Transgenic expression of Tbx2 in the prechamber myocardium completely prevented chamber formation and repressed chamber-specific genes Nppa, Cx40, and Chisel.
Does Tbx2 expression repress differentiation and formation of cardiac chambers in embryonic hearts?
Tbx2 acts as a critical transcriptional repressor that prevents chamber differentiation in specific regions of the embryonic heart tube.
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.
Christoffels et al. (Wed,) conducted a other in Embryonic heart development. Tbx2 expression was evaluated on Chamber formation and chamber myocardium-specific gene expression. Transgenic expression of Tbx2 in the prechamber myocardium completely prevented chamber formation and repressed chamber-specific genes Nppa, Cx40, and Chisel.
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