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（miRNA）是小的非编码RNA分子，可在转录后水平调节基因表达。近年来，已经在各种多细胞生物中鉴定出数百个miRNA，许多miRNA在进化上是保守的。尽管大多数miRNA的生物学功能仍然未知，但预计它们将广泛调节基因翻译和mRNA稳定性。此外，最近的研究暗示了miRNA在癌症形成中，并表明miRNA水平的变化可能会带来细微的致病缺陷。在这项赠款提案中，我们将检验以下假设：miRNA是功能性肾脏发展的关键参与者。关于miRNA和肾脏开发的信息很少。因此，我们首先建议使用原位杂交在发育的不同阶段对所有鉴定的miRNA的表达曲线进行分类。其次，将通过比较这些肾脏特异性miRNA与Xenopus促脑肾脏中的肾脏特异性miRNA的表达来鉴定进化保守的miRNA。最后，将直接通过消除从Xenopus胚胎中消除miRNA生物发生的关键成分来直接测试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，组织学和生理研究对脑力脑的发育和近端模式的影响进行研究。该提案将为小鼠肾脏发育期间对单个miRNA的未来研究提供基础。此外，从小鼠肾脏中获得一组MiRNA表达数据的可用性对社区非常有帮助。例如，它将促进对各种肾脏疾病小鼠模型中miRNA的快速有效分析。该项目介绍了一种非编码小RNA（microRNA）在肾脏发育中的作用。已显示MicroRNA参与许多疾病过程，包括神经系统疾病，例如Tourette综合征，癌症形成和疱疹病毒等病毒的传播。肾脏中microRNA的识别和表征将提供一个起点，以解决microRNA是否在某些肾脏疾病中发挥作用。