DEVELOPMENT AND MIGRATION OF LHRH NEURONS

合成促黄体生成激素释放激素（LHRH）的神经元 在控制脊椎动物的繁殖方面起着关键作用。的图案 LHRH表达的变化提示LHRH神经元从 在哺乳动物中已经发现了嗅觉上皮到大脑。这代表 这是少数几个神经元从外周迁移到 中枢神经系统LHRH神经元不能迁移到 CNS与人类疾病Kallman综合征有关。我们 对小鸡的初步研究也表明，LHRH神经元可能迁移， 从嗅觉上皮细胞到大脑自从小鸡的胚胎 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 和LHRH神经元的功能。为了证实所有脑内LHRH 神经元起源于嗅上皮，我们将切除 嗅觉上皮在发育早期，我们假设 产生一只没有LHRH神经元的小鸡。此外，我们将 鹌鹑嗅上皮切除后移植到鸡胚上 嗅上皮，其将允许标记所有来源于 从嗅上皮细胞中分离出来在电子显微镜研究中，我们将 研究LHRH神经元和它们的基底之间的相互作用， 它们穿过三种不同的地形：嗅上皮， 神经和大脑。正如许多作者所指出的， 嗅神经鞘起源于嗅上皮， 我们将用特异性抗体（1 E8）标记这些细胞， 确定胶质细胞发育与神经元发育之间的关系， LHRH神经元。我们发现高水平的N-CAM表达 是在小鸡的嗅觉系统中发现的。我们将 用免疫细胞化学双标记法检测粘附细胞 和/或细胞外基质分子以高水平表达， 在空间和时间上受到限制的小鸡发育时期， 与LHRH迁移途径相对应。最后，我们将开发一个 离体外植体培养系统的最终目的是直接 测试是否有特定的粘附或细胞外基质分子 参与LHRH神经元迁移。

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.