title: CXXC5 is required for cardiac looping relating to TGFβ signaling pathway in zebrafish.
abstract: BACKGROUND
  CXXC-type zinc-finger protein CXXC5 has been reported to be associated with the development of cardiovascular disease. Recently, through signaling pathway screening we found that CXXC5 activated Tgfβ and myocardial differentiation signaling pathways simultaneously. Although the physiological and pathological function of CXXC5 in many organs has been well elucidated, its function in heart remains unclear.
  
  
  RESULTS
  Here, we found that zebrafish CXXC5 and SMAD were interacting through ZF-CXXC and MH1 domain. Over-expression of CXXC5 in cardiomyocyte increased the luciferase report activity of Tgfβ signaling pathway. Spatiotemporal expression profile of cxxc5 showed that it consistently expressed during cardiogenesis. Knockdown of cxxc5 in zebrafish displayed looping defects, cardiac dysplasia, pericardial edema, and decreased contraction ability, accompanied with down-regulation of members referring to cardiac looping downstream genes of Tgfβ signaling pathway, such as nkx2.5, hand2, and has2. Co-injection of hand2 mRNA with cxxc5 morpholino rescued the cardiac looping detects.
  
  
  CONCLUSIONS
  Our study is the first to provide an in vivo evidence for cxxc5 regulating heart development and cardiac looping via Tgfβ related signaling pathway. This finding suggested that CXXC5 may serve as a possible marker that has potential diagnostic and prognostic value in fetus with congenital heart disease.
authors.affiliation: The Center for Heart Development, Key Lab of MOE for Development Biology and Protein Chemistry, College of Life Sciences, Hunan Normal University, Changsha, Hunan 410081, China.
authors.forename: Xiyang
authors.initials: X
authors.lastname: Peng
authors.affiliation: The Center for Heart Development, Key Lab of MOE for Development Biology and Protein Chemistry, College of Life Sciences, Hunan Normal University, Changsha, Hunan 410081, China.
authors.forename: Guanming
authors.initials: G
authors.lastname: Li
authors.affiliation: The Center for Heart Development, Key Lab of MOE for Development Biology and Protein Chemistry, College of Life Sciences, Hunan Normal University, Changsha, Hunan 410081, China.
authors.forename: Yuequn
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Cardiovascular Surgery, Guangdong Cardiovascular Institute, Guangdong General Hospital, Guangdong Academy of Medical Sciences, Guangzhou 510100, China.
authors.forename: Jian
authors.initials: J
authors.lastname: Zhuang
authors.affiliation: The Center for Heart Development, Key Lab of MOE for Development Biology and Protein Chemistry, College of Life Sciences, Hunan Normal University, Changsha, Hunan 410081, China.
authors.forename: Rong
authors.initials: R
authors.lastname: Luo
authors.affiliation: Cardiovascular Surgery, Guangdong Cardiovascular Institute, Guangdong General Hospital, Guangdong Academy of Medical Sciences, Guangzhou 510100, China.
authors.forename: Jimei
authors.initials: J
authors.lastname: Chen
authors.affiliation: The Center for Heart Development, Key Lab of MOE for Development Biology and Protein Chemistry, College of Life Sciences, Hunan Normal University, Changsha, Hunan 410081, China.
authors.forename: Fa
authors.initials: F
authors.lastname: Chen
authors.affiliation: The Center for Heart Development, Key Lab of MOE for Development Biology and Protein Chemistry, College of Life Sciences, Hunan Normal University, Changsha, Hunan 410081, China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Shi
authors.affiliation: Cardiovascular Surgery, Guangdong Cardiovascular Institute, Guangdong General Hospital, Guangdong Academy of Medical Sciences, Guangzhou 510100, China.
authors.forename: Jiani
authors.initials: J
authors.lastname: Li
authors.affiliation: The Center for Heart Development, Key Lab of MOE for Development Biology and Protein Chemistry, College of Life Sciences, Hunan Normal University, Changsha, Hunan 410081, China.
authors.forename: Zuoqiong
authors.initials: Z
authors.lastname: Zhou
authors.affiliation: The Center for Heart Development, Key Lab of MOE for Development Biology and Protein Chemistry, College of Life Sciences, Hunan Normal University, Changsha, Hunan 410081, China.
authors.forename: Xiaoyang
authors.initials: X
authors.lastname: Mo
authors.affiliation: The Center for Heart Development, Key Lab of MOE for Development Biology and Protein Chemistry, College of Life Sciences, Hunan Normal University, Changsha, Hunan 410081, China.
