Mechanisms of Asymmetric RNA segregation in C. elegans Development

线虫发育中 RNA 不对称分离的机制

基本信息

批准号：
8706912
负责人：
JASON D LIEB
金额：
$ 24.42万
依托单位：
UNIVERSITY OF CHICAGO
依托单位国家：
美国
项目类别：
财政年份：
2013
资助国家：
美国
起止时间：
2013-08-01 至 2017-06-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8706912
关键词：
Address Adult Animals Anterior Antibodies Biological Biological Process Biological Testing Caenorhabditis elegans Cell Lineage Cell division Cells Characteristics Chimeric Proteins Congenital Abnormality Data Databases Defect Development Disease Elements Embryo Embryonic Development Event Failure Fluorescent in Situ Hybridization Functional RNA Generations Genetic Transcription Genomics Goals Grant Hand Hepatocyte High-Throughput Nucleotide Sequencing Human Human Development Lead Maps Methods MicroRNAs Modification Molecular Mutagenesis Names Organism Pathway interactions Phenotype Production Proteins Protocols documentation RNA RNA Decay RNA Interference RNA Sequences RNA-Binding Proteins Research Resolution Small RNA Staging System Techniques Testing Trans-Activators Transcript Untranslated Regions Video Microscopy carcinogenesis cell type daughter cell embryo stage 2 genome-wide analysis heart cell molecular asymmetry mutant new technology novel strategies promoter public health relevance segregation single molecule stem stem cell division tissue regeneration tool transcriptome sequencing

项目摘要

DESCRIPTION (provided by applicant): The three aims of this project address the function of molecular asymmetries that occur very early in animal development, and the mechanisms by which they arise. Asymmetric cell division is essential for generation of cell-type diversity during differentiation and development. Failure o properly undergo asymmetric cell divisions can lead to defects in stem-cell renewal, tissue regeneration, and can contribute to carcinogenesis. We propose to use a near-ideal natural system, the early C. elegans embryo, to characterize the mechanisms of asymmetric distribution of cellular contents in specific blastomeres with modern genomic tools and analysis, followed by tests of function. Specifically, this proposal aims (1) to use blastomere-specific isolation, RNA- seq, and other high-throughput sequencing applications to comprehensively map RNA inheritance and transcriptional activity of seven invariant cell divisions in early C. elegans development, (2) to test the biological significance of asymmetric RNA segregation in development, and (3) to define the cis and trans-acting mechanisms required for asymmetric RNA segregation. To achieve these goals, we will also apply new approaches and technologies to the study of asymmetric segregation of cellular components. Our research plan is likely to identify cell-fate determinants and mechanisms that are generalizable to other systems, including humans.

描述（由申请人提供）：该项目的三个目的解决了动物发育早期发生的分子不对称的功能以及它们出现的机制。不对称细胞分裂对于分化和发育过程中的细胞类型多样性至关重要。失败o正确地发生不对称的细胞分裂可能会导致干细胞更新，组织再生的缺陷，并可能导致致癌作用。我们建议使用近乎理想的天然系统，即早期的秀丽隐杆线虫胚胎，以用现代基因组工具和分析，随后进行功能测试，以特定的特定胚泡中细胞含量的不对称分布的机理。具体而言，该建议的目的（1）旨在使用胚胎特异性隔离，RNA-SEQ和其他高通量测序应用，以全面地绘制秀丽杆菌开发中七个不变细胞分裂的七个不变细胞分裂的RNA遗传和转录活性（2），以测试对未成年人的开发和（3）的生物学作用，以实现AS-Metric RNA sementric and（3），以适用于（3），以定为3）。 RNA分离。为了实现这些目标，我们还将应用新的方法和技术来研究细胞成分的不对称分离。我们的研究计划可能会确定可推广到包括人类在内的其他系统的细胞命运决定因素和机制。