MicroRNA Function in the Developing Vertebrate Limb

MicroRNA 在脊椎动物肢体发育中的功能

• 批准号: 7054901
• 负责人: Kimberly Lynn Cooper
• 金额: $ 4.6万
• 依托单位: HARVARD MEDICAL SCHOOL
• 依托单位国家: 美国
• 财政年份: 2006
• 资助国家: 美国
• 起止时间: 2006-05-01 至 2009-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7054901
• 关键词: Retroviridae; bioinformatics; biotechnology; cartilage development; cell differentiation; chemical cleavage; chemical structure function; chick embryo; chondrocytes; computational biology; developmental genetics; embryogenesis; gene expression; gene induction /repression; genetically modified animals; intermolecular interaction; laboratory mouse; limbs; microRNAs; microarray technology; postdoctoral investigator; transfection /expression vector; vertebrate embryology

DESCRIPTION (provided by applicant): The interest in small interfering, non-coding microRNAs has exploded due to emerging discoveries of their diversity and prevalence across animal species. For all of the enthusiasm that they have garnered in the field, very little is known of their individual target genes and biological functions. The goal of this proposal is to determine the function of a set of microRNAs expressed in the developing vertebrate limb bud by combining molecular biology, computational bioinformatics, and classical embryology. Specific Aim 1 will test the hypothesis that let-7e functions in the limb to inhibit inappropriate chondrogenesis. Specific Aim 2 will use similar experimental methods to investigate the functions of five additional microRNAs expressed strongly in the vertebrate limb. Specific Aim 3 will focus on elucidating the requirement for the microRNA assocated protein Argonaute 2 and its cognate microRNAs by generating a conditional null allele of Ago2 in the mouse and performing a microarray analysis. The results of these investigations will reveal functions of microRNAs in the developing embryo and will open avenues to research that may allow development of antisense RNA technology for therapeutic applications.

描述（由申请人提供）：由于小干扰非编码 microRNA 在动物物种中的多样性和普遍性的不断发现，人们对它们的兴趣激增。尽管它们在该领域获得了极大的热情，但人们对它们各自的靶基因和生物学功能知之甚少。该提案的目标是通过结合分子生物学、计算生物信息学和经典胚胎学来确定发育中的脊椎动物肢芽中表达的一组 microRNA 的功能。具体目标 1 将检验 let-7e 在肢体中发挥抑制不适当软骨形成作用的假设。具体目标 2 将使用类似的实验方法来研究在脊椎动物肢体中强烈表达的另外 5 种 microRNA 的功能。具体目标 3 将重点通过在小鼠中生成 Ago2 的条件无效等位基因并进行微阵列分析来阐明对 microRNA 相关蛋白 Argonaute 2 及其同源 microRNA 的需求。这些研究的结果将揭示 microRNA 在发育胚胎中的功能，并为开发用于治疗应用的反义 RNA 技术开辟研究途径。