Follistatin调控脊椎动物左右不对称发育的机制研究

批准号:
31970757
项目类别:
面上项目
资助金额:
57.0 万元
负责人:
徐鹏飞
依托单位:
学科分类:
早期胚胎发育及细胞谱系建立
结题年份:
2023
批准年份:
2019
项目状态:
已结题
项目参与者:
徐鹏飞
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中文摘要
脊椎动物的左-右不对称图式在发育过程中逐步建立,包括对称的打破,不对称信号的放大和维持,以及不对称信号的应答等。在这些过程中TGF-β家族成员Nodal和BMP的相互作用至关重要,BMP过高或过低均导致左右不对称发育异常,但BMP在此过程中的作用机理和如何被调控尚不清楚。我们的前期研究显示,BMP的负性调控因子-Follistatin-对左右不对称发育起重要作用,在斑马鱼中敲低或敲除follistatin导致原只在左侧表达的nodal等基因双侧表达,并进一步引起心脏等的左右位置随机分布。本项目拟利用斑马鱼及小鼠模型,结合基因编辑、活体实时成像等技术,对Follistatin如何调控TGF-β信号通路而影响左-右不对称发育的机制进行研究,并对该基因在不同物种间功能上的保守性进行比较。该研究有望发现左右不对称建立和维持新的分子机制,帮助我们更好地理解身体图式形成的基本原理。
英文摘要
Under the bilateral external symmetry, the internal organs of vertebrates are positioned asymmetrically along the left-right (LR) axis. Left-right patterning is progressively established during embryonic development, the processes mainly include symmetry breaking, the propagation of asymmetric signals, amplification and maintenance of asymmetry, and response to asymmetric signals. The Transforming Growth Factor-β (TGF-β) family members, such as Nodal, BMP, are key regulators of these processes. Our preliminary data showed that Follinstatin, which is an inhibitor of BMP, plays an important role during the development of left-right asymmetry. In zebrafish, both knockdown and knockout of follistatin result in bilateral expression of nodal, which only express at the left side in wild type embryo, the loss-of-function of Follistatin further lead to the randomized left-right distribution of internal organs such as the heart. We plan to use both zebrafish and mouse models, utilizing technologies such as gene editing, live imaging, developmental and molecular techniques to study how Follistatin affects left-right patterning by fine regulating TGF-β signaling pathway in vertebrates, and explore the functional conservation of Follistatin among different species. This research is expected to reveal new molecular mechanisms of the establishment and maintenance of left-right asymmetry, to provid a new perspective for understanding this important developmental biology question.
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DOI:10.1073/pnas.2219649120
发表时间:2023-06-13
期刊:PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
影响因子:11.1
作者:Fu, Xin-Xin;Zhuo, Ding-Hao;Zhang, Ying-Jie;Li, Yun-Fei;Liu, Xiang;Xing, Yan-Yi;Huang, Ying;Wang, Yi-Fan;Cheng, Tao;Wang, Dan;Chen, Si-Han;Chen, Yi-Jian;Jiang, Guan-Nan;Lu, Fu-, I;Feng, Yu;Huang, Xiao;Ma, Jun;Liu, Wei;Bai, Ge;Xu, Peng-Fei
通讯作者:Xu, Peng-Fei
DOI:--
发表时间:2023
期刊:Cell Reports
影响因子:8.8
作者:Tao Cheng;Yan-Yi Xing;Cong Liu;Yun-Fei Li;Ying Huang;Xiang Liu;Ying-Jie Zhang;Guo-Qin Zhao;Yang Dong;Xin-Xin Fu;Yi-Meng Tian;Li-Ping Shu;Sean Megason;Peng-Fei Xu
通讯作者:Peng-Fei Xu
形态发生素体外诱导胚胎和器官生成
- 批准号:32050109
- 项目类别:专项基金项目
- 资助金额:300万元
- 批准年份:2020
- 负责人:徐鹏飞
- 依托单位:
国内基金
海外基金
