title: Chemical inducers and transcriptional markers of oligodendrocyte differentiation.
abstract: Oligodendrocytes generate and maintain myelin, which is essential for axonal function and protection of the mammalian central nervous system. To advance our molecular understanding of differentiation by these cells, we screened libraries of pharmacologically active compounds and identified inducers of differentiation of Oli-neu, a stable cell line of mouse oligodendrocyte precursors (OPCs). We identified four broad classes of inducers, namely, forskolin/cAMP (protein kinase A activators), steroids (glucocorticoids and retinoic acid), ErbB2 inhibitors, and nucleoside analogs, and confirmed the activity of these compounds on rat primary oligodendrocyte precursors and mixed cortical cultures. We also analyzed transcriptional responses in the chemically induced mouse and rat OPC differentiation processes and compared these with earlier studies. We confirm the view that ErbB2 is a natural signaling component that is required for OPC proliferation, whereas ErbB2 inhibition or genetic knockdown results in OPC differentiation.
authors.affiliation: Merck Serono, Geneva 1202, Switzerland.
authors.forename: Lara
authors.initials: L
authors.lastname: Joubert
authors.forename: Isabelle
authors.initials: I
authors.lastname: Foucault
authors.forename: Yves
authors.initials: Y
authors.lastname: Sagot
authors.forename: Lilia
authors.initials: L
authors.lastname: Bernasconi
authors.forename: François
authors.initials: F
authors.lastname: Duval
authors.forename: Chantal
authors.initials: C
authors.lastname: Alliod
authors.forename: Marie-José
authors.initials: MJ
authors.lastname: Frossard
authors.forename: Rosanna
authors.initials: R
authors.lastname: Pescini Gobert
authors.forename: Marie-Laure
authors.initials: ML
authors.lastname: Curchod
authors.forename: Catherine
authors.initials: C
authors.lastname: Salvat
authors.forename: Anthony
authors.initials: A
authors.lastname: Nichols
authors.forename: Sandrine
authors.initials: S
authors.lastname: Pouly
authors.forename: Christian
authors.initials: C
authors.lastname: Rommel
authors.forename: Arthur
authors.initials: A
authors.lastname: Roach
authors.forename: Rob
authors.initials: R
authors.lastname: Hooft van Huijsduijnen
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D015415:Biomarkers / Q000032:analysis / Q000378:metabolism; D002454:Cell Differentiation / Q000187:drug effects / Q000502:physiology*; D002460:Cell Line; D049109:Cell Proliferation / Q000187:drug effects*; D002478:Cells, Cultured; D002540:Cerebral Cortex / Q000166:cytology / Q000378:metabolism*; D005576:Colforsin / Q000378:metabolism / Q000494:pharmacology; D000242:Cyclic AMP / Q000378:metabolism / Q000494:pharmacology; D036341:Intercellular Signaling Peptides and Proteins / Q000235:genetics / Q000378:metabolism / Q000494:pharmacology; D051379:Mice; D009836:Oligodendroglia / Q000166:cytology / Q000378:metabolism*; D034622:RNA Interference / Q000502:physiology; D051381:Rats; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000037:antagonists & inhibitors / Q000172:deficiency / Q000235:genetics; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology*; D013234:Stem Cells / Q000166:cytology / Q000378:metabolism*; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism / Q000494:pharmacology
chemical_list: D015415:Biomarkers; D005576:Colforsin; D000242:Cyclic AMP; D036341:Intercellular Signaling Peptides and Proteins; D018719:Erb-b2 Receptor Tyrosine Kinases; D014157:Transcription Factors; C524056:Erbb2 protein, mouse