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Publication : T-box transcription factor Tbx2 represses differentiation and formation of the cardiac chambers.

First Author  Christoffels VM Year  2004
Journal  Dev Dyn Volume  229
Issue  4 Pages  763-70
PubMed ID  15042700 Mgi Jnum  J:89198
Mgi Id  MGI:3039059 Doi  10.1002/dvdy.10487
Citation  Christoffels VM, et al. (2004) T-box transcription factor Tbx2 represses differentiation and formation of the cardiac chambers. Dev Dyn 229(4):763-70
abstractText  Specific regions of the embryonic heart tube differentiate into atrial and ventricular chamber myocardium, whereas the inflow tract, atrioventricular canal, inner curvatures, and outflow tract do not. These regions express Tbx2, a transcriptional repressor. Here, we tested its role in chamber formation. The temporal and spatial pattern of Tbx2 mRNA and protein expression in mouse hearts was found to be complementary to that of chamber myocardium-specific genes Nppa, Cx40, Cx43, and Chisel, and was conserved in human. In vitro, Tbx2 repressed the activity of regulatory fragments of Cx40, Cx43, and Nppa. Hearts of transgenic embryos that expressed Tbx2 in the prechamber myocardium completely failed to form chambers and to express the chamber myocardium-specific genes Nppa, Cx40, and Chisel, whereas other cardiac genes were normally expressed. These findings provide the first evidence that Tbx2 is a determinant in the local repression of chamber-specific gene expression and chamber differentiation.
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