Developmental Compartments of the Zebrafish Neurocranium

描述（由申请人提供）：人类出现大量颅面畸形；然而，人们对神经头盖骨的正常发育以及这些畸形是如何发生的知之甚少。这里提出的研究将扩大对以斑马鱼为模型系统的神经颅发育的理解。首先，细胞谱系追踪将用于确定神经头盖骨的起源。这一分析为理解神经颅骨发育提供了一个基本工具，并对畸形发生的细胞病因进行了研究。其次，将进行功能丧失和功能获得实验，以确定Shh在指定神经颅骨前软骨中的作用。第三，将进行细胞移植实验，以确定Shh效应基因的突变在发育过程中是细胞自主作用还是非细胞自主作用。最后，将使用正向遗传筛选来发现影响神经颅骨软骨发育的新突变。

DESCRIPTION (provided by applicant): A vast number of craniofacial dysmorphologies arise in humans; however, little is known about the normal development of the neurocranium and how these dysmorphologies occur. The research proposed here will broaden the understanding of neurocranial development using the zebrafish as a model system. First, cell-lineage tracing will be used to determine the origins of the neurocranium. This analysis provides a basic tool for understanding neurocranial development and gives inroads to the cellular etiology of dysmorphogenesis. Second, loss- and gain-of-function experiments will be carried out to determine the role of Shh in specifying the anterior cartilages of the neurocranium. Third, cell transplantation experiments will be performed to determine if mutations in Shh effector genes act cell autonomously or non-cell autonomously in development. Last, a forward genetic screen will be used to discover new mutations that affect the development of neurocranial cartilages.