YAP functions as a mechanotransducer in oligodendrocyte morphogenesis and maturation.
Oligodendrocytes (OLs) are myelinating cells of the central nervous system. Recent studies have shown that mechanical factors influence various cell properties. Mechanical stimuli can be transduced into intracellular biochemical signals through mechanosensors and intracellular mechanotransducers, such as YAP. However, the molecular mechanisms underlying mechanical regulation of OLs by YAP remain unknown. We found that OL morphology and interactions between OLs and neuronal axons were affected by knocking down YAP. Mechanical stretching of OL precursor cells induced nuclear YAP accumulation and assembly of focal adhesion, key platforms for mechanotransduction. Shear stress decreased the number of OL processes, whereas a dominant-negative form of YAP suppressed these effects. To investigate the roles of YAP in postnatal OLs in vivo, we constructed a novel YAP knock-in mouse and found that in vivo overexpression of YAP widely affected OL maturation. These results indicate that YAP regulates OL morphology and maturation in response to mechanical factors. GLIA 2017;65:360-374.
Division of Neurobiology and Bioinformatics, National Institute for Physiological Sciences, Okazaki, Aichi, 444-8787, Japan.|Department of Physiological Sciences, School of Life Sciences, SOKENDAI, (The Graduate University for Advanced Studies), Okazaki, Aichi, 444-8585, Japan.
Takeshi
T
Shimizu
Division of Neurobiology and Bioinformatics, National Institute for Physiological Sciences, Okazaki, Aichi, 444-8787, Japan.|Department of Physiological Sciences, School of Life Sciences, SOKENDAI, (The Graduate University for Advanced Studies), Okazaki, Aichi, 444-8585, Japan.
Yasuyuki
0000-0001-7285-7546
Y
Osanai
Department of Neuropsychiatry, School of Medicine, Keio University, Tokyo, 160-8582, Japan.
Kenji F
KF
Tanaka
Department of Cellular Neurobiology, Brain Research Institute, Niigata University, Niigata, Japan.
Manabu
M
Abe
Department of Cellular Neurobiology, Brain Research Institute, Niigata University, Niigata, Japan.
Rie
R
Natsume
Department of Cellular Neurobiology, Brain Research Institute, Niigata University, Niigata, Japan.
Kenji
K
Sakimura
Division of Neurobiology and Bioinformatics, National Institute for Physiological Sciences, Okazaki, Aichi, 444-8787, Japan.|Department of Physiological Sciences, School of Life Sciences, SOKENDAI, (The Graduate University for Advanced Studies), Okazaki, Aichi, 444-8585, Japan.
Kazuhiro
K
Ikenaka
D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D000831:Animals, Newborn; D002452:Cell Count; D018797:Cell Cycle Proteins; D002454:Cell Differentiation / Q000235:genetics / Q000502:physiology*; D002478:Cells, Cultured; D002540:Cerebral Cortex / Q000166:cytology; D005260:Female; D005727:Ganglia, Spinal / Q000166:cytology; D018507:Gene Expression Regulation, Developmental / Q000235:genetics*; D008297:Male; D040542:Mechanotransduction, Cellular / Q000235:genetics / Q000502:physiology*; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D009024:Morphogenesis / Q000235:genetics / Q000502:physiology*; D018991:Myelin Proteolipid Protein / Q000235:genetics / Q000378:metabolism; D063308:Myelin-Oligodendrocyte Glycoprotein / Q000378:metabolism; D000076104:Oligodendrocyte Transcription Factor 2 / Q000378:metabolism; D009836:Oligodendroglia / Q000378:metabolism*; D009900:Optic Nerve / Q000166:cytology; D010750:Phosphoproteins / Q000235:genetics / Q000378:metabolism*; D051381:Rats; D000091102:YAP-Signaling Proteins
D048868:Adaptor Proteins, Signal Transducing; D018797:Cell Cycle Proteins; D018991:Myelin Proteolipid Protein; D063308:Myelin-Oligodendrocyte Glycoprotein; D000076104:Oligodendrocyte Transcription Factor 2; D010750:Phosphoproteins; D000091102:YAP-Signaling Proteins; C486223:Yap1 protein, mouse
YAP; mechanotransduction; oligodendrocyte