Ubiquitination and deubiquitination of 4E-T regulate neural progenitor cell maintenance and neurogenesis by controlling P-body formation.
During embryogenesis, neural stem/progenitor cells (NPCs) proliferate and differentiate to form brain tissues. Here, we show that in the developing murine cerebral cortex, the balance between the NPC maintenance and differentiation is coordinated by ubiquitin signals that control the formation of processing bodies (P-bodies), cytoplasmic membraneless organelles critical for cell state regulation. We find that the deubiquitinase Otud4 and the E3 ligase Trim56 counter-regulate the ubiquitination status of a core P-body protein 4E-T to orchestrate the assembly of P-bodies in NPCs. Aberrant induction of 4E-T ubiquitination promotes P-body assembly in NPCs and causes a delay in their cell cycle progression and differentiation. In contrast, loss of 4E-T ubiquitination abrogates P-bodies and results in premature neurogenesis. Thus, our results reveal a critical role of ubiquitin-dependent regulation of P-body formation in NPC maintenance and neurogenesis during brain development.
Pubmed ID: 35830814
Research resources used in this publication
- pT7-EGFP-C1-HsNot7 (RRID:Addgene_37325) (plasmid)
- pCDNA3-Flag-hDcp2 (RRID:Addgene_72213) (plasmid)
- pT7-EGFP-C1-HsDCP1a (RRID:Addgene_25030) (plasmid)
- pRK5-HA-Ubiquitin-WT (RRID:Addgene_17608) (plasmid)
- HEK293 (RRID:CVCL_0045) (cell line)
- pCAGIG (RRID:Addgene_11159) (plasmid)
- B6.129-Gt(ROSA)26Sortm1(cre/ERT2)Tyj/J (RRID:IMSR_JAX:008463) (organism)
Additional research tools detected in this publication
Antibodies used in this publication
- Ki67 antibody - Proliferation Marker (RRID:AB_443209)
- Purified Mouse Anti-Ki-67 Clone B56 (RRID:AB_393778)
- Rabbit Anti-Mouse TBR2 / Eomes Polyclonal Antibody, Unconjugated (RRID:AB_778267)
- EOMES Monoclonal Antibody (Dan11mag), eBioscience (RRID:AB_11043546)
- Neuronal Class III beta-Tubulin (TUJ1) Monoclonal Antibody, Purified (RRID:AB_2313773)
- Ctip2 antibody [25B6] - ChIP Grade (RRID:AB_2064130)
- Mouse Anti-Human SATB2 Monoclonal Antibody, Unconjugated, Clone SATBA4B10 (RRID:AB_882455)
- Sox2 (C70B1) Rabbit mAb (IHC Preferred) (RRID:AB_2194037)
- Human/Mouse/Rat SOX2 Antibody (RRID:AB_355110)
- Purified anti-Pax-6 (RRID:AB_2565003)
- Mouse Anti-PAX6 Monoclonal Antibody, Unconjugated, Clone AD2.38 (RRID:AB_1566562)
- Mouse Anti-Human DCP1A Monoclonal Antibody, Unconjugated, Clone 3G4 (RRID:AB_530021)
- BrdU (RRID:AB_10015219)
- Rat Anti-BrdU Monoclonal Antibody, Unconjugated, Clone BU1 / 75 (ICR1) (RRID:AB_305426)
- Phospho-Histone H3 (Ser10) Monoclonal Antibody (K.872.3) (RRID:AB_11008586)
- EDC4/Ge-1 Antibody (RRID:AB_10621246)
- 4E-T Antibody (RRID:AB_2095735)
- EIF4ENIF1 MaxPab mouse polyclonal antibody (B01) (RRID:AB_1113607)
- GFP (B-2) (RRID:AB_627695)
- Anti-Green Fluorescent Protein Antibody (RRID:AB_90890)
- LSM14A Polyclonal Antibody (RRID:AB_2643581)
- PATL1 antibody (RRID:AB_10975274)
- Rabbit Anti-Myc tag Polyclonal Antibody, Unconjugated (RRID:AB_307014)
- Rabbit Anti-DDDDK tag Polyclonal Antibody, Unconjugated (RRID:AB_298215)
- GFP-avictoria (RRID:AB_303395)
- V5 Tag Monoclonal Antibody (SV5-Pk1) (RRID:AB_2556564)
Associated grants
- Agency: CIHR, Canada
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This is a list of tools and resources that we have found mentioned in this publication.
