Microglial colonisation of the developing brain is facilitated by clonal expansion of highly proliferative progenitors and follows an allometric scaling

Microglia are the resident immune cells of the brain and arise from yolk sac-derived macrophages during early embryogenesis. On entering the brain, microglia undergo in situ proliferation and eventually colonise the entire brain by the second and third postnatal weeks in mice. However, the intricate dynamics of their developmental expansion remain unclear. Here, we examine and characterise the proliferative dynamics of microglia during embryonic and postnatal development. Using complementary fate-mapping techniques, we demonstrate that the developmental colonisation of the brain by microglia is facilitated by clonal expansion of highly proliferative microglial progenitors that occupy spatial niches throughout the brain. We also find that the distribution of microglia switches from a clustered to a random pattern between embryonic and late postnatal development. Moreover, the developmental increase in microglia follows the proportional growth of the brain in an allometric manner with the density of microglia eventually stabilising when the mosaic distribution has been established. Overall, our findings offer insight into how the competition for space acts as a driving force for microglial colonisation by clonal expansion during development.