A Genetic Mosaic Screen Reveals Ecdysone-Responsive Genes Regulating Drosophila Oogenesis.
A Genetic Mosaic Screen Reveals Ecdysone-Responsive Genes Regulating Drosophila Oogenesis.
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DOI：
10.1534/g3.116.028951
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发表时间：
2016-08-09
期刊：
影响因子：
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通讯作者：
Drummond-Barbosa D
中科院分区：
文献类型：
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作者：
Ables ET;Hwang GH;Finger DS;Hinnant TD;Drummond-Barbosa D
果蝇卵子发生的多个方面，包括生殖干细胞活性、生殖细胞分化和卵泡存活，都受到类固醇激素蜕皮激素的调节。虽然蜕皮激素信号在发育过程中的转录靶点已被广泛研究，但卵巢中的靶点仍在很大程度上未知。唾液腺多线染色体的早期研究导致蜕皮激素刺激分级转录级联的模型，其中蜕皮激素敏感性转录因子的核心组通过激活转录靶点的次级分支诱导组织特异性反应。最近，全基因组方法已经确定了数百个推定的蜕皮激素反应靶点。然而，确定这些推定的靶点是否代表体内真正的靶点，需要通过传统的突变体分析以细胞类型特异性方式对其进行测试。为了研究蜕皮激素信号调节卵子发生的分子机制，我们使用遗传镶嵌分析来筛选在卵子发生的最早阶段控制中可能的蜕皮激素反应基因的新角色。我们鉴定了一组干细胞维持、干细胞和祖细胞增殖以及卵泡包裹、生长和存活所需的基因。这些基因编码转录因子、染色质调节因子和RNA运输、稳定性和核糖体生物合成所需的因子，表明蜕皮激素可能控制卵子发生过程中的广泛分子过程。我们的研究结果表明，虽然已知蜕皮激素靶基因具有细胞类型特异性作用，但许多控制幼虫或蛹细胞类型的蜕皮激素反应基因在发育过渡期被粘附地用于成虫卵巢。这些结果提供了新的见解蜕皮激素信号控制卵子发生的分子机制，奠定了新的基础，为未来的研究。
Multiple aspects of Drosophila oogenesis, including germline stem cell activity, germ cell differentiation, and follicle survival, are regulated by the steroid hormone ecdysone. While the transcriptional targets of ecdysone signaling during development have been studied extensively, targets in the ovary remain largely unknown. Early studies of salivary gland polytene chromosomes led to a model in which ecdysone stimulates a hierarchical transcriptional cascade, wherein a core group of ecdysone-sensitive transcription factors induce tissue-specific responses by activating secondary branches of transcriptional targets. More recently, genome-wide approaches have identified hundreds of putative ecdysone-responsive targets. Determining whether these putative targets represent bona fide targets in vivo, however, requires that they be tested via traditional mutant analysis in a cell-type specific fashion. To investigate the molecular mechanisms whereby ecdysone signaling regulates oogenesis, we used genetic mosaic analysis to screen putative ecdysone-responsive genes for novel roles in the control of the earliest steps of oogenesis. We identified a cohort of genes required for stem cell maintenance, stem and progenitor cell proliferation, and follicle encapsulation, growth, and survival. These genes encode transcription factors, chromatin modulators, and factors required for RNA transport, stability, and ribosome biogenesis, suggesting that ecdysone might control a wide range of molecular processes during oogenesis. Our results suggest that, although ecdysone target genes are known to have cell type-specific roles, many ecdysone response genes that control larval or pupal cell types at developmental transitions are used reiteratively in the adult ovary. These results provide novel insights into the molecular mechanisms by which ecdysone signaling controls oogenesis, laying new ground for future studies.