Cthrc1 is a negative regulator of myelination in schwann cells

Authors

  • Caroline Apra,

    1. Ecole Normale Supérieure, IBENS, Developmental Biology Section, 75230 Paris cedex 05, France
    2. INSERM, U1024, 75230 Paris cedex 05, France
    3. CNRS, UMR 8197, 75230 Paris cedex 05, France
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  • Laurence Richard,

    1. Laboratoire de Neurologie, CHU Dupuytren, 87042 Limoges, France
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  • Fanny Coulpier,

    1. Ecole Normale Supérieure, IBENS, Developmental Biology Section, 75230 Paris cedex 05, France
    2. INSERM, U1024, 75230 Paris cedex 05, France
    3. CNRS, UMR 8197, 75230 Paris cedex 05, France
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  • Corinne Blugeon,

    1. Ecole Normale Supérieure, IBENS, Developmental Biology Section, 75230 Paris cedex 05, France
    2. INSERM, U1024, 75230 Paris cedex 05, France
    3. CNRS, UMR 8197, 75230 Paris cedex 05, France
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  • Pascale Gilardi-Hebenstreit,

    1. Ecole Normale Supérieure, IBENS, Developmental Biology Section, 75230 Paris cedex 05, France
    2. INSERM, U1024, 75230 Paris cedex 05, France
    3. CNRS, UMR 8197, 75230 Paris cedex 05, France
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  • Jean-Michel Vallat,

    1. Laboratoire de Neurologie, CHU Dupuytren, 87042 Limoges, France
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  • Volkhard Lindner,

    1. MMCRI, Scarborough, Maine
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  • Patrick Charnay,

    Corresponding author
    1. Ecole Normale Supérieure, IBENS, Developmental Biology Section, 75230 Paris cedex 05, France
    2. INSERM, U1024, 75230 Paris cedex 05, France
    3. CNRS, UMR 8197, 75230 Paris cedex 05, France
    • IBENS-Section Développement, Ecole Normale Supérieure, 46 rue d'Ulm, 75230 Paris cedex 05, France
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  • Laurence Decker

    1. Ecole Normale Supérieure, IBENS, Developmental Biology Section, 75230 Paris cedex 05, France
    2. INSERM, U1024, 75230 Paris cedex 05, France
    3. CNRS, UMR 8197, 75230 Paris cedex 05, France
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Abstract

The analysis of the molecular mechanisms involved in the initial interaction between neurons and Schwann cells is a key issue in understanding the myelination process. We recently identified Cthrc1 (Collagen triple helix repeat containing 1) as a gene upregulated in Schwann cells upon interaction with the axon. Cthrc1 encodes a secreted protein previously shown to be involved in migration and proliferation in different cell types. We performed a functional analysis of Cthrc1 in Schwann cells by loss-of- and gain-of-function approaches using RNA interference knockdown in cell culture and a transgenic mouse line that overexpresses the gene. This work establishes that Cthrc1 enhances Schwann cell proliferation but prevents myelination. In particular, time-course analysis of myelin formation intransgenic animals reveals that overexpression of Cthrc1 in Schwann cells leads to a delay in myelin formation with cells maintaining a proliferative state. Our data, therefore, demonstrate that Cthrc1 plays a negative regulatory role, fine-tuning the onset of peripheral myelination. © 2011 Wiley Periodicals, Inc.

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