Web-based Atlas of Zebrafish Microanatomy as a Community Resource

描述(申请人提供)：斑马鱼现在是一种常见的、非哺乳动物的人类疾病模型，因为它具有小尺寸、透明度和强大的遗传工具等实验特征。为了响应NIH赞助的斑马鱼和水生模型工作组的建议，美国科学基础设施的一个重要部分正在以基于网络的解剖学、组织学和病理学地图集的形式建立。这份地图集将从www.zfarlas.psu.edu和俄勒冈大学斑马鱼信息网(ZFIN)(www.zfin.org)获取。正常解剖学将作为研究遗传缺陷和疾病引起的异常解剖学的关键背景。该图集的人员、成像和计算机硬件和网站构成了基础设施，用户可以在2D和3D的正常背景下查看突变/变异/患病的斑马鱼。具体目标1是从建立的突变体集合开始，将异常表型整合到图集中，创建一种非破坏性的机制，用于远程标记基于网络的最先进的虚拟幻灯片，允许以不同的能力查看组织切片，将斑马鱼图集与其他基于网络的资源整合，包括斑马鱼基于网络的资源之家(www.zfin.org)，并使用网络界面显示一系列突变表型。具体目标2是开发分析和显示3D斑马鱼数据的机制。我们将从斑马鱼的数字3D表示中分割和标记不同的器官，并探索、测试和实现虚拟幻灯片和通过亚细胞分辨率的MicroCT成像创建的3D斑马鱼表示之间的集成接口。具体目标3是为跨模型系统的结构和功能集成奠定基础。这个目标将利用斑马鱼、老鼠和人类作为感兴趣的生物，并使用特定的骨骼、眼睛和皮肤颜色突变作为描述模型系统在理解生物功能和疾病中的作用的范例。这一目标将集中在所有三个物种共有的正常组织上，然后是所有三个物种共有的病理学。这一社区资源的整合将作为所有模型系统网站的模型，为整个国家卫生研究院的多个任务提供服务。 公共卫生相关性(由申请人提供)：令人信服的实验特征使斑马鱼成为包括癌症、心脏病和感染在内的各种人类疾病的模型。该地图集(www.zfarlas.psu.edu)包含正常斑马鱼和建议的异常斑马鱼的高分辨率2D和3D表示。通过与其他示范系统相互参照，地图集还将为综合、多学科项目提供基础设施。

DESCRIPTION (provided by applicant): The zebrafish is now a common, non-mammalian model of human disease due to experimental features such as small size, transparency, and powerful genetic tools. In response to NIH-sponsored Zebrafish and Aquatic Models working groups' recommendations, an important piece of American scientific infrastructure is being established in the form of a web-based atlas of anatomy, histology, and pathology. This atlas will be accessible from www.zfatlas.psu.edu and the Zebrafish Information Network (ZFIN) at the University of Oregon (www.zfin.org). Normal anatomy will serve as critical context for the study of abnormal anatomy caused by genetic deficiencies and disease. The atlas' personnel, imaging and computer hardware and web site comprise the infrastructure for users to view mutant/morphant/diseased zebrafish in the context of normal, in both 2D and 3D. Specific Aim 1 is to integrate abnormal phenotypes into the atlas starting with an established mutant collection, to create a nondestructive mechanism for remote labeling of web-based, state-of-the-art virtual slides that allows viewing of histological tissue sections at different powers, to integrate the zebrafish atlas with other web-based resources including the home of zebrafish web-based resources (www.zfin.org), and to use the web interface to display a range of mutant phenotypes. Specific Aim 2 is to develop mechanisms for analyzing and displaying 3D zebrafish data. We will segment and label different organs from digital 3D representations of zebrafish, and explore, test, and implement integrated interfaces between virtual slides and 3D representations of zebrafish created by microCT imaging at subcellular resolutions. Specific Aim 3 is to build a foundation for structural and functional integration across models systems. This aim will utilize zebrafish, mouse, and human as the organisms of interest, and use specific skeletal, eye, and skin color mutations as a paradigm for describing the roles of model systems in understanding a biological function and disease. This aim will focus on normal tissues shared by all three species followed by pathology shared by all three species. The integrations of this community resource will serve as a model for all model system web sites, serving multiple missions across the NIH. PUBLIC HEALTH RELEVANCE (provided by applicant): Compelling experimental features have made the zebrafish a model for a wide range of human maladies, including cancer, heart disease, and infection. The atlas (www.zfatlas.psu.edu) contains high-resolution 2D and 3D representations of normal and, as proposed, abnormal zebrafish. By cross-referencing with other model systems, the atlas will also provide infrastructure for integrative, multidisciplinary projects.