GnRH Multiplicity: Molecular and Developmental Studies

GnRH 多样性：分子和发育研究

• 批准号: 0548620
• 负责人: Yonathan Zohar
• 金额: $ 29万
• 依托单位: University of Maryland Biotechnology Institute
• 依托单位国家: 美国
• 项目类别: Continuing Grant
• 财政年份: 2006
• 资助国家: 美国
• 起止时间: 2006-02-01 至 2010-01-31
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=0548620&HistoricalAwards=false
• 关键词: GnRH; Multiplicity; Molecular; Developmental; Studies

The gonadotropin-releasing hormone (GnRH) neuropeptides function as keyhormones in the control of reproduction in all vertebrates, and it is now firmly established thateach species expresses more than one form of GnRH. Several lines of evidence indicate thateach form has distinct, and possibly multiple, functions within an organism, although anunderstanding of what these functions are and how they are coordinated is far from complete.An emerging area of investigation in the study of GnRH functionality concerns theirpresence during embryonic and juvenile development. These studies will examine the expression patterns and functional aspects of GnRH during development in the zebrafish, a modelorganism in which two forms of GnRH have been characterized. Building on preliminary data that demonstrates different patterns of expression for each form of GnRH during embryonic and early larval development in zebrafish, these studies will achieve two general objectives. First, using techniques to localize and quantitate gene expression, the ontogeny and detailed expression patterns of GnRH-I and GnRH-II within the zebrafish brain during embryonic and larval life stages will be determined, and correlated with several parameters of brain, pituitary and gonadal development. Second, functional roles of each form of GnRH in terms of establishment of the reproductive axis will be examined by determining the effects of disrupted GnRH-I and GnRH-II expression on development of the brain, pituitary and gonad in embryonic and larval zebrafish. This objective will be achieved by 1) temporarily knocking down GnRH expression during development by injecting antisense oligonucleotides into zebrafish embryos and 2) creating transgenic zebrafish that constantly under-express the GnRH peptides in a tissue-specific manner. To date, there has been no in-depth analysis of the expression of GnRHsduring embryonic or juvenile development in vertebrates. These studies will alleviateshortcomings in the current state of knowledge in the field of GnRH research, and provide abetter understanding of the functional significance of GnRH multiplicity. These studies will alsoestablish the necessary tools and baseline data for further studies of GnRH functionality in a model system that is universally recognized as ideal for studying development and regulation of gene expression patterns, which is currently lacking in the field. The use of transgenic technologies will enable the modeling of physiological states in which there is an induced or genetically inherited disruption of proper GnRH expression. Thus, aside from the basic knowledge to be gained, these studies will have broader impacts for the understanding of reproductive development in vertebrates generally, and will potentially impact the manipulation of reproduction in farmed and captive animals. These studies will provide state-of-the-art training for postdoctoral, graduate and undergraduate researchers. In addition, because of the chosen model system, the experimental tools derived from these studies will be easily adapted to develop teaching modules that will give hands-on experience in neurobiology, embryonic development and molecular analysis of gene expression to high school and undergraduate students and secondary school teachers.

促性腺激素释放激素（GNRH）神经肽在所有脊椎动物中的繁殖控制中起着钥匙激素的作用，现在牢固地确定了Each物种表达多种形式GNRH。几条证据表明，尽管对这些功能是什么以及它们的协调方式的歧视，但在生物体中具有不同的功能，甚至可能是多重的功能。胚胎和少年发展。这些研究将研究斑马鱼发育过程中GnRH的表达模式和功能方面，斑马鱼是一种模型生物，其中已经表征了两种形式的GnRH。这些研究将在Zebrafish的胚胎和早期幼虫发育过程中显示出不同形式的GnRH表达模式的基础，这些研究将实现两个一般目标。首先，使用技术来定位和量化基因表达，在胚胎和幼虫生命阶段期间斑马鱼大脑内GnRH-I和GnRH-II的个体发育和详细的表达模式将得到确定，并与大脑，垂体和GONADAL和GONADAL的几个参数相关发展。其次，将通过确定破坏的GnRH-I和GnRH-II表达对大脑，垂体和性腺在胚胎和幼虫Zebrafish中的发育中的影响来检查每种形式的GNRH的功能作用。该目标将通过1）通过将反义寡核苷酸注入斑马鱼胚胎和2）创建转基因斑马鱼在发育过程中暂时敲击GNRH表达，从而在组织特异性的方式中不断地表达GNRH肽。迄今为止，尚无对脊椎动物中胚胎或青少年发育的gnRHSDS表达的深入分析。这些研究将减轻GNRH研究领域的当前知识状态，并提供对GnRH多重性功能意义的教be的理解。这些研究还将在模型系统中进一步研究GNRH功能的必要工具和基线数据，该模型被普遍认为是研究基因表达模式的开发和调节，该模式目前缺乏该领域。转基因技术的使用将实现生理状态的建模，在这种状态下，存在诱导或遗传遗传的适当GNRH表达的破坏。因此，除了要获得的基本知识外，这些研究将对理解脊椎动物的生殖发育产生更大的影响，并有可能影响养殖和圈养动物繁殖的操纵。这些研究将为博士后，研究生和本科研究人员提供最先进的培训。此外，由于选择了模型系统，因此从这些研究中得出的实验工具将很容易适应开发教学模块，这些教学模块将在神经生物学，胚胎发展，胚胎发展和对基因表达的分子分析中对高中以及本科生以及本科生以及本科生以及本科生的分子分析进行调整。中学老师。