| First Author | Iezaki T | Year | 2018 |
| Journal | Stem Cell Reports | Volume | 11 |
| Issue | 1 | Pages | 228-241 |
| PubMed ID | 30008325 | Mgi Jnum | J:289698 |
| Mgi Id | MGI:6434607 | Doi | 10.1016/j.stemcr.2018.05.020 |
| Citation | Iezaki T, et al. (2018) Translational Control of Sox9 RNA by mTORC1 Contributes to Skeletogenesis. Stem Cell Reports 11(1):228-241 |
| abstractText | 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. |
