CAREER: Development of the Ascidian Peripheral Nervous System

职业：海鞘周围神经系统的发育

• 批准号: 0347937
• 负责人: Robert Zeller
• 金额: $ 59.53万
• 依托单位: San Diego State University Foundation
• 依托单位国家: 美国
• 项目类别: Continuing Grant
• 财政年份: 2004
• 资助国家: 美国
• 起止时间: 2004-03-01 至 2010-02-28
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=0347937&HistoricalAwards=false
• 关键词: CAREER; Development; Ascidian; Peripheral; Nervous

A key step in the evolution of vertebrates was the development of a large bony head containing specialized paired sensory organs that allowed vertebrates to become active predators. Vertebrate heads and the associated cells of the paired sensory organs are largely derived from two populations of cells, the neural crest and cranial placodes. Although research has led to a greater understanding of how neural crest and placodes are specified during vertebrate development, very little is known about their evolutionary origins. The proposed research will investigate the evolutionary and embryological origins of cranial placodes by examining the development of the ascidian larva peripheral nervous system (PNS). Ascidians are invertebrate chordates ideally suited for studying the evolution of chordate characteristics. The larval PNS, consisting of about three dozen cells that are primarily epidermal sensory neurons, shows similarities with placode-derived sensory cells both morphologically as well as in the expression patterns of key regulatory molecules. This research will determine the cell lineage and function of the PNS, and begin to define the gene-regulatory network specifying PNS development in the ascidian embryo. Graduate and undergraduate students will pioneer the use of three technologies to study marine invertebrate embryo development: (1) transgene-based cell-lineage analysis, (2) selective cell killing by the intracellular expression of a toxin and (3) in-vivo assays of gene function using RNA inhibition. Additionally, comparative-genomics approaches, in-situ hybridization, quantitative real-time PCR and analysis of transgenic embryos will be employed to decipher the PNS gene-regulatory network. These experiments will provide insights into the functional and gene-regulatory similarities between the ascidian larval PNS and vertebrate cranial placodes.This project will contribute to the development of the PI as a teacher-scholar. It incorporates educational programs for undergraduate, graduate, postgraduate and elementary school students and teachers. The proposed research will be performed primarily by graduate and undergraduate students. Student research will be published in scientific journals, and students will be encouraged to present their findings at scientific meetings. A series of year-long research opportunities for undergraduates, including a summer program, will provide 4 to 6 students with independent projects and a journal club focused on developmental biology and experimental techniques. New experimental approaches will be incorporated into an intense laboratory/lecture section on ascidian development for advanced graduate and postdoctoral fellows in the Woods Hole Embryology Course. Finally, an interactive Web site will be created for elementary-schoolstudents, providing them with a feel for biological research. The Web site will bring the laboratory into the classroom, exposing young students to the creativity and excitement involved in scientific research. This innovative program will serve as a model to encourage other laboratories to partner with elementary-school classrooms to provide improved science education to children.

脊椎动物进化的一个关键步骤是发育出含有专门的成对感觉器官的大型骨头，使脊椎动物能够成为活跃的捕食者。 脊椎动物的头部和配对感觉器官的相关细胞主要源自两个细胞群：神经嵴和颅板。尽管研究使人们对脊椎动物发育过程中神经嵴和基板的具体化有了更深入的了解，但人们对它们的进化起源知之甚少。拟议的研究将通过检查海鞘幼虫周围神经系统（PNS）的发育来研究颅板的进化和胚胎学起源。海鞘是无脊椎动物脊索动物，非常适合研究脊索动物特征的进化。幼虫PNS由大约三打细胞组成，主要是表皮感觉神经元，在形态上以及关键调节分子的表达模式上都显示出与基板衍生的感觉细胞的相似性。这项研究将确定 PNS 的细胞谱系和功能，并开始定义指定海鞘胚胎中 PNS 发育的基因调控网络。研究生和本科生将率先使用三种技术来研究海洋无脊椎动物胚胎发育：(1) 基于转基因的细胞谱系分析，(2) 通过细胞内表达毒素选择性杀死细胞，以及 (3) 使用 RNA 抑制进行基因功能体内测定。此外，比较基因组学方法、原位杂交、定量实时 PCR 和转基因胚胎分析将用于破译 PNS 基因调控网络。这些实验将深入了解海鞘幼虫 PNS 和脊椎动物颅板之间的功能和基因调控相似性。该项目将为 PI 作为教师学者的发展做出贡献。它包含针对本科生、研究生、研究生和小学生和教师的教育计划。拟议的研究将主要由研究生和本科生进行。学生的研究将发表在科学期刊上，并鼓励学生在科学会议上展示他们的发现。一系列为期一年的本科生研究机会，包括暑期项目，将为 4 至 6 名学生提供独立项目和专注于发育生物学和实验技术的期刊俱乐部。新的实验方法将被纳入伍兹霍尔胚胎学课程的高级研究生和博士后研究员关于海鞘发育的密集实验室/讲座部分。最后，将为小学生创建一个互动网站，让他们体验生物研究。该网站将把实验室带入课堂，让年轻学生接触到科学研究中的创造力和兴奋感。这一创新计划将作为一个模型，鼓励其他实验室与小学教室合作，为儿童提供更好的科学教育。