Department of Biology, Miami University, Oxford, OH, 45056, USA.
Department of Biology, University of Rochester, Rochester, NY, 14627, USA.
Sci Rep. 2024 May 2;14(1):10078. doi: 10.1038/s41598-024-60432-9.
Comparative analyses between traditional model organisms, such as the fruit fly Drosophila melanogaster, and more recent model organisms, such as the red flour beetle Tribolium castaneum, have provided a wealth of insight into conserved and diverged aspects of gene regulation. While the study of trans-regulatory components is relatively straightforward, the study of cis-regulatory elements (CREs, or enhancers) remains challenging outside of Drosophila. A central component of this challenge has been finding a core promoter suitable for enhancer-reporter assays in diverse insect species. Previously, we demonstrated that a Drosophila Synthetic Core Promoter (DSCP) functions in a cross-species manner in Drosophila and Tribolium. Given the over 300 million years of divergence between the Diptera and Coleoptera, we reasoned that DSCP-based reporter constructs will be useful when studying cis-regulation in a variety of insect models across the holometabola and possibly beyond. To this end, we sought to create a suite of new DSCP-based reporter vectors, leveraging dual compatibility with piggyBac and PhiC31-integration, the 3xP3 universal eye marker, GATEWAY cloning, different colors of reporters and markers, as well as Gal4-UAS binary expression. While all constructs functioned properly with a Tc-nub enhancer in Drosophila, complications arose with tissue-specific Gal4-UAS binary expression in Tribolium. Nevertheless, the functionality of these constructs across multiple holometabolous orders suggests a high potential compatibility with a variety of other insects. In addition, we present the piggyLANDR (piggyBac-LoxP AttP Neutralizable Destination Reporter) platform for the establishment of proper PhiC31 landing sites free from position effects. As a proof-of-principle, we demonstrated the workflow for piggyLANDR in Drosophila. The potential utility of these tools ranges from molecular biology research to pest and disease-vector management, and will help advance the study of gene regulation beyond traditional insect models.
比较传统模式生物,如黑腹果蝇 Drosophila melanogaster,和最近的模式生物,如赤拟谷盗 Tribolium castaneum,为基因调控的保守和分化方面提供了丰富的见解。虽然对转录调节成分的研究相对简单,但在果蝇之外,对顺式调节元件(CREs,或增强子)的研究仍然具有挑战性。这一挑战的核心是为不同昆虫物种的增强子报告基因实验找到合适的核心启动子。此前,我们证明了一种果蝇合成核心启动子(DSCP)在果蝇和赤拟谷盗中以跨物种的方式发挥作用。鉴于双翅目和鞘翅目之间超过 3 亿年的分化,我们推断基于 DSCP 的报告基因构建体在研究各种昆虫模型的顺式调控时将非常有用,这些模型跨越了完全变态和可能更远的范围。为此,我们试图创建一套新的基于 DSCP 的报告载体,利用 piggyBac 和 PhiC31 整合的双重兼容性、3xP3 通用眼标记、GATEWAY 克隆、不同颜色的报告基因和标记,以及 Gal4-UAS 二元表达。虽然所有构建体在果蝇中都能与 Tc-nub 增强子正常工作,但在赤拟谷盗中组织特异性 Gal4-UAS 二元表达出现了问题。尽管如此,这些构建体在多个完全变态目中的功能表明它们与各种其他昆虫具有很高的兼容性。此外,我们还提出了 piggyLANDR(piggyBac-LoxP AttP 可中和的目的报告基因)平台,用于建立不受位置效应影响的适当 PhiC31 着陆位点。作为原理验证,我们在果蝇中展示了 piggyLANDR 的工作流程。这些工具的潜在用途从分子生物学研究到害虫和疾病载体管理,将有助于超越传统的昆虫模型来推进基因调控的研究。