Microglia regulate the number of neural precursor cells in the developing cerebral cortex

By Christopher L Cunningham, V. Martínez‐Cerdeño, S. Noctor. Journal of Neuroscience, 2013

872 citations recorded by the source corpus.

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.

Subfields: Developmental Neuroscience, Immunology, Neurology

View Paper: https://www.semanticscholar.org/paper/d5b9220e2d3488019cea088da6227dec07d49eff

How researchers see this paper

The researchers whose trusted networks rank it highest, strongest advocate first. Every researcher gets a different order.

In Developmental Neuroscience

1. E. Taverna
2. W. Huttner
3. M. Götz
4. Chao Gao
5. Shengdi Chen
6. Yuyan Tan
7. Jingwen Jiang
8. Amanda Sierra

In Immunology

1. V. Perry
2. Chao Gao
3. Shengdi Chen
4. Yuyan Tan
5. Jingwen Jiang
6. M. Cragg

In Neurology

1. V. Perry
2. M. Götz
3. Chao Gao
4. Shengdi Chen
5. Yuyan Tan
6. Jingwen Jiang
7. Amanda Sierra
8. C. Cunningham

Citations in the corpus

• Coupled Proliferation and Apoptosis Maintain the Rapid Turnover of Microglia in the Adult Brain (2017, background): “…in brain communication and the control of inflammation in brain disease (Gomez-Nicola and Perry, 2015), the developmental control of neurogenesis (Cunningham et al., 2013), wiring (Squarzoni et al., 2014) and synaptic pruning (Paolicelli et al., 2011), the monitoring of synaptic activity (Wake…”
• Neuronal Cell Death. (2018, neutral): “Knockout of these receptors also increased the number of neuronal precursors in the mice and microglia have also been found to phagocytose live neural precursor cells in rat and monkey cortex (142).”
• The cell biology of neurogenesis: toward an understanding of the development and evolution of the neocortex. (2014, background): “There is increasing evidence that microglia affect neurogenesis, including that in the developing neocortex (e.g., Antony et al. 2011, Cunningham et al. 2013).”
• Pax6 interacts with Iba1 and shows age-associated alterations in brain of aging mice. (2017, background): “In the cerebral cortex (Cc), microglia regulates the size of the neural precursor cell pool (Cunningham et al., 2013) and Pax6 is known to regulate cortical neurogenesis.”
• Microglia in neurodegenerative diseases: mechanism and potential therapeutic targets (2023, background): “Microglia limit the production of cortical neurons by phagocytosing neural precursor cells 99 ; at the same time, microglia also promote neurogenesis, as microglia depletion in mice reduces basal progenitors into the cerebral cortex.”