Research Progress of Tbx3 in Cardiac Biological Pacemaker_Journal of Biomedical Engineering

Authors：

LIYong ,  LIBingong

Department of Cardiology, the First Affiliated Hospital, Nanchang University;Jiangxi Institute of Hypertensive Diseases, Nanchang 330006, China;

Corresponding author：

LIBingong, Email: libingong08@163.com

Keywords：

Tbx3; biological pacemaker; cardiac conduction system

DOI：

10.7507/1001-5515.20140173

Video：

Export PDF Favorites Scan Get Citation

Abstract Full text Figures/Tables Video References Cited by

The early cardiac biological pacemaker studies were mostly around HCN channel, and how to build a biological pacemaker through the enhanced If current. In recent years, however, people found that the genes of Tbx3 could play an important role in the development of cardiac conduction system, especially in processes of the maturity of the sinoatrial node and maintenance of its function. And the Tbx3 can further optimize the biological pacemaker. Therefore, it could be a new therapeutic focus in biological pacemaker and treatment of cardiac conduction system disease. This paper summarizes some of the latest research progress of the Tbx3 in biological pacemaker in recent years. We hope that this review could provide theoretical basis for the clinical applications of Tbx3.

Citation： LIYong, LIBingong. Research Progress of Tbx3 in Cardiac Biological Pacemaker. Journal of Biomedical Engineering, 2014, 31(4): 923-926. doi: 10.7507/1001-5515.20140173 Copy

1.	GREULICH F, RUDAT C, KISPERT A. Mechanisms of T-box gene function in the developing heart[J]. Cardiovasc Res, 2011, 91(2):212-222.
2.	DAVENPORT T G, JEROME-MAJEWKA L A, PAPAIOANNOU V E. Mammary gland, limb and yolk sac defects in mice lacking Tbx3, the gene mutated in human ulnar mammary syndrome[J]. Development, 2003, 130(10):2263-2273.
3.	AANHAANEN W T, MOMMERSTEEG M T, NORDEN J, et al. Developmental origin, growth, and three-dimensional architecture of the atrioventricular conduction axis of the mouse heart[J]. Circ Res, 2010, 107(6):728-736.
4.	LAI D, LIU X, FORRAI A, et al. Neuregulin 1 sustains the gene regulatory network in both trabecular and nontrabecular myocardium[J]. Circ Res, 2010, 107(6):715-727.
5.	HOOGAARS W M, ENGEL A, BRONS J F, et al. Tbx3 controls the sinoatrial node gene program and imposes pacemaker function on the atria[J]. Genes Dev, 2007, 21(9):1098-1112.
6.	SIZAROV A, YA J, DE BOER B A, et al. Formation of the building plan of the human heart: morphogenesis, growth, and differentiation[J]. Circulation, 2011, 123(10):1125-1135.
7.	SIZAROV A, DEVALLA H D, ANDERSON R H, et al. Molecular analysis of patterning of conduction tissues in the developing human heart[J]. Circ Arrhythm Electrophysiol, 2011, 4(4):532-542.
8.	SINGH R, HOOGAARS W M, BAMETT P, et al. Tbx2 and Tbx3 induce atrioventricular myocardial development and endocardial cushion formation[J]. Cell Mol Life Sci, 2012, 69(8):1377-1389.
9.	WIESE C, GRIESKAMP T, AIRIK R, et al. Formation of the sinus node head and differentiation of sinus node myocardium are independently regulated by Tbx18 and Tbx3[J]. Circ Res, 2009, 104(3):388-397.
