Division of Life Science, State Key Laboratory of Molecular Neuroscience and Center of Systems Biology and Human Health, Hong Kong University of Science and Technology, Clear Water Bay, Kowloon, Hong Kong, P.R. China.
Division of Life Science, State Key Laboratory of Molecular Neuroscience and Center of Systems Biology and Human Health, Hong Kong University of Science and Technology, Clear Water Bay, Kowloon, Hong Kong, P.R. China.
Dev Cell. 2016 Jul 25;38(2):214-22. doi: 10.1016/j.devcel.2016.06.018. Epub 2016 Jul 14.
Microglia are CNS-resident macrophages and play important roles in neural development and function. However, how microglial precursors born in peripheral tissues colonize the CNS remains undefined. Using in vivo imaging and genetic manipulation of zebrafish, we showed that microglial precursors enter the optic tectum of the midbrain, where the majority of microglia reside during early development, via the lateral periphery between the eyes and brain and the ventral periphery of the brain in a circulation-independent manner. The colonization of the optic tectum by microglial precursors is dynamic and driven by apoptotic neuronal death, which occurs naturally in the midbrain during neurogenesis. We further show that lysophosphatidylcholine, a phospholipid known to be released from apoptotic cells, can promote microglial precursor entry into the brain via its cognate receptors grp132b. Our study reveals that microglia colonization of developing zebrafish midbrain is triggered by apoptotic neuronal death, possibly via releasing lysophosphatidylcholine.
小胶质细胞是中枢神经系统（CNS）常驻巨噬细胞，在神经发育和功能中发挥重要作用。然而，外周组织中产生的小胶质前体细胞如何定植到中枢神经系统尚不清楚。通过对斑马鱼的体内成像和遗传操作，我们发现小胶质前体细胞通过眼睛和大脑之间的外侧边缘以及大脑的腹侧边缘，以非循环依赖的方式进入中脑的视顶盖（optic tectum），视顶盖是大多数小胶质细胞在早期发育过程中所在的位置。小胶质前体细胞对视顶盖的定植是动态的，由神经发生过程中中脑自然发生的凋亡性神经元死亡所驱动。我们进一步表明，溶血磷脂酰胆碱（一种已知从凋亡细胞释放的磷脂）可以通过其同源受体 grp132b 促进小胶质前体细胞进入大脑。我们的研究揭示了凋亡性神经元死亡可能通过释放溶血磷脂酰胆碱触发了发育中的斑马鱼中脑神经细胞的小胶质细胞定植。
