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 ca rdiac 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 g ene enhancer can be used to selectively express transgenes in the atriovent ricular (AV) conduction system as it becomes manifest in the developing mul tichambered mouse heart. Furthermore, our analysis of staged cGATA-6/lacZ e mbryos revealed that the activity of this heart-region-specific enhancer ca n be traced back essentially to the outset of the cardiogenic program. We p rovide evidence that this enhancer reads medial/lateral and anterior/poster ior 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 th at a deeply-rooted heart-region-specific transcriptional program serves to coordinate AV valve placement and AV conduction system formation. Lastly, w e show that cGATA-6/Cre mice can be used to delete flexed genes in the resp ective subsets of specialized heart cells. (C) 2001 Elsevier Science Irelan d Ltd. All rights reserved.