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

Roberts, SL; Dun, X-P; Doddrell, RDS; Mindos, T; Drake, LK; Onaitis, MW; Florio, F; ... Parkinson, DB; + view all (2017) Sox2 expression in Schwann cells inhibits myelination in vivo and induces influx of macrophages to the nerve. Development , 144 (17) pp. 3114-3125. 10.1242/dev.150656.

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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 and maintenance 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.

Type: Article
Title: Sox2 expression in Schwann cells inhibits myelination in vivo and induces influx of macrophages to the nerve
DOI: 10.1242/dev.150656
Publisher version: http://doi.org/10.1242/dev.150656
Language: English
Additional information: This version is the version of record. For information on re-use, please refer to the publisher’s terms and conditions.
Keywords: Science & Technology, Life Sciences & Biomedicine, Developmental Biology, Schwann cell, Myelination, Sox2, Repair, Peripheral nervous system, Mouse, CONGENITAL HYPOMYELINATING NEUROPATHY, C-JUN ACTIVATION, DISEASE TYPE 1B, PERIPHERAL-NERVE, N-CADHERIN, NEGATIVE REGULATOR, SIGNALING PATHWAY, TRANSGENIC MICE, ERK1/2 MAPK, DIFFERENTIATION
UCL classification: UCL > School of Life and Medical Sciences
UCL > School of Life and Medical Sciences > Faculty of Life Sciences
URI: http://discovery.ucl.ac.uk/id/eprint/1573224
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