Gli1 expressing neural stem cells, in the subventricular zone of the adult mammalian brain, respond to demyelination injury by differentiating into oligodendrocytes. We have identified Gpnmb as a novel regulator of oligodendrogenesis in Gli1 neural stem cells, whose expression is induced by TGFβ1 signaling via Gli1, in response to a demyelinating injury. Upregulation of Gpnmb further activates the TGFβ1 pathway by increasing the expression of the TGFβ1 binding receptor subunit, TGFβR2. Thus the TGFβ1→Gli1→Gpnmb→TGFβR2 signaling pathway forms a feed forward loop for sustained activation of TGFβ1 signaling in Gli1 neural stem cells, resulting in inhibition of their differentiation into mature oligodendrocytes following demyelination.
LINGO-1 Regulates Oligodendrocyte Differentiation through the Cytoplasmic Gelsolin Signaling Pathway
