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

• DOI: 10.1038/ncomms5046
• Publication Date: 2014-06-05T11:47:11Z
• Authors: Fargol Mazaheri; Oksana Breus; Sevi Durdu; Petra Haas; Jochen Wittbrodt; Darren Gilmour; Francesca Peri
• Keywords: Neurons; 0303 health sciences; General Physics and Astronomy; Membrane Proteins; 1600 General Chemistry; Genetics and Molecular Biology; Apoptosis; Nerve Tissue Proteins; Receptors, Cell Surface; General Chemistry; Zebrafish Proteins; 10124 Institute of Molecular Life Sciences; 3100 General Physics and Astronomy; 03 medical and health sciences; Phagocytosis; 1300 General Biochemistry, Genetics and Molecular Biology; General Biochemistry; 570 Life sciences; biology; Animals; Hepatitis A Virus Cellular Receptor 1; Microglia; Angiogenic Proteins; Zebrafish

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.