Molecular Signal Integration for Root Growth Control

摘要 多细胞生物必须精确控制组织和器官的生长和大小。为此，细胞 可重复且准确地解释由外部信号传达并被大型阵列感知的信息 传感机械。这些生长调节通路的故障会降低机体的适合度，并可能 会导致癌症等疾病。虽然控制器官和组织生长的几个主要途径一直很好 有两个非常重要的领域没有得到很好的理解。首先，多个通常是多少 相互冲突的增长监管外部信号整合在一起影响增长吗？第二，自然遗传是如何 变异会影响这些生长途径及其对外部信号的反应吗？ 模式植物拟南芥的根是研究遗传和分子基础 器官生长是基于多个信号，以及这些反应是如何由基因调节的。这 是因为植物，特别是它们的根系统，进化出了紧密协调所有方面的机制 生长和发展对环境条件的影响。此外，有可能高效地和定量地 在不牺牲生物体的情况下(哺乳动物的情况就是这样)，长期监测根的生长。 此外，有可能并行监测数千种植物，从而实现大规模的遗传方法 评估多种环境条件。到目前为止，已有1135个拟南芥同基因株系完全 测序，其中许多菌株以不同的方式对环境信号做出反应，为 表型组学和全基因组关联研究以确定导致这些对比的基因变异 成长反应。总之，拟南芥的根是一个研究器官生长如何的独特系统。 与多种环境信号的协调，以及这种协调是如何由基因调节的。 最近的研究表明，根系生长对低铁水平的反应在很大程度上是由自然遗传决定的 一组受体激酶和一种蛋白激酶的变异。其中至少有两个基因也参与其中。 在对鞭毛蛋白的反应中，一种病原体相关的分子模式。基于这些数据，已经建立了一个模型 这种受体激酶“模块”整合了铁和防御信号(促进和抑制 生长)来调节根的生长。在这项提案中，实验将检验蛋白质- 该受体激酶模块内的蛋白质相互作用及其动力学调节根的生长 铁和鞭毛蛋白(目标1)，受体激酶模块中等位基因变异决定了生长敏感性 铁和微生物信号，以及这些信号的整合(目标2)。最后，机械论研究将 以确定调控根生长的分子过程对铁水平的反应 (目标3)。总体而言，这个项目将提供关于如何整合多种信号来调节器官生长的见解， 以及每个个体的基因如何调节这一过程。

Abstract Multicellular organisms must precisely control the growth and size of tissues and organs. For this, cells reproducibly and accurately interpret information conveyed by extrinsic signals and perceived by a large array of sensing machinery. Malfunction of these growth-regulatory pathways decreases organismal fitness and can lead to diseases like cancer. While several major pathways controlling organ and tissue growth have been well characterized, there are two very important areas that are not well understood. First, how are multiple, often conflicting growth regulatory extrinsic signals integrated to impact growth? Second, how does natural genetic variation impact these growth pathways and their responses to extrinsic signals? The root of the model plant Arabidopsis thaliana is ideal for studying the genetic and molecular bases for how organ growth is adjusted based on multiple signals, and how these responses are modulated by genotype. This is because plants, in particular their root systems, have evolved mechanisms for tightly coordinating all aspects of growth and development to environmental conditions. Moreover, it is possible to efficiently and quantitatively monitor root growth over long periods of time without sacrificing the organism (as is the case for mammals). Moreover, it is possible to monitor thousands of plants in parallel, enabling large-scale genetic approaches for assessing multiple environmental conditions. To date, 1135 isogenic strains of Arabidopsis have been fully sequenced and many of these strains respond in distinct ways to environmental signals, providing a platform for phenomics and genome-wide association studies to identify gene variants responsible for these contrasting growth responses. Taken together, the Arabidopsis root is a unique system for studying how organ growth is coordinated to multiple environmental signals, and how this coordination is modulated by genotype. It has recently been shown that root growth responses to low iron levels are largely determined by natural genetic variation within a group of receptor kinases and a protein kinase. At least two of these genes are also involved in responses to flagellin, a pathogen associated molecular pattern. Based on these data, a model has been formulated that this receptor kinase "module" integrates iron and defense cues (which promote and inhibit growth, respectively) to regulate root growth. In this proposal, experiments will test the hypotheses that protein- protein interactions and their dynamics within this receptor kinase module modulate root growth in response to iron and flagellin (Aim 1), and that allelic variation in the receptor kinase module determines growth sensitivities to iron and microbial signals, as well as the integration of these signals (Aim 2). Finally, mechanistic studies will be performed to determine the molecular processes by which root growth is regulated in response to iron levels (Aim 3). Overall, this project will provide insights into how multiple signals are integrated to regulate organ growth, and how each individual's genotype modulates this process.