Expression profiling of the forming atrioventricular node using a novel Tbx3-based node-specific transgenic reporter

The atrioventricular (AV) node is a recurrent source of potentially life-threatening arrhythmias. Nevertheless, limited data are available on its developmental control or molecular phenotype. We used a novel AV node-specific reporter mouse to gain insight into the gene programs determining the formation and phenotype of the AV node. In the transgenic reporter, green fluorescent protein (GFP) expression was driven by 160 kbp of Tbx3 and flanking sequences. GFP was selectively expressed in the AV canal of embryos, and in the AV node of adults, while all other Tbx3+ conduction system components, including the AV bundle, were devoid of GFP expression. Fluorescent AV nodal (Tbx3BAC-Egfp) and complementary working (NppaBAC336-Egfp) myocardial cell populations of E10.5 embryos and E17.5 fetuses were purified using fluorescence-activated cell sorting, and their expression profiles were assessed by microarray analysis. We constructed a comprehensive list of sodium, calcium, and potassium channels specific for the nodal or working myocard. Furthermore, the data revealed that the AV node and the working myocardium phenotypes diverge during development, but that the functional gene classes characteristic for both compartments are maintained. Interestingly, the AV node-specific gene repertoire consisted of multiple neurotrophic factors not yet appreciated to play a role in nodal development. These data present the first genome-wide transcription profiles of the AV node during development, providing valuable information concerning its molecular identity.

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Horsthuis T, Buermans HP, Brons JF, Verkerk AO, Bakker ML, Wakker V, Clout DE, Moorman AF, 't Hoen PA, Christoffels VM