Cdc42 and Rac1 signaling are both required for and act synergistically in the correct formation of myelin sheaths in the CNS.

TY - JOUR

T1 - Cdc42 and Rac1 signaling are both required for and act synergistically in the correct formation of myelin sheaths in the CNS.

AU - Thurnherr, Tina

AU - Benninger, Yves

AU - Wu, Xunwei

AU - Chrostek, Anna

AU - Krause, Sven M

AU - Nave, Klaus-Armin

AU - Franklin, Robin J M

AU - Brakebusch, Cord

AU - Suter, Ueli

AU - Relvas, João B

N1 - Keywords: Animals; Cell Movement; Cells, Cultured; Central Nervous System; Mice; Mice, Knockout; Myelin Proteins; Myelin Sheath; Signal Transduction; cdc42 GTP-Binding Protein; rac1 GTP-Binding Protein

PY - 2006

Y1 - 2006

N2 - 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.

AB - 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.

U2 - 10.1523/JNEUROSCI.2158-06.2006

DO - 10.1523/JNEUROSCI.2158-06.2006

M3 - Journal article

C2 - 17021167

SN - 0270-6474

VL - 26

SP - 10110

EP - 10119

JO - The Journal of neuroscience : the official journal of the Society for Neuroscience

JF - The Journal of neuroscience : the official journal of the Society for Neuroscience

IS - 40

ER -