NERVOUS TERMINALIS RELAY OF CHEMICAL SIGNALS

这是一个香农奖，为研究项目提供部分支持 不属于指定研究所的资助范围，但在 卓越的边缘。 香农奖旨在提供支持 测试该方法的可行性;开发进一步的测试和改进 研究技术;对现有数据集进行二次分析; 或进行离散的项目，可以证明PI的研究 能力或增加已经有价值的 应用程序. 以下摘要摘自原始文件 由主要研究者提交。 这项研究的长期目标是表征和 研究终神经（终神经）的作用， 哺乳动物，作为一种媒介，在中继的化学信号，从 外部环境对大脑神经内分泌细胞的影响， 确定它是单独作用还是与嗅觉、犁鼻 和/或三叉神经。 最近发现促黄体激素- 释放激素（LHRH）神经元（沿着与神经节细胞的 终末神经）起源于内侧嗅窝的上皮 并沿着末端神经的轴突沿着迁移到大脑， 调查领域，包括 嗅觉、辅助嗅觉和LHRH神经内分泌系统。 本次调查的具体目标是：一。检验这一假设 所有LHRH神经元都起源于内侧嗅基板， 沿着终末神经的分支沿着迁移到前脑。 手术切除嗅板或前脑靶组织 培养的完整小鼠胚胎或脑和鼻区域的外植体 将被用来测试基板起源的LHRH神经元。 二.测试 假设LHRH细胞迁移发生在沿着轴突的 它依赖于神经末梢内的化学或分子信号， 迁移路线。 II A. 1)迁移路线的化学组成 将用细胞粘附分子的抗体和/或探针进行检查 （包括L1、钙粘蛋白、整合蛋白、接触蛋白）。 神经胶质（S100）或 神经元（NSE）标记物将被用来检查分布 沿着LHRH细胞从鼻的迁移路线的神经元和/或神经胶质 进入前脑II A. 2)调查发现的组件功能 通过引入抗体或拮抗剂， 这些组件来破坏迁移。II B. 1)调查的作用 类维生素A信号在中膜细胞诱导和分化中的作用 嗅板及其衍生物，包括终末神经和 LHRH神经元的起源和迁移 视黄酸受体RAR-、RAR-β和RAR-β的探针或抗体， RAR结合LHRH免疫细胞化学定位。 II B.（二） 通过注射抗体来研究这些受体的功能 或反义寡核苷酸的特异性视黄酸受体， 体内或培养的完整小鼠胚胎或脑和鼻的外植体中 组织. 三.研究人类终末神经的发育， 检验LHRH神经元的起源和迁移是 在整个脊椎动物进化过程中都是保守的。 发展研究 终末神经和人类胚胎中LHRH神经元的迁移46 天和更老的将提供一个明确的描述这一现象 在人类身上。 本研究的重点是LHRH神经元的过程 穿过前脑

This is a Shannon Award providing partial support for research projects that fall short of the assigned institute's funding range but are in the margin of excellence. The Shannon award is intended to provide support to test the feasibility of the approach; develop further tests and refine research techniques; perform secondary analysis of available data sets; or conduct discrete projects that can demonstrate the PI's research capabilities or lend additional weight to an already meritorious application. The abstract below is taken from the original document submitted by the principal investigator. The long-term objective of this research is to characterize and investigate the role of the nervus terminalis (terminal nerve), in mammals, as an intermediary in the relay of chemical signals from the external environment to the neuroendocrine cells of the brain and to determine if it acts alone or in concert with the olfactory, vomeronasal and/or trigeminal nerves. The recent discovery that luteinizing hormone- releasing hormone (LHRH) neurons (along with ganglion cells of the terminal nerve) originate in the epithelium of the medial olfactory pit and migrate into the brain along axons of the terminal nerve, opens new areas of investigation including a possible connection between the olfactory, accessory olfactory and the LHRH neuroendocrine systems. The specific objectives of this investigation are: I. Test the hypothesis that all LHRH neurons originate in the medial olfactory placode and migrate into the forebrain along branches of the terminal nerve. Surgical removal of the olfactory placode or target tissue forebrain in whole mouse embryos in culture or explants of brain and nasal regions will be used to test the placodal origin of LHRH neurons. II. Test the hypothesis that LHRH cell migration takes place along axons of the terminal nerve and is dependent on chemical or molecular signals within the migration route. II A. 1) The chemical makeup of the migration route will be examined with antibodies and/or probes to cell adhesion molecules (including L1, Cadherins, Integrins, Contactin). Glial (S100) or neuronal (NSE) markers will be used to examine the distribution of neurons and/or glia along the migration route of LHRH cells from the nose into the forebrain. II A. 2) Investigate the function of components found on the migration route by introduction of antibodies or antagonists to these components to disrupt migration. II B. 1) Investigate the role of retinoid signalling in induction and differentiation of the medial olfactory placode and derivatives, including the terminal nerve and the origin and migration of LHRH neurons using in situ hybridization with probes or antibodies for the retinoic acid receptors RAR-, RAR-beta, and RAR-combined with immunocytochemical localization of LHRH. II B. 2) Investigate the function of these receptors by injections of antibodies or anti-sense oligonucleotides to specific retinoic acid receptors in vivo or in cultured whole mouse embryos or explants of brain and nasal tissue. III. Examine the development of the terminal nerve in humans and test the hypothesis that the origin and migration of LHRH neurons is conserved throughout vertebrate evolution. Study of the development of the terminal nerve and the migration of LHRH neurons in human embryos 46 days and older will provide a definitive description of this phenomenon in humans. The focus of this study is on the course of LHRH neurons through the forebrain.