Role of transmembrane semaphorin Sema6A in oligodendrocyte differentiation and myelination

Authors

  • Frédéric Bernard,

    1. CNRS, UMR 7102, Paris, France
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    • Frédéric Bernard and Caroline Moreau-Fauvarque contributed equally to this work.

  • Caroline Moreau-Fauvarque,

    1. CNRS, UMR 7102, Paris, France
    2. Institut de la Vision, INSERM, UMRS 968, Paris, France
    3. INSERM, U968, Paris, France
    4. UPMC Univ Paris 06, UMR_S 968, Institut de la Vision, Paris, France
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    • Frédéric Bernard and Caroline Moreau-Fauvarque contributed equally to this work.

  • Céline Heitz-Marchaland,

    1. CNRS, UMR 7102, Paris, France
    2. Institut de la Vision, INSERM, UMRS 968, Paris, France
    3. INSERM, U968, Paris, France
    4. UPMC Univ Paris 06, UMR_S 968, Institut de la Vision, Paris, France
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  • Yvrick Zagar,

    1. CNRS, UMR 7102, Paris, France
    2. Institut de la Vision, INSERM, UMRS 968, Paris, France
    3. INSERM, U968, Paris, France
    4. UPMC Univ Paris 06, UMR_S 968, Institut de la Vision, Paris, France
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  • Laura Dumas,

    1. CNRS, UMR 7102, Paris, France
    2. Institut de la Vision, INSERM, UMRS 968, Paris, France
    3. INSERM, U968, Paris, France
    4. UPMC Univ Paris 06, UMR_S 968, Institut de la Vision, Paris, France
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  • Stéphane Fouquet,

    1. Institut de la Vision, INSERM, UMRS 968, Paris, France
    2. INSERM, U968, Paris, France
    3. UPMC Univ Paris 06, UMR_S 968, Institut de la Vision, Paris, France
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  • Xinhua Lee,

    1. Biogen Idec Inc., Department of Discovery Biology, 14 Cambridge Center, Cambridge, Massachusetts
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  • Zhaohui Shao,

    1. Biogen Idec Inc., Department of Discovery Biology, 14 Cambridge Center, Cambridge, Massachusetts
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  • Sha Mi,

    1. Biogen Idec Inc., Department of Discovery Biology, 14 Cambridge Center, Cambridge, Massachusetts
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  • Alain Chédotal

    Corresponding author
    1. CNRS, UMR 7102, Paris, France
    2. Institut de la Vision, INSERM, UMRS 968, Paris, France
    3. INSERM, U968, Paris, France
    4. UPMC Univ Paris 06, UMR_S 968, Institut de la Vision, Paris, France
    5. AP-HP, Groupe Hospitalier Pitié-Salpêtrière, Fédération de Neurologie, 91 Boulevard de l'Hôpital, Paris, France
    • Dr. Alain Chédotal, Institut de la Vision, Paris, France
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Abstract

Myelination is regulated by extracellular proteins, which control interactions between oligodendrocytes and axons. Semaphorins are repulsive axon guidance molecules, which control the migration of oligodendrocyte precursors during normal development and possibly in demyelinating diseases. We show here that the transmembrane semaphorin 6A (Sema6A) is highly expressed by myelinating oligodendrocytes in the postnatal mouse brain. In adult mice, Sema6A expression is upregulated in demyelinating lesions in cuprizone-treated mice. The analysis of the optic nerve and anterior commissure of Sema6A-deficient mice revealed a marked delay of oligodendrocyte differentiation. Accordingly, the development of the nodes of Ranvier is also transiently delayed. We also observed an arrest in the in vitro differentiation of purified oligodendrocytes lacking Sema6A, with a reduction of the expression level of Myelin Basic Protein. Their morphology is also abnormal, with less complex and ramified processes than wild-type oligodendrocytes. In myelinating co-cultures of dorsal root ganglion neurons and purified oligodendrocytes we found that myelination is perturbed in absence of Sema6A. These results suggest that Sema6A might have a role in myelination by controlling oligodendrocyte differentiation. © 2012 Wiley Periodicals, Inc

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