Gene expression in the preimplantation mouse embryo

植入前小鼠胚胎中的基因表达

• 批准号: 8502932
• 负责人: Brian D Gregory
• 金额: $ 31.48万
• 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 2018-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8502932
• 关键词: Affect; Assisted Reproductive Technology; Attention; 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 Profile; Gene Expression Regulation; Genes; Genetic Transcription; Genome; Germ Cells; Grant; Guanosine; 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; Protein Binding; Proteins; RNA Degradation; RNA-Binding Proteins; Role; Series; Small RNA; Solutions; Staging; Structure; Testing; Transcript; Translations; base; blastocyst; egg; embryo cell; embryo stage 2; insight; mRNA Decay; mRNA Instability; mRNA Stability; mRNA Transcript Degradation; oocyte maturation; preimplantation; public health relevance; research study; transcription factor; zygote; Affect; Assisted Reproductive Technology; Attention; 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 Profile; Gene Expression Regulation; Genes; Genetic Transcription; Genome; Germ Cells; Grant; Guanosine; 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; Protein Binding; Proteins; RNA Degradation; RNA-Binding Proteins; Role; Series; Small RNA; Solutions; Staging; Structure; Testing; Transcript; Translations; base; blastocyst; egg; embryo cell; embryo stage 2; insight; mRNA Decay; mRNA Instability; mRNA Stability; mRNA Transcript Degradation; oocyte maturation; preimplantation; public health relevance; research study; transcription factor; 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）：鸡蛋到embryo的过渡需要将高度分化的卵母细胞转化为全能的囊泡，这代表了必须成功刺激以持续发展的最早障碍之一。 母体mRNA（在卵母细胞成熟过程中启动）和重编程基因表达（在2细胞胚胎中显而易见）的降解是这种过渡的核心。 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基本事件中的每个事件的分子基础，即母体mRNA的降解和重编程基因表达。 卵到胚胎过渡的一个明显普遍特征是在成熟期间或受精/基因组激活后不久，母体mRNA降解。 由于mRNA降解受到高度调节，因此mRNA的降解方式正在增加注意力。 此外，越来越多的共识是，孕产妇mRNA的降解对于卵到胚胎过渡至关重要。 具体目标1将检验以下假设：编码DCP1A和2的母体mRNA导致5'mRNA降解途径作为主要途径。 拟议的研究还将定义DCP2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对卵母细胞成熟过程中母体mRNA降解的详细了解。 基因表达的重编程如何发生并使用母体遗传的转录设备仍然存在神秘性。 具体目标2将检验以下假设：编码染色质重塑的mRNA卵母细胞成熟过程中的募集和转录因子对于重编程基因表达至关重要。 这些研究的结果可能会为此问题提供简单而优雅的解决方案。 转录后机制正在迅速引起人们的注意，这是基因表达调节的主要基因座，尤其是microRNA（miRNA）在mRNA降解中的作用。 尽管卵母细胞表达了大量的miRNA及其功能的介体，但导致mRNA降解在卵母细胞中的功能较差并抑制miRNA生物发生的miRNA活性对卵母细胞和植入前发育没有明显影响。 具体目标3将确定miRNA失败无法促进卵母细胞中靶mRNA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。 综上所述，拟议的研究的结果将产生对卵向至胚胎过渡的两个关键过程的详细理解，即母体mRNA降解和重编程基因表达。