MTORC1 Signaling Promotes Limb Bud Cell Growth and Chondrogenesis. Issue 4 (29th December 2016)

• Record Type: Journal Article
• Authors: Jiang, Ming; Fu, Xuejie; Yang, Huilin; Long, Fanxin; Chen, Jianquan
• Is Part Of: Journal of cellular biochemistry. Volume 118:Issue 4(2017)
• Page Start: 748
• Page End: 753
• Publication Date: 2016-12-29
• Subjects: mTORC1 -- RAPTOR -- CHONDROGENESIS -- CELL SIZE; Cytochemistry -- Periodicals; 572
• DOI: 10.1002/jcb.25728
• Languages: English
• ISSNs: 0730-2312

Abstract

ABSTRACT: mTORC1 signaling has been shown to promote limb skeletal growth through stimulation of protein synthesis in chondrocytes. However, potential roles of mTORC1 in prechondrogenic mesenchyme have not been explored. In this study, we first deleted Raptor, a unique and essential component of mTORC1, in prechondrogenic limb mesenchymal cells. Deletion of Raptor reduced the size of limb bud cells, resulting in overall diminution of the limb bud without affecting skeletal patterning. We then examined the potential role of mTORC1 in chondrogenic differentiation in vitro. Both pharmacological and genetic disruption of mTORC1 significantly suppressed the number and size of cartilage nodules in micromass cultures of limb bud mesenchymal cells. Similarly, inhibition of mTORC1 signaling in chondrogenic ATDC5 cells greatly impaired cartilage nodule formation, and decreased the expression of the master transcriptional factor Sox9, along with the cartilage matrix genes Acan and Col2a1 . Thus, we have identified an important role for mTORC1 signaling in promoting limb mesenchymal cell growth and chondrogenesis during embryonic development. J. Cell. Biochem. 118: 748–753, 2017. © 2016 Wiley Periodicals, Inc. Abstract : By employing both genetic and pharmacological approaches to disrupt mTORC1 signaling, we provided direct evidence that mTORC1 promotes limb bud cell growth and chondrogenesis.