TY - JOUR
T1 - Teneurin-4 is a novel regulator of oligodendrocyte differentiation and myelination of small-diameter axons in the CNS
AU - Suzuki, Nobuharu
AU - Fukushi, Masaya
AU - Kosaki, Keisuke
AU - Doyle, Andrew D.
AU - de Vega, Susana
AU - Yoshizaki, Keigo
AU - Akazawa, Chihiro
AU - Arikawa-Hirasawa, Eri
AU - Yamada, Yoshihiko
PY - 2012/8/22
Y1 - 2012/8/22
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=84865251304&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84865251304&partnerID=8YFLogxK
U2 - 10.1523/JNEUROSCI.2045-11.2012
DO - 10.1523/JNEUROSCI.2045-11.2012
M3 - Article
C2 - 22915103
AN - SCOPUS:84865251304
VL - 32
SP - 11586
EP - 11599
JO - Journal of Neuroscience
JF - Journal of Neuroscience
SN - 0270-6474
IS - 34
ER -