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 p...
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Veröffentlicht in: | International journal of cardiology 2016-07, Vol.214, p.246-253 |
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container_title | International journal of cardiology |
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creator | Peng, Xiyang Li, Guanming Wang, Yuequn Zhuang, Jian Luo, Rong Chen, Jimei Chen, Fa Shi, Yan Li, Jiani Zhou, Zuoqiong Mo, Xiaoyang Liu, Xianchu Yuan, Wuzhou Zeng, Qun Li, Yongqing Jiang, Zhigang Wan, Yongqi Ye, Xiangli Xu, Wei Wang, Xijun Fan, Xiongwei Zhu, Ping Wu, Xiushan Deng, Yun |
description | 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. Methods and 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. Conclusion 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. |
doi_str_mv | 10.1016/j.ijcard.2016.03.201 |
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fullrecord | <record><control><sourceid>proquest_cross</sourceid><recordid>TN_cdi_proquest_miscellaneous_1811886731</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><els_id>S0167527316306684</els_id><sourcerecordid>1788225558</sourcerecordid><originalsourceid>FETCH-LOGICAL-c450t-76a4d58b0f3f2ff041846f6845112781c82c1bf493c6d309fa82156f3f4c2bfe3</originalsourceid><addsrcrecordid>eNqFkk9PHCEUwEnTpm5tv0FjOPYyK_9hLyZmU62JiYfaxhthGFDG2WGFmTbbj-UH8TMJWdtDL54e8H68F34PAD5jtMQIi-N-GXprUrckZbdEtMY3YIGVZA2WnL0Fi5KQDSeSHoAPOfcIIbZaqffggEgkC0IX4Of65mbNYcgwuYc5JNdBHxOshYOxcIhxG8bbkhzMVBdThNfnZ0-PMIfb0Qz1aGumu99mB8MI_7g2GR_y3Ufwzpshu08v8RD8OPt6vf7WXF6dX6xPLxvLOJoaKQzruGqRp554jxhWTHihGMeYSIWtIha3nq2oFR1FK28UwVwUmlnSekcPwZd93W2KD7PLk96EbN0wmNHFOWusMFZKSIpfR6VShHDOVUHZHrUp5pyc19sUNibtNEa6yte93svXVb5GtMZy7eilw9xuXPfv0l_bBTjZA64o-RVc0tkGN1rXFfF20l0Mr3X4v4AtIwjWDPdu53If51SGUt6iM9FIf68foM4fC4pE0UqfAZ09q0Y</addsrcrecordid><sourcetype>Aggregation Database</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>1788225558</pqid></control><display><type>article</type><title>CXXC5 is required for cardiac looping relating to TGFβ signaling pathway in zebrafish</title><source>MEDLINE</source><source>Elsevier ScienceDirect Journals</source><creator>Peng, Xiyang ; Li, Guanming ; Wang, Yuequn ; Zhuang, Jian ; Luo, Rong ; Chen, Jimei ; Chen, Fa ; Shi, Yan ; Li, Jiani ; Zhou, Zuoqiong ; Mo, Xiaoyang ; Liu, Xianchu ; Yuan, Wuzhou ; Zeng, Qun ; Li, Yongqing ; Jiang, Zhigang ; Wan, Yongqi ; Ye, Xiangli ; Xu, Wei ; Wang, Xijun ; Fan, Xiongwei ; Zhu, Ping ; Wu, Xiushan ; Deng, Yun</creator><creatorcontrib>Peng, Xiyang ; Li, Guanming ; Wang, Yuequn ; Zhuang, Jian ; Luo, Rong ; Chen, Jimei ; Chen, Fa ; Shi, Yan ; Li, Jiani ; Zhou, Zuoqiong ; Mo, Xiaoyang ; Liu, Xianchu ; Yuan, Wuzhou ; Zeng, Qun ; Li, Yongqing ; Jiang, Zhigang ; Wan, Yongqi ; Ye, Xiangli ; Xu, Wei ; Wang, Xijun ; Fan, Xiongwei ; Zhu, Ping ; Wu, Xiushan ; Deng, Yun</creatorcontrib><description>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. Methods and 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. Conclusion 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.