Tbx20 Transcription Factor Is a Downstream Mediator for Bone Morphogenetic Protein-10 in Regulating Cardiac Ventricular Wall Development and Function

Zhang, Wenjun; Chen, Hanying; Wang, Yong; Yong, Weidong; Zhu, Wuqiang; Liu, Yunlong; Wagner, Gregory R.; Payne, R. Mark; Field, Loren J.; Xin, Hong‐Bo; Cai, Chen; Shou, Weinian

doi:10.1074/jbc.m111.279679

Cited by 51 publications

(38 citation statements)

References 41 publications

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“…Statistical significance was determined by Student's t-test, * compared to β-gal controls and # compared to Ad-Tbx20; p b 0.05 (exact p-values are indicated) for n = 3-4 independent experiments per group. [20,41]. Tbx20 does not promote BMP10 expression in neonatal cardiomyocytes, demonstrating a temporal restriction in BMP isoform activation by Tbx20 in neonatal versus fetal cardiomyocytes.…”

Section: Discussionmentioning

confidence: 94%

Tbx20 promotes cardiomyocyte proliferation and persistence of fetal characteristics in adult mouse hearts

Chakraborty

Sengupta

Yutzey

2013

Journal of Molecular and Cellular Cardiology

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Section: Discussionmentioning

confidence: 94%

Tbx20 promotes cardiomyocyte proliferation and persistence of fetal characteristics in adult mouse hearts

Chakraborty

Sengupta

Yutzey

2013

Journal of Molecular and Cellular Cardiology

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“…Here we demonstrate that Tbx20 overexpression in fetal cardiomyocytes leads to increased Bmp10 expression and pSmad1/5/8 activation. In addition, Bmp10 is necessary and sufficient to activate Tbx20 expression in the fetal myocardium, and a conserved Smad binding site mediates Bmp10 induction of Tbx20 proximal promoter sequences in cell culture studies (Zhang et al, 2011). Together, these data provide evidence for a feedforward regulatory mechanism of Tbx20 and Bmp10 during heart chamber maturation.…”

Section: Discussionmentioning

confidence: 99%

Tbx20 regulation of cardiac cell proliferation and lineage specialization during embryonic and fetal development in vivo

Chakraborty

Yutzey

2012

Developmental Biology

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TBX20 gain-of-function mutations in humans are associated with congenital heart malformations and myocardial defects. However the effects of increased Tbx20 function during cardiac chamber development and maturation have not been reported previously. CAG-CAT-Tbx20 transgenic mice were generated for Cre-dependent induction of Tbx20 in myocardial lineages in the developing heart. βMHCCre-mediated overexpression of Tbx20 in fetal ventricular cardiomyocytes results in increased thickness of compact myocardium, induction of cardiomyocyte proliferation, and increased expression of Bmp10 and pSmad1/5/8 at embryonic day (E) 14.5. βMHCCre-mediated Tbx20 overexpression also leads to increased expression of cardiac conduction system (CCS) genes Tbx5, Cx40, and Cx43 throughout the ventricular myocardium. In contrast, Nkx2.5Cre mediated overexpression of Tbx20 in the embryonic heart results in reduced cardiomyocyte proliferation, increased expression of a cell cycle inhibitor, p21CIP1, and decreased expression of Tbx2, Tbx5, and N-myc1 at E9.5, concomitant with decreased phospho-ERK1/2 expression. Together, these analyses demonstrate that Tbx20 differentially regulates cell proliferation and cardiac lineage specification in embryonic versus fetal cardiomyocytes. Induction of pSmad1/5/8 at E14.5 and inhibition of dpERK expression at E9.5 are consistent with selective Tbx20 regulation of these pathways in association with stage-specific effects on cardiomyocyte proliferation. Together, these in vivo data support distinct functions for Tbx20 in regulation of cardiomyocyte lineage maturation and cell proliferation at embryonic and fetal stages of heart development.

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“…107 N1ICD then associates with its transcriptional cofactor RBPJK and translocates to the nucleus 108, 109 N1ICD/RBPJk upregulates myocardial expression of BMP10 , which stimulates proliferation by decreasing the activity of cell cycle inhibitor P57 kip2 and by up-regulating Tbx20 and Hey2 activity. 110, 111 Since Notch1 is predominantly expressed in endocardial cells lining the base of trabeculae at E9.0, Notch activity therefore promotes growth of the trabecular myocardium. 101 Endothelial-specific ablation of a N1ICD inhibitor, Fkbp1a , accordingly results in hypertrabeculation.…”

Section: Trabeculation Of the Ventricular Myocardiummentioning

confidence: 99%

Molecular Regulation of Cardiomyocyte Differentiation

Paige¹,

Plonowska²,

Xu³

et al. 2015

Circulation Research

189

159

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The heart is the first organ to form during embryonic development. Given the complex nature of cardiac differentiation and morphogenesis, it is not surprising that some form of congenital heart disease is present in approximately one percent of newborns. The molecular determinants of heart development have received much attention over the past several decades. This has been driven in large part by an interest in understanding the etiology of congenital heart disease coupled with the potential of utilizing knowledge from developmental biology to generate functional cells and tissues that could be used for regenerative medicine purposes. In this review, we highlight the critical signaling pathways and transcription factor networks that regulate cardiomyocyte lineage specification in both in vivo and in vitro models. Special focus will be given to epigenetic regulators that drive the commitment of cardiomyogenic cells from nascent mesoderm and their differentiation into chamber-specific myocytes as well as regulation of myocardial trabeculation.

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Tbx20 Transcription Factor Is a Downstream Mediator for Bone Morphogenetic Protein-10 in Regulating Cardiac Ventricular Wall Development and Function

Cited by 51 publications

References 41 publications

Tbx20 promotes cardiomyocyte proliferation and persistence of fetal characteristics in adult mouse hearts

Tbx20 promotes cardiomyocyte proliferation and persistence of fetal characteristics in adult mouse hearts

Tbx20 regulation of cardiac cell proliferation and lineage specialization during embryonic and fetal development in vivo

Molecular Regulation of Cardiomyocyte Differentiation

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