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.

Reviewing Editor

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

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).

Version 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.

Metrics

  • 4,465
    Page views
  • 525
    Downloads
  • 46
    Citations

Article citation count generated by polling the highest count across the following sources: Scopus, Crossref, PubMed Central.

Download links

A two-part list of links to download the article, or parts of the article, in various formats.

Downloads (link to download the article as PDF)

Open citations (links to open the citations from this article in various online reference manager services)

Cite this article (links to download the citations from this article in formats compatible with various reference manager tools)

  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

Share this article

https://doi.org/10.7554/eLife.47699

Further reading

    1. Cell Biology
    2. Physics of Living Systems
    Camille Morel, Eline Lemerle ... Emmanuel Lemichez
    Research Article

    Large transcellular pores elicited by bacterial mono-ADP-ribosyltransferase (mART) exotoxins inhibiting the small RhoA GTPase compromise the endothelial barrier. Recent advances in biophysical modeling point toward membrane tension and bending rigidity as the minimal set of mechanical parameters determining the nucleation and maximal size of transendothelial cell macroaperture (TEM) tunnels induced by bacterial RhoA-targeting mART exotoxins. We report that cellular depletion of caveolin-1, the membrane-embedded building block of caveolae, and depletion of cavin-1, the master regulator of caveolae invaginations, increase the number of TEMs per cell. The enhanced occurrence of TEM nucleation events correlates with a reduction in cell height due to the increase in cell spreading and decrease in cell volume, which, together with the disruption of RhoA-driven F-actin meshwork, favor membrane apposition for TEM nucleation. Strikingly, caveolin-1 specifically controls the opening speed of TEMs, leading to their dramatic 5.4-fold larger widening. Consistent with the increase in TEM density and width in siCAV1 cells, we record a higher lethality in CAV1 KO mice subjected to a catalytically active mART exotoxin targeting RhoA during staphylococcal bloodstream infection. Combined theoretical modeling with independent biophysical measurements of plasma membrane bending rigidity points toward a specific contribution of caveolin-1 to membrane stiffening in addition to the role of cavin-1/caveolin-1-dependent caveolae in the control of membrane tension homeostasis.

    1. Physics of Living Systems
    Davin Jeong, Guang Shi ... D Thirumalai
    Research Article

    Compartment formation in interphase chromosomes is a result of spatial segregation between euchromatin and heterochromatin on a few megabase pairs (Mbp) scale. On the sub-Mbp scales, topologically associating domains (TADs) appear as interacting domains along the diagonal in the ensemble averaged Hi-C contact map. Hi-C experiments showed that most of the TADs vanish upon deleting cohesin, while the compartment structure is maintained, and perhaps even enhanced. However, closer inspection of the data reveals that a non-negligible fraction of TADs is preserved (P-TADs) after cohesin loss. Imaging experiments show that, at the single-cell level, TAD-like structures are present even without cohesin. To provide a structural basis for these findings, we first used polymer simulations to show that certain TADs with epigenetic switches across their boundaries survive after depletion of loops. More importantly, the three-dimensional structures show that many of the P-TADs have sharp physical boundaries. Informed by the simulations, we analyzed the Hi-C maps (with and without cohesin) in mouse liver and human colorectal carcinoma cell lines, which affirmed that epigenetic switches and physical boundaries (calculated using the predicted 3D structures using the data-driven HIPPS method that uses Hi-C as the input) explain the origin of the P-TADs. Single-cell structures display TAD-like features in the absence of cohesin that are remarkably similar to the findings in imaging experiments. Some P-TADs, with physical boundaries, are relevant to the retention of enhancer–promoter/promoter–promoter interactions. Overall, our study shows that preservation of a subset of TADs upon removing cohesin is a robust phenomenon that is valid across multiple cell lines.