Regulation of skeletal myogenesis by the mTOR signaling network
type: CreativeWork
description: Skeletal muscle is composed of post-mitotic multinucleated myofibers. During embryonic skeletal myogenesis, cells in somites commit to myogenic lineage and differentiate into myoblasts, which then fuse to form multinucleated myofibers. Post-natal growth, repair, and maintenance of skeletal muscle are dependent on muscle satellite cells, which in response to stimuli differentiate and fuse to form new myofibers. Developmental or post-natal failure of skeletal myogenesis results in diverse muscular dystrophies and atrophies, largely impairing life quality and sