Germ Cell Lineage Homeostasis in Drosophila Requires the Vasa RNA Helicase
Germ Cell Lineage Homeostasis in Drosophila Requires the Vasa RNA Helicase
复制标题
DOI：
10.1534/genetics.119.302558
复制
发表时间：
2019-11-01
期刊：
影响因子：
3.3
通讯作者：
Ephrussi, Anne
中科院分区：
文献类型：
--
作者：
Durdevic, Zeljko;Ephrussi, Anne
保守的RNA解旋酶Vasa是许多生物体生殖细胞发育所必需的。在果蝇中，PIWI相互作用的RNA通路组分（包括Vasa）的丢失导致Chk2依赖性卵子发生停滞。然而，这种停滞是否是由于特定阶段的Chk2信号传导，以及这种停滞是否需要持续的Chk2信号传导尚不清楚。在这里，我们表明，Vasa在生殖阶段的情况下导致Chk2依赖的卵子发生停滞。此外，我们报告的卵巢管数量的年龄依赖性下降，在苍蝇缺乏Vasa表达，只有在生殖器和功能丧失的Vasa突变苍蝇。我们表明，Chk2激活专门在生殖区是足以中断卵子发生，并减少卵巢数量在老龄苍蝇。一旦在生殖器中诱导，Chk 2介导的生殖细胞发育停滞不能通过恢复Vasa或通过在停滞的卵室中下调Chk 2来克服。这些发现，连同本研究中鉴定的Vasa相关蛋白的身份，证明了解旋酶在生殖细胞谱系维持中的重要作用，并表明Vasa在生殖系干细胞稳态中的功能。
The conserved RNA helicase Vasa is required for germ cell development in many organisms. In Drosophila melanogaster loss of PIWI-interacting RNA pathway components, including Vasa, causes Chk2-dependent oogenesis arrest. However, whether the arrest is due to Chk2 signaling at a specific stage and whether continuous Chk2 signaling is required for the arrest is unknown. Here, we show that absence of Vasa during the germarial stages causes Chk2-dependent oogenesis arrest. Additionally, we report the age-dependent decline of the ovariole number both in flies lacking Vasa expression only in the germarium and in loss-of-function vasa mutant flies. We show that Chk2 activation exclusively in the germarium is sufficient to interrupt oogenesis and to reduce ovariole number in aging flies. Once induced in the germarium, Chk2-mediated arrest of germ cell development cannot be overcome by restoration of Vasa or by downregulation of Chk2 in the arrested egg chambers. These findings, together with the identity of Vasa-associated proteins identified in this study, demonstrate an essential role of the helicase in the germ cell lineage maintenance and indicate a function of Vasa in germline stem cell homeostasis.