Control of oligodendrocyte differentiation by the Nkx2.2 homeodomain transcription factor

Oligodendrocytes are derived from glial precursors that arise from the vent ral neural tube early in development. In the developing chicken CNS, oligod endrocyte progenitors selectively express Nkx2.2 homeodomain transcription factor, raising the possibility that Nkx2.2 may directly regulate oligoglio genesis. In this study, we have examined Nkx2.2 expression in rodent glial precursors and studied the effect of a loss of Nkx2.2 on oligodendrocyte an d astrocyte differentiation. We show that Nkx2.2 is also expressed in mamma lian oligodendrocyte progenitors and that the differentiation of MBP-positi ve and PLP-DM20-positive oligodendrocytes is dramatically retarded in Nkx2. 2-null mutants along the entire rostrocaudal axis. In contrast, no effect i s seen on astrocytic differentiation. Interestingly, absence of Nkx2.2 expr ession leads to a ventral expansion of the Olig1/Olig2 expression in neuroe pithelial cells into the Nkx2.2 domain and a consequent increase in the pro duction of Olig1/Olig2-positive and platelet-derived growth factor receptor alpha -positive oligodendrocyte progenitors. These results strongly sugges t that Nkx2.2 regulates the differentiation and/or maturation, but not the initial specification, of oligodendrocyte progenitors. Consistent with this suggestion, overproduction of Nkx2.2 protein in fibroblast cells can induc e gene expression from the proteolipid protein promoter.