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          Institute: MPI für experimentelle Medizin     Collection: Neurogenetics     Display Documents



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ID: 292147.0, MPI für experimentelle Medizin / Neurogenetics
Cdc42 and Rac1 signaling are both required for and act synergistically in the correct formation of myelin sheaths in the CNS
Authors:Thurnherr, Tina; Benninger, Yves; Wu, Xunwei; Chrostek, Anna; Krause, Sven M.; Nave, Klaus-Armin; Franklin, Robin J. M.; Brakebusch, Cord; Suter, Ueli; Relvas, Joao B.
Language:English
Date of Publication (YYYY-MM-DD):2006-10
Title of Journal:Journal of Neuroscience
Journal Abbrev.:J. Neurosci.
Volume:26
Issue / Number:40
Start Page:10110
End Page:10119
Review Status:Peer-review
Audience:Experts Only
Abstract / Description:The formation of myelin sheaths in the CNS is the result of a complex series of events involving oligodendrocyte progenitor cell (OPC) proliferation, directed migration, and the morphological changes associated with axon ensheathment and myelination. To examine the role of Rho GTPases in oligodendrocyte biology, we have used a conditional tissue-specific gene-targeting approach. Ablation of Cdc42 in cells of the oligodendrocyte lineage did not affect OPC proliferation, directed migration, or in vitro differentiation, but it led to the formation of a unique and stage-specific myelination phenotype. This was characterized by the extraordinary enlargement of the inner tongue of the oligodendrocyte process and concomitant formation of a myelin outfolding as a result of abnormal accumulation of cytoplasm in this region. Ablation of Rac1 also resulted in the abnormal accumulation of cytoplasm in the inner tongue of the oligodendrocyte process, and we provide genetic evidence that rac1 synergizes with cdc42 in a gene dosage-dependent way to regulate myelination.
Free Keywords:cdc42; rac1; Rho GTPase; myelin; CNS; oligodendrocyte CELL-CELL ADHESION; RHO-GTPASES; SPINAL-CORD; GROWTH-FACTOR; OLIGODENDROCYTES; MIGRATION; DIFFERENTIATION; BETA-1-INTEGRIN; ORGANIZATION; CYTOSKELETON
External Publication Status:published
Document Type:Article
Communicated by:Klaus-Armin Nave
Affiliations:MPI für experimentelle Medizin/Neurogenetics
Relations:Has References-DOI:10.1523/JNEUROSCI.2158-06.2006
Identifiers:ISSN:0270-6474 [ID No:1]
ISI:000241192700005 [ID No:2]
ISI:000241192700005 [ID No:3]
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