Meiotic spindle formation in Drosophila females

雌性果蝇减数分裂纺锤体的形成

基本信息

批准号：
8000111
负责人：
KIM S MCKIM
金额：
$ 8.4万
依托单位：
RUTGERS, THE STATE UNIV OF N.J.
依托单位国家：
美国
项目类别：
财政年份：
2010
资助国家：
美国
起止时间：
2010-02-12 至 2010-12-31
项目状态：
已结题

项目摘要

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, Turner's or Klinefelter's syndrome. In many organisms, including humans and flies, the oocyte meiotic spindle lacks centrioles and the classical microtubule-organizing center at the poles. Since the centrosomes and their constituent proteins usually organize bipolar spindles, spindle pole organization in oocyte meiosis must occur by another mechanism. Drosophila melanogaster oocytes are an excellent system to elucidate the mechanisms of acentrosomal spindle formation. Subito is the Drosophila homolog of human Mitotic Kinesin Like Protein 2 (MKLP2) and is required for bipolar spindle formation during female meiosis. Subito is required for the development of the central spindle at meiotic metaphase and this structure may be critical for formation of a bipolar spindle in the absence of centrosomes. The goals of this study are: i) analyze the structure and function of Subito. This will provide insights into how this protein functions and is regulated. ii) characterize the interactions between Subito and the Passenger proteins or the Ran pathway. This will determine which proteins interact with Subito and what is their function in spindle assembly. iii) determine the timing of bipolar spindle formation and chromosomes orientation. This will test the relative importance of interpolar and kinetochore microtubules and investigate how pairs of homologous chromosomes orient on the acentrosomal spindle. iv) analyze new genes required for meiotic spindle assembly. This will identify new genes required for acentrosomal spindle assembly using a relatively unbiased approach. During the first meiotic division, the chromosome number is reduced in half by separating pairs of homologous chromosomes into the gametes. In humans, errors in meiosis lead to aneuploidy, an abnormal number of chromosomes in a sperm or egg, and is the leading cause of spontaneous abortions, infertility in women and diseases such as Down's, Turner's or Klinefelter's syndrome. The objective of these studies is to understand how these errors occur.

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，它们会出现诸如Down，Turner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，卵母细胞减数分裂纺锤体缺少中心粒和波兰的经典微管组织中心。由于中心体及其成分蛋白通常会组织双极纺锤体，因此必须通过另一种机制发生卵母细胞减数分裂中的纺锤体组织。果蝇果蝇卵母细胞是阐明敏捷纺锤体形成机制的绝佳系统。 Subito是人类有丝分裂驱动蛋白（如蛋白2（MKLP2））的果蝇同源物，在女性减数分裂过程中是双极纺锤体形成所必需的。 Subito对于减数分裂中期的中央主轴的发展是必需的，并且这种结构对于在没有中心体的情况下形成双极纺锤可能至关重要。这项研究的目标是：i）分析Subito的结构和功能。这将提供有关该蛋白质功能和调节方式的见解。 ii）表征Subito与载客蛋白或RAN途径之间的相互作用。这将确定哪些蛋白质与Subito相互作用，以及它们在纺锤体组件中的功能是什么。 iii）确定双极纺锤体形成和染色体方向的时间。这将测试近极和动齿微管的相对重要性，并研究如何在摄像体纺锤体上对同源染色体的正向对成对。 iv）分析减数分裂纺锤体组件所需的新基因。这将使用相对无偏的方法来确定艾面纺锤体组件所需的新基因。在第一个减数分裂部门中，通过将成对的同源染色体分离为配子，将染色体数减少了一半。在人类中，减数分裂的错误导致非整倍性，精子或卵中的染色体数量异常，并且是自发性堕胎，女性和疾病（如Down's，Turner's或Klinefelter综合征）的主要原因。这些研究的目的是了解这些错误是如何发生的。

项目成果

期刊论文数量（10）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

Dual roles of Incenp crucial to the assembly of the acentrosomal metaphase spindle in female meiosis.

DOI：
10.1242/dev.022624
发表时间：
2008-10
期刊：
DEVELOPMENT
影响因子：
4.6
作者：
Colombie, Nathalie;Cullen, C. Fiona;Brittle, Amy L.;Jang, Janet K.;Earnshaw, William C.;Carmena, Mar;Mckim, Kim;Ohkura, Hiroyuki
通讯作者：
Ohkura, Hiroyuki