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Updated: Jun 14, 2025
Author Spotlight: Using Zebrafish to Explore Microglia Migration During Brain Development
Published on: May 17, 2024
Evolution of Microglia
Elena Guffart1, Marco Prinz2,3,4
1Institute of Neuropathology, Faculty of Medicine, University of Freiburg, Freiburg, Germany.
Abstract:
Microglial cells are unique tissue-resident macrophages located in the parenchyma of the central nervous system (CNS). A recent comparative transcriptional study on microglia across more than 20 species from leach across chicken and many more up to humans revealed multiple conserved features. The results indicate the imperative role of microglia over the last 500 million years (Geirsdottir et al. Cell 181:746, 2020). Improved understanding of microglial evolution provides essential insights into conserved and divergent microglial pathways and will have implications for future development of microglia-based therapies to treat CNS disorders. Not only therapeutic approaches may be rethought, but also the understanding of sex specificity of the immune system within the CNS needs to be renewed. Besides revealing the highly detailed characteristics of microglia, the former paradigm of microglia being the only CNS-resident immune cells was outdated by the identification of CNS-associated macrophages (CAMs) as CNS interface residents, who, most likely, accompanied microglia in evolution over the past million years.
Insights
Microglia, the brain's immune cells, have evolved over 500 million years, showing conserved functions across species. This research highlights their crucial role and informs new therapies for central nervous system disorders.
Area of Science:
- Neuroimmunology
- Evolutionary Biology
- Cell Biology
Background:
- Microglial cells are unique macrophages residing in the central nervous system (CNS) parenchyma.
- A recent comparative study analyzed microglial transcriptomes across diverse species, from leeches to humans.
- Understanding microglial evolution is key to deciphering conserved and divergent pathways.
Purpose of the Study:
- To investigate the evolutionary history and conserved features of microglial cells.
- To explore the implications of microglial evolution for developing novel CNS disorder therapies.
- To re-evaluate the understanding of sex specificity in the CNS immune system.
Main Methods:
- Comparative transcriptional analysis of microglial cells across over 20 species.
- Identification of conserved genetic features and evolutionary pathways of microglia.
- Re-examination of the CNS immune cell landscape, including CNS-associated macrophages (CAMs).
Main Results:
- Microglia exhibit highly conserved features across a vast evolutionary timescale (over 500 million years).
- The study identified multiple conserved characteristics of microglia, underscoring their vital role.
- CNS-associated macrophages (CAMs) were identified as CNS interface residents, co-evolving with microglia.
Conclusions:
- Microglial evolution provides critical insights into conserved and divergent pathways, impacting CNS disorder therapies.
- Future therapeutic strategies for CNS disorders may need reevaluation based on microglial evolution.
- The identification of CAMs updates the paradigm of CNS-resident immune cells and their evolutionary history.
