title: Wnt/Rspondin/β-catenin signals control axonal sorting and lineage progression in Schwann cell development.
abstract: 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.
authors.affiliation: Cancer Research Program and Neuroscience Program, Max Delbrück Center for Molecular Medicine, 13125 Berlin, Germany.
authors.forename: Tamara
authors.initials: T
authors.lastname: Grigoryan
authors.forename: Simone
authors.initials: S
authors.lastname: Stein
authors.forename: Jingjing
authors.initials: J
authors.lastname: Qi
authors.forename: Hagen
authors.initials: H
authors.lastname: Wende
authors.forename: Alistair N
authors.initials: AN
authors.lastname: Garratt
authors.forename: Klaus-Armin
authors.initials: KA
authors.lastname: Nave
authors.forename: Carmen
authors.initials: C
authors.lastname: Birchmeier
authors.forename: Walter
authors.initials: W
authors.lastname: Birchmeier
mesh_terms: D000818:Animals; D001369:Axons / Q000502:physiology*; D015153:Blotting, Western; D019070:Cell Lineage / Q000502:physiology*; D017931:DNA Primers / Q000235:genetics; D005434:Flow Cytometry; D017403:In Situ Hybridization; D051379:Mice; D008822:Mice, Transgenic; D046228:Microarray Analysis; D009154:Mutation / Q000235:genetics; D019899:Paracrine Communication / Q000502:physiology; D060888:Real-Time Polymerase Chain Reaction; D012583:Schwann Cells / Q000502:physiology*; D012584:Sciatic Nerve / Q000502:physiology / Q000648:ultrastructure; D019699:Thrombospondins / Q000378:metabolism*; D060449:Wnt Signaling Pathway / Q000502:physiology*; D051176:beta Catenin / Q000235:genetics / Q000378:metabolism*
chemical_list: D017931:DNA Primers; C518903:RSPO1 protein, mouse; D019699:Thrombospondins; D051176:beta Catenin
keywords: Axin2-LacZ reporter mice; Lgr5 receptor; lamellipodia; myelination; paracrine mechanism