Musashi1 RNA-binding protein regulates oligodendrocyte lineage cell differentiation and survival.

Expression of Musashi1 (Msi1), an evolutionarily conserved RNA-binding protein, in neural stem cells of the subventricular zone in the postnatal and adult CNS indicates a potential role in the generation of oligodendrocytes. We now show Msi1 expression in a subset of oligodendrocyte progenitor (OP) cells in white matter areas temporally and spatially associated with oligodendrogenesis in the postnatal CNS. Msi1 function was evaluated by infection of OP cells with retroviral transduction of Msi1 or knockdown of endogenous Msi1. Retroviral expression of Msi1 significantly reduced the proportion of mature oligodendrocytes generated from OP cells in vitro and in vivo during myelination. Msi1 transduction also promoted OP survival, particularly under conditions of challenge from oxidative stress, while Msi1 siRNA knockdown resulted in dramatic OP cell death. Furthermore, in experimental demyelination Msi1 expression was increased among cells associated with lesions, including OP cells, indicating a potential role in the generation of remyelinating oligodendrocytes.