Regulation of kidney field specification by transcriptional regulation of microRNAs

The transcriptional events driving specification of the kidney field have been well characterized. However, it remains unknown how the initial field size is established, patterned, and proportioned. Lhx1 is a transcription factor expressed in the kidney anlage and is required for specification of the kidney field, but few Lhx1 interacting cofactors or downstream targets have been identified. By tandem-affinity purification, we isolated Furry (FRY), a multifunctional protein that acts as a transcriptional co-repressor of microRNAs. We found that Xenopus embryos depleted of fry exhibit loss of the kidney field, phenocopying the lhx1 depleted animals. In addition, we demonstrated a synergism between Fry and Lhx1, identified candidate microRNAs regulated by the protein pair, and show at least two microRNA clusters influence specification of the kidney field. Therefore, our data shows that a tissue-specific transcription factor, Lhx1, can interact with a broadly expressed microRNA repressor, Fry, to establish the kidney field. Overall design: miRNA Deep sequencing of 3 Xenopus laevis samples