转录共激活因子RBM14(CoAA)在模式生物斑马鱼神经发育中的作用

项目名称： 转录共激活因子RBM14(CoAA)在模式生物斑马鱼神经发育中的作用

项目编号： No.31271327

项目类型： 面上项目

立项/批准年度： 2013

项目学科： 生物科学

项目作者： 杨哲琼

作者单位： 武汉大学

项目金额： 79万元

中文摘要： 核受体共激活因子RBM14参与调节基因转录及与转录偶联的前mRNA剪切。我们前期的研究结果已从离体细胞水平证实RBM14在干细胞神经定向分化中的重要调控作用。为从整体动物水平全面认识RBM14在干细胞分化和胚胎发育中的作用和地位，本课题拟选用模式生物斑马鱼，检测RBM14在其体内的时空表达模式；并通过显微注射特异性敲低RBM14的Morpholino或加帽RBM14 mRNA以分别下调和上调斑马鱼胚胎内RBM14表达水平，进而观察斑马鱼胚胎神经发育的变化；并借助酵母双杂交系统等方法寻找介导RBM14神经发育调控作用的靶蛋白；我们还将观察斑马鱼胚胎脊髓神经祖细胞非对称分裂过程中，RBM14在子细胞中的分布情况，及RBM14表达水平异常对脊髓神经祖细胞非对称分裂过程及相关调控基因的影响，以探讨RBM14在干细胞非对称分裂过程中的作用。本研究将为了解干细胞分化和胚胎发育机制提供重要的参考资料。

中文关键词： RBM14；神经发育；凋亡；分化；模式生物

英文摘要： Nuclear receptor coactivator RBM14 is involved in the regulation of gene transcription and transcription coupled pre-mRNA splicing. Our previous study showed that RBM14 exerts an important function in the regulation of neural differentiation in cultured stem cells. In order to further understand the role of RBM14 in stem cell differentiation and embryonic development in animal model, we choose a model organism, zebrafish. The spatio-temporal expression pattern of RBM14 in zebrafish will be measured. To observe the change in neural development of zebrafish embryos caused by the abnormal expression of RBM14, we are going to down-regulate and up-regulate the RBM14 expression in zebrafish embryos via microinjection of morpholino against RBM14 or capped RBM14 mRNA. By using the yeast two-hybrid system, GST pull-down, Co-IP and bioinformatics analysis, we intend to find the target proteins which mediate the action of RBM14 in neural development. During asymmetric division of the neural progenitors in spinal cord of zebra fish embryos, the distribution of RBM14 in daughter cells will also be observed. To discuss the role of RBM14 in asymmetric division of stem cell, the change in asymmetric division of neural progenitor in spinal cord induced by the aberrant expression of RBM14 will be measured. The results of this s

英文关键词： RBM14；neurodevelopment；apoptosis；differentiation；model organism