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Gene expression during preimplantation development in the mouse embryo.

机译:小鼠胚胎着床前发育过程中的基因表达。

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摘要

Mouse preimplantation development is marked with pronounced changes in the patterns of reprogramming of gene expression during distinct transitions, namely the maternal-to-zygotic transition, compaction and blastocyst formation. This work examines RNA transcript profiles during the different stages of mouse preimplantation development. Using microarray analysis, combined with functional genomics tools such as Expression Analysis Systematic Explorer (EASE) and Ingenuity Pathway Analysis (IPA), we characterized global changes in gene expression and identified biological processes that accompany and likely underlie these transitions. This study confirmed previously described processes and events, but more important, revealed new insights. Response to DNA damage and DNA repair genes are over-represented in the oocyte and may reflect the oocyte's response to selective pressures to insure genomic integrity; fertilization results in changes in the transcript profile in the 1-cell embryo that are far greater than previously recognized; and genome activation during the 2-cell stage may not be as global and promiscuous as previously proposed, but rather more selective, with genes involved in transcription and RNA processing being preferentially expressed. Further transcription profiling in 1-cell and 2-cell mouse embryos treated with transcription inhibitor alpha-amanitin confirmed this finding and identified genes that are activated during the course of zygotic gene activation; for example, Myc and Hdac1 could be critical players involved in genome activation and repression in the preimplantation mouse embryo. This work also reports the development of a linear mRNA amplification method from small amounts of mouse oocytes and preimplantation embryos and the subsequent generation of oocyte-specific and 8-cell-specific cDNA libraries using suppression subtractive hybridization; and these libraries were partially characterized. This work represents an extensive study on the global and temporal patterns of gene expression in the mouse oocyte and early embryo stages. The results validate this hypothesis-generating approach by identifying genes involved in critical biological processes that can now be the subject of more traditional hypothesis-driven study.
机译:小鼠植入前的发育在不同的过渡过程中,即从母体到合子的过渡,紧实和囊胚形成过程中,基因表达的重编程模式发生了明显变化。这项工作检查了小鼠植入前发育不同阶段的RNA转录谱。使用微阵列分析,并与功能基因组学工具(例如,表达分析系统浏览器(EASE)和创造力途径分析(IPA))相结合,我们表征了基因表达的总体变化,并确定了伴随并可能是这些转变的生物学过程。这项研究证实了先前描述的过程和事件,但更重要的是,它揭示了新的见解。对DNA损伤和DNA修复基因的反应在卵母细胞中过度存在,可能反映了卵母细胞对选择压力的反应,以确保基因组完整性。受精导致1-细胞胚胎中转录物谱的变化远大于以前的认识; 2细胞阶段的基因组激活可能不像之前提出的那样全面和复杂,而是更具选择性,涉及转录和RNA加工的基因被优先表达。在用转录抑制剂α-amanitin处理的1细胞和2细胞小鼠胚胎中进一步的转录谱证实了这一发现并鉴定了在合子基因激活过程中被激活的基因。例如,Myc和Hdac1可能是植入前小鼠胚胎中基因组激活和抑制的关键参与者。这项工作还报告了从少量小鼠卵母细胞和植入前胚胎中线性线性mRNA扩增方法的发展,以及随后通过抑制消减杂交技术生成卵母细胞特异性和8细胞特异性cDNA文库的方法;这些库的部分特征。这项工作代表了对小鼠卵母细胞和早期胚胎期基因表达的整体和时间模式的广泛研究。结果通过鉴定关键生物学过程中涉及的基因来验证这种假设生成方法,这些基因现在可以成为更传统的假设驱动研究的主题。

著录项

  • 作者

    Zeng, Fanyi.;

  • 作者单位

    University of Pennsylvania.;

  • 授予单位 University of Pennsylvania.;
  • 学科 Biology Molecular.; Biology Genetics.
  • 学位 Ph.D.
  • 年度 2005
  • 页码 257 p.
  • 总页数 257
  • 原文格式 PDF
  • 正文语种 eng
  • 中图分类 分子遗传学;遗传学;
  • 关键词

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