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Development and maintenance of the brain's immune toolkit: microglia and non-parenchymal brain macrophages

Development and maintenance of the brain's immune toolkit: microglia and non-parenchymal brain macrophages
Development and maintenance of the brain's immune toolkit: microglia and non-parenchymal brain macrophages
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.
1932-846X
561-579
Lopez-Atalaya, Jose P.
34940da8-b336-401a-8a59-7a66497be195
Askew, Katharine E.
ffc96fb4-f94c-4cb7-8479-e9f0b2dae0c7
Sierra, Amanda
d4ebfb5f-f928-4e90-b3b9-cc71e06c9254
Gomez-Nicola, Diego
0680aa66-9dee-47cf-a8d3-e39c988f85b5
Lopez-Atalaya, Jose P.
34940da8-b336-401a-8a59-7a66497be195
Askew, Katharine E.
ffc96fb4-f94c-4cb7-8479-e9f0b2dae0c7
Sierra, Amanda
d4ebfb5f-f928-4e90-b3b9-cc71e06c9254
Gomez-Nicola, Diego
0680aa66-9dee-47cf-a8d3-e39c988f85b5

Lopez-Atalaya, Jose P., Askew, Katharine E., Sierra, Amanda and Gomez-Nicola, Diego (2017) Development and maintenance of the brain's immune toolkit: microglia and non-parenchymal brain macrophages. Developmental Neurobiology, 78 (6), 561-579. (doi:10.1002/dneu.22545).

Record type: Review

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.

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Accepted/In Press date: 6 October 2017
e-pub ahead of print date: 14 October 2017

Identifiers

Local EPrints ID: 414920
URI: http://eprints.soton.ac.uk/id/eprint/414920
ISSN: 1932-846X
PURE UUID: cbce4814-9dc6-44a4-bc10-eab4daf583df
ORCID for Diego Gomez-Nicola: ORCID iD orcid.org/0000-0002-5316-2682

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Date deposited: 17 Oct 2017 16:30
Last modified: 16 Mar 2024 05:50

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Contributors

Author: Jose P. Lopez-Atalaya
Author: Katharine E. Askew
Author: Amanda Sierra

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