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Title: Translational Control of Sox9 RNA by mTORC1 Contributes to Skeletogenesis
Authors: Iezaki, Takashi
Horie, Tetsuhiro
Fukasawa, Kazuya
Kitabatake, Makoto  kyouindb  KAKEN_id
Nakamura, Yuka
Park, Gyujin
Onishi, Yuki
Ozaki, Kakeru
Kanayama, Takashi
Hiraiwa, Manami
Kitaguchi, Yuka
Kaneda, Katsuyuki
Manabe, Takayuki
Ishigaki, Yasuhito
Ohno, Mutsuhito
Hinoi, Eiichi
Author's alias: 北畠, 真
大野, 睦人
Keywords: mTORC1
translation
Sox9
undifferentiated mesenchymal cells
Issue Date: 10-Jul-2018
Publisher: Elsevier BV
Journal title: Stem Cell Reports
Volume: 11
Issue: 1
Start page: 228
End page: 241
Abstract: The mechanistic/mammalian target of rapamycin complex 1 (mTORC1) regulates cellular function in various cell types. Although the role of mTORC1 in skeletogenesis has been investigated previously, here we show a critical role of mTORC1/4E-BPs/SOX9 axis in regulating skeletogenesis through its expression in undifferentiated mesenchymal cells. Inactivation of Raptor, a component of mTORC1, in limb buds before mesenchymal condensations resulted in a marked loss of both cartilage and bone. Mechanistically, we demonstrated that mTORC1 selectively controls the RNA translation of Sox9, which harbors a 5′ terminal oligopyrimidine tract motif, via inhibition of the 4E-BPs. Indeed, introduction of Sox9 or a knockdown of 4E-BP1/2 in undifferentiated mesenchymal cells markedly rescued the deficiency of the condensation observed in Raptor-deficient mice. Furthermore, introduction of the Sox9 transgene rescued phenotypes of deficient skeletal growth in Raptor-deficient mice. These findings highlight a critical role of mTORC1 in mammalian skeletogenesis, at least in part, through translational control of Sox9 RNA.
Rights: © 2018 The Author(s). This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).
URI: http://hdl.handle.net/2433/232693
DOI(Published Version): 10.1016/j.stemcr.2018.05.020
PubMed ID: 30008325
Appears in Collections:Journal Articles

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