Jumu is required for circulating hemocyte differentiation and phagocytosis in Drosophila
Jumu is required for circulating hemocyte differentiation and phagocytosis in Drosophila
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Jumu 是果蝇循环血细胞分化和吞噬作用所必需的
DOI：
10.1186/s12964-018-0305-3
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发表时间：
2018-12-05
影响因子：
8.4
通讯作者：
Jin, Li Hua
中科院分区：
文献类型：
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作者：
Hao, Yangguang;Yu, Shichao;Jin, Li Hua
造血和细胞免疫的调节机制在昆虫和哺乳动物之间显示出高度的相似性，果蝇已成为研究细胞免疫应答的良好模型。Jumeau（Jumu）是翼螺旋/叉头（FKH）转录因子家族的成员，并且是果蝇发育所必需的。成年jumu突变果蝇表现出有缺陷的血细胞吞噬功能和较弱的防御能力，对病原体感染。在此，我们进一步研究了巨母在调节幼虫血细胞发育和吞噬作用中的作用。采用体内吞噬实验、免疫组化、荧光定量PCR和免疫印迹等方法研究巨母对血细胞吞噬功能的影响。采用5-溴-2-脱氧尿苷（BrdU）标记、磷酸化组蛋白H3（PH 3）和TdT介导的dUTP缺口末端标记（TUNEL）法检测血细胞增殖和凋亡;采用免疫组织化学和镶嵌分析结合抑制性细胞标记（MARCM）克隆分析法检测Jumu在Toll通路激活中的作用。Jumu通过调节NimC 1的表达和细胞骨架重组来间接控制血细胞的吞噬作用。jumu的缺失也会导致循环血细胞的异常增殖和分化。我们的研究结果表明，严重缺乏jumu导致产生扩大的多核血细胞，通过影响正常的细胞有丝分裂过程，并通过激活Toll通路诱导大量的板层细胞。Jumu调节果蝇循环血细胞分化和吞噬作用。我们的研究结果提供了新的见解细胞骨架调节蛋白在吞噬作用的机制作用，并建立了基础，为进一步分析哺乳动物直系同源物的Jumu在哺乳动物先天免疫的调节机制。
The regulatory mechanisms of hematopoiesis and cellular immunity show a high degree of similarity between insects and mammals, and Drosophila has become a good model for investigating cellular immune responses. Jumeau (Jumu) is a member of the winged-helix/forkhead (FKH) transcription factor family and is required for Drosophila development. Adult jumu mutant flies show defective hemocyte phagocytosis and a weaker defense capability against pathogen infection. Here, we further investigated the role of jumu in the regulation of larval hemocyte development and phagocytosis. In vivo phagocytosis assays, immunohistochemistry, Real-time quantitative PCR and immunoblotting were performed to investigate the effect of Jumu on hemocyte phagocytosis. 5-Bromo-2-deoxyUridine (BrdU) labeling, phospho-histone H3 (PH3) and TdT-mediated dUTP Nick-End Labeling (TUNEL) staining were performed to analyze the proliferation and apoptosis of hemocyte; immunohistochemistry and Mosaic analysis with a repressible cell marker (MARCM) clone analysis were performed to investigate the role of Jumu in the activation of Toll pathway. Jumu indirectly controls hemocyte phagocytosis by regulating the expression of NimC1 and cytoskeleton reorganization. The loss of jumu also causes abnormal proliferation and differentiation in circulating hemocytes. Our results suggest that a severe deficiency of jumu leads to the generation of enlarged multinucleate hemocytes by affecting the normal cell mitosis process and induces numerous lamellocytes by activating the Toll pathway. Jumu regulates circulating hemocyte differentiation and phagocytosis in Drosophila. Our findings provide new insight into the mechanistic roles of cytoskeleton regulatory proteins in phagocytosis and establish a basis for further analyses of the regulatory mechanism of the mammalian ortholog of Jumu in mammalian innate immunity.