The DOI matches its Crossref record; 35 of the 35 references it cites were found in a registry or an index.
The transcriptional repressor Tbx3 delineates the developing central conduction system of the heart
Abstract
OBJECTIVE: The molecular mechanisms that regulate the formation of the conduction system are poorly understood. We studied the developmental expression pattern and functional aspects of the T-box transcription factor Tbx3, a novel marker for the murine central conduction system (CCS). METHODS: The patterns of expression of Tbx3, and of Cx40, Cx43, and Nppa, which are markers for atrial and ventricular chamber-type myocardium in the developing heart, were analyzed in mice by in situ hybridization and three-dimensional reconstruction analysis. The function of Tbx3 in regulating Nppa and Cx40 promoter activity was studied in vitro. RESULTS: In the formed heart, Tbx3 is expressed in the sinoatrial node (SAN), atrioventricular node (AVN), bundle and proximal bundle branches (BBs), as well as the internodal regions and the atrioventricular region. Throughout cardiac development, Tbx3 is expressed in an uninterrupted myocardial domain that extends from the sinoatrial node to the atrioventricular region. This expression domain is present in the looping heart tube from E8.5 onwards. Expression of the chamber-type myocardial markers is specifically absent from the Tbx3 expression domain. Tbx3 is able to repress Nppa and Cx40 promoter activity and abolish the synergistic activation of the Nppa promoter by Tbx5 and Nkx2.5. CONCLUSION: We identified the T-box transcription factor Tbx3 as a novel and accurate marker for the central conduction system. Our analysis implicates a role for Tbx3 in repressing a chamber-specific program of gene expression in regions from which the components of the central conduction system are subsequently formed.
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Bruneau, B. G., Nemer, G., Schmitt, J. P., Charron, F., Robitaille, L., Caron, S., Conner, D. A., Gessler, M., Nemer, M., Seidman, C. E., et al. (2001) · Cell · doi:10.1016/s0092-8674(01)00493-7 · Cited by 1,061
Cardiac Chamber Formation: Development, Genes, and Evolution
MOORMAN, A. F. M., & CHRISTOFFELS, V. M. (2003) · Physiological Reviews · doi:10.1152/physrev.00006.2003 · Cited by 738
Expression of the T-box family genes,Tbx1-Tbx5, during early mouse development
Chapman, D. L., Garvey, N., Hancock, S., Alexiou, M., Agulnik, S. I., Gibson-Brown, J. J., Cebra-Thomas, J., Bollag, R. J., Silver, L. M., & Papaioannou, V. E. (1996) · Developmental Dynamics · doi:10.1002/(sici)1097-0177(199608)206:4<379::aid-aja4>3.0.co;2-f · Cited by 655
Tbx5 associates with Nkx2-5 and synergistically promotes cardiomyocyte differentiation
Hiroi, Y., Kudoh, S., Monzen, K., Ikeda, Y., Yazaki, Y., Nagai, R., & Komuro, I. (2001) · Nature Genetics · doi:10.1038/90123 · Cited by 599
Chamber-Specific Cardiac Expression of Tbx5 and Heart Defects in Holt–Oram Syndrome
Bruneau, B. G., Logan, M., Davis, N., Levi, T., Tabin, C. J., Seidman, J. G., & Seidman, C. E. (1999) · Developmental Biology · doi:10.1006/dbio.1999.9298 · Cited by 507
Habets, P. E. M. H., Moorman, A. F. M., Clout, D. E. W., van Roon, M. A., Lingbeek, M., van Lohuizen, M., Campione, M., & Christoffels, V. M. (2002) · Genes & Development · doi:10.1101/gad.222902 · Cited by 366
Davenport, T. G., Jerome-Majewska, L. A., & Papaioannou, V. E. (2003) · Development · doi:10.1242/dev.00431 · Cited by 295
Development of the Cardiac Conduction System
Moorman, A. F. M., de Jong, F., Denyn, M. M. F. J., & Lamers, W. H. (1998) · Circulation Research · doi:10.1161/01.res.82.6.629 · Cited by 290
T‐box transcription factor Tbx2 represses differentiation and formation of the cardiac chambers
Christoffels, V. M., Hoogaars, W. M. H., Tessari, A., Clout, D. E. W., Moorman, A. F. M., & Campione, M. (2004) · Developmental Dynamics · doi:10.1002/dvdy.10487 · Cited by 272
Self-citationVisualization and functional characterization of the developing murine cardiac conduction system
Rentschler, S., Vaidya, D. M., Tamaddon, H., Degenhardt, K., Sassoon, D., Morley, G. E., Jalife, J., & Fishman, G. I. (2001) · Development · doi:10.1242/dev.128.10.1785 · Cited by 268
Cited by
Tbx3 controls the sinoatrial node gene program and imposes pacemaker function on the atria
Hoogaars, W. M. H., Engel, A., Brons, J. F., Verkerk, A. O., de Lange, F. J., Wong, L. Y. E., Bakker, M. L., Clout, D. E., Wakker, V., Barnett, P., et al. (2007) · Genes & Development · doi:10.1101/gad.416007 · Cited by 409
Self-citationIsl1Cre reveals a common Bmp pathway in heart and limb development
Yang, L., Cai, C.-L., Lin, L., Qyang, Y., Chung, C., Monteiro, R. M., Mummery, C. L., Fishman, G. I., Cogen, A., & Evans, S. (2006) · Development · doi:10.1242/dev.02322 · Cited by 267
Zhu, W.-Z., Xie, Y., Moyes, K. W., Gold, J. D., Askari, B., & Laflamme, M. A. (2010) · Circulation Research · doi:10.1161/circresaha.110.223917 · Cited by 228
Cooperative and antagonistic interactions between Sall4 and Tbx5 pattern the mouse limb and heart
Koshiba-Takeuchi, K., Takeuchi, J. K., Arruda, E. P., Kathiriya, I. S., Mo, R., Hui, C.-C., Srivastava, D., & Bruneau, B. G. (2006) · Nature Genetics · doi:10.1038/ng1707 · Cited by 170
Connexins: Key Mediators of Endocrine Function
Bosco, D., Haefliger, J.-A., & Meda, P. (2011) · Physiological Reviews · doi:10.1152/physrev.00027.2010 · Cited by 169
Metadata
- Authors
- HOOGAARS, W.
- Venue
- Cardiovascular Research
- Publisher
- Oxford University Press (OUP)
- Published
- 2004-06
- Volume
- 62
- Issue
- 3
- Pages
- 489-499
- ISSN
- 0008-6363 (ISSN-L)
- OpenAlex
- W2102254218
- Cited by
- 339
- References
- 35
- FWCI
- 7.11
- Type
- journal article
- Language
- en
- Open access
- closed
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