Meiotic spindle pole formation in Drosophila females

描述（由申请人提供）：在第一次减数分裂中，由交叉连接的同源染色体与纺锤体微管相互作用并分离到相反的两极。这个过程中的缺陷会导致受精卵的非整倍性，并对发育产生严重后果，经常导致发育中的胚胎死亡。在人类中，非整倍体是女性自然流产和不孕的主要原因。如果非整倍体存活下来，它们会表现为唐氏综合症、Tumer综合症或Klinefelter综合症等疾病。在包括人类和苍蝇在内的许多生物中，雌性减数分裂纺锤体在两极缺乏中心粒和经典的微管组织中心。中心体及其组成蛋白通常被认为组织双极纺锤体，因此，在雌性减数分裂中，纺锤体极的组织必须通过一种新的机制发生。通过利用强大的遗传和细胞学技术，我们的长期目标是阐明无丝胞体减数分裂纺锤体形成的机制以及它们如何分离染色体。我们发现，在果蝇雌性减数分裂过程中，双极纺锤体的形成和同源分离都需要subto（亚）基因。亚编码一种类似运动蛋白的运动蛋白，在早期胚胎发生和雄性减数分裂中是必需的，这一发现刺激了一些新的实验。本研究的目的是确定SUB在纺锤体形成中的作用，并了解减数分裂纺锤体如何形成和在没有中心体的情况下分离染色体的功能。遗传学、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三个关键领域来研究纺锤体生物学：1)确定亚蛋白在减数分裂纺锤体中的亚细胞定位，并表征sub如何与微管相互作用；2)确定其他蛋白质与sub相互作用；3)通过实时分析野生型和突变体的减数分裂和有丝分裂，使用实时成像技术研究纺锤体极形成的机制。这些研究结果将为减数分裂和有丝分裂过程中纺锤体形成和同源分离的机制提供见解。

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.