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

Research output: Contribution to journalArticle

37 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

Fingerprint

Nephrons
Genes
Kidney
Transcription Factors
Apoptosis
Gene Expression
DNA

All Science Journal Classification (ASJC) codes

  • Nephrology

Cite this

Kanda, S., Tanigawa, S., Ohmori, T., Taguchi, A., Kudo, K., Suzuki, Y., ... 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

Sall1 maintains nephron progenitors and nascent nephrons by acting as both an activator and a repressor. / Kanda, Shoichiro; Tanigawa, Shunsuke; Ohmori, Tomoko; Taguchi, Atsuhiro; Kudo, Kuniko; Suzuki, Yutaka; Sato, Yuki; Hino, Shinjiro; Sander, Maike; Perantoni, Alan O.; Sugano, Sumio; Nakao, Mitsuyoshi; Nishinakamura, Ryuichi.

In: Journal of the American Society of Nephrology, Vol. 25, No. 11, 01.11.2014, p. 2584-2595.

Research output: Contribution to journalArticle

Kanda, S, Tanigawa, S, Ohmori, T, Taguchi, A, Kudo, K, Suzuki, Y, Sato, Y, Hino, S, Sander, M, Perantoni, AO, 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, vol. 25, no. 11, pp. 2584-2595. https://doi.org/10.1681/ASN.2013080896
Kanda, Shoichiro ; Tanigawa, Shunsuke ; Ohmori, Tomoko ; Taguchi, Atsuhiro ; Kudo, Kuniko ; Suzuki, Yutaka ; Sato, Yuki ; Hino, Shinjiro ; Sander, Maike ; Perantoni, Alan O. ; Sugano, Sumio ; Nakao, Mitsuyoshi ; Nishinakamura, Ryuichi. / Sall1 maintains nephron progenitors and nascent nephrons by acting as both an activator and a repressor. In: Journal of the American Society of Nephrology. 2014 ; Vol. 25, No. 11. pp. 2584-2595.
@article{e4f3fd6199d84fe79694e809fb00fbe1,
title = "Sall1 maintains nephron progenitors and nascent nephrons by acting as both an activator and a repressor",
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.",
author = "Shoichiro Kanda and Shunsuke Tanigawa and Tomoko Ohmori and Atsuhiro Taguchi and Kuniko Kudo and Yutaka Suzuki and Yuki Sato and Shinjiro Hino and Maike Sander and Perantoni, {Alan O.} and Sumio Sugano and Mitsuyoshi Nakao and Ryuichi Nishinakamura",
year = "2014",
month = "11",
day = "1",
doi = "10.1681/ASN.2013080896",
language = "English",
volume = "25",
pages = "2584--2595",
journal = "Journal of the American Society of Nephrology : JASN",
issn = "1046-6673",
publisher = "American Society of Nephrology",
number = "11",

}

TY - JOUR

T1 - Sall1 maintains nephron progenitors and nascent nephrons by acting as both an activator and a repressor

AU - Kanda, Shoichiro

AU - Tanigawa, Shunsuke

AU - Ohmori, Tomoko

AU - Taguchi, Atsuhiro

AU - Kudo, Kuniko

AU - Suzuki, Yutaka

AU - Sato, Yuki

AU - Hino, Shinjiro

AU - Sander, Maike

AU - Perantoni, Alan O.

AU - Sugano, Sumio

AU - Nakao, Mitsuyoshi

AU - Nishinakamura, Ryuichi

PY - 2014/11/1

Y1 - 2014/11/1

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=84923950723&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84923950723&partnerID=8YFLogxK

U2 - 10.1681/ASN.2013080896

DO - 10.1681/ASN.2013080896

M3 - Article

C2 - 24744442

AN - SCOPUS:84923950723

VL - 25

SP - 2584

EP - 2595

JO - Journal of the American Society of Nephrology : JASN

JF - Journal of the American Society of Nephrology : JASN

SN - 1046-6673

IS - 11

ER -