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

• Published in: Nature communications 2014-06, Vol.5 (1), p.4046-4046, Article 4046
• Main Authors: Mazaheri, Fargol, Breus, Oksana, Durdu, Sevi, Haas, Petra, Wittbrodt, Jochen, Gilmour, Darren, Peri, Francesca
• Format: Article
• Language: English
• Subjects: 14; 14/19; 14/63; 631/136; 631/378/1934; 631/378/2596/1953; 631/80/86; 64; 64/116; Angiogenic Proteins - metabolism; Animals; Apoptosis; Apoptosis - physiology; Brain; Cell death; Humanities and Social Sciences; Membrane Proteins - metabolism; Microglia - metabolism; Microglia - physiology; Molecular biology; multidisciplinary; Nerve Tissue Proteins - metabolism; Neurons - metabolism; Phagocytosis - physiology; Receptors, Cell Surface - metabolism; Science; Science (multidisciplinary); Zebrafish; Zebrafish Proteins - metabolism
• ISSN: 2041-1723; 2041-1723
• DOI: 10.1038/ncomms5046

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. The removal of dying neurons by microglia plays a key role in both vertebrate nervous system development and several diseases. Here, the authors use a quantitative live imaging approach to investigate neuronal-microglial interactions at single-cell resolution and establish the functions of the phosphatidylserine receptors, TIM-4 and BAI1, in neuronal engulfment.