Signaling to Cellular Intercalation in Arabidopsis

描述（由申请人提供）：该项目的长期目标是阐明细胞极性和形态发生是如何沿着器官表面局部（相邻细胞之间）和全局（细胞领域）协调的，因为这些知识对于理解发育和模式形成机制是非常需要的。本项目主要研究细胞嵌入的机制，细胞嵌入是人类和动物胚胎发生和植物形态发生的重要基础过程。尽管一些潜在的信号事件（如Rho gtpase和细胞骨架）在动物和植物界都是保守的，但细胞嵌入的局部和全局协调机制的特征却很差。在模式植物拟南芥中，细胞嵌入对叶表皮的发育起着重要的作用，铺装细胞（PC）发育出交错的裂片和凹痕，形成拼图外观。PI的团队已经建立了PC作为细胞嵌入的模型系统，并发现了一个复杂的Rho GTPase信号网络，支持PC嵌入，其中包括两个相互作用但相互排斥的Rho信号通路：激活叶状突起的rop2 - ric4 -肌动蛋白通路和促进压痕的rop6 - ric1 -微管通路。这两种途径互补地定位于细胞壁的两侧，但都被一种被称为生长素的小分子激素通过细胞表面ABP1受体激活；而ROP2通路通过激活PIN1的极化形成一个正反馈回路，PIN1向细胞壁输出生长素。这种生长素调节的网络被认为是局部协调PC嵌入，并与叶尖和叶缘高生长素梯度介导的全局协调相关联，这显然是由依赖于核TIR1/AFB生长素受体的基于转录的生长素信号通路产生的。本研究的目的是验证这样一种假设，即PC插入是由分层生长素信号传导协调的，这可能反映在调节动物发育模式的WNT信号传导中。Aim 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，它们对两种Rho通路的差异激活，pin1介导的局部细胞外生长素及其对这些通路的协调。目的2将阐明ROP2通过内体PIN1转运激活PIN1极化的机制。目的3将确定TIR1/AFB通路及其靶基因在全球协调中的作用。这项工作将提供在多个层面上协调细胞插入的机制的全面观点。考虑到植物和人类细胞插层和平面细胞极性（PCP）背后的Rho信号的保守性，这项工作可能为趋同扩展（CE）和其他PCP介导的过程提供新的见解。由于妊娠失败会导致神经管缺陷，这是一种常见的发育障碍（千分之一的妊娠），因此这项研究可能最终与改善人类健康有关。

DESCRIPTION (provided by applicant): 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, PIN1-mediated local extracellular auxin, and its 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.