Sussex Neuroscience, School of Life Sciences, University of Sussex, Brighton BN1 9QG, UK.
Sussex Neuroscience, School of Life Sciences, University of Sussex, Brighton BN1 9QG, UK
Development. 2018 Oct 16;145(20):dev161133. doi: 10.1242/dev.161133.
Disruptions of normal Hox gene expression can lead to severe morphological defects, revealing a link between the regulation of Hox expression and pattern formation. Here, we explore these links, focusing on the impact of microRNA regulation on the expression of the Hox gene () during haltere development. Through a combination of bioinformatic and transcriptomic analyses, we identify the miR-310/313 cluster () as a candidate regulator of Several experiments confirm this. First, and Ubx protein show complementary expression patterns in haltere imaginal discs; second, artificial activation of expression in haltere discs leads to -like phenotypes. Third, expression of a fluorescent reporter bearing 3'UTR sequences is reduced when co-expressed with Fourth, deletion of leads to upregulation and changes the array of mechanosensory sensilla at the base of the haltere. Fifth, an artificial increase of levels within the expression domain phenocopies the mechanosensory defects observed in mutants. We propose that -mediated repression delimits fine-grain expression, contributing to the sculpting of complex morphologies in the haltere with implications for flight control. Our work reveals a novel role of microRNA regulation in the control of Hox gene expression with impact on morphology.
正常 Hox 基因表达的中断可导致严重的形态缺陷,这揭示了 Hox 表达调控与形态发生之间的联系。在这里,我们探讨这些联系,重点研究 microRNA 调控对平衡棒发育过程中 Hox 基因 () 表达的影响。通过生物信息学和转录组分析的结合,我们确定了 miR-310/313 簇 () 是调节 的候选调控因子。多项实验证实了这一点。首先, 和 Ubx 蛋白在平衡棒 imaginal 盘上表现出互补的表达模式;其次,在平衡棒盘上人工激活 表达可导致类似的表型。第三,当与 共表达时,携带 3'UTR 序列的荧光报告基因的表达减少。第四, 缺失导致 上调,并改变平衡棒基部机械感受器感觉毛的排列。第五,在 表达域内人工增加 水平可模拟在 突变体中观察到的机械感觉缺陷。我们提出,-介导的抑制限制了 的精细表达,有助于塑造平衡棒的复杂形态,这对飞行控制具有重要意义。我们的工作揭示了 microRNA 调控在 Hox 基因表达调控中的新作用,对形态发生有影响。