ArticleThe EMBO journal2020
Local externalization of phosphatidylserine mediates developmental synaptic pruning by microglia.
Article in The EMBO journal, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 267 papers.
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Who cites it
267 citing papers in PubMed, 400 citations in OpenAlex.
- Translational modelling of human microglia from cultures to chimeras.Experimental & molecular medicine · 2026Review
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- Metabolomics and Proteomics Analyses Reveal the Protective Effect of Crocetin Against Depressive-Like Behaviors Mice.Neurochemical research · 2026Article
- Microglia deploy TAM receptors to kill motor neurons in a mouse model of amyotrophic lateral sclerosis.Nature communications · 2026Article
- The Xkr protein family-From apoptosis executors to diverse physiological functions regulators.FEBS letters · 2026Review
- Perisynaptic Astrocytic Processes as Communication Hubs and Early Sites of Dysfunction.The Neuroscientist : a review journal bringing neurobiology, neurology and psychiatry · 2026Review
- The microglial TREM2 receptor programs hippocampal development in a mouse model of childhood deprivation.Brain, behavior, and immunity · 2026Article
- Microglia extract neuronal proteolytic organelles via skoupocytosis.bioRxiv : the preprint server for biology · 2026Article
- Phospholipid flippases ATP8A1 and ATP8A2 regulate GABAiScience · 2026Article
- Microglia-mediated synaptic pruning in neural circuit remodeling: multidimensional control in homeostasis and neuropathology.BMC medicine · 2026Review
- Brain targeting and trafficking of extracellular vesicles in central nervous system diseases: a therapeutic roadmap.Nanomedicine (London, England) · 2026Review
- Microglia maintain retinal redox homeostasis following ablation of rod photoreceptors in zebrafish.The Journal of biological chemistry · 2026Article
- Synaptic activity controls local exposure of an 'eat-me' signal via ANO3-ITPR1 signaling.bioRxiv : the preprint server for biology · 2026Article
- Differential selectivity of microglia and astrocytes in HIV-1 gp120-induced synaptic pruning.Brain : a journal of neurology · 2026Article
- Atypical involvement of Alzheimer's tau proteins in diseases beyond tauopathies.Life medicine · 2026Review
- Therapeutic targeting of neuroimmune mechanisms in neurodegeneration.Nature reviews. Drug discovery · 2026Review
- TREM2-mediated microglial phagocytosis of inhibitory synapses contributes to prolonged FS-induced epileptogenesis.Cell death discovery · 2026Article
- Calcium dependent activation of the TMEM16F scramblase and ion channel.Nature structural & molecular biology · 2026Article
207 more citing papers are in PubMed but not listed here.
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Authors and funding
17 authors at 5 institutions in 3 countries.
Funding
Abstract
Neuronal circuit assembly requires the fine balance between synapse formation and elimination. Microglia, through the elimination of supernumerary synapses, have an established role in this process. While the microglial receptor TREM2 and the soluble complement proteins C1q and C3 are recognized as key players, the neuronal molecular components that specify synapses to be eliminated are still undefined. Here, we show that exposed phosphatidylserine (PS) represents a neuronal "eat-me" signal involved in microglial-mediated pruning. In hippocampal neuron and microglia co-cultures, synapse elimination can be partially prevented by blocking accessibility of exposed PS using Annexin V or through microglial loss of TREM2. In vivo, PS exposure at both hippocampal and retinogeniculate synapses and engulfment of PS-labeled material by microglia occurs during established developmental periods of microglial-mediated synapse elimination. Mice deficient in C1q, which fail to properly refine retinogeniculate connections, have elevated presynaptic PS exposure and reduced PS engulfment by microglia. These data provide mechanistic insight into microglial-mediated synapse pruning and identify a novel role of developmentally regulated neuronal PS exposure that is common among developing brain structures.
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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.