Zebrafish macrophage developmental arrest underlies depletion of microglia and reveals Csf1r-independent metaphocytes
- University Medical Center Rotterdam, Netherlands
- Université Libre de Bruxelles, Belgium
- 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
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Zebrafish mpeg+ cellsNCBI Gene Expression Omnibus, GSE149789.
Article and author information
Author details
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.
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.
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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