title: Adenomatous polyposis coli regulates radial axonal sorting and myelination in the PNS.
abstract: The tumor suppressor protein adenomatous polyposis coli (APC) is multifunctional - it participates in the canonical Wnt/β-catenin signal transduction pathway as well as modulating cytoskeleton function. Although APC is expressed by Schwann cells, the role that it plays in these cells and in the myelination of the peripheral nervous system (PNS) is unknown. Therefore, we used the Cre-lox approach to generate a mouse model in which APC expression is specifically eliminated from Schwann cells. These mice display hindlimb weakness and impaired axonal conduction in sciatic nerves. Detailed morphological analyses revealed that APC loss delays radial axonal sorting and PNS myelination. Furthermore, APC loss delays Schwann cell differentiation in vivo, which correlates with persistent activation of the Wnt signaling pathway and results in perturbed extension of Schwann cell processes and disrupted lamellipodia formation. In addition, APC-deficient Schwann cells display a transient diminution of proliferative capacity. Our data indicate that APC is required by Schwann cells for their timely differentiation to mature, myelinating cells and plays a crucial role in radial axonal sorting and PNS myelination.
authors.affiliation: Department of Neurology, Center for Peripheral Neuropathy, University of Chicago, Chicago, IL 60637, USA.
authors.forename: Benayahu
authors.initials: B
authors.lastname: Elbaz
authors.affiliation: Department of Neurology, Center for Peripheral Neuropathy, University of Chicago, Chicago, IL 60637, USA.
authors.forename: Maria
authors.initials: M
authors.lastname: Traka
authors.affiliation: Department of Neurology, Center for Peripheral Neuropathy, University of Chicago, Chicago, IL 60637, USA.
authors.forename: Rejani B
authors.initials: RB
authors.lastname: Kunjamma
authors.affiliation: Department of Neurology, Center for Peripheral Neuropathy, University of Chicago, Chicago, IL 60637, USA.
authors.forename: Danuta
authors.initials: D
authors.lastname: Dukala
authors.affiliation: Stanford University School of Medicine, Department of Neurobiology, Fairchild Building Room D235, 299 Campus Drive, Stanford, CA 94305-5125, USA.
authors.forename: Amanda
authors.initials: A
authors.lastname: Brosius Lutz
authors.affiliation: UNC Neuroscience Center and the Department of Cell and Molecular Physiology, University of North Carolina School of Medicine, Chapel Hill, NC 27599, USA.
authors.forename: E S
authors.initials: ES
authors.lastname: Anton
authors.affiliation: Stanford University School of Medicine, Department of Neurobiology, Fairchild Building Room D235, 299 Campus Drive, Stanford, CA 94305-5125, USA.
authors.forename: Ben A
authors.initials: BA
authors.lastname: Barres
authors.affiliation: Department of Neurology, Center for Peripheral Neuropathy, University of Chicago, Chicago, IL 60637, USA.
authors.forename: Betty
authors.initials: B
authors.lastname: Soliven
authors.affiliation: Department of Neurology, Center for Peripheral Neuropathy, University of Chicago, Chicago, IL 60637, USA bpopko@uchicago.edu.
authors.forename: Brian
authors.identifier: 0000-0001-9948-2553
authors.initials: B
authors.lastname: Popko
mesh_terms: D025601:Adenomatous Polyposis Coli Protein / Q000378:metabolism*; D000818:Animals; D001369:Axons / Q000378:metabolism*; D002454:Cell Differentiation / Q000235:genetics; D006614:Hindlimb / Q000473:pathology; D019426:Integrases / Q000378:metabolism; D051379:Mice; D009186:Myelin Sheath / Q000378:metabolism*; D017933:Peripheral Nervous System / Q000378:metabolism*; D011554:Pseudopodia / Q000378:metabolism; D012583:Schwann Cells / Q000166:cytology / Q000378:metabolism; D012584:Sciatic Nerve / Q000378:metabolism; D060449:Wnt Signaling Pathway / Q000235:genetics
chemical_list: D025601:Adenomatous Polyposis Coli Protein; C000613192:adenomatous polyposis coli protein, mouse; C045073:Cre recombinase; D019426:Integrases
keywords: Adenomatous polyposis coli; PNS; Radial axonal sorting; Schwann cells; Wnt signaling