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 在看似统一的，未分化的细胞中复杂组织模式的出现 开发是所有多细胞生物的重要特征。最突出的理论之一 通常调用以解释生物模式形成的机制是反应扩散（RD）模型，该模型是该模型 假设局部激活模式分化因子与长期抑制 这些因素的活性可以产生动态的自组织空间模式。许多经验和 仿真研究表明，RD机制是广泛的模式形成的基础 过程。但是，我们仍然对编码假设活动的实际基因知之甚少 和大多数经验系统中的抑制因子，甚至不太了解这些因素的生物物理特性 鉴定了候选基因的地方，几乎没有关于如何调节的特性 这些激活因子和抑制剂会影响自然界的模式演变。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（Monkeyflowers）的色素图案形成和演变，一个系统 适合严格的遗传分析，发育进行和表型扰动。工作 在这里提出的将基于我们先前的努力，该努力确定了形成的一对Myb蛋白 分散在毛ul菜花中的花青素色素斑。这对MYB对形成本地自催化 反馈循环和远程抑制反馈回路，实现经典激活器抑制剂的宗旨 RD模型。我们未来几年的目标是：（i）实验确定 激活物抑制剂对，包括其差异系数，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 从分散的斑点到密切相关物种之间的纵向条纹的演变； （iii）确定 构成激活剂抑制剂相互作用网络并测试功能的关键顺式调节元素 这种两组分的激活剂抑制剂模块在其他组织类型和异源系统中。向 这些末端我们将使用一套方法，包括荧光成像，遗传映射，转基因 操作和数学建模。我们的努力将提供深入的观点 机制会产生自组织的空间模式，并在实际生物学中调节模式演变 系统，为数学优雅但有些争议的RD模型提供经验支持。