ABNORMALITIES OF NEURAL MIGRATION IN OPTIC TECTUM

视顶盖神经迁移异常

• 批准号: 2259416
• 负责人: STEVEN M LEBER
• 金额: $ 9.07万
• 依托单位: UNIVERSITY OF MICHIGAN AT ANN ARBOR
• 依托单位国家: 美国
• 财政年份: 1991
• 资助国家: 美国
• 起止时间: 1991-08-01 至 1996-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2259416
• 关键词: autoradiography; cell migration; chick embryo; congenital nervous system disorder; electron microscopy; embryogenesis; epilepsy; ethanol; hypoxia; mental retardation; methylmercury; neuroanatomy; neurogenesis; radiobiology; superior colliculus; teratogens; transposon /insertion element

Abnormal lamination of the cerebral cortex is presumed to result from an interference with neuronal migration during development. Despite recent gains in our understanding of normal development, analysis of the pathogenesis of migrational abnormalities has been limited by the inaccessibility of mammalian embryos and by our inability to directly visualize the abnormal migratory patterns. Recently, however, recombinant retroviruses have been developed that allow neural progenitors to be labeled at any stage of embryogenesis. The progeny of single infected cells can be visualized by histochemical staining and their routes of migration discerned from their arrangement as they leave their birthplace. Retroviral studies of normal migration within the chick optic tectum have allowed detection of even small numbers of atypically migrating cells. The tectum is a tissue that shares many structural, functional, and morphogenetic features with the mammalian cortex, yet is more accessible to injection of virus and to experimental manipulation during early development. It therefore has the potential to serve as an excellent model system in which to study the pathogenesis of migrational abnormalities. The immediate goals are to determine whether lamination and migration in the chick optic tectum are disrupted by hypoxia, radiation, infarction, toxins, and surgical manipulation, and to determine whether the migrational changes account for the induced pathology. Migratory pathways will be assessed with recombinant retroviruses, and routine histological stains, cell type-specific antibodies, electron microscopy and axonal tracing methods will be used to detect pathology. A combination of iodo- and bromodeoxyuridine labeling will be employed to determine the relationship between a cell's birthdate and position. A novel retroviral marker and Dil will be used to learn if malpositioned neurons have abnormal axonal projections. The major question to be answered is whether discrete types of migrational abnormalities cause specific classes of lamination defects. The long term goal is to establish a system not only in which to screen potential teratogens for their effects on the neuronal migration but also in which the mechanisms of action of these agents may be determined.

假定脑皮质的异常层压是由 发育过程中对神经元迁移的干扰。 尽管最近 我们对正常发展的理解，分析 移民异常的发病机理已受到限制 哺乳动物胚胎的难以及性，并且由于我们无法直接 可视化异常的迁移模式。 但是，最近， 已经开发了重组逆转录病毒，允许神经 祖细胞在任何胚胎发生的任何阶段被标记。 后代 单个感染细胞可以通过组织化学染色和 他们离开时，他们的迁移路线与安排有所不同 他们的出生地。 逆转录病毒研究在 雏鸡视神经凹形已允许检测到少量 非典型迁移细胞。 底漆是一个共享许多的组织 哺乳动物的结构，功能和形态发生特征 皮质，但更容易被病毒注射和实验 早期发展过程中的操纵。 因此，它具有潜力 作为一个出色的模型系统，可以在其中研究发病机理 移民异常。 直接的目标是确定是否在 雏鸡视神经膜受到缺氧，辐射，梗塞的破坏， 毒素和手术操作，并确定是否是否 移民变化解释了诱发的病理。 迁移 途径将通过重组逆转录病毒和常规进行评估 组织学染色，细胞类型特异性抗体，电子显微镜 和轴突跟踪方法将用于检测病理。 一个 碘和溴脱氧尿苷标签的组合将用于 确定细胞的生日和位置之间的关系。 一个 新颖的逆转录病毒标记和DIL将用于学习是否错误 神经元具有异常的轴突投射。 主要问题 回答是离散类型的移民异常是否导致 特定类别的层压缺陷。 长期目标是 建立一个系统，不仅在该系统中筛选潜在的畸胎体 它们对神经元迁移的影响，也对机制的作用 可以确定这些药物的作用。