</description><identifier>ISSN: 0167-5273</identifier><identifier>EISSN: 1874-1754</identifier><identifier>DOI: 10.1016/j.ijcard.2016.03.201</identifier><identifier>PMID: 27077543</identifier><language>eng</language><publisher>Netherlands: Elsevier Ireland Ltd</publisher><subject>Animals ; Binding Sites ; Cardiogenesis ; Cardiovascular ; Cell Line ; Congenital heart diseases ; CXXC5 ; DNA-Binding Proteins - chemistry ; DNA-Binding Proteins - metabolism ; HEK293 Cells ; Humans ; Intracellular Signaling Peptides and Proteins - chemistry ; Intracellular Signaling Peptides and Proteins - metabolism ; Myocytes, Cardiac - cytology ; Myocytes, Cardiac - metabolism ; Protein Binding ; Rats ; Signal Transduction ; Smad Proteins - chemistry ; Smad Proteins - metabolism ; Tgfβ signaling pathway ; Transforming Growth Factor beta - metabolism ; Zebrafish - metabolism ; Zebrafish Proteins - chemistry ; Zebrafish Proteins - metabolism</subject><ispartof>International journal of cardiology, 2016-07, Vol.214, p.246-253</ispartof><rights>2016 Elsevier Ireland Ltd</rights><rights>Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c450t-76a4d58b0f3f2ff041846f6845112781c82c1bf493c6d309fa82156f3f4c2bfe3</citedby><cites>FETCH-LOGICAL-c450t-76a4d58b0f3f2ff041846f6845112781c82c1bf493c6d309fa82156f3f4c2bfe3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://www.sciencedirect.com/science/article/pii/S0167527316306684$$EHTML$$P50$$Gelsevier$$H</linktohtml><link.rule.ids>314,776,780,3537,27901,27902,65306</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/27077543$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Peng, Xiyang</creatorcontrib><creatorcontrib>Li, Guanming</creatorcontrib><creatorcontrib>Wang, Yuequn</creatorcontrib><creatorcontrib>Zhuang, Jian</creatorcontrib><creatorcontrib>Luo, Rong</creatorcontrib><creatorcontrib>Chen, Jimei</creatorcontrib><creatorcontrib>Chen, Fa</creatorcontrib><creatorcontrib>Shi, Yan</creatorcontrib><creatorcontrib>Li, Jiani</creatorcontrib><creatorcontrib>Zhou, Zuoqiong</creatorcontrib><creatorcontrib>Mo, Xiaoyang</creatorcontrib><creatorcontrib>Liu, Xianchu</creatorcontrib><creatorcontrib>Yuan, Wuzhou</creatorcontrib><creatorcontrib>Zeng, Qun</creatorcontrib><creatorcontrib>Li, Yongqing</creatorcontrib><creatorcontrib>Jiang, Zhigang</creatorcontrib><creatorcontrib>Wan, Yongqi</creatorcontrib><creatorcontrib>Ye, Xiangli</creatorcontrib><creatorcontrib>Xu, Wei</creatorcontrib><creatorcontrib>Wang, Xijun</creatorcontrib><creatorcontrib>Fan, Xiongwei</creatorcontrib><creatorcontrib>Zhu, Ping</creatorcontrib><creatorcontrib>Wu, Xiushan</creatorcontrib><creatorcontrib>Deng, Yun</creatorcontrib><title>CXXC5 is required for cardiac looping relating to TGFβ signaling pathway in zebrafish</title><title>International journal of cardiology</title><addtitle>Int J Cardiol</addtitle><description>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. Methods and 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. Conclusion 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.</description><subject>Animals</subject><subject>Binding Sites</subject><subject>Cardiogenesis</subject><subject>Cardiovascular</subject><subject>Cell Line</subject><subject>Congenital heart diseases</subject><subject>CXXC5</subject><subject>DNA-Binding Proteins - chemistry</subject><subject>DNA-Binding Proteins - metabolism</subject><subject>HEK293 Cells</subject><subject>Humans</subject><subject>Intracellular Signaling Peptides and Proteins - chemistry</subject><subject>Intracellular Signaling Peptides and Proteins - metabolism</subject><subject>Myocytes, Cardiac - cytology</subject><subject>Myocytes, Cardiac - metabolism</subject><subject>Protein Binding</subject><subject>Rats</subject><subject>Signal