In vivo RNAi screen identifies candidate signaling genes required for collective cell migration in Drosophila ovary
In vivo RNAi screen identifies candidate signaling genes required for collective cell migration in Drosophila ovary
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DOI：
10.1007/s11427-014-4786-z
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发表时间：
2015-04-01
影响因子：
9.1
通讯作者：
Chen Jiong
中科院分区：
文献类型：
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作者：
Luo Jun;Zuo JunTao;Chen Jiong
松散或密切相关的细胞群的集体迁移在动物发育、生理事件和癌症转移中普遍存在。然而，我们对集体细胞迁移机制的理解并不完整。果蝇边缘细胞提供了强大的体内遗传模型来研究集体迁移并识别该过程的必需基因。在果蝇中使用边界细胞特异性 RNAi 沉默，我们敲低了成年果蝇中的 360 个保守信号转导基因，以确定边界细胞迁移的重要途径和基因。我们发现了大量的信号基因，其中很大一部分在边缘细胞中尚未被报道，包括 Rack1（激活的 C 激酶受体）和 brk（brinker）、mad（母亲对抗 dpp）和 sax（萨克斯管），它们编码 TGF-β 信号传导的三个组件。 RNAi 敲低表型通过 Rack1 突变体的克隆分析得到验证。我们的数据表明，Rack1 对 Src 活性的抑制可能对于边界细胞迁移和簇内聚力维持很重要。最后，我们的筛选结果不仅可以揭示胚胎发生和器官发生过程中集体迁移所涉及的信号通路，而且可以帮助我们了解参与癌症转移的保守人类基因的功能。
Collective migration of loosely or closely associated cell groups is prevalent in animal development, physiological events, and cancer metastasis. However, our understanding of the mechanisms of collective cell migration is incomplete. Drosophila border cells provide a powerful in vivo genetic model to study collective migration and identify essential genes for this process. Using border cell-specific RNAi-silencing in Drosophila, we knocked down 360 conserved signaling transduction genes in adult flies to identify essential pathways and genes for border cell migration. We uncovered a plethora of signaling genes, a large proportion of which had not been reported for border cells, including Rack1 (Receptor of activated C kinase) and brk (brinker), mad (mother against dpp), and sax (saxophone), which encode three components of TGF-beta signaling. The RNAi knock down phenotype was validated by clonal analysis of Rack1 mutants. Our data suggest that inhibition of Src activity by Rack1 may be important for border cell migration and cluster cohesion maintenance. Lastly, results from our screen not only would shed light on signaling pathways involved in collective migration during embryogenesis and organogenesis in general, but also could help our understanding for the functions of conserved human genes involved in cancer metastasis.