Connexins in Cardiac Development: Expression, Role, and Transcriptional Control

Gros, Daniël; Alcoléa, Sébastien; Dupays, Laurent; Meysen, S.; Théveniau-Ruissy, Magali; Teunissen, Birgit E.J.; Bierhuizen, Marti F.A.

doi:10.1007/3-540-28621-7_3

Cited by 5 publications

(3 citation statements)

References 93 publications

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“…The eGFP expression starts in the ventricles at day E9.5 and is mainly observed in the trabecular layer of both ventricles. By E15.5, eGFP expression is seen in the AVB and in the ventricular conduction system (Gros et al, 2005). eGFP expression in Nkx2.5 +/− /Cx40 +/eGFP embryos was indistinguishable from that of Nkx2.5 +/+ /Cx40 +/eGFP embryos between E13.5 to E18.5 (Figs.…”

Section: Hypoplasia Of Purkinje Fiber Network Is Associated With Abno...mentioning

confidence: 96%

Nkx2.5 cell-autonomous gene function is required for the postnatal formation of the peripheral ventricular conduction system

Meysen

Marger

Hewett

et al. 2007

Developmental Biology

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The ventricular conduction system is responsible for rapid propagation of electrical activity to coordinate ventricular contraction. To investigate the role of the transcription factor Nkx2.5 in the morphogenesis of the ventricular conduction system, we crossed Nkx2.5(+/-) mice with Cx40(eGFP/+) mice in which eGFP expression permits visualization of the His-Purkinje conduction system. Major anatomical and functional disturbances were detected in the His-Purkinje system of adult Nkx2.5(+/-)/Cx40(eGFP/+) mice, including hypoplasia of eGFP-positive Purkinje fibers and the disorganization of the Purkinje fiber network in the ventricular apex. Although the action potential properties of the individual eGFP-positive cells were normal, the deficiency of Purkinje fibers in Nkx2.5 haploinsufficient mice was associated with abnormalities of ventricular electrical activation, including slowed and decremented conduction along the left bundle branch. During embryonic development, eGFP expression in the ventricular trabeculae of Nkx2.5(+/-) hearts was qualitatively normal, with a measurable deficiency in eGFP-positive cells being observed only after birth. Chimeric analyses showed that maximal Nkx2.5 levels are required cell-autonomously. Reduced Nkx2.5 levels are associated with a delay in cell cycle withdrawal in surrounding GFP-negative myocytes. Our results suggest that the formation of the peripheral conduction system is time- and dose-dependent on the transcription factor Nkx2.5 that is cell-autonomously required for the postnatal differentiation of Purkinje fibers.

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Section: Hypoplasia Of Purkinje Fiber Network Is Associated With Abno...mentioning

confidence: 96%

Nkx2.5 cell-autonomous gene function is required for the postnatal formation of the peripheral ventricular conduction system

Meysen

Marger

Hewett

et al. 2007

Developmental Biology

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“…At the early stages of cardiac morphogenesis Cx45 expression is widespread throughout the heart, but in the adult heart it is only detectable in some specific regions (sinoatrial and atrioventricular nodes, the conduction system, and the peripheral regions of the IVS) (Gros et al, 2005). Besides the heart, Cx45 expression has been found in several other tissues as well.…”

Section: Discussionmentioning

confidence: 99%

“…Mice lacking Cx45 conditionally in cardiac myocytes also displayed lethality around embryonic day 10 due to heart failure (Nishii et al, 2003). Proper expression of Cx45 thus appears to be essential for cardiac development. In the early stages of cardiac morphogenesis Cx45 expression is widespread throughout the heart, but it is gradually downregulated and finally restricted to some specialized regions in the adult heart, including the sinoatrial and atrioventricular nodes, the conduction system, and the peripheral regions of the interventricular septum (IVS) (Gros et al, 2005). This characteristic developmental and regional expression pattern of Cx45 in the heart suggests tight spatiotemporal regulation.…”

Section: Introductionmentioning

confidence: 98%

Primary Structure, Organization, and Expression of the Rat Connexin45 Gene

Teunissen

Jansen

Mutsaers

et al. 2007

DNA and Cell Biology

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In the mammalian heart, the gap junction protein connexin45 (Cx45) has a characteristic spatiotemporal expression pattern and is involved in mediating the rapid spreading of the electrical impulse that precedes coordinated contraction. The aim of this study was to isolate and characterize the rat Cx45 gene and to investigate its expression pattern in various tissues and cell lines. The gene consists of four exons (termed E1a, E1b, E2, and E3), of which the complete protein-coding sequence as well as a small part of the 5' -untranslated region (5'-UTR) reside on E3. 5' -Rapid amplification of cDNA ends (5' -RACE) analysis demonstrated the existence of four transcripts, which all contained the same coding region (derived from E3) but differed in the composition of their 5'-UTR. Analysis of Cx45 RNA expression in various rat tissues and cultured cell lines revealed that the transcripts composed of either E1a, E2, and E3 (i.e., E1a/2/3) or of E1b, E2, and E3 (E1b/2/3) sequences are both ubiquitously expressed. Comparison of the rat Cx45 gene structure with its murine ortholog indicated both similarities and species-specific differences in Cx45 gene organization. These findings will allow for the mapping and characterization of the rat Cx45 gene regulatory regions.

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Connexins in the Heart

Severs

2009

Connexins

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Connexins in Cardiac Development: Expression, Role, and Transcriptional Control

Cited by 5 publications

References 93 publications

Nkx2.5 cell-autonomous gene function is required for the postnatal formation of the peripheral ventricular conduction system

Nkx2.5 cell-autonomous gene function is required for the postnatal formation of the peripheral ventricular conduction system

Primary Structure, Organization, and Expression of the Rat Connexin45 Gene

Connexins in the Heart

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