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.