Gpnmb inhibits oligodendrocyte differentiation of adult neural stem cells by amplifying TGFβ1 signaling

Abstract

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 TGF{beta}1 signaling via Gli1, in response to a demyelinating injury. Upregulation of Gpnmb further activates the TGF{beta}1 pathway by increasing the expression of the TGF{beta}1 binding receptor subunit, TGF{beta}R2. Thus the TGF{beta}1[->]Gli1[->]Gpnmb[->]TGF{beta}R2 signaling pathway forms a feed forward loop for sustained activation of TGF{beta}1 signaling in Gli1 neural stem cells, resulting in inhibition of their differentiation into mature oligodendrocytes following demyelination.