

Cite this

Rentschler, S., Vaidya, D., Tamaddon, H., Degenhardt, K., Sassoon, D., Morley, G. E., ... Fishman, G. I. (2001). Visualization and functional characterization of the developing murine cardiac conduction system. Development, 128(10), 1785-1792.

Visualization and functional characterization of the developing murine cardiac conduction system. / Rentschler, S.; Vaidya, Dhananjay; Tamaddon, H.; Degenhardt, K.; Sassoon, D.; Morley, G. E.; Jalife, J.; Fishman, G. I.

In: Development, Vol. 128, No. 10, 2001, p. 1785-1792.

Research output: Contribution to journalArticle

Rentschler, S, Vaidya, D, Tamaddon, H, Degenhardt, K, Sassoon, D, Morley, GE, Jalife, J & Fishman, GI 2001, 'Visualization and functional characterization of the developing murine cardiac conduction system', Development, vol. 128, no. 10, pp. 1785-1792.
Rentschler S, Vaidya D, Tamaddon H, Degenhardt K, Sassoon D, Morley GE et al. Visualization and functional characterization of the developing murine cardiac conduction system. Development. 2001;128(10):1785-1792.
Rentschler, S. ; Vaidya, Dhananjay ; Tamaddon, H. ; Degenhardt, K. ; Sassoon, D. ; Morley, G. E. ; Jalife, J. ; Fishman, G. I. / Visualization and functional characterization of the developing murine cardiac conduction system. In: Development. 2001 ; Vol. 128, No. 10. pp. 1785-1792.
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