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The molecular determinants of microglial developmental dynamics

Nature Reviews Neuroscience (2024)Cite this article

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Abstract

Microglia constitute the largest population of parenchymal macrophages in the brain and are considered a unique subset of central nervous system glial cells owing to their extra-embryonic origins in the yolk sac. During development, microglial progenitors readily proliferate and eventually colonize the entire brain. In this Review, we highlight the origins of microglial progenitors and their entry routes into the brain and discuss the various molecular and non-molecular determinants of their fate, which may inform their specific functions. Specifically, we explore recently identified mechanisms that regulate microglial colonization of the brain, including the availability of space, and describe how the expansion of highly proliferative microglial progenitors facilitates the occupation of the microglial niche. Finally, we shed light on the factors involved in establishing microglial identity in the brain.

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Fig. 1: Entry of microglia to the embryonic brain.
Fig. 2: Colonization of the mouse brain by microglia during development.
Fig. 3: Drivers of microglial proliferation.
Fig. 4: Stepwise maturation of microglia during development.

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Acknowledgements

The authors were funded by the Leverhulme Trust (RPG-2016-311) and the Medical Research Council (MR/P024572/1).

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Authors and Affiliations

  1. Nutrineuro, UMR 1286 INRAE, Bordeaux University, Bordeaux INP, Bordeaux, France

    Liam Barry-Carroll

  2. School of Biological Sciences, University of Southampton, Southampton General Hospital, Southampton, UK

    Diego Gomez-Nicola

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Glossary

Choroid plexus

A network of blood vessels and cells in the ventricles of the brain.

Clonal expansion

A process of cell division that results in the multiplication of genetically identical cell clones from a single-cell parent cell.

Contact inhibition

A process through which cell proliferation is arrested when cells come in contact with each other.

Fate mapping

A method of tracking cells based on unique gene expression driving reporter systems. Also known as lineage tracing.

Haematopoietic stem cell

(HSC). A stem cell that gives rise to blood cells.

Induced pluripotent stem cells

(iPS cells). Pluripotent stems cells that can be obtained by reprogramming differentiated cells.

Macrophage

A type of white blood cell specialized in the detection and destruction of harmful organisms.

Mesodermal

Related to the mesoderm, the embryonic layer that gives rise to most muscle, skeletal and connective tissues.

Microbiome

The microorganisms present in a particular environment, including the body.

Monocytes

Immune cells that originate from the bone marrow and travel through the bloodstream to tissues to become macrophages or dendritic cells.

Neuroectodermal

Related to the neuroectoderm, the part of the ectoderm that gives rise to the nervous system.

Single-cell RNA sequencing

A method that identifies and quantifies the complexity of RNA transcripts within individual cells.

Subventricular zone

A neurogenic and gliogenic niche situated on the wall of each lateral ventricle of the brain.

Yolk sac

A membranous structure attached to the embryo.

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Barry-Carroll, L., Gomez-Nicola, D. The molecular determinants of microglial developmental dynamics. Nat. Rev. Neurosci. (2024). https://doi.org/10.1038/s41583-024-00813-1

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