Wnt/Rspondin/β-catenin signals control axonal sorting and lineage progression in Schwann cell development

• Published in: Proceedings of the National Academy of Sciences - PNAS 2013-11, Vol.110 (45), p.18174-18179
• Main Authors: Grigoryan, Tamara, Stein, Simone, Qi, Jingjing, Wende, Hagen, Garratt, Alistair N., Nave, Klaus-Armin, Birchmeier, Carmen, Birchmeier, Walter
• Format: Article
• Language: English
• Subjects: Animals; Axons; Axons - physiology; beta Catenin - genetics; beta Catenin - metabolism; Biological Sciences; Blotting, Western; cell cycle; Cell Lineage - physiology; DNA Primers - genetics; Flow Cytometry; Genetic mutation; In Situ Hybridization; ligands; Mice; Mice, Transgenic; Microarray Analysis; mutation; Mutation - genetics; Myelination; Nerves; Neuroglia; Neurons; Neuroscience; Paracrine Communication - physiology; Pseudopodia; Real-Time Polymerase Chain Reaction; Schwann cells; Schwann Cells - physiology; Sciatic Nerve - physiology; Sciatic Nerve - ultrastructure; Stem cells; Thrombospondins - metabolism; Wnt Signaling Pathway - physiology
• ISSN: 0027-8424; 1091-6490
• DOI: 10.1073/pnas.1310490110

During late Schwann cell development, immature Schwann cells segregate large axons from bundles, a process called “axonal radial sorting.” Here we demonstrate that canonical Wnt signals play a critical role in radial sorting and assign a role to Wnt and Rspondin ligands in this process. Mice carrying β-catenin loss-of-function mutations show a delay in axonal sorting; conversely, gain-of-function mutations result in accelerated sorting. Sorting deficits are accompanied by abnormal process extension, differentiation, and aberrant cell cycle exit of the Schwann cells. Using primary cultured Schwann cells, we analyze the upstream effectors, Wnt and Rspondin ligands that initiate signaling, and downstream genetic programs that mediate the Wnt response. Our analysis contributes to a better understanding of the mechanisms of Schwann cell development and fate decisions.