Signaling to Cellular Intercalation in Arabidopsis

拟南芥中细胞嵌入的信号转导

• 批准号: 8539018
• 负责人: Zhenbiao Yang
• 金额: $ 28.03万
• 依托单位: UNIVERSITY OF CALIFORNIA RIVERSIDE
• 依托单位国家: 美国
• 财政年份: 2007
• 资助国家: 美国
• 起止时间: 2007-09-01 至 2015-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8539018
• 关键词: Actins; Active Sites; Animals; Appearance; Arabidopsis; Auxins; Award; Biological Assay; Biological Models; Cell Polarity; Cell Wall; Cell surface; Cells; Clathrin; Cytokinins; Cytoskeleton; Development; Embryonic Development; Endocytosis; Epidermis; Event; Exhibits; Failure; Feedback; Gene Targeting; Generations; Genes; Genetic Transcription; Goals; Growth; Guanosine Triphosphate Phosphohydrolases; Health; Hereditary Disease; Hormones; Human; Image; In Vitro; Intercalated Cell; Investigation; Knowledge; Link; Lobe; Mediating; Microtubules; Modeling; Morphogenesis; Neural Tube Defects; Nuclear; Organ; Organism; Pathway interactions; Pattern; Pattern Formation; Phosphotransferases; Plant Leaves; Plant Model; Plants; Pregnancy; Process; Protein Kinase; Recycling; Reporter; Research; Role; Side; Signal Pathway; Signal Transduction; Site; Surface; System; Testing; WNT Signaling Pathway; Work; auxin-binding protein 1; base; cell growth; design; developmental disease; in vivo; insight; intercalation; interest; mathematical model; mutant; novel; receptor; response; rho; rho GTP-Binding Proteins; sensor; small molecule; time use; trafficking

The long-term goal of this project is to elucidate how cell polarity and morphogenesis is coordinated locally (between adjacent cells) and globally (in a field of cells) along the organ surface, because this knowledge is sorely needed to understand mechanisms of development and pattern formation. This project focuses the mechanisms underlying cellular intercalation, a fundamental process critical for human and animal embryogenesis and plant morphogenesis. Mechanisms for the local and global coordination of cellular intercalation are poorly characterized, although some underlying signaling events (e.g., Rho GTPases and the cytoskeleton) are 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 (PC) develop interdigitated lobes and indentations to form the puzzle-piece appearance. The PI's group has established PC as a model system for cell intercalation and has discovered an elaborate Rho GTPase signaling network underpinning the PC intercalation, which involves two interplaying but mutually exclusive Rho signaling pathways: The ROP2-RIC4-actin pathway activating lobe formation and the ROP6-RIC1-microtubule pathway promoting indentation. The two pathways are complementarily localized at the opposing sides of the cell wall, but are both activated by a small molecule hormone known as auxin via the cell-surface ABP1 receptor; and the ROP2 pathway forms a positive feedback loop by activating the polarization of PIN1, which exports auxin to the cell wall. This auxin-modulated network is proposed to locally coordinate PC intercalation and to be linked to the global coordination mediated by leaf tip- and margin-high auxin gradients, which are apparently generated by a different transcription-based auxin-signaling pathway dependent on the nuclear TIR1/AFB auxin receptor. The objective of this proposal is to test the hypothesis that PC intercalation is coordinated by hierarchical auxin signaling, which may be mirrored by WNT signaling that modulates developmental patterns in animals. Aim 1 focuses detailed mechanisms by which auxin locally coordinates PC intercalation, including putative ABP1 co-receptors that are transmembrane receptor-like kinases, their differential activation of the two Rho pathways, and the role of PIN1 in the coordination of these pathways. Aim 2 will elucidate the mechanisms by which ROP2 activates PIN1 polarization via endosomal PIN1 trafficking. Aim 3 will determine roles of the TIR1/AFB pathway and its target genes in the global coordination. The work will provide a comprehensive view of the mechanisms coordinating cellular intercalation at multiple levels. Given the conserved Rho signaling underlying cell intercalation and planar cell polarity (PCP) across plants and humans, the proposed work may provide new insights into convergent extension (CE) and other PCP-mediated processes. Because failure in CE causes neural tube defects, a common developmental disorder (1 out of 1000 pregnancies), this research might ultimately be relevant to human health improvements.

这个项目的长期目标是阐明细胞极性和形态发生是如何在局部协调的 （在相邻细胞之间）和全局（在细胞场中）沿着器官表面，因为这种知识是 迫切需要了解发展和模式形成的机制。该项目的重点是 细胞嵌入机制，人类和动物的关键基本过程 胚胎发生和植物形态发生。蜂窝通信的局部和全局协调机制 尽管一些潜在的信号事件（例如，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， 插层对于叶表皮的发育是重要的，其中铺路细胞（PC）发育 指状交叉的凸起和缺口以形成拼图块的外观。PI的小组已经建立了PC 作为细胞嵌入的模型系统，并发现了一个精心设计的Rho GT3信号网络， 支持PC嵌入，这涉及两个相互作用但相互排斥的Rho信号传导 途径：ROP2-RIC 4-肌动蛋白途径激活叶形成和ROP6-RIC 1-微管途径 促进缩进。这两条途径互补地位于细胞壁的相对侧， 但两者都被称为生长素的小分子激素通过细胞表面ABP1受体激活; ROP2通路通过激活输出生长素的PIN1的极化形成正反馈回路 到细胞壁。这种生长素调制的网络被提出来局部协调PC嵌入， 与叶尖和边缘高生长素梯度介导的全局协调有关，这显然是 由依赖于核TIR1/AFB的不同的基于转录的生长素信号传导途径产生 生长素受体本提案的目的是测试PC嵌入是由以下因素协调的假设 层次生长素信号，这可能是反映了WNT信号，调节发育模式 在动物身上。目标1关注生长素局部协调PC嵌入的详细机制，包括 假定的ABP1共受体是跨膜受体样激酶，它们对这两种受体的差异活化 Rho通路，以及PIN1在协调这些通路中的作用。目标2将阐明 ROP 2通过内体PIN1运输激活PIN1极化的机制。目标3将决定 TIR1/AFB通路及其靶基因在全局协调中的作用。这项工作将提供一个 在多个水平上协调细胞嵌入的机制的全面视图。鉴于 保守的Rho信号转导是跨植物和人类的细胞嵌入和平面细胞极性（PCP）的基础， 这项工作可能为收敛扩展（CE）和其他PCP介导的 流程.因为CE失败会导致神经管缺陷，这是一种常见的发育障碍（1/10）， 1000例妊娠），这项研究最终可能与人类健康改善有关。