Zrf1 is required to establish and maintain neural progenitor identity.
The molecular mechanisms underlying specification from embryonic stem cells (ESCs) and maintenance of neural progenitor cells (NPCs) are largely unknown. Recently, we reported that the Zuotin-related factor 1 (Zrf1) is necessary for chromatin displacement of the Polycomb-repressive complex 1 (PRC1). We found that Zrf1 is required for NPC specification from ESCs and that it promotes the expression of NPC markers, including the key regulator Pax6. Moreover, Zrf1 is essential to establish and maintain Wnt ligand expression levels, which are necessary for NPC self-renewal. Reactivation of proper Wnt signaling in Zrf1-depleted NPCs restores Pax6 expression and the self-renewal capacity. ESC-derived NPCs in vitro resemble most of the characteristics of the self-renewing NPCs located in the developing embryonic cortex, which are termed radial glial cells (RGCs). Depletion of Zrf1 in vivo impairs the expression of key self-renewal regulators and Wnt ligand genes in RGCs. Thus, we demonstrate that Zrf1 plays an essential role in NPC generation and maintenance.
Centre for Genomic Regulation (CRG), Universitat Pompeu Fabra, 08003 Barcelona, Spain;
Luigi
L
Aloia
Bruno
B
Di Stefano
Alessandro
A
Sessa
Lluis
L
Morey
Alexandra
A
Santanach
Arantxa
A
Gutierrez
Luca
L
Cozzuto
Salvador Aznar
SA
Benitah
Thomas
T
Graf
Vania
V
Broccoli
Luciano
L
Di Croce
D000818:Animals; D002454:Cell Differentiation; D002460:Cell Line; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D053595:Embryonic Stem Cells / Q000166:cytology; D005136:Eye Proteins / Q000235:genetics; D018507:Gene Expression Regulation, Developmental; D018398:Homeodomain Proteins / Q000235:genetics; D006801:Humans; D008024:Ligands; D051379:Mice; D018832:Molecular Chaperones; D054258:Neural Plate / Q000166:cytology* / Q000378:metabolism*; D055495:Neurogenesis / Q000235:genetics; D015513:Oncogene Proteins / Q000235:genetics / Q000378:metabolism*; D000071841:PAX6 Transcription Factor; D051761:Paired Box Transcription Factors / Q000235:genetics; D016601:RNA-Binding Proteins; D012097:Repressor Proteins / Q000235:genetics; D015398:Signal Transduction; D013234:Stem Cells / Q000166:cytology* / Q000378:metabolism*; D051153:Wnt Proteins / Q000378:metabolism
D004268:DNA-Binding Proteins; C414672:DNAJC2 protein, human; D005136:Eye Proteins; D018398:Homeodomain Proteins; D008024:Ligands; D018832:Molecular Chaperones; D015513:Oncogene Proteins; D000071841:PAX6 Transcription Factor; C000605730:PAX6 protein, human; D051761:Paired Box Transcription Factors; C000605732:Pax6 protein, mouse; D016601:RNA-Binding Proteins; D012097:Repressor Proteins; D051153:Wnt Proteins
Wnt ligands; embryonic stem cell; neural specification