| First Author | Mi S | Year | 2005 |
| Journal | Nat Neurosci | Volume | 8 |
| Issue | 6 | Pages | 745-51 |
| PubMed ID | 15895088 | Mgi Jnum | J:99078 |
| Mgi Id | MGI:3581086 | Doi | 10.1038/nn1460 |
| Citation | Mi S, et al. (2005) LINGO-1 negatively regulates myelination by oligodendrocytes. Nat Neurosci 8(6):745-51 |
| abstractText | 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. |
