TY - JOUR
T1 - Zrf1 is required to establish and maintain neural progenitor identity
AU - Aloia, Luigi
AU - Di Stefano, Bruno
AU - Sessa, Alessandro
AU - Morey, Lluis
AU - Santanach, Alexandra
AU - Gutierrez, Arantxa
AU - Cozzuto, Luca
AU - Benitah, Salvador Aznar
AU - Graf, Thomas
AU - Broccoli, Vania
AU - Di Croce, Luciano
N1 - Copyright:
Copyright 2014 Elsevier B.V., All rights reserved.
PY - 2014/1/15
Y1 - 2014/1/15
N2 - 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.
AB - 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.
KW - Embryonic stem cell
KW - Neural specification
KW - Wnt ligands
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U2 - 10.1101/gad.228510.113
DO - 10.1101/gad.228510.113
M3 - Article
C2 - 24449271
AN - SCOPUS:84892685799
VL - 28
SP - 182
EP - 197
JO - Genes and Development
JF - Genes and Development
SN - 0890-9369
IS - 2
ER -