Polarity mechanisms driving complex morphogenesis

驱动复杂形态发生的极性机制

• 批准号: 10712428
• 负责人: Andrew D Muroyama
• 金额: $ 39.5万
• 依托单位: UNIVERSITY OF CALIFORNIA, SAN DIEGO
• 依托单位国家: 美国
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-08-01 至 2028-07-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10712428
• 关键词: Animals; Arabidopsis; Area; Automobile Driving; Binding; Biomedical Engineering; Cell Polarity; Cell division; Cell physiology; Cells; Complex; Development; Disease; Future; Genetic; Health; Homeostasis; Human; In Situ; In Vitro; Individual; Investigation; Knowledge; Logic; Modeling; Molecular; Morphogenesis; Organelles; Pathway interactions; Plant Leaves; Plants; Population; Positioning Attribute; Productivity; Regulation; Research; Resolution; Signal Transduction; System; Testing; Tissues; Work; Yeasts; analysis pipeline; imaging platform; insight; member; novel; progenitor; tool; tumorigenesis

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.

项目摘要 要成为集体的生产成员，单元格必须精确，动态地对其自己的内容进行分区。 因此，在细胞中产生不对称的途径通常称为极性，对于 发展和体内平衡。细胞如何产生从头极性和线束不对称以使细胞多样化 形态发生过程中的种群仍然重要和开放的研究领域。生成的分子逻辑 并且维持高度保守的极性结构域已在动物和酵母中进行了彻底研究，并已领导 创建能够在体外产生极性的合成回路。但是，仍然很重要 询问这些途径的挑战，在这种情况下，技术限制使得很难跟踪个人 在动物通过多种身份传播时，会在发育中的几天内进行细胞。为了克服这个障碍， 拟议的工作将询问正在发展的植物组织中的极性途径，在其中观察到亚细胞 动态可以与单细胞分辨率的全面发展决策进行长期跟踪。植物 与动物细胞相同功能的线束极性，包括调节不对称细胞分裂 和细胞器定位。重要的是，我们最近研究细胞的形成和功能的进展 在发展拟南芥中的极性散发着这些极性电路的亮点， 动物的规范极性途径的差异。因此，我们的调查将进步 广泛地理解极性机制，并引入实验性障碍和独立的实验性。 进化的系统以测试极性模型的通用性。 具体而言，我们的目标是1）确定在叶子祖细胞中产生极性的分子相互作用， 2）描述夫妇极性到组织形成的途径，3）确定 控制点外部信号调节极性途径。我们已经开发了成像平台，新的 遗传工具和分析管道将使我们能够快速进步。总的来说，我们 期望我们将确定利用细胞中极性的新颖手段，并将未来的应用作为工具 为生物工程目的和人类健康施加空间控制。