Coordinate control of axon defasciculation and myelination by laminin-2 and -8

Dongren Yang, Jesse Bierman, Yukie S. Tarumi, Yong Ping Zhong, Reshma Rangwala, Thomas M. Proctor, Yuko Miyagoe-Suzuki, Shin'Ichi Takeda, Jeffrey H. Miner, Larry S. Sherman, Bruce G. Gold, Bruce L. Patton

Research output: Contribution to journalArticle

119 Scopus citations

Abstract

Schwann cells form basal laminae (BLs) containing laminin-2 (Ln-2; heterotrimer α2β1γ1) and Ln-8 (α4β1γ1). Loss of Ln-2 in humans and mice carrying α2-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 (α5β1γ1) 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.

Original languageEnglish (US)
Pages (from-to)655-666
Number of pages12
JournalJournal of Cell Biology
Volume168
Issue number4
DOIs
StatePublished - Feb 14 2005

ASJC Scopus subject areas

  • Cell Biology

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    Yang, D., Bierman, J., Tarumi, Y. S., Zhong, Y. P., Rangwala, R., Proctor, T. M., Miyagoe-Suzuki, Y., Takeda, SI., Miner, J. H., Sherman, L. S., Gold, B. G., & Patton, B. L. (2005). Coordinate control of axon defasciculation and myelination by laminin-2 and -8. Journal of Cell Biology, 168(4), 655-666. https://doi.org/10.1083/jcb.200411158