DEVELOPMENT AND MIGRATION OF LHRH NEURONS

合成黄体生成素释放激素(LHRH)的神经元 在控制脊椎动物繁殖方面起着举足轻重的作用。一种模式 LHRH表达提示LHRH神经元从 在哺乳动物中已经发现了嗅觉上皮到大脑的存在。这代表了 少数几个神经元从外周向外周迁移的例子之一 中枢神经系统。促肾上腺皮质激素释放激素神经元未能迁移到 中枢神经系统与一种人类疾病--卡尔曼综合征有关。我们的 对雏鸡的初步研究也表明LHRH神经元可能会迁移 从嗅觉上皮到大脑。因为小鸡的胚胎 比哺乳动物胚胎更容易进行扰动实验， 雏鸟提供了独特的机会来研究起源、迁徙 和LHRH神经元的功能。确认所有脑部LHRH 神经元起源于嗅觉上皮，我们将消融 嗅觉上皮在发育的早期，我们假设它会 产下一只没有LHRH神经元的雏鸡。此外，我们还将 将鹌鹑嗅觉上皮移植到消融鸡胚中 将允许标记所有来源的细胞的嗅觉上皮 来自嗅觉上皮。在电子显微镜研究中，我们将 观察LHRH神经元与其底物之间的相互作用。 他们穿越三个不同的地形：嗅觉上皮，嗅觉 神经和大脑。正如许多作者提出的那样，胶质细胞 嗅神经的套鞘起源于嗅觉上皮， 我们将用特定的抗体(1E8)标记这些细胞，并 确定神经胶质发育与发育的关系 LHRH神经元。我们发现高水平的N-CAM表达 在雏鸟发育中的嗅觉系统中被发现。我们会 用双标记免疫细胞化学方法确定粘附性 和/或细胞外基质分子在 雏鸡发育的空间和时间受限时期 与LHRH迁移途径相对应。最后，我们将开发一个In 组织块体外培养系统的最终目标是直接 检测特殊的黏附或细胞外基质分子 参与了LHRH神经元的迁移。

Neurons which synthesize luteinizing hormone-releasing hormone (LHRH) play a pivotal role in the control of vertebrate reproduction. A pattern of LHRH expression suggestive of migration of LHRH neurons from olfactory epithelium to brain has been found in mammals. This represents one of the few examples of neuronal migration from the periphery to the central nervous system. The failure of LHRH neurons to migrate into the CNS has been linked to a human disease, Kallman's syndrome. Our preliminary studies in chicks also suggest that LHRH neurons may migrate from the olfactory epithelium to the brain. Since the embryos of chicks are more accessible for perturbation experiments than mammalian embryos, the chick provides unique opportunities to study the origin, migration and function of LHRH neurons. To confirm that all encephalic LHRH neurons originate within the olfactory epithelium, we will ablate the olfactory epithelium early in development which we hypothesize will produce a chick without any LHRH neurons. In addition, we will transplant quail olfactory epithelium to chick embryos with ablated olfactory epitheliums which will permit labeling of all cells derived from the olfactory epithelium. In electron microscopic studies, we will examine interactions between LHRH neurons and their substratum in the three different terrains they traverse: olfactory epithelium, olfactory nerve and brain. As a number of authors have suggested that the glia ensheathing the olfactory nerve originate in the olfactory epithelium, we will label these cells with specific antibodies (1E8) and will determine the relationship between glial development and the development of the LHRH neurons. We have found that high levels of N-CAM expression are found within the developing olfactory system in the chick. We will use double-label immunocytochemistry to determine whether adhesion and/or extracellular matrix molecules are expressed at high levels at spatially and temporally restricted periods of chick development that correspond to the LHRH migration pathway. Finally, we will develop an in vitro explant slice culture system with the ultimate goal of directly testing whether particular adhesion or extracellular matrix molecules are involved in LHRH neuron migration.