University Nice Sophia Antipolis, CNRS, Inserm, iBV, Nice 06100, France.
Nat Commun. 2016 Nov 22;7:13505. doi: 10.1038/ncomms13505.
Coordination of organ growth during development is required to generate fit individuals with fixed proportions. We recently identified Drosophila Dilp8 as a key hormone in coupling organ growth with animal maturation. In addition, dilp8 mutant flies exhibit elevated fluctuating asymmetry (FA) demonstrating a function for Dilp8 in ensuring developmental stability. The signals regulating Dilp8 activity during normal development are not yet known. Here, we show that the transcriptional co-activators of the Hippo (Hpo) pathway, Yorkie (Yki, YAP/TAZ) and its DNA-binding partner Scalloped (Sd), directly regulate dilp8 expression through a Hpo-responsive element (HRE) in the dilp8 promoter. We further demonstrate that mutation of the HRE by genome-editing results in animals with increased FA, thereby mimicking full dilp8 loss of function. Therefore, our results indicate that growth coordination of organs is connected to their growth status through a feedback loop involving Hpo and Dilp8 signalling pathways.
器官在发育过程中的协调生长对于产生具有固定比例的个体是必需的。我们最近发现果蝇 Dilp8 是将器官生长与动物成熟相耦合的关键激素。此外，dilp8 突变体苍蝇表现出升高的波动性不对称（FA），表明 Dilp8 在确保发育稳定性方面的功能。目前尚不清楚在正常发育过程中调节 Dilp8 活性的信号。在这里，我们表明 Hippo（Hpo）途径的转录共激活因子 Yorkie（Yki、YAP/TAZ）及其 DNA 结合伙伴 Scalloped（Sd）通过 dilp8 启动子中的 Hpo 反应元件（HRE）直接调节 dilp8 的表达。我们进一步证明，通过基因组编辑突变 HRE 会导致 FA 增加的动物，从而模拟完全失去 dilp8 功能。因此，我们的结果表明，器官的生长协调通过涉及 Hpo 和 Dilp8 信号通路的反馈环与它们的生长状态相关联。
