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

• Published in: Science (American Association for the Advancement of Science) Vol. 325; no. 5946; pp. 1402 - 1405
• Main Authors: Monk, Kelly R, Naylor, Stephen G, Glenn, Thomas D, Mercurio, Sara, Perlin, Julie R, Dominguez, Claudia, Moens, Cecilia B, Talbot, William S
• Format: Journal Article
• Language: English
• Published: Washington, DC American Association for the Advancement of Science 11.09.2009; The American Association for the Advancement of Science
• Subjects: Animals; Axons; Axons - physiology; Axons - ultrastructure; Biological and medical sciences; Cell Differentiation; Cell differentiation, maturation, development, hematopoiesis; Cell physiology; Cellular biology; Cyclic AMP - metabolism; Cyclic AMP-Dependent Protein Kinases - metabolism; Danio rerio; Early Growth Response Protein 2 - genetics; Early Growth Response Protein 2 - metabolism; Embryo, Nonmammalian - cytology; Embryo, Nonmammalian - metabolism; Embryos; Fish; Fundamental and applied biological sciences. Psychology; Gene expression; Larvae; Lateral Line System - innervation; Messenger RNA; Molecular and cellular biology; Molecular Sequence Data; Mutation; Myelin; Myelin Basic Protein - metabolism; Myelin Sheath - physiology; Myelination; Nerves; Nervous system; Neuregulin-1 - metabolism; Neurons; Octamer Transcription Factor-6 - genetics; Octamer Transcription Factor-6 - metabolism; Proteins; Receptor, ErbB-3 - genetics; Receptor, ErbB-3 - metabolism; Receptors; Receptors, G-Protein-Coupled - genetics; Receptors, G-Protein-Coupled - metabolism; Schwann cells; Schwann Cells - cytology; Schwann Cells - metabolism; Signal Transduction; Zebrafish - embryology; Zebrafish - genetics; Zebrafish - growth & development; Zebrafish - metabolism; Zebrafish Proteins - genetics; Zebrafish Proteins - metabolism; Vertebrata; Brachydanio rerio; Myelination; Schwann cell; Myelin; G protein coupled receptor; Pisces; Cell differentiation
• ISSN: 0036-8075; 1095-9203
• DOI: 10.1126/science.1173474

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.