1. Developmental Biology
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Transient hypothyroidism favors oligodendrocyte generation providing functional remyelination in the adult mouse brain

  1. Sylvie REMAUD
  2. Fernando C Ortiz
  3. Marie Perret-Jeanneret
  4. Marie-Stéphane Aigrot
  5. Jean-David Gothié
  6. Csaba Fekete
  7. Zsuzsanna Kvárta-Papp
  8. Balázs Gereben
  9. Dominique Langui
  10. Catherine Lubetzki
  11. Maria Cecilia Angulo
  12. Bernard Zalc
  13. Barbara Demeneix  Is a corresponding author
  1. Muséum d'Histoire Naturelle, Sorbonne Universités, France
  2. INSERM U1128, France
  3. Sorbonne Universités UPMC Univ Paris 06, Inserm, CNRS, France
  4. Institute of Experimental Medicine, Hungarian Academy of Sciences, Hungary
Research Article
  • Cited 27
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Cite this article as: eLife 2017;6:e29996 doi: 10.7554/eLife.29996

Abstract

In the adult brain, both neurons and oligodendrocytes can be generated from neural stem cells located within the Sub-Ventricular Zone (SVZ). Physiological signals regulating neuronal versus glial fate are largely unknown. Here we report that a thyroid hormone (T3)-free window, with or without a demyelinating insult, provides a favorable environment for SVZ-derived oligodendrocyte progenitor generation. After demyelination, oligodendrocytes derived from these newly-formed progenitors provide functional remyelination, restoring normal conduction speed. The cellular basis for neuronal versus glial determination in progenitors involves asymmetric partitioning of EGFR and TRα1, expression of which favor glio-and neurogenesis, respectively. Moreover, EGFR+ oligodendrocyte progenitors, but not neuroblasts, express high levels of a T3-inactivating deiodinase, Dio3. Thus, TRα absence with high levels of Dio3 provides double-pronged blockage of T3 action during glial lineage commitment. These findings not only transform our understanding of how T3 orchestrates adult brain lineage decisions, but also provide potential insight into demyelinating disorders.

Article and author information

Author details

  1. Sylvie REMAUD

    CNRS UMR 7221, Muséum d'Histoire Naturelle, Sorbonne Universités, Paris, France
    Competing interests
    The authors declare that no competing interests exist.
  2. Fernando C Ortiz

    INSERM U1128, Paris, France
    Competing interests
    The authors declare that no competing interests exist.
  3. Marie Perret-Jeanneret

    CNRS UMR 7221, Muséum d'Histoire Naturelle, Sorbonne Universités, Paris, France
    Competing interests
    The authors declare that no competing interests exist.
  4. Marie-Stéphane Aigrot

    ICM-GH Pitié-Salpêtrière, Sorbonne Universités UPMC Univ Paris 06, Inserm, CNRS, Paris, France
    Competing interests
    The authors declare that no competing interests exist.
  5. Jean-David Gothié

    CNRS UMR 7221, Muséum d'Histoire Naturelle, Sorbonne Universités, Paris, France
    Competing interests
    The authors declare that no competing interests exist.
  6. Csaba Fekete

    Department of Endocrine Neurobiology, Institute of Experimental Medicine, Hungarian Academy of Sciences, Budapest, Hungary
    Competing interests
    The authors declare that no competing interests exist.
  7. Zsuzsanna Kvárta-Papp

    Department of Endocrine Neurobiology, Institute of Experimental Medicine, Hungarian Academy of Sciences, Budapest, Hungary
    Competing interests
    The authors declare that no competing interests exist.
  8. Balázs Gereben

    Department of Endocrine Neurobiology, Institute of Experimental Medicine, Hungarian Academy of Sciences, Budapest, Hungary
    Competing interests
    The authors declare that no competing interests exist.
  9. Dominique Langui

    ICM-GH Pitié-Salpêtrière, Sorbonne Universités UPMC Univ Paris 06, Inserm, CNRS, Paris, France
    Competing interests
    The authors declare that no competing interests exist.
  10. Catherine Lubetzki

    ICM-GH Pitié-Salpêtrière, Sorbonne Universités UPMC Univ Paris 06, Inserm, CNRS, Paris, France
    Competing interests
    The authors declare that no competing interests exist.
  11. Maria Cecilia Angulo

    INSERM U1128, Paris, France
    Competing interests
    The authors declare that no competing interests exist.
  12. Bernard Zalc

    ICM-GH Pitié-Salpêtrière, Sorbonne Universités UPMC Univ Paris 06, Inserm, CNRS, Paris, France
    Competing interests
    The authors declare that no competing interests exist.
  13. Barbara Demeneix

    CNRS UMR 7221, Muséum d'Histoire Naturelle, Sorbonne Universités, Paris, France
    For correspondence
    bdem@mnhn.fr
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0003-4544-971X

Funding

Association Française contre les Myopathies

  • Sylvie REMAUD
  • Barbara Demeneix

European Commission

  • Barbara Demeneix

Agence Nationale de la Recherche

  • Sylvie REMAUD
  • Bernard Zalc
  • Barbara Demeneix

Fondation pour la Recherche Médicale

  • Maria Cecilia Angulo

The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.

Ethics

Animal experimentation: All experimental procedures involving mice in our study were approved by the French Ministry of Agriculture (authorization number, 01169.02).

Reviewing Editor

  1. Klaus-Armin Nave, Max-Planck-Institute for Experimental Medicine, Germany

Publication history

  1. Received: June 29, 2017
  2. Accepted: September 5, 2017
  3. Accepted Manuscript published: September 6, 2017 (version 1)
  4. Accepted Manuscript updated: September 7, 2017 (version 2)
  5. Version of Record published: September 20, 2017 (version 3)

Copyright

© 2017, REMAUD et al.

This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.

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