The University of Southampton
University of Southampton Institutional Repository

Microglia colonize the developing brain by clonal expansion of highly proliferative progenitors, following allometric scaling

Microglia colonize the developing brain by clonal expansion of highly proliferative progenitors, following allometric scaling
Microglia colonize the developing brain by clonal expansion of highly proliferative progenitors, following allometric scaling
Microglia arise from the yolk sac and enter the brain during early embryogenesis. Upon entry, microglia undergo in situ proliferation and eventually colonize the entire brain by the third postnatal week in mice. However, the intricacies of their developmental expansion remain unclear. Here, we characterize the proliferative dynamics of microglia during embryonic and postnatal development using complementary fate-mapping techniques. We demonstrate that the developmental colonization of the brain is facilitated by clonal expansion of highly proliferative microglial progenitors that occupy spatial niches throughout the brain. Moreover, the spatial distribution of microglia switches from a clustered to a random pattern between embryonic and late postnatal development. Interestingly, the developmental increase in microglial numbers follows the proportional growth of the brain in an allometric manner until a mosaic distribution has been established. Overall, our findings offer insight into how the competition for space may drive microglial colonization by clonal expansion during development.
CP: Immunology, CP: Neuroscience, RGB, brain development, clonality, fate mapping, microglia, neareast neighbour distance
2211-1247
Barry-Carroll, Liam
2ea75b82-34cd-4283-9d28-8ac0f7a2bbde
Greulich, Philip
65da32ad-a73a-435a-86e0-e171437430a9
Marshall, Abigail Rose
121b3b1f-eab6-44f4-b926-13ac41e775c8
Riecken, Kristoffer
0eca316e-6c54-4cda-80e0-92c571263996
Fehse, Boris
c4936883-d98d-48fc-91f4-691ef0c7ee5a
Askew, Katharine Elizabeth
ffc96fb4-f94c-4cb7-8479-e9f0b2dae0c7
Li, Kaizhen
49fd8b31-e763-4b28-946f-e78fcd74fd7a
Garaschuk, Olga
f751209b-b876-41b8-9d83-b999f3ce1f82
Menassa, David
eeb394a6-c72b-49d7-a820-95b0256c22d5
Gomez-Nicola, Diego
0680aa66-9dee-47cf-a8d3-e39c988f85b5
Barry-Carroll, Liam
2ea75b82-34cd-4283-9d28-8ac0f7a2bbde
Greulich, Philip
65da32ad-a73a-435a-86e0-e171437430a9
Marshall, Abigail Rose
121b3b1f-eab6-44f4-b926-13ac41e775c8
Riecken, Kristoffer
0eca316e-6c54-4cda-80e0-92c571263996
Fehse, Boris
c4936883-d98d-48fc-91f4-691ef0c7ee5a
Askew, Katharine Elizabeth
ffc96fb4-f94c-4cb7-8479-e9f0b2dae0c7
Li, Kaizhen
49fd8b31-e763-4b28-946f-e78fcd74fd7a
Garaschuk, Olga
f751209b-b876-41b8-9d83-b999f3ce1f82
Menassa, David
eeb394a6-c72b-49d7-a820-95b0256c22d5
Gomez-Nicola, Diego
0680aa66-9dee-47cf-a8d3-e39c988f85b5

Barry-Carroll, Liam, Greulich, Philip, Marshall, Abigail Rose, Riecken, Kristoffer, Fehse, Boris, Askew, Katharine Elizabeth, Li, Kaizhen, Garaschuk, Olga, Menassa, David and Gomez-Nicola, Diego (2023) Microglia colonize the developing brain by clonal expansion of highly proliferative progenitors, following allometric scaling. Cell Reports, 42 (5), [112425]. (doi:10.1016/j.celrep.2023.112425).

Record type: Article

Abstract

Microglia arise from the yolk sac and enter the brain during early embryogenesis. Upon entry, microglia undergo in situ proliferation and eventually colonize the entire brain by the third postnatal week in mice. However, the intricacies of their developmental expansion remain unclear. Here, we characterize the proliferative dynamics of microglia during embryonic and postnatal development using complementary fate-mapping techniques. We demonstrate that the developmental colonization of the brain is facilitated by clonal expansion of highly proliferative microglial progenitors that occupy spatial niches throughout the brain. Moreover, the spatial distribution of microglia switches from a clustered to a random pattern between embryonic and late postnatal development. Interestingly, the developmental increase in microglial numbers follows the proportional growth of the brain in an allometric manner until a mosaic distribution has been established. Overall, our findings offer insight into how the competition for space may drive microglial colonization by clonal expansion during development.

