Conducting Myelination

Science Signaling  03 Feb 2009:
Vol. 2, Issue 56, pp. ec40
DOI: 10.1126/scisignal.256ec40

The myelin sheaths that surround some vertebrate neurons and facilitate the transmission of fast action potentials are formed by neural crest–derived Schwann cells. In the mouse, neuregulin signaling through its receptor ErbB is required for Schwann cell development, as is the transcription factor Krox20, which coordinates expression of a subset of myelin proteins. Kao et al. observed that nuclear factor of activated T cells (NFAT) was active in the neural crest during Schwann cell development and investigated the role of the phosphatase calcineurin in this process. Calcineurin dephosphorylates NFATc molecules, which are sequestered in the cytoplasm until dephosphorylation allows them to enter the nucleus to act as transcription factors. Abrogating calcineurin activity by deleting the gene encoding the calcineurin B1 subunit specifically from neural crest cells caused defects in Schwann cell development and myelination. In cultured dorsal root ganglia explants, neuregulin signaling through ErbB activated calcineurin, which, in turn, dephosphorylated NFATc3 and NFATc4. In the nucleus, NFATc4 and Sox10 formed stable complexes and bound to the promoter of Krox20. Calcineurin and NFAT therefore mediate neuregulin signaling to promote differentiation of Schwann cells.

S.-C. Kao, H. Wu, J. Xie, C.-P. Chang, J. A. Ranish, I. A. Graef, G. R. Crabtree, Calcineurin/NFAT signaling is required for neuregulin-regulated Schwann cell differentiation. Science 323, 651–654 (2009). [Abstract] [Full Text]