Development of ramified microglia from early macrophages in the zebrafish optic tectum
Development of ramified microglia from early macrophages in the zebrafish optic tectum
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DOI：
10.1002/dneu.22039
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发表时间：
2013-01-01
影响因子：
3
通讯作者：
Becker, Thomas S.
中科院分区：
文献类型：
--
作者：
Svahn, Adam J.;Graeber, Manuel B.;Becker, Thomas S.
小胶质细胞是大脑中驻留的巨噬细胞前体，是维持组织内稳态所必需的，并被广泛的病理刺激激活。它们在免疫和炎症反应中起着关键作用。早期的小胶质细胞来源于原始的巨噬细胞，然而，从早期的活动形式到分支的成熟的常驻小胶质细胞的转变还没有被实时检测到。为了提供这样的分析，我们使用了斑马鱼转基因系，其中荧光报告基因的表达是由巨噬细胞表达基因1(mpeg1；Ellet等人)的启动子驱动的。[2011]：血液117(4)：e49e56)。这使得研究这些细胞在活的、完整的幼虫中的发育成为可能。我们发现，小胶质细胞从参与吞噬凋亡细胞体的高运动性阿米巴细胞发展成一种在阿米巴和分支形态之间快速来回变化的小胶质细胞类型。这些正在变形的小胶质细胞最终稳定下来，形成典型的成熟分支形态。发育中的小胶质细胞经常与脑内的毛细血管接触，也经常相互接触。受精后10d，小胶质细胞出现对称性分裂。在成年视顶盖内，小胶质细胞高度分枝，类似于哺乳动物的小胶质细胞。此外，转基因mpeg1还标记了受精后几天视顶盖上的皮肤中的高度分枝细胞，这些细胞可能代表朗格汉斯细胞。因此，斑马鱼小胶质细胞的发育及其细胞相互作用的研究是在完整发育的大脑中实时和细胞分辨率进行的。(C)2012年Wiley期刊公司开发神经生物学，2013年
Microglia, the resident macrophage precursors of the brain, are necessary for the maintenance of tissue homeostasis and activated by a wide range of pathological stimuli. They have a key role in immune and inflammatory responses. Early microglia stem from primitive macrophages, however the transition from early motile forms to the ramified mature resident microglia has not been assayed in real time. In order to provide such an assay, we used zebrafish transgenic lines in which fluorescent reporter expression is driven by the promoter of macrophage expressed gene 1 (mpeg1; Ellet et al. [2011]: Blood 117(4): e49e56,). This enabled the investigation of the development of these cells in live, intact larvae. We show that microglia develop from highly motile amoeboid cells that are engaged in phagocytosis of apoptotic cell bodies into a microglial cell type that rapidly morphs back and forth between amoeboid and ramified morphologies. These morphing microglia eventually settle into a typical mature ramified morphology. Developing microglia frequently come into contact with blood capillaries in the brain, and also frequently contact each other. Up to 10 days postfertilization, microglia were observed to undergo symmetric division. In the adult optic tectum, the microglia are highly branched, resembling mammalian microglia. In addition, the mpeg1 transgene also labeled highly branched cells in the skin overlying the optic tectum from 89 days postfertilization, which likely represent Langerhans cells. Thus, the development of zebrafish microglia and their cellular interactions was studied in the intact developing brain in real time and at cellular resolution. (C) 2012 Wiley Periodicals, Inc. Develop Neurobiol, 2013