Gene expression in the preimplantation mouse embryo

植入前小鼠胚胎中的基因表达

• 批准号: 8843478
• 负责人: Brian D Gregory
• 金额: $ 30.67万
• 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 2016-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8843478
• 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; 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; 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; 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）：卵子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，并且是持续发育必须成功克服的最早障碍之一。 母体 mRNA 的降解（在卵母细胞成熟期间开始）和重新编程基因表达（在 2 细胞胚胎中非常明显）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，以更深入地了解每个潜在事件的分子基础，即母体 mRNA 的降解和基因表达的重编程。 卵子到胚胎转变的一个明显的普遍特征是母体 mRNA 在成熟过程中或受精/基因组激活后不久的降解。 由于 mRNA 降解受到高度调控，因此 mRNA 的降解方式越来越受到关注。 此外，越来越多的人认为母体 mRNA 的降解对于卵子到胚胎的转变至关重要。 具体目标 1 将检验以下假设：编码 DCP1A 和 2 的母体 mRNA 的募集导致 5' mRNA 降解途径成为主要途径。 拟议的研究还将确定成熟相关的 DCP2 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 将检验以下假设：卵母细胞成熟期间编码染色质重塑剂和转录因子的 mRNA 的募集对于重编程基因表达至关重要。 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，尤其是 microRNA (miRNA) 在 mRNA 降解中的作用，迅速引起人们的关注。 尽管卵母细胞表达大量的 miRNA 及其功能介导物，但导致 mRNA 降解的 miRNA 活性在卵母细胞中功能不佳，并且抑制 miRNA 生物合成对卵母细胞和植入前发育没有显着影响。 具体目标 3 将确定 miRNA 未能促进其目标 mRNA 在卵母细胞中降解的分子基础。 了解这种失败的原因将进一步阐明小 RNA 在卵母细胞发育中的作用。 总而言之，拟议研究的结果将产生对卵子到胚胎转变的两个关键过程的详细了解，即母体 mRNA 降解和重编程基因表达。