Asymmetric Meiotic Cell Division of Mammalian Oocytes

哺乳动物卵母细胞的不对称减数分裂

• 批准号: 9352238
• 负责人: RONG LI
• 金额: $ 33.93万
• 依托单位: JOHNS HOPKINS UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2016
• 资助国家: 美国
• 起止时间: 2016-09-12 至 2020-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9352238
• 关键词: ANGPTL2 gene; Actins; Actomyosin; Aging; Automobile Driving; Biological Models; Cell Polarity; Cell division; Cells; Chromatin; Chromosomes; Clinical; Complex; Congenital Abnormality; Cytoplasm; Cytoplasmic streaming; Cytoskeleton; Data; Defect; Development; Embryonic Development; Endoplasmic Reticulum; Experimental Models; F-Actin; Family; Fertility; Fertilization; Future; Generations; Genome; Goals; Human; Imaging technology; Importins; Infertility; Knowledge; Liquid substance; Measurement; Measures; Mediating; Meiosis; Membrane; Methods; Modeling; Molecular; Molecular Genetics; Morphology; Movement; Mus; Myosin Type II; Nuclear; Oocytes; Organelles; Organism; Pathway interactions; Pattern; Peripheral; Positioning Attribute; Process; Production; Property; Research; Signal Transduction; Site; Stem cells; System; Testing; biological systems; biophysical tools; cell type; design; fascinate; improved; innovation; insight; mathematical analysis; migration; novel; novel therapeutics; prevent; segregation; self organization; spatiotemporal; treadmill; vector; zygote

The goal of this project is to understand how a mammalian organism initiates its multicellular development by completing its very first asymmetric cell divisions (ACD) - during meiotic maturation and fertilization of the oocyte. Meiotic ACD not only is critically important for successful fertilization and full developmental potential of the zygote, but also offers unique and fascinating insights into the mechanism of self-organization, a most fundamental property of biological systems. Recent studies from our lab and others using mouse oocytes as the model system have begun to unravel dynamic and bi-directional interplays between the chromosomes and the actin cytoskeleton in setting up oocyte cell polarity for ACD and potentially also for future embryonic development. In the proposed research, we plan to build on these exciting recent findings to answer three mechanistic questions: 1) how actin dynamics drive oocyte symmetry breaking (Aim1); 2) how the nuclear genome directly signals morphological reorganization on the cellular level (Aim2); and 3) how an unusual mechanism of dynamic force production patterns a large cell (the oocyte) and potentially impacts organelle segregation and early embryonic development (Aim3). To answer these questions, we will employ a highly innovative approach that entails a full integration of molecular genetic methods with cutting-edge imaging technologies, biophysical tools and mathematical analysis. Because clinical evidence suggests that defects in the polarized organization of mature oocytes are associated with aging-related infertility, our study not only has the potential for novel intellectual contribution to the understanding of self-organization in cellular systems but may also provide the basis for future development of new methods that help improve human fertility and prevent birth defects.

该项目的目标是了解哺乳动物生物体如何启动其多细胞 通过完成其第一次不对称细胞分裂（ACD）-在减数分裂期间 卵母细胞的成熟和受精。减数分裂ACD不仅对成功的 受精和充分发展潜力的合子，而且还提供了独特的和迷人的 对自组织机制的深入了解，这是生物学最基本的特性， 系统.我们实验室和其他人最近使用小鼠卵母细胞作为模型系统的研究表明， 开始解开染色体和肌动蛋白之间的动态和双向相互作用 细胞骨架在建立ACD的卵母细胞极性中的作用，也可能在未来的胚胎发育中起作用。 发展在拟议的研究中，我们计划在这些令人兴奋的最新发现的基础上， 回答三个机制问题：1）肌动蛋白动力学如何驱动卵母细胞对称性破缺 （Aim 1）; 2）核基因组如何直接信号细胞上的形态重组 水平（Aim 2）;以及3）动态力产生的不寻常机制如何使大细胞图案化 (the卵母细胞），并可能影响细胞器分离和早期胚胎发育 （目标3）。为了回答这些问题，我们将采用一种高度创新的方法， 将分子遗传学方法与尖端成像技术、生物物理学工具 和数学分析。因为临床证据表明， 成熟卵母细胞的组织与衰老相关的不孕症有关，我们的研究不仅有 为理解细胞自组织做出新的智力贡献的潜力 系统，但也可能为未来开发新方法提供基础， 人类生育能力和防止出生缺陷。