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

Blood vessels guide Schwann cell migration in the adult demyelinated CNS through Eph/ephrin signaling
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DOI:
10.1007/s00401-019-02011-1
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发表时间:
2019-09-01
影响因子:
12.7
通讯作者:
Baron-Van Evercooren, Anne
Baron-Van Evercooren, Anne
中科院分区:
医学1区
文献类型:
--
作者:
Garcia-Diaz, Beatriz;Bachelin, Corinne;Baron-Van Evercooren, Anne

文献摘要

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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 integrin beta 1 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.