Coordinate post-transcriptional repression of Dpp-dependent transcription factors attenuates signal range during development.
Coordinate post-transcriptional repression of Dpp-dependent transcription factors attenuates signal range during development.
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DOI：
10.1242/dev.123273
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发表时间：
2015-10-01
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影响因子：
--
通讯作者：
Ashe HL
中科院分区：
文献类型：
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作者：
Newton FG;Harris RE;Sutcliffe C;Ashe HL
精确控制信号分子作用的范围对于发育过程中正确的细胞命运模式至关重要。例如，果蝇卵巢生殖干细胞（GSC）是通过来自小生境的精确短程BMP信号来维持的。在缺乏BMP信号传导的情况下，一个GSC子代分化成囊细胞（CB），并且这种命运通过脑肿瘤（Brat）和Pumilio（Pum）介导的mRNA的转录后抑制而稳定，包括编码Dpp转换器Mad的mRNA。然而，其他抑制的mRNA的身份和转录后抑制的机制目前尚不清楚。在这里，我们确定了美狄亚和schnurri的mRNA，其编码的转录调节所需的激活和/或抑制的DPP靶基因，作为额外的泵-布拉特目标，这表明三重抑制的换能器部署脱敏CB的DPP。此外，我们表明，Pum-Brat的抑制需要招募CCR 4和Pop 2去腺苷酸酶，在体内敲低去腺苷酸酶引起异位GSC。与此一致，Pum-Brat抑制导致组织培养细胞中的聚腺苷酸尾缩短和mRNA降解，并且我们基于单分子mRNA定量检测到CB中相对于GSC的Mad和shn转录物数量减少。最后，我们通过证明Brat还减弱了早期胚胎中的pMad和Dpp信号传导范围来显示该机制的一般性。总之，我们的数据作为一个平台，了解转录后抑制如何限制BMP和其他细胞信号的解释，以允许在发育过程中强大的细胞命运模式。总结：翻译抑制子Brat和Pumilio减弱果蝇雌性生殖系和早期胚胎中的Dpp信号传导范围，以确保精确的细胞命运模式。
Precise control of the range of signalling molecule action is crucial for correct cell fate patterning during development. For example, Drosophila ovarian germline stem cells (GSCs) are maintained by exquisitely short-range BMP signalling from the niche. In the absence of BMP signalling, one GSC daughter differentiates into a cystoblast (CB) and this fate is stabilised by Brain tumour (Brat) and Pumilio (Pum)-mediated post-transcriptional repression of mRNAs, including that encoding the Dpp transducer, Mad. However, the identity of other repressed mRNAs and the mechanism of post-transcriptional repression are currently unknown. Here, we identify the Medea and schnurri mRNAs, which encode transcriptional regulators required for activation and/or repression of Dpp target genes, as additional Pum-Brat targets, suggesting that tripartite repression of the transducers is deployed to desensitise the CB to Dpp. In addition, we show that repression by Pum-Brat requires recruitment of the CCR4 and Pop2 deadenylases, with knockdown of deadenylases in vivo giving rise to ectopic GSCs. Consistent with this, Pum-Brat repression leads to poly(A) tail shortening and mRNA degradation in tissue culture cells, and we detect a reduced number of Mad and shn transcripts in the CB relative to the GSC based on single molecule mRNA quantitation. Finally, we show generality of the mechanism by demonstrating that Brat also attenuates pMad and Dpp signalling range in the early embryo. Together our data serve as a platform for understanding how post-transcriptional repression restricts interpretation of BMPs and other cell signals in order to allow robust cell fate patterning during development. Summary: The translational repressors Brat and Pumilio attenuate Dpp signalling range in the Drosophila female germline and early embryo to ensure precise cell fate patterning.