PUBLICATION

Il34-Csf1r Pathway Regulates the Migration and Colonization of Microglial Precursors

Authors
Wu, S., Xue, R., Hassan, S., Nguyen, T.M.L., Wang, T., Pan, H., Xu, J., Liu, Q., Zhang, W., Wen, Z.
ID
ZDB-PUB-180913-20
Date
2018
Source
Developmental Cell   46: 552-563.e4 (Journal)
Registered Authors
Wen, Zilong
Keywords
Csf1r, Il34, colonization, microglia, migration, neuronal apoptosis, zebrafish
MeSH Terms
  • Zebrafish/genetics
  • Zebrafish/growth & development*
  • Zebrafish/metabolism
  • Embryonic Development
  • Cell Differentiation
  • Cell Movement*
  • Animals
  • Brain/cytology
  • Brain/physiology*
  • Interleukins/genetics
  • Interleukins/metabolism*
  • Receptors, Colony-Stimulating Factor/genetics
  • Receptors, Colony-Stimulating Factor/metabolism*
  • Microglia/cytology
  • Microglia/physiology*
  • Neurons/cytology
  • Neurons/physiology*
  • Apoptosis
(all 18)
PubMed
30205037 Full text @ Dev. Cell
Abstract
Microglia are the major immune cells in the central nervous system (CNS). Born in peripheral hematopoietic tissues, microglial precursors colonize the CNS during early embryogenesis and maintain themselves thereafter. However, the mechanism underlying this colonization process remains elusive. We have recently demonstrated that neuronal apoptosis contributes to microglia colonization in zebrafish. Here, we further show that prior to neuronal apoptosis, microglial precursors are attracted to the proximal brain regions by brain-derived interleukin 34 (il34) and its receptor colony-stimulating factor 1 receptor a (csf1ra). In both il34- and csf1ra-deficient zebrafish larva, embryonic macrophages fail to migrate to the anterior head and colonize the CNS, but their initial development and colonization to peripheral tissues remain largely unaffected. Activation of Il34-Csf1ra pathway is sufficient to attract embryonic macrophages to the CNS independent of neuronal apoptosis. Our study shows that cytokine signaling and neuronal apoptosis synergistically orchestrate the colonization of microglia in early zebrafish development.
Genes / Markers
Figures
Figure Gallery (10 images)
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Expression
Phenotype
Mutations / Transgenics
Allele Construct Type Affected Genomic Region
hkz9
    Insertion
    hkz10
      Small Deletion
      hkz11
        Small Deletion
        hkz013tTgTransgenic Insertion
          hkz15TgTransgenic Insertion
            hkz16TgTransgenic Insertion
              hkz17TgTransgenic Insertion
                hkz18TgTransgenic Insertion
                  hkz019tTgTransgenic Insertion
                    j4e1
                      Point Mutation
                      1 - 10 of 12
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                      Human Disease / Model
                      No data available
                      Sequence Targeting Reagents
                      Target Reagent Reagent Type
                      csf1aCRISPR1-csf1aCRISPR
                      csf1bCRISPR1-csf1bCRISPR
                      il34CRISPR1-il34CRISPR
                      spi1bMO6-spi1bMRPHLNO
                      1 - 4 of 4
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                      Fish
                      Antibodies
                      Orthology
                      No data available
                      Engineered Foreign Genes
                      Marker Marker Type Name
                      CreEFGCre
                      DsRedxEFGDsRedx
                      EGFPEFGEGFP
                      GFPEFGGFP
                      KaedeEFGKaede
                      mCherryEFGmCherry
                      1 - 6 of 6
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                      Mapping
                      No data available