Marygold Steven J, Walker Cherryl, Orme Mariam, Leevers Sally
University of Cambridge, Cambridge, UK.
Fly (Austin). 2011 Oct-Dec;5(4):291-303. doi: 10.4161/fly.5.4.18276. Epub 2011 Oct 1.
The ebi gene of Drosophila melanogaster has been implicated in diverse signalling pathways, cellular functions and developmental processes. However, a thorough genetic analysis of this gene has been lacking and the true extent of its biological roles is unclear. Here, we characterize eleven ebi mutations and find that ebi has a novel role in promoting growth of the wing imaginal disc: viable combinations of mutant alleles give rise to adults with small wings. Wing discs with reduced EBI levels are correspondingly small and exhibit down-regulation of Notch target genes. Furthermore, we show that EBI colocalizes on polytene chromosomes with Smrter (SMR), a transcriptional corepressor, and Suppressor of Hairless (SU(H)), the primary transcription factor involved in Notch signalling. Interestingly, the mammalian orthologs of ebi, transducin β-like 1 (TBL1) and TBL-related 1 (TBLR1), function as corepressor/coactivator exchange factors and are required for transcriptional activation of Notch target genes. We hypothesize that EBI acts to activate (de-repress) transcription of Notch target genes important for Drosophila wing growth by functioning as a corepressor/coactivator exchange factor for SU(H).
黑腹果蝇的ebi基因已被证明参与多种信号通路、细胞功能和发育过程。然而,对该基因的全面遗传分析一直缺乏,其生物学作用的真正范围尚不清楚。在这里,我们对11个ebi突变进行了表征,发现ebi在促进翅成虫盘生长方面具有新作用:突变等位基因的可行组合会导致成虫翅膀变小。EBI水平降低的翅成虫盘相应变小,并表现出Notch靶基因的下调。此外,我们发现EBI在多线染色体上与转录共抑制因子Smrter(SMR)以及参与Notch信号传导的主要转录因子Hairless抑制因子(SU(H))共定位。有趣的是,ebi的哺乳动物直系同源物转导素β样1(TBL1)和TBL相关1(TBLR1)作为共抑制因子/共激活因子交换因子发挥作用,并且是Notch靶基因转录激活所必需的。我们推测,EBI通过作为SU(H)的共抑制因子/共激活因子交换因子,来激活(去抑制)对果蝇翅膀生长重要的Notch靶基因的转录。