Functional analysis of neural crest & palate: Imaging craniofacial development

描述（由申请人提供）：该研究计划将完善和部署一套先进的工具，用于颅面发育过程中组织结构，基因表达域和细胞动力学的成像。体积成像工具将用于创建精确的3D图谱，可以对其进行数字解剖，以便更好地理解正常、突变和受干扰的小鼠和鸟类胚胎形成面中的组织相互作用和细胞事件。分子显像剂，优化成像完整的组织，将被用来创建这些胚胎的分子相关图谱。最后，病毒内成像工具将用于研究细胞和组织的相互作用，为执行颅面发育的动态事件提供一个视图。这些数据将被组装成地图集，为探索颅面发育的细胞、组织和分子相关性提供前所未有的工具。这些地图集将通过本地创建的在线资源广泛提供给Face Base联盟的其他人和更广泛的颅面研究人员社区。此外，它们将通过已建立的枢纽与其他Face Base资源连接，以便我们的地图集中的数据可以与联盟其他成员提供的分子和结构数据一起使用。在这里建立的数据采集管道与Yang Chai博士（南加州大学）和Marianne Bronner-Fraser博士（加州理工学院）的实验室密切合作，将创建一个模型，可以扩展到表型和分析其他实验系统。

DESCRIPTION (provided by applicant): The research plan will refine and deploy a set of advanced tools for the imaging of tissue structure, gene expression domains and cellular dynamics during craniofacial development. Volumetric imaging tools will be used td create accurate 3D atlases that can be digitally dissected to permit the tissue interactions and cellular events to be better understood in the forming faces of normal, mutant and perturbed mouse and avian embryos. Molecular imaging agents, optimized for imaging intact tissues, will be employed to create atlases of the molecular correlates of these embryos. Finally, intraviral imaging tools will be used to study cell and tissue interactions as they take place, offering a view into the dynamic events that execute craniofacial development. The data will be assembled into atlases that will offer unprecedented tools for exploring the cellular, tissue and molecular correlates of craniofacial development. These atlases will be made widely available for the use of others in the Face Base consortium and the broader community of craniofacial researchers through an online resource created locally. In addition, they will be linked to other Face Base resources through established hubs, so that the data in our atlases can be used in concert with the molecular and structural data provided by other members of the consortium. The data acquisition pipeline established here in close collaboration with the laboratories of Dr. Yang Chai (University of Southern California) and Dr. Marianne Bronner-Fraser (Caltech) will create a model that can be expanded to phenotype and analyze other experimental systems. PUBLIC HEALTH RELEVANCE: Cleft palate, with or without cleft lip. is one of the more common birth defects, affecting approximately one in 2500 live births. The basic events by which cells of different origin come together to form the face have long been known, but the exact tissue movements and the signals that guide them remain undefined. The goal of this work is to help fill this void by imaging the morphology of normal craniofacial development, the abnormal development seen in cleft palate, and providing a means to experimentally test the roles of signaling pathways in the tissue interactions that build the face. This work offers a powerful platform for devising and testing potential therapeutic approaches.