10.	MCNALLY E M, SVENSSON E C. Setting the pace: Tbx3 and Tbx18 in cardiac conduction system development[J]. Circ Res, 2009, 104(3):285-287.
11.	GREENER I D, MONFREDI O, INADA S, et al. Molecular architecture of the human specialised atrioventricular conduction axis[J]. J Mol Cell Cardiol, 2011, 50(4):642-651.
12.	DIFRANCESCO D. The role of the funny current in pacemaker activity[J]. Circ Res, 2010, 106(3):434-446.
13.	FRANK D U, CARTER K L, THOMAS K R, et al. Lethal arrhythmias in Tbx3-deficient mice reveal extreme dosage sensitivity of cardiac conduction system function and homeostasis[J]. Proceedings of the National Academy of Sciences of the United States of America, 2012, 109(3):E154-E163.
14.	CHEN D, QIAO Y, MENG H, et al. Genetic analysis of the TBX3 gene promoter in ventricular septal defects[J]. Gene, 2013, 512(2):185-188.
15.	BAKKER M L, BOINK G J, BOUKENS B J, et al. T-box transcription factor TBX3 reprogrammes mature cardiac myocytes into pacemaker-like cells[J]. Cardiovasc Res, 2012, 94(3):439-449.
16.	ZHU W Z, XIE Y, MOYES K W, et al. Neuregulin/ErbB signaling regulates cardiac subtype specification in differentiating human embryonic stem cells[J]. Circ Res, 2010, 107(6):776-786.
17.	EVANS W H, BUITYNCK G, LEYBAERT L. Manipulating connexin communication channels: use of peptidomimetics and the translational outputs[J]. J Membr Biol, 2012, 245(8):437-449.
18.	BOOGERD C J, WONG L Y, BAKKER M L, et al. Sox4 mediates Tbx3 transcriptional regulation of the gap junction protein Cx43[J]. Cell Mol Life Sci , 2011, 68(23):3949-3961.
19.	ESPINOZA-LEWIS R A, YU L, HE F, et al. Shox2 is essential for the differentiation of cardiac pacemaker cells by repressing Nkx2-5[J]. Dev Biol, 2009, 327(2):376-385.
20.	ESPINOZA-LEWIS R A, LIU H, SUN C, et al. Ectopic expression of Nkx2.5 suppresses the formation of the sinoatrial node in mice[J]. Dev Biol, 2011, 356(2):359-369.
21.	PUSKARIC S, SCHMITTECKERT S, MORI A D, et al. Shox2 mediates Tbx5 activity by regulating Bmp4 in the pacemaker region of the developing heart[J]. Human Mol Gene, 2010, 19(23):4625-4633.
22.	ZHANG X, GUO J P, CHI Y L et al. Endothelin-induced differentiation of Nkx2.5(+) cardiac progenitor cells into pacemaking cells[J]. Mol Cell Biochem, 2012, 366(1-2):309-318.
23.	ESMAILPOUR T, HUANG T. TBX3 promotes human embryonic stem cell proliferation and neuroepithelial differentiation in a differentiation stage-dependent manner[J]. Stem Cells, 2012, 30(10):2152-2163.
24.	LU R, YANG A, JIN Y. Dual functions of T-box 3^[Tbx3] in the control of self-renewal and extraembryonic endoderm differentiation in mouse embryonic stem cells[J]. J Biol Chem, 2011, 286(10):8425-8436.
25.	HAN J, YUAN P, YANG H, et al. Tbx3 improves the germ-line competency of induced pluripotent stem cells[J]. Nature, 2010, 463(7284):1096-1100.
26.	VAN DEN BOOGAARD M, WONG L Y, TESSADORI F, et al. Genetic variation in T-box binding element functionally affects SCN5A/SCN10A enhancer[J]. J Clin Invest, 2012, 122(7):2519-2530.

