Germline Proliferation Is Regulated by Somatic Endocytic Genes via JNK and BMP Signaling in Drosophila.
Germline Proliferation Is Regulated by Somatic Endocytic Genes via JNK and BMP Signaling in Drosophila.
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果蝇中体细胞内吞基因通过 JNK 和 BMP 信号传导调节种系增殖
DOI：
10.1534/genetics.116.196535
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发表时间：
2017-05
期刊：
影响因子：
3.3
通讯作者：
Wang Z
中科院分区：
文献类型：
--
作者：
Tang Y;Geng Q;Chen D;Zhao S;Liu X;Wang Z
来自微环境的信号对肿瘤发生有很大贡献。其内在机制需要彻底调查。在这里，我们使用果蝇睾丸作为一个模型系统来解决这个问题，利用容易区分生殖细胞和体细胞，并跟踪细胞数量的优势。在EMS诱变筛选中，我们确定了Rab 5，一个内吞作用的关键因子，在种系增殖中的非自主作用。Rab 5在体细胞胞囊细胞中的破坏，其护送生殖系谱系的发育，诱导了未分化但遗传野生型生殖细胞的过度增殖。我们证明，这种非自主效应介导的转录激活Dpp [苍蝇同源的骨形态发生蛋白（BMP）]通过检查Dpp-报告基因的表达和敲低Dpp阻止种系过度生长。因此，Bam的蛋白水平，生殖系前分化因子通常积累在BMP/Dpp信号的情况下，在过度增殖的生殖细胞中下降。此外，我们发现JNK信号通路在Rab 5和Dpp之间起作用，因为在包囊细胞中同时抑制JNK通路和Rab 5阻止了dpp转录和生殖系肿瘤生长。此外，我们发现，多个内吞基因，如avl，TSG 101，Vps 25，或Cdc 42，需要在体细胞孢囊细胞限制生殖系扩增。这些发现表明，当周围细胞的内吞状态受损时，遗传野生型生殖细胞过度生长。这种肿瘤发生的非自主模型提供了一个简单的系统来剖析肿瘤与其生态位之间的关系。
Signals derived from the microenvironment contribute greatly to tumorigenesis . The underlying mechanism requires thorough investigation. Here, we use Drosophila testis as a model system to address this question, taking the advantage of the ease to distinguish germline and somatic cells and to track the cell numbers. In an EMS mutagenesis screen, we identified Rab5, a key factor in endocytosis, for its nonautonomous role in germline proliferation. The disruption of Rab5 in somatic cyst cells, which escort the development of germline lineage, induced the overproliferation of underdifferentiated but genetically wild-type germ cells. We demonstrated that this nonautonomous effect was mediated by the transcriptional activation of Dpp [the fly homolog of bone morphogenetic protein (BMP)] by examining the Dpp-reporter expression and knocking down Dpp to block germline overgrowth. Consistently, the protein levels of Bam, the germline prodifferentiation factor normally accumulated in the absence of BMP/Dpp signaling, decreased in the overproliferating germ cells. Further, we discovered that the JNK signaling pathway operated between Rab5 and Dpp, because simultaneously inhibiting the JNK pathway and Rab5 in cyst cells prevented both dpp transcription and germline tumor growth. Additionally, we found that multiple endocytic genes, such as avl, TSG101, Vps25, or Cdc42, were required in the somatic cyst cells to restrict germline amplification. These findings indicate that when the endocytic state of the surrounding cells is impaired, genetically wild-type germ cells overgrow. This nonautonomous model of tumorigenesis provides a simple system to dissect the relation between tumor and its niche.
影响因子：
64.5
作者：
Reilly KM;Van Dyke T
通讯作者：
Van Dyke T