PUBLICATION

Developmental Apoptosis Mediates Entry and Positioning of Microglia in the Zebrafish Brain

Authors
Casano, A.M., Albert, M., Peri, F.
ID
ZDB-PUB-160720-8
Date
2016
Source
Cell Reports   16(4): 897-906 (Journal)
Registered Authors
Peri, Francesca
Keywords
none
MeSH Terms
  • Animals
  • Brain Injuries/pathology
  • Cell Death/physiology
  • Brain/physiology*
  • Microglia/physiology*
  • Zebrafish/physiology*
  • Neurons/physiology
  • Apoptosis/physiology*
  • Signal Transduction/physiology
(all 9)
PubMed
27425604 Full text @ Cell Rep.
Abstract
In the brain, neurons that fail to assemble into functional circuits are eliminated. Their clearance depends on microglia, immune cells that colonize the CNS during embryogenesis. Despite the importance of these cells in development and disease, the mechanisms that target and position microglia within the brain are unclear. Here we show that, in zebrafish, attraction of microglia into the brain exploits differences in developmental neuronal apoptosis and that these provide a mechanism for microglial distribution. Reducing neuronal cell death results in fewer microglia, whereas increased apoptosis enhances brain colonization, resulting in more microglia at later stages. Interestingly, attraction into the brain depends on nucleotide signaling, the same signaling system used to guide microglia toward brain injuries. Finally, this work uncovers a cell-non-autonomous role for developmental apoptosis. Classically considered a wasteful process, programmed cell death is exploited here to configure the immune-neuronal interface of the brain.
Genes / Markers
Figures
Figure Gallery (8 images)
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Expression
Phenotype
Fish Conditions Stage Phenotype Figure
WT + MO1-casp3a + MO1-spi1bchemical treatment: Z-Val-Ala-Asp(OMe)-CH2FDay 4
gl24Tg; hdb7Tg; s1999tTgchemical ablation: neuron, chemical treatment by environment: metronidazoleDay 4
gl24Tg; hdb7Tg; s1999tTgchemical ablation: neuron, chemical treatment by environment: metronidazoleDay 4
gl24Tg; hdb7Tg; s1999tTgchemical ablation: neuron, chemical treatment by environment: metronidazoleDay 4
gl24Tg; hdb7Tg; s1999tTgchemical ablation: neuron, chemical treatment by environment: metronidazoleDay 4
gl24Tg; hdb7Tg; s1999tTgchemical ablation: neuron, chemical treatment by environment: metronidazoleDay 4
gl24Tg; hdb7Tg; s1999tTgchemical ablation: neuron, chemical treatment by environment: metronidazoleDay 4
gl24Tg; hdb7Tg; s1999tTgchemical ablation: neuron, chemical treatment by environment: metronidazoleDay 4
gl24Tg; hdb7Tg; s1999tTgchemical ablation: neuron, chemical treatment by environment: metronidazoleDays 7-13
gl24Tg; hdb7Tg; s1999tTgchemical ablation: neuron, chemical treatment by environment: metronidazoleDays 7-13
1 - 10 of 29
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Mutations / Transgenics
Allele Construct Type Affected Genomic Region
gl24TgTransgenic Insertion
    hdb2TgTransgenic Insertion
      hdb4TgTransgenic Insertion
        hdb7TgTransgenic Insertion
          s1999tTgTransgenic Insertion
            1 - 5 of 5
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            Human Disease / Model
            No data available
            Sequence Targeting Reagents
            Target Reagent Reagent Type
            casp3aMO1-casp3aMRPHLNO
            panx1aMO2-panx1aMRPHLNO
            spi1bMO1-spi1bMRPHLNO
            tp53MO1-tp53MRPHLNO
            1 - 4 of 4
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            Fish
            Antibodies
            Name Type Antigen Genes Isotypes Host Organism
            Ab2-lcp1polyclonalRabbit
            1 - 1 of 1
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            Orthology
            No data available
            Engineered Foreign Genes
            Marker Marker Type Name
            GAL4EFGGAL4
            KaedeEFGKaede
            mCherryEFGmCherry
            NTREFGNTR
            TagRFPEFGTagRFP
            1 - 5 of 5
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            Mapping
            No data available