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Distinct roles for BAI1 and TIM-4 in the engulfment of dying neurons by microglia

Author

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  • Fargol Mazaheri

    (Developmental Biology Unit, European Molecular Biology Laboratory (EMBL) Heidelberg, Meyerhofstrasse 1)

  • Oksana Breus

    (Developmental Biology Unit, European Molecular Biology Laboratory (EMBL) Heidelberg, Meyerhofstrasse 1)

  • Sevi Durdu

    (Cell Biology and Biophysics Unit, Molecular Biology Laboratory (EMBL) Heidelberg, Meyerhofstrasse 1)

  • Petra Haas

    (Center for Organismal Studies (COS), Im Neuenheimer Feld 230
    Present address: Leica Microsystems Frankfurt Am Main, Germany)

  • Jochen Wittbrodt

    (Center for Organismal Studies (COS), Im Neuenheimer Feld 230)

  • Darren Gilmour

    (Cell Biology and Biophysics Unit, Molecular Biology Laboratory (EMBL) Heidelberg, Meyerhofstrasse 1)

  • Francesca Peri

    (Developmental Biology Unit, European Molecular Biology Laboratory (EMBL) Heidelberg, Meyerhofstrasse 1)

Abstract

The removal of dying neurons by microglia has a key role during both development and in several diseases. To date, little is known about the cellular and molecular processes underlying neuronal engulfment in the brain. Here we took a live imaging approach to quantify neuronal cell death progression in embryonic zebrafish brains and studied the response of microglia. We show that microglia engulf dying neurons by extending cellular branches that form phagosomes at their tips. At the molecular level we found that microglia lacking the phosphatidylserine receptors BAI1 and TIM-4, are able to recognize the apoptotic targets but display distinct clearance defects. Indeed, BAI1 controls the formation of phagosomes around dying neurons and cargo transport, whereas TIM-4 is required for phagosome stabilization. Using this single-cell resolution approach we established that it is the combined activity of BAI1 and TIM-4 that allows microglia to remove dying neurons.

Suggested Citation

  • Fargol Mazaheri & Oksana Breus & Sevi Durdu & Petra Haas & Jochen Wittbrodt & Darren Gilmour & Francesca Peri, 2014. "Distinct roles for BAI1 and TIM-4 in the engulfment of dying neurons by microglia," Nature Communications, Nature, vol. 5(1), pages 1-11, September.
    • Handle: RePEc:nat:natcom:v:5:y:2014:i:1:d:10.1038_ncomms5046
    DOI: 10.1038/ncomms5046
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    Cited by:

    1. Joanna Zareba & Elena F. Cattaneo & Ambra Villani & Alaa Othman & Sebastian Streb & Francesca Peri, 2024. "NPC1 links cholesterol trafficking to microglial morphology via the gastrosome," Nature Communications, Nature, vol. 15(1), pages 1-15, December.
    2. Nicholas J. Silva & Leah C. Dorman & Ilia D. Vainchtein & Nadine C. Horneck & Anna V. Molofsky, 2021. "In situ and transcriptomic identification of microglia in synapse-rich regions of the developing zebrafish brain," Nature Communications, Nature, vol. 12(1), pages 1-12, December.

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