The axons of mature neurons in the mammalian CNS are encased in an insulating myelin sheath, which is made by oligodendrocytes. Although the regulation of earlier stages of oligodendrocyte development is relatively well understood, it is unclear how myelination is controlled. The identification by Wang and colleagues of a new transcription regulator (Zfp488) that controls this process is, therefore, an important advance (see ). Zfp488 is an oligodendrocyte-specific zinc-finger transcriptional repressor that cooperates with the bHLH transcription factor Olig2 to promote oligodendrocyte differentiation. The researchers identified Zfp488 by screening for genes that were downregulated in the optic nerves of Olig1-null mice, in which myelin formation is severely compromised. They show that Zfp488 cooperates with Olig2 to induce ectopic and precocious oligodendrocyte differentiation in the developing chick neural tube, and report that RNAi knockdown of Zfp488 downregulates myelin gene expression in an oligodendroglial cell line. Thus, they conclude, Zfp488 acts as a transcriptional co-regulator during oligodendrocyte maturation and myelination.
