A Molecular Genetic Analysis of Root Morphogenesis

根形态发生的分子遗传学分析

• 批准号: 10380600
• 负责人: Philip N Benfey
• 金额: $ 30.41万
• 依托单位: DUKE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2019
• 资助国家: 美国
• 起止时间: 2019-04-01 至 2024-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10380600
• 关键词: Address; Animals; Arabidopsis; Biological Process; Cell division; Cells; Coupled; Daughter; Development; Developmental Biology; Disease; Ectopic Expression; Heart; Image; Light; Logic; Maps; Microscopy; Modeling; Molecular; Molecular Genetics; Morphogenesis; Organism; Pathway interactions; Plant Roots; Plants; Pluripotent Stem Cells; Process; Public Health; Regenerative Medicine; Regulation; Testing; Time; Tissue Differentiation; Work; developmental disease; genetic analysis; genome-wide; health knowledge; insight; mathematical model; neoplastic cell; network models; real-time images; regenerative treatment; stem cell population; stem cells; tissue regeneration

A central question in developmental biology is, “How do cells progress from pluripotent stem cells to fully differentiated tissues.” Stem cells divide asymmetrically to give daughters that are launched on different trajectories. On each trajectory, cells pass through different states as they progress toward end-stage differentiation. There are surprisingly few cases in which this whole process has been mapped out and there are no cases in which the regulation of the entire process is understood. Answers to this question lie at the heart of regenerative medicine and treatment of developmental disorders. We address this question using the root of Arabidopsis as a tractable model. Comparing and contrasting pathways to differentiation in animals and plants allows us to understand their underlying logic, as these evolved completely independently. Our work has identified the core molecular network required for the division and differentiation of one stem cell population. Mathematical modeling of this network generated hypotheses as to how it functions. We are now experimentally testing those hypotheses as well as imaging network dynamics in real time. We have also identified key regulators of differentiation in this lineage. Ectopic expression of these regulators provided insights into the stability of cell fate and the requirements for acquiring cell fate. Our progress in characterizing the path from stem cell to differentiated tissue in the root will allow us to address fundamental questions including, “How are formative asymmetric cell divisions regulated?” and “What controls differentiation?” To address these questions, we will use real time imaging with light sheet microscopy during asymmetric cell divisions and single-cell genome-wide expression analysis during the acquisition of cell fate. To fully understand the network motifs controlling these processes we will reengineer them using synthetic components. Observing network dynamics in a multicellular organism is a unique approach and has the potential to inform basic questions regarding network function in other biological processes. Generating synthetic network motifs coupled with mathematical modeling will provide key insights into the logic of regulatory networks that control development as well as into disease processes that disrupt them.

发育生物学的一个核心问题是，“细胞是如何从多能性发展而来的？