Nanog safeguards early embryogenesis against global activation of maternal β-catenin activity by interfering with TCF factors

Abstract

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