【摘 要】
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Many essential factors controlling heart development have been identified in vertebrates.The T-box transcription factor Tbx5 plays a crucial role in the formation of the cardiac chambers in a dose-dep
【机 构】
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Key Laboratory of Cell Proliferation and Differentiation of Ministry of Education,Center of Developm
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Many essential factors controlling heart development have been identified in vertebrates.The T-box transcription factor Tbx5 plays a crucial role in the formation of the cardiac chambers in a dose-dependent manner.Its deregulation leads to congenital heart disease(CHD).However,little is known regarding its regulation.We isolated a zebrafish mutant with heart malformations,called 34c.Based on positional cloning,the affected gene was identified as kctd10,a member of the potassium channel tetramerization domain(KCTD)-containing family.In the mutant,the marker genes specifically expressed in the atrioventricular canal(AVC),such as tbx2b,hyaluronan synthase 2(has2),notch1b and bmp4,were mis-expressed.The morpholino knockdown of tbx5 rescued the ectopic expression of has2,and knockdown of either tbx5a or has2 alleviated the heart defect.We also showed that Kctd10 directly bound to Tbx5 to moderate its transcriptional activity.Our results reveal a new essential factor for cardiac development and suggest KCTD10 to be considered as a new causative gene of CHD.
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