MRC National Institute for Medical Research, London
Science for Health
Regulating growth in the forming heart
27 July 2009
In all vertebrates, the heart first appears in the early embryo as a simple, peristaltic tube. In mammals and birds, it undergoes rapid expansion and growth during the first half of gestation as the linear heart tube is transformed into a complex, four-chambered organ capable of supporting embryo growth. Until recently, dramatic growth of the embryonic heart was assumed to be the result of high levels of cell proliferation, which are known to occur, for example, during formation of heart chambers. We now know however that much of heart growth at the earliest stages is due to migration of cells from the splanchnic mesoderm into the developing heart. Uncovering the mechanisms that regulate migration of those cells is therefore decisive for understanding growth and differentiation of the early heart.
In studies in Tim Mohun’s lab, in NIMR's Division of Developmental Biology, Laurent Dupays has developed a genetic system to manipulate expression of cardiac transcription factors during embryo development. Using this, he has altered expression of the T-box transcription factor, Tbx2, which is normally expressed in non-chamber myocardium (the outflow tract and atrioventricular canal) where it is believed to prevent chamber differentiation. He has found that early misexpression throughout the myocardium causes severe defects in patterning of the anterior heart tube and in subsequent heart growth. Reduced heart size is due not only to a decrease in myocardial cell proliferation, but importantly, also to a defect in migration of cardiac progenitor cells into the anterior end of the cardiac tube.
Our misexpression model shows that Tbx2 is capable of severely impairing cardiac growth of the heart tube, through combined effects on myocardial proliferation and second heart field deployment. Our results are further evidence that Tbx2 is part of a regulatory gene network controlling heart growth, through coordinated control of cell proliferation and correct deployment cardiac progenitors.
Tim Mohun
Original article
The research findings are published in full in:
Laurent Dupays, Surendra Kotecha and Timothy J. Mohun (2009)
Tbx2 misexpression impairs deployment of second heart field derived progenitor cells to the arterial pole of the embryonic heart
Developmental Biology, epub ahead of print. Pubmed abstract
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