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

动物的结构是由不同细胞类型的组合和排列构成的，是发育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它们的命运呢？这项研究以一种简单而又极其多样化的动物结构——蝴蝶翅膀上的颜色模式——来解决这个基本的生物学问题。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，黑色和黄色的翅膀鳞片）在翅膀表面的分布而产生的。与复杂器官不同的是，形成这些模式的细胞决定在非迁移细胞的平面画布上展开。这一特性极大地简化了理解基因之间相互作用的过程，以及这些相互作用在整个发育过程中如何变化以形成特定模式。本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策。该项目通过一个为期6个月的实习项目得到加强，该项目针对传统上代表性不足的群体，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，向各种受众（学童、教师和终身学习者）传授基因、发育、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方面所起的作用。进化过程不断产生和重新排列特化的细胞类型，形成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的决定联系起来。然而，这方面的研究主要集中在少数物种的早期胚胎发育或复杂器官的发育轨迹。尽管这些研究很强大，但它们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，通过描述控制细胞规范的规则-从信号到接收，转导，转录激活和命运决定，在关键的发育时期，蝴蝶的翅膀模式建立。在这里，对翅膀颜色图案的生态和进化意义的广泛了解，实验的可操作性和奇妙的多样性使Heliconius成为一个强大的实验系统，用于理解细胞规范过程如何被自然选择修改以产生多样性。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，包括复制相同翅膀模式的独立进化案例，该项目将确定控制细胞在发育过程中如何沟通和获得特殊命运的规则，以及如何应用这些规则来产生多样性。该奖项反映了美国国家科学基金会的法定使命，并通过使用基金会的知识价值和更广泛的影响审查标准进行评估，被认为值得支持。

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.