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Title Zrf1 is required to establish and maintain neural progenitor identity

Authors 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
Date 2014-01-15

Publisher Genes & Development
DOI 10.1101/gad.228510.113
Tag Animals, Cell Differentiation, Cell Line, DNA-Binding Proteins, Embryonic Stem Cells, Eye Proteins, Gene Expression Regulation, Developmental, Homeodomain Proteins, Humans, Ligands, Mice, Neural Plate, Neurogenesis, Oncogene Proteins, PAX6 Transcription Factor, Paired Box Transcription Factors, Repressor Proteins, Signal Transduction, Stem Cells, Wnt Proteins, Wnt ligands, embryonic stem cell, neural specification

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.

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