Journal
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
Volume 110, Issue 45, Pages 18174-18179Publisher
NATL ACAD SCIENCES
DOI: 10.1073/pnas.1310490110
Keywords
Axin2-LacZ reporter mice; paracrine mechanism; lamellipodia; myelination; Lgr5 receptor
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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 beta-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.
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