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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.

在第一次减数分裂中，同源染色体通过交叉连接到微管上，主轴的相反极性（双向），然后分离。染色体分离错误卵母细胞导致非整倍体，并且是流产、不育和出生缺陷的主要原因。在卵母细胞中，许多生物，包括哺乳动物和昆虫，减数分裂纺锤体组装在缺乏中心体我们使用雌性黑腹果蝇作为模型来了解促进黑腹果蝇生长的机制。在卵母细胞的无中心体纺锤体上准确分离染色体。我们有兴趣了解双定向的机制和卵母细胞纺锤体的特征使其对染色体敏感分离错误从我们以前的研究中，我们已经表明，动粒相互作用，微管以两种方式。第一，横向附着，其中动粒沿着细胞的侧部沿着移动，微管，建立双向定位。第二，端部附着，其中动粒构成稳定的连接到微管的末端，保持与极点的连接并分离同源物。稳定末端连接太快导致染色体分离错误。横向相互作用对于动粒与纺锤体之间存在双向取向，由相互重叠构成反平行微管，可能是特别重要的无核小体卵母细胞。我们建议的研究是重点是了解动粒和中央纺锤体如何相互作用，以调节从侧向端对附件和准确地分离染色体。 1)探讨减数分裂动粒组装的机制 2)研究减数分裂动粒如何确保精确的双向定位 3)研究中央纺锤体如何与动粒相互作用并促进双向定位这三个目标是由一个目标联系在一起的，即理解染色体分离的机制，卵母细胞在完成这项工作时，我们将确定动粒组装所需的机制，用于调节从侧向和端部运动舞蹈微管附着的过渡。我们还将决定了主轴在这一过程中的作用，我们认为这是一种双向定位机制，在无中心体卵母细胞中尤为重要。

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.

减数分裂的CENP-C是一个牧羊人：在时空和空间上桥接了丝粒和动粒之间的空间。