Polarity mechanisms driving complex morphogenesis

项目摘要 要成为一个集体的生产成员，一个细胞必须精确和动态地划分自己的内容。 因此，在细胞中产生不对称性的途径，通常被称为极性，对于 发育和体内平衡。细胞如何创造新的极性和利用不对称性来使细胞多样化 形态发生期间的种群仍然是重要和开放的研究领域。分子逻辑产生 并维持高度保守的极性结构域已经在动物和酵母中进行了彻底的研究， 能够在体外产生极性的合成电路的创建。然而，仍有重大 在现场询问这些途径的挑战，由于技术限制，很难跟踪个人 细胞在发育中的动物中经历了数天，因为它们通过多种身份过渡。为了克服这一障碍， 拟议的工作将询问发育中的植物组织内的极性通路，在那里观察亚细胞的极性通路。 动态可以配对到单细胞分辨率的完整发育决策的长期跟踪。植物 利用极性来实现许多与动物细胞相同的功能，包括调节不对称细胞分裂 和细胞器定位。重要的是，我们最近在研究细胞的形成和功能方面取得了进展， 拟南芥叶片发育中的极性突出了这些极性电路既有共性， 与动物中典型极性途径的差异。因此，我们的调查将 广泛理解极性机制，并介绍了一个实验上易于处理和独立的 进化系统来测试极性模型的通用性。 具体来说，我们的目标是1）确定在叶祖细胞内产生极性的分子相互作用， 2)描绘将极性耦合到用于组织形成的细胞器拓扑结构的途径，以及3）识别 外部信号调节极性通路的控制点。我们开发了成像平台，新的 基因工具和分析管道，这将使我们能够在我们的目标上取得快速进展。总之，我们 我希望我们能找到利用细胞极性的新方法，并将其作为潜在的未来应用工具 为生物工程和人类健康进行空间控制。

Project Summary To be a productive member of a collective, a cell must precisely and dynamically partition its own contents. Therefore, pathways that generate asymmetry in the cell, commonly referred to as polarity, are essential for development and homeostasis. How cells create de novo polarity and harness asymmetry to diversify cellular populations during morphogenesis remain important and open areas of study. The molecular logic that generates and sustains highly conserved polarity domains has been thoroughly studied in animals and yeast and has led to the creation of synthetic circuits capable of generating polarity in vitro. However, there are still significant challenges to interrogating these pathways in situ, where technical limitations make it difficult to track individual cells over days in developing animals as they transit through multiple identities. To overcome this hurdle, the proposed work will interrogate polarity pathways within developing plant tissues, where observation of subcellular dynamics can be paired to long-term tracking of full developmental decisions at single-cell resolution. Plants harness polarity for many of the same functions as animal cells, including regulation of asymmetric cell division and organelle positioning. Importantly, our recent progress investigating the formation and functions for cell polarity in developing Arabidopsis leaves highlights that these polarity circuits have both commonalities with and differences from canonical polarity pathways in animals. Therefore, our investigations will advance understanding of polarity mechanisms broadly and introduce an experimentally tractable and independently evolved system to test the generality of polarity models. Specifically, our aims are to 1) determine the molecular interactions that create polarity within leaf progenitors, 2) delineate the pathways that couple polarity to organelle topography for tissue formation, and 3) identify the control points where extrinsic signals regulate polarity pathways. We have developed imaging platforms, new genetic tools, and analysis pipelines that will allow us to make rapid progress on our aims. Taken together, we expect that we will identify novel means of harnessing polarity in cells, with potential future applications as tools to exert spatial control for bioengineering purposes and human health.