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. ? ? ?
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| Tran, Uyen; Zakin, Lise; Schweickert, Axel et al. (2010) The RNA-binding protein bicaudal C regulates polycystin 2 in the kidney by antagonizing miR-17 activity. Development 137:1107-16 |
| White, Jeffrey T; Zhang, Bo; Cerqueira, Debora M et al. (2010) Notch signaling, wt1 and foxc2 are key regulators of the podocyte gene regulatory network in Xenopus. Development 137:1863-73 |
| Wessely, Oliver; Agrawal, Raman; Tran, Uyen (2010) MicroRNAs in kidney development: lessons from the frog. RNA Biol 7:296-9 |
| Agrawal, Raman; Tran, Uyen; Wessely, Oliver (2009) The miR-30 miRNA family regulates Xenopus pronephros development and targets the transcription factor Xlim1/Lhx1. Development 136:3927-36 |
