title: SOX10 transactivates S100B to suppress Schwann cell proliferation and to promote myelination.
abstract: Schwann cells are an important cell source for regenerative therapy for neural disorders. We investigated the role of the transcription factor sex determining region Y (SRY)-box 10 (SOX10) in the proliferation and myelination of Schwann cells. SOX10 is predominantly expressed in rat sciatic nerve-derived Schwann cells and is induced shortly after birth. Among transcription factors known to be important for the differentiation of Schwann cells, SOX10 potently transactivates the S100B promoter. In cultures of Schwann cells, overexpressing SOX10 dramatically induces S100B expression, while knocking down SOX10 with shRNA suppresses S100B expression. Here, we identify three core response elements of SOX10 in the S100B promoter and intron 1 with a putative SOX motif. Knockdown of either SOX10 or S100B enhances the proliferation of Schwann cells. In addition, using dissociated cultures of dorsal root ganglia, we demonstrate that suppressing S100B with shRNA impairs myelination of Schwann cells. These results suggest that the SOX10-S100B signaling axis critically regulates Schwann cell proliferation and myelination, and therefore is a putative therapeutic target for neuronal disorders.
authors.affiliation: Departments of Sensory & Motor System Medicine, Faculty of Medicine, University of Tokyo, Tokyo, Japan.
authors.forename: Sayaka
authors.initials: S
authors.lastname: Fujiwara
authors.affiliation: Departments of Sensory & Motor System Medicine, Faculty of Medicine, University of Tokyo, Tokyo, Japan.
authors.forename: Shinya
authors.initials: S
authors.lastname: Hoshikawa
authors.affiliation: Departments of Sensory & Motor System Medicine, Faculty of Medicine, University of Tokyo, Tokyo, Japan.
authors.forename: Takaaki
authors.initials: T
authors.lastname: Ueno
authors.affiliation: Departments of Sensory & Motor System Medicine, Faculty of Medicine, University of Tokyo, Tokyo, Japan.
authors.forename: Makoto
authors.initials: M
authors.lastname: Hirata
authors.affiliation: Bone and Cartilage Regenerative Medicine, Faculty of Medicine, University of Tokyo, Tokyo, Japan.
authors.forename: Taku
authors.initials: T
authors.lastname: Saito
authors.affiliation: Departments of Sensory & Motor System Medicine, Faculty of Medicine, University of Tokyo, Tokyo, Japan.
authors.forename: Toshiyuki
authors.initials: T
authors.lastname: Ikeda
authors.affiliation: Departments of Sensory & Motor System Medicine, Faculty of Medicine, University of Tokyo, Tokyo, Japan.
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Kawaguchi
authors.affiliation: Departments of Sensory & Motor System Medicine, Faculty of Medicine, University of Tokyo, Tokyo, Japan.
authors.forename: Kozo
authors.initials: K
authors.lastname: Nakamura
authors.affiliation: Departments of Sensory & Motor System Medicine, Faculty of Medicine, University of Tokyo, Tokyo, Japan.
authors.forename: Sakae
authors.initials: S
authors.lastname: Tanaka
authors.affiliation: Department of Rehabilitation for the Movement Functions, Research Institute, National Rehabilitation Center for Persons with Disabilities, Saitama, Japan.
authors.forename: Toru
authors.initials: T
authors.lastname: Ogata
mesh_terms: D000818:Animals; D001483:Base Sequence; D015415:Biomarkers / Q000378:metabolism; D002454:Cell Differentiation; D002460:Cell Line; D049109:Cell Proliferation; D055785:Gene Knockdown Techniques; D006801:Humans; D007438:Introns / Q000235:genetics; D051379:Mice; D008969:Molecular Sequence Data; D018993:Myelin P0 Protein / Q000378:metabolism; D009186:Myelin Sheath / Q000378:metabolism*; D011485:Protein Binding / Q000235:genetics; D051381:Rats; D020218:Response Elements / Q000235:genetics; D064568:S100 Calcium Binding Protein beta Subunit / Q000235:genetics* / Q000378:metabolism; D055757:SOXE Transcription Factors / Q000235:genetics / Q000378:metabolism*; D012583:Schwann Cells / Q000166:cytology* / Q000378:metabolism; D015398:Signal Transduction / Q000235:genetics; D015533:Transcriptional Activation / Q000235:genetics*
chemical_list: D015415:Biomarkers; C560548:Mpz protein, rat; D018993:Myelin P0 Protein; D064568:S100 Calcium Binding Protein beta Subunit; C579158:S100b protein, rat; D055757:SOXE Transcription Factors; C527925:Sox10 protein, rat