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First published online 22 October 2003
doi: 10.1242/dev.00797
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1 Graduate School of Biological Sciences, Nara Institute of Science and
Technology, 8916-5, Takayama, Ikoma, Nara 630-0101, Japan
2 Division of Molecular Biology, Institute for Molecular and Cellular Biology,
Osaka University, and Core Research for Evolutional Science and Technology
Corporation, Osaka 565-0871, Japan
3 Department of Developmental Neurobiology, Institute of Development, Aging and
Cancer, Tohoku University, Sendai 980-8575, Japan
Author for correspondence (e-mail:
ogura{at}idac.tohoku.ac.jp).
Accepted 11 August 2003
Extensive misexpression studies were carried out to explore the roles played by Tbx5, the expression of which is excluded from the right ventricle (RV) during cardiogenesis. When Tbx5 was misexpressed ubiquitously, ventricular septum was not formed, resulting in a single ventricle. In such heart, left ventricle (LV)-specific ANF gene was induced. In search of the putative RV factor(s), we have found that chick Tbx20 is expressed in the RV, showing a complementary fashion to Tbx5. In the Tbx5-misexpressed heart, this gene was repressed. When misexpression was spatially partial, leaving small Tbx5-negative area in the right ventricle, ventricular septum was shifted rightwards, resulting in a small RV with an enlarged LV. Focal expression induced an ectopic boundary of Tbx5-positive and -negative regions in the right ventricle, at which an additional septum was formed. Similar results were obtained from the transient transgenic mice. In such hearts, expression patterns of dHAND and eHAND were changed with definitive cardiac abnormalities. Furthermore, we report that human ANF promoter is synergistically activated by Tbx5, Nkx2.5 and GATA4. This activation was abrogated by Tbx20, implicating the pivotal roles of interactions among these heart-specific factors. Taken together, our data indicate that Tbx5 specifies the identity of LV through tight interactions among several heart-specific factors, and highlight the essential roles of Tbx5 in cardiac development.
Key words: Heart development, Ventricular septum, Tbx5, Tbx20, dHand/eHand
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