Microglia Regulate the Number of Neural Precursor Cells in the Developing Cerebral Cortex
Open accessAbstract
Neurogenesis must be properly regulated to ensure that cell production does not exceed the requirements of the growing cerebral cortex, yet our understanding of mechanisms that restrain neuron production remains incomplete. We investigated the function of microglial cells in the developing cerebral cortex of prenatal and postnatal macaques and rats and show that microglia limit the production of cortical neurons by phagocytosing neural precursor cells. We show that microglia selectively colonize the cortical proliferative zones and phagocytose neural precursor cells as neurogenesis nears completion. We found that deactivating microglia in utero with tetracyclines or eliminating microglia from the fetal cerebral cortex with liposomal clodronate significantly increased the number of neural precursor cells, while activating microglia in utero through maternal immune activation significantly decreased the number of neural precursor cells. These data demonstrate that microglia play a fundamental role in regulating the size of the precursor cell pool in the developing cerebral cortex, expanding our understanding of the mechanisms that regulate cortical development. Furthermore, our data suggest that any factor that alters the number or activation state of microglia in utero can profoundly affect neural development and affect behavioral outcomes.
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Brain organoids currently lack some cell types present in primary cortex, such as endothelial cells and microglia.
“Brain organoids currently lack some of the cell types present in primary cortex, such as endothelial cells (which have been shown to influence progenitor cell behaviour62,63) and microglia (which also have a role in early stages of cortical development64) (FIG. 2b).”
From The use of brain organoids to investigate neural development and disease (2017) · cites this paper as [64]
During development, microglia secrete trophic factors like IGF-1 and TGFβ.
“secrete trophic factors like insulin-like growth factor I (IGF-1) and TGFβ”
From Immune mediators in the brain and peripheral tissues in autism spectrum disorder (2015) · cites this paper as [214]
During development, microglia participate in activity-dependent elimination of synaptic connections.
“participate in activity-dependent elimination of synaptic connections212–214”
From Immune mediators in the brain and peripheral tissues in autism spectrum disorder (2015) · cites this paper as [214]
In development, microglia influence neurogenesis by engulfing neural precursor cells.
“regulate neurogenesis through phagocytosis of neural precursor cells”
From Immune mediators in the brain and peripheral tissues in autism spectrum disorder (2015) · cites this paper as [214]
In development, microglia clear debris left by natural cell death.
“During development, microglia phagocytize debris from naturally-occurring cell death”
From Immune mediators in the brain and peripheral tissues in autism spectrum disorder (2015) · cites this paper as [214]
A significant fraction of cerebellar microglia contains lysosomes carrying cell nuclei fragments, as determined by DAPI-positive nuclear material.
“A significant fraction of microglia in the cerebellum contains lysosomes carrying cell nuclei fragments as determined by the presence of DAPI-positive nuclear material (Fig. 1b, Supplementary Fig. 1d), which is indicative of apoptotic cell clearance17.”
From Epigenetic regulation of brain region-specific microglia clearance activity (2018) · cites this paper as [17]
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- Authors
- Cunningham, C. L., Martínez-Cerdeño, V., & Noctor, S. C.
- Affiliations
- University of California, Davis (US)
- Venue
- The Journal of Neuroscience
- Publisher
- Society for Neuroscience
- Published
- 2013-03-06
- Volume
- 33
- Issue
- 10
- Pages
- 4216-4233
- ISSN
- 0270-6474 (ISSN-L)
- 1529-2401
- PMC
- PMC3711552
- OpenAlex
- W2029190354
- Cited by
- 976
- References
- 87
- Citations by year
- 2026: 41 · 2025: 69 · 2024: 93 · 2023: 93 · 2022: 94 · 2021: 102 · 2020: 93 · 2019: 81 · 2018: 86 · 2017: 61 · 2016: 46 · 2015: 48 · 2014: 51 · 2013: 18
- FWCI
- 20.17
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Journal of Neuroscience (publishedVersion, cc-by-nc-sa)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- Funders
- National Institutes of Health
- National Institute of Mental Health (R01MH101188, R01MH094681)
- Topics
- Life Sciences › Neuroscience › Developmental Neuroscience › Neurogenesis and neuroplasticity mechanisms
- Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
- Health Sciences › Medicine › Pediatrics, Perinatology and Child Health › Neonatal and fetal brain pathology
- Keywords
- microglia, neural progenitor cells, neurogenesis, cortical development, phagocytosis, microglial activation, maternal immune activation, tetracycline, clodronate liposomes, prenatal development, macaque, rats
- MeSH terms
- Age Factors, Analysis of Variance, Animals, Animals, Newborn, Calcium-Binding Proteins, Cell Count, Cerebral Cortex, Cerebral Ventricles, Embryo, Mammalian, Female, HLA-DR Antigens, Indoles, Lipopolysaccharides, Luminescent Proteins, Macaca, Male, Microfilament Proteins, Minocycline, Nerve Tissue Proteins, Phagocytosis, Pregnancy, Prenatal Exposure Delayed Effects, Microglia, Microscopy, Confocal, Proliferating Cell Nuclear Antigen, Lipopolysaccharide Receptors, T-Box Domain Proteins, Rats, Nitric Oxide Synthase Type II, Neurogenesis, Neural Stem Cells
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