REN: A novel, developmentally regulated gene that promotes neural cell differentiation

Rita Gallo, Francesca Zazzeroni, Edoardo Alesse, Claudia Mincione, Ugo Borello, Pasquale Buanne, Roberta D'Eugenio, Andrew R. Mackay, Beatrice Argenti, Roberto Gradini, Matteo A. Russo, Marella Maroder, Giulio Cossu, Luigi Frati, Isabella Screpanti, Alberto Gulino

Research output: Contribution to journalArticlepeer-review


Expansion and fate choice of pluripotent stem cells along the neuroectodermal lineage is regulated by a number of signals, including EGF, retinoic acid, and NGF, which also control the proliferation and differentiation of central nervous system (CNS) and peripheral nervous system (PNS) neural progenitor cells. We report here the identification of a novel gene, REN, upregulated by neurogenic signals (retinoic acid, EGF, and NGF) in pluripotent embryonal stem (ES) cells and neural progenitor cell lines in association with neurotypic differentiation. Consistent with a role in neural promotion, REN overexpression induced neuronal differentiation as well as growth arrest and p27Kip1 expression in CNS and PNS neural progenitor cell lines, and its inhibition impaired retinoic acid induction of neurogenin-1 and NeuroD expression. REN expression is developmentally regulated, initially detected in the neural fold epithelium of the mouse embryo during gastrulation, and subsequently throughout the ventral neural tube, the outer layer of the ventricular encephalic neuroepithelium and in neural crest derivatives including dorsal root ganglia. We propose that REN represents a novel component of the neurogenic signaling cascade induced by retinoic acid, EGF, and NGF, and is both a marker and a regulator of neuronal differentiation.

Original languageEnglish
Pages (from-to)731-740
Number of pages10
JournalJournal of Cell Biology
Issue number4
Publication statusPublished - Aug 19 2002


  • EGF
  • Neural cell
  • Neurogenic bHLH
  • NGF
  • Retinoic acid

ASJC Scopus subject areas

  • Cell Biology

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