School of Biological Sciences, University of Southampton, Southampton General Hospital, Southampton, UK.
School of Mathematical Sciences, University of Southampton, Southampton, UK; Institute for Life Sciences (IfLS), University of Southampton, Southampton, UK.
Cell Rep. 2023 May 30;42(5):112425. doi: 10.1016/j.celrep.2023.112425. Epub 2023 Apr 25.
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.
小胶质细胞起源于卵黄囊，并在胚胎早期进入大脑。进入大脑后，小胶质细胞经历原位增殖，并在小鼠出生后第三周最终遍布整个大脑。然而，它们的发育扩张的复杂性仍不清楚。在这里，我们使用互补的谱系追踪技术来描述胚胎和出生后发育中小胶质细胞的增殖动态。我们证明，大脑的发育定植是通过占据大脑各个区域空间位的高度增殖的小胶质前体细胞的克隆扩增来促进的。此外，小胶质细胞的空间分布在胚胎期和晚期出生后发育之间从聚类模式转变为随机模式。有趣的是，小胶质细胞数量的发育增加以一种比例生长的方式遵循大脑的比例生长，直到建立了镶嵌式分布。总的来说，我们的研究结果提供了一个深入了解的机会，即空间竞争如何通过克隆扩增来驱动发育中小胶质细胞的定植。
