Ren

Author:

Gallo Rita1,Zazzeroni Francesca1,Alesse Edoardo1,Mincione Claudia2,Borello Ugo34,Buanne Pasquale1,D'Eugenio Roberta1,Mackay Andrew R.1,Argenti Beatrice2,Gradini Roberto2,Russo Matteo A.2,Maroder Marella2,Cossu Giulio34,Frati Luigi25,Screpanti Isabella26,Gulino Alberto2

Affiliation:

1. Department of Experimental Medicine, University of L'Aquila, 67100 L'Aquila, Italy

2. Department of Experimental Medicine and Pathology, Pasteur Institute, University La Sapienza, 00161 Rome, Italy

3. Department of Histology and Embryology, Pasteur Institute, University La Sapienza, 00161 Rome, Italy

4. Stem Cell Research Institute, Dibit, H. San Raffaele, 20132 Milan, Italy

5. Neuromed Institute, 86077 Pozzilli, Italy

6. Cenci-Bolognetti Foundation, Pasteur Institute, University La Sapienza, 00161 Rome, Italy

Abstract

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.

Publisher

Rockefeller University Press

Subject

Cell Biology

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