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

22 Scopus citations

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 (US)
Pages (from-to)182-197
Number of pages16
JournalGenes and Development
Volume28
Issue number2
DOIs
StatePublished - Jan 15 2014

Keywords

  • Embryonic stem cell
  • Neural specification
  • Wnt ligands

ASJC Scopus subject areas

  • Genetics
  • Developmental Biology

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  • Cite this

    Aloia, L., Di Stefano, B., Sessa, A., Morey, L., Santanach, A., Gutierrez, A., Cozzuto, L., Benitah, S. A., Graf, T., Broccoli, V., & 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