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Torres-Mejia, E. ; Trümbach, D. ; Kleeberger, C.* ; Dornseifer, U.* ; Orschmann, T. ; Bäcker, T. ; Brenke, J.K. ; Hadian, K. ; Wurst, W. ; López-Schier, H. ; Desbordes, S.C.

Sox2 controls Schwann cell self-organization through fibronectin fibrillogenesis.

Sci. Rep. 10:1984 (2020)
Verlagsversion Forschungsdaten DOI PMC
Open Access Gold
Creative Commons Lizenzvertrag
The extracellular matrix is known to modulate cell adhesion and migration during tissue regeneration. However, the molecular mechanisms that fine-tune cells to extra-cellular matrix dynamics during regeneration of the peripheral nervous system remain poorly understood. Using the RSC96 Schwann cell line, we show that Sox2 directly controls fibronectin fibrillogenesis in Schwann cells in culture, to provide a highly oriented fibronectin matrix, which supports their organization and directional migration. We demonstrate that Sox2 regulates Schwann cell behaviour through the upregulation of multiple extracellular matrix and migration genes as well as the formation of focal adhesions during cell movement. We find that mouse primary sensory neurons and human induced pluripotent stem cell-derived motoneurons require the Sox2-dependent fibronectin matrix in order to migrate along the oriented Schwann cells. Direct loss of fibronectin in Schwann cells impairs their directional migration affecting the alignment of the axons in vitro. Furthermore, we show that Sox2 and fibronectin are co-expressed in proregenerative Schwann cells in vivo in a time-dependent manner during sciatic nerve regeneration. Taken together, our results provide new insights into the mechanisms by which Schwann cells regulate their own extracellular microenvironment in a Sox2-dependent manner to ensure the proper migration of neurons.
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Publikationstyp Artikel: Journalartikel
Dokumenttyp Wissenschaftlicher Artikel
Schlagwörter Extracellular-matrix; Nerve Regeneration; Migration; Adhesion; Expression; Injury; Myelin; Roles; Lines
Sprache englisch
Veröffentlichungsjahr 2020
HGF-Berichtsjahr 2020
ISSN (print) / ISBN 2045-2322
e-ISSN 2045-2322
Zeitschrift Scientific Reports
Quellenangaben Band: 10, Heft: 1, Seiten: , Artikelnummer: 1984 Supplement: ,
Verlag Nature Publishing Group
Verlagsort London
Begutachtungsstatus Peer reviewed
Institut(e) Institute of Developmental Genetics (IDG)
Research Unit Sensory Biology and Organogenesis (SBO)
Institute of Molecular Toxicology and Pharmacology (TOX)
POF Topic(s) 30204 - Cell Programming and Repair
30203 - Molecular Targets and Therapies
Forschungsfeld(er) Genetics and Epidemiology
Stem Cell and Neuroscience
Enabling and Novel Technologies
PSP-Element(e) G-500591-001
G-500100-001
G-500500-001
G-505293-001
G-500500-005
DOI 10.1038/s41598-019-56877-y
WOS ID WOS:000559759000015
Scopus ID 85079069546
PubMed ID 32029747
Erfassungsdatum 2020-02-09
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