Mechanism of asymmetric cell division during female meiosis.

 描述(申请人提供)：在雌性减数分裂过程中，3/4的染色体被消除，只有1/4的染色体被单个卵子遗传。相反，在雄性减数分裂过程中，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，在所有动物门中都是保守的，这表明了一些基本的选择优势。该项目的长期目标是阐明染色体消除的分子机制，并阐明不对称减数分裂的选择优势。减数分裂中的错误导致10-30%的人类胚胎中缺少一条染色体(单体)或存在额外的染色体(三体)，这些非整倍体中的大多数会导致胚胎死亡。通过阐明线虫减数分裂染色体消除的机制，我们将识别在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3个具体目标：1.阐明阻止精子与卵母细胞减数分裂纺锤体相互作用的机制。2.确定减数分裂纺锤体如何附着在皮层上，以促进染色体向极体挤出。3.确定未配对的染色体选择性地挤入极体以纠正三体的机制。这些目标将通过对减数分裂胚胎内荧光蛋白融合的延时成像来实现，减数分裂胚胎已经通过RNA干扰耗尽了关键的细胞骨架调节因子和细胞周期调节因子。

 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 3 specific aims: 1. Elucidate mechanisms that prevent the sperm from interacting with the oocyte meiotic spindle. 2. Determine how the meiotic spindle is attached at the cortex to facilitate extrusion of chromosomes into polar bodies. 3. Determine the mechanisms by which unpaired chromosomes are selectively extruded into polar bodies to correct 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.