斑马鱼心脏发育阶段特异表达基因FhlA调控心脏腔室发育的分子机制

项目名称： 斑马鱼心脏发育阶段特异表达基因FhlA调控心脏腔室发育的分子机制

项目编号： No.31472060

项目类型： 面上项目

立项/批准年度： 2015

项目学科： 动物学

项目作者： 邓云

作者单位： 湖南师范大学

项目金额： 82万元

中文摘要： 前人研究表明：人类FHL1基因突变导致心脏疾病的发生，但其发病机制未知。申请者前期研究发现： FHL1的斑马鱼同源基因FhlA在心脏前体细胞中特异表达，该基因通过负调控心脏前体细胞的数目控制心脏腔室大小的发育，其对心脏发育的调控可能与视黄酸信号通路有关。为了进一步研究fhlA调控心脏腔室大小的分子机制，申请者拟通过FhlA基因敲除和转基因斑马鱼模型，研究FhlA基因调控心肌细胞增殖的机理，探讨FhlA基因是否通过视黄酸信号通路调控心脏腔室大小的发育过程；基于申请人鉴定的FhlA与视黄酸受体调控蛋白PP2A有相互作用的基础上，研究FhlA和PP2Ac两者通过视黄酸信号相互作用协同调控心脏腔室的大小及调控心肌细胞增殖的的分子机理。该研究对揭示FHL1导致人类心脏疾病发生的机制具有重要意义。

中文关键词： 斑马鱼；心脏发育；FhlA基因；视黄酸；PP2A

英文摘要： Studies have shown that the expression of the human FHL1 gene was related to cardiovascular disease. But the function of FHL1 in heart development is not clear. The results of applicant preliminary study showed that the FhlA, the highly homologous gene of the human FHL1, was specific expressed in the zebrafish heart from 22 somite stage and regulated of the developmental cardiac chamber size through negative regulation of cardiac precursor cell proliferation. And the retinoic acid signaling pathway may be related to the regulation of the FhlA in the heart development. The applicant intends to study the molecular mechanism of FhlA gene regulation in cardiomyocyte proliferation and explore FhlA gene function in the retinoic acid signaling pathway that regulate the cardiac chamber size, by establishing FhlA gene knockout and transgenic experimental model. On the basis of the the preliminary identification of the interaction between FhlA and PP2A catalytic subunit, a retinoic acid receptor regulatory protein, the applicant intends to explore molecular mechanism of Synergistic efficacy of the interaction between FhlA and PP2Ac in the retinoic acid signal regulation of the heart chamber size and myocardial cell proliferation. The research is of great significance for FHL1 function of the human heart development.

英文关键词： zebrafish;heart development;FhlA gene;retinoic;PP2A