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bioRxiv · 10.1101/2021.08.13.456269

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

Radecki, D. Z.·Wang, A. R.·Johnson, A. S.·Overman, C. A.·Thatcher, M. M.·Iyer, G.·Samanta, J.
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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.

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Radecki, D. Z., Wang, A. R., Johnson, A. S., Overman, C. A., Thatcher, M. M., Iyer, G., Samanta, J.. 2021-08-14. Gpnmb inhibits oligodendrocyte differentiation of adult neural stem cells by amplifying TGFβ1 signaling. https://doi.org/10.1101/2021.08.13.456269

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