Wnt/β-catenin信号通路有着重要的生物学功能，研究发现其除了受到β-catenin转运入核的调控之外，在核内还存在调控β-catenin活性的因子。如我们发现Lbx2与Groucho结合干扰Groucho/TCF转录抑制复合体的形成，从而促进β-catenin的转录活性（Nature Communications, 2014）。Nanog是调控细胞全能性的关键因子。在前期研究中，我们发现斑马鱼早期发育中β-catenin活性受到Nanog的抑制并利用TALEN技术构建了nanog的母源合子突变体（MZnanog）。申报项目拟在此基础上，利用MZnanog模型，开展组学分析并结合实验生物学手段，从Nanog是否从转录水平调控Wnt/β-catenin信号通路相关因子，或以蛋白-蛋白互作方式在核内调控β-catenin信号活性这两方面入手，揭示Nanog抑制Wnt信号通路的分子机制。

Wnt/β-catenin signaling pathway plays important roles in different biological processes. Previous studies have shown that its activity is not only controlled by the nuclear transportation of stabilized β-catenin, but also modulated by certain nuclear factors. For instance, our previous study have revealed the positive regulation of β-catenin transcriptional activity by Lbx2, which interacts with Groucho and thereafter interferes the formation of Groucho/TCF transcriptional repressor complex (Nature Communications, 2014). Nanog has shown to mediate acquisition of both embryonic and induced pluripotency. We have found that the β-catenin transcriptional activity was negatively regulated by Nanog in zebrafish early development, and we further generated the maternal-zygotic mutants of nanog (MZnanog). The proposed project will utilize the MZnanog mutants, by using a combination of omics and experimental approaches, to study the molecular mechanism underlying the fact that Nanog represses Wnt/β-catenin signaling, at two levels, i.e., transcriptional regulation of Wnt/β-catenin signaling factors by homeobox protein Nanog, and protein-interaction-regulation of nuclear β-catenin transcriptional activity by nuclear factor Nanog.