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The Ecdysone-inducible zinc-finger transcription factor Crol regulates Wg transcription and cell cycle progression in Drosophila.

机译:蜕皮激素诱导的锌指转录因子Crol调节果蝇中的Wg转录和细胞周期进程。

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The steroid hormone Ecdysone is crucial for developmental cell death, proliferation and morphogenesis in Drosophila. Herein, we delineate a molecular pathway linking Ecdysone signalling to cell cycle regulation in the Drosophila developing wing. We present evidence that the Ecdysone-inducible zinc-finger transcription factor Crol provides a crucial link between the Ecdysone steroid hormone pathway and the Wingless (Wg) signalling pathway in Drosophila. We identified Crol as a strong enhancer of a wing phenotype generated by overexpression of the Wg-inducible cell cycle inhibitor Hfp. We demonstrate that Crol is required for cell cycle progression: crol mutant clones have reduced cell cycles and are removed by apoptosis, while upregulation of Crol overrides the Wg-mediated developmental cell cycle arrest in the zone of non-proliferating cells in the wing disc. Furthermore, we show that Crol acts to repress wg transcription. We also show that overexpression of crol results in downregulation of Hfp, consistent with the identification of the crol mutant as a dominant enhancer of the Hfp overexpression phenotype. Taken together, our studies have revealed a novel mechanism for cell cycle regulation, whereby Crol links steroid hormone signals to Wg signalling and the regulation of crucial cell cycle targets.
机译:类固醇激素蜕皮激素对果蝇中发育性细胞死亡,增殖和形态发生至关重要。在本文中,我们描述了将蜕皮激素信号传导与果蝇发育中的细胞周期调控联系起来的分子途径。我们目前的证据表明,蜕皮激素诱导的锌指转录因子Crol在果蝇中提供了蜕皮激素甾体激素途径与Wingless(Wg)信号传导途径之间的关键联系。我们确定Crol是由Wg诱导的细胞周期抑制剂Hfp的过表达产生的翼表型的强增强剂。我们证明Crol是细胞周期发展所必需的:crol突变体克隆具有减少的细胞周期,并通过凋亡被清除,而Crol的上调则覆盖了Wg介导的翼盘非增殖细胞区域中发育细胞周期的停滞。此外,我们表明Crol起到抑制wg转录的作用。我们还显示,crol的过度表达导致Hfp的下调,与crol突变体作为Hfp过度表达表型的主要增强子的鉴定相一致。综上所述,我们的研究揭示了一种新的细胞周期调控机制,其中Crol将类固醇激素信号与Wg信号联系起来,并调控关键的细胞周期靶标。

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