Examining the re-use and specialization of an organ-forming gene regulatory network

检查器官形成基因调控网络的重用和专业化

• 批准号: 10193507
• 负责人: Mark J Rebeiz
• 金额: $ 23.48万
• 依托单位: UNIVERSITY OF PITTSBURGH AT PITTSBURGH
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-04-01 至 2023-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10193507
• 关键词: Address; Adult; Biological Models; Body Regions; CRISPR/Cas technology; Cell physiology; Cells; Collection; Color; Data; Development; Developmental Gene; Disease; Drosophila genus; Ectopic Expression; Event; Gene Expression; Gene Expression Profile; Genes; Genetic Transcription; Genital; Genitalia; Goals; Hair; Human; Knowledge; Location; Molecular; Morphology; Muscle; Neurons; Organ; Organ Size; Organism; Outcome; Pattern; Phenotype; Play; Positioning Attribute; Process; Processed Genes; Proteins; Recurrence; Regulation; Regulator Genes; Research; Resolution; Role; Shapes; Signal Pathway; Specific qualifier value; Structure; System; Technology; Time; Tissues; To specify; Work; bone; experimental study; insight; interest; novel; physical property; programs; reconstitution; spatiotemporal; transcription factor

PROJECT SUMMARY The goal of this research is to examine how gene networks are re-used and specialized to generate repeated organs in the body, such as hairs, neurons, or muscles. Gene regulatory networks are assemblages of genes that transcriptionally regulate one another. These networks govern which proteins are produced in a cell to derive its own unique physical properties such as size, shape, or color. We have known for some time that many networks are re-used during development to generate various types of repeated organs across the body. This makes sense, as it would be much faster to re-use an existing network rather than completely build one from scratch. However, we have very few model systems in which the specifics of gene regulatory network re-usage can be studied. Experimental systems in which the usage of a network can be induced are particularly powerful for investigating how this process works. A second related problem is that of specialization. While repeated organs share many commonalities, it is the differences between them that we would often like to understand. How is a network that is used in hundreds of locations across the body individualized to generate a position-specific morphology? Here, we will examine a gene regulatory network that has been re-used to generate a new set of hair organs in Drosophila. Of particular interest, these hairs are highly specialized and are far larger than the other hairs that have been documented in this species. We have identified a gene that was critical to the re-use of this hair-forming network, and have made the remarkable discovery that we can induce hairs in species that lack these structures by simply activating this gene in the right developmental tissue. This finding led us to propose an exploratory set of experiments that will rapidly illuminate how this gene regulatory network was re-used and specialized: (A) We will examine the expression of genes known to be part of the ancestral larval hair network in the species which possesses these new highly specialized hairs. (B) We will seek out new genes that contribute to the spectrum of diversity of hair morphologies we have observed. (C) Using CRISPR/Cas9 and gene mis-expression technologies, we will determine whether genes identified to be important for generating specialized hairs are required or sufficient to do so. This research will inform the how processes of network re-use and specialization molecularly operate, providing insights into how specific genes and cellular processes may play roles in the regulation of organ size and shape.

项目摘要 这项研究的目的是研究基因网络是如何被重复使用和专门化的 在体内产生重复的器官，如毛发、神经元或肌肉。基因调控 网络是基因的集合，它们在转录上相互调节。这些网络 决定了哪些蛋白质在细胞中产生，以获得其独特的物理特性， 尺寸、形状或颜色。一段时间以来，我们已经知道许多网络在 在整个身体中产生各种类型的重复器官。这是有道理的， 因为重新使用现有网络要比完全从 抓痒.你知道然而，我们很少有模型系统，其中基因调控的细节 可以研究网络重用。实验系统，其中网络的使用可以 在研究这一过程如何运作方面，诱导的作用尤其强大。 第二个相关的问题是专业化。虽然重复的器官共享许多 我们常常想了解的是它们之间的差异。怎么样 一个网络，用于身体的数百个位置， 位置特异性形态学 在这里，我们将研究一个基因调控网络，该网络已被重新用于产生一个新的 果蝇的一组毛发器官。特别有趣的是，这些毛发是高度特化的， 比该物种中已记录的其他毛发大得多。我们已经确定了一 基因，这是至关重要的再利用这个头发形成网络，并取得了显着的 我们发现，我们可以诱导缺乏这些结构的物种的头发，只要激活这个 基因在正确的发育组织中。这一发现使我们提出了一套探索性的 这些实验将迅速阐明这种基因调控网络是如何被重新利用的， 专业化：（A）我们将检查已知是祖先幼虫的一部分的基因的表达 拥有这些新的高度特化的毛发的物种的毛发网络。(B)我们将寻求 我们发现了一些新的基因，这些基因对我们观察到的毛发形态的多样性有贡献。 (C)使用CRISPR/Cas9和基因错误表达技术，我们将确定基因是否 被鉴定为对于产生特化毛发重要的细胞是需要的或足以这样做。 这项研究将告知如何网络重用和专业化的过程 分子运作，提供了对特定基因和细胞过程如何发挥作用的见解， 在调节器官大小和形状中的作用。