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

项目总结 这项研究的目标是研究基因网络是如何被重新利用和专业化的 在体内产生重复的器官，如毛发、神经元或肌肉。基因调控 网络是转录上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，如 大小、形状或颜色。我们很早就知道，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， 因为重新使用现有网络要比完全从 抓伤。然而，我们很少有模型系统在其中对基因调控的细节 可以研究网络的再利用。实验系统，其中网络的使用可以 对于研究这一过程是如何工作的，诱导的方法尤其强大。 第二个相关问题是专业化。虽然重复的器官共享许多 共同点，正是它们之间的区别，我们经常想要了解。你好吗？ 在身体的数百个位置使用的网络，它被个性化地生成 特定位置的形态特征？ 在这里，我们将研究一个基因调控网络，它已经被重新使用来产生一个新的 果蝇的一套毛发器官。特别有趣的是，这些毛发高度专门化， 比在本种中记录的其他毛大得多。我们已经确定了一个 对重新利用这个毛发形成网络至关重要的基因，并使 发现我们可以通过简单地激活这个来诱导缺乏这些结构的物种的毛发 在正确的发育组织中的基因。这一发现促使我们提出了一套探索性的 这些实验将迅速阐明这个基因调控网络是如何被重新利用和 专门化：(A)我们将研究已知为祖先幼虫一部分的基因的表达 拥有这些高度专业化的新毛发的物种中的毛发网络。(B)我们会寻求 找出了新的基因，这些基因有助于我们观察到的头发形态的多样性。 (C)使用CRISPR/Cas9和基因错误表达技术，我们将确定基因 被确定为对产生专门化毛发重要的毛发是必需的或足够的。 这项研究将揭示网络重用和专业化的过程 分子操作，提供对特定基因和细胞过程可能如何发挥作用的洞察 在调节器官大小和形状方面的作用。

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.