A GATA-6 gene heart-region-specific enhancer provides a novel means to mark and probe a discrete component of the mouse cardiac conduction system

The transcriptional programs that specify the distinct components of the cardiac conduction system are poorly understood, in part due to a paucity of definitive molecular markers. In the present study we show that a cGATA-6 gene enhancer can be used to selectively express transgenes in the atriovent...

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Bibliographic Details
Published in:Mechanisms of development 2001-10, Vol.108 (1), p.105-119
Main Authors: Davis, Dorene L., Edwards, Angela V., Juraszek, Amy L., Phelps, Aimee, Wessels, Andy, Burch, John B.E.
Format: Article
Language:English
Subjects:
Animals
Atrioventricular Node - drug effects
Atrioventricular Node - embryology
Base Sequence
Cardiac conduction system
Cre recombinase
DNA - genetics
DNA-Binding Proteins - genetics
DNA-Binding Proteins - physiology
Endocardium - embryology
Enhancer Elements, Genetic
GATA-6
GATA6 Transcription Factor
Gene Deletion
Gene Expression Regulation, Developmental - drug effects
Heart Conduction System - drug effects
Heart Conduction System - embryology
Heart development
Integrases - genetics
Lac Operon
Mice
Mice, Transgenic
Molecular Sequence Data
Transcription Factors - genetics
Transcription Factors - physiology
Tretinoin - pharmacology
Viral Proteins - genetics
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Summary:The transcriptional programs that specify the distinct components of the cardiac conduction system are poorly understood, in part due to a paucity of definitive molecular markers. In the present study we show that a cGATA-6 gene enhancer can be used to selectively express transgenes in the atrioventricular (AV) conduction system as it becomes manifest in the developing multichambered mouse heart. Furthermore, our analysis of staged cGATA-6/lacZ embryos revealed that the activity of this heart-region-specific enhancer can be traced back essentially to the outset of the cardiogenic program. We provide evidence that this enhancer reads medial/lateral and anterior/posterior positional information before the heart tube forms and we show that the activity of this enhancer becomes restricted at the heart looping stage to AV myocardial cells that induce endocardial cushion formation. We infer that a deeply-rooted heart-region-specific transcriptional program serves to coordinate AV valve placement and AV conduction system formation. Lastly, we show that cGATA-6/Cre mice can be used to delete floxed genes in the respective subsets of specialized heart cells.
ISSN:0925-4773
1872-6356
DOI:10.1016/S0925-4773(01)00500-7