Phosphorylation State of Olig2 Regulates Proliferation of Neural Progenitors

The bHLH transcription factors that regulate early development of the central nervous system can generally be classified as either antineural or proneural. Initial expression of antineural factors prevents cell cycle exit and thereby expands the pool of neural progenitors. Subsequent (and typically transient) expression of proneural factors promotes cell cycle exit, subtype specification, and differentiation. Against this backdrop, the bHLH transcription factor Olig2 in the oligodendrocyte lineage is unorthodox, showing antineural functions in multipotent CNS progenitor cells but also sustained expression and proneural functions in the formation of oligodendrocytes. We show here that the proliferative function of Olig2 is controlled by developmentally regulated phosphorylation of a conserved triple serine motif within the amino-terminal domain. In the phosphorylated state, Olig2 maintains antineural (i.e., promitotic) functions that are reflected in human glioma cells and in a genetically defined murine model of primary glioma. ► The bHLH transcription factor Olig2 is a phosphoprotein ► The phosphorylation state of Olig2 is developmentally regulated ► When phosphorylated, Olig2 stimulates proliferation of neural progenitors ► Phosphorylation of Olig2 correlates with malignant potential in astrocytoma