Sall1 maintains nephron progenitors and nascent nephrons by acting as both an activator and a repressor

Shoichiro Kanda, Shunsuke Tanigawa, Tomoko Ohmori, Atsuhiro Taguchi, Kuniko Kudo, Yutaka Suzuki, Yuki Sato, Shinjiro Hino, Maike Sander, Alan O. Perantoni, Sumio Sugano, Mitsuyoshi Nakao, Ryuichi Nishinakamura

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40 Citations (Scopus)

Abstract

The balanced self-renewal and differentiation of nephron progenitors are critical for kidney development and controlled, in part, by the transcription factor Six2, which antagonizes canonical Wnt signaling-mediated differentiation. A nuclear factor, Sall1, is expressed in Six2-positive progenitors as well as differentiating nascent nephrons, and it is essential for kidney formation. However, the molecular functions and targets of Sall1, especially the functions and targets in the nephron progenitors, remain unknown. Here, we report that Sall1 deletion in Six2-positive nephron progenitors results in severe progenitor depletion and apoptosis of the differentiating nephrons inmice. Analysis ofmice with an inducible Sall1 deletion revealed that Sall1 activates genes expressed in progenitors while repressing genes expressed in differentiating nephrons. Sall1 and Six2 co-occupied many progenitor-related gene loci, and Sall1 bound to Six2 biochemically. In contrast, Sall1 did not bind to the Wnt4 locus suppressed by Six2. Sall1-mediated repressionwas also independent of its binding to DNA. Thus, Sall1maintains nephron progenitors and their derivatives by a unique mechanism, which partly overlaps but is distinct fromthat of Six2: Sall1 activates progenitor-related genes in Six2-positive nephron progenitors and represses gene expression in Six2-negative differentiating nascent nephrons.

Original languageEnglish
Pages (from-to)2584-2595
Number of pages12
JournalJournal of the American Society of Nephrology
Volume25
Issue number11
DOIs
Publication statusPublished - Nov 1 2014

All Science Journal Classification (ASJC) codes

  • Nephrology

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    Kanda, S., Tanigawa, S., Ohmori, T., Taguchi, A., Kudo, K., Suzuki, Y., Sato, Y., Hino, S., Sander, M., Perantoni, A. O., Sugano, S., Nakao, M., & Nishinakamura, R. (2014). Sall1 maintains nephron progenitors and nascent nephrons by acting as both an activator and a repressor. Journal of the American Society of Nephrology, 25(11), 2584-2595. https://doi.org/10.1681/ASN.2013080896