Chemical inducers and transcriptional markers of oligodendrocyte differentiation.
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.
Joubert
Lara
L
Merck Serono, Geneva 1202, Switzerland.
Foucault
Isabelle
I
Sagot
Yves
Y
Bernasconi
Lilia
L
Duval
François
F
Alliod
Chantal
C
Frossard
Marie-José
MJ
Pescini Gobert
Rosanna
R
Curchod
Marie-Laure
ML
Salvat
Catherine
C
Nichols
Anthony
A
Pouly
Sandrine
S
Rommel
Christian
C
Roach
Arthur
A
Hooft van Huijsduijnen
Rob
R
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
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