WormGUIDES: A Resource for Global Understanding in Dynamic Embryonic Systems

项目摘要 神经科学的一个主要挑战是理解胚胎细胞的分化是如何从头开始的。 构成神经系统的工作回路和网络。我们提出WormGUIDES，一个资源， 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;神经突形成，定向生长和捆绑;最终，突触 功能电路的形成和调整-从概念到孵化，具有单细胞分辨率。建筑 在第一个融资周期的创新基础上，我们建议使用ShootingStar，一个新颖的平台， 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 成像捕捉神经束动力学和单细胞生长在早期发育的胚胎时， 神经系统的主要结构被构建。我们还将分配所有核身份和位置 从第一次细胞分裂到孵化最后，我们将通过以下方式与社区分享知识： WormGUIDES Atlas软件，显示模型，支持图像和原始数据。完成 WormGUIDES资源最终将补充现有的细胞谱系，成人神经系统结构， 以及蠕虫的集体基因组和遗传数据，创造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.