Development and maintenance of the brain’s immune toolkit: microglia and non-parenchymal brain macrophages
Open accessAbstract
Microglia and non-parenchymal macrophages located in the perivascular space, the meninges and the choroid plexus are independent immune populations that play vital roles in brain development, homeostasis, and tissue healing. Resident macrophages account for a significant proportion of cells in the brain and their density remains stable throughout the lifespan thanks to constant turnover. Microglia develop from yolk sac progenitors, later evolving through intermediate progenitors in a fine-tuned process in which intrinsic factors and external stimuli combine to progressively sculpt their cell type-specific transcriptional profiles. Recent evidence demonstrates that non-parenchymal macrophages are also generated during early embryonic development. In recent years, the development of powerful fate mapping approaches combined with novel genomic and transcriptomic methodologies have greatly expanded our understanding of how brain macrophages develop and acquire specialized functions, and how cell population dynamics are regulated. Here, we review the transcription factors, epigenetic remodeling, and signaling pathways orchestrating the embryonic development of microglia and non-parenchymal macrophages. Next, we describe the dynamics of the macrophage populations of the brain and discuss the role of progenitor cells, to gain a better understanding of their functions in the healthy and diseased brain. © 2017 Wiley Periodicals, Inc. Develop Neurobiol 78: 561-579, 2018.
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The daily turnover rate of microglia in adult zebrafish is much higher than that reported in mice and human.
“Via EdU pulse-chase labeling assay, we found that the daily turnover rate of microglia in adult zebrafish is about 2.5%, much higher than that reported in mice and human (Lopez-Atalaya et al., 2018).”
From Pu.1/Spi1 dosage controls the turnover and maintenance of microglia in zebrafish and mammals (2025) · cites this paper as Lopez-Atalaya et al., 2018
The 'Cell Cycle and Proliferation Rates of Microglia' section (page not supplied) reports mouse rates of 0.3–0.7% and human rates of 0.08–0.14%, supporting the comparison with the citing authors’ 2.5% zebrafish estimate. But it also reports a 2% human proliferation rate, so the source does not support saying the zebrafish rate is much higher than all reported human rates. The zebrafish estimate is the citing authors’ own result, not a finding attributed to this source. (LLM, conf=0.85)
Experimental — accuracy not yet measuredMicroglial gene enhancers form complexes with lineage-determining transcription factors including PU.1 and SALL1 and become co-activators regulating transcription of targeted genes.
“Microglial gene enhancers form complexes with lineage-determining transcription factors including PU.1 and SALL1, and become co-activators to regulate the transcription of targeted genes [33].”
From Transcriptional and Epigenetic Regulation of Microglia in Health and Disease (2019) · cites this paper as [33]
The daily turnover rate of microglia in adult zebrafish is about 2.5%, much higher than that reported in mice and human.
“Via EdU pulse-chase labelling assay, we found that the daily turnover rate of microglia in adult zebrafish is about 2.5%, much higher than that reported in mice and human (Lopez-Atalaya, Askew et al., 2018).”
From Pu.1/Spi1 dosage controls the turnover and maintenance of microglia in zebrafish and mammals (2023) · cites this paper as Lopez-Atalaya, Askew et al., 2018
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Microglia Actively remodel adult hippocampal neurogenesis through the phagocytosis secretome
Diaz-Aparicio, I., Paris, I., Sierra-Torre, V., Plaza-Zabala, A., Rodríguez-Iglesias, N., Márquez-Ropero, M., Beccari, S., Huguet, P., Abiega, O., Alberdi, E., et al. (2020) · The Journal of Neuroscience · doi:10.1523/jneurosci.0993-19.2019 · Cited by 333 · see citing works
Self-citationTranscriptional and Epigenetic Regulation of Microglia in Health and Disease
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Pu.1/Spi1 dosage controls the turnover and maintenance of microglia in zebrafish and mammals
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Pu.1/Spi1 dosage controls the turnover and maintenance of microglia in zebrafish and mammals
Wu, Y., Guo, W., Kuang, H., Wu, X., Trinh, T. H., Wang, Y., Zhao, S., Wen, Z., & Yu, T. (2023) · bioRxiv (Preprint) · doi:10.1101/2023.12.14.570333 · Cited by 1 · see citing works
- Authors
- Lopez‐Atalaya, J. P., Askew, K. E., Sierra, A., & Gomez‐Nicola, D.
- Affiliations
- Instituto de Neurociencias de Alicante, Universidad Miguel Hernández‐Consejo Superior de Investigaciones Científicas (UMH‐CSIC), Avenida Ramón y Cajal, s/n, Sant Joan d'Alacant Spain
- Southampton General Hospital (GB)
- Ikerbasque (ES)
- Southampton General Hospital, Biological Sciences, University of Southampton, South Lab&Path Block, LD80C, MP840 SO166YD Southampton United Kingdom
- Corresponding author
- Sierra, Amanda
- Venue
- Developmental Neurobiology
- Publisher
- Wiley
- Published
- 2017-10-24
- Volume
- 78
- Issue
- 6
- Pages
- 561-579
- ISSN
- 1932-8451 (ISSN-L)
- 1932-846X
- PMC
- PMC6001428
- OpenAlex
- W2764187051
- Cited by
- 49
- References
- 140
- Citations by year
- 2026: 1 · 2025: 8 · 2024: 2 · 2023: 2 · 2022: 7 · 2021: 7 · 2020: 9 · 2019: 8 · 2018: 4 · 2017: 1
- FWCI
- 0.58
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Developmental Neurobiology (publishedVersion, cc-by)
- Europe PMC (PubMed Central) (publishedVersion, other-oa)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- ePrints Soton (University of Southampton) (acceptedVersion)
- DIGITAL.CSIC (Spanish National Research Council (CSIC)) (submittedVersion, cc-by)
- Communities in ADDI (Universidad del Pais Vasco) (submittedVersion, cc-by)
- Communities in ADDI (University of the Basque Country) (submittedVersion, cc-by)
- LA Referencia (Red Federada de Repositorios Institucionales de Publicaciones Científicas) (submittedVersion, cc-by)
- LA Referencia (Red Federada de Repositorios Institucionales de Publicaciones Científicas) (submittedVersion, other-oa)
- Hispana (submittedVersion, cc-by)
- Funders
- BBVA Foundation (PI_2016_1_0011)
- European Social Fund (RYC‐2015‐18056)
- Ministerio de Economía y Competitividad (SAF2014‐60233‐JIN)
- Medical Research Council
- Topics
- Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
- Life Sciences › Neuroscience › Developmental Neuroscience › Neurogenesis and neuroplasticity mechanisms
- Life Sciences › Neuroscience › Neurology › Barrier Structure and Function Studies
- Keywords
- microglia, choroid plexus macrophages, meningeal macrophages, perivascular macrophages, transcription factors, epigenetic remodeling, signaling pathways, macrophage turnover, fate mapping, brain homeostasis, neuroinflammation
- MeSH terms
- Animals, Brain, Humans, Macrophages, Microglia
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Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
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