Regulatory Systems Controlling Plant Cell Axis Formation and Regenerative Stem Cell Formation

多细胞生物体中细胞获得不同细胞命运以形成功能上有意义的身体模式（称为生物模式形成）的分子机制在很大程度上仍然未知。更好地理解模式形成的分子对于避免大多数多细胞生物体中的非计划性癌细胞增殖，特别是在植物中，对于优化生长、资源分配、某些类型的胁迫抗性以及因此提高产量也是重要的。产量的提高反过来又会给世界生态、经济和人类发展带来好处。理解模式形成的一个关键组成部分是确定定义各种干细胞小生境的精确分子决定因素。特别是在植物中，我们对干细胞生态位形成的分子见解不足，严重阻碍了育种和生物技术，因为它使许多农艺学上非常重要的植物物种无法进行体外再生，这是营养繁殖、性状质量评估、濒危物种拯救和转化的先决条件。近年来，在一些模式生物中，主要基于遗传方法，其次是大规模基因组和靶向分子策略，在更好地理解模式形成方面取得了重大进展。在植物中，这些方法已经汇聚在多细胞模式与单个植物细胞极性获取的迷人细胞生物学互连中。事实证明，大量看似独立的图案化过程，包括胚轴的形成，顶端分生组织的内部组织，芽和根中侧部器官的形成，甚至叶序和维管图案化，都可以归因于单个简单分子吲哚乙酸（IAA，一种生长素“植物激素”）通过单个细胞的极性运输和反馈控制分布。生长素被感知并转化为基因调节反应，包括通过生长素反应（转录）因子（ARF）及其Aux/IAA家族的核共调节因子控制其转运的那些反应（1）。基于对生长素转录调控基因的广泛研究，该提案概述了以下策略：（a）使用特定的遗传开关来显著增加植物再生特性以及侧分生组织中的干细胞活性，（B）基于小化合物筛选的结果分析控制植物中干细胞特性的其他途径，（c）通过新型ARF变体继续揭示ARF-Aux/IAA调节网络的功能基因组学，以及（d）基于鉴定的数量性状基因座鉴定控制血管细胞特性的新型调节剂。

The molecular mechanisms by which cells in multicellular organisms acquire distinct cell fates to form functionally meaningful body patterns, termed biological pattern formation, are still largely unknown. A better molecular understanding of pattern formation is important for avoidance of unscheduled cancerous cell proliferation in most multicellular organisms and specifically in plants also for optimized growth, resource allocation, certain types of stress resistance and hence improved yield. Yield improvements, in turn, are associated with benefits for the world’s ecology, economy and human development. A critical component in understanding pattern formation is the identification of the precise molecular determinants that define various stem cell niches. Specifically in plants, our insufficient molecular insights into stem cell niche formation has severely handicapped breeding and biotechnology, as it has kept many agronomically highly important plant species recalcitrant to in-vitro regeneration, a prerequisite for vegetative propagation, mass assessment of traits, rescue of endangered species and transformation. In recent years, significant progress to better understand pattern formation has been made in a number of model organisms, predominantly based on genetic approaches followed by large-scale genomic and targeted molecular strategies. In plants, these approaches have converged in the fascinating cell-biological interconnection of multicellular patterning with polarity acquisition of the individual plant cell. As it turned out, a huge number of seemingly separate patterning processes, including embryo axis formation, internal organization in both apical meristems, the formation of lateral organs in shoots and roots and even phyllotaxis and vascular patterning could be attributed to the polar transport and feed-back controlled distribution of a single simple molecule, indole-acetic acid (IAA, an auxin "phytohormone”) through individual cells. Auxin is perceived and translated into gene-regulatory responses, including those controlling its transport by Auxin Response (transcription) Factors (ARFs) and their nuclear co-regulators of the Aux/IAA family (1). Based on extensive work with the auxin transcriptional regulation genes, this proposal outlines strategies to (a) use specific genetic switches to dramatically increase plant regeneration properties as well as stem cell activities in lateral meristems, (b) analyze other pathways controlling stem cell properties in plants based on the results of small compound screens, (c) continue to unravel the functional genomics of the ARF-Aux/IAA regulatory network through a novel type of ARF variants and (d) identify novel regulators controlling vascular cell properties based on identified Quantitative Trait Loci.