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Abstract
Schwann cells respond to nerve injury by cellular reprogramming that generates cells
specialized for promoting regeneration and repair. These repair cells clear redundant
myelin, attract macrophages, support survival of damaged neurons, encourage axonal
growth, and guide axons back to their targets. There are interesting parallels between
this response and that found in other tissues. At the cellular level, many other tissues
also react to injury by cellular reprogramming, generating cells specialized to promote
tissue homeostasis and repair. And at the molecular level, a common feature possessed
by Schwann cells and many other cells is the injury-induced activation of genes associated
with epithelial-mesenchymal transitions and stemness, differentiation states that
are linked to cellular plasticity and that help injury-induced tissue remodeling.
The number of signaling systems regulating Schwann cell plasticity is rapidly increasing.
Importantly, this includes mechanisms that are crucial for the generation of functional
repair Schwann cells and nerve regeneration, although they have no or a minor role
elsewhere in the Schwann cell lineage. This encourages the view that selective tools
can be developed to control these particular cells, amplify their repair supportive
functions and prevent their deterioration. In this review, we discuss the emerging
similarities between the injury response seen in nerves and in other tissues and survey
the transcription factors, epigenetic mechanisms, and signaling cascades that control
repair Schwann cells, with emphasis on systems that selectively regulate the Schwann
cell injury response.