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Development and maintenance of the brain's immune toolkit: Microglia and non-parenchymal brain macrophages
Jose P Lopez-Atalaya1, Katharine E Askew2, Amanda Sierra3,4,5
1Instituto de Neurociencias de Alicante, Universidad Miguel Hernández-Consejo Superior de Investigaciones Científicas (UMH-CSIC), Avenida Ramón y Cajal, s/n, Sant Joan d'Alacant, Spain.
Abstract:
Microglia and non-parenchymal macrophages located in the perivascular space, the meninges and the choroid plexus are independent immune populations that play vital roles in brain development, homeostasis, and tissue healing. Resident macrophages account for a significant proportion of cells in the brain and their density remains stable throughout the lifespan thanks to constant turnover. Microglia develop from yolk sac progenitors, later evolving through intermediate progenitors in a fine-tuned process in which intrinsic factors and external stimuli combine to progressively sculpt their cell type-specific transcriptional profiles. Recent evidence demonstrates that non-parenchymal macrophages are also generated during early embryonic development. In recent years, the development of powerful fate mapping approaches combined with novel genomic and transcriptomic methodologies have greatly expanded our understanding of how brain macrophages develop and acquire specialized functions, and how cell population dynamics are regulated. Here, we review the transcription factors, epigenetic remodeling, and signaling pathways orchestrating the embryonic development of microglia and non-parenchymal macrophages. Next, we describe the dynamics of the macrophage populations of the brain and discuss the role of progenitor cells, to gain a better understanding of their functions in the healthy and diseased brain. © 2017 Wiley Periodicals, Inc. Develop Neurobiol 78: 561-579, 2018.
Insights
Microglia and non-parenchymal macrophages are crucial brain immune cells. This review details their development, regulation, and roles in brain health and disease.
Area of Science:
- Neurobiology
- Immunology
- Developmental Biology
Background:
- Microglia and non-parenchymal macrophages are distinct brain immune cell populations vital for brain development, homeostasis, and repair.
- These resident macrophages constitute a significant cell proportion in the brain, maintaining stable density throughout life via continuous turnover.
- Both microglia and non-parenchymal macrophages originate from embryonic progenitors, with their development shaped by intrinsic and extrinsic factors.
Purpose of the Study:
- To review the molecular mechanisms governing the embryonic development of microglia and non-parenchymal macrophages.
- To describe the population dynamics of brain macrophages and the role of progenitor cells.
- To enhance understanding of brain macrophage functions in both healthy and diseased states.
Main Methods:
- Review of recent literature on brain macrophage development and function.
- Focus on fate mapping, genomic, and transcriptomic methodologies.
- Analysis of transcription factors, epigenetic remodeling, and signaling pathways.
Main Results:
- Elucidation of the developmental pathways for microglia and non-parenchymal macrophages from embryonic progenitors.
- Detailed description of the regulation of brain macrophage population dynamics.
- Identification of key molecular players including transcription factors, epigenetic modifiers, and signaling pathways.
Conclusions:
- Understanding the developmental origins and regulatory mechanisms of brain macrophages is crucial for comprehending their roles in neurological health and disease.
- Advanced techniques have significantly improved our knowledge of brain macrophage biology.
- Further research into progenitor cells and regulatory pathways will offer insights into therapeutic strategies for brain disorders.
