LINGO-1 negatively regulates myelination by oligodendrocytes - PubMed (original) (raw)

doi: 10.1038/nn1460. Epub 2005 May 15.

Robert H Miller, Xinhua Lee, Martin L Scott, Svetlane Shulag-Morskaya, Zhaohui Shao, Jufang Chang, Greg Thill, Melissa Levesque, Mingdi Zhang, Cathy Hession, Dinah Sah, Bruce Trapp, Zhigang He, Vincent Jung, John M McCoy, R Blake Pepinsky

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LINGO-1 negatively regulates myelination by oligodendrocytes

Sha Mi et al. Nat Neurosci. 2005 Jun.

Abstract

The control of myelination by oligodendrocytes in the CNS is poorly understood. Here we show that LINGO-1 is an important negative regulator of this critical process. LINGO-1 is expressed in oligodendrocytes. Attenuation of its function by dominant-negative LINGO-1, LINGO-1 RNA-mediated interference (RNAi) or soluble human LINGO-1 (LINGO-1-Fc) leads to differentiation and increased myelination competence. Attenuation of LINGO-1 results in downregulation of RhoA activity, which has been implicated in oligodendrocyte differentiation. Conversely, overexpression of LINGO-1 leads to activation of RhoA and inhibition of oligodendrocyte differentiation and myelination. Treatment of oligodendrocyte and neuron cocultures with LINGO-1-Fc resulted in highly developed myelinated axons that have internodes and well-defined nodes of Ranvier. The contribution of LINGO-1 to myelination was verified in vivo through the analysis of LINGO-1 knockout mice. The ability to recapitulate CNS myelination in vitro using LINGO-1 antagonists and the in vivo effects seen in the LINGO-1 knockout indicate that LINGO-1 signaling may be critical for CNS myelination.

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