PUBLICATION

Embryonic Microglia Derive from Primitive Macrophages and Are Replaced by cmyb-Dependent Definitive Microglia in Zebrafish

Authors
Ferrero, G., Mahony, C.B., Dupuis, E., Yvernogeau, L., Di Ruggiero, E., Miserocchi, M., Caron, M., Robin, C., Traver, D., Bertrand, J.Y., Wittamer, V.
ID
ZDB-PUB-180705-4
Date
2018
Source
Cell Reports   24: 130-141 (Journal)
Registered Authors
Bertrand, Julien, Mahony, Christopher, Traver, David, Wittamer, Valerie
Keywords
cmyb, developmental hematopoiesis, erythro-myeloid progenitors, fate mapping, hematopoietic stem cells, microglia, ontogeny, primitive macrophages
MeSH Terms
  • Embryonic Development
  • Animals
  • Hematopoietic Stem Cells/cytology
  • Hematopoietic Stem Cells/metabolism
  • Zebrafish/embryology*
  • Embryo, Nonmammalian/cytology*
  • Zebrafish Proteins/metabolism*
  • Macrophages/cytology*
  • Macrophages/metabolism
  • Microglia/metabolism*
  • Kinetics
(all 11)
PubMed
29972775 Full text @ Cell Rep.
Abstract
Microglia, the tissue-resident macrophages of the CNS, represent major targets for therapeutic intervention in a wide variety of neurological disorders. Efficient reprogramming protocols to generate microglia-like cells in vitro using patient-derived induced pluripotent stem cells will, however, require a precise understanding of the cellular and molecular events that instruct microglial cell fates. This remains a challenge since the developmental origin of microglia during embryogenesis is controversial. Here, using genetic tracing in zebrafish, we uncover primitive macrophages as the unique source of embryonic microglia. We also demonstrate that this initial population is transient, with primitive microglia later replaced by definitive microglia that persist throughout adulthood. The adult wave originates from cmyb-dependent hematopoietic stem cells. Collectively, our work challenges the prevailing model establishing erythro-myeloid progenitors as the sole and direct microglial precursor and provides further support for the existence of multiple waves of microglia, which originate from distinct hematopoietic precursors.
Genes / Markers
Figures
Figure Gallery (10 images)
Show all Figures
Expression
Phenotype
Fish Conditions Stage Phenotype Figure
acvr1ltm110b/tm110bstandard conditionsProtruding-mouth
acvr1ltm110b/tm110bstandard conditionsProtruding-mouth
mybt25127/t25127standard conditionsDay 6
1 - 3 of 3
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Mutations / Transgenics
Allele Construct Type Affected Genomic Region
gl22TgTransgenic Insertion
    gl24TgTransgenic Insertion
      la2TgTransgenic Insertion
        s898TgTransgenic Insertion
          s1999tTgTransgenic Insertion
            sd3TgTransgenic Insertion
              sd5TgTransgenic Insertion
                sd6TgTransgenic Insertion
                  sd32TgTransgenic Insertion
                    t25127
                      		Point Mutation
                      1 - 10 of 13
                      Show
                      Human Disease / Model
                      No data available
                      Sequence Targeting Reagents
                      Target Reagent Reagent Type
                      tnnt2aMO1-tnnt2aMRPHLNO
                      1 - 1 of 1
                      Show
                      Fish
                      Fish
                      acvr1ltm110b/tm110b
                      gl22Tg
                      gl22Tg; s898Tg; sd5Tg
                      gl22Tg; sd32Tg; sd5Tg; zd17Tg
                      mybt25127/t25127
                      sd3Tg; sd6Tg
                      tfecug103/ug103
                      WT
                      1 - 8 of 8
                      Show
                      Antibodies
                      No data available
                      Orthology
                      No data available
                      Engineered Foreign Genes
                      Marker Marker Type Name
                      CreEFGCre
                      DsRedEFGDsRed
                      DsRedxEFGDsRedx
                      EGFPEFGEGFP
                      GAL4EFGGAL4
                      KaedeEFGKaede
                      KALTA4EFGKALTA4
                      VenusEFGVenus
                      1 - 8 of 8
                      Show
                      Mapping
                      No data available
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                      Citation
                      Ferrero, G., Mahony, C.B., Dupuis, E., Yvernogeau, L., Di Ruggiero, E., Miserocchi, M., Caron, M., Robin, C., Traver, D., Bertrand, J.Y., Wittamer, V. (2018) Embryonic Microglia Derive from Primitive Macrophages and Are Replaced by cmyb-Dependent Definitive Microglia in Zebrafish. Cell Reports. 24:130-141.