Meiotic spindle pole formation in Drosophila females

雌性果蝇减数分裂纺锤体极的形成

• 批准号: 6562800
• 负责人: KIM S MCKIM
• 金额: $ 22.49万
• 依托单位: RUTGERS, THE STATE UNIV OF N.J.
• 依托单位国家: 美国
• 财政年份: 2003
• 资助国家: 美国
• 起止时间: 2003-01-01 至 2006-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6562800
• 关键词: Drosophilidae; aneuploidy; cell cycle; centrosome; chromosome movement; cytogenetics; egg /ovum; embryogenesis; female; female reproductive system; fluorescent in situ hybridization; gene mutation; green fluorescent proteins; immunocytochemistry; kinesin; meiosis; microtubules; mitotic spindle apparatus; mutant; protein localization; protein protein interaction; protein structure function; spindle pole body

DESCRIPTION (provided by applicant): During the first meiotic division, homologous chromosomes linked by chiasmata interact with the spindle microtubules and segregate to opposite poles. Defects in this process lead to aneuploidy in the fertilized egg and have serious consequences on development, often resulting in death of the developing embryo. In humans, aneuploidy is a leading cause of spontaneous abortions and infertility in women. If aneuploids do survive, they manifest with diseases such as Down's, Tumer's or Klinefelter's syndrome. In many organisms, including humans and flies, the female meiotic spindle lacks centrioles and the classical microtubule-organizing center at the poles. The centrosomes and their constituent proteins are usually thought to organize bipolar spindles and therefore, in female meiosis, spindle pole organization must occur by a novel mechanism. By utilizing the powerful genetic and cytological techniques available in studies involving Drosophila melanogaster females, it is our long-term goal to elucidate the mechanism by which acentrosomal meiotic spindles form and how they function to segregate the chromosomes. We have found that the subito (sub) gene is required for bipolar spindle formation and homolog segregation during female meiosis in Drosophila. The findings that sub encodes a kinesin-like motor protein and is required during early embryogenesis and male meiosis has stimulated several new experiments. The aims of this study are to identify the role of SUB in spindle formation and understand how the meiotic spindle forms and functions to segregate chromosomes in the absence of centrosomes. A combination of genetic, immunological and cytological techniques will be used to illuminate the functions of SUB. These studies will investigate three critical areas of spindle biology by: 1) determining the subcellular localization of the sub protein in meiotic spindles and characterize how SUB interacts with the microtubules, 2) determining what other proteins interacts with SUB, and 3) using live imaging techniques to investigate the mechanism of spindle pole formation through a real time analysis of meiosis and mitosis in wild-type and mutants. The results of these studies will provide insights into the mechanisms of spindle formation and homolog segregation during meiosis and mitosis.

描述（由申请人提供）：在第一个减数分裂师期间，Chiasmata连接的同源染色体与纺锤微管相互作用并分离到相反的杆子。在此过程中的缺陷导致受精卵中的非整倍性，并对发育产生严重后果，通常导致发育中的胚胎死亡。在人类中，非整倍性是女性自发堕胎和不孕症的主要原因。如果非整倍体能够生存，它们会表现出诸如Down，Tumer或Klinefelter综合征之类的疾病。在包括人类和苍蝇在内的许多生物中，女性减数分裂纺锤体缺少中心粒和波兰的经典微管组织中心。通常认为中心体及其组成蛋白会组织双极纺锤体，因此，在女性减数分裂中，纺锤体组织必须通过一种新型机制进行。通过利用涉及果蝇果蝇女性的研究中可用的强大遗传和细胞学技术，我们的长期目标是阐明艾剂肉眼减数分裂纺锤体形成且如何脱离染色体的机制。我们发现，果蝇女性减数分裂过程中双极纺锤体形成和同源分离所必需的subito（sub）基因。 SUB编码驱动蛋白样运动蛋白的发现，在早期胚胎发生和男性减数分裂过程中需要刺激了几个新实验。这项研究的目的是确定子在纺锤体形成中的作用，并了解减数分裂纺锤体在没有中心体的情况下如何分离染色体的功能。遗传，免疫学和细胞学技术的结合将用于阐明SUB的功能。这些研究将通过以下方式研究纺锤体生物学的三个关键领域：1）确定减数分裂纺锤体中亚蛋白的亚细胞定位，并表征子蛋白与微管的相互作用，2）2）确定其他蛋白质与Subs subs subs subsing and Mei sissis和Meti sissis和Metiss的旋转机械的机制，确定其他蛋白质与Subs和Subs subs的相互作用。这些研究的结果将提供有关减数分裂和有丝分裂期间纺锤体形成和同源分离机制的见解。