Zebrafish macrophage developmental arrest underlies depletion of microglia and reveals Csf1r-independent metaphocytes

  1. Laura E Kuil
  2. Nynke Oosterhof
  3. Guliano Ferrero
  4. Tereza Mikulášová
  5. Martina Hason
  6. Jordy Dekker
  7. Mireia Rovira
  8. Herma C van der Linde
  9. Paulina MH van Strien
  10. Emma de Pater
  11. Gerben Schaaf
  12. Erik MJ Bindels
  13. Valerie Wittamer  Is a corresponding author
  14. Tjakko J van Ham  Is a corresponding author
  1. University Medical Center Rotterdam, Netherlands
  2. Université Libre de Bruxelles, Belgium
  3. Institute of Molecular Genetics of the ASCR, Czech Republic

Abstract

Macrophages derive from multiple sources of hematopoietic progenitors. Most macrophages require colony-stimulating factor 1 receptor (CSF1R), but some macrophages persist in the absence of CSF1R. Here, we analyzed mpeg1:GFP–expressing macrophages in csf1r-deficient zebrafish and report that embryonic macrophages emerge followed by their developmental arrest. In larvae, mpeg1+ cell numbers then increased showing two distinct types in the skin: branched, putative Langerhans cells, and amoeboid cells. In contrast, although numbers also increased in csf1r-mutants, exclusively amoeboid mpeg1+ cells were present, which we showed by genetic lineage tracing to have a non-hematopoietic origin. They expressed macrophage-associated genes, but also showed decreased phagocytic gene expression and increased epithelial-associated gene expression, characteristic of metaphocytes, recently discovered ectoderm-derived cells. We further demonstrated that juvenile csf1r-deficient zebrafish exhibit systemic macrophage depletion. Thus, Csf1r deficiency disrupts embryonic to adult macrophage development. Csf1r-deficient zebrafish are viable and permit analyzing the consequences of macrophage loss throughout life.

Data availability

The data discussed in this publication have been deposited in NCBI's Gene Expression Omnibus (Edgar et al., 2002) and are accessible through GEO Series accession number GSE149789

The following data sets were generated

Article and author information

Author details

  1. Laura E Kuil

    Clinical Genetics, University Medical Center Rotterdam, Rotterdam, Netherlands
    Competing interests
    The authors declare that no competing interests exist.
  2. Nynke Oosterhof

    Clinical Genetics, University Medical Center Rotterdam, Rotterdam, Netherlands
    Competing interests
    The authors declare that no competing interests exist.
  3. Guliano Ferrero

    IRIBHM, Université Libre de Bruxelles, Brussels, Belgium
    Competing interests
    The authors declare that no competing interests exist.
  4. Tereza Mikulášová

    Laboratory of Cell Differentiation, Institute of Molecular Genetics of the ASCR, Prague, Czech Republic
    Competing interests
    The authors declare that no competing interests exist.
  5. Martina Hason

    Laboratory of Cell Differentiation, Institute of Molecular Genetics of the ASCR, Prague, Czech Republic
    Competing interests
    The authors declare that no competing interests exist.
  6. Jordy Dekker

    Clinical Genetics, University Medical Center Rotterdam, Rotterdam, Netherlands
    Competing interests
    The authors declare that no competing interests exist.
  7. Mireia Rovira

    IRIBHM, Université Libre de Bruxelles, Brussels, Belgium
    Competing interests
    The authors declare that no competing interests exist.
  8. Herma C van der Linde

    Clinical Genetics, University Medical Center Rotterdam, Rotterdam, Netherlands
    Competing interests
    The authors declare that no competing interests exist.
  9. Paulina MH van Strien

    Hematology, University Medical Center Rotterdam, Rotterdam, Netherlands
    Competing interests
    The authors declare that no competing interests exist.
  10. Emma de Pater

    Hematology, University Medical Center Rotterdam, Rotterdam, Netherlands
    Competing interests
    The authors declare that no competing interests exist.
  11. Gerben Schaaf

    Clinical Genetics, University Medical Center Rotterdam, Rotterdam, Netherlands
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0003-0189-9073
  12. Erik MJ Bindels

    Hematology, University Medical Center Rotterdam, Rotterdam, Netherlands
    Competing interests
    The authors declare that no competing interests exist.
  13. Valerie Wittamer

    IRIBHM, Université Libre de Bruxelles, Brussels, Belgium
    For correspondence
    vwittame@ulb.ac.be
    Competing interests
    The authors declare that no competing interests exist.
  14. Tjakko J van Ham

    Clinical Genetics, University Medical Center Rotterdam, Rotterdam, Netherlands
    For correspondence
    t.vanham@erasmusmc.nl
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-2175-8713

Funding

Erasmus University Fellowship

  • Tjakko J van Ham

WELBIO (WELBIO-CR-2015S-04)

  • Valerie Wittamer

Marie Curie (322368)

  • Tjakko J van Ham

ZonMw (VENI 016.136.150)

  • Tjakko J van Ham

Fonds de la Recherche Scientifique FNRS under Incentive Grant for Scientific Research (F451218F)

  • Valerie Wittamer

Czech Science Foundation (18-18363S)

  • Tereza Mikulášová

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

Reviewing Editor

  1. Alex Fantin, Università degli Studi di Milano, Italy

Ethics

Animal experimentation: All experimental procedures were approved and in accordance with the recommendations of the Animal Experimentation Committee at Erasmus MC, Rotterdam or the ULB ethical committee for animal welfare (CEBEA) (protocol 594N). Zebrafish over 5 days old were euthanized using ice water and/or high dose MS-222.

Version history

  1. Received: November 7, 2019
  2. Accepted: April 24, 2020
  3. Accepted Manuscript published: May 5, 2020 (version 1)
  4. Version of Record published: May 19, 2020 (version 2)

Copyright

© 2020, Kuil 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. Laura E Kuil
  2. Nynke Oosterhof
  3. Guliano Ferrero
  4. Tereza Mikulášová
  5. Martina Hason
  6. Jordy Dekker
  7. Mireia Rovira
  8. Herma C van der Linde
  9. Paulina MH van Strien
  10. Emma de Pater
  11. Gerben Schaaf
  12. Erik MJ Bindels
  13. Valerie Wittamer
  14. Tjakko J van Ham
(2020)
Zebrafish macrophage developmental arrest underlies depletion of microglia and reveals Csf1r-independent metaphocytes
eLife 9:e53403.
https://doi.org/10.7554/eLife.53403

Share this article

https://doi.org/10.7554/eLife.53403

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