Mechanisms of asymmetric cell division during female meiosis.

女性减数分裂过程中不对称细胞分裂的机制。

• 批准号: 8643247
• 负责人: Francis J McNally
• 金额: $ 29.48万
• 依托单位: UNIVERSITY OF CALIFORNIA AT DAVIS
• 依托单位国家: 美国
• 财政年份: 2007
• 资助国家: 美国
• 起止时间: 2007-07-15 至 2016-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8643247
• 关键词: Address; Affinity; Anaphase; Aneuploidy; Animals; Binding; Caenorhabditis elegans; Cell Cycle; Cell division; Cells; Centrioles; Centrosome; Cessation of life; Chimeric Proteins; Chromosome Segregation; Chromosome abnormality; Chromosomes; Chromosomes, Human, Pair 4; Complex; Conceptions; Cytoplasm; DNA; Data; Defect; Deposition; Diploidy; Dynein ATPase; Embryo; Excision; Female; Frequencies; Genetic Nondisjunction; Genome; Germ Cells; Goals; Grant; Haploidy; Human; Image; In Vitro; Inherited; Kinesin; Lead; Mediating; Meiosis; Mental Retardation; Metaphase; Microtubule Bundle; Microtubules; Mitotic spindle; Modeling; Molecular; Monosomy; Mothers; Movement; Oocytes; Pathway interactions; Phosphorylation; Positioning Attribute; Production; Property; Protein Biochemistry; Protein Dephosphorylation; Proteins; Public Health; RNA Interference; Reproduction; Research; Role; Rotation; Sister Chromatid; Site; Skates; Skating; Spermatocytes; Testing; Thick; Thinking; Time; Trisomy; X Chromosome; Xenopus; anaphase-promoting complex; dynactin; egg; human disease; katanin; male; mutant; offspring; premature; prevent; sperm cell; ubiquitin ligase; zygote

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.

描述（由申请人提供）：在雌性减数分裂期间，3/4的染色体被消除，并且只有1/4的染色体由单个卵子遗传。相比之下，在雄性减数分裂期间，所有染色体都分布在 4 个精子中。消除 3/4 的基因组以允许仅遗传 1/4 的染色体在所有动物门中都是保守的，这表明存在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，阐明不对称减数分裂的选择性优势。减数分裂错误导致 10-30% 的人类受孕中缺乏一条染色体（单体）或存在一条额外染色体（三体），其中大多数非整倍体导致胚胎死亡。通过阐明线虫减数分裂染色体消除的机制，我们将确定人类减数分裂期间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. 阐明阻止精子紫苑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向皮层的一根纺锤体极。 3. 确定剑素如何介导心粒纺锤体极组装。 4.测试未配对的染色体是否被选择性地挤压到极体中以防止三体性。这些目标将通过对减数分裂胚胎内的荧光蛋白融合进行延时成像来实现，这些胚胎已通过 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。