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Acta Neuropathol. 2019 Sep;138(3):457-476. doi: 10.1007/s00401-019-02011-1. Epub 2019 Apr 22.

Blood vessels guide Schwann cell migration in the adult demyelinated CNS through Eph/ephrin signaling.

Author information

1
Institut du Cerveau et de la Moelle Epinière-Groupe Hospitalier Pitié-Salpêtrière, INSERM, U1127; CNRS, UMR 7225; Sorbonne Universités, Université Pierre et Marie Curie Paris 06, UM-75, Paris, France. beatriz.garcia@icm-institute.org.
2
Unidad de Gestión Clínica de Neurociencias, IBIMA, Hospital Regional Universitario de Málaga, Malaga, 29009, Spain. beatriz.garcia@icm-institute.org.
3
Institut du Cerveau et de la Moelle Epinière-Groupe Hospitalier Pitié-Salpêtrière, INSERM, U1127; CNRS, UMR 7225; Sorbonne Universités, Université Pierre et Marie Curie Paris 06, UM-75, Paris, France.
4
Ecole normale supérieure, PSL Research University, CNRS, Inserm, Institut de Biologie de l'Ecole normale supérieure (IBENS), 75005, Paris, France.
5
Institut du Cerveau et de la Moelle Epinière-Groupe Hospitalier Pitié-Salpêtrière, INSERM, U1127; CNRS, UMR 7225; Sorbonne Universités, Université Pierre et Marie Curie Paris 06, UM-75, Paris, France. anne.baron@upmc.fr.

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.

KEYWORDS:

Blood vessels; Central nervous system; EphrinB3; Migration; Schwann cells

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