Microglia are the resident macrophages of the CNS that serve critical roles in brain construction. Although human brains contain microglia by 4 weeks gestation, an understanding of the earliest microglia that seed the brain during its development remains unresolved. Using time-lapse imaging in zebrafish, we discovered a mrc1a⁺ microglia precursor population that seeds the brain before traditionally described microglia. These early microglia precursors are dependent on lymphatic vasculature that surrounds the brain and are independent of pu1⁺ yolk sac-derived microglia. Single-cell RNA-sequencing datasets reveal Mrc1⁺ microglia in the embryonic brains of mice and humans. We then show in zebrafish that these early mrc1a⁺ microglia precursors preferentially expand during pathophysiological states in development. Taken together, our results identify a critical role of lymphatics in the microglia precursors that seed the early embryonic brain.

小胶质细胞是中枢神经系统的常驻巨噬细胞，在大脑构造中发挥着关键作用。尽管人类大脑在妊娠 4 周时就含有小胶质细胞，但对在大脑发育过程中植入大脑的最早的小胶质细胞的了解仍然悬而未决。利用斑马鱼的延时成像，我们发现了一种mrc1a ⁺小胶质细胞前体群体，它在传统描述的小胶质细胞之前在大脑中播种。这些早期小胶质细胞前体依赖于大脑周围的淋巴脉管系统，并且独立于pu1 ⁺卵黄囊衍生的小胶质细胞。单细胞 RNA 测序数据集揭示了小鼠和人类胚胎大脑中的Mrc1 ^{+小胶质细胞。}然后，我们在斑马鱼中证明，这些早期mrc1a ⁺小胶质细胞前体在发育的病理生理状态期间优先扩张。综上所述，我们的结果确定了淋巴管在播种早期胚胎大脑的小胶质细胞前体中的关键作用。