1. GREULICH F, RUDAT C, KISPERT A. Mechanisms of T-box gene function in the developing heart[J]. Cardiovasc Res, 2011, 91(2):212-222.
2. DAVENPORT T G, JEROME-MAJEWKA L A, PAPAIOANNOU V E. Mammary gland, limb and yolk sac defects in mice lacking Tbx3, the gene mutated in human ulnar mammary syndrome[J]. Development, 2003, 130(10):2263-2273.
3. AANHAANEN W T, MOMMERSTEEG M T, NORDEN J, et al. Developmental origin, growth, and three-dimensional architecture of the atrioventricular conduction axis of the mouse heart[J]. Circ Res, 2010, 107(6):728-736.
4. LAI D, LIU X, FORRAI A, et al. Neuregulin 1 sustains the gene regulatory network in both trabecular and nontrabecular myocardium[J]. Circ Res, 2010, 107(6):715-727.
5. HOOGAARS W M, ENGEL A, BRONS J F, et al. Tbx3 controls the sinoatrial node gene program and imposes pacemaker function on the atria[J]. Genes Dev, 2007, 21(9):1098-1112.
6. SIZAROV A, YA J, DE BOER B A, et al. Formation of the building plan of the human heart: morphogenesis, growth, and differentiation[J]. Circulation, 2011, 123(10):1125-1135.
7. SIZAROV A, DEVALLA H D, ANDERSON R H, et al. Molecular analysis of patterning of conduction tissues in the developing human heart[J]. Circ Arrhythm Electrophysiol, 2011, 4(4):532-542.
8. SINGH R, HOOGAARS W M, BAMETT P, et al. Tbx2 and Tbx3 induce atrioventricular myocardial development and endocardial cushion formation[J]. Cell Mol Life Sci, 2012, 69(8):1377-1389.
9. WIESE C, GRIESKAMP T, AIRIK R, et al. Formation of the sinus node head and differentiation of sinus node myocardium are independently regulated by Tbx18 and Tbx3[J]. Circ Res, 2009, 104(3):388-397.
10. MCNALLY E M, SVENSSON E C. Setting the pace: Tbx3 and Tbx18 in cardiac conduction system development[J]. Circ Res, 2009, 104(3):285-287.
11. GREENER I D, MONFREDI O, INADA S, et al. Molecular architecture of the human specialised atrioventricular conduction axis[J]. J Mol Cell Cardiol, 2011, 50(4):642-651.
12. DIFRANCESCO D. The role of the funny current in pacemaker activity[J]. Circ Res, 2010, 106(3):434-446.
13. FRANK D U, CARTER K L, THOMAS K R, et al. Lethal arrhythmias in Tbx3-deficient mice reveal extreme dosage sensitivity of cardiac conduction system function and homeostasis[J]. Proceedings of the National Academy of Sciences of the United States of America, 2012, 109(3):E154-E163.
14. CHEN D, QIAO Y, MENG H, et al. Genetic analysis of the TBX3 gene promoter in ventricular septal defects[J]. Gene, 2013, 512(2):185-188.
15. BAKKER M L, BOINK G J, BOUKENS B J, et al. T-box transcription factor TBX3 reprogrammes mature cardiac myocytes into pacemaker-like cells[J]. Cardiovasc Res, 2012, 94(3):439-449.
16. ZHU W Z, XIE Y, MOYES K W, et al. Neuregulin/ErbB signaling regulates cardiac subtype specification in differentiating human embryonic stem cells[J]. Circ Res, 2010, 107(6):776-786.
17. EVANS W H, BUITYNCK G, LEYBAERT L. Manipulating connexin communication channels: use of peptidomimetics and the translational outputs[J]. J Membr Biol, 2012, 245(8):437-449.
18. BOOGERD C J, WONG L Y, BAKKER M L, et al. Sox4 mediates Tbx3 transcriptional regulation of the gap junction protein Cx43[J]. Cell Mol Life Sci , 2011, 68(23):3949-3961.
19. ESPINOZA-LEWIS R A, YU L, HE F, et al. Shox2 is essential for the differentiation of cardiac pacemaker cells by repressing Nkx2-5[J]. Dev Biol, 2009, 327(2):376-385.
20. ESPINOZA-LEWIS R A, LIU H, SUN C, et al. Ectopic expression of Nkx2.5 suppresses the formation of the sinoatrial node in mice[J]. Dev Biol, 2011, 356(2):359-369.
21. PUSKARIC S, SCHMITTECKERT S, MORI A D, et al. Shox2 mediates Tbx5 activity by regulating Bmp4 in the pacemaker region of the developing heart[J]. Human Mol Gene, 2010, 19(23):4625-4633.
22. ZHANG X, GUO J P, CHI Y L et al. Endothelin-induced differentiation of Nkx2.5(+) cardiac progenitor cells into pacemaking cells[J]. Mol Cell Biochem, 2012, 366(1-2):309-318.
23. ESMAILPOUR T, HUANG T. TBX3 promotes human embryonic stem cell proliferation and neuroepithelial differentiation in a differentiation stage-dependent manner[J]. Stem Cells, 2012, 30(10):2152-2163.
24. LU R, YANG A, JIN Y. Dual functions of T-box 3^[Tbx3] in the control of self-renewal and extraembryonic endoderm differentiation in mouse embryonic stem cells[J]. J Biol Chem, 2011, 286(10):8425-8436.
25. HAN J, YUAN P, YANG H, et al. Tbx3 improves the germ-line competency of induced pluripotent stem cells[J]. Nature, 2010, 463(7284):1096-1100.
26. VAN DEN BOOGAARD M, WONG L Y, TESSADORI F, et al. Genetic variation in T-box binding element functionally affects SCN5A/SCN10A enhancer[J]. J Clin Invest, 2012, 122(7):2519-2530.

Previous Article
A Three-dimensional Transrectal Ultrasound Imaging System
Next Article
Research on Medical Application of Bacterial Cellulose as Nano-biomaterials

Journal of Biomedical Engineering

Research Progress of Tbx3 in Cardiac Biological Pacemaker

Abstract Full text Figures/Tables Video References Cited by

Previous Article

Next Article

Format

Content