title: Smad4 is required for the development of cardiac and skeletal muscle in zebrafish.
abstract: Transforming growth factor-beta (TGF-beta) regulates cellular functions and plays key roles in development and carcinogenesis. Smad4 is the central intracellular mediator of TGF-beta signaling and plays crucial roles in tissue regeneration, cell differentiation, embryonic development, regulation of the immune system and tumor progression. To clarify the role of smad4 in development, we examined both the pattern of smad4 expression in zebrafish embryos and the effect of smad4 suppression on embryonic development using smad4-specific antisense morpholino-oligonucleotides. We show that smad4 is expressed in zebrafish embryos at all developmental stages examined and that embryonic knockdown of smad4 results in pericardial edema, decreased heartbeat and defects in the trunk structure. Additionally, these phenotypes were associated with abnormal expression of the two heart-chamber markers, cmlc2 and vmhc, as well as abnormal expression of three makers of myogenic terminal differentiation, mylz2, smyhc1 and mck. Furthermore, a notable increase in apoptosis was apparent in the smad4 knockdown embryos, while no obvious reduction in cell proliferation was observed. Collectively, these data suggest that smad4 plays an important role in heart and skeletal muscle development.
authors.affiliation: Cancer Biology Research Centre, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, 430030 PR China. Electronic address: yangjie@tjh.tjmu.edu.cn.
authors.forename: Jie
authors.initials: J
authors.lastname: Yang
authors.affiliation: Cancer Biology Research Centre, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, 430030 PR China. Electronic address: 865646064@qq.com.
authors.forename: Junnai
authors.initials: J
authors.lastname: Wang
authors.affiliation: Cancer Biology Research Centre, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, 430030 PR China. Electronic address: 304527694@qq.com.
authors.forename: Zhen
authors.initials: Z
authors.lastname: Zeng
authors.affiliation: Cancer Biology Research Centre, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, 430030 PR China. Electronic address: 498801939@qq.com.
authors.forename: Long
authors.initials: L
authors.lastname: Qiao
authors.affiliation: Cancer Biology Research Centre, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, 430030 PR China. Electronic address: mrzhuangliang@126.com.
authors.forename: Liang
authors.initials: L
authors.lastname: Zhuang
authors.affiliation: Cancer Biology Research Centre, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, 430030 PR China. Electronic address: 278308418@qq.com.
authors.forename: Lijun
authors.initials: L
authors.lastname: Jiang
authors.affiliation: Cancer Biology Research Centre, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, 430030 PR China. Electronic address: 191320607@qq.com.
authors.forename: Juncheng
authors.initials: J
authors.lastname: Wei
authors.affiliation: Cancer Biology Research Centre, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, 430030 PR China. Electronic address: 99213704@qq.com.
authors.forename: Quanfu
authors.initials: Q
authors.lastname: Ma
authors.affiliation: Cancer Biology Research Centre, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, 430030 PR China. Electronic address: wumingfuwh@aliyun.com.
authors.forename: Mingfu
authors.initials: M
authors.lastname: Wu
authors.affiliation: Cancer Biology Research Centre, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, 430030 PR China. Electronic address: 29011378@qq.com.
authors.forename: Shuangmei
authors.initials: S
authors.lastname: Ye
authors.affiliation: Cancer Biology Research Centre, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, 430030 PR China. Electronic address: 2482880446@qq.com.
authors.forename: Qinglei
authors.initials: Q
authors.lastname: Gao
authors.affiliation: Cancer Biology Research Centre, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, 430030 PR China. Electronic address: dma@tjh.tjmu.edu.cn.
authors.forename: Ding
authors.initials: D
authors.lastname: Ma
authors.affiliation: Cancer Biology Research Centre, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, 430030 PR China. Electronic address: huangxy@tjh.tjmu.edu.cn.
authors.forename: Xiaoyuan
authors.initials: X
authors.lastname: Huang
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000235:genetics; D024722:Cardiac Myosins / Q000235:genetics; D002454:Cell Differentiation / Q000235:genetics*; D049109:Cell Proliferation / Q000235:genetics; D047108:Embryonic Development / Q000235:genetics*; D018507:Gene Expression Regulation, Developmental; D006321:Heart / Q000254:growth & development; D024510:Muscle Development / Q000235:genetics*; D018482:Muscle, Skeletal / Q000254:growth & development; D018994:Myosin Light Chains / Q000235:genetics; D051901:Smad4 Protein / Q000235:genetics*; D016212:Transforming Growth Factor beta; D015027:Zebrafish / Q000235:genetics / Q000254:growth & development; D029961:Zebrafish Proteins / Q000235:genetics*
chemical_list: D018994:Myosin Light Chains; D051901:Smad4 Protein; D016212:Transforming Growth Factor beta; D029961:Zebrafish Proteins; C532159:myl7 protein, zebrafish; C107184:myosin light chain 2; C490809:smad4a protein, zebrafish; D024722:Cardiac Myosins
keywords: Apoptosis; Development; Heart; Smad4; Trunk