R Project for Statistical Computing (tool)
RRID:SCR_001905
Software environment and programming language for statistical computing and graphics. R is integrated suite of software facilities for data manipulation, calculation and graphical display. Can be extended via packages. Some packages are supplied with the R distribution and more are available through CRAN family.It compiles and runs on wide variety of UNIX platforms, Windows and MacOS.
View all literature mentionsKi67 antibody - Proliferation Marker (antibody)
RRID:AB_443209
This polyclonal targets Ki67 antibody - Proliferation Marker
View all literature mentionsPurified Mouse Anti-Ki-67 Clone B56 (antibody)
RRID:AB_393778
This monoclonal targets Ki-67
View all literature mentionsRabbit Anti-Mouse TBR2 / Eomes Polyclonal Antibody, Unconjugated (antibody)
RRID:AB_778267
This polyclonal targets Mouse TBR2 / Eomes
View all literature mentionsEOMES Monoclonal Antibody (Dan11mag), eBioscience (antibody)
RRID:AB_11043546
This monoclonal targets EOMES
View all literature mentionsNeuronal Class III beta-Tubulin (TUJ1) Monoclonal Antibody, Purified (antibody)
RRID:AB_2313773
This monoclonal targets Neuronal Class III beta-Tubulin (TUJ1) Purified
View all literature mentionsCtip2 antibody [25B6] - ChIP Grade (antibody)
RRID:AB_2064130
This monoclonal targets Ctip2
View all literature mentionsMouse Anti-Human SATB2 Monoclonal Antibody, Unconjugated, Clone SATBA4B10 (antibody)
RRID:AB_882455
This monoclonal targets Human SATB2
View all literature mentionsSox2 (C70B1) Rabbit mAb (IHC Preferred) (antibody)
RRID:AB_2194037
This monoclonal targets Sox2 (C70B1)
View all literature mentionsHuman/Mouse/Rat SOX2 Antibody (antibody)
RRID:AB_355110
This polyclonal targets SOX2
View all literature mentionsPurified anti-Pax-6 (antibody)
RRID:AB_2565003
This unknown targets Pax-6
View all literature mentionsMouse Anti-PAX6 Monoclonal Antibody, Unconjugated, Clone AD2.38 (antibody)
RRID:AB_1566562
This monoclonal targets PAX6
View all literature mentionsMouse Anti-Human DCP1A Monoclonal Antibody, Unconjugated, Clone 3G4 (antibody)
RRID:AB_530021
This monoclonal targets Human DCP1A
View all literature mentionsRat Anti-BrdU Monoclonal Antibody, Unconjugated, Clone BU1 / 75 (ICR1) (antibody)
RRID:AB_305426
This monoclonal targets BrdU
View all literature mentionsPhospho-Histone H3 (Ser10) Monoclonal Antibody (K.872.3) (antibody)
RRID:AB_11008586
This monoclonal targets Phospho-Histone H3 (Ser10)
View all literature mentionsEDC4/Ge-1 Antibody (antibody)
RRID:AB_10621246
This polyclonal targets EDC4/Ge-1
View all literature mentionsEIF4ENIF1 MaxPab mouse polyclonal antibody (B01) (antibody)
RRID:AB_1113607
This polyclonal targets EIF4ENIF1 MaxPab mouse polyclonal antibody (B01)
View all literature mentionsAnti-Green Fluorescent Protein Antibody (antibody)
RRID:AB_90890
This polyclonal targets Green Fluorescent Protein
View all literature mentionsLSM14A Polyclonal Antibody (antibody)
RRID:AB_2643581
This unknown targets LSM14A
View all literature mentionsPATL1 antibody (antibody)
RRID:AB_10975274
This polyclonal targets PATL1 antibody
View all literature mentionsRabbit Anti-Myc tag Polyclonal Antibody, Unconjugated (antibody)
RRID:AB_307014
This polyclonal targets Myc tag
View all literature mentionsRabbit Anti-DDDDK tag Polyclonal Antibody, Unconjugated (antibody)
RRID:AB_298215
This polyclonal targets DDDDK tag
View all literature mentionsV5 Tag Monoclonal Antibody (SV5-Pk1) (antibody)
RRID:AB_2556564
This monoclonal targets V5 Tag
View all literature mentionsHEK293 (cell line)
RRID:CVCL_0045
Cell line HEK293 is a Transformed cell line with a species of origin Homo sapiens (Human)
View all literature mentionsB6.129-Gt(ROSA)26Sortm1(cre/ERT2)Tyj/J (organism)
RRID:IMSR_JAX:008463
Mus musculus with name B6.129-Gt(ROSA)26Sortm1(cre/ERT2)Tyj/J from IMSR.
View all literature mentions
