title: Distinct roles for BAI1 and TIM-4 in the engulfment of dying neurons by microglia.
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.
authors.affiliation: 1] Developmental Biology Unit, European Molecular Biology Laboratory (EMBL) Heidelberg, Meyerhofstrasse 1, 69117 Heidelberg, Germany [2].
authors.forename: Fargol
authors.initials: F
authors.lastname: Mazaheri
authors.affiliation: 1] Developmental Biology Unit, European Molecular Biology Laboratory (EMBL) Heidelberg, Meyerhofstrasse 1, 69117 Heidelberg, Germany [2].
authors.forename: Oksana
authors.initials: O
authors.lastname: Breus
authors.affiliation: Cell Biology and Biophysics Unit, Molecular Biology Laboratory (EMBL) Heidelberg, Meyerhofstrasse 1, 69117 Heidelberg, Germany.
authors.forename: Sevi
authors.initials: S
authors.lastname: Durdu
authors.affiliation: 1] Center for Organismal Studies (COS), Im Neuenheimer Feld 230, 69120 Heidelberg, Germany [2].
authors.forename: Petra
authors.initials: P
authors.lastname: Haas
authors.affiliation: Center for Organismal Studies (COS), Im Neuenheimer Feld 230, 69120 Heidelberg, Germany.
authors.forename: Jochen
authors.initials: J
authors.lastname: Wittbrodt
authors.affiliation: Cell Biology and Biophysics Unit, Molecular Biology Laboratory (EMBL) Heidelberg, Meyerhofstrasse 1, 69117 Heidelberg, Germany.
authors.forename: Darren
authors.initials: D
authors.lastname: Gilmour
authors.affiliation: Developmental Biology Unit, European Molecular Biology Laboratory (EMBL) Heidelberg, Meyerhofstrasse 1, 69117 Heidelberg, Germany.
authors.forename: Francesca
authors.initials: F
authors.lastname: Peri
mesh_terms: D042501:Angiogenic Proteins / Q000378:metabolism*; D000818:Animals; D017209:Apoptosis / Q000502:physiology*; D000072596:Hepatitis A Virus Cellular Receptor 1; D008565:Membrane Proteins / Q000378:metabolism*; D017628:Microglia / Q000378:metabolism* / Q000502:physiology; D009419:Nerve Tissue Proteins / Q000378:metabolism*; D009474:Neurons / Q000378:metabolism*; D010587:Phagocytosis / Q000502:physiology*; D011956:Receptors, Cell Surface / Q000378:metabolism*; D015027:Zebrafish; D029961:Zebrafish Proteins / Q000378:metabolism*
chemical_list: D042501:Angiogenic Proteins; D000072596:Hepatitis A Virus Cellular Receptor 1; D008565:Membrane Proteins; D009419:Nerve Tissue Proteins; D011956:Receptors, Cell Surface; D029961:Zebrafish Proteins; C000601659:adgrb1 protein, zebrafish; C000601658:havcr1 protein, zebrafish