T-box transcription factor Tbx2 represses differentiation and formation of the cardiac chambers.
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
Vincent M
VM
Experimental and Molecular Cardiology Group, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands.
Hoogaars
Willem M H
WM
Tessari
Alessandra
A
Clout
Danielle E W
DE
Moorman
Antoon F M
AF
Campione
Marina
M
D000818:Animals; D009320:Atrial Natriuretic Factor; D055396:Bone Morphogenetic Protein 2; D019485:Bone Morphogenetic Proteins / Q000235:genetics / Q000378:metabolism; D018031:Connexin 43 / Q000235:genetics; D017630:Connexins / Q000235:genetics; D015536:Down-Regulation; D004622:Embryo, Mammalian / Q000378:metabolism; D015870:Gene Expression; D018507:Gene Expression Regulation, Developmental; D006321:Heart / Q000033:anatomy & histology / Q000196:embryology*; D006801:Humans; D007150:Immunohistochemistry; D017404:In Situ Hybridization, Fluorescence; D051379:Mice; D009124:Muscle Proteins / Q000235:genetics / Q000378:metabolism; D020098:Natriuretic Peptide, C-Type / Q000235:genetics / Q000378:metabolism; D011401:Promoter Regions, Genetic / Q000235:genetics; D011498:Protein Precursors / Q000235:genetics / Q000378:metabolism; D020825:T-Box Domain Proteins / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D016212:Transforming Growth Factor beta; D000097003:Gap Junction alpha-5 Protein
D009320:Atrial Natriuretic Factor; D055396:Bone Morphogenetic Protein 2; D019485:Bone Morphogenetic Proteins; D018031:Connexin 43; D017630:Connexins; D009124:Muscle Proteins; D020098:Natriuretic Peptide, C-Type; D011498:Protein Precursors; D020825:T-Box Domain Proteins; D016212:Transforming Growth Factor beta; D000097003:Gap Junction alpha-5 Protein; C525718:BMP2 protein, human; C525719:Bmp2 protein, mouse; C431578:Nppa protein, mouse; C433890:SMPX protein, human; C499035:Smpx protein, mouse; C097348:T-Box Domain Protein 2; C103172:T-box transcription factor 5