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Blood vessels guide Schwann cell migration in the adult demyelinated CNS through Eph/ephrin signaling.
- Source :
-
Acta neuropathologica [Acta Neuropathol] 2019 Sep; Vol. 138 (3), pp. 457-476. Date of Electronic Publication: 2019 Apr 22. - Publication Year :
- 2019
-
Abstract
- Schwann cells (SC) enter the central nervous system (CNS) in pathophysiological conditions. However, how SC invade the CNS to remyelinate central axons remains undetermined. We studied SC migratory behavior ex vivo and in vivo after exogenous transplantation in the demyelinated spinal cord. The data highlight for the first time that SC migrate preferentially along blood vessels in perivascular extracellular matrix (ECM), avoiding CNS myelin. We demonstrate in vitro and in vivo that this migration route occurs by virtue of a dual mode of action of Eph/ephrin signaling. Indeed, EphrinB3, enriched in myelin, interacts with SC Eph receptors, to drive SC away from CNS myelin, and triggers their preferential adhesion to ECM components, such as fibronectin via integrinβ1 interactions. This complex interplay enhances SC migration along the blood vessel network and together with lesion-induced vascular remodeling facilitates their timely invasion of the lesion site. These novel findings elucidate the mechanism by which SC invade and contribute to spinal cord repair.
- Subjects :
- Animals
Demyelinating Diseases pathology
Female
Fibronectins metabolism
Mice
Mice, Inbred C57BL
Mice, Transgenic
Signal Transduction physiology
Spinal Cord pathology
Blood Vessels
Cell Movement physiology
Ephrin-B3 metabolism
Remyelination physiology
Schwann Cells physiology
Spinal Cord metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 1432-0533
- Volume :
- 138
- Issue :
- 3
- Database :
- MEDLINE
- Journal :
- Acta neuropathologica
- Publication Type :
- Academic Journal
- Accession number :
- 31011859
- Full Text :
- https://doi.org/10.1007/s00401-019-02011-1