Development of Epibranchial Placodes and Ganglia in Zebrafish

描述(申请人提供)：在脊椎动物中，来自外胚层胎盘的副交感神经节(EB)的感觉神经元对于形成嗅觉、躯体感觉和味觉等颅脑感觉系统是必不可少的。尽管它们很重要，但人们对控制EB安慰剂和神经节不同发育方面的分子机制知之甚少。这项应用的总体目标是：1)确定导致早期EB前体与共同胎盘区域分离的细胞和分子机制；2)利用斑马鱼中先进的遗传工具，以确定与EB胎盘和神经节发育有关的新基因。 这位候选人对发育生物学有着长期的兴趣。在他的研究生和博士后研究中，一个统一的主题是解决幼稚的祖细胞如何分离以产生最终形成器官的不同细胞类型的问题。当这个问题应用到脊椎动物神经系统时，这个问题的重要性就更加深刻了，因为脊椎动物神经系统中存在数百种细胞类型。在这项应用的K99部分，他将研究成纤维细胞生长因子信号如何调节EB胎盘前体从共同的祖细胞领域分离出来。这项工作是他目前研究成纤维细胞生长因子信号在EB胎盘发育中的作用的NRSA研究的直接延伸。候选人计划继续开发技术，帮助他研究颅骨安慰剂和神经节，包括斑马鱼转基因系的产生和测试，这将极大地促进在R00阶段提出的突变筛选。在完成博士后工作后，候选人计划在学术环境中建立一个独立的基础研究项目。他预计，在K99部分培训中获得的实践和理论知识将帮助他启动自己的独立研究，并使他能够冒险进入斑马鱼生物学的新领域。

DESCRIPTION (provided by applicant): In vertebrates, sensory neurons of the parasympathetic epibranchial (EB) ganglia derived from ectodermal placodes are essential for the formation of cranial sensory systems such as smell, somatosensation, and taste. Despite their importance, very little is known about molecular mechanisms that govern various developmental aspects of EB placodes and ganglia. The overall goals of this application are: 1) to define the cellular and molecular mechanisms that are responsible for segregation of the early EB precursors from the common placodal field, and 2) to take advantage of advanced genetic tools in zebrafish in order to identify novel genes responsible for EB placode and ganglia development. The candidate has a long-standing interest in developmental biology. One unifying theme during his graduate and postdoctoral research was to address the question how naive progenitor cells segregate to give rise to diverse cell types that eventually form an organ. The importance of this question is even more profound when applied to a vertebrate nervous system, where hundreds of cell types exist. During the K99 part of this application, he will study how Fgf signaling regulates segregation of EB placode precursors from a common progenitor field. This work is a direct extension of his current NRSA fellowship to study roles of Fgf signaling during EB placode development. The candidate plans to continue developing technology that will assist him in studying cranial placodes and ganglia, including generation and testing of zebrafish transgenic lines, which will greatly facilitate the mutagenesis screen proposed during the R00 phase. Following postdoctoral work, the candidate plans to establish an independent basic research program in an academic setting. He expects that practical and theoretical knowledge gained during the K99 part of the training will help him to jump-start his own independent studies and will also allow him to venture into new aspects of zebrafish biology.