| 论文摘要： |
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 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 beta-catenin signaling to safeguard the embryo against hyperactivation of maternal beta-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/beta-catenin activities, and the maternal zygotic mutant of nanog (MZnanog) showed strong activation of maternal beta-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 beta-catenin signaling activation. Mechanistically, the N terminal of Nanog directly interacts with T-cell factor (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. |
