Mechanisms of Schwann cell plasticity involved in peripheral nerve repair after injury
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Cellular and Molecular Life Sciences
REVIEW
Mechanisms of Schwann cell plasticity involved in peripheral nerve repair after injury Gianluigi Nocera1 · Claire Jacob1 Received: 4 January 2020 / Revised: 9 March 2020 / Accepted: 30 March 2020 © The Author(s) 2020
Abstract The great plasticity of Schwann cells (SCs), the myelinating glia of the peripheral nervous system (PNS), is a critical feature in the context of peripheral nerve regeneration following traumatic injuries and peripheral neuropathies. After a nerve damage, SCs are rapidly activated by injury-induced signals and respond by entering the repair program. During the repair program, SCs undergo dynamic cell reprogramming and morphogenic changes aimed at promoting nerve regeneration and functional recovery. SCs convert into a repair phenotype, activate negative regulators of myelination and demyelinate the damaged nerve. Moreover, they express many genes typical of their immature state as well as numerous de-novo genes. These genes modulate and drive the regeneration process by promoting neuronal survival, damaged axon disintegration, myelin clearance, axonal regrowth and guidance to their former target, and by finally remyelinating the regenerated axon. Many signaling pathways, transcriptional regulators and epigenetic mechanisms regulate these events. In this review, we discuss the main steps of the repair program with a particular focus on the molecular mechanisms that regulate SC plasticity following peripheral nerve injury. Keywords Schwann cell · Plasticity · Reprogramming · Chromatin remodeling enzymes · Transcription factors · Signaling pathways · Nerve injury and repair · Axonal regeneration · Remyelination
Schwann cells and peripheral nerve injuries Axonal repair in the central nervous system (CNS) is extremely limited after injury. In contrast, the PNS exhibits a high regenerative capacity. This ability is to a large extent due to the remarkable plasticity of SCs. During development, myelinating SCs form a one-to-one relationship with large caliber axons and wrap them in a myelin sheath, while non-myelinating SCs, also called Remak SCs, surround multiple small caliber axons without producing myelin. Upon axon injury, myelinating and nonmyelinating SCs undergo extensive reprogramming that promotes and guides axonal repair. SCs lose contact with and demyelinate the distal stump axon and convert into a repair phenotype. This phenotypic transformation involves the downregulation of several pro-myelinating genes. * Claire Jacob cjacob@uni‑mainz.de 1
Faculty of Biology, Institute of Developmental Biology and Neurobiology, Johannes Gutenberg University, Mainz, Germany
Repair SCs are characterized by a specific profile which enables the regeneration process. SC reprogramming involves the upregulation of several genes and the activation of multiple transcriptional mechanisms [1–3]. Among the main players, c-Jun, mitogen-activated protein kinase (MAPK) pathways, Sonic Hedgehog (Shh) and chromatin modifications control and regulate the repair prog
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