Text
2022.09.15.507569v1.full - Author's Original
Available under License Creative Commons Attribution.
Download (1MB)
Text
Accepted paper Barry-Carroll - Accepted Manuscript
Available under License Creative Commons Attribution.
Download (2MB)
Text
1-s2.0-S2211124723004369-main - Version of Record
Available under License Creative Commons Attribution.
Download (6MB)

More information

Accepted/In Press date: 6 April 2023
e-pub ahead of print date: 25 April 2023
Published date: 30 May 2023
Additional Information: Funding Information: We thank the Southampton Flow Cytometry Facility and the Imaging Unit for technical advice and the Biomedical Research Facility for assistance with animal breeding and maintenance. We thank Georgina Dawes for technical assistance and Maria Olmedillas del Moral, Cris Richter, and Bianca Brawek for analyses of the specificity of mir-RGB vectors. We thank Professor Mark Cragg for provision of Vav-Bcl2 mice, and Dr. Salah Elias for provision of RosamT/mG mice. The research was funded by the Leverhulme Trust (RPG-2016-311), the Medical Research Council (MR/P024572/1), and the Deutsche Forschungsgemeinschaft (SFB841/SP01 to K.R. and B.F.). D.G.-N. designed the study, secured the funding, and supervised the project. L.B.-C. performed most of experiments and analyzed the data. A.R.M. and K.E.A. contributed experimental work and analysis. K.R. and B.F. provided SFFV-RGB vectors. K.L. and O.G. provided the mir-RGB vectors. P.G. performed mathematical modeling of the data. L.B.-C. D.A.M. and D.G.-N. wrote the manuscript. All authors contributed to drafting and read and approved the final manuscript. The authors declare no competing interests. We support inclusive, diverse, and equitable conduct of research. Funding Information: We thank the Southampton Flow Cytometry Facility and the Imaging Unit for technical advice and the Biomedical Research Facility for assistance with animal breeding and maintenance. We thank Georgina Dawes for technical assistance and Maria Olmedillas del Moral, Cris Richter, and Bianca Brawek for analyses of the specificity of mir-RGB vectors. We thank Professor Mark Cragg for provision of Vav-Bcl2 mice, and Dr. Salah Elias for provision of Rosa mT/mG mice. The research was funded by the Leverhulme Trust ( RPG-2016-311 ), the Medical Research Council ( MR/P024572/1 ), and the Deutsche Forschungsgemeinschaft ( SFB841/SP01 to K.R. and B.F.). Publisher Copyright: © 2023 The Author(s)
Keywords: CP: Immunology, CP: Neuroscience, RGB, brain development, clonality, fate mapping, microglia, neareast neighbour distance

Identifiers

Local EPrints ID: 473429
URI: http://eprints.soton.ac.uk/id/eprint/473429
ISSN: 2211-1247
PURE UUID: 01e42b5e-254a-4122-86e5-841d5970e3f9
ORCID for Philip Greulich: ORCID iD orcid.org/0000-0001-5247-6738
ORCID for Diego Gomez-Nicola: ORCID iD orcid.org/0000-0002-5316-2682

Catalogue record

Date deposited: 18 Jan 2023 17:30
Last modified: 18 Mar 2024 03:27

Export record

Altmetrics

Contributors

Author: Liam Barry-Carroll
Author: Philip Greulich ORCID iD
Author: Abigail Rose Marshall
Author: Kristoffer Riecken
Author: Boris Fehse
Author: Katharine Elizabeth Askew
Author: Kaizhen Li
Author: Olga Garaschuk
Author: David Menassa

Download statistics

Downloads from ePrints over the past year. Other digital versions may also be available to download e.g. from the publisher's website.

View more statistics

Atom RSS 1.0 RSS 2.0

Contact ePrints Soton: eprints@soton.ac.uk

ePrints Soton supports OAI 2.0 with a base URL of http://eprints.soton.ac.uk/cgi/oai2

This repository has been built using EPrints software, developed at the University of Southampton, but available to everyone to use.

We use cookies to ensure that we give you the best experience on our website. If you continue without changing your settings, we will assume that you are happy to receive cookies on the University of Southampton website.

×