WormGUIDES: A Resource for Global Understanding in Dynamic Embryonic Systems

项目摘要 神经科学中的一个主要挑战是理解胚胎细胞分化是如何从头开始的 组成神经系统的工作回路和网络。我们提出了WormGUIDES，这是一种 将有助于从各个角度理解整个神经系统的细胞起源--细胞诞生， 迁移和分化；轴突的形成；靶向突起和捆绑；最终，突触 功能电路的形成和调谐--从受孕到孵化，单细胞分辨率。建房 关于我们在第一个融资周期中建立的创新，我们建议使用Shootingstar，一个新的平台 用于实时细胞跟踪和光学操作以标记单个神经元，以及各向同性高分辨率DiSPIM 成像捕捉早期发育胚胎中神经束动力学和单细胞生长 神经系统的主要结构被构建起来。我们还将分配所有核身份和立场 从第一次细胞分裂到孵化。最后，我们会透过以下途径与社会人士分享有关知识 WormGUIDES Atlas软件，显示模型、支持图像和原始数据。已完成的 蠕虫资源最终将补充现有的细胞谱系，成人神经系统结构， 以及收集蠕虫的基因组和遗传数据，创建了系统级知识的第四个支柱， 将增强我们对神经发育的理解。

Project Summary A major challenge in neuroscience is to comprehend how differentiating embryonic cells fashion de novo the working circuits and networks that make up a nervous system. We propose WormGUIDES, a resource that would facilitate understanding the cellular origins of an entire nervous system from all angles—cell birth, migration and differentiation; neurite formation, targeted outgrowth and bundling; and ultimately, synapse formation and tuning of functional circuits—with single cell resolution, from conception until hatching. Building on the innovations we established in the first funding cycle, we propose to use ShootingStar, a novel platform for real-time cell tracking and optical manipulation to label single neurons, and isotropic high-resolution diSPIM imaging to capture nerve bundling dynamics and single cell outgrowth in the early developing embryo when the major architecture of the nervous system is constructed. We will also assign all nuclear identities and positions from the first cell division until hatching. Finally, we will share the knowledge with the community through WormGUIDES Atlas software, displaying models, supporting images and primary data. Completion of the WormGUIDES resource will ultimately complement the existing cell lineage, adult nervous system structure, and collective genomic and genetic data for the worm, creating a fourth pillar of systems-level knowledge that will enhance our understanding of neurodevelopment.