Sox2 controls Schwann cell self-organization through fibronectin fibrillogenesis.

Autor:	Torres-Mejía E; Stem Cells in Neural Development and Disease group, Helmholtz Zentrum München, German Research Center for Environmental Health, 85764, Munich-Neuherberg, Germany.; Research Unit Sensory Biology and Organogenesis, Helmholtz Zentrum München, German Research Center for Environmental Health, 85764, Munich-Neuherberg, Germany.; Institute of Developmental Genetics, Helmholtz Zentrum München, German Research Center for Environmental Health, 85764, Munich-Neuherberg, Germany., Trümbach D; Institute of Developmental Genetics, Helmholtz Zentrum München, German Research Center for Environmental Health, 85764, Munich-Neuherberg, Germany., Kleeberger C; Department of Plastic, Reconstructive, Hand and Burn Surgery, Academic Hospital Bogenhausen, Munich, 81925, Germany., Dornseifer U; Department of Plastic, Reconstructive, Hand and Burn Surgery, Academic Hospital Bogenhausen, Munich, 81925, Germany., Orschmann T; Stem Cells in Neural Development and Disease group, Helmholtz Zentrum München, German Research Center for Environmental Health, 85764, Munich-Neuherberg, Germany.; Institute of Developmental Genetics, Helmholtz Zentrum München, German Research Center for Environmental Health, 85764, Munich-Neuherberg, Germany.; Stem Cell Based-Assay Development Platform (SCADEV), Helmholtz Zentrum München, German Research Center for Environmental Health, 85764, Munich-Neuherberg, Germany., Bäcker T; Stem Cells in Neural Development and Disease group, Helmholtz Zentrum München, German Research Center for Environmental Health, 85764, Munich-Neuherberg, Germany.; Institute of Developmental Genetics, Helmholtz Zentrum München, German Research Center for Environmental Health, 85764, Munich-Neuherberg, Germany.; Stem Cell Based-Assay Development Platform (SCADEV), Helmholtz Zentrum München, German Research Center for Environmental Health, 85764, Munich-Neuherberg, Germany., Brenke JK; Assay Development and Screening Platform, Helmholtz Zentrum München, German Research Center for Environmental Health, 85764, Munich-Neuherberg, Germany., Hadian K; Assay Development and Screening Platform, Helmholtz Zentrum München, German Research Center for Environmental Health, 85764, Munich-Neuherberg, Germany., Wurst W; Institute of Developmental Genetics, Helmholtz Zentrum München, German Research Center for Environmental Health, 85764, Munich-Neuherberg, Germany.; Chair of Developmental Genetics, Technische Universität München-Weihenstephan, 85350, Freising-Weihenstephan, Germany.; German Center for Neurodegenerative Diseases (DZNE), 81377, Munich, Germany., López-Schier H; Research Unit Sensory Biology and Organogenesis, Helmholtz Zentrum München, German Research Center for Environmental Health, 85764, Munich-Neuherberg, Germany., Desbordes SC; Stem Cells in Neural Development and Disease group, Helmholtz Zentrum München, German Research Center for Environmental Health, 85764, Munich-Neuherberg, Germany. sabrina.desbordes@isarbioscience.de.; Institute of Developmental Genetics, Helmholtz Zentrum München, German Research Center for Environmental Health, 85764, Munich-Neuherberg, Germany. sabrina.desbordes@isarbioscience.de.; Stem Cell Based-Assay Development Platform (SCADEV), Helmholtz Zentrum München, German Research Center for Environmental Health, 85764, Munich-Neuherberg, Germany. sabrina.desbordes@isarbioscience.de.; ISAR Bioscience GmbH, Institute for Stem Cell & Applied Regenerative Medicine Research, Semmelweisstr. 5, 82152, Munich, Germany. sabrina.desbordes@isarbioscience.de.
Jazyk:	angličtina
Zdroj:	Scientific reports [Sci Rep] 2020 Feb 06; Vol. 10 (1), pp. 1984. Date of Electronic Publication: 2020 Feb 06.
DOI:	10.1038/s41598-019-56877-y
Abstrakt:	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.
Databáze:	MEDLINE
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