Development and evolution of self-organizing pigmentation patterns

自组织色素沉着模式的发展和演变

• 批准号: 10317040
• 负责人: Yaowu Yuan
• 金额: $ 35.29万
• 依托单位: UNIVERSITY OF CONNECTICUT STORRS
• 依托单位国家: 美国
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-12-15 至 2024-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10317040
• 关键词: Address; Affect; Alleles; Animals; Anthocyanins; Binding; Biological; Biological Models; Biology; Candidate Disease Gene; Cells; Chromosome Mapping; Color; Complex; Computer Simulation; Development; Developmental Process; Diffusion; Digit structure; Distant; Embryo; Evolution; Exhibits; Feedback; Flowers; Genes; Genetic; Genetic Transcription; Goals; Hair Root; Hair follicle structure; Health; Human; Insecta; Lung; Mathematics; Metabolic Clearance Rate; Mimulus; Modeling; Molecular; Mouse-ear Cress; Movement; Mutation; Nature; Organism; Pattern; Pattern Formation; Phenotype; Pigmentation physiologic function; Pigments; Plants; Process; Property; Proteins; Reaction; Regulatory Element; Role; Spottings; System; Testing; Time; Tissues; Transgenic Organisms; Translating; Undifferentiated; Ursidae Family; Variant; Vertebrates; Wing; Work; base; biological systems; biophysical properties; cell fate specification; experimental study; fluorescence imaging; genetic analysis; inhibitor; insight; mathematical model; morphogens; mutant; plant genetics; simulation; trait; transcription factor; virtual

Project Summary The emergence of complex tissue patterns from seemingly uniform, undifferentiated cells during development is an essential feature of all multicellular organisms. One of the most prominent theoretical mechanisms often invoked to explain biological pattern formation is the reaction-diffusion (RD) model, which postulates that local activation of pattern differentiation factors combined with long-range inhibition of the activity of those factors can produce dynamic, self-organizing spatial patterns. Numerous empirical and simulation studies have suggested that the RD mechanism underlies a wide range of pattern formation processes. However, we still know very little about the actual genes encoding the hypothetical activation and inhibition factors in most empirical systems, even less about the biophysical properties of these factors where candidate genes have been identified, and virtually nothing about how modulation of the properties of these activators and inhibitors affects pattern evolution in nature. The overall objective of this project is to address these fundamental questions by elucidating the detailed genetic and developmental mechanisms of pigment pattern formation and evolution in the wildflower genus Mimulus (monkeyflowers), a system amenable to rigorous genetic analysis, developmental interrogation, and phenotypic perturbation. The work proposed here will build on our prior efforts that identified a pair of MYB proteins underlying the formation of dispersed anthocyanin pigment spots in Mimulus flowers. This MYB pair forms a local autocatalytic feedback loop and a long-range inhibitory feedback loop, fulfilling the tenets of a classical activator-inhibitor RD model. Our goals in the coming years are to: (i) experimentally determine the biophysical properties of the activator-inhibitor pair, including their diffusion coefficients, degradation (clearance) rates, and relative activation and inhibition constants; (ii) characterize the genetic and developmental bases of pattern evolution from dispersed spots to longitudinal stripes between closely related species; and (iii) identify the key cis-regulatory elements that constitute the activator-inhibitor interacting network and test the function of this two-component, activator-inhibitor module in other tissue types and heterologous systems. Towards these ends we will use a suite of approaches, including fluorescence imaging, genetic mapping, transgenic manipulation, and mathematical modeling. Together our efforts will provide an in-depth view of how the RD mechanism generates self-organizing spatial patterns and modulates pattern evolution in a real biological system, lending empirical support to the mathematically elegant but somewhat controversial RD model.

项目摘要 从看似均匀、未分化的细胞中出现复杂的组织模式 发育是所有多细胞生物体的基本特征。最突出的理论之一 常被引用来解释生物模式形成的机制是反应扩散(RD)模型，该模型 假设模式分化因子的局部激活与长期抑制 这些因素的活动可以产生动态的、自组织的空间模式。无数的经验主义和 模拟研究表明，RD机制是一系列花样形成的基础 流程。然而，我们仍然对编码假想激活的实际基因知之甚少。 以及大多数经验系统中的抑制因素，甚至更少关于这些因素的生物物理性质 在哪里发现了候选基因，几乎没有关于如何调节 这些激活剂和抑制物会影响自然界中的模式进化。这个项目的总体目标是 通过阐明详细的遗传和发育机制来解决这些基本问题 野花属(猴头花属)色素花纹的形成和进化 服从严格的遗传分析、发育讯问和表型扰动。这项工作 在此提出的建议将建立在我们之前的工作基础上，即fi鉴定了一对myb蛋白，这些蛋白是形成 紫薇花中分散的花青素色素斑点。这种MYB对形成局部自催化 反馈回路和远程抑制反馈回路，实现了经典的激活-抑制原理 RD模型。我们在未来几年的目标是：(I)通过实验确定 活化剂-抑制剂对，包括它们的扩散系数、降解(清除)速率和相对 激活和抑制常数；(Ii)表征模式的发生和发展基础 在密切相关物种之间从分散的斑点到纵向条纹的进化；以及(Iii)识别 构成激活剂-抑制物相互作用网络的关键顺式调控元件，并测试 在其他组织类型和异种系统中，这种由两种成分组成的激活-抑制模块。朝向 这些目的我们将使用一套方法，包括荧光成像，遗传图谱，转基因 操控和数学建模。我们的共同努力将提供一个深入的视角，如何研发 机制在真实生物中产生自组织的空间模式并调节模式进化 系统，为数学上优雅但有些有争议的RD模型提供了经验支持。