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: 10530603
• 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/10530603
• 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; 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; Specific qualifier value; Spottings; System; Testing; Time; Tissues; Transgenic Organisms; Translating; Undifferentiated; Variant; Vertebrates; Wing; Work; base; biological systems; biophysical properties; cell fate specification; experimental study; fluorescence imaging; genetic analysis; genetic manipulation; inhibitor; insight; mathematical model; morphogens; mutant; plant genetics; self organization; 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.

项目概要 在看似均匀、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的基本特征。最突出的理论之一 经常被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相结合 这些因素的活动可以产生动态的、自组织的空间模式。大量的经验和 模拟研究表明，RD 机制是多种模式形成的基础 流程。然而，我们对编码假设激活的实际基因仍然知之甚少 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特性 候选基因已被识别，但几乎没有关于如何调节其特性的信息 这些激活剂和抑制剂影响自然界的模式进化。该项目的总体目标是 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 Mimulus（猴花）色素模式的形成和进化，一个系统 经得起严格的遗传分析、发育询问和表型扰动。工作 这里提出的建议将建立在我们之前的努力的基础上，我们之前的努力鉴定了一对 MYB 蛋白，这些蛋白是形成 酸浆花中分散的花青素色素斑点。该 MYB 对形成局部自催化 反馈环路和长程抑制反馈环路，满足经典激活剂-抑制剂的原则 研发型号。我们未来几年的目标是：（i）通过实验确定生物物理特性 激活剂-抑制剂对，包括它们的扩散系数、降解（清除）率和相对 激活和抑制常数； (ii) 表征模式的遗传和发育基础 密切相关的物种之间从分散的斑点进化为纵向条纹； (iii) 确定 构成激活剂-抑制剂相互作用网络并测试其功能的关键顺式调节元件 这种由两部分组成的激活剂-抑制剂模块存在于其他组织类型和异源系统中。向 为了达到这些目的，我们将使用一套方法，包括荧光成像、基因图谱、转基因 操作和数学建模。通过我们的共同努力，我们将深入了解 RD 如何 机制产生自组织空间模式并调节真实生物中的模式进化 系统，为数学上优雅但有些争议的 RD 模型提供了实证支持。