1. Developmental Biology
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Intracellular uptake of macromolecules by brain lymphatic endothelial cells during zebrafish embryonic development

  1. Max van Lessen
  2. Shannon Shibata-Germanos
  3. Andreas van Impel
  4. Thomas A Hawkins
  5. Jason Rihel
  6. Stefan Schulte-Merker  Is a corresponding author
  1. Westfälische Wilhelms-Universität Münster, Germany
  2. University College London, United Kingdom
Research Article
  • Cited 46
  • Views 4,417
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Cite this article as: eLife 2017;6:e25932 doi: 10.7554/eLife.25932

Abstract

The lymphatic system controls fluid homeostasis and the clearance of macromolecules from interstitial compartments. In mammals brain lymphatics were only recently discovered, with significant implications for physiology and disease. We examined zebrafish for the presence of brain lymphatics and found loosely connected endothelial cells with lymphatic molecular signature covering parts of the brain without forming endothelial tubular structures. These brain lymphatic endothelial cells (BLECs) derive from venous endothelium, are distinct from macrophages, and are sensitive to loss of Vegfc. BLECs endocytose macromolecules in a selective manner, which can be blocked by injection of mannose receptor ligands. This first report on brain lymphatic endothelial cells in a vertebrate embryo identifies cells with unique features, including the uptake of macromolecules at a single cell level. Future studies will address whether this represents an uptake mechanism that is conserved in mammals and how these cells affect functions of the embryonic and adult brain.

Article and author information

Author details

  1. Max van Lessen

    Institute of Cardiovascular Organogenesis and Regeneration, Westfälische Wilhelms-Universität Münster, Münster, Germany
    Competing interests
    The authors declare that no competing interests exist.
  2. Shannon Shibata-Germanos

    Department of Cell and Developmental Biology, University College London, London, United Kingdom
    Competing interests
    The authors declare that no competing interests exist.
  3. Andreas van Impel

    Institute of Cardiovascular Organogenesis and Regeneration, Westfälische Wilhelms-Universität Münster, Münster, Germany
    Competing interests
    The authors declare that no competing interests exist.
  4. Thomas A Hawkins

    Department of Cell and Developmental Biology, University College London, London, United Kingdom
    Competing interests
    The authors declare that no competing interests exist.
  5. Jason Rihel

    Department of Cell and Developmental Biology, University College London, London, United Kingdom
    Competing interests
    The authors declare that no competing interests exist.
  6. Stefan Schulte-Merker

    Institute for Cardiovascular Organogenesis and Regeneration, Westfälische Wilhelms-Universität Münster, Muenster, Germany
    For correspondence
    schultes@ukmuenster.de
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0003-3617-8807

Funding

Deutsche Forschungsgemeinschaft (FOR2325)

  • Stefan Schulte-Merker

Deutsche Forschungsgemeinschaft (CiM 1003)

  • Max van Lessen

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

Ethics

Animal experimentation: Experimental procedures were conducted under project licence awarded to J.R. from the UK Home Office (Permit Number: 70/7612), according to the UK Animals (Scientific Procedures) Act 1986.

Reviewing Editor

  1. Holger Gerhardt, Max Delbrück Centre for Molecular Medicine, Germany

Publication history

  1. Received: February 10, 2017
  2. Accepted: May 11, 2017
  3. Accepted Manuscript published: May 12, 2017 (version 1)
  4. Version of Record published: June 2, 2017 (version 2)

Copyright

© 2017, van Lessen 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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