Induced expression of Olig2 is sufficient for oligodendrocyte specification but not for motoneuron specification and astrocyte repression.
To dissect out interactions between the transcription factor Olig2 and other intrinsic and extrinsic factors in neural cell fate determination, we established a mouse embryonic stem (ES) cell line with induced expression of Olig2 along neural differentiation. During neuronal differentiation, both the control and Olig2-induced groups produced a similar proportion of HB9-expressing motoneurons in the presence of retinoic acid (RA) and sonic hedgehog (SHH), but both generated few motoneurons in the absence of SHH. Induced Olig2 expression did not alter the pattern of gene transcription without SHH, suggesting that Olig2 requires cooperation with RA and SHH for motoneuron specification. During glial differentiation, the Olig2-induced group generated significantly more oligodendrocytes and fewer neurons and astrocytes than the control group. This effect was not blocked by inhibition of SHH signaling, suggesting that Olig2 bypasses the need of SHH in oligodendrocyte specification. However, treatment with ciliary neurotropic factor (CNTF) markedly increased astrocyte and decreased oligodendrocyte differentiation even when Olig2 is sustained in the nuclei, suggesting that Olig2 cannot bypass the CNTF-STAT signaling to repress astrocyte differentiation.
Du
Zhong-Wei
ZW
Department of Anatomy, School of Medicine and Public Health, Waisman Center, WiCell Institute, University of Wisconsin, Madison, WI 53705, USA.
Li
Xue-Jun
XJ
Nguyen
Giang D
GD
Zhang
Su-Chun
SC
D000818:Animals; D001253:Astrocytes / Q000378:metabolism*; D051792:Basic Helix-Loop-Helix Proteins / Q000235:genetics / Q000378:metabolism*; D002454:Cell Differentiation / Q000187:drug effects / Q000502:physiology*; D002460:Cell Line; D002642:Chick Embryo; D020934:Ciliary Neurotrophic Factor / Q000494:pharmacology; D004622:Embryo, Mammalian; D018507:Gene Expression Regulation, Developmental / Q000187:drug effects / Q000502:physiology*; D053823:Hedgehog Proteins / Q000494:pharmacology; D018398:Homeodomain Proteins / Q000378:metabolism; D007150:Immunohistochemistry / Q000379:methods; D051379:Mice; D009046:Motor Neurons / Q000378:metabolism*; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism*; D000076104:Oligodendrocyte Transcription Factor 2; D009836:Oligodendroglia / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction / Q000379:methods; D013234:Stem Cells / Q000187:drug effects / Q000502:physiology; D014157:Transcription Factors / Q000378:metabolism; D014162:Transfection / Q000379:methods; D014212:Tretinoin / Q000494:pharmacology
D051792:Basic Helix-Loop-Helix Proteins; D020934:Ciliary Neurotrophic Factor; D053823:Hedgehog Proteins; D018398:Homeodomain Proteins; D009419:Nerve Tissue Proteins; D000076104:Oligodendrocyte Transcription Factor 2; D012333:RNA, Messenger; D014157:Transcription Factors; D014212:Tretinoin; C512773:Olig2 protein, mouse; C465570:Shh protein, mouse; C084059:Hb9 protein, mouse