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.

项目摘要 复杂的组织模式从看似均匀的未分化细胞中出现， 发育是所有多细胞生物的基本特征。最著名的理论之一 通常用来解释生物模式形成的机制是反应扩散（RD）模型， 假设局部激活的模式分化因子结合远程抑制的， 这些因素的活动可以产生动态的、自组织的空间模式。许多经验和 模拟研究已经表明，RD机制是各种图案形成的基础 流程.然而，我们仍然对编码假设激活的实际基因知之甚少 和抑制因子在大多数经验系统，更少关于这些因素的生物物理性质 候选基因已经被确定，几乎没有关于如何调制的属性， 这些激活剂和抑制剂影响自然界中的模式进化。该项目的总体目标是 解决这些基本问题，阐明详细的遗传和发育机制， 野生花属Mimulus（monkeyflowers）色素模式的形成和进化， 服从严格的遗传分析，发育询问和表型干扰。工作 这里提出的将建立在我们先前的努力，艾德了一对MYB蛋白的形成基础上， 花青苷色素斑点分散。这种MYB对形成局部自催化 反馈回路和长距离抑制反馈回路，实现经典的激活抑制器的原理 RD模型。我们在未来几年的目标是：（一）实验确定的生物物理特性的 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）表征模式的遗传和发育基础 在密切相关的物种之间从分散的斑点进化为纵向条纹;以及（iii）确定 关键的顺式调节元件，构成激活剂-抑制剂相互作用网络，并测试功能， 在其他组织类型和异源系统中的这种双组分激活剂-抑制剂模块。朝向 为此，我们将使用一系列方法，包括荧光成像、遗传图谱、转基因 操纵和数学建模。我们的共同努力将提供一个深入了解如何研发 一种机制产生自组织的空间模式，并调节真实的生物模式的进化 系统，贷款经验支持数学优雅，但有点争议的RD模型。