authors.forename: Xianchu
authors.initials: X
authors.lastname: Liu
authors.affiliation: The Center for Heart Development, Key Lab of MOE for Development Biology and Protein Chemistry, College of Life Sciences, Hunan Normal University, Changsha, Hunan 410081, China.
authors.forename: Wuzhou
authors.initials: W
authors.lastname: Yuan
authors.affiliation: The Center for Heart Development, Key Lab of MOE for Development Biology and Protein Chemistry, College of Life Sciences, Hunan Normal University, Changsha, Hunan 410081, China.
authors.forename: Qun
authors.initials: Q
authors.lastname: Zeng
authors.affiliation: The Center for Heart Development, Key Lab of MOE for Development Biology and Protein Chemistry, College of Life Sciences, Hunan Normal University, Changsha, Hunan 410081, China.
authors.forename: Yongqing
authors.initials: Y
authors.lastname: Li
authors.affiliation: The Center for Heart Development, Key Lab of MOE for Development Biology and Protein Chemistry, College of Life Sciences, Hunan Normal University, Changsha, Hunan 410081, China.
authors.forename: Zhigang
authors.initials: Z
authors.lastname: Jiang
authors.affiliation: The Center for Heart Development, Key Lab of MOE for Development Biology and Protein Chemistry, College of Life Sciences, Hunan Normal University, Changsha, Hunan 410081, China.
authors.forename: Yongqi
authors.initials: Y
authors.lastname: Wan
authors.affiliation: The Center for Heart Development, Key Lab of MOE for Development Biology and Protein Chemistry, College of Life Sciences, Hunan Normal University, Changsha, Hunan 410081, China.
authors.forename: Xiangli
authors.initials: X
authors.lastname: Ye
authors.affiliation: The Center for Heart Development, Key Lab of MOE for Development Biology and Protein Chemistry, College of Life Sciences, Hunan Normal University, Changsha, Hunan 410081, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Xu
authors.affiliation: The Center for Heart Development, Key Lab of MOE for Development Biology and Protein Chemistry, College of Life Sciences, Hunan Normal University, Changsha, Hunan 410081, China.
authors.forename: Xijun
authors.initials: X
authors.lastname: Wang
authors.affiliation: The Center for Heart Development, Key Lab of MOE for Development Biology and Protein Chemistry, College of Life Sciences, Hunan Normal University, Changsha, Hunan 410081, China. Electronic address: fansha1234@aliyun.com.
authors.forename: Xiongwei
authors.initials: X
authors.lastname: Fan
authors.affiliation: Cardiovascular Surgery, Guangdong Cardiovascular Institute, Guangdong General Hospital, Guangdong Academy of Medical Sciences, Guangzhou 510100, China. Electronic address: tanganqier@163.com.
authors.forename: Ping
authors.initials: P
authors.lastname: Zhu
authors.affiliation: The Center for Heart Development, Key Lab of MOE for Development Biology and Protein Chemistry, College of Life Sciences, Hunan Normal University, Changsha, Hunan 410081, China. Electronic address: xiushanwu@yahoo.com.
authors.forename: Xiushan
authors.initials: X
authors.lastname: Wu
authors.affiliation: The Center for Heart Development, Key Lab of MOE for Development Biology and Protein Chemistry, College of Life Sciences, Hunan Normal University, Changsha, Hunan 410081, China. Electronic address: dengyun@hunnu.edu.cn.
authors.forename: Yun
authors.initials: Y
authors.lastname: Deng
mesh_terms: D000818:Animals; D001665:Binding Sites; D002460:Cell Line; D004268:DNA-Binding Proteins / Q000737:chemistry / Q000378:metabolism*; D057809:HEK293 Cells; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000737:chemistry / Q000378:metabolism*; D032383:Myocytes, Cardiac / Q000166:cytology* / Q000378:metabolism*; D011485:Protein Binding; D051381:Rats; D015398:Signal Transduction; D051785:Smad Proteins / Q000737:chemistry / Q000378:metabolism*; D016212:Transforming Growth Factor beta / Q000378:metabolism*; D015027:Zebrafish / Q000378:metabolism*; D029961:Zebrafish Proteins / Q000737:chemistry / Q000378:metabolism*
chemical_list: D004268:DNA-Binding Proteins; D047908:Intracellular Signaling Peptides and Proteins; D051785:Smad Proteins; D016212:Transforming Growth Factor beta; D029961:Zebrafish Proteins; C000621506:cxxc5a protein, zebrafish
keywords: CXXC5; Cardiogenesis; Congenital heart diseases; Tgfβ signaling pathway