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 in mice. Analysis of mice 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 repression was also independent of its binding to DNA. Thus, Sall1 maintains nephron progenitors and their derivatives by a unique mechanism, which partly overlaps but is distinct from that of Six2: Sall1 activates progenitor-related genes in Six2-positive nephron progenitors and represses gene expression in Six2-negative differentiating nascent nephrons.
authors.affiliation: Departments of Kidney Development and.
authors.forename: Shoichiro
authors.initials: S
authors.lastname: Kanda
authors.affiliation: Departments of Kidney Development and.
authors.forename: Shunsuke
authors.initials: S
authors.lastname: Tanigawa
authors.affiliation: Departments of Kidney Development and.
authors.forename: Tomoko
authors.initials: T
authors.lastname: Ohmori
authors.affiliation: Departments of Kidney Development and.
authors.forename: Atsuhiro
authors.initials: A
authors.lastname: Taguchi
authors.affiliation: Departments of Kidney Development and.
authors.forename: Kuniko
authors.initials: K
authors.lastname: Kudo
authors.affiliation: Department of Medical Genome Sciences, University of Tokyo, Tokyo, Japan;
authors.forename: Yutaka
authors.initials: Y
authors.lastname: Suzuki
authors.affiliation: Priority Organization for Innovation and Excellence, Kumamoto University, Kumamoto, Japan;
authors.forename: Yuki
authors.initials: Y
authors.lastname: Sato
authors.affiliation: Medical Cell Biology, Institute of Molecular Embryology and Genetics, and.
authors.forename: Shinjiro
authors.initials: S
authors.lastname: Hino
authors.affiliation: Departments of Pediatrics and Cellular and Molecular Medicine, University of California at San Diego, La Jolla, California;
authors.forename: Maike
authors.initials: M
authors.lastname: Sander
authors.affiliation: Cancer and Developmental Biology Laboratory, National Cancer Institute, National Institutes of Health, Frederick, Maryland; and.
authors.forename: Alan O
authors.initials: AO
authors.lastname: Perantoni
authors.affiliation: Department of Medical Genome Sciences, University of Tokyo, Tokyo, Japan;
authors.forename: Sumio
authors.initials: S
authors.lastname: Sugano
authors.affiliation: Medical Cell Biology, Institute of Molecular Embryology and Genetics, and CREST, Japan Science and Technology Agency, Saitama, Japan.
authors.forename: Mitsuyoshi
authors.initials: M
authors.lastname: Nakao
authors.affiliation: Departments of Kidney Development and CREST, Japan Science and Technology Agency, Saitama, Japan ryuichi@kumamoto-u.ac.jp.
authors.forename: Ryuichi
authors.initials: R
authors.lastname: Nishinakamura
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000502:physiology; D002454:Cell Differentiation / Q000502:physiology; D005260:Female; D017353:Gene Deletion; D018507:Gene Expression Regulation, Developmental; D018398:Homeodomain Proteins / Q000235:genetics / Q000378:metabolism; D007668:Kidney / Q000166:cytology / Q000196:embryology* / Q000502:physiology; D008822:Mice, Transgenic; D009399:Nephrons / Q000166:cytology / Q000196:embryology* / Q000502:physiology; D009924:Organ Culture Techniques; D011247:Pregnancy; D015398:Signal Transduction / Q000502:physiology; D013234:Stem Cells / Q000166:cytology / Q000502:physiology; D014157:Transcription Factors / Q000235:genetics* / Q000378:metabolism*
chemical_list: D018398:Homeodomain Proteins; C491254:Sall1 protein, mouse; C497420:Six2 protein, mouse; D014157:Transcription Factors
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