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rdf:type |
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lifeskim:mentions |
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pubmed:issue |
6
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pubmed:dateCreated |
2005-5-26
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pubmed: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.
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pubmed:language |
eng
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pubmed:journal |
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pubmed:citationSubset |
IM
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pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/FYN protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/Fyn protein, mouse,
http://linkedlifedata.com/resource/pubmed/chemical/Fyn protein, rat,
http://linkedlifedata.com/resource/pubmed/chemical/LINGO1 protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/Membrane Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Myelin-Associated Glycoprotein,
http://linkedlifedata.com/resource/pubmed/chemical/Nerve Tissue Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Proto-Oncogene Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Proto-Oncogene Proteins c-fyn,
http://linkedlifedata.com/resource/pubmed/chemical/Receptors, Cell Surface,
http://linkedlifedata.com/resource/pubmed/chemical/rhoA GTP-Binding Protein,
http://linkedlifedata.com/resource/pubmed/chemical/src-Family Kinases
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pubmed:status |
MEDLINE
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pubmed:month |
Jun
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pubmed:issn |
1097-6256
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pubmed:author |
pubmed-author:ChangJufangJ,
pubmed-author:HeZhigangZ,
pubmed-author:HessionCathyC,
pubmed-author:JungVincentV,
pubmed-author:LeeXinhuaX,
pubmed-author:LevesqueMelissaM,
pubmed-author:McCoyJohn MJM,
pubmed-author:MillerRobert HRH,
pubmed-author:PepinskyR BlakeRB,
pubmed-author:SahDinahD,
pubmed-author:ScottMartin LML,
pubmed-author:ShaoZhaohuiZ,
pubmed-author:Shulag-MorskayaSvetlaneS,
pubmed-author:ThillGregG,
pubmed-author:TrappBruceB,
pubmed-author:UsaSS,
pubmed-author:ZhangMingdiM
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pubmed:issnType |
Print
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pubmed:volume |
8
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
745-51
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pubmed:dateRevised |
2009-11-19
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pubmed:meshHeading |
pubmed-meshheading:15895088-Animals,
pubmed-meshheading:15895088-Cell Differentiation,
pubmed-meshheading:15895088-Cells, Cultured,
pubmed-meshheading:15895088-Central Nervous System,
pubmed-meshheading:15895088-Coculture Techniques,
pubmed-meshheading:15895088-Down-Regulation,
pubmed-meshheading:15895088-Gene Expression Regulation, Developmental,
pubmed-meshheading:15895088-Humans,
pubmed-meshheading:15895088-Membrane Proteins,
pubmed-meshheading:15895088-Mice,
pubmed-meshheading:15895088-Mice, Knockout,
pubmed-meshheading:15895088-Microscopy, Electron, Transmission,
pubmed-meshheading:15895088-Myelin Sheath,
pubmed-meshheading:15895088-Myelin-Associated Glycoprotein,
pubmed-meshheading:15895088-Nerve Fibers, Myelinated,
pubmed-meshheading:15895088-Nerve Tissue Proteins,
pubmed-meshheading:15895088-Oligodendroglia,
pubmed-meshheading:15895088-Proto-Oncogene Proteins,
pubmed-meshheading:15895088-Proto-Oncogene Proteins c-fyn,
pubmed-meshheading:15895088-RNA Interference,
pubmed-meshheading:15895088-Ranvier's Nodes,
pubmed-meshheading:15895088-Rats,
pubmed-meshheading:15895088-Rats, Long-Evans,
pubmed-meshheading:15895088-Receptors, Cell Surface,
pubmed-meshheading:15895088-Signal Transduction,
pubmed-meshheading:15895088-rhoA GTP-Binding Protein,
pubmed-meshheading:15895088-src-Family Kinases
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pubmed:year |
2005
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pubmed:articleTitle |
LINGO-1 negatively regulates myelination by oligodendrocytes.
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pubmed:affiliation |
Department of Discovery Biology, Biogen Idec, Inc., 14 Cambridge Center, Cambridge, Massachusetts 02142, USA. sha.mi@biogenidec.com
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pubmed:publicationType |
Journal Article
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