Department of Biological Science, Florida State University, Tallahassee, FL 32306-4295, USA.
Development. 2013 Feb;140(4):897-905. doi: 10.1242/dev.080192. Epub 2013 Jan 16.
Development in multicellular organisms includes both small incremental changes and major switches of cell differentiation and proliferation status. During Drosophila oogenesis, the follicular epithelial cells undergo two major developmental switches that cause global changes in the cell-cycle program. One, the switch from the endoreplication cycle to a gene-amplification phase, during which special genomic regions undergo repeated site-specific replication, is attributed to Notch downregulation, ecdysone signaling activation and upregulation of the zinc-finger protein Tramtrack69 (Ttk69). Here, we report that the microRNA miR-7 exerts an additional layer of regulation in this developmental switch by regulating Ttk69 transcripts. miR-7 recognizes the 3' UTR of ttk69 transcripts and regulates Ttk69 expression in a dose-dependent manner. Overexpression of miR-7 effectively blocks the switch from the endocycle to gene amplification through its regulation of ttk69. miR-7 and Ttk69 also coordinate other cell differentiation events, such as vitelline membrane protein expression, that lead to the formation of the mature egg. Our studies reveal the important role miR-7 plays in developmental decision-making in association with signal-transduction pathways.
在多细胞生物的发育过程中,既有微小的渐进变化,也有细胞分化和增殖状态的重大转变。在果蝇卵子发生过程中,滤泡上皮细胞经历了两个主要的发育转变,导致细胞周期程序的全局变化。一个是从内复制周期到基因扩增阶段的转变,在此期间,特殊的基因组区域经历重复的特定部位复制,归因于 Notch 下调、蜕皮激素信号激活和锌指蛋白 Tramtrack69(Ttk69)的上调。在这里,我们报告说,microRNA miR-7 通过调节 Ttk69 转录本在这个发育开关中发挥了额外的调节作用。miR-7 识别 ttk69 转录本的 3'UTR,并以剂量依赖的方式调节 Ttk69 的表达。miR-7 的过表达通过其对 ttk69 的调节有效地阻止了从内复制周期到基因扩增的转变。miR-7 和 Ttk69 还协调其他细胞分化事件,如卵黄膜蛋白的表达,导致成熟卵子的形成。我们的研究揭示了 miR-7 在与信号转导途径相关的发育决策中所起的重要作用。