ONTOGENY OF THE LUTINIZING HORMONE RELEASING HORMONE SYSTEM

黄化激素释放激素系统的个体发育

• 批准号: 3860909
• 负责人: S WRAY
• 金额: --
• 依托单位: NATIONAL INSTITUTE OF NEUROLOGICAL DISORDERS AND STROKE
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/3860909
• 关键词: cell migration; central nervous system; developmental neurobiology; ectoderm; embryo /fetus tissue /cell culture; embryology; extracellular matrix; fibronectins; genetically modified animals; histochemistry /cytochemistry; human genetic material tag; human tissue; immunocytochemistry; in situ hybridization; laboratory mouse; neural cell adhesion molecules; neurons; reproductive system disorder; simian virus 40; tumor antigens

LHRH neurons are derived from the olfactory placode and migrate into the brain. The factors which dictate cell-specific LHRH gene expression and the migratory mechanism(s) used by the LHRH neurons during their movement into the CNS are currently unknown. Using immunocytochemistry and in situ hybridization histochemistry, we are examining the prenatal development of the LHRH system. We have found that an extracellular matrix molecule fibronectin, borders but does not enter the migratory pathway, whereas N-CAM, a cell adhesion molecule, is abundantly present within it. Hence, we propose the hypothesis that LHRH cells migrate to the brain using a positive (binding) interaction with N-CAM, and a negative interaction with fibronectin, and are testing this hypothesis using organotypic cultures of embryonic tissues. Transgenic mice in which the human LHRH promoter was fused to the SV 40 T-antigen have been generated, and these animals show abnormal reproductive function. No LHRH cells were found within the CNS but tumor masses in the nasal region were detected. From these tumors, a stable LHRH-positive cell line is being established.

LHRH神经元来源于嗅觉胎盘，并迁移到 大脑。决定细胞特异性LHRH基因表达的因素和 促性腺激素释放激素神经元在运动过程中的迁移机制(S) 进入中枢神经系统的基因目前尚不清楚。使用免疫细胞化学和In 原位杂交组织化学，我们正在检查产前 开发LHRH系统。我们发现了一种细胞外的 基质分子纤维连接蛋白，边界但不进入迁移性 途径，而N-CAM是一种细胞黏附分子，大量存在 在它里面。因此，我们提出了LHRH细胞迁移到 大脑使用与N-CAM的正(结合)相互作用，以及 与纤维连接蛋白的负相互作用，并正在检验这一假说 使用胚胎组织的器官类型培养。中国转基因小鼠 人LHRH启动子与SV 40 T抗原的融合 这些动物表现出异常的生殖功能。不是 中枢神经系统内可见LHRH细胞，鼻区可见肿块 都被检测到。从这些肿瘤中，稳定的LHRH阳性细胞系是 正在建立中。