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题名: Transcriptional Factors Smad1 and Smad9 Act Redundantly to Mediate Zebrafish Ventral Specification Downstream of Smad5
作者: Wei, Chang-Yong1, 2; Wang, Hou-Peng1; Zhu, Zuo-Yan1; Sun, Yong-Hua1
通讯作者: Sun, YH (reprint author), Chinese Acad Sci, Inst Hydrobiol, State Key Lab Freshwater Ecol & Biotechnol, 7 Donghu South Rd, Wuhan 430072, Peoples R China.
关键词: Bone Morphogenetic Protein (BMP) ; Development ; Gene Regulation ; SMAD Transcription Factor ; Zebrafish ; Dorso-ventral Patterning ; Myelopoiesis
刊名: JOURNAL OF BIOLOGICAL CHEMISTRY
发表日期: 2014-03-07
DOI: 10.1074/jbc.M114.549758
卷: 289, 期:10, 页:6604-6618
收录类别: SCI
文章类型: Article
部门归属: [Wei, Chang-Yong ; Wang, Hou-Peng ; Zhu, Zuo-Yan ; Sun, Yong-Hua] Chinese Acad Sci, Inst Hydrobiol, State Key Lab Freshwater Ecol & Biotechnol, Wuhan 430072, Peoples R China ; [Wei, Chang-Yong] Univ Chinese Acad Sci, Beijing 100049, Peoples R China
WOS标题词: Science & Technology ; Life Sciences & Biomedicine
资助者: China 973 Project [2010CB126306, 2012CB944504]; National Natural Science Foundation of China (NSFC) [31222052]; NSFC [30771100]; FEBL Grant [2011FBZ23]
类目[WOS]: Biochemistry & Molecular Biology
研究领域[WOS]: Biochemistry & Molecular Biology
摘要: Background: Ventral specification is regulated by Smad1-, Smad5-, and/or Smad9-mediated bone morphogenetic protein (BMP) signaling. Results: Double knockdown instead of single knockdown of smad1 and smad9 induces dorsalization, which cannot be rescued by smad5 overexpression. Conclusion:smad1 and smad9 act redundantly and downstream of smad5 to mediate ventral specification. Significance: The regulation network and cooperative roles of BMP R-Smads in early development are clarified. Bone morphogenetic proteins (BMPs) are multifunctional growth factors that play crucial roles during embryonic development and cell fate determination. Nuclear transduction of BMP signals requires the receptor type Smad proteins, Smad1, Smad5, and Smad9. However, how these Smad proteins cooperate in vivo to regulate various developmental processes is largely unknown. In zebrafish, it was widely believed that the maternally expressed smad5 is essential for dorso-ventral (DV) patterning, and the zygotically transcribed smad1 is not required for normal DV axis establishment. In the present study, we have identified zygotically expressed smad9, which cooperates with smad1 downstream of smad5, to mediate zebrafish early DV patterning in a functional redundant manner. Although knockdown of smad1 or smad9 alone does not lead to visible dorsalization, double knockdown strongly dorsalizes zebrafish embryos, which cannot be efficiently rescued by smad5 overexpression, whereas the dorsalization induced by smad5 knockdown can be fully rescued by overexpression of smad1 or smad9. We have further revealed that the transcription initiations of smad1 and smad9 are repressed by each other, that they are direct transcriptional targets of Smad5, and that smad9, like smad1, is required for myelopoiesis. In conclusion, our study uncovers that smad1 and smad9 act redundantly to each other downstream of smad5 to mediate ventral specification and to regulate embryonic myelopoiesis.
英文摘要: Background: Ventral specification is regulated by Smad1-, Smad5-, and/or Smad9-mediated bone morphogenetic protein (BMP) signaling. Results: Double knockdown instead of single knockdown of smad1 and smad9 induces dorsalization, which cannot be rescued by smad5 overexpression. Conclusion:smad1 and smad9 act redundantly and downstream of smad5 to mediate ventral specification. Significance: The regulation network and cooperative roles of BMP R-Smads in early development are clarified.
关键词[WOS]: DORSOVENTRAL PATTERN-FORMATION ; BETA SIGNAL-TRANSDUCTION ; DORSAL SPINAL-CORD ; DANIO-RERIO ; EMBRYO ; PROTEIN ; GENES ; EXPRESSION ; MOUSE ; DEFECTS
语种: 英语
WOS记录号: WOS:000332389400025
ISSN号: 0021-9258
Citation statistics:
内容类型: 期刊论文
URI标识: http://ir.ihb.ac.cn/handle/342005/20045
Appears in Collections:鱼类生物学及渔业生物技术研究中心_期刊论文

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作者单位: 1.Chinese Acad Sci, Inst Hydrobiol, State Key Lab Freshwater Ecol & Biotechnol, Wuhan 430072, Peoples R China
2.Univ Chinese Acad Sci, Beijing 100049, Peoples R China

Recommended Citation:
Wei, Chang-Yong; Wang, Hou-Peng; Zhu, Zuo-Yan; Sun, Yong-Hua.Transcriptional Factors Smad1 and Smad9 Act Redundantly to Mediate Zebrafish Ventral Specification Downstream of Smad5,JOURNAL OF BIOLOGICAL CHEMISTRY,2014,289(10):6604-6618
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