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. How-ever, 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 expan-sion 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 pro-portional 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.

Automated summary

Microglia are derived from the yolk sac and migrate into the brain during early embryonic development. They undergo in situ proliferation and ultimately colonize the entire brain by the third postnatal week in mice. This study reveals that their colonization is facilitated by clonal expansion of highly proliferative microglial progenitors distributed throughout the brain. Additionally, the spatial distribution of microglia changes from clustered to random during development.