Origin and role of the cerebrospinal fluid bidirectional flow in the central canal

  1. Olivier Thouvenin
  2. Ludovic Keiser
  3. Yasmine Cantaut-Belarif1
  4. Martin Carbo-Tano
  5. Frederik Verweij
  6. Nathalie Jurisch-Yaksi
  7. Pierre-Luc Bardet
  8. Guillaume van Niel
  9. Francois Gallaire  Is a corresponding author
  10. Claire Wyart  Is a corresponding author
  1. Hôpital Pitié-Salpêtrière, Sorbonne Universités, UPMC Univ Paris 06, Inserm, CNRS, France
  2. École Polytechnique Fédérale de Lausanne, Switzerland
  3. Institute of Psychiatry and Neuroscience of Paris, Hôpital Saint-Anne, Université Descartes, INSERM U1266, France
  4. Norwegian University of Science and Technology, Norway

Abstract

Circulation of the cerebrospinal fluid (CSF) contributes to body axis formation and brain development. Here, we investigated the unexplained origins of the CSF flow bidirectionality in the central canal of the spinal cord of 30 hpf zebrafish embryos and its impact on development. Experiments combined with modeling and simulations demonstrate that the CSF flow is generated locally by caudally-polarized motile cilia along the ventral wall of the central canal. The closed geometry of the canal imposes the average flow rate to be null, explaining the reported bidirectionality. We also demonstrate that at this early stage, motile cilia ensure the proper formation of the central canal. Furthermore, we demonstrate that the bidirectional flow accelerates the transport of particles in the CSF via a coupled convective-diffusive transport process. Our study demonstrates that cilia activity combined with muscle contractions sustain the long-range transport of extracellular lipidic particles, enabling embryonic growth.

Data availability

The data enabling to plot all graphs for figures and supplemental videos have been deposited to the Dryad Digital Repository doi:10.5061/dryad.4mj3pv1.The full MATLAB script can be found on Github https://github.com/wyartlab/eLife_2019_OriginAndRole

The following data sets were generated

Article and author information

Author details

  1. Olivier Thouvenin

    Institut du Cerveau et la Moelle épinière, Hôpital Pitié-Salpêtrière, Sorbonne Universités, UPMC Univ Paris 06, Inserm, CNRS, Paris, France
    Competing interests
    No competing interests declared.
  2. Ludovic Keiser

    Laboratory of Fluid Mechanics and Instabilities, École Polytechnique Fédérale de Lausanne, Lausanne, Switzerland
    Competing interests
    No competing interests declared.
  3. Yasmine Cantaut-Belarif1

    Institut du Cerveau et la Moelle épinière, Hôpital Pitié-Salpêtrière, Sorbonne Universités, UPMC Univ Paris 06, Inserm, CNRS, Paris, France
    Competing interests
    No competing interests declared.
  4. Martin Carbo-Tano

    Institut du Cerveau et la Moelle épinière, Hôpital Pitié-Salpêtrière, Sorbonne Universités, UPMC Univ Paris 06, Inserm, CNRS, Paris, France
    Competing interests
    No competing interests declared.
  5. Frederik Verweij

    Institute of Psychiatry and Neuroscience of Paris, Hôpital Saint-Anne, Université Descartes, INSERM U1266, Paris, France
    Competing interests
    No competing interests declared.
  6. Nathalie Jurisch-Yaksi

    Kavli Institute for Systems Neuroscience, Norwegian University of Science and Technology, Trondheim, Norway
    Competing interests
    No competing interests declared.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-8767-6120
  7. Pierre-Luc Bardet

    Institut du Cerveau et la Moelle épinière, Hôpital Pitié-Salpêtrière, Sorbonne Universités, UPMC Univ Paris 06, Inserm, CNRS, Paris, France
    Competing interests
    No competing interests declared.
  8. Guillaume van Niel

    Institute of Psychiatry and Neuroscience of Paris, Hôpital Saint-Anne, Université Descartes, INSERM U1266, Paris, France
    Competing interests
    No competing interests declared.
  9. Francois Gallaire

    Laboratory of Fluid Mechanics and Instabilities, École Polytechnique Fédérale de Lausanne, Lausanne, Switzerland
    For correspondence
    francois.gallaire@epfl.ch
    Competing interests
    No competing interests declared.
  10. Claire Wyart

    Institut du Cerveau et la Moelle épinière, Hôpital Pitié-Salpêtrière, Sorbonne Universités, UPMC Univ Paris 06, Inserm, CNRS, Paris, France
    For correspondence
    claire.wyart@icm-institute.org
    Competing interests
    Claire Wyart, Reviewing editor, eLife.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-1668-4975

Funding

Human Frontier Science Program (RGP00063/2018)

  • Francois Gallaire
  • Claire Wyart

NIH Blueprint for Neuroscience Research (U19NS104653)

  • Martin Carbo-Tano
  • Claire Wyart

European Research Council (311673)

  • Yasmine Cantaut-Belarif1
  • Martin Carbo-Tano
  • Claire Wyart

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 procedures were performed on zebrafish embryos before 2 days post fertilization in accordance with the European Communities Council Directive (2010/63/EU) and French law (87/848) and approved by the Brain and Spine Institute (Institut du Cerveau et de la Moelle épinière).

Reviewing Editor

  1. Julien Vermot, Institut de Génétique et de Biologie Moléculaire et Cellulaire, France

Publication history

  1. Received: April 15, 2019
  2. Accepted: January 7, 2020
  3. Accepted Manuscript published: January 9, 2020 (version 1)
  4. Version of Record published: January 29, 2020 (version 2)

Copyright

© 2020, Thouvenin 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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  1. Olivier Thouvenin
  2. Ludovic Keiser
  3. Yasmine Cantaut-Belarif1
  4. Martin Carbo-Tano
  5. Frederik Verweij
  6. Nathalie Jurisch-Yaksi
  7. Pierre-Luc Bardet
  8. Guillaume van Niel
  9. Francois Gallaire
  10. Claire Wyart
(2020)
Origin and role of the cerebrospinal fluid bidirectional flow in the central canal
eLife 9:e47699.
https://doi.org/10.7554/eLife.47699
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