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

Dev Dyn. 2004 Apr;229(4):763-70. doi: 10.1002/dvdy.10487.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Bone Morphogenetic Protein 2
  • Bone Morphogenetic Proteins / genetics
  • Bone Morphogenetic Proteins / metabolism
  • Connexin 43 / genetics
  • Connexins / genetics
  • Down-Regulation
  • Embryo, Mammalian / metabolism
  • Gene Expression
  • Gene Expression Regulation, Developmental
  • Heart / anatomy & histology
  • Heart / embryology*
  • Humans
  • Immunohistochemistry
  • In Situ Hybridization, Fluorescence
  • Mice
  • Muscle Proteins / genetics
  • Muscle Proteins / metabolism
  • Natriuretic Peptide, C-Type / genetics
  • Natriuretic Peptide, C-Type / metabolism
  • Promoter Regions, Genetic / genetics
  • Protein Precursors / genetics
  • Protein Precursors / metabolism
  • T-Box Domain Proteins / genetics
  • T-Box Domain Proteins / metabolism
  • T-Box Domain Proteins / physiology*
  • Transforming Growth Factor beta*

Substances

  • BMP2 protein, human
  • Bmp2 protein, mouse
  • Bone Morphogenetic Protein 2
  • Bone Morphogenetic Proteins
  • Connexin 43
  • Connexins
  • Muscle Proteins
  • Nppa protein, mouse
  • Protein Precursors
  • SMPX protein, human
  • Smpx protein, mouse
  • T-Box Domain Protein 2
  • T-Box Domain Proteins
  • T-box transcription factor 5
  • Transforming Growth Factor beta
  • connexin 40
  • Natriuretic Peptide, C-Type