ArticleeLife2022
A role for the centrosome in regulating the rate of neuronal efferocytosis by microglia in vivo.
Article in eLife, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers.
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Who cites it
23 citing papers in PubMed, 34 citations in OpenAlex.
- Ubiquitination of LMP-1 by UFD-2 regulates apoptotic cell clearance.Cell death and differentiation · 2026Article
- A scalable human-zebrafish xenotransplantation model reveals gastrosome-mediated processing of dying neurons by human microglia.Communications biology · 2026Article
- Microglial cathepsin B is necessary for neuronal efferocytosis in zebrafish and mice during brain development.Nature communications · 2026Article
- A centrally positioned cluster of multiple centrioles in antigen-presenting cells fosters T cell activation.Nature communications · 2026Article
- Targeting microglia microtubules: cytoskeletal remodeling as a druggable hub in neuroinflammation and neurodegeneration.Frontiers in neuroscience · 2026Review
- Macrophages discriminate and sort pathogenic bacteria and apoptotic material during dual-target phagocytosis.PloS one · 2026Article
- Mitochondria are absent from microglial processes performing surveillance, chemotaxis, and phagocytic engulfment.Nature communications · 2025Article
- Microtubules regulate tissue-level navigation in skin-resident macrophages.Journal of cell science · 2025Article
- Impaired Efferocytosis of Pericytes and Vascular Smooth Muscle Cells in Diabetic Retinopathy.Cells · 2025Review
- Downregulation of Fidgetin-Like 2 Increases Microglial Function: The Relationship Between Microtubules, Morphology, and Activity.Molecular neurobiology · 2025Article
- Microglia contact cerebral vasculature through gaps between astrocyte endfeet.Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism · 2024Article
- Centrioles are frequently amplified in early B cell development but dispensable for humoral immunity.Nature communications · 2024Article
- NPC1 links cholesterol trafficking to microglial morphology via the gastrosome.Nature communications · 2024Article
- Amplified centrosomes-more than just a threat.EMBO reports · 2024Review
- Microglia as integrators of brain-associated molecular patterns.Trends in immunology · 2024Review
- Principles of organelle positioning in motile and non-motile cells.EMBO reports · 2024Review
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- Intercellular contact and cargo transfer between Müller glia and to microglia precede apoptotic cell clearance in the developing retina.Development (Cambridge, England) · 2024Article
- Extra centrosomes induce PIDD1-mediated inflammation and immunosurveillance.The EMBO journal · 2023Article
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Authors and funding
6 authors at 1 institution in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
During brain development, many newborn neurons undergo apoptosis and are engulfed by microglia, the tissue-resident phagocytes of the brain, in a process known as efferocytosis. A hallmark of microglia is their highly branched morphology characterized by the presence of numerous dynamic extensions that these cells use for scanning the brain parenchyma and engulfing unwanted material. The mechanisms driving branch formation and apoptotic cell engulfment in microglia are unclear. By taking a live-imaging approach in zebrafish, we show that while microglia generate multiple microtubule-based branches, they only successfully engulf one apoptotic neuron at a time. Further investigation into the mechanism underlying this sequential engulfment revealed that targeted migration of the centrosome into one branch is predictive of phagosome formation and polarized vesicular trafficking. Moreover, experimentally doubling centrosomal numbers in microglia increases the rate of engulfment and even allows microglia to remove two neurons simultaneously, providing direct supporting evidence for a model where centrosomal migration is a rate-limiting step in branch-mediated efferocytosis. Conversely, light-mediated depolymerization of microtubules causes microglia to lose their typical branched morphology and switch to an alternative mode of engulfment, characterized by directed migration towards target neurons, revealing unexpected plasticity in their phagocytic ability. Finally, building on work focusing on the establishment of the immunological synapse, we identified a conserved signalling pathway underlying centrosomal movement in engulfing microglia.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.