title: Sox4 participates in the modulation of Schwann cell myelination.
abstract: In order to identify new regulators of Schwann cell myelination potentially playing a role in peripheral nervous system (PNS) pathologies, we analysed gene expression profiling data from three mouse models of demyelinating neuropathies and from the developing PNS. This analysis revealed that Sox4, which encodes a member of the Sry-related high-mobility group box protein family, was consistently upregulated in all three analysed models of neuropathy. Moreover, Sox4 showed a peak in its expression during development that corresponded with the onset of myelination. To gain further insights into the role of Sox4 in PNS development, we generated a transgenic mouse that specifically overexpresses Sox4 in Schwann cells. Sox4 overexpression led to a temporary delay in PNS myelination without affecting axonal sorting. Importantly, we observed that, whereas Sox4 mRNA could be efficiently overexpressed, Sox4 protein expression in Schwann cells was strictly regulated. Finally, our data showed that enforced expression of Sox4 in the mouse model for Charcot-Marie-Tooth 4C aggravated its neuropathic phenotype. Together, these observations reveal that Sox4 contributes to the regulation of Schwann cell myelination, and also indicates its involvement in the pathophysiology of peripheral neuropathies.
authors.affiliation: Department of Medical Genetics, University of Lausanne, Lausanne, Switzerland.|Department of Neuroscience and Department of Clinical Neuroscience, Karolinska Institutet, Retzius väg 8, 171 77, Stockholm, Sweden.
authors.forename: Luca
authors.initials: L
authors.lastname: Bartesaghi
authors.affiliation: Department of Medical Genetics, University of Lausanne, Lausanne, Switzerland.
authors.forename: Estelle
authors.initials: E
authors.lastname: Arnaud Gouttenoire
authors.affiliation: Department of Medical Genetics, University of Lausanne, Lausanne, Switzerland.|Swiss Institute of Bioinformatics, University of Lausanne, Lausanne, Switzerland.
authors.forename: Andrea
authors.initials: A
authors.lastname: Prunotto
authors.affiliation: Department of Medical Genetics, University of Lausanne, Lausanne, Switzerland.
authors.forename: Jean-Jacques
authors.initials: JJ
authors.lastname: Médard
authors.affiliation: Department of Medical Genetics, University of Lausanne, Lausanne, Switzerland.|Swiss Institute of Bioinformatics, University of Lausanne, Lausanne, Switzerland.
authors.forename: Sven
authors.initials: S
authors.lastname: Bergmann
authors.affiliation: Department of Medical Genetics, University of Lausanne, Lausanne, Switzerland.|Department of Neuroscience and Department of Clinical Neuroscience, Karolinska Institutet, Retzius väg 8, 171 77, Stockholm, Sweden.
authors.forename: Roman
authors.initials: R
authors.lastname: Chrast
mesh_terms: D000367:Age Factors; D000818:Animals; D000831:Animals, Newborn; D001426:Bacterial Proteins / Q000235:genetics / Q000378:metabolism; D002352:Carrier Proteins / Q000235:genetics; D004195:Disease Models, Animal; D018507:Gene Expression Regulation, Developmental / Q000235:genetics*; D057809:HEK293 Cells; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins; D008164:Luminescent Proteins / Q000235:genetics / Q000378:metabolism; D051379:Mice; D008822:Mice, Transgenic; D009154:Mutation / Q000235:genetics; D009186:Myelin Sheath / Q000378:metabolism*; D017933:Peripheral Nervous System / Q000378:metabolism*; D010523:Peripheral Nervous System Diseases / Q000235:genetics / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics; D055751:SOXC Transcription Factors / Q000235:genetics / Q000378:metabolism*; D012583:Schwann Cells / Q000378:metabolism*; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism; D014162:Transfection
chemical_list: D001426:Bacterial Proteins; D002352:Carrier Proteins; D047908:Intracellular Signaling Peptides and Proteins; D008164:Luminescent Proteins; D012333:RNA, Messenger; D055751:SOXC Transcription Factors; C552538:Sh3tc2 protein, mouse; C489990:Sox4 protein, mouse; D014157:Transcription Factors; C054562:yellow fluorescent protein, Bacteria
keywords: Charcot-Marie-Tooth 4C; SRY-related high-mobility group box gene 4; peripheral neuropathy; transcription factor