Transcriptional regulation in the mouse atrioventricular conduction system.
We identified a GATA6 gene enhancer that selectively marks the developing atrioventricular conduction system (AVCS) in transgenic mice. This enhancer reads anterior/posterior and medial/lateral positional information early in the cardiogenic programme and remains active in progressively more restricted subsets of heart cells leading up to AVCS formation. Additional experiments will be required to determine if the potential to be recruited into the AVCS is similarly restricted to a subset of myocardial cells early in the cardiogenic programme or if this enhancer can also be activated de novo in cells that initially reside outside this field. We are using several strategies to identify factors that regulate this and other AVCS enhancers and hence govern AVCS function. We are also using this enhancer to make transgenic mice that express Cre, or an inducible form of Cre, to track lineages and to delete floxed genes in the developing or mature AVCS. This Cre/lox approach provides a means to deconstruct complex congenital heart phenotypes that involve the conduction system and to test whether genes are required to form the AVCS or to maintain AVCS function. Lastly, we are exploring strategies to isolate and analyse AVCS cells from normal and affected hearts.
Edwards
Angela V
AV
Department of Cell and Developmental Biology, Fox Chase Cancer Center, Philadelphia, PA 19111, USA.
Davis
Dorene L
DL
Juraszek
Amy L
AL
Wessels
Andy
A
Burch
John B E
JB
D000818:Animals; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism; D004742:Enhancer Elements, Genetic; D050993:GATA6 Transcription Factor; D005786:Gene Expression Regulation; D006321:Heart / Q000033:anatomy & histology / Q000196:embryology*; D006329:Heart Conduction System / Q000196:embryology / Q000502:physiology*; D018398:Homeodomain Proteins / Q000235:genetics / Q000378:metabolism; D051379:Mice; D008822:Mice, Transgenic; D009024:Morphogenesis; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism; D014158:Transcription, Genetic
D004268:DNA-Binding Proteins; D050993:GATA6 Transcription Factor; C494760:Gata6 protein, mouse; D018398:Homeodomain Proteins; D014157:Transcription Factors