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
Barry-Carroll, Liam
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Greulich, Philip
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Marshall, Abigail Rose
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Riecken, Kristoffer
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Fehse, Boris
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Askew, Katharine Elizabeth
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Li, Kaizhen
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Garaschuk, Olga
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Menassa, David
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Gomez-Nicola, Diego
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30 May 2023
Barry-Carroll, Liam
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Greulich, Philip
65da32ad-a73a-435a-86e0-e171437430a9
Marshall, Abigail Rose
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Riecken, Kristoffer
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Fehse, Boris
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Askew, Katharine Elizabeth
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Li, Kaizhen
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Garaschuk, Olga
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Menassa, David
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Gomez-Nicola, Diego
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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).
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.
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2022.09.15.507569v1.full
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Accepted paper Barry-Carroll
- Accepted Manuscript
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1-s2.0-S2211124723004369-main
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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
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Date deposited: 18 Jan 2023 17:30
Last modified: 06 Jun 2024 01:52
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Contributors
Author:
Liam Barry-Carroll
Author:
Abigail Rose Marshall
Author:
Kristoffer Riecken
Author:
Boris Fehse
Author:
Katharine Elizabeth Askew
Author:
Kaizhen Li
Author:
Olga Garaschuk
Author:
David Menassa
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