REN: a novel, developmentally regulated gene that promotes neural cell differentiation.
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.
Department of Experimental Medicine, University of L'Aquila, 67100 L'Aquila, Italy.
Rita
R
Gallo
Francesca
F
Zazzeroni
Edoardo
E
Alesse
Claudia
C
Mincione
Ugo
U
Borello
Pasquale
P
Buanne
Roberta
R
D'Eugenio
Andrew R
AR
Mackay
Beatrice
B
Argenti
Roberto
R
Gradini
Matteo A
MA
Russo
Marella
M
Maroder
Giulio
G
Cossu
Luigi
L
Frati
Isabella
I
Screpanti
Alberto
A
Gulino
D000595:Amino Acid Sequence; D000818:Animals; D051792:Basic Helix-Loop-Helix Proteins; D015415:Biomarkers; D018797:Cell Cycle Proteins / Q000235:genetics / Q000378:metabolism; D002454:Cell Differentiation / Q000502:physiology*; D002455:Cell Division / Q000502:physiology; D002478:Cells, Cultured; D003001:Cloning, Molecular; D050760:Cyclin-Dependent Kinase Inhibitor p27; D018076:DNA, Complementary; D004815:Epidermal Growth Factor / Q000494:pharmacology; D018507:Gene Expression Regulation, Developmental / Q000187:drug effects / Q000502:physiology; D051379:Mice; D008969:Molecular Sequence Data; D020932:Nerve Growth Factor / Q000494:pharmacology; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D009474:Neurons / Q000166:cytology*; D013234:Stem Cells / Q000378:metabolism; D014157:Transcription Factors; D014166:Transferases; D014212:Tretinoin / Q000494:pharmacology; D025521:Tumor Suppressor Proteins / Q000235:genetics / Q000378:metabolism
D051792:Basic Helix-Loop-Helix Proteins; D015415:Biomarkers; D018797:Cell Cycle Proteins; D050760:Cyclin-Dependent Kinase Inhibitor p27; D018076:DNA, Complementary; D004815:Epidermal Growth Factor; D020932:Nerve Growth Factor; D009419:Nerve Tissue Proteins; D014157:Transcription Factors; D014166:Transferases; D014212:Tretinoin; D025521:Tumor Suppressor Proteins; C493961:Cdkn1b protein, mouse; C093564:Neurogenic differentiation factor 1; C486336:Neurog1 protein, mouse; C466095:Kctd11 protein, mouse