The role of microtubule dynamics in midzone driven chromosome segregation in anaphase

摘要 有丝分裂期间染色体的忠实分离是一个基本而重要的过程，发生在 在人的一生中大约有一千万亿次。有丝分裂中的错误具有严重的影响 往往不利于生物体的发育、健康和生存。微管是主要的结构。 有丝分裂纺锤体的块，是癌症治疗的一个非常重要的靶点。我们知道微管，在 特别是着丝粒微管，对染色体施加力量，使它们最初位于中期 培养板，然后将它们分裂成两个子细胞。然而，最近的研究表明， 中心纺锤体在染色体分离中也起着重要作用。精确的机制是如何 中央纺锤体调节染色体分离的机制目前还不完全清楚。有一系列证据表明 这表明中央纺锤体可以产生向外推动的力量来移动染色体，但它也 已经有令人信服的证据表明，它可以通过充当突破口来减缓染色体分离的速度。这样做的目的是 建议解剖中央纺锤体在后期的功能，并确定中央纺锤体是如何 产生有助于染色体分离的力量。我们的进一步目标是确定贡献 微管动力学对中枢纺锤体功能的影响。为了实现这一目标，我们使用了微观结构数据 从野生型和突变型条件下的断层扫描来监测微管的排列和性质 在后期的中心纺锤体，并确定潜在的相互作用和力量产生机制。 我们将用以下方式获得的中区微管的动态数据来补充精确的结构数据 尖端光学显微镜分析。我们将使用数学建模来开发和检验假设 纺锤体中间区对后期染色体分离的影响。我们研究的最终目的是 就是了解中央纺锤体如何产生调节染色体分离的力量，并 确定这一过程中的分子关键角色

Summary The faithful segregation of chromosomes during mitosis is a fundamental and important process, happening approximately a quadrillion time throughout a human life span. Errors in mitosis have severe implications and are often detrimental to development, health and survival of the organism. Microtubules are the main building blocks of mitotic spindles and are a very important target for cancer therapy. We know that microtubules, in particular kinetochore microtubules, exert forces on chromosomes to initially position them on the metaphase plate and consequently divide them to the two daughter cells. However, recent research has shown that the central spindle also plays an important role in chromosome segregation. The precise mechanisms of how the central spindle regulates chromosome segregation are not fully understood today. A line of evidence has suggested that the central spindle can generate outward pushing forces to move chromosomes, but it has also been convincingly shown to slow chromosome segregation down by acting like a break. The goal of this proposal is to dissect the function of the central spindle during anaphase and to identify how the central spindle generates forces contributing to the segregation of chromosomes. We further aim to establish the contribution of microtubule dynamics for central spindle function. To achieve this goal, we use the microstructural data from tomography in wild type and mutant conditions to monitor the microtubule arrangement and properties in the central spindle during anaphase and to identify potential interactions and force generating mechanisms. We will complement the precise structural data with dynamic data on microtubules in the midzone obtained by cutting edge light-microscopic analysis. We will use mathematical modeling to develop and test hypothesis of how the spindle midzone contributes to chromosome segregation in anaphase. The ultimate goal of our study is to understand how the central spindle generates forces that regulate the segregation of chromosomes and to identify the molecular key players of this process