Teneurin-4 Is a Novel Regulator of Oligodendrocyte Differentiation and Myelination of Small-Diameter Axons in the CNS

Abstract

Myelination is essential for proper functioning of the central nervous system (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 peripheral nervous system (PNS). In the spinal cord of the furue mice, myelination of small diameter axons was dramatically reduced and differentiation of oligodendrocytes, the myelin-forming cells in the CNS, was inhibited. We subsequently found that the furue mutation was associated with a transgene insertion into the teneurin-4 (Ten-4/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 following suppression of Ten-4 expression by shRNA. Further, Ten-4 positively regulated focal adhesion kinase (FAK), 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.

Muscle Satellite Cell Protein Teneurin-4 Regulates Differentiation During Muscle Regeneration

“…For analyses of the Ten‐4 function in satellite cells, we used the furue ( fur ) mutant mouse line whose Ten‐4 expression is absent because of a transgene insertion in the Ten‐4 gene ( Odz4 / Tenm4 ) 23. The mutant fur / fur mice are hereafter referred to as Ten‐4−/− mice.…”

“…Adhesion to the basement membrane and the myofiber plasma membrane is crucial for the quiescence of satellite cells in their niche 28. We have previously reported that Ten‐4 regulates the activation of focal adhesion kinase, a critical downstream molecule of integrins and dystroglycan, in neural and glial cells 23, 28, 29. Therefore, Ten‐4 may play a key role in satellite cells at the quiescent state together with these proteins.…”

Latrophilins Function as Heterophilic Cell-adhesion Molecules by Binding to Teneurins

“…In mice, deletions of teneurin-3 result in impairments of axonal guidance in the visual system and cause mistargeting of axons from the retina to the geniculate nucleus and the superior colliculus (18,19). In contrast, deletions of teneurin-4 impair oligodendrocyte differentiation and myelination (20). In Drosophila, conversely, teneurin mutations produce a defect in motor axon guidance, although overexpression studies suggested a role for teneurins in target selection during synaptogenesis (8,9).…”

Bipolar Bozukluğun Genetik Altyapıs

“…Teneurin proteinlerinin hücre haberleşmesinde ve oligodentrosit diferensiasyonu, santral sinir sistemindeki sinirlerin miyelinizasyonu gibi kritik roller oynadığına dair çalışmalar literatür çalışmaları yayınlanmaya başlamıştır (22).…”