MicroRNAs in Kidney Development

描述（由申请人提供）：肾脏发育中的MicroRNAs MicroRNAs （miRNAs）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经鉴定出数百种mirna，其中许多mirna是进化保守的。尽管大多数mirna的生物学功能尚不清楚，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。在这项拨款申请中，我们将验证mirna在功能肾脏的发育中起关键作用的假设。关于mirna和肾脏发育的信息很少。因此，我们建议首先使用原位杂交技术对小鼠肾脏不同发育阶段中所有已鉴定的mirna的表达谱进行分类。其次，通过比较小鼠肾脏特异性mirna的表达与爪蟾肾原肾中相应mirna的表达来鉴定进化保守的mirna。最后，通过从非洲爪蟾胚胎中去除miRNA生物发生的关键成分Dicer，直接测试miRNA在肾脏发育中的潜在作用。然后将使用肾脏特异性标记基因、组织学和生理学研究小组研究对肾原的发育和近端-远端模式的影响。这一建议将为今后研究小鼠肾脏发育过程中单个mirna提供基础。此外，一套完整的小鼠肾脏miRNA表达数据的可用性将对社区非常有帮助。例如，它将促进对各种肾脏疾病小鼠模型中的mirna进行快速有效的分析。该项目解决了一种非编码小rna （microRNAs）在肾脏发育中的作用。研究表明，microRNAs与许多疾病过程有关，包括神经系统疾病，如妥瑞氏综合征，癌症的形成和疱疹病毒等病毒的传播。肾脏中microRNAs的鉴定和表征将为解决microRNAs是否也在某些肾脏疾病中发挥作用提供一个起点。

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.