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

Liam Barry-Carroll1, Philip Greulich2, Abigail R Marshall1

  • 1School of Biological Sciences, University of Southampton, Southampton General Hospital, Southampton, UK.

Cell Reports
|April 26, 2023
PubMed

Insights

Microglia colonization of the brain is driven by the clonal expansion of progenitor cells. This process ensures microglia numbers scale with brain growth, establishing a random distribution.

Area of Science:

  • Neuroscience
  • Developmental Biology
  • Immunology

Background:

  • Microglia, the brain's resident immune cells, originate from the yolk sac and colonize the brain during early development.
  • Their proliferation and colonization patterns throughout embryogenesis and early postnatal life are not fully understood.

Purpose of the Study:

  • To investigate the proliferative dynamics and spatial distribution of microglia during embryonic and postnatal brain development.
  • To elucidate the mechanisms driving microglial colonization and expansion in the developing brain.

Main Methods:

  • Utilized complementary fate-mapping techniques to track microglial development.
  • Analyzed microglial proliferation, spatial distribution, and number changes in relation to brain growth.

Main Results:

  • Demonstrated that microglial colonization is facilitated by clonal expansion of progenitor cells residing in specific brain niches.
  • Observed a switch in microglial distribution from clustered to random patterns between embryonic and late postnatal stages.
  • Found that microglial population expansion scales allometrically with brain growth until a mosaic distribution is achieved.

Conclusions:

  • Microglial colonization is driven by the spatial expansion of progenitor clones, influenced by niche availability.
  • The developmental increase in microglia numbers is proportionally linked to brain growth.
  • Competition for space likely plays a role in driving microglial colonization through clonal expansion.