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Updated: Jun 1, 2025
Author Spotlight: In Vitro Co-Culture Model for Studying Microglia-Neuronal Interactions in Disease Conditions
Published on: July 26, 2024
Propagation of neuronal micronuclei regulates microglial characteristics
Sarasa Yano1,2, Natsu Asami3, Yusuke Kishi4,5
1Graduate School of Life and Environmental Sciences, University of Tsukuba, Tsukuba, Japan.
Abstract:
Microglia-resident immune cells in the central nervous system-undergo morphological and functional changes in response to signals from the local environment and mature into various homeostatic states. However, niche signals underlying microglial differentiation and maturation remain unknown. Here, we show that neuronal micronuclei (MN) transfer to microglia, which is followed by changing microglial characteristics during the postnatal period. Neurons passing through a dense region of the developing neocortex give rise to MN and release them into the extracellular space, before being incorporated into microglia and inducing morphological changes. Two-photon imaging analyses have revealed that microglia incorporating MN tend to slowly retract their processes. Loss of the cGAS gene alleviates effects on micronucleus-dependent morphological changes. Neuronal MN-harboring microglia also exhibit unique transcriptome signatures. These results demonstrate that neuronal MN serve as niche signals that transform microglia, and provide a potential mechanism for regulation of microglial characteristics in the early postnatal neocortex.
Insights
Neuronal micronuclei (MN) transfer to microglia, altering their characteristics during early brain development. This discovery reveals a novel mechanism regulating microglial maturation via these transferred nuclear fragments.
Area of Science:
- Neuroscience
- Immunology
- Cell Biology
Background:
- Microglia, the resident immune cells of the central nervous system (CNS), adapt their morphology and function based on environmental cues.
- The specific niche signals that guide microglial differentiation and maturation remain largely unidentified.
Purpose of the Study:
- To investigate the role of neuronal micronuclei (MN) as potential niche signals influencing microglial development in the early postnatal neocortex.
Main Methods:
- Utilizing two-photon imaging to observe the transfer of neuronal MN to microglia in vivo.
- Analyzing morphological and transcriptomic changes in microglia that have incorporated MN.
- Investigating the impact of cGAS gene deletion on MN-dependent microglial alterations.
Main Results:
- Neuronal MN are released by developing cortical neurons and subsequently incorporated by microglia.
- Microglia containing MN exhibit altered morphology, characterized by retracted processes.
- The cGAS gene plays a role in mediating MN-induced microglial morphological changes.
- Neuronal MN-containing microglia display distinct transcriptome signatures.
Conclusions:
- Neuronal micronuclei act as critical niche signals that induce transformations in microglia.
- This mechanism provides a novel pathway for regulating microglial characteristics during early neocortical development.
