MECHANISMS OF GNRH NEURON MIGRATION DURING DEVELOPMENT

发育过程中 GNRH 神经元迁移的机制

• 批准号: 2025714
• 负责人: GERALD A SCHWARTING
• 金额: $ 26.65万
• 依托单位: EUNICE KENNEDY SHRIVER CTR MTL RETARDATN
• 依托单位国家: 美国
• 财政年份: 1997
• 资助国家: 美国
• 起止时间: 1997-01-01 至 2000-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2025714
• 关键词: axon; cell adhesion molecules; cell migration; complementary DNA; developmental neurobiology; gamma aminobutyrate; genetic promoter element; genetically modified animals; gonadotropin releasing factor; green fluorescent proteins; laboratory mouse; neuronal guidance; neurons; olfactory nerve; prosencephalon; recombinant proteins; tissue /cell culture; video microscopy; vomeronasal systems

The secretion of gonadotropin-releasing hormone (GnRH) is critical for regulating the pituitary-gonadal axis and ensuring reproductive competence for virtually all vertebrates. GnRH neurons migrate from the olfactory placode across the cribriform plate and olfactory bulb, into the forebrain and hypothalamus during embryonic and early postnatal development. The majority of GnRH neurons migrate along the VNN through the nasal cavity. GnRH neurons then leave the main VNN and follow a small group of axons directly into the brain. We have recently identified the migratory track as a subset of the vomeronasal nerve. Preliminary studies suggest that 3 events play a role in the regulation of GnRH migration: i) GnRH neurons interact specifically with ligands on the migratory pathway; and ii) a group of co-migrating GABAergic neurons modulates the migration of GnRH neurons , and iii) selective axon branching and guidance of the caudal VNN establishes a chemically unique track for GnRH neurons. Our objective is to determine the molecular basis of directed GnRH neuron migration. Perturbation studies with enzymes, peptides, ligands, proteins and antibodies using in vitro slice cultures of the nose and forebrain, and in vivo will define the factors that regulate movement along the known route of GnRH cell migration. We will develop an in vivo marker for GnRH neurons in transgenic mice using transgenes containing the human GnRH promoter fused to green fluorescent protein cDNA. Green fluorescent protein (GFP)containing transgenic GnRH cells fluoresce when exposed to 395- 470nm light, and are thus identifiable microscopically in living tissue. GFP transgenic mice, in conjunction with slice cultures will allow us to test hypotheses that GnRH neurons use caudal branches of the VNN as guides for migration into the forebrain. The developmental relationship of the olfactory system and the forebrain is clinically significant. X-linked Kallmann syndrome is caused by a defect in the development of the olfactory system. This syndrome is characterized primarily by the inability to smell, anosmia; and abnormal development of the gonads, hypogonadotrophic hypogonadism. it has also been associated with numerous other neurological problems, including mental retardation. Results from these studies will aid our understanding of the development of the nervous system.

促性腺激素释放激素（GNRH）的分泌对于 调节垂体轴轴并确保生殖 几乎所有脊椎动物的能力。 GnRH神经元从 嗅觉片段穿过丝布状板和嗅球，进入 胚胎和早期产后的前脑和下丘脑 发展。大多数GnRH神经元沿VNN迁移 鼻腔。然后，GnRH神经元离开主vnn，然后跟随 一小组轴突直接进入大脑。我们最近有 将迁移轨迹确定为呕吐神经的子集。 初步研究表明，3个事件在法规中起作用 GnRH迁移：i）GnRH神经元与配体特别相互作用 在迁徙途径上； ii）一组共同迁移的GABA能 神经元调节GNRH神经元的迁移，iii）选择性 轴突分支和尾vnn的指导建立了化学上的 GNRH神经元的独特曲目。我们的目标是确定 定向GNRH神经元迁移的分子基础。扰动研究 使用酶，肽，配体，蛋白质和抗体使用体外 鼻子和前脑的切片培养物，体内将定义 调节沿已知gnRH细胞途径运动的因素 迁移。我们将为GnRH神经元中的体内标记 使用含有人类GnRH启动子的转基因的转基因小鼠 融合到绿色荧光蛋白cDNA中。绿色荧光蛋白 （GFP）含有转基因GNRH细胞荧光，暴露于395-- 470nm的光，因此在生命中可识别 组织。 GFP转基因小鼠与切片培养 允许我们检验GNRH神经元使用尾分支的假设 VNN作为向前脑迁移的指南。发展 嗅觉系统和前脑的关系在临床上是 重要的。 X连锁Kallmann综合征是由缺陷引起的 嗅觉系统的开发。该综合征的特征是 主要是由于无法闻起来的厌食症；和异常发展 在性腺，性腺自治性性低肿瘤。也一直 与许多其他神经系统问题有关，包括心理 迟钝。这些研究的结果将有助于我们理解 神经系统的发展。