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
- 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
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping