Boundary Cap Cells are Highly Competitive for CNS Remyelination: Fast Migration and Efficient Differentiation in PNS and CNS Myelin-Forming Cells

Authors

  • V. Zujovic,

    1. Université Pierre et Marie Curie-Paris 6, Centre de Recherche de l'Institut du Cerveau et de la Moelle Epinière, UMR-S975, Paris, France
    2. Inserm, U975, Paris, France
    3. CNRS, UMR 7225, Paris, France
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  • J. Thibaud,

    1. Université Pierre et Marie Curie-Paris 6, Centre de Recherche de l'Institut du Cerveau et de la Moelle Epinière, UMR-S975, Paris, France
    2. Inserm, U975, Paris, France
    3. CNRS, UMR 7225, Paris, France
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  • C. Bachelin,

    1. Université Pierre et Marie Curie-Paris 6, Centre de Recherche de l'Institut du Cerveau et de la Moelle Epinière, UMR-S975, Paris, France
    2. Inserm, U975, Paris, France
    3. CNRS, UMR 7225, Paris, France
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  • M. Vidal,

    1. Université Pierre et Marie Curie-Paris 6, Centre de Recherche de l'Institut du Cerveau et de la Moelle Epinière, UMR-S975, Paris, France
    2. Inserm, U975, Paris, France
    3. CNRS, UMR 7225, Paris, France
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  • F. Coulpier,

    1. Inserm, U784, Paris, France
    2. Ecole Normale Supérieure, Paris, France
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  • P. Charnay,

    1. Inserm, U784, Paris, France
    2. Ecole Normale Supérieure, Paris, France
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  • P. Topilko,

    1. Inserm, U784, Paris, France
    2. Ecole Normale Supérieure, Paris, France
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  • A. Baron-Van Evercooren

    Corresponding author
    1. Université Pierre et Marie Curie-Paris 6, Centre de Recherche de l'Institut du Cerveau et de la Moelle Epinière, UMR-S975, Paris, France
    2. Inserm, U975, Paris, France
    3. CNRS, UMR 7225, Paris, France
    4. AP-HP, Hôpital Pitié-Salpétrière, Fédération de Neurologie
    • INSERM UMR-S 975, CHU Pitié-Salpêtrière, 105 boulevard de l'Hôpital, 75634 cedex 13, Paris, France

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    • Telephone: +33-1-4077-8129; Fax: +33-1-4077-8117


  • Author contributions: V.Z.: Conception and design, collection and/or assembly of data, data analysis and interpretation, manuscript writing, final approval of manuscript; J.T.: Collection and/or assembly of data, data analysis and interpretation; C.B.: Collection and/or assembly of data, data analysis and interpretation; M.V.: Collection and/or assembly of data, data analysis and interpretation; F.C.: Provision of study material or patients; P.C.: Provision of study material or patients, manuscript writing; P.T.: Provision of study material or patients, manuscript writing; A.B.-V.E.: Conception and design, data analysis and interpretation, financial support, administrative support, manuscript writing, final approval of manuscript.

  • Disclosure of potential conflicts of interest is found at the end of this article.

  • First published online in STEM CELLSEXPRESS December 28, 2009.

Abstract

During development, boundary cap cells (BC) and neural crest cell (NCC) derivatives generate Schwann cells (SC) of the spinal roots and a subpopulation of neurons and satellite cells in the dorsal root ganglia. Despite their stem-like properties, their therapeutic potential in the diseased central nervous system (CNS) was never explored. The aim of this work was to explore BC therapeutic potential for CNS remyelination. We derived BC from Krox20Cre × R26RYfp embryos at E12.5, when Krox20 is exclusively expressed by BC. Combining microdissection and cell fate mapping, we show that acutely isolated BC are a unique population closely related but distinct from NCC and SC precursors. Moreover, when grafted in the demyelinated spinal cord, BC progeny expands in the lesion through a combination of time-regulated processes including proliferation and differentiation. Furthermore, when grafted away from the lesion, BC progeny, in contrast to committed SC, show a high migratory potential mediated through enhanced interactions with astrocytes and white matter, and possibly with polysialylated neural cell adhesion molecule expression. In response to demyelinated axons of the CNS, BC progeny generates essentially myelin-forming SC. However, in contact with axons and astrocytes, some of them generate also myelin-forming oligodendrocytes. There are two primary outcomes of this study. First, the high motility of BC and their progeny, in addition to their capacity to remyelinate CNS axons, supports the view that BC are a reservoir of interest to promote CNS remyelination. Second, from a developmental point of view, BC behavior in the demyelinated CNS raises the question of the boundary between central and peripheral myelinating cells. STEM CELLS 2010;28:470–479

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