Axon Degeneration and the Schwann Cell Early Injury Response: A Study in Mouse and Zebrafish
type: CreativeWork
description: After peripheral nervous system injury, axons degenerate through a process termed Wallerian degeneration and Schwann cells transform into a repair phenotype. Axon degeneration is regulated by a signalling pathway controlled by the pro-degenerative axon death molecule sterile-alpha and toll/interleukin 1 receptor motif containing protein 1 (SARM1). Meanwhile, Schwann cells activate a distinct transcriptional response, digest myelin using myelinophagy, attract macrophages, and support the survival of damaged neurons and their growth and guidance to their target. The early Schwann cell injury response prior to and around the timing of axon degeneration has, however, not been investigated in great detail, and the identity of an axonal injury signal that induces this Schwann cell injury response remains elusive. In order to investigate axon Schwann cell interactions in vitro, I developed a novel compartmentalised dissociated dorsal root ganglion neuron and Schwann cell coculture model. I show that in this model, Schwann cells are initially axo-protective, as their presence delays degeneration, irrespective of their myelination status. In later phases after injury, they are then axo-destructive and fragment and phagocytose axons. To further investigate the role of Schwann cells after injury, I then characterised an in vivo model of peripheral nervous system injury in larval zebrafish. I describe the rate of axon degeneration after laser axotomy of the peripheral lateral line nerve in wildtype, as well as in sarm1 mutant animals. I show a characteristic delay in axon degeneration in sarm1 mutant zebrafish, while their myelination is normal. I then performed cell specific reexpression experiments with human SARM1 and show that neuronal SARM1 is sufficient to rescue axon degeneration. In a more traditional mouse model of peripheral nervous system injury, I performed a bulk RNA sequencing study of the distal tibial nerve after cut injury at the sciatic notch at early timepoin…
abstract: After peripheral nervous system injury, axons degenerate through a process termed Wallerian degeneration and Schwann cells transform into a repair phenotype. Axon degeneration is regulated by a signalling pathway controlled by the pro-degenerative axon death molecule sterile-alpha and toll/interleukin 1 receptor motif containing protein 1 (SARM1). Meanwhile, Schwann cells activate a distinct transcriptional response, digest myelin using myelinophagy, attract macrophages, and support the survival of damaged neurons and their growth and guidance to their target. The early Schwann cell injury response prior to and around the timing of axon degeneration has, however, not been investigated in great detail, and the identity of an axonal injury signal that induces this Schwann cell injury response remains elusive. In order to investigate axon Schwann cell interactions in vitro, I developed a novel compartmentalised dissociated dorsal root ganglion neuron and Schwann cell coculture model. I show that in this model, Schwann cells are initially axo-protective, as their presence delays degeneration, irrespective of their myelination status. In later phases after injury, they are then axo-destructive and fragment and phagocytose axons. To further investigate the role of Schwann cells after injury, I then characterised an in vivo model of peripheral nervous system injury in larval zebrafish. I describe the rate of axon degeneration after laser axotomy of the peripheral lateral line nerve in wildtype, as well as in sarm1 mutant animals. I show a characteristic delay in axon degeneration in sarm1 mutant zebrafish, while their myelination is normal. I then performed cell specific reexpression experiments with human SARM1 and show that neuronal SARM1 is sufficient to rescue axon degeneration. In a more traditional mouse model of peripheral nervous system injury, I performed a bulk RNA sequencing study of the distal tibial nerve after cut injury at the sciatic notch at early timepoin…
author: Mutschler, Clara
language: eng
keywords: Axon degeneration, Peripheral nervous system injury, Schwann cell
license: https://www.repository.cam.ac.uk/bitstreams/a6da0b9e-4dd4-4b8f-9f40-5a658fc4064d/download
license: https://www.rioxx.net/licenses/all-rights-reserved/
date published: 2023-08-01
date modified: 2026-07-22T22:24:17Z
provider: Cambridge University
publisher: Networked Digital Library of Theses and Dissertations
type: WebPage
source organization: University of Cambridge

PropertyValue
property ID: DOI
value: 10.17863/CAM.106748