Microglia colonize the developing brain by clonal expansion of highly proliferative progenitors, following allometric scaling
Cell Reports. 2023-05-01; 42(5): 112425
DOI: 10.1016/j.celrep.2023.112425
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1. Cell Rep. 2023 May 30;42(5):112425. doi: 10.1016/j.celrep.2023.112425. Epub
2023 Apr 25.
Microglia colonize the developing brain by clonal expansion of highly
proliferative progenitors, following allometric scaling.
Barry-Carroll L(1), Greulich P(2), Marshall AR(1), Riecken K(3), Fehse B(3),
Askew KE(1), Li K(4), Garaschuk O(4), Menassa DA(5), Gomez-Nicola D(6).
Author information:
(1)School of Biological Sciences, University of Southampton, Southampton General
Hospital, Southampton, UK.
(2)School of Mathematical Sciences, University of Southampton, Southampton, UK;
Institute for Life Sciences (IfLS), University of Southampton, Southampton, UK.
(3)Research Department Cell and Gene Therapy, University Medical Center
Hamburg-Eppendorf, Hamburg, Germany.
(4)Department of Neurophysiology, University of Tübingen, Tübingen, Germany.
(5)School of Biological Sciences, University of Southampton, Southampton General
Hospital, Southampton, UK; The Queen’s College, University of Oxford, Oxford,
UK.
(6)School of Biological Sciences, University of Southampton, Southampton General
Hospital, Southampton, UK; Institute for Life Sciences (IfLS), University of
Southampton, Southampton, UK. Electronic address: .
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.
Copyright © 2023 The Author(s). Published by Elsevier Inc. All rights reserved.
DOI: 10.1016/j.celrep.2023.112425
PMID: 37099424 [Indexed for MEDLINE]
Conflict of interest statement: Declaration of interests The authors declare no
competing interests.