Signaling to Cell Intercalation in Arabidopsis

描述（由申请人提供）：该项目的长期目标是了解细胞嵌入的潜在信号机制，其中相邻细胞改变其形状以相互嵌入。细胞嵌入对于多细胞生物体的正常发育和形态发生至关重要。在动物和人类胚胎的原肠胚形成、神经胚形成、轴的伸长和器官发生过程中，细胞嵌入是会聚延伸过程所必需的。然而，控制这一基本过程的信号和途径的特征很差，尽管一些潜在的信号事件（例如，已知Rho GTP酶和细胞骨架在动物和植物界中是保守的。在模式植物拟南芥中，细胞插入对于叶表皮的发育是重要的，其中铺路细胞发育出插入裂片和凹陷，形成拼图外观。Pi的小组已经开发了路面细胞作为细胞嵌入的模型系统，并建立了控制这一过程的Rho GTP酶依赖性细胞内信号网络的第一个框架。它是由两个抵消途径：ROP 2-RIC 4-肌动蛋白途径激活叶形成和ROP 6-RIC 1-微管途径促进压痕。在这个项目中，信号，受体和新的组件将被确定并连接到这个框架。在目的1中，激活ROP 2 GT3的信号传导事件，例如，将使用生物化学、遗传学和细胞生物学方法研究SPK 1 ROP鸟嘌呤核苷酸交换因子的信号传导。在目标2中，将使用类似的方法确定R 0 P6 GTd 3上游的分子，并且将研究R 0 P6和R 0 P2途径之间的细胞间信号传导，以了解如何在相邻细胞之间协调成瓣和缩进。目的三是探讨生长素梯度作为发育信号，如何诱导插层生长。ROP突变体和生物化学和细胞生物学测定的组合将用于确定生长素是否激活ROP 2或ROP 6途径。将测试中间生长所需的TMK受体样激酶参与生长素感知。从这些目标，一个全面的图片的分子和细胞机制的夹层生长将被揭示。考虑到植物和人类细胞插入的信号机制的保守性，从这项研究中获得的知识可能会为我们理解收敛延伸提供新的见解。由于会聚延伸失败会导致神经管缺陷（NTD），这是一种常见的发育障碍（每1000例妊娠中有1例），因此这项研究与人类健康改善有关。

DESCRIPTION (provided by applicant): The long-term goal of this project is to understand the underlying signaling mechanisms of cell intercalation, in which neighboring cells change their shapes to become intercalated with each other. Cell intercalation is critical for the proper development and morphogenesis of multi-cellular organisms. Cell intercalation is required for the process of convergent extension during gastrulation, neurulation, axis elongation, and organogenesis of animal and human embryos. However, signals and pathways governing this fundamental process are poorly characterized, though some underlying signaling events (e.g., Rho GTPases and the cytoskeleton) are known to be conserved across animal and plant kingdoms. In the model plant Arabidopsis, cell intercalation is important for the development of the leaf epidermis, in which pavement cells develop intercalary lobes and indentations to form the jigsaw-puzzle appearance. The Pi's group has developed the pavement cell as a model system for cell intercalation, and has established the first framework of a Rho GTPase-dependent intracellualr signaling network that controls this process. It is composed of two counteracting pathways: a ROP2-RIC4-actin pathway activating lobe formation and a ROP6-RIC1- microtubule pathway promoting indentation. In this project, signals, receptors and new components will be determined and linked to this framework. In aim 1, signaling events activating the ROP2 GTPase, e.g., signaling by the SPK1 ROP guanine nucleotide exchange factor, will be investigated using biochemical, genetic, and cell biological methods. In aim 2, molecules upstream of the ROP6 GTPase will be determined using similar approaches, and the intercellular signaling between the ROP6 and the ROP2 pathways will be investigated to understand how lobing and indenting are coordinated between the neighboring cells. Aim 3 is to investigate how auxin gradients, acting as a developmental signal, induce intercalary growth. A combination of rop mutants and biochemical and cell biological assays will be used to determine whether auxin activates the ROP2 or ROP6 pathway. The TMK receptor-like kinases that are required for intercalary growth will be tested for their participation in auxin perception. From these aims, a comprehensive picture of the molecular and cellular mechanisms for intercalary growth will be revealed. Given the conservation of the signaling mechanisms underlying cell intercalation across plants and humans, the knowledge gained from this research may provide new insights into our understanding of convergent extension. Because failure in convergent extension causes neural tube defects (NTDs), a common developmental disorder (1 out of 1000 pregnancies), this research is relevant to human health improvements.