Trans-regulation of oligodendrocyte myelination by neurons through small GTPase Arf6-regulated secretion of fibroblast growth factor-2

Masahiro Akiyama, Hiroshi Hasegawa, Tsunaki Hongu, Michael A. Frohman, Akihiro Harada, Hiroyuki Sakagami and Yasunori Kanaho ()
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Masahiro Akiyama: Faculty of Medicine, Graduate School of Comprehensive Human Sciences, University of Tsukuba, 1-1-1 Tennodai, Tsukuba, Ibaraki 305-8575, Japan
Hiroshi Hasegawa: Faculty of Medicine, Graduate School of Comprehensive Human Sciences, University of Tsukuba, 1-1-1 Tennodai, Tsukuba, Ibaraki 305-8575, Japan
Tsunaki Hongu: Faculty of Medicine, Graduate School of Comprehensive Human Sciences, University of Tsukuba, 1-1-1 Tennodai, Tsukuba, Ibaraki 305-8575, Japan
Michael A. Frohman: Center for Developmental Genetics, Stony Brook University
Akihiro Harada: Graduate School of Medicine, Osaka University
Hiroyuki Sakagami: Kitasato University School of Medicine
Yasunori Kanaho: Faculty of Medicine, Graduate School of Comprehensive Human Sciences, University of Tsukuba, 1-1-1 Tennodai, Tsukuba, Ibaraki 305-8575, Japan

Nature Communications, 2014, vol. 5, issue 1, 1-8

Abstract: Abstract The small G protein ADP-ribosylation factor 6 (Arf6) plays important roles in a wide variety of membrane dynamics-based cellular events such as neurite outgrowth and spine formation in vitro. However, little is known about physiological function of Arf6 in vivo. Here we generate conditional knockout mice lacking Arf6 in neurons, oligodendrocytes, or both cell lineages, and unexpectedly find that Arf6 expression in neurons, but not in oligodendrocytes, is crucial for oligodendrocyte myelination in the hippocampal fimbria and the corpus callosum during development, and that this is through the regulation of secretion of fibroblast growth factor-2, a guidance factor for migration of oligodendrocyte precursor cells (OPCs). These results suggest that Arf6 in neurons plays an important role in OPC migration through regulation of FGF-2 secretion during neuronal development.

Date: 2014
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DOI: 10.1038/ncomms5744

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