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Publication : Iroquois homeobox gene 3 establishes fast conduction in the cardiac His-Purkinje network.

First Author  Zhang SS Year  2011
Journal  Proc Natl Acad Sci U S A Volume  108
Issue  33 Pages  13576-81
PubMed ID  21825130 Mgi Jnum  J:175992
Mgi Id  MGI:5288100 Doi  10.1073/pnas.1106911108
Citation  Zhang SS, et al. (2011) Iroquois homeobox gene 3 establishes fast conduction in the cardiac His-Purkinje network. Proc Natl Acad Sci U S A 108(33):13576-81
abstractText  Rapid electrical conduction in the His-Purkinje system tightly controls spatiotemporal activation of the ventricles. Although recent work has shed much light on the regulation of early specification and morphogenesis of the His-Purkinje system, less is known about how transcriptional regulation establishes impulse conduction properties of the constituent cells. Here we show that Iroquois homeobox gene 3 (Irx3) is critical for efficient conduction in this specialized tissue by antithetically regulating two gap junction-forming connexins (Cxs). Loss of Irx3 resulted in disruption of the rapid coordinated spread of ventricular excitation, reduced levels of Cx40, and ectopic Cx43 expression in the proximal bundle branches. Irx3 directly represses Cx43 transcription and indirectly activates Cx40 transcription. Our results reveal a critical role for Irx3 in the precise regulation of intercellular gap junction coupling and impulse propagation in the heart.
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