MicroRNAs in Kidney Development

MicroRNA 在肾脏发育中的作用

• 批准号: 7238835
• 负责人: Oliver Wessely
• 金额: $ 24.85万
• 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 2009-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7238835
• 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（由申请人提供）：肾脏发育中的 MicroRNA MicroRNA (miRNA) 是在转录后水平调节基因表达的小非编码 RNA 分子。近年来，在各种多细胞生物中已鉴定出数百种 miRNA，其中许多 miRNA 在进化上是保守的。尽管大多数 miRNA 的生物学功能仍不清楚，但预计它们可以广泛调节基因翻译和 mRNA 稳定性。此外，最近的研究表明 miRNA 与癌症形成有关，并表明 miRNA 水平的变化可能会产生微妙的致病缺陷。在这项资助提案中，我们将检验 miRNA 在功能性肾脏发育中发挥关键作用的假设。关于 miRNA 和肾脏发育的信息非常少。因此，我们建议首先使用原位杂交对处于不同发育阶段的小鼠肾脏中所有已识别的 miRNA 的表达谱进行编目。其次，通过将小鼠肾脏特异性 miRNA 的表达与爪蟾前肾中对应物的表达进行比较，可以鉴定进化上保守的 miRNA。最后，将通过从非洲爪蟾胚胎中消除 miRNA 生物发生的关键成分 Dicer 来直接测试 miRNA 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远端模式的影响。该提案将为小鼠肾脏发育过程中个体 miRNA 的未来研究提供基础。此外，获得小鼠肾脏的全套 miRNA 表达数据将对社区非常有帮助。例如，它将促进各种肾脏疾病小鼠模型中 miRNA 的快速有效分析。该项目探讨了一种非编码小 RNA (microRNA) 在肾脏发育中的作用。 microRNA已被证明参与许多疾病过程，包括抽动秽语综合征等神经系统疾病、癌症形成和疱疹病毒等病毒传播。肾脏中 microRNA 的鉴定和表征将为解决 microRNA 是否也在某些肾脏疾病中发挥作用提供一个起点。