File:Schwann cell myelination and dedifferentiation.jpg

Regulation of Schwann cell myelination and dedifferentiation

(A) Schwann cell differentiation is regulated by expression of specific transcription factors.

Immature Schwann cells receive axonal signals, including neuregulin 1 (NRG), which up-regulate expression of transcription factors including NFκB, Oct-6, and Brn2. These transcription factors promote the promyelinating stage, in which Schwann cells acquire a one/one association with the axon and express early myelin markers. Up-regulation of Krox-20 is required for Schwann cells to form myelin sheaths and express myelin-specific proteins. (In the mature nerve, other Schwann cells that do not express these promyelinating transcription factors remain unmyelinated and segregate off multiple small axons as Remak bundles). Upon injury (i.e., axotomy), there is a rapid up-regulation of c-Jun and Sox-2. The former contributes to the down-regulation of Krox-20 and the dedifferentiation of Schwann cells.

(B) Cross-inhibition of Krox-20 and c-Jun promotes a switch in transcriptional complexes.

Promyelinating signals from the axon, such as NRG, drive expression of Krox-20, potentially via the phosphatidylinositol 3-kinase pathway. Activation of the JNK pathway during injury is likely to promote expression of c-Jun. The signals that activate this pathway in Schwann cells after injury are not known. These two transcription factors cross-inhibit each other's expression as shown.

Original file name: Figure 1. http://jcb.rupress.org/content/181/4/575/F1.expansion.html

Reference

<pubmed>18490509</pubmed>| PMC2386097 | JCB

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