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First published online 5 January 2005
doi: 10.1242/dev.01596

Development 132, 553-563 (2005)
Published by The Company of Biologists 2005
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Tbx5 and Tbx20 act synergistically to control vertebrate heart morphogenesis

Daniel D. Brown1,2, Shauna N. Martz1, Olav Binder1, Sarah C. Goetz1,2, Brenda M. J. Price3, Jim C. Smith3 and Frank L. Conlon1,2,*

1 Department of Genetics, Fordham Hall, UNC-Chapel Hill, Chapel Hill, NC 27599-3280, USA
2 Department of Biology, Fordham Hall, UNC-Chapel Hill, Chapel Hill, NC 27599-3280, USA
3 Wellcome Trust/Cancer Research UK Gurdon Institute of Cancer and Developmental Biology and Department of Zoology, University of Cambridge, Tennis Court Road, Cambridge CB2 1QR, UK

* Author for correspondence (e-mail: frank_conlon{at}med.unc.edu)

Accepted 23 November 2004

Members of the T-box family of proteins play a fundamental role in patterning the developing vertebrate heart; however, the precise cellular requirements for any one family member and the mechanism by which individual T-box genes function remains largely unknown. In this study, we have investigated the cellular and molecular relationship between two T-box genes, Tbx5 and Tbx20. We demonstrate that blocking Tbx5 or Tbx20 produces phenotypes that display a high degree of similarity, as judged by overall gross morphology, molecular marker analysis and cardiac physiology, implying that the two genes are required for and have non-redundant functions in early heart development. In addition, we demonstrate that although co-expressed, Tbx5 and Tbx20 are not dependent on the expression of one another, but rather have a synergistic role during early heart development. Consistent with this proposal, we show that TBX5 and TBX20 can physically interact and map the interaction domains, and we show a cellular interaction for the two proteins in cardiac development, thus providing the first evidence for direct interaction between members of the T-box gene family.

Key words: Tbx5, Tbx20, T-Box, T-domain, Cardiogenesis, Cardiac, Heart, Development, Xenopus laevis




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