Maternal β-catenin activity is essential and critical for dorsal induction and its dorsal activation has been thoroughly studied. However, how the maternal β-catenin activity is suppressed in the nondorsal cells remains poorly understood. Nanog is known to play a central role for maintenance of the pluripotency and maternal -zygotic transition (MZT). Here, we reveal a novel role of Nanog as a strong repressor of maternal β-catenin signaling to safeguard the embryo against hyperactivation of maternal β-catenin activity and hyperdorsalization. In zebrafish, knockdown of nanog at different levels led to either posteriorization or dorsalization, mimicking zygotic or maternal activation of Wnt/β-catenin activities, and the maternal zygotic mutant of nanog (MZnanog) showed strong activation of maternal β-catenin activity and hyperdorsalization. Although a constitutive activator-type Nanog (Vp16-Nanog, lacking the N terminal) perfectly rescued the MZT defects of MZnanog, it did not rescue the phenotypes resulting from β-catenin signaling activation. Mechanistically, the N terminal of Nanog directly interacts with T-cell factor (TCF) and interferes with the binding of β-catenin to TCF, thereby attenuating the transcriptional activity of β-catenin. Therefore, our study establishes a novel role for Nanog in repressing maternal β-catenin activity and demonstrates a transcriptional switch between β-catenin/TCF and Nanog/TCF complexes, which safeguards the embryo from global activation of maternal β-catenin activity.

母体β-catenin的活性对于背诱导是必不可少的，并且它的背激活已被深入研究。但是，如何在非背侧细胞中抑制母体β-catenin的活性仍知之甚少。已知Nanog在维持多能性和母体-合子转换（MZT）中起着核心作用。在这里，我们揭示了Nanog作为母体β-catenin信号转导的强阻遏物的新作用，以保护胚胎免受母体β-catenin活性的过度激活和超背化。在斑马鱼中，不同水平的nanog敲低导致后验或背侧化，模仿Wnt /β-catenin活性的合子或母体激活，以及nanog的母体合子突变体（MZ nanog）表现出强烈的母体β-catenin活性激活和超背化。尽管本构激活剂型Nanog（Vp16-Nanog，缺少N末端）完全挽救了MZ nanog的MZT缺陷，但它没有挽救由β-catenin信号激活产生的表型。从机制上讲，Nanog的N末端直接与T细胞因子（TCF）相互作用，并干扰β-catenin与TCF的结合，从而减弱β-catenin的转录活性。因此，我们的研究建立了Nanog抑制母体β-catenin活性的新作用，并证明了β-catenin/ TCF和Nanog / TCF复合体之间的转录转换，从而保护了胚胎免受母体β-catenin活性的整体激活。