Transduction</subject><subject>Smad Proteins - chemistry</subject><subject>Smad Proteins - metabolism</subject><subject>Tgfβ signaling pathway</subject><subject>Transforming Growth Factor beta - metabolism</subject><subject>Zebrafish - metabolism</subject><subject>Zebrafish Proteins - chemistry</subject><subject>Zebrafish Proteins - metabolism</subject><issn>0167-5273</issn><issn>1874-1754</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2016</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqFkk9PHCEUwEnTpm5tv0FjOPYyK_9hLyZmU62JiYfaxhthGFDG2WGFmTbbj-UH8TMJWdtDL54e8H68F34PAD5jtMQIi-N-GXprUrckZbdEtMY3YIGVZA2WnL0Fi5KQDSeSHoAPOfcIIbZaqffggEgkC0IX4Of65mbNYcgwuYc5JNdBHxOshYOxcIhxG8bbkhzMVBdThNfnZ0-PMIfb0Qz1aGumu99mB8MI_7g2GR_y3Ufwzpshu08v8RD8OPt6vf7WXF6dX6xPLxvLOJoaKQzruGqRp554jxhWTHihGMeYSIWtIha3nq2oFR1FK28UwVwUmlnSekcPwZd93W2KD7PLk96EbN0wmNHFOWusMFZKSIpfR6VShHDOVUHZHrUp5pyc19sUNibtNEa6yte93svXVb5GtMZy7eilw9xuXPfv0l_bBTjZA64o-RVc0tkGN1rXFfF20l0Mr3X4v4AtIwjWDPdu53If51SGUt6iM9FIf68foM4fC4pE0UqfAZ09q0Y</recordid><startdate>20160701</startdate><enddate>20160701</enddate><creator>Peng, Xiyang</creator><creator>Li, Guanming</creator><creator>Wang, Yuequn</creator><creator>Zhuang, Jian</creator><creator>Luo, Rong</creator><creator>Chen, Jimei</creator><creator>Chen, Fa</creator><creator>Shi, Yan</creator><creator>Li, Jiani</creator><creator>Zhou, Zuoqiong</creator><creator>Mo, Xiaoyang</creator><creator>Liu, Xianchu</creator><creator>Yuan, Wuzhou</creator><creator>Zeng, Qun</creator><creator>Li, Yongqing</creator><creator>Jiang, Zhigang</creator><creator>Wan, Yongqi</creator><creator>Ye, Xiangli</creator><creator>Xu, Wei</creator><creator>Wang, Xijun</creator><creator>Fan, Xiongwei</creator><creator>Zhu, Ping</creator><creator>Wu, Xiushan</creator><creator>Deng, Yun</creator><general>Elsevier Ireland Ltd</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7X8</scope><scope>7TS</scope></search><sort><creationdate>20160701</creationdate><title>CXXC5 is required for cardiac looping relating to TGFβ signaling pathway in zebrafish</title><author>Peng, Xiyang ; Li, Guanming ; Wang, Yuequn ; Zhuang, Jian ; Luo, Rong ; Chen, Jimei ; Chen, Fa ; Shi, Yan ; Li, Jiani ; Zhou, Zuoqiong ; Mo, Xiaoyang ; Liu, Xianchu ; Yuan, Wuzhou ; Zeng, Qun ; Li, Yongqing ; Jiang, Zhigang ; Wan, Yongqi ; Ye, Xiangli ; Xu, Wei ; Wang, Xijun ; Fan, Xiongwei ; Zhu, Ping ; Wu, Xiushan ; Deng, Yun</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c450t-76a4d58b0f3f2ff041846f6845112781c82c1bf493c6d309fa82156f3f4c2bfe3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2016</creationdate><topic>Animals</topic><topic>Binding Sites</topic><topic>Cardiogenesis</topic><topic>Cardiovascular</topic><topic>Cell Line</topic><topic>Congenital heart diseases</topic><topic>CXXC5</topic><topic>DNA-Binding Proteins - chemistry</topic><topic>DNA-Binding Proteins - metabolism</topic><topic>HEK293 Cells</topic><topic>Humans</topic><topic>Intracellular Signaling Peptides and Proteins - chemistry</topic><topic>Intracellular Signaling Peptides and Proteins - metabolism</topic><topic>Myocytes, Cardiac - cytology</topic><topic>Myocytes, Cardiac - metabolism</topic><topic>Protein Binding</topic><topic>Rats</topic><topic>Signal Transduction</topic><topic>Smad Proteins - chemistry</topic><topic>Smad Proteins - metabolism</topic><topic>Tgfβ signaling pathway</topic><topic>Transforming Growth Factor beta - metabolism</topic><topic>Zebrafish - metabolism</topic><topic>Zebrafish Proteins - chemistry</topic><topic>Zebrafish Proteins - metabolism</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Peng, Xiyang</creatorcontrib><creatorcontrib>Li, Guanming</creatorcontrib><creatorcontrib>Wang, Yuequn</creatorcontrib><creatorcontrib>Zhuang, Jian</creatorcontrib><creatorcontrib>Luo, Rong</creatorcontrib><creatorcontrib>Chen, Jimei</creatorcontrib><creatorcontrib>Chen, Fa</creatorcontrib><creatorcontrib>Shi, Yan</creatorcontrib><creatorcontrib>Li, Jiani</creatorcontrib><creatorcontrib>Zhou, Zuoqiong</creatorcontrib><creatorcontrib>Mo, Xiaoyang</creatorcontrib><creatorcontrib>Liu, Xianchu</creatorcontrib><creatorcontrib>Yuan, Wuzhou</creatorcontrib><creatorcontrib>Zeng, Qun</creatorcontrib><creatorcontrib>Li, Yongqing</creatorcontrib><creatorcontrib>Jiang, Zhigang</creatorcontrib><creatorcontrib>Wan, Yongqi</creatorcontrib><creatorcontrib>Ye, Xiangli</creatorcontrib><creatorcontrib>Xu, Wei</creatorcontrib><creatorcontrib>Wang, Xijun</creatorcontrib><creatorcontrib>Fan, Xiongwei</creatorcontrib><creatorcontrib>Zhu, Ping</creatorcontrib><creatorcontrib>Wu, Xiushan</creatorcontrib><creatorcontrib>Deng, Yun</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><collection>Physical Education Index</collection><jtitle>International journal of cardiology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Peng, Xiyang</au><au>Li, Guanming</au><au>Wang, Yuequn</au><au>Zhuang, Jian</au><au>Luo, Rong</au><au>Chen, Jimei</au><au>Chen, Fa</au><au>Shi, Yan</au><au>Li, Jiani</au><au>Zhou, Zuoqiong</au><au>Mo, Xiaoyang</au><au>Liu, Xianchu</au><au>Yuan, Wuzhou</au><au>Zeng, Qun</au><au>Li, Yongqing</au><au>Jiang, Zhigang</au><au>Wan, Yongqi</au><au>Ye, Xiangli</au><au>Xu, Wei</au><au>Wang, Xijun</au><au>Fan, Xiongwei</au><au>Zhu, Ping</au><au>Wu, Xiushan</au><au>Deng, Yun</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>CXXC5 is required for cardiac looping relating to TGFβ signaling pathway in zebrafish</atitle><jtitle>International journal of cardiology</jtitle><addtitle>Int J Cardiol</addtitle><date>2016-07-01</date><risdate>2016</risdate><volume>214</volume><spage>246</spage><epage>253</epage><pages>246-253</pages><issn>0167-5273</issn><eissn>1874-1754</eissn><abstract>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. Methods and 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. Conclusion 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.</abstract><cop>Netherlands</cop><pub>Elsevier Ireland Ltd</pub><pmid>27077543</pmid><doi>10.1016/j.ijcard.2016.03.201</doi><tpages>8</tpages></addata></record> |
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subjects | Animals Binding Sites Cardiogenesis Cardiovascular Cell Line Congenital heart diseases CXXC5 DNA-Binding Proteins - chemistry DNA-Binding Proteins - metabolism HEK293 Cells Humans Intracellular Signaling Peptides and Proteins - chemistry Intracellular Signaling Peptides and Proteins - metabolism Myocytes, Cardiac - cytology Myocytes, Cardiac - metabolism Protein Binding Rats Signal Transduction Smad Proteins - chemistry Smad Proteins - metabolism Tgfβ signaling pathway Transforming Growth Factor beta - metabolism Zebrafish - metabolism Zebrafish Proteins - chemistry Zebrafish Proteins - metabolism |
title | CXXC5 is required for cardiac looping relating to TGFβ signaling pathway in zebrafish |
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