Xi Rongwen, Doan Choung, Liu Dazhi, Xie Ting
Stowers Institute for Medical Research, 1000 E. 50th Street, Kansas City, MO 64110, USA.
Development. 2005 Dec;132(24):5365-74. doi: 10.1242/dev.02151. Epub 2005 Nov 9.
In the Drosophila ovary, germline stem cell (GSC) self-renewal is controlled by both extrinsic and intrinsic factors. The Bmp signal from niche cells controls GSC self-renewal by directly repressing a Bam-dependent differentiation pathway in GSCs. pelota (pelo), which has been previously shown to be required for Drosophila male meiosis, was identified in our genetic screen as a dominant suppressor of the dpp overexpression-induced GSC tumor phenotype. In this study, we reveal the unexpected new role of Pelo in controlling GSC self-renewal by repressing a Bam-independent differentiation pathway. In pelo mutant ovaries, GSCs are lost rapidly owing to differentiation. Results from genetic mosaic analysis and germ cell-specific rescue show that it functions as an intrinsic factor to control GSC self-renewal. In pelo mutant GSCs, Bmp signaling activity detected by Dad-lacZ expression is downregulated, but bam expression is still repressed. Furthermore, bam mutant germ cells are still able to differentiate into cystocytes without pelo function, indicating that Pelo is involved in repressing a Bam-independent differentiation pathway. Consistent with its homology to the eukaryotic translation release factor 1alpha, we show that Pelo is localized to the cytoplasm of the GSC. Therefore, Pelo controls GSC self-renewal by repressing a Bam-independent differentiation pathway possibly through regulating translation. As Pelo is highly conserved from Drosophila to mammals, it may also be involved in the regulation of adult stem cell self-renewal in mammals, including humans.
在果蝇卵巢中，生殖系干细胞（GSC）的自我更新受外在和内在因素共同控制。来自龛细胞的Bmp信号通过直接抑制GSC中依赖Bam的分化途径来控制GSC的自我更新。pelota（pelo）先前已被证明是果蝇雄性减数分裂所必需的，在我们的遗传筛选中被鉴定为dpp过表达诱导的GSC肿瘤表型的显性抑制因子。在本研究中，我们揭示了Pelo通过抑制不依赖Bam的分化途径在控制GSC自我更新方面出人意料的新作用。在pelo突变体卵巢中，GSC由于分化而迅速丢失。遗传镶嵌分析和生殖细胞特异性拯救的结果表明，它作为一种内在因子来控制GSC的自我更新。在pelo突变体GSC中，通过Dad-lacZ表达检测到的Bmp信号活性下调，但bam表达仍受到抑制。此外，bam突变的生殖细胞在没有pelo功能的情况下仍能分化为囊细胞，这表明Pelo参与抑制不依赖Bam的分化途径。与其与真核生物翻译释放因子1α的同源性一致，我们表明Pelo定位于GSC的细胞质中。因此，Pelo可能通过调节翻译来抑制不依赖Bam的分化途径，从而控制GSC的自我更新。由于Pelo从果蝇到哺乳动物都高度保守，它也可能参与包括人类在内的哺乳动物成体干细胞自我更新的调节。
