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Science 325 (5946): 1402-1405

Copyright © 2009 by the American Association for the Advancement of Science

A G Protein–Coupled Receptor Is Essential for Schwann Cells to Initiate Myelination

Kelly R. Monk,1 Stephen G. Naylor,1 Thomas D. Glenn,1 Sara Mercurio,1 Julie R. Perlin,1 Claudia Dominguez,1 Cecilia B. Moens,2 William S. Talbot1

Abstract: The myelin sheath allows axons to conduct action potentials rapidly in the vertebrate nervous system. Axonal signals activate expression of specific transcription factors, including Oct6 and Krox20, that initiate myelination in Schwann cells. Elevation of cyclic adenosine monophosphate (cAMP) can mimic axonal contact in vitro, but the mechanisms that regulate cAMP levels in vivo are unknown. Using mutational analysis in zebrafish, we found that the G protein–coupled receptor Gpr126 is required autonomously in Schwann cells for myelination. In gpr126 mutants, Schwann cells failed to express oct6 and krox20 and were arrested at the promyelinating stage. Elevation of cAMP in gpr126 mutants, but not krox20 mutants, could restore myelination. We propose that Gpr126 drives the differentiation of promyelinating Schwann cells by elevating cAMP levels, thereby triggering Oct6 expression and myelination.

1 Department of Developmental Biology, Stanford University School of Medicine, Stanford, CA 94305, USA.
2 Howard Hughes Medical Institute and Division of Basic Science, Fred Hutchinson Cancer Research Center, Seattle, WA 98109, USA.

* To whom correspondence should be addressed. E-mail: william.talbot{at}stanford.edu

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