Gene expression in the preimplantation mouse embryo

植入前小鼠胚胎中的基因表达

• 批准号: 9058124
• 负责人: Brian D Gregory
• 金额: $ 4.95万
• 依托单位: UNIVERSITY OF PENNSYLVANIA
• 依托单位国家: 美国
• 财政年份: 1987
• 资助国家: 美国
• 起止时间: 1987-09-01 至 2016-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9058124
• 关键词: Affect; Assisted Reproductive Technology; Attention; Binding Proteins; Biogenesis; Biological Models; Blushing; CDC2 Protein Kinase; Cells; Chromatin; Chromatin Structure; Complex; Consensus; Degradation Pathway; Development; Embryo; Eukaryotic Cell; Event; Excision; Exonuclease; Failure; Fertilization; Gene Expression; Gene Expression Regulation; Genes; Genetic Transcription; Genome; Germ Cells; Grant; Guanosine; Health; Heart; Human; Infertility; Inherited; Light; Maternal Messenger RNA; Mediating; Mediator of activation protein; Meiosis; Messenger RNA; MicroRNAs; Molecular; Mus; Oocytes; Outcome; Pathway interactions; Pattern; Phase; Phosphorylation; Play; Poly(A) Tail; Process; Proteins; RNA Degradation; RNA-Binding Proteins; Role; Series; Small RNA; Staging; Structure; Testing; Totipotent; Transcript; Translations; base; blastocyst; egg; embryo cell; embryo stage 2; insight; mRNA Decay; mRNA Instability; mRNA Stability; mRNA Transcript Degradation; oocyte maturation; preimplantation; research study; transcription factor; transcriptome; zygote

DESCRIPTION (provided by applicant): The egg-to-embryo transition entails transforming a highly differentiated oocyte into totipotent blastomeres, and represents one of the earliest obstacles that must be successfully hurdled for continued development. Degradation of maternal mRNAs (which initiates during oocyte maturation) and reprogramming gene expression (which is clearly evident in 2-cell embryos) lie at the heart of this transition. The overarching objective of the proposed studies is to use mouse as a model system to gain deeper insights into the molecular basis for each of these underlying events, i.e., degradation of maternal mRNA and reprogramming gene expression. An apparently universal feature of the egg-to-embryo transition is degradation of maternal mRNAs either during maturation or shortly after fertilization/genome activation. How mRNAs are degraded is gaining increased attention because mRNA degradation is highly regulated. Moreover, there is growing consensus that degradation of maternal mRNA is essential for the egg-to-embryo transition. Specific Aim 1 will test the hypothesis that recruitment of maternal mRNAs encoding DCP1A &2 results in the 5' mRNA degradation pathway as the dominant pathway. The proposed studies will also define the role of the maturation-associated phosphorylation of DCP2 in mRNA degradation. Results of these studies will provide a detailed understanding of degradation of maternal mRNAs during the course of oocyte maturation. How reprogramming of gene expression occurs and uses a maternally inherited transcription apparatus remains enigmatic. Specific Aim 2 will test the hypothesis that recruitment during oocyte maturation of mRNAs encoding chromatin remodelers and transcription factors is essential for reprogramming gene expression. Results of these studies will likely provide a simple and elegant solution to this problem. Post-transcriptional mechanisms are rapidly gaining attention as a major locus of regulation of gene expression, and in particular, the role of microRNAs (miRNA) in mRNA degradation. Although oocytes express a plethora of miRNAs, as well as mediators of their function, miRNA activity that leads to mRNA degradation functions poorly in oocytes and inhibiting miRNA biogenesis has no marked effect on oocyte and preimplantation development. Specific Aim 3 will identify the molecular basis for failure of miRNAs to promote degradation of their target mRNAs in oocytes. Understanding the basis for this failure will shed further light on the role of small RNAs in oocyte development. Taken together, results of the proposed studies will generate a detailed understanding of two critical processes that underly the egg-to- embryo transition, i.e., maternal mRNA degradation and reprogramming gene expression.

描述（由申请人提供）：卵到胚胎的转变需要将高度分化的卵母细胞转化为全能卵裂球，并且代表了必须成功跨越以继续发育的最早障碍之一。 母体mRNA的降解（在卵母细胞成熟过程中启动）和重编程基因表达（在2细胞胚胎中很明显）是这一转变的核心。 拟议研究的总体目标是使用小鼠作为模型系统，以更深入地了解这些潜在事件中每一个的分子基础，即，母体mRNA降解和重编程基因表达。 卵到胚胎转变的一个明显的普遍特征是在成熟期间或受精/基因组激活后不久母体mRNA的降解。 mRNA的降解方式受到越来越多的关注，因为mRNA的降解受到高度调控。 此外，越来越多的共识认为，母体mRNA的降解是卵到胚胎过渡所必需的。 具体目标1将检验这样的假设，即编码DCP 1A &2的母体mRNA的募集导致5' mRNA降解途径作为主导途径。 拟议的研究还将确定DCP 2成熟相关磷酸化在mRNA降解中的作用。 这些研究的结果将提供一个详细的了解在卵母细胞成熟过程中的母体mRNA的降解。 基因表达的重编程是如何发生的，以及如何使用母系遗传的转录装置仍然是个谜。 具体目标2将测试的假设，在卵母细胞成熟的mRNA编码染色质重塑和转录因子的招聘是必不可少的重编程基因表达。 这些研究的结果可能会为这个问题提供一个简单而优雅的解决方案。 转录后机制作为基因表达调控的主要位点，特别是microRNA（miRNA）在mRNA降解中的作用，正迅速获得关注。 尽管卵母细胞表达过多的miRNA及其功能的介导物，但导致mRNA降解的miRNA活性在卵母细胞中功能较差，并且抑制miRNA生物合成对卵母细胞和植入前发育没有显著影响。 特异性目标3将确定miRNAs未能促进其靶mRNA在卵母细胞中降解的分子基础。 了解这种失败的基础将进一步阐明小RNA在卵母细胞发育中的作用。 总之，拟议研究的结果将详细了解卵子到胚胎过渡的两个关键过程，即，母体mRNA降解和重编程基因表达。