title: Coordinate control of axon defasciculation and myelination by laminin-2 and -8.
abstract: Schwann cells form basal laminae (BLs) containing laminin-2 (Ln-2; heterotrimer alpha2beta1gamma1) and Ln-8 (alpha4beta1gamma1). Loss of Ln-2 in humans and mice carrying alpha2-chain mutations prevents developing Schwann cells from fully defasciculating axons, resulting in partial amyelination. The principal pathogenic mechanism is thought to derive from structural defects in Schwann cell BLs, which Ln-2 scaffolds. However, we found loss of Ln-8 caused partial amyelination in mice without affecting BL structure or Ln-2 levels. Combined Ln-2/Ln-8 deficiency caused nearly complete amyelination, revealing Ln-2 and -8 together have a dominant role in defasciculation, and that Ln-8 promotes myelination without BLs. Transgenic Ln-10 (alpha5beta1gamma1) expression also promoted myelination without BL formation. Rather than BL structure, we found Ln-2 and -8 were specifically required for the increased perinatal Schwann cell proliferation that attends myelination. Purified Ln-2 and -8 directly enhanced in vitro Schwann cell proliferation in collaboration with autocrine factors, suggesting Lns control the onset of myelination by modulating responses to mitogens in vivo.
authors.affiliation: Center for Research on Occupational and Environmental Toxicology, Oregon Health and Science University, Portland, OR 97239, USA.
authors.forename: Dongren
authors.initials: D
authors.lastname: Yang
authors.forename: Jesse
authors.initials: J
authors.lastname: Bierman
authors.forename: Yukie S
authors.initials: YS
authors.lastname: Tarumi
authors.forename: Yong-Ping
authors.initials: YP
authors.lastname: Zhong
authors.forename: Reshma
authors.initials: R
authors.lastname: Rangwala
authors.forename: Thomas M
authors.initials: TM
authors.lastname: Proctor
authors.forename: Yuko
authors.initials: Y
authors.lastname: Miyagoe-Suzuki
authors.forename: Shin'ichi
authors.initials: S
authors.lastname: Takeda
authors.forename: Jeffrey H
authors.initials: JH
authors.lastname: Miner
authors.forename: Larry S
authors.initials: LS
authors.lastname: Sherman
authors.forename: Bruce G
authors.initials: BG
authors.lastname: Gold
authors.forename: Bruce L
authors.initials: BL
authors.lastname: Patton
mesh_terms: D000818:Animals; D001369:Axons / Q000378:metabolism* / Q000473:pathology; D001485:Basement Membrane / Q000378:metabolism* / Q000473:pathology; D001522:Behavior, Animal; D002448:Cell Adhesion / Q000502:physiology; D049109:Cell Proliferation; D002478:Cells, Cultured; D002490:Central Nervous System / Q000378:metabolism / Q000473:pathology; D006801:Humans; D007797:Laminin / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D008822:Mice, Transgenic; D009186:Myelin Sheath / Q000378:metabolism* / Q000473:pathology; D051381:Rats; D012583:Schwann Cells / Q000378:metabolism* / Q000473:pathology
chemical_list: D007797:Laminin