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Updated: Jul 17, 2025

Derivation of a Human Brain Organoid with Microglia Development
Published on: January 17, 2025
Microglial contribution to the pathology of neurodevelopmental disorders in humans
Rugile Matuleviciute1,2, Elizabeth T Akinluyi3,4, Tim A O Muntslag5
1MRC Centre for Neurodevelopmental Disorders, King's College London, London, UK.
Abstract:
Microglia are the brain's resident macrophages, which guide various developmental processes crucial for brain maturation, activity, and plasticity. Microglial progenitors enter the telencephalic wall by the 4th postconceptional week and colonise the fetal brain in a manner that spatiotemporally tracks key neurodevelopmental processes in humans. However, much of what we know about how microglia shape neurodevelopment comes from rodent studies. Multiple differences exist between human and rodent microglia warranting further focus on the human condition, particularly as microglia are emerging as critically involved in the pathological signature of various cognitive and neurodevelopmental disorders. In this article, we review the evidence supporting microglial involvement in basic neurodevelopmental processes by focusing on the human species. We next concur on the neuropathological evidence demonstrating whether and how microglia contribute to the aetiology of two neurodevelopmental disorders: autism spectrum conditions and schizophrenia. Next, we highlight how recent technologies have revolutionised our understanding of microglial biology with a focus on how these tools can help us elucidate at unprecedented resolution the links between microglia and neurodevelopmental disorders. We conclude by reviewing which current treatment approaches have shown most promise towards targeting microglia in neurodevelopmental disorders and suggest novel avenues for future consideration.
Insights
Microglia, the brain's immune cells, are vital for neurodevelopment in humans. This review explores their role in brain maturation and neurodevelopmental disorders like autism and schizophrenia.
Area of Science:
- Neuroscience
- Immunology
- Developmental Biology
Background:
- Microglia are essential for brain development, maturation, and plasticity.
- Human microglial development differs from rodents, necessitating species-specific research.
- Microglia are implicated in the pathology of neurodevelopmental and cognitive disorders.
Purpose of the Study:
- To review microglial roles in human neurodevelopment.
- To examine microglial contributions to autism spectrum conditions and schizophrenia.
- To highlight technological advancements in studying microglia and neurodevelopmental disorders.
Main Methods:
- Review of existing scientific literature.
- Analysis of neuropathological evidence.
- Discussion of recent technological innovations.
Main Results:
- Microglia play a crucial role in human brain development.
- Evidence links microglia to the etiology of autism spectrum conditions and schizophrenia.
- New technologies offer unprecedented resolution for studying microglia-neurodevelopmental disorder links.
Conclusions:
- Targeting microglia shows promise for treating neurodevelopmental disorders.
- Further research is needed to elucidate microglial roles and develop novel therapies.
- Focusing on human-specific microglial biology is critical for understanding neurodevelopmental disorders.

