Zrf1 is required to establish and maintain neural progenitor identity

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  • dc.contributor.author Aloia, Luigi
  • dc.contributor.author Di Stefano, Bruno, 1984-
  • dc.contributor.author Sessa, Alessandro
  • dc.contributor.author Morey, Lluis
  • dc.contributor.author Santanach, Alexandra
  • dc.contributor.author Gutierrez, Arantxa
  • dc.contributor.author Cozzuto, Luca
  • dc.contributor.author Aznar Benitah, Salvador
  • dc.contributor.author Graf, T. (Thomas)
  • dc.contributor.author Broccoli, Vania
  • dc.contributor.author Di Croce, Luciano
  • dc.date.accessioned 2023-02-13T08:54:59Z
  • dc.date.available 2023-02-13T08:54:59Z
  • dc.date.issued 2014
  • dc.description.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.
  • dc.description.sponsorship We are grateful to Dr. Veronica A. Raker for critical reading of the manuscript, and Dr. Austin Smith for Sox1-GFP cells. We also thank Dr. Pedro Vizán, Dr. Malte Beringer, Dr. Pia Cosma, Dr. Luigi Ombrato, and Dr. Serena Mirra for helpful discussions. We are indebted to the CRG animal facility, CRG FACS facility, and CRG microarray and genomic facility. This work was supported by grants from the Spanish ‘‘Ministerio de Educación y Ciencia’’ (BFU2010-18692), the Agència de Gestió d’Ajuts Universitaris i de Recerca (AGAUR), the American Institute for Cancer Research (AICR) (10-0177), and the European Commission’s 7th Framework Program 4DCellFate (grant no. 277899) to L.D.C., and the AdERC (grant 340527) to V.B. B.D.S has a la Caixa International PhD fellowship, and A.S. has a Formación de Personal Investigador (FPI) PhD fellowship.
  • dc.format.mimetype application/pdf
  • dc.identifier.citation 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 Dev. 2014 Jan 15;28(2):182-97. DOI: 10.1101/gad.228510.113
  • dc.identifier.doi http://dx.doi.org/10.1101/gad.228510.113
  • dc.identifier.issn 0890-9369
  • dc.identifier.uri http://hdl.handle.net/10230/55734
  • dc.language.iso eng
  • dc.publisher Cold Spring Harbor Laboratory Press (CSHL Press)
  • dc.relation.ispartof Genes & development. 2014 Jan 15;28(2):182-97
  • dc.relation.projectID info:eu-repo/grantAgreement/EC/FP7/277899
  • dc.relation.projectID info:eu-repo/grantAgreement/EC/FP7/340527
  • dc.relation.projectID info:eu-repo/grantAgreement/ES/3PN/BFU2010-18692
  • dc.rights ©2014 Aloia et al. This article is distributed exclusively by Cold Spring Harbor Laboratory Press for the first six months after the fullissue publication date (see http://genesdev.cshlp.org/site/misc/terms.xhtml). After six months, it is available under a Creative Commons License (Attribution-NonCommercial 3.0 Unported), as described at http://creativecommons.org/licenses/by-nc/3.0/.
  • dc.rights.accessRights info:eu-repo/semantics/openAccess
  • dc.rights.uri http://creativecommons.org/licenses/by-nc/3.0/
  • dc.subject.keyword Wnt ligands
  • dc.subject.keyword Embryonic stem cell
  • dc.subject.keyword Neural specification
  • dc.title Zrf1 is required to establish and maintain neural progenitor identity
  • dc.type info:eu-repo/semantics/article
  • dc.type.version info:eu-repo/semantics/publishedVersion

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