The Lhx1-Ldb1 complex interacts with Furry to regulate microRNA expression during pronephric kidney development

• Published in: Scientific reports 2018-10, Vol.8 (1), p.16029-16, Article 16029
• Main Authors: Espiritu, Eugenel B., Crunk, Amanda E., Bais, Abha, Hochbaum, Daniel, Cervino, Ailen S., Phua, Yu Leng, Butterworth, Michael B., Goto, Toshiyasu, Ho, Jacqueline, Hukriede, Neil A., Cirio, M. Cecilia
• Format: Article
• Language: English
• Subjects: 631/136; 631/136/2060; 64/114; 82/58; Embryos; Humanities and Social Sciences; Kidneys; Mesoderm; MicroRNAs; miRNA; multidisciplinary; Protein purification; Science; Science (multidisciplinary); Synergism
• ISSN: 2045-2322; 2045-2322
• DOI: 10.1038/s41598-018-34038-x

The molecular events driving specification of the kidney have been well characterized. However, how the initial kidney field size is established, patterned, and proportioned is not well characterized. Lhx1 is a transcription factor expressed in pronephric progenitors and is required for specification of the kidney, but few Lhx1 interacting proteins or downstream targets have been identified. By tandem-affinity purification, we isolated FRY like transcriptional coactivator (Fryl), one of two paralogous genes, fryl and furry ( fry) , have been described in vertebrates. Both proteins were found to interact with the Ldb1-Lhx1 complex, but our studies focused on Lhx1/Fry functional roles, as they are expressed in overlapping domains. We found that Xenopus embryos depleted of fry exhibit loss of pronephric mesoderm, phenocopying the Lhx1 - depleted animals. In addition, we demonstrated a synergism between Fry and Lhx1, identified candidate microRNAs regulated by the pair, and confirmed these microRNA clusters influence specification of the kidney. Therefore, our data shows that a constitutively-active Ldb1-Lhx1 complex interacts with a broadly expressed microRNA repressor, Fry, to establish the kidney field.