The mir-7 and bag of marbles genes regulate Hedgehog pathway signaling in blood cell progenitors in Drosophila larval lymph glands.
The mir-7 and bag of marbles genes regulate Hedgehog pathway signaling in blood cell progenitors in Drosophila larval lymph glands.
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DOI：
10.1002/dvg.23210
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发表时间：
2018-05
期刊：
影响因子：
--
通讯作者：
Schulz RA
中科院分区：
文献类型：
--
作者：
Tokusumi T;Tokusumi Y;Schulz RA
Hedgehog（Hh）信号通路对果蝇三龄幼虫淋巴腺造血器官中血细胞祖细胞的维持至关重要。我们实验室以前的研究同样显示了mir-7和弹珠袋（bam）基因在维持祖细胞状态中的重要性。因此，我们试图研究Hh途径和mir-7/bam在该造血组织内的原血细胞群体中的可能相互作用。mir-7功能的获得能够挽救由这些细胞中Hh途径信号传导的Patched（Ptc）抑制引起的血细胞祖细胞耗竭表型。类似地，Ptc的显性/阴性形式的表达能够挽救由于bam功能丧失而导致的原血细胞的严重减少。此外，我们证明了另一种已知的Hh信号抑制剂Suppressor of fused [Su（fu）]可能是mir-7 miRNA的翻译抑制靶点。我们的研究结果表明mir-7/bam组合通过抑制Su（fu）来调节Hh信号网络，以维持幼虫淋巴腺中的血细胞祖细胞。
Hedgehog (Hh) pathway signaling is crucial for the maintenance of blood cell progenitors in the lymph gland hematopoietic organ present in Drosophila third instar larvae. Previous studies from our lab have likewise shown the importance of the mir-7 and bag of marbles (bam) genes in maintaining the progenitor state. Thus we sought to investigate a possible interaction between the Hh pathway and mir-7/bam in the prohemocyte population within this hematopoietic tissue. Gain of function mir-7 was able to rescue a blood cell progenitor depletion phenotype caused by Patched (Ptc) inhibition of Hh pathway signaling in these cells. Similarly, expression of a dominant/negative version of Ptc was able to rescue the severe reduction of prohemocytes due to bam loss of function. Furthermore, we demonstrated that Suppressor of fused [Su(fu)], another known inhibitor of Hh signaling, likely serves as a translational repression target of the mir-7 miRNA. Our results suggest the mir-7/bam combination regulates the Hh signaling network through repression of Su(fu) to maintain hemocyte progenitors in the larval lymph gland.
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