MicroRNAs in Kidney Development

MicroRNA 在肾脏发育中的作用

• 批准号: 7436337
• 负责人: Oliver Wessely
• 金额: $ 13.92万
• 依托单位: LSU HEALTH SCIENCES CENTER
• 依托单位国家: 美国
• 财政年份: 2007
• 资助国家: 美国
• 起止时间: 2007-06-15 至 2010-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7436337
• 关键词: Address; African; Amphibia; Anabolism; Animals; Applications Grants; Binding; Biogenesis; Biological Models; Biological Process; Cataloging; Catalogs; Communities; Complement; Data; Defect; Development; Disease; Distal; Embryo; Embryonic Development; Epithelial Cells; Event; Functional RNA; Future; Gene Expression; Genes; Genetic; Genetic Translation; Gilles de la Tourette syndrome; Hand; Hematopoiesis; Herpesviridae; Histology; Hour; Human; In Situ Hybridization; Individual; Investigation; Kidney; Kidney Diseases; Limb structure; Lung; Malignant Neoplasms; Mesonephric structure; Metanephric structure; MicroRNAs; Modeling; Molecular; Molecular Profiling; Mus; Nucleotides; Organism; Pathogenesis; Pattern; Physiological; Plants; Play; Process; Pronephric structure; Proteins; Research; Role; Skin; Small RNA; Staging; System; Testing; Time; Tissues; Untranslated Regions; Urine; Virus; Xenopus; Xenopus sp.; base; body system; human DICER1 protein; loss of function; mRNA Stability; mouse model; nephrogenesis; nervous system disorder; research study

DESCRIPTION (provided by applicant): MicroRNAs in Kidney Development MicroRNAs (miRNAs) are small non-coding RNA molecules that regulate gene expression at the post-transcriptional level. In recent years, hundreds of miRNAs have been identified in various multicellular organisms and many of the miRNAs are evolutionarily conserved. Although the biological functions of most miRNAs are still unknown, they are predicted to broadly regulate gene translation and mRNA stability. In addition, recent studies implicate miRNAs in cancer formation and suggest that changes in miRNA levels can have subtle disease-causing defects. In this grant proposal, we will test the hypothesis that miRNAs are crucial players in the development of a functional kidney. Very little information is available about miRNAs and kidney development. Therefore, we propose first to catalogue the expression profile of all identified miRNAs in the mouse kidney at different stages of development using in situ hybridization. Secondly, evolutionarily conserved miRNAs will be identified by comparing the expression of these kidney-specific miRNAs in mouse to the expression of their counterparts in the pronephric kidney of Xenopus. Finally, a potential role for miRNAs in kidney development will be tested directly by eliminating the key component of miRNA biogenesis, Dicer, from Xenopus embryos. The effect on development and proximal-distal patterning of the pronephros will then be studied using a panel of kidney-specific marker genes, histology and physiological studies. This proposal will provide the basis for future studies of individual miRNAs during mouse kidney development. In addition, the availability of a complete set of miRNA expression data from the mouse kidney will be extremely helpful for the community. It will - for example - facilitate a fast and efficient analysis of miRNAs in various mouse models of kidney diseases. This project addresses the role of a species of non-coding small RNAs (microRNAs) in kidney development. microRNAs have been shown to be involved in many disease processes including neurological disorders such as Tourette's syndrome, cancer formation and the propagation of virus such as Herpes Virus. The identification and characterization of microRNAs in the kidney will provide a starting point to address whether microRNAs also play a role in some of the kidney diseases.

描述(申请人提供)：肾脏发育中的microRNAs(MiRNAs)是在转录后水平调节基因表达的非编码小RNA分子。近年来，在各种多细胞生物中发现了数百种miRNAs，其中许多miRNAs在进化上是保守的。尽管大多数miRNAs的生物学功能尚不清楚，但预计它们将广泛调控基因翻译和mRNA的稳定性。此外，最近的研究表明miRNAs与癌症的形成有关，并表明miRNA水平的变化可能具有微妙的致病缺陷。在这项拨款提案中，我们将检验miRNAs在功能性肾脏发育中起关键作用的假设。关于miRNAs和肾脏发育的信息很少。因此，我们建议首先使用原位杂交对所有已鉴定的miRNAs在小鼠肾脏不同发育阶段的表达谱进行分类。其次，通过比较这些肾脏特异的miRNAs在小鼠中的表达和它们在非洲爪哇前肾中的表达，可以鉴定进化上保守的miRNAs。最后，将通过从非洲爪哇胚胎中去除miRNA生物发生的关键成分迪格尔，直接测试miRNAs在肾脏发育中的潜在作用。然后，将使用一组肾脏特异性标记基因、组织学和生理学研究来研究对前肾发育和近端-远端模式的影响。这一建议将为未来对小鼠肾脏发育过程中单个miRNAs的研究提供基础。此外，从小鼠肾脏获得一套完整的miRNA表达数据将对社区非常有帮助。例如，它将有助于快速有效地分析各种肾脏疾病小鼠模型的miRNAs。该项目涉及一种非编码小RNA(MicroRNAs)在肾脏发育中的作用。MicroRNAs参与了许多疾病的过程，包括抽动症、癌症的形成和疱疹病毒等病毒的传播等神经系统疾病。肾脏中microRNAs的鉴定和特征将为解决microRNAs是否也在某些肾脏疾病中发挥作用提供了一个起点。