中文摘要
胚层的正确分化是一系列信号协同调节的结果。在非洲爪蛙胚层分化过程中,母源因子beta-catenin和VegT启动合子Nodal/Activin信号通路,从而诱导中、内胚层的分化。表观遗传修饰因子通过其染色质调控功能以及对非组蛋白的调节从而调控胚胎的发育过程。申请者近来的研究发现组蛋白去甲基化酶Kdm2a/b通过对beta-catenin的去甲基化修饰调节Wnt信号通路激活后入核的beta-catenin的稳定性,从而调节胚胎的体轴形成。在后续的研究中,申请者发现beta-catenin存在多个位点的赖氨酸甲基化修饰。也发现组蛋白去甲基化酶Lsd1与VegT存在结合,而且初步研究结果表明Lsd1参与胚层形成。在本项目中,我们欲研究特异位点赖氨酸甲基化修饰对beta-catenin的调节作用,在胚层的分化中的功能和机制,以及Lsd1与VegT的相互作用对胚层分化的调节功能和机制。
英文摘要
Coordinated regulation of germ layer differentiation by multiple signals is essential for subsequent tissue diffenetiation and organogenesis. During the germ layer differentiation of Xenopus embryos, maternal factors beta-catenin and VegT initiate zygotic Nodal/Activin signaling, thereby inducing mesendoderm differentiation. Epigenetic factors are also key regulators of germ layer formation via their functions not only in chromatin modification but also in the mediation of non-histone proteins. Our recent research identified that histone demethylases Kdm2a/b exert demethylation effect on the nuclear beta-catenin after Wnt activation, hence regulating the formation of embryonic body axis. In the subsequent experiments, we found that there are several lysine methylation sites in beta-catenin, and that histone demethylase Lsd1 interacts with VegT. Moreover, preliminary results also showed that Lsd1 is involved in germ layer differentiation. In the present project, we aims to investigate the regulatory effects of the methylation of the specific lysine residues on the activity of beta-catenin, their funtions in the regulation of germ layer formation, and the mechanisms underneath. We will also try to figure out the functional significance of Lsd1 and VegT interaction during germ layer differentiation, and investigate the underlying mechanism by which it regulates germ layer formation.
