Zrf1 is required to establish and maintain neural progenitor identity

Luigi Aloia, Bruno Di Stefano, Alessandro Sessa, Lluis Morey, Alexandra Santanach, Arantxa Gutierrez, Luca Cozzuto, Salvador Aznar Benitah, Thomas Graf, Vania Broccoli, Luciano Di Croce

Research output: Contribution to journalArticle

18 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)182-197
Number of pages16
JournalGenes and Development
Volume28
Issue number2
DOIs
Publication statusPublished - Jan 15 2014

Fingerprint

Stem Cells
Embryonic Stem Cells
Ependymoglial Cells
Polycomb Repressive Complex 1
Maintenance
Ligands
Chromatin
Genes

Keywords

  • Embryonic stem cell
  • Neural specification
  • Wnt ligands

ASJC Scopus subject areas

  • Genetics
  • Developmental Biology

Cite this

Aloia, L., Di Stefano, B., Sessa, A., Morey, L., Santanach, A., Gutierrez, A., ... Di Croce, L. (2014). Zrf1 is required to establish and maintain neural progenitor identity. Genes and Development, 28(2), 182-197. https://doi.org/10.1101/gad.228510.113

Zrf1 is required to establish and maintain neural progenitor identity. / Aloia, Luigi; Di Stefano, Bruno; Sessa, Alessandro; Morey, Lluis; Santanach, Alexandra; Gutierrez, Arantxa; Cozzuto, Luca; Benitah, Salvador Aznar; Graf, Thomas; Broccoli, Vania; Di Croce, Luciano.

In: Genes and Development, Vol. 28, No. 2, 15.01.2014, p. 182-197.

Research output: Contribution to journalArticle

Aloia, L, Di Stefano, B, Sessa, A, Morey, L, Santanach, A, Gutierrez, A, Cozzuto, L, Benitah, SA, Graf, T, Broccoli, V & Di Croce, L 2014, 'Zrf1 is required to establish and maintain neural progenitor identity', Genes and Development, vol. 28, no. 2, pp. 182-197. https://doi.org/10.1101/gad.228510.113
Aloia L, Di Stefano B, Sessa A, Morey L, Santanach A, Gutierrez A et al. Zrf1 is required to establish and maintain neural progenitor identity. Genes and Development. 2014 Jan 15;28(2):182-197. https://doi.org/10.1101/gad.228510.113
Aloia, Luigi ; Di Stefano, Bruno ; Sessa, Alessandro ; Morey, Lluis ; Santanach, Alexandra ; Gutierrez, Arantxa ; Cozzuto, Luca ; Benitah, Salvador Aznar ; Graf, Thomas ; Broccoli, Vania ; Di Croce, Luciano. / Zrf1 is required to establish and maintain neural progenitor identity. In: Genes and Development. 2014 ; Vol. 28, No. 2. pp. 182-197.
@article{1cffc13a668149539a944c1fac0d40e1,
title = "Zrf1 is required to establish and maintain neural progenitor identity",
abstract = "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.",
keywords = "Embryonic stem cell, Neural specification, Wnt ligands",
author = "Luigi Aloia and {Di Stefano}, Bruno and Alessandro Sessa and Lluis Morey and Alexandra Santanach and Arantxa Gutierrez and Luca Cozzuto and Benitah, {Salvador Aznar} and Thomas Graf and Vania Broccoli and {Di Croce}, Luciano",
year = "2014",
month = "1",
day = "15",
doi = "10.1101/gad.228510.113",
language = "English",
volume = "28",
pages = "182--197",
journal = "Genes and Development",
issn = "0890-9369",
publisher = "Cold Spring Harbor Laboratory Press",
number = "2",

}

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

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

UR - http://www.scopus.com/inward/record.url?scp=84892685799&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84892685799&partnerID=8YFLogxK

U2 - 10.1101/gad.228510.113

DO - 10.1101/gad.228510.113

M3 - Article

VL - 28

SP - 182

EP - 197

JO - Genes and Development

JF - Genes and Development

SN - 0890-9369

IS - 2

ER -