Key result
Tbx2 and Tbx3 control embryonic heart remodeling by repressing chamber genes and regulating cell proliferation.
Why the study?
The roles of Tbx2 and Tbx3 transcription factors in regulating cell proliferation and chamber-specific genetic programs during heart remodeling were not fully understood.
Tbx2 and Tbx3 are essential for controlling cell proliferation and regionalization during embryonic heart development, highlighting their conserved role in cardiac morphogenesis.
No immediate clinical implications; leaves open relevance of Tbx2/Tbx3 to human congenital heart disease.
BACKGROUND: The heart forms from a linear tube that is subject to complex remodeling during embryonic development. Hallmarks of this remodeling are the looping of the heart tube and the regionalization into chamber and non-chamber myocardium. Cardiomyocytes in the future chamber myocardium acquire different cellular and physiological characteristics through activation of a chamber-specific genetic program, which is in part mediated by T-box genes. METHODOLOGY/PRINCIPAL FINDING: We characterize two new zebrafish T-box transcription factors, tbx3b and tbx2a, and analyze their role during the development of the atrioventricular canal. Loss- and gain-of-function analyses demonstrate that tbx3b and tbx2a are necessary to repress the chamber-genetic program in the non-chamber myocardium. We also show that tbx3b and tbx2a are required to control cell proliferation in the atrioventricular canal and that misregulation of cell proliferation in the heart tube influences looping. Furthermore, we characterize the heart phenotype of a novel Tbx3 mutation in mice and show that both the control of cell proliferation and the repression of chamber-specific genetic program in the non-chamber myocardium are conserved roles of Tbx3 in this species. CONCLUSIONS/SIGNIFICANCE: Taken together, our results uncover an evolutionarily conserved role of Tbx2/3 transcription factors during remodeling of the heart myocardium and highlight the importance of controlling cell proliferation as a driving force of morphogenesis.
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Ribeiro et al. (2007) studied Heart remodeling and embryonic development. Tbx2 and Tbx3 loss- and gain-of-function vs. Wild type / control embryos was evaluated on Heart looping, chamber formation, and cell proliferation dynamics. Tbx2 and Tbx3 transcription factors are essential for repressing the chamber-specific genetic program in non-chamber myocardium and controlling cell proliferation dynamics during embryonic heart remodeling.
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