MECHANISMS OF GNRH NEURON MIGRATION DURING DEVELOPMENT

促性腺激素释放激素（GnRH）的分泌对于 调节垂体-性腺轴，确保生殖 几乎所有脊椎动物的能力。促性腺激素释放激素神经元从 嗅板穿过筛板和嗅球， 胚胎期和出生后早期前脑和下丘脑 发展大多数GnRH神经元通过以下途径沿着VNN迁移： 鼻腔。GnRH神经元然后离开主要的VNN，并遵循 一小群轴突直接进入大脑我们最近 将迁移轨迹确定为犁鼻神经的一个子集。 初步研究表明，3个事件在调节中起作用 GnRH迁移：i）GnRH神经元与配体特异性相互作用 在迁移途径上;和ii）一组共迁移的GABA能 神经元调节GnRH神经元的迁移，和iii）选择性 轴突分支和尾侧VNN的引导建立了化学上的 GnRH神经元的独特轨迹。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 与酶、肽、配体、蛋白质和抗体在体外 切片培养的鼻子和前脑，并在体内将定义 调节GnRH细胞沿已知途径运动的因子 迁移我们将开发一种GnRH神经元的体内标记物， 使用含有人GnRH启动子的转基因的转基因小鼠 与绿色荧光蛋白cDNA融合。绿色荧光蛋白 含有GFP的转基因GnRH细胞在暴露于395- 470nm的光，因此在活体中可在显微镜下识别 组织. GFP转基因小鼠，与切片培养物结合， 使我们能够测试GnRH神经元使用尾侧支的假设， VNN作为迁移到前脑的向导。发育 嗅觉系统和前脑的关系在临床上是 显著X连锁卡尔曼综合征是由一个缺陷， 嗅觉系统的发展。这种综合征的特点是 主要是由于嗅觉障碍、嗅觉丧失和发育异常 低促性腺激素性腺功能减退症还已经 与许多其他神经系统问题有关，包括精神疾病， 迟钝这些研究的结果将有助于我们了解 神经系统的发展。

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.