2014-11-012024-05-13https://scholars.lib.ntu.edu.tw/handle/123456789/646588摘要：在細胞分裂中，成對染色體在分開之後必需被正確地分配到不同細胞中。在體細胞有 絲分裂及卵子減數分裂中，cyclin B/Cdk, auroraB kinase 以及 Spindle assembly checkpoint (SAC)協同決定染色體分離的起始。這樣的控管機制確保在分開前成對染色 體排列在正確的方位，以避免染色體分配錯誤造成anuploidy。雖然此一把關機制在有 絲分裂與卵子減數分裂中已被深入研究，因為精子形成過程中特有的染色質結構重 整，迄今我們仍不清楚精子減數分裂是否受到相同的控管。我之前利用線蟲的系統研 究，發現精原細胞在細胞分裂及染色質結構上都展現了異於卵母細胞及體細胞的組 成。由此我假設在精子減數分裂中，有一套特化的機制經這些精原細胞特異的結構來 監控成對染色體的排列正確與否。首先，我將用細胞生物學的方法來仔細檢視精原細 胞分裂的動態以及相關分子在此過程中的重要性。第二，我將檢視在精子減數分裂中 由metaphase進入到anaphase的過程是否也受SAC所監控。在活體正常精原細胞中， 一系列的染色體分配動態將被仔細紀錄做為基準；之後藉由破壞纺綞體或kinetochore 結構的方式來檢視是否染色體分配動態受到干攪。這項研究是迄今第一個在分子層次 研究精子減數分裂調節，將我們對精子形成的品管以及生殖成功的了解更向上一層次。<br> Abstract: Accurate chromosome segregation is a crucial aspect of cell division. In both mitosis and oocyte meiosis, the initiation of chromosome separation is regulated by cyclin B/Cdk, aurora B kinase and the spindle assembly checkpoint (SAC). Such quality control ensures proper orientation of sister chromatids prior to depart from each other, and therefore avoids anuploidy. Whether spermatogenic meiosis is under the same control is unknown, and is relevant given the unique structure and composition of sperm chromatin. My recent C. elegans studies suggest that spermatocytes exhibit cytological and chromatin features distinct from oocytes or embryonic cells. I hypothesize that specialized checkpoint mechanisms act on these unique features to regulate chromosome segregation in spermatocytes. First, I will characterize the chromosome segregation events during sperm meiotic divisions using cytological approaches. Second, to determine whether metaphase-anaphase transitions in spermatocytes are subject to SAC control, I will establish assays for major cellular events during chromosome segregation. These assays will be used to reveal SAC activation upon disruption of kinetechores or spindles. This study will be the first to elucidate the molecular basis of spermatogenic chromosome segregation and will shed light on how quality control mechanisms are adapted for sperm function and reproductive success.