Abstract
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.
Highlights
The Wnt/β-catenin signaling pathway, known as the canonical Wnt signaling pathway, is highly conserved during evolution
Both ctnnb2 and wnt8a were shown to be maternally expressed in developing oocytes and in unfertilized eggs (Fig 1B), suggesting that a certain amount of βcatenin might be existing in the nuclei of all the blastoderm cells, and its transcriptional activity should be repressed in the nondorsal cells
One possibility is the presence of certain antagonistic factors of β-catenin inside nucleus, e.g., Gro/transducin-like enhancer of split (TLE), which binds to suppressive T-cell factor (TCF) and interacts with histone deacetylases to maintain the chromatin in a transcriptionally inactive state [10,11,12,13,58]
Summary
The Wnt/β-catenin signaling pathway, known as the canonical Wnt signaling pathway, is highly conserved during evolution. It plays crucial roles in embryonic development, organogenesis, tissue homeostasis, self-renewal and differentiation of stem cell, reproduction, and carcinogenesis [1,2,3,4,5]. Decades of studies have shown that the central scheme of the Wnt/βcatenin pathway is to stabilize the transcription coactivator β-catenin and protect it from phosphorylation-dependent degradation [6,7]. The Wnt/β-catenin pathway is well known for its “on/off” regulation model. In the presence of Wnt ligand, a receptor complex forms between.
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