Teneurin-4 is a novel regulator of oligodendrocyte differentiation and myelination of small-diameter axons in the CNS

Nobuharu Suzuki, Masaya Fukushi, Keisuke Kosaki, Andrew D. Doyle, Susana de Vega, Keigo Yoshizaki, Chihiro Akazawa, Eri Arikawa-Hirasawa, Yoshihiko Yamada

Research output: Contribution to journalArticlepeer-review

47 Citations (Scopus)

Abstract

Myelination is essential for proper functioning of the CNS. In this study, we have identified a mouse mutation, designated furue, which causes tremors and hypomyelination in the CNS, particularly in the spinal cord, but not in the sciatic nerve of the PNS. In the spinal cord of the furue mice, myelination of small-diameter axons was dramatically reduced, and differentiation of oligodendrocytes, the myelinforming cells in the CNS, was inhibited.Wesubsequently found that the furue mutation was associated with a transgene insertion into the teneurin-4 (Ten-4, Ten-m4/Odz4) gene, encoding a transmembrane protein of unknown function. Ten-4 was strongly expressed in the spinal cord of wild-type mice and was induced during normal oligodendrocyte differentiation. In contrast, in the furue mice, the expression of Ten-4 was absent. Differentiation and cellular process formation of oligodendrocytes were inhibited in primary cell culture from the furue mice. Cell differentiation and process formation were also inhibited in the oligodendrocyte progenitor cell line CG-4 after suppression of Ten-4 expression by shRNA. Furthermore, Ten-4 positively regulated focal adhesion kinase, an essential signaling molecule for oligodendrocyte process formation and myelination of small-diameter axons. These findings suggest that Ten-4 is a novel regulator of oligodendrocyte differentiation and that it plays a critical role in the myelination of small-diameter axons in the CNS.

Original languageEnglish
Pages (from-to)11586-11599
Number of pages14
JournalJournal of Neuroscience
Volume32
Issue number34
DOIs
Publication statusPublished - Aug 22 2012
Externally publishedYes

All Science Journal Classification (ASJC) codes

  • Neuroscience(all)

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