The Role of MicroRNAs in Vertebrate Ectodermal Specification

MicroRNA 在脊椎动物外胚层规范中的作用

• 批准号: 1147047
• 负责人: Amy Sater
• 金额: $ 51.86万
• 依托单位: University of Houston
• 依托单位国家: 美国
• 项目类别: Continuing Grant
• 财政年份: 2012
• 资助国家: 美国
• 起止时间: 2012-01-01 至 2015-12-31
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=1147047&HistoricalAwards=false
• 关键词: Role; MicroRNAs; Vertebrate; Ectodermal; Specification

During the development of vertebrate embryos, ectoderm cells choose between two developmental pathways: one leads to the formation of the nervous system, while the other produces the epidermis. This study investigates the role of microRNAs, small RNA molecules that can inhibit the expression of other genes, in the process by which these cells become committed to neural or epidermal fates. MicroRNAs are thought to play important roles in the control of gene expression both in embryonic development and the normal functions of adult tissues; they have been implicated in the differentiation of stem cells into specific cell types, as well as in many forms of cancer and other human diseases. Their specific functions in the initiation of neural development, however, are unknown. These experiments test hypotheses on the role of a specific microRNA known to restrict expression of a gene critical to epidermal commitment and on how the expression of microRNAs may differ between newly committed neural or epidermal ectoderm. In addition, these studies will identify genes that are regulated by microRNAs in newly committed neural ectoderm and epidermal ectoderm; computational methods will be used to identify candidate microRNAs that target these genes. These results will reveal molecular mechanisms that underlie the formation of the central nervous system, and establish new roles for microRNAs in embryonic development. They will also contribute to the development of stem cell-based therapies for neurological disease or injury. In addition, these studies will provide opportunities for undergraduate and graduate students to receive research training in molecular biology and bioinformatics, as well as vertebrate developmental biology.

在脊椎动物胚胎的发育过程中，外胚层细胞在两条发育途径中进行选择：一条是形成神经系统，另一条是产生表皮。这项研究调查了microRNAs，一种可以抑制其他基因表达的小RNA分子，在这些细胞致力于神经或表皮命运的过程中所起的作用。MicroRNAs被认为在胚胎发育和成人组织的正常功能中都发挥着重要的基因表达调控作用；它们参与了干细胞向特定细胞类型的分化，以及许多形式的癌症和其他人类疾病。然而，它们在启动神经发育中的具体功能尚不清楚。这些实验测试了已知的限制对表皮承诺至关重要的基因表达的特定microRNA的作用，以及新承诺的神经或表皮外胚层中microRNA的表达可能如何不同的假设。此外，这些研究将确定新确定的神经外胚层和表皮外胚层中受microRNAs调控的基因；将使用计算方法来确定针对这些基因的候选microRNAs。这些结果将揭示中枢神经系统形成的分子机制，并确立microRNAs在胚胎发育中的新角色。他们还将为神经疾病或损伤的干细胞疗法的开发做出贡献。此外，这些研究将为本科生和研究生提供接受分子生物学和生物信息学以及脊椎动物发育生物学的研究培训的机会。