Functional evolution of segmentation gene regulatory networks in insects

昆虫分段基因调控网络的功能进化

• 批准号: 10386801
• 负责人: Leslie Pick
• 金额: $ 30.68万
• 依托单位: UNIV OF MARYLAND, COLLEGE PARK
• 依托单位国家: 美国
• 财政年份: 2015
• 资助国家: 美国
• 起止时间: 2015-05-01 至 2023-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10386801
• 关键词: Animals; Anopheles Genus; Arthropods; Asian; Biological Models; Black Currant; Cells; Clustered Regularly Interspaced Short Palindromic Repeats; Culicidae; DNA Binding; Defect; Development; Drosophila genus; Embryo; Embryonic Development; Essential Genes; Evolution; FAIRE sequencing; Family member; Flour; Gene Expression; Gene Expression Profile; Gene Expression Regulation; Gene Transfer Techniques; Genes; Genetic Screening; Genetic Variation; Genome; Hand; Health; Hemiptera; Homeobox Genes; Human; Insecta; Knowledge; Light; Maintenance; Modeling; Molecular; Molecular Biology; Molecular Evolution; Molecular Genetics; Morphogenesis; Morphology; Mutation; Nature; Nuclear Receptors; Order Coleoptera; Orthologous Gene; Pattern; Pigmentation physiologic function; Postdoctoral Fellow; Proteins; Protocols documentation; RNA Interference; Radiation; Regulation; Regulator Genes; Regulatory Element; Regulatory Pathway; Risk; System; Techniques; Testing; Transcriptional Activation; Translational Research; Tribolium; Variant; Work; base; cofactor; design; experimental study; gene function; gene interaction; gene regulatory network; genetic approach; genetic evolution; graduate student; human disease; in vivo; insight; knock-down; malaria mosquito; member; mutation screening; novel; post-doctoral training; protein function; tool; tool development; trait; transcription factor; transcriptome sequencing; translational study; undergraduate student; vector

Abstract A central question in the field of Evo-Devo is how genes controlling embryonic development change during evolution. Many recent advances in Evo-Devo have identified genetic changes that are associated with the acquisition of, or changes in, external body features, such as alterations in pigmentation patterns or development of body armor. In contrast, our studies are novel in this field as they have revealed unexpected genetic variation underlying a highly conserved trait: the shared segmented body plan of insects. The genes controlling segmentation encode transcription factors that are required for embryonic development and viability. Thus, it has been surprising to find large differences in the presence, expression, or function of these genes in different insect taxa. The work proposed here is designed to understand the mechanistic changes underlying this observed genetic variation, in different insect lineages. To carry out functional studies, we have developed molecular genetic approaches in diverse insect species in our lab. The establishment of multiple non-model systems simultaneously within one lab has synergistic effects due to sharing of protocols and troubleshooting strategies, allowing us to more effectively develop new techniques in different species. With these tools in hand, we will examine the underlying bases of specific scenarios of regulatory gene variation: Aim 1. Re-wiring of gene regulatory interactions that permit loss of a conserved regulator in mosquitoes; Aim 2. Stability of target gene regulation despite switches in transcription factor partners: Ftz-F1 regulates target genes without Ftz in Tribolium. Aim 3. Regulation of segmentation by non-canonical PRGs in Hemiptera. These studies will contribute to our understanding of fundamental mechanisms regulating embryonic development and how these mechanisms have changed during the radiation of insects. This project will train postdoctoral fellows, one graduate student, and at least four undergraduate students in molecular biology, genetics and molecular evolution. Establishment of molecular techniques in non-model and emerging model insect species, including expression analysis, RNA interference, CRISPR, FAIRE-seq, and transgenesis, not only allows us to answer fundamental questions about embryonic development, but also provides molecular tools for translational studies of insects that pose a risk to human health.

抽象的 Evo-Devo领域的一个中心问题是基因如何控制胚胎发育 进化过程中的变化。 Evo-Devo 的许多最新进展已经确定了基因变化 与外部身体特征的获得或变化相关的，例如 色素沉着模式的改变或防弹衣的发展。相比之下，我们的研究是 在这个领域是新颖的，因为他们揭示了高度潜在的意想不到的遗传变异 保守性状：昆虫共享的分段身体结构。基因控制 分段编码胚胎发育所需的转录因子 生存能力。因此，令人惊讶的是发现存在、表达或 这些基因在不同昆虫类群中的功能。这里提出的工作旨在 了解这种观察到的遗传变异背后的机制变化，在不同的情况下 昆虫谱系。为了进行功能研究，我们开发了分子遗传学 我们实验室中不同昆虫物种的方法。建立多个非模型 由于协议和协议的共享，同一实验室内同时运行的系统具有协同效应 故障排除策略，使我们能够更有效地开发不同领域的新技术 物种。有了这些工具，我们将检查特定场景的底层基础 调控基因变异：目标 1. 重新连接基因调控相互作用，从而导致基因缺失 蚊子中保守的调节因子；目标 2. 尽管存在开关，但靶基因调控的稳定性 转录因子伙伴：在谷盗中，Ftz-F1 在没有 Ftz 的情况下调节靶基因。目标3。 半翅目中非规范 PRG 的分段调节。这些研究将有助于 我们对调节胚胎发育的基本机制的理解以及如何 这些机制在昆虫的辐射过程中发生了变化。本项目将训练 博士后研究员、一名研究生和至少四名本科生 分子生物学、遗传学和分子进化。分子技术的建立 非模式和新兴模式昆虫物种，包括表达分析、RNA 干扰、CRISPR、FAIRE-seq 和转基因，不仅使我们能够回答基本问题 有关胚胎发育的问题，还提供了转化的分子工具 对对人类健康构成威胁的昆虫的研究。