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.

动物的结构是由不同细胞类型的组合和排列组成的，是发育过程中复杂细胞决策的产物。但是，含有相同遗传信息的细胞如何决定它们的命运呢？这项研究解决了这个基本的生物学问题，在一个简单的，但异常多样的动物结构-颜色模式的翅膀上的Heliconius蝴蝶。虽然Heliconius的翅膀图案是高度多样化的，但它们是通过改变三种细胞类型（红色，黑色和黄色翅膀鳞片）在翅膀表面的分布而形成的。与复杂器官不同，创造这些模式的细胞决定在非迁移细胞的平坦画布上展开。这个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在整个发育过程中如何变化以创建特定模式的过程。这项研究利用这一事实和新兴的基因组工具来表征决定发育中的翼细胞如何被指定为三种不同规模细胞类型之一的分子决定。该项目通过为期6个月的实习计划得到加强，该计划针对传统上代表性不足的群体，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合作，该项目将创建双语（英语和西班牙语）体验式学习资源，利用蝴蝶的潜力教育各种受众（学生，教师和终身学习者）关于基因，发展，自然选择，以及它们之间的相互作用在产生地球生物多样性中所起的作用。进化过程不断地产生和重新排列专门的细胞类型，锻造生物多样性的形态维度。研究开始将基因表达和开放染色质的变化与细胞命运决定联系起来。然而，这项研究主要集中在早期胚胎发育或少数物种复杂器官的发育轨迹上。尽管这些研究很有说服力，但并没有明确的目标将细胞命运决定的变化与表型变化联系起来。这项研究填补了这一重要的知识空白，通过表征管理细胞规格的规则-从信号，到接收，转导，转录激活和命运决定在关键的发展时期，当Heliconius蝴蝶的翅膀模式建立。在这里，广泛的知识的生态和进化意义的翅膀的颜色模式，实验的易处理性，和奇妙的多样性，使Heliconius一个强大的实验系统，了解细胞规格的过程是如何修改的自然选择，以产生多样性。通过在进化框架内进行单细胞转录组学，开放染色质分析和CRISPR功能丧失实验，该框架包括相同翅膀模式独立进化的复制案例，该项目将确定管理细胞如何通信的规则，并在发育过程中获得专门的命运，该奖项反映了NSF的法定使命，并被认为值得通过使用基金会的知识价值和更广泛的影响进行评估来支持审查标准。