Sox2 expression in schwann cells inhibits myelination in vivo and induces influx of macrophages to the nerve

SL Roberts, XP Dun, RDS Doddrell, T Mindos, LK Drake, MW Onaitis, F Florio, A Quattrini, AC Lloyd, M D’Antonio, DB Parkinson

Research output: Contribution to journalArticle

Abstract

Correct myelination is crucial for the function of the peripheral nervous system. Both positive and negative regulators within the axon and Schwann cell function to ensure the correct onset and progression of myelination during both development and following peripheral nerve injury and repair. The Sox2 transcription factor is well known for its roles in the development andmaintenance of progenitor and stem cell populations, but has also been proposed in vitro as a negative regulator of myelination in Schwann cells. We wished to test fully whether Sox2 regulates myelination in vivo and show here that, in mice, sustained Sox2 expression in vivo blocks myelination in the peripheral nerves and maintains Schwann cells in a proliferative non-differentiated state, which is also associated with increased inflammation within the nerve. The plasticity of Schwann cells allows them to re-myelinate regenerated axons following injury and we show that re-myelination is also blocked by Sox2 expression in Schwann cells. These findings identify Sox2 as a physiological regulator of Schwann cell myelination in vivo and its potential to play a role in disorders of myelination in the peripheral nervous system. © 2017. Published by The Company of Biologists Ltd.
Original languageEnglish
Pages (from-to)3114-3125
Number of pages12
JournalDevelopment (Cambridge)
Volume144
Issue number17
DOIs
Publication statusPublished - 2017

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Schwann Cells
Macrophages
Peripheral Nervous System
Axons
Stem Cells
Peripheral Nerve Injuries
Peripheral Nerves
Transcription Factors
Inflammation
Wounds and Injuries
Population

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Roberts, SL., Dun, XP., Doddrell, RDS., Mindos, T., Drake, LK., Onaitis, MW., ... Parkinson, DB. (2017). Sox2 expression in schwann cells inhibits myelination in vivo and induces influx of macrophages to the nerve. Development (Cambridge), 144(17), 3114-3125. https://doi.org/10.1242/dev.150656

Sox2 expression in schwann cells inhibits myelination in vivo and induces influx of macrophages to the nerve. / Roberts, SL; Dun, XP; Doddrell, RDS; Mindos, T; Drake, LK; Onaitis, MW; Florio, F; Quattrini, A; Lloyd, AC; D’Antonio, M; Parkinson, DB.

In: Development (Cambridge), Vol. 144, No. 17, 2017, p. 3114-3125.

Research output: Contribution to journalArticle

Roberts, SL, Dun, XP, Doddrell, RDS, Mindos, T, Drake, LK, Onaitis, MW, Florio, F, Quattrini, A, Lloyd, AC, D’Antonio, M & Parkinson, DB 2017, 'Sox2 expression in schwann cells inhibits myelination in vivo and induces influx of macrophages to the nerve', Development (Cambridge), vol. 144, no. 17, pp. 3114-3125. https://doi.org/10.1242/dev.150656
Roberts, SL ; Dun, XP ; Doddrell, RDS ; Mindos, T ; Drake, LK ; Onaitis, MW ; Florio, F ; Quattrini, A ; Lloyd, AC ; D’Antonio, M ; Parkinson, DB. / Sox2 expression in schwann cells inhibits myelination in vivo and induces influx of macrophages to the nerve. In: Development (Cambridge). 2017 ; Vol. 144, No. 17. pp. 3114-3125.
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AB - Correct myelination is crucial for the function of the peripheral nervous system. Both positive and negative regulators within the axon and Schwann cell function to ensure the correct onset and progression of myelination during both development and following peripheral nerve injury and repair. The Sox2 transcription factor is well known for its roles in the development andmaintenance of progenitor and stem cell populations, but has also been proposed in vitro as a negative regulator of myelination in Schwann cells. We wished to test fully whether Sox2 regulates myelination in vivo and show here that, in mice, sustained Sox2 expression in vivo blocks myelination in the peripheral nerves and maintains Schwann cells in a proliferative non-differentiated state, which is also associated with increased inflammation within the nerve. The plasticity of Schwann cells allows them to re-myelinate regenerated axons following injury and we show that re-myelination is also blocked by Sox2 expression in Schwann cells. These findings identify Sox2 as a physiological regulator of Schwann cell myelination in vivo and its potential to play a role in disorders of myelination in the peripheral nervous system. © 2017. Published by The Company of Biologists Ltd.

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