ArticleDevelopment (Cambridge, England)2013
Analysis of Gpr126 function defines distinct mechanisms controlling the initiation and maturation of myelin.
Article in Development (Cambridge, England), 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 59 papers.
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Who cites it
59 citing papers in PubMed, 86 citations in OpenAlex.
- Beyond Neurodegeneration: White Matter Vacuolation as a Primary Myelin Defect.International journal of molecular sciences · 2026Review
- Oligodendrocyte Piezo2 is a regulator of age-dependent myelin integrity and dysregulated in multiple sclerosis.Communications biology · 2026Article
- Adhesion G-Protein Coupled Receptors in Neurological and Psychiatric Disorders.Journal of psychiatry and brain science · 2025Article
- Exploring the presence of the GPR126 single nucleotide polymorphism (rs536714306) in periodontal patients of European ancestry.BMC research notes · 2025Article
- Schwann cells in the inner ear: development, disease, and regeneration.Frontiers in cellular neuroscience · 2025Review
- Identification of a novel prognostic marker ADGRG6 in pancreatic adenocarcinoma: multi-omics analysis and experimental validation.Frontiers in immunology · 2025Article
- Structure, ligands, and roles of GPR126/ADGRG6 in the development and diseases.Genes & diseases · 2024Review
- Genetic Variants in the Adhesive G Protein-Coupled Receptor ADGRG6 are Associated with Increased Susceptibility to COPD in the Elderly Han Chinese Population of Southern China.International journal of chronic obstructive pulmonary disease · 2024Article
- A screen of pharmacologically active compounds to identify modulators of the Adgrg6/Gpr126 signalling pathway in zebrafish embryos.Basic & clinical pharmacology & toxicology · 2023Article
- Noncoding SNP at rs1663689 represses ADGRG6 via interchromosomal interaction and reduces lung cancer progression.EMBO reports · 2023Article
- Review
- Adhesion G protein-coupled receptor Gpr126/Adgrg6 is essential for placental development.Science advances · 2021Article
- Myelin Biology.Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics · 2021Review
- Schwann cell interactions during the development of the peripheral nervous system.Developmental neurobiology · 2021Review
- GPR126 regulates colorectal cancer cell proliferation by mediating HDAC2 and GLI2 expression.Cancer science · 2021Article
- The adhesion GPCR Adgrg6 (Gpr126): Insights from the zebrafish model.Genesis (New York, N.Y. : 2000) · 2021Review
- Adhesion GPCRs as a paradigm for understanding polycystin-1 G protein regulation.Cellular signalling · 2020Review
- Article
- Regulation of body length and bone mass by Gpr126/Adgrg6.Science advances · 2020Article
- Brain Dysfunction in LAMA2-Related Congenital Muscular Dystrophy: Lessons From Human Case Reports and Mouse Models.Frontiers in molecular neuroscience · 2020Article
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Authors and funding
2 authors at 1 institution in 1 country.
Funding
Abstract
In peripheral nerves, Schwann cells form the myelin sheath, which allows the efficient propagation of action potentials along axons. The transcription factor Krox20 regulates the initiation of myelination in Schwann cells and is also required to maintain mature myelin. The adhesion G protein-coupled receptor (GPCR) Gpr126 is essential for Schwann cells to initiate myelination, but previous studies have not addressed the role of Gpr126 signaling in myelin maturation and maintenance. Through analysis of Gpr126 in zebrafish, we define two distinct mechanisms controlling the initiation and maturation of myelin. We show that gpr126 mutant Schwann cells elaborate mature myelin sheaths and maintain krox20 expression for months, provided that the early signaling defect is bypassed by transient elevation of cAMP. At the onset of myelination, Gpr126 and protein kinase A (PKA) function as a switch that allows Schwann cells to initiate krox20 expression and myelination. After myelination is initiated, krox20 expression is maintained and myelin maturation proceeds independently of Gpr126 signaling. Transgenic analysis indicates that the Krox20 cis-regulatory myelinating Schwann cell element (MSE) becomes active at the onset of myelination and that this activity is dependent on Gpr126 signaling. Activity of the MSE declines after initiation, suggesting that other elements are responsible for maintaining krox20 expression in mature nerves. We also show that elevated cAMP does not initiate myelination in the absence of functional Neuregulin 1 (Nrg1) signaling. These results indicate that the mechanisms regulating the initiation of myelination are distinct from those mediating the maturation and maintenance of myelin.
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