Mitchell Naomi C, Lin Jane I, Zaytseva Olga, Cranna Nicola, Lee Amanda, Quinn Leonie M
Department of Anatomy and Cell Biology, University of Melbourne, Parkville 3010, Melbourne, Australia.
BMC Dev Biol. 2013 Jul 13;13:28. doi: 10.1186/1471-213X-13-28.
Ecdysone triggers transcriptional changes via the ecdysone receptor (EcR) to coordinate developmental programs of apoptosis, cell cycle and differentiation. Data suggests EcR affects cell cycle gene expression indirectly and here we identify Wingless as an intermediary factor linking EcR to cell cycle.
We demonstrate EcR patterns cell cycle across the presumptive Drosophila wing margin by constraining wg transcription to modulate CycB expression, but not the previously identified Wg-targets dMyc or Stg. Furthermore co-knockdown of Wg restores CycB patterning in EcR knockdown clones. Wg is not a direct target of EcR, rather we demonstrate that repression of Wg by EcR is likely mediated by direct interaction between the EcR-responsive zinc finger transcription factor Crol and the wg promoter.
Thus we elucidate a critical mechanism potentially connecting ecdysone with patterning signals to ensure correct timing of cell cycle exit and differentiation during margin wing development.
蜕皮激素通过蜕皮激素受体(EcR)触发转录变化,以协调细胞凋亡、细胞周期和分化的发育程序。数据表明EcR间接影响细胞周期基因表达,在此我们确定无翅基因(Wingless)是连接EcR与细胞周期的中间因子。
我们证明EcR通过限制wg转录来调节CycB表达,从而在果蝇假定的翅边缘形成细胞周期模式,但不影响先前鉴定的Wg靶标dMyc或Stg。此外,在EcR敲低克隆中共同敲低Wg可恢复CycB模式。Wg不是EcR的直接靶标,相反,我们证明EcR对Wg的抑制可能是由EcR反应性锌指转录因子Crol与wg启动子之间的直接相互作用介导的。
因此,我们阐明了一种潜在的关键机制,该机制可能将蜕皮激素与模式信号联系起来,以确保在翅边缘发育过程中细胞周期退出和分化的正确时间。