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
  • Macrophages/metabolism
  • Zebrafish Proteins/genetics*
  • Zebrafish Proteins/metabolism
  • Phagocytes/metabolism
  • Embryo, Nonmammalian/metabolism
  • Receptor Protein-Tyrosine Kinases/genetics
  • Receptor Protein-Tyrosine Kinases/metabolism
  • Embryonic Development
  • Microglia/metabolism*
  • Mutation/genetics*
  • Gene Expression Regulation, Developmental
  • Hematopoietic Stem Cells/metabolism
  • Aging/genetics
  • Hematopoiesis
  • Protein-Tyrosine Kinases/genetics*
  • Protein-Tyrosine Kinases/metabolism
  • Animals
  • Zebrafish/embryology
  • Zebrafish/genetics*
  • Myeloid Cells/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
Human Disease / Model
No data available
Sequence Targeting Reagents
No data available
Fish
Fish
csf1raj4e1/j4e1
csf1raj4e1/j4e1; csf1rbre01/re01
csf1raj4e1/j4e1; csf1rbre01/re01; gl22Tg; s898Tg; sd5Tg
csf1raj4e1/j4e1; gl22Tg; s898Tg; sd5Tg
csf1raj4e1/j4e1; gl22Tg; sd5Tg
csf1rbre01/re01
csf1rbre01/re01; gl22Tg; s898Tg; sd5Tg
csf1rbre01/re01; gl22Tg; sd5Tg
csf1rbsa1503/sa1503
runx1hg1/hg1
1 - 10 of 12
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Antibodies
No data available
Orthology
No data available
Engineered Foreign Genes
Marker Marker Type Name
CreEFGCre
DsRedEFGDsRed
DsRedxEFGDsRedx
EGFPEFGEGFP
1 - 4 of 4
Show
Mapping
No data available
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Citation
Ferrero, G., Miserocchi, M., Di Ruggiero, E., Wittamer, V. (2020) A csf1rb mutation uncouples two waves of microglia development in zebrafish. Development (Cambridge, England). 148(1):.