Eye Development: Molecular Genetics of Nuclear Migration

眼睛发育：核迁移的分子遗传学

• 批准号: 6622807
• 负责人: JANICE A. FISCHER
• 金额: $ 22.5万
• 依托单位: UNIVERSITY OF TEXAS AT AUSTIN
• 依托单位国家: 美国
• 财政年份: 2002
• 资助国家: 美国
• 起止时间: 2002-04-01 至 2006-02-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6622807
• 关键词: Drosophilidae; antibody; arthropod genetics; brain disorders; cell nucleus; compound eye; confocal scanning microscopy; developmental genetics; developmental neurobiology; eye; gene expression; genetic screening; genetically modified animals; immunologic techniques; intracellular transport; molecular cloning; molecular genetics; neurogenetics; organelles; protein binding; protein localization; protein protein interaction; protein structure function; tissue /cell culture; transmission electron microscopy; visual photoreceptor

It is proposed to characterize the genes and gene products required for developmentally regulated nuclear migrations in photoreceptors of the Drosophila compound eye. Nuclear migration is of universal importance in animal development. For example, the human brain disorder, Lissencephaly, is the result of neural nuclei failing to migrate appropriately during brain development. Moreover, the Drosophila homolog of the human Lissencephaly gene, Lis1, is essential for photoreceptor nuclear migrations in Drosophila. Thus, the genes and proteins that will be identified and studied are directly relevant to human development and disease. Nuclear migration is an important phenomenon to understand also because of its relationship to other critical processes in eukaryotic development. Many of the proteins important for nuclear migration are also required for the transport of other organelles, establishment of cell polarity, and morphogen localization within the cell. There are four specific goals of the research proposed. The first is a structure/function analysis of Klarsicht, a protein required for photoreceptor nuclear migration. Transgenic flies expressing partial Klarsicht proteins will be used to correlate subcellular localization, protein binding, and organelle migration functions with protein structure. The second aim is to clone and characterize the egk1 gene, which like klarsicht, is essential for photoreceptor nuclear migration. Thirdly, antibodies to a variety of proteins will be used to order four nuclear migration genes, klarsicht, egk1, BicD and DLis-1, into a pathway. In addition, the possibility of physical interactions between Klarsicht and Egk1 proteins will be explored using in vivo and in vitro assays. Finally, a variety of different genetic screening approaches will be used to identify additional genes in the klarsicht/egk1 pathway.

提议表征果蝇复合眼感光体中发育调节的核迁移所需的基因和基因产物。核迁移在动物发展中至关重要。 例如，人脑疾病（Lissencephaly）是神经核在脑发育过程中无法适当迁移的结果。 此外，人类lissencephaly基因lis1的果蝇同源物对于果蝇的感光核迁移至关重要。 因此，将被鉴定和研究的基因和蛋白质与人类发育和疾病直接相关。核迁移是一个重要的现象，因为它与真核发展中其他关键过程的关系也是如此。 对于其他细胞器的运输，细胞极性的建立以及细胞内的形态学定位也需要许多对核迁移重要的蛋白质。该研究提出了四个具体目标。 首先是Klarsicht的结构/功能分析，Klarsicht是光感受器核迁移所需的蛋白质。 表达部分klarsicht蛋白的转基因蝇将用于将亚细胞定位，蛋白质结合和细胞器迁移功能与蛋白质结构相关联。 第二个目的是克隆并表征像克拉尔西特一样的EGK1基因，对于感光器核迁移至关重要。 第三，各种蛋白质的抗体将用于订购四个核迁移基因Klarsicht，Egk1，BICD和DLIS-1，以进入途径。 此外，将使用体内和体外测定法探索Klarsicht和EGK1蛋白之间物理相互作用的可能性。 最后，将使用多种不同的遗传筛查方法来识别Klarsicht/EGK1途径中的其他基因。