Mechanisms of asymmetric cell division during female meiosis.

描述（申请人提供）：在女性减数分裂过程中，3/4的染色体被淘汰，只有1/4的染色体被单个卵子遗传。而在雄性减数分裂时，所有的染色体都分布在4个精子中。消除3/4的基因组，只允许1/4的染色体遗传，这在所有动物门中都是保守的，这表明一些基本的选择优势。本项目的长期目标是阐明染色体消除的分子机制，阐明不对称减数分裂的选择优势。在10-30%的人类受孕中，减数分裂错误导致缺少一条染色体（单体）或存在一条额外的染色体（三体），其中大多数非整倍体导致胚胎死亡。通过阐明秀丽隐杆线虫的减数分裂染色体消除机制，我们将确定人类减数分裂过程中可能存在缺陷的机制。在这个项目中，我们将追求4个具体目标：1。阐明阻止精子加速捕获卵母细胞减数分裂纺锤体的机制。2. 确定细胞质动力蛋白如何定位皮层的一个纺锤极。3. 确定katanin如何调节无中心主轴杆组装。4. 检测未配对染色体是否选择性地挤压到极体中以防止三体。这些目标将通过对减数分裂胚胎中荧光蛋白融合的延时成像来解决，这些胚胎已经被RNA干扰和蛋白质生物化学耗尽了关键的细胞骨架调节剂和细胞周期调节剂。

DESCRIPTION (provided by applicant): During female meiosis, 3/4 of the chromosomes are eliminated and only 1/4 of the chromosomes are inherited by a single egg. In contrast, all chromosomes are distributed among 4 sperm during male meiosis. The elimination of 3/4 of the genome to allow inheritance of only 1/4 of the chromosomes is conserved in all animal phyla, suggesting some fundamental selective advantage. The long-term goals of this project are to elucidate the molecular mechanisms of chromosome elimination and elucidate the selective advantages of asymmetric meiotic division. Errors in meiosis lead to the absence of one chromosome (monosomy) or the presence of an extra chromosome (trisomy) in 10-30% of human conceptions with the majority of these aneuploidies leading to embryonic death. By elucidating the mechanisms of meiotic chromosome elimination in C. elegans, we will identify mechanisms likely to be defective during human meiosis. In this project we will pursue 4 specific aims: 1. Elucidate mechanisms that prevent the sperm aster from capturing the oocyte meiotic spindle. 2. Determine how cytoplasmic dynein orients one spindle pole at the cortex. 3. Determine how katanin mediates acentriolar spindle pole assembly. 4. Test whether unpaired chromosomes are selectively extruded into polar bodies to prevent trisomy. These aims will be addressed by time-lapse imaging of fluorescent protein fusions within meiotic embryos that have been depleted of key cytoskeletal regulators and cell-cycle regulators by RNA interference and by protein biochemistry.