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

基本信息

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
项目类别：
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

项目摘要

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.

项目概要这项研究的目标是研究基因网络如何被重用和专门化在体内生成重复的器官，例如毛发、神经元或肌肉。基因调控网络是通过转录方式相互调节的基因的集合。这些网络控制细胞中产生哪些蛋白质以获得其独特的物理特性，例如尺寸、形状或颜色。一段时间以来，我们已经知道许多网络在发育以在全身产生各种类型的重复器官。这是有道理的，因为重用现有网络比完全构建一个网络要快得多划痕。然而，我们的模型系统很少，其中基因调控的细节可以研究网络重用。可以使用网络的实验系统诱导对于研究这个过程如何运作特别有用。第二个相关问题是专业化问题。虽然重复的器官有许多共同点我们常常想了解它们之间的共性，但它们之间的差异。怎么样一个用于全身数百个位置的网络，可个性化生成特定位置形态？在这里，我们将检查一个基因调控网络，该网络已被重新用于生成新的果蝇的一组毛器官。特别有趣的是，这些毛发高度专业化，比该物种已记录的其他毛发大得多。我们已经确定了一个该基因对于头发形成网络的再利用至关重要，并取得了非凡的成就发现我们可以通过简单地激活这种结构来在缺乏这些结构的物种中诱导毛发正确发育组织中的基因。这一发现促使我们提出了一套探索性的实验将迅速阐明该基因调控网络是如何被重新利用的专门化：（A）我们将检查已知为祖先幼虫一部分的基因的表达拥有这些新的高度特化毛发的物种中的毛发网络。 (B) 我们将寻求找出有助于我们观察到的头发形态多样性的新基因。 (C) 利用CRISPR/Cas9和基因错误表达技术，我们将确定基因是否被认为对产生特殊毛发很重要的物质是必需的或足以做到这一点。这项研究将告知网络重用和专业化的过程如何分子运作，提供对特定基因和细胞过程如何发挥作用的见解在器官大小和形状的调节中发挥作用。