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

Fargol Mazaheri, Oksana Breus, Sevi Durdu, Petra Haas, Jochen Wittbrodt, Darren Gilmour and Francesca Peri ()
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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
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

Nature Communications, 2014, vol. 5, issue 1, 1-11

Abstract: 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.

Date: 2014
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DOI: 10.1038/ncomms5046

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