The regulation of the homeostasis and regeneration of peripheral nerve is distinct from the CNS and independent of a stem cell population.

Salome Stierli,Anne-Laure Cattin,Julie Nihouarn,Liza Malong,Alison C Lloyd,Noelia Garcia Calavia,Anthony Monteza Cabrejos,Kaylene M Young,Ilaria Napoli,Richard Williams,Ian J White,William D Richardson,Sara Ribeiro

doi:10.1242/dev.170316

Abstract

ABSTRACTPeripheral nerves are highly regenerative, in contrast to the poor regenerative capabilities of the central nervous system (CNS). Here, we show that adult peripheral nerve is a more quiescent tissue than the CNS, yet all cell types within a peripheral nerve proliferate efficiently following injury. Moreover, whereas oligodendrocytes are produced throughout life from a precursor pool, we find that the corresponding cell of the peripheral nervous system, the myelinating Schwann cell (mSC), does not turn over in the adult. However, following injury, all mSCs can dedifferentiate to the proliferating progenitor-like Schwann cells (SCs) that orchestrate the regenerative response. Lineage analysis shows that these newly migratory, progenitor-like cells redifferentiate to form new tissue at the injury site and maintain their lineage, but can switch to become a non-myelinating SC. In contrast, increased plasticity is observed during tumourigenesis. These findings show that peripheral nerves have a distinct mechanism for maintaining homeostasis and can regenerate without the need for an additional stem cell population.This article has an associated ‘The people behind the papers’ interview.

Highlights

Once formed in the adult, peripheral nerves are relatively stable structures, befitting their role in transmitting signals back and forth between tissues and organs and the central nervous system (CNS)
We used a number of transgenic mice with lineage-specific expression of fluorescent labels, along with immunostaining of endogenous markers to quantify the prevalence of each cell type using immunofluorescence (IF) and electron microscopy (EM) analysis
We have systematically characterised the cells that make up the endoneurium of peripheral nerves, we cannot rule out a failure to detect rare cells that are not labelled by any of our methodologies

Summary

Introduction

Once formed in the adult, peripheral nerves are relatively stable structures, befitting their role in transmitting signals back and forth between tissues and organs and the central nervous system (CNS). In contrast to the CNS, peripheral nerves are able to regenerate following an injury (Mahar and Cavalli, 2018) This requires the regrowth of the neurons but the creation of new tissue to repair the wound site, together with the remodelling of the. SCs exist in one of two states: myelinating Schwann cells (mSCs), which myelinate larger axons in a 1:1 ratio, and non-myelinating Schwann cells (nmSCs), which bundle together groups of smaller axons in structures known as Remak bundles (Harty and Monk, 2017; Monk et al, 2015) Following injury, these highly specialised cells have the capacity to dedifferentiate to a proliferating, progenitor-like SC, which orchestrates the regenerative response (Jessen and Mirsky, 2016; Napoli et al, 2012). Once the axons have regrown, the dedifferentiated SCs are thought to redifferentiate in response to axonal signals, and the regenerative state resolves to return to the homeostatic state (Cattin and Lloyd, 2016; Zochodne, 2008)

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Conclusion