Collaborative Research: RoL: The intersection between cell fate decisions and phenotypic diversification in a rapidly radiating butterfly lineage

合作研究：RoL：快速辐射蝴蝶谱系中细胞命运决定和表型多样化之间的交叉点

• 批准号: 2110533
• 负责人: Gregory Wray
• 金额: $ 71.02万
• 依托单位: Duke University
• 依托单位国家: 美国
• 项目类别: Continuing Grant
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-08-15 至 2025-07-31
• 项目状态: 未结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=2110533&HistoricalAwards=false
• 关键词: Collaborative; Research; RoL; intersection; between

Animal structures are made of combinations and arrangements of distinct cell types, the product of complex cell decision-making during development. But how do cells, which contain identical genetic information, decide their fate? This research addresses this fundamental biological question in a simple, yet spectacularly diverse animal structure–the color patterns on the wings of Heliconius butterflies. Although Heliconius wing patterns are highly diverse, they are created by altering the distribution of just three cell types (red, black and yellow wing scales) across the wing surface. Unlike in a complex organ, the cell decisions that create these patterns unfold on a flat canvas of non-migrating cells. This attribute greatly simplifies the process of understanding the interactions among genes and how these interactions change throughout development to create a specific pattern. This research capitalizes on this fact and emerging genomic tools to characterize the molecular decisions that determine how a developing wing cell becomes specified into one of the three different scale cell types. The project is strengthened by a 6-month internship program that targets traditionally underrepresented groups and offers an in-depth research experience and hands-on professional development. Moreover, through partnerships with science museums, this project will create bilingual (English and Spanish) experiential learning resources that harness the potential of butterflies to educate a variety of audiences (school children, teachers, and life-long learners) about genes, development, natural selection, and the role that interactions among them play in generating Earth’s biodiversity.Evolutionary processes constantly generate and rearrange specialized cell types, forging the morphological dimension of biodiversity. Research is starting to connect changes in gene expression and open chromatin to cell fate decisions. However, this research has mostly focused on early embryonic development or on the developmental trajectories of complex organs in a few species. Although powerful, these studies do not have an explicit goal of linking changes in cell fate decisions to phenotypic change. This research fills this important knowledge gap by characterizing the rules governing cell specification– from signals, to reception, transduction, transcriptional activation, and fate determination during the critical developmental period when the wing patterns of Heliconius butterflies are established. Here, extensive knowledge of the ecological and evolutionary significance of wing color patterns, experimental tractability, and fantastic diversity make Heliconius a powerful experimental system for understanding how the processes of cell specification are modified by natural selection to produce diversity. By casting single-cell transcriptomics, open chromatin profiling and CRISPR loss-of-function experiments within an evolutionary framework that includes replicated cases of the independent evolution of identical wing patterns, this project will determine the rules that govern how cells communicate and acquire a specialized fate during development, and how those rules are applied to generate diversity.This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.

动物结构是由不同细胞类型的组合和排列制成的，这是开发过程中复杂细胞决策的产物。但是，包含相同遗传信息的细胞如何决定其命运？这项研究以简单但壮观的动物结构（Heliconius蝴蝶的翅膀上的颜色模式）解决了这个基本的生物学问题。尽管Heliconius机翼模式高度多样，但它们是通过更改三种细胞类型（红色，黑色和黄翼尺度）的分布来创建的。与复杂的器官不同，创建这些模式的细胞决策在非迁移细胞的平坦画布上展开。这种属性大大简化了理解基因之间的相互作用以及这些相互作用如何在整个开发中变化以创建特定模式的过程。这项研究利用了这一事实和新兴的基因组工具来表征分子决策，这些决策决定了发展中的机翼细胞如何将其指定为三种不同尺度细胞类型之一。该项目通过为期6个月的实习计划加强了该项目，该计划以传统上代表性不足的群体为目标，并提供深入的研究经验和实践专业发展。此外，通过与科学博物馆的伙伴关系，该项目将创造双语（英语和西班牙语）经验丰富的学习资源，可以利用蝴蝶的潜力来教育各种受众（小学生，老师和终身学习者）基因，发展，自然选择，自然选择以及它们之间的互动以及它们在生成地球的生物际启动的互动中，并逐步促进了进化的繁殖，并逐渐构成了繁殖的杂物，并将其逐步化繁殖，并逐渐繁殖，又有序言，又有序言繁殖的繁殖范围，既富有繁殖的杂物，又是繁殖的，这生物多样性。研究开始将基因表达的变化和开放性染色质连接到细胞脂肪决策。但是，这项研究主要集中在早期胚胎发育或一些物种中复杂器官的发育轨迹上。尽管强大，但这些研究并没有将细胞脂肪决策变化与表型变化联系起来的明确目标。这项研究通过表征有关细胞规范的规则（从信号到接收，转导，转录，转录激活和脂肪确定的规则）来填补这一重要的知识差距，并确定了Heliconius蝴蝶的机翼模式。在这里，对机翼颜色模式，实验性障碍和奇妙多样性的生态和进化意义的广泛了解使Heliconius成为强大的实验系统，以了解如何通过自然选择来改变细胞规范的过程以产生多样性。通过在进化框架内施放单细胞转录组，开放染色质分析和CRISPR功能丧失实验，包括包括复制的相同机翼模式的独立演变的复制案例，该项目将确定细胞在开发过程中的沟通和获得专业的命运的规则，以及如何通过生成多样化的奖励来反映出这些规则，并反映了该规则的宣传。智力优点和更广泛的影响审查标准。