title: Kctd10 regulates heart morphogenesis by repressing the transcriptional activity of Tbx5a in zebrafish.
abstract: The T-box transcription factor Tbx5 (Tbx5a in zebrafish) plays a crucial role in the formation of cardiac chambers in a dose-dependent manner. Its deregulation leads to congenital heart disease. However, little is known regarding its regulation. Here we isolate a zebrafish mutant with heart malformations, called 34c. The affected gene is identified as kctd10, a member of the potassium channel tetramerization domain (KCTD)-containing family. In the mutant, the expressions of the atrioventricular canal marker genes, such as tbx2b, hyaluronan synthase 2 (has2), notch1b and bmp4, are changed. The knockdown of tbx5 rescues the ectopic expression of has2, and knockdown of either tbx5a or has2 alleviates the heart defects. We show that Kctd10 directly binds to Tbx5 to repress its transcriptional activity. Our results reveal a new essential factor for cardiac development and suggest that KCTD10 could be considered as a new causative gene of congenital heart disease.
authors.affiliation: 1] Key Laboratory of Cell Proliferation and Differentiation of Ministry of Education, College of Life Sciences, Peking University, Beijing 100871, PR China [2].
authors.forename: Xiangjun
authors.initials: X
authors.lastname: Tong
authors.affiliation: 1] Key Laboratory of Cell Proliferation and Differentiation of Ministry of Education, College of Life Sciences, Peking University, Beijing 100871, PR China [2].
authors.forename: Yao
authors.initials: Y
authors.lastname: Zu
authors.affiliation: 1] State Key Laboratory Breeding Base of Marine Genetic Resources, Third Institute of Oceanography, State Oceanic Administration, 184 University Road, Xiamen 361005, Fujian Province, PR China [2].
authors.forename: Zengpeng
authors.initials: Z
authors.lastname: Li
authors.affiliation: Key Laboratory of Cell Proliferation and Differentiation of Ministry of Education, College of Life Sciences, Peking University, Beijing 100871, PR China.
authors.forename: Wenyuan
authors.initials: W
authors.lastname: Li
authors.affiliation: Key Laboratory of Cell Proliferation and Differentiation of Ministry of Education, College of Life Sciences, Peking University, Beijing 100871, PR China.
authors.forename: Lingxiao
authors.initials: L
authors.lastname: Ying
authors.affiliation: Key Laboratory of Cell Proliferation and Differentiation of Ministry of Education, College of Life Sciences, Peking University, Beijing 100871, PR China.
authors.forename: Jing
authors.initials: J
authors.lastname: Yang
authors.affiliation: Key Laboratory of Cell Proliferation and Differentiation of Ministry of Education, College of Life Sciences, Peking University, Beijing 100871, PR China.
authors.forename: Xin
authors.initials: X
authors.lastname: Wang
authors.affiliation: Key Laboratory of Cell Proliferation and Differentiation of Ministry of Education, College of Life Sciences, Peking University, Beijing 100871, PR China.
authors.forename: Shuonan
authors.initials: S
authors.lastname: He
authors.affiliation: Key Laboratory of Cell Proliferation and Differentiation of Ministry of Education, College of Life Sciences, Peking University, Beijing 100871, PR China.
authors.forename: Da
authors.initials: D
authors.lastname: Liu
authors.affiliation: Key Laboratory of Cell Proliferation and Differentiation of Ministry of Education, College of Life Sciences, Peking University, Beijing 100871, PR China.
authors.forename: Zuoyan
authors.initials: Z
authors.lastname: Zhu
authors.affiliation: State Key Laboratory Breeding Base of Marine Genetic Resources, Third Institute of Oceanography, State Oceanic Administration, 184 University Road, Xiamen 361005, Fujian Province, PR China.
authors.forename: Jianming
authors.initials: J
authors.lastname: Chen
authors.affiliation: Department of Molecular, Cell and Developmental Biology, University of California Los Angeles, Los Angeles, California 90095-1606, USA.
authors.forename: Shuo
authors.initials: S
authors.lastname: Lin
authors.affiliation: Key Laboratory of Cell Proliferation and Differentiation of Ministry of Education, College of Life Sciences, Peking University, Beijing 100871, PR China.
authors.forename: Bo
authors.initials: B
authors.lastname: Zhang
mesh_terms: D000818:Animals; D055785:Gene Knockdown Techniques; D009024:Morphogenesis; D014158:Transcription, Genetic / Q000502:physiology*; D015027:Zebrafish / Q000196:embryology*; D029961:Zebrafish Proteins / Q000235:genetics / Q000502:physiology*
chemical_list: D029961:Zebrafish Proteins