NERVOUS TERMINALIS RELAY OF CHEMICAL SIGNALS

这是一个为研究项目提供部分支持的香农奖 低于指定研究所的资助范围，但在 卓越边际。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； 或进行独立的项目，以证明PI的研究 能力或为已经功成名就的 申请。下面的摘要摘自原始文件 由首席调查员提交。 这项研究的长期目标是表征和 研究终神经(终末神经)在 哺乳动物，作为传递化学信号的媒介 外部环境对大脑的神经内分泌细胞和 确定它是单独作用还是与嗅觉、犁鼻共同作用 和/或三叉神经。最近的研究发现促黄体激素- 释放激素(LHRH)神经元(连同 终末神经)起源于内侧嗅窝上皮 并沿着末梢神经的轴突迁移到大脑中，打开了新的 调查的领域包括 嗅觉、副嗅觉和LHRH神经内分泌系统。 本次调查的具体目标是：一、检验假设 所有的LHRH神经元都起源于内侧嗅觉胎盘和 沿着末梢神经的分支迁移到前脑。 前脑嗅觉定位或靶区切除的手术治疗 脑和鼻区培养或外植体中的完整小鼠胚胎 将被用来测试LHRH神经元的胎盘起源。二、测试 假设LHRH细胞沿轴突发生迁移 末端神经，依赖于体内的化学或分子信号 迁徙路线。二.1)迁徙路线的化学成分 将用抗体和/或细胞黏附分子探针进行检查 (包括L1、钙粘附素、整合素、Contactin)。神经胶质(S100)或 神经元(NSE)标志物将被用来检查 LHRH细胞沿鼻部迁移路线上的神经元和/或胶质细胞 进入前脑。二.2)调查所发现的部件的功能 通过引入抗体或拮抗剂的迁移路线 这些组件会中断迁移。二、B.1)调查 视黄醇信号在内侧神经节诱导和分化中的作用 嗅觉定位器及其衍生物，包括末梢神经和 用原位杂交技术研究LHRH神经元的起源和迁移 视黄酸受体RAR-、RAR-β和RAR的探针或抗体 RAR-结合免疫细胞化学定位LHRH。II B.2) 通过注射抗体研究这些受体的功能 或针对特定视黄酸受体的反义寡核苷酸 在体内或在培养的小鼠全胚胎或脑和鼻腔外植体中 组织。检查人类末梢神经的发育和 检验LHRH神经元起源和迁移是 在脊椎动物的整个进化过程中都是保守的。关于中国农业发展的研究 人胚胎末梢神经与LHRH神经元的迁移 天数和年龄更大的人将对这一现象提供明确的描述 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.