PUBLICATION

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

Authors
Kuil, L.E., Oosterhof, N., Ferrero, G., Mikulášová, T., Hason, M., Dekker, J., Rovira, M., van der Linde, H.C., van Strien, P.M., de Pater, E., Schaaf, G., Bindels, E.M., Wittamer, V., van Ham, T.J.
ID
ZDB-PUB-200506-11
Date
2020
Source
eLIFE   9: (Journal)
Registered Authors
Keywords
developmental biology, zebrafish
Datasets
GEO:GSE149787, GEO:GSE149789, GEO:GSE149788, GEO:GSE149786
MeSH Terms
  • Receptors, Granulocyte-Macrophage Colony-Stimulating Factor/metabolism
  • Receptors, Granulocyte-Macrophage Colony-Stimulating Factor/physiology*
  • Animals
  • Gene Expression Profiling
  • Microglia/metabolism
  • Microglia/physiology*
  • Protein-Tyrosine Kinases/metabolism*
  • Zebrafish Proteins/metabolism
  • Zebrafish Proteins/physiology*
  • Macrophages/metabolism
  • Macrophages/physiology*
  • Zebrafish/embryology
  • Cell Proliferation
(all 13)
PubMed
32367800 Full text @ Elife
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.
Genes / Markers
Figures
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Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Antibodies
Orthology
Engineered Foreign Genes
Mapping
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Citation
Kuil, L.E., Oosterhof, N., Ferrero, G., Mikulášová, T., Hason, M., Dekker, J., Rovira, M., van der Linde, H.C., van Strien, P.M., de Pater, E., Schaaf, G., Bindels, E.M., Wittamer, V., van Ham, T.J. (2020) Zebrafish macrophage developmental arrest underlies depletion of microglia and reveals Csf1r-independent metaphocytes. eLIFE. 9:.