Shcherbata Halyna R, Ward Ellen J, Fischer Karin A, Yu Jenn-Yah, Reynolds Steven H, Chen Chun-Hong, Xu Peizhang, Hay Bruce A, Ruohola-Baker Hannele
Department of Biochemistry, Institute for Stem Cell and Regenerative Medicine, University of Washington, Seattle, WA 98195, USA.
Cell Stem Cell. 2007 Dec 13;1(6):698-709. doi: 10.1016/j.stem.2007.11.007.
In this study, we uncover a role for microRNAs in Drosophila germline stem cell (GSC) maintenance. Disruption of Dicer-1 function in GSCs during adult life results in GSC loss. Surprisingly, however, loss of Dicer-1 during development does not result in a GSC maintenance defect, although a defect is seen if both Dicer-1 and Dicer-2 function are disrupted. Loss of the bantam microRNA mimics the Dicer-1 maintenance defect when induced in adult GSCs, suggesting that bantam plays a key role in GSC self-renewal. Mad, a component of the TGF-beta pathway, behaves similarly to Dicer-1: adult GSC maintenance requires Mad if it is lost during adult life, but not if it is lost during pupal development. Overall, these results show stage-specific differential sensitivity of GSC maintenance to certain perturbations, and suggest that there may be Dcr-2 dependent redundancy of GSC maintenance mechanisms during development that is lost in later life.
在本研究中,我们揭示了微小RNA在果蝇生殖系干细胞(GSC)维持中的作用。成年期GSCs中Dicer-1功能的破坏会导致GSC丢失。然而,令人惊讶的是,发育过程中Dicer-1的缺失并不会导致GSC维持缺陷,不过如果Dicer-1和Dicer-2的功能都被破坏,则会出现缺陷。当在成年GSCs中诱导时,bantam微小RNA的缺失模拟了Dicer-1维持缺陷,这表明bantam在GSC自我更新中起关键作用。Mad是TGF-β信号通路的一个组成部分表现与Dicer-1类似:如果在成年期丢失,成年GSC维持需要Mad,但如果在蛹发育期间丢失则不需要。总体而言,这些结果表明GSC维持对某些扰动具有阶段特异性差异敏感性,并表明在发育过程中可能存在GSC维持机制的Dcr-2依赖性冗余,而在后期生活中这种冗余会丧失。