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Nkx2.2 homeodomain transcriptional factor is initially expressed in differentiating oligodendrocyte precursor cells (OPCs) and plays a critical role in regulating the differentiation process.Recent studies showed that Nkx2.2 expression in oligodendrocytes is rapidly down-regulated as OPCs undergo terminal differentiation, but regained in mature myelinating oligodendrocytes in mature OLs.This biphasic pattern of Nkx2.2 expression in oligodendrocyte lineage suggests that Nkx2.2 may have distinct functions during oligodendrocyte lineage progression.To define the role of Nkx2.2 in oligodendrocyte differentiation and maturation, we have used tetracycline-inducible expression system to specifically induce Nkx2.2 expression in oligodendrocyte cells at different developmental stages.Our results demonstrated that Nkx2.2 promoted OPC differentiation at embryonic stages, but repressed myelin protein production at neonatal stages, indicating that regulation of oligodendrocyte differentiation and myelin gene expression by Nkx2.2 is stage-dependent.