1. Developmental Biology

Proper migration of lymphatic endothelial cells requires survival and guidance cues from arterial mural cells

  1. Di Peng
  2. Koji Ando  Is a corresponding author
  3. Melina Hußmann
  4. Marleen Gloger
  5. Renae Skoczylas
  6. Naoki Mochizuki.
  7. Christer Betsholtz
  8. Shigetomo Fukuhara
  9. Stefan Schulte-Merker
  10. Nathan D Lawson
  11. Katarzyna Koltowska  Is a corresponding author
  1. Uppsala University, Sweden
  2. Nippon Medical School, Japan
  3. WWU Münster, Germany
  4. National Cerebral and Cardiovascular Center, Japan
  5. University of Massachusetts Medical School, United States
https://doi.org/10.7554/eLife.74094
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Cite this article
  1. Di Peng
  2. Koji Ando
  3. Melina Hußmann
  4. Marleen Gloger
  5. Renae Skoczylas
  6. Naoki Mochizuki.
  7. Christer Betsholtz
  8. Shigetomo Fukuhara
  9. Stefan Schulte-Merker
  10. Nathan D Lawson
  11. Katarzyna Koltowska
(2022)
Proper migration of lymphatic endothelial cells requires survival and guidance cues from arterial mural cells
eLife 11:e74094.
https://doi.org/10.7554/eLife.74094
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Abstract

The migration of lymphatic endothelial cells (LECs) is key for the development of the complex and vast lymphatic vascular network that pervades most tissues in an organism. In zebrafish, arterial intersegmental vessels together with chemokines have been shown to promote lymphatic cell migration from the horizontal myoseptum (HM). We observed that emergence of mural cells around the intersegmental arteries coincides with lymphatic departure from HM which raised the possibility that arterial mural cells promote LEC migration. Our live imaging and cell ablation experiments revealed that LECs migrate slower and fail to establish the lymphatic vascular network in the absence of arterial mural cells. We determined that mural cells are a source for the C-X-C motif chemokine 12 (Cxcl12a and Cxcl12b), Vascular endothelial growth factor C (Vegfc) and Collagen and calcium-binding EGF domain-containing protein 1 (Ccbe1). We showed that chemokine and growth factor signalling function cooperatively to induce robust LEC migration. Specifically, Vegfc-Vegfr3 signalling, but not chemokines, induces extracellular signal-regulated kinase (ERK) activation in LECs, and has an additional pro-survival role in LECs during the migration. Together, the identification of mural cells as a source for signals that guide LEC migration and survival will be important in the future design for rebuilding lymphatic vessels in disease contexts.

Data availability

All data generated or analysed during this study are included in the manuscript and all the source are uploaded

The following previously published data sets were used

Article and author information

Author details

  1. Di Peng

    Department of Immunology, Genetics and Pathology, Uppsala University, Uppsala, Sweden
    Competing interests
    The authors declare that no competing interests exist.

  2. Koji Ando

    Department of Molecular Pathophysiology, Nippon Medical School, Kawasaki, Japan
    For correspondence
    koji-ando@nms.ac.jp
    Competing interests
    The authors declare that no competing interests exist.

  3. Melina Hußmann

    Institute of Cardiovascular Organogenesis and Regeneration, WWU Münster, Münster, Germany
    Competing interests
    The authors declare that no competing interests exist.

  4. Marleen Gloger

    Department of Immunology, Genetics and Pathology, Uppsala University, Uppsala, Sweden
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-3319-7642

  5. Renae Skoczylas

    Department of Immunology, Genetics and Pathology, Uppsala University, Uppsala, Sweden
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-8570-7368

  6. Naoki Mochizuki.

    Department of Cell Biology, National Cerebral and Cardiovascular Center, Suita, Japan
    Competing interests
    The authors declare that no competing interests exist.

  7. Christer Betsholtz

    Department of Immunology, Genetics and Pathology, Uppsala University, Uppsala, Sweden
    Competing interests
    The authors declare that no competing interests exist.

  8. Shigetomo Fukuhara

    Department of Molecular Pathophysiology, Nippon Medical School, Kawasaki, Japan
    Competing interests
    The authors declare that no competing interests exist.

  9. Stefan Schulte-Merker

    Institute of Cardiovascular Organogenesis and Regeneration, WWU Münster, Münster, Germany
    Competing interests
    The authors declare that no competing interests exist.

  10. Nathan D Lawson

    Department of Molecular, Cell and Cancer Biology, University of Massachusetts Medical School, Worcester, United States
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0001-7788-9619

  11. Katarzyna Koltowska

    Department of Immunology, Genetics and Pathology, Uppsala University, Uppsala, Sweden
    For correspondence
    kaska.koltowska@igp.uu.se
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-6841-8900

Funding

Knut och Alice Wallenbergs Stiftelse (2017.0144)

  • Katarzyna Koltowska

Ragnar Söderbergs stiftelse (M13/17)

  • Katarzyna Koltowska

Vetenskapsrådet (VR-MH-2016-01437)

  • Katarzyna Koltowska

Ragnar Söderbergs stiftelse (M13/17)

  • Di Peng

Jeanssons Stiftelser (n/a)

  • Katarzyna Koltowska

Deutsche Forschungsgemeinschaft (CRC1348B08)

  • Melina Hußmann

Deutsche Forschungsgemeinschaft (CRC1348B08)

  • Stefan Schulte-Merker

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

Ethics

Animal experimentation: Animal experiments were carried out under ethical approval from the Swedish Board of Agriculture (5.2.18-7558/14).

Copyright

© 2022, Peng 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. Di Peng
  2. Koji Ando
  3. Melina Hußmann
  4. Marleen Gloger
  5. Renae Skoczylas
  6. Naoki Mochizuki.
  7. Christer Betsholtz
  8. Shigetomo Fukuhara
  9. Stefan Schulte-Merker
  10. Nathan D Lawson
  11. Katarzyna Koltowska
(2022)
Proper migration of lymphatic endothelial cells requires survival and guidance cues from arterial mural cells
eLife 11:e74094.
https://doi.org/10.7554/eLife.74094

Share this article

https://doi.org/10.7554/eLife.74094

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