A G protein-coupled receptor is essential for Schwann cells to initiate myelination.
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.
Monk
Kelly R
KR
Department of Developmental Biology, Stanford University School of Medicine, Stanford, CA 94305, USA.
Naylor
Stephen G
SG
Glenn
Thomas D
TD
Mercurio
Sara
S
Perlin
Julie R
JR
Dominguez
Claudia
C
Moens
Cecilia B
CB
Talbot
William S
WS
D000818:Animals; D001369:Axons / Q000502:physiology / Q000648:ultrastructure; D002454:Cell Differentiation; D000242:Cyclic AMP / Q000378:metabolism; D017868:Cyclic AMP-Dependent Protein Kinases / Q000378:metabolism; D051767:Early Growth Response Protein 2 / Q000235:genetics / Q000378:metabolism; D004625:Embryo, Nonmammalian / Q000166:cytology / Q000378:metabolism; D053403:Lateral Line System / Q000294:innervation; D008969:Molecular Sequence Data; D009154:Mutation; D004676:Myelin Basic Protein / Q000378:metabolism; D009186:Myelin Sheath / Q000502:physiology*; D020890:Neuregulin-1 / Q000378:metabolism; D050816:Octamer Transcription Factor-6 / Q000235:genetics / Q000378:metabolism; D020893:Receptor, ErbB-3 / Q000235:genetics / Q000378:metabolism; D043562:Receptors, G-Protein-Coupled / Q000235:genetics / Q000378:metabolism*; D012583:Schwann Cells / Q000166:cytology / Q000378:metabolism*; D015398:Signal Transduction; D015027:Zebrafish / Q000196:embryology / Q000235:genetics / Q000254:growth & development / Q000378:metabolism*; D029961:Zebrafish Proteins / Q000235:genetics / Q000378:metabolism*
D051767:Early Growth Response Protein 2; D004676:Myelin Basic Protein; D020890:Neuregulin-1; D043562:Receptors, G-Protein-Coupled; D029961:Zebrafish Proteins; C543742:stx7l protein, zebrafish; D050816:Octamer Transcription Factor-6; D000242:Cyclic AMP; D020893:Receptor, ErbB-3; D017868:Cyclic AMP-Dependent Protein Kinases