Homolog bi-orientation and segregation in oocyte acentrosomal meiosis

卵母细胞中心体减数分裂的同源双向和分离

基本信息

批准号：
10797658
负责人：
KIM S MCKIM
金额：
$ 0.93万
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：
2013
资助国家：
美国
起止时间：
2013-09-01 至 2025-08-31
项目状态：
未结题

项目摘要

In the first meiotic division, homologous chromosomes linked by chiasmata attach to microtubules from opposite poles of the spindle (bi-orientation) and then segregate. Errors in chromosome segregation in the oocyte lead to aneuploidy and are the leading cause of miscarriage, infertility and birth defects. In the oocytes of many organisms, including mammals and insects, meiotic spindle assembly occurs in the absence of centrosomes. We use Drosophila melanogaster females as a model to understand the mechanisms that promote accurate chromosome segregation on the acentrosomal spindle of oocytes. We are interested in understanding the mechanisms of bi-orientation and the features of the oocyte spindle that make it susceptible to chromosome segregation errors. From our previous research we have shown that the kinetochore interacts with the microtubules in two ways. First, lateral attachments, where the kinetochores move along the sides of microtubules, establish bi-orientation. Second, end-on attachments, where the kinetochores make a stable attachment to the ends of microtubules, maintain connections to a pole and segregate the homologs. Stabilizing end-on attachments too rapidly leads to errors in chromosome segregation. The lateral interactions important for bi-orientation occur between the kinetochores and central spindle, which are composed of overlapping antiparallel microtubules and may be particularly important for acentrosomal oocytes. Our proposed studies are focused on understanding how the kinetochores and central spindle interact to regulate the transition from lateral to end-on attachments and accurately segregate chromosomes. 1) Investigate the mechanisms of meiotic kinetochore assembly 2) Investigate how the meiotic kinetochore ensures accurate bi-orientation 3) Investigate how the central spindle interacts with kinetochores and promotes bi-orientation These three Aims are linked by a goal to understand the mechanisms of chromosome segregation important to oocytes. In completing this work, we will have identified mechanisms required for kinetochore assembly and for regulating the transition from lateral and end-on kinetochore-microtubule attachments. We will also determine the role of the central spindle in this process, which we believe is a mechanism of bi-orientation that is particularly important in acentrosomal oocytes.

在第一个减数分裂师中，chiasmata连接到微管的同源染色体纺锤体的相对极（双向），然后分离。染色体隔离的错误卵母细胞导致非整倍性，是流产，不育症和出生缺陷的主要原因。在卵母细胞许多生物，包括哺乳动物和昆虫，减数分裂的纺锤体组装发生在没有的情况下中心体。我们使用果蝇的Melanogaster女性作为了解促进机制的模型卵母细胞刺刺纺锤体上的准确染色体分离。我们有兴趣理解双向定向的机制和卵母细胞的特征，使其容易受到染色体的影响隔离错误。从我们以前的研究中，我们已经表明了动力学与微管以两种方式。首先，横向附件，动力学沿着侧面移动微管，建立双向方向。其次，末端附件，动力学使稳定附着在微管的末端，保持与极点的连接并隔离同源物。稳定末端附件太快导致染色体隔离的错误。横向相互作用对于双向方向发生在动力学和中央主轴之间，由重叠组成反平行的微管，对于牙入牙齿卵母细胞可能尤其重要。我们提出的研究是专注于理解动力学和中央主轴如何相互作用以调节从侧向附着的侧面和准确分离染色体。 1）研究减数分裂动物组件的机制 2）研究减数分裂动物如何确保准确的双向取向 3）研究中央主轴如何与动力学相互作用并促进双向方向这三个目的是通过一个目标来了解对染色体隔离机制的目标。卵母细胞。在完成这项工作时，我们将确定KineTochore组装所需的机制和用于调节从横向和末端微动物附着的过渡。我们也会确定中央主轴在此过程中的作用，我们认为这是双向定向的机制，在牙入牙科卵母细胞中尤其重要。

项目成果

期刊论文数量（6）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

A Brief History of Drosophila (Female) Meiosis.

DOI：
10.3390/genes13050775
发表时间：
2022-04-27
期刊：
GENES
影响因子：
3.5
作者：
Fellmeth, Jessica E.;McKim, Kim S.
通讯作者：
McKim, Kim S.

Aurora B and cyclin B have opposite effects on the timing of cytokinesis abscission in Drosophila germ cells and in vertebrate somatic cells.

DOI：
10.1016/j.devcel.2013.07.005
发表时间：
2013-08-12
期刊：
Developmental cell
影响因子：
11.8
作者：
Mathieu J;Cauvin C;Moch C;Radford SJ;Sampaio P;Perdigoto CN;Schweisguth F;Bardin AJ;Sunkel CE;McKim K;Echard A;Huynh JR
通讯作者：
Huynh JR

Meiotic CENP-C is a shepherd: bridging the space between the centromere and the kinetochore in time and space.