PUBLICATION

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

Authors
He, M., Zhang, R., Jiao, S., Zhang, F., Ye, D., Wang, H., Sun, Y.
ID
ZDB-PUB-200724-27
Date
2020
Source
PLoS Biology   18: e3000561 (Journal)
Registered Authors
He, Mudan, Sun, Yonghua, Ye, Ding
Keywords
none
MeSH Terms
  • Embryonic Development/genetics*
  • Gene Expression Regulation, Developmental
  • Nanog Homeobox Protein/chemistry
  • Nanog Homeobox Protein/genetics
  • Nanog Homeobox Protein/metabolism*
  • Zygote/metabolism
  • Transcription, Genetic
  • beta Catenin/metabolism*
  • Repressor Proteins/metabolism
  • Cell Nucleus/metabolism
  • Animals
  • Zebrafish/embryology*
  • Zebrafish/genetics*
  • Protein Binding
  • Protein Transport
  • Male
  • Trans-Activators/metabolism*
  • Body Patterning/genetics
  • Zebrafish Proteins/chemistry
  • Zebrafish Proteins/genetics
  • Zebrafish Proteins/metabolism*
  • Female
  • Gene Knockdown Techniques
  • Mutation/genetics
  • Wnt Signaling Pathway/genetics
(all 25)
PubMed
32702011 Full text @ PLoS Biol.
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.
Genes / Markers
Figures
Figure Gallery (8 images)
Show all Figures
Expression
Gene Antibody Fish Conditions Stage Qualifier Anatomy Assay Figure
blfnanogihb97/ihb97standard conditionsShieldISH
blfnanogihb98/ihb98standard conditionsShieldISH
blfWTstandard conditionsShieldISH
chrdnanogihb97/ihb97standard conditionsSphereRTPCR
chrdnanogihb97/ihb97standard conditions30%-epibolyISH
chrdnanogihb97/ihb97standard conditionsDomeISH
chrdnanogihb97/ihb97 + MO1-ctnnb1standard conditions30%-epibolyISH
chrdnanogihb97/ihb97 + MO1-ctnnb1standard conditionsSphereRTPCR
chrdnanogihb97/ihb97 + MO1-ctnnb2standard conditions30%-epibolyISH
chrdnanogihb97/ihb97 + MO1-ctnnb2standard conditionsSphereRTPCR
1 - 10 of 151
Show
Phenotype
Fish Conditions Stage Phenotype Figure
WT + MO1-nanogstandard conditions64-cell
WT + MO1-nanogstandard conditions1k-cell
WT + MO1-nanogstandard conditionsSphere
WT + MO1-nanogstandard conditionsSphere
WT + MO1-nanogstandard conditionsSphere
WT + MO1-nanogstandard conditionsShield
WT + MO1-nanogstandard conditionsShield
WT + MO1-nanogstandard conditions75%-epiboly
WT + MO1-nanogstandard conditions75%-epiboly
WT + MO1-nanogstandard conditions75%-epiboly
1 - 10 of 116
Show
Mutations / Transgenics
Allele Construct Type Affected Genomic Region
ihb97
    		Small Deletion
    ihb98
      		Insertion
      ihb354
        		Insertion
        ihb355
          		Small Deletion
          1 - 4 of 4
          Show
          Human Disease / Model
          No data available
          Sequence Targeting Reagents
          Target Reagent Reagent Type
          ctnnb1MO1-ctnnb1MRPHLNO
          ctnnb2MO1-ctnnb2MRPHLNO
          nanogMO1-nanogMRPHLNO
          tcf7l1aMO1-tcf7l1aMRPHLNO
          tle2aMO1-tle2aMRPHLNO
          tle3aCRISPR1-tle3aCRISPR
          tle3aMO3-tle3aMRPHLNO
          tle3bMO3-tle3bMRPHLNO
          wnt8aMO1-wnt8aMRPHLNO
          wnt8aMO2-wnt8aMRPHLNO
          1 - 10 of 10
          Show
          Fish
          Fish
          nanogihb97/ihb97
          nanogihb97/ihb97 + MO1-ctnnb1
          nanogihb97/ihb97 + MO1-ctnnb2
          nanogihb98/ihb98
          nanogihb98/ihb98 + MO1-ctnnb1
          nanogihb98/ihb98 + MO1-ctnnb2
          tle3aihb355/ihb355
          tle3aihb355/ihb355; tle3bihb354/ihb354
          tle3bihb354/ihb354
          WT
          1 - 10 of 16
          Show
          Antibodies
          Name Type Antigen Genes Isotypes Host Organism
          Ab1-mycmonoclonal
            		IgG1Mouse
            Ab17-ctnnbmonoclonal
              		IgGRabbit
              1 - 2 of 2
              Show
              Orthology
              No data available
              Engineered Foreign Genes
              No data available
              Mapping
              No data available
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              Citation
              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.