Coordinate control of axon defasciculation and myelination by laminin-2 and -8.
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.
Yang
Dongren
D
Center for Research on Occupational and Environmental Toxicology, Oregon Health and Science University, Portland, OR 97239, USA.
Bierman
Jesse
J
Tarumi
Yukie S
YS
Zhong
Yong-Ping
YP
Rangwala
Reshma
R
Proctor
Thomas M
TM
Miyagoe-Suzuki
Yuko
Y
Takeda
Shin'ichi
S
Miner
Jeffrey H
JH
Sherman
Larry S
LS
Gold
Bruce G
BG
Patton
Bruce L
BL
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
D007797:Laminin