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

  • Liam Barry-Carroll
  • Philip Greulich
  • Abigail R Marshall
  • Kristoffer Riecken
  • Boris Fehse
  • Katharine E Askew
  • Kaizhen Li
  • Olga Garaschuk
  • David A Menassa
  • Diego Gomez-Nicola

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.

Bibliographical data

Original languageEnglish
ISSN2211-1247
DOIs
Publication statusPublished - 30.05.2023

Comment Deanary

Copyright © 2023 The Author(s). Published by Elsevier Inc. All rights reserved.

PubMed 37099424