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Publication : A molecular pathway including Id2, Tbx5, and Nkx2-5 required for cardiac conduction system development.

First Author  Moskowitz IP Year  2007
Journal  Cell Volume  129
Issue  7 Pages  1365-76
PubMed ID  17604724 Mgi Jnum  J:122971
Mgi Id  MGI:3716040 Doi  10.1016/j.cell.2007.04.036
Citation  Moskowitz IP, et al. (2007) A molecular pathway including Id2, Tbx5, and Nkx2-5 required for cardiac conduction system development. Cell 129(7):1365-76
abstractText  The cardiac conduction system is an anatomically discrete segment of specialized myocardium that initiates and propagates electrical impulses to coordinate myocardial contraction. To define the molecular composition of the mouse ventricular conduction system we used microdissection and transcriptional profiling by serial analysis of gene expression (SAGE). Conduction-system-specific expression for Id2, a member of the Id gene family of transcriptional repressors, was identified. Analyses of Id2-deficient mice demonstrated structural and functional conduction system abnormalities, including left bundle branch block. A 1.2 kb fragment of the Id2 promoter proved sufficient for cooperative regulation by Nkx2-5 and Tbx5 in vitro and for conduction-system-specific gene expression in vivo. Furthermore, compound haploinsufficiency of Tbx5 and Nkx2-5 or Tbx5 and Id2 prevented embryonic specification of the ventricular conduction system. We conclude that a molecular pathway including Tbx5, Nkx2-5, and Id2 coordinates specification of ventricular myocytes into the ventricular conduction system lineage.
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