|ZFIN ID: ZDB-PUB-200724-27|
Nanog safeguards early embryogenesis against global activation of maternal β-catenin activity by interfering with TCF factors
He, M., Zhang, R., Jiao, S., Zhang, F., Ye, D., Wang, H., Sun, Y.
|Source:||PLoS Biology 18: e3000561 (Journal)|
|Registered Authors:||He, Mudan, Sun, Yonghua, Ye, Ding|
|PubMed:||32702011 Full text @ PLoS Biol.|
He, M., Zhang, R., Jiao, S., Zhang, F., Ye, D., Wang, H., Sun, Y. (2020) Nanog safeguards early embryogenesis against global activation of maternal β-catenin activity by interfering with TCF factors. PLoS Biology. 18:e3000561.
ABSTRACTMaternal 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.