PUBLICATION

A csf1rb mutation uncouples two waves of microglia development in zebrafish

Authors
Ferrero, G., Miserocchi, M., Di Ruggiero, E., Wittamer, V.
ID
ZDB-PUB-201212-14
Date
2020
Source
Development (Cambridge, England)   148(1): (Journal)
Registered Authors
Wittamer, Valerie
Keywords
Colony-stimulating factor 1 receptor, Development, Hematopoiesis, Macrophages, Microglia, Zebrafish
MeSH Terms
  • Gene Expression Regulation, Developmental
  • Hematopoietic Stem Cells/metabolism
  • Zebrafish/embryology
  • Zebrafish/genetics*
  • Hematopoiesis
  • Zebrafish Proteins/genetics*
  • Zebrafish Proteins/metabolism
  • Embryonic Development
  • Aging/genetics
  • Embryo, Nonmammalian/metabolism
  • Myeloid Cells/metabolism
  • Receptor Protein-Tyrosine Kinases/genetics
  • Receptor Protein-Tyrosine Kinases/metabolism
  • Macrophages/metabolism
  • Phagocytes/metabolism
  • Protein-Tyrosine Kinases/genetics*
  • Protein-Tyrosine Kinases/metabolism
  • Animals
  • Mutation/genetics*
  • Microglia/metabolism*
(all 20)
PubMed
33298459 Full text @ Development
Abstract
In vertebrates, the ontogeny of microglia, the resident macrophages of the central nervous system, initiates early during development from primitive macrophages. While murine embryonic microglia then persist through life, in zebrafish these cells are transient, as they are fully replaced by an adult population originating from larval hematopoietic stem cell (HSC)-derived progenitors. Colony-stimulating factor receptor 1 (csf1r) is a fundamental regulator of microglia ontogeny in vertebrates, including zebrafish which possess two paralogous genes: csf1ra and csf1rb While previous work showed mutation in both genes completely abrogates microglia development, the specific contribution of each paralog remains largely unknown. Here, using a fate-mapping strategy to discriminate between the two microglial waves, we uncover non-overlapping roles for csf1ra and csf1rb in hematopoiesis, and identified csf1rb as an essential regulator of adult microglia development. Notably, we demonstrate that csf1rb positively regulates HSC-derived myelopoiesis, resulting in macrophage deficiency, including microglia, in adult mutant animals. Overall, this study contributes to new insights into evolutionary aspects of Csf1r signaling and provides an unprecedented framework for the functional dissection of embryonic versus adult microglia in vivo.
Genes / Markers
Figures
Figure Gallery (6 images)
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Expression
Phenotype
Mutations / Transgenics
Allele Construct Type Affected Genomic Region
gl22TgTransgenic Insertion
    hg1
      Point Mutation
      j4e1
        Point Mutation
        re01
          Small Deletion
          s898TgTransgenic Insertion
            sa1503
              Point Mutation
              sd3TgTransgenic Insertion
                sd5TgTransgenic Insertion
                  sd6TgTransgenic Insertion
                    1 - 9 of 9
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                    Human Disease / Model
                    No data available
                    Sequence Targeting Reagents
                    No data available
                    Fish
                    Antibodies
                    No data available
                    Orthology
                    No data available
                    Engineered Foreign Genes
                    Marker Marker Type Name
                    CreEFGCre
                    DsRedEFGDsRed
                    DsRedxEFGDsRedx
                    EGFPEFGEGFP
                    1 - 4 of 4
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                    Mapping
                    No data available