Pre-myelinating oligodendrocyte ADGRG1 is required for axon ensheathment and CNS myelin formation
Year: 2026
Type: preprint
Abstract: Myelin is essential for axonal health and rapid propagation of action potentials. In the central nervous system (CNS), myelination is initiated with axon ensheathment by pre-myelinating oligodendrocytes (preOLs), followed by iterative membrane wrapping and longitudinal extension along the axon. The molecular mechanisms that govern preOL development remain largely unknown. In this study, we identify the adhesion G protein-coupled receptor ADGRG1 (also called GPR56) as a key, evolutionarily conserved regulator of this process. We show that ADGRG1 is highly expressed in preOLs and that its conditional deletion in mouse preOLs leads to simplified preOL morphology and defective axon ensheathment, resulting in CNS hypomyelination. Live imaging in zebrafish demonstrated conserved function of Adgrg1 in axon ensheathment. Mechanistically, we show that ADGRG1 promotes preOL maturation by RhoA activation. Collectively, these findings reveal an ADGRG1-mediated RhoA signaling pathway that governs axon ensheathment and myelin formation.
Language: English
Subfield: Developmental Neuroscience
Field: Neuroscience
Domain: Life Sciences
Open Access status: green
Awards: Adhesion GPCR interactome landscaping by in vivo biotinylation proteomics, Regulation of node of Ranvier formation and maintenance by astrocytes, Glial Mechanisms Of Developmental Synapse Refinement, The role of P/Q-type channels in oligodendrocyte lineage cell development, Adhesion G Protein-Coupled Receptors in CNS Development and Regeneration
OpenAlex ID: W7125836701