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 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.
Davis
D L
DL
Department of Cell and Developmental Biology, Fox Chase Cancer Center, Philadelphia, PA 19111, USA.
Edwards
A V
AV
Juraszek
A L
AL
Phelps
A
A
Wessels
A
A
Burch
J B
JB
D000818:Animals; D001283:Atrioventricular Node / Q000187:drug effects / Q000196:embryology; D001483:Base Sequence; D004247:DNA / Q000235:genetics; D004268:DNA-Binding Proteins / Q000235:genetics* / Q000502:physiology*; D004699:Endocardium / Q000196:embryology; D004742:Enhancer Elements, Genetic; D050993:GATA6 Transcription Factor; D017353:Gene Deletion; D018507:Gene Expression Regulation, Developmental / Q000187:drug effects; D006329:Heart Conduction System / Q000187:drug effects / Q000196:embryology*; D019426:Integrases / Q000235:genetics; D007763:Lac Operon; D051379:Mice; D008822:Mice, Transgenic; D008969:Molecular Sequence Data; D014157:Transcription Factors / Q000235:genetics* / Q000502:physiology*; D014212:Tretinoin / Q000494:pharmacology; D014764:Viral Proteins / Q000235:genetics
D004268:DNA-Binding Proteins; D050993:GATA6 Transcription Factor; C494760:Gata6 protein, mouse; D014157:Transcription Factors; D014764:Viral Proteins; D014212:Tretinoin; D004247:DNA; C045073:Cre recombinase; D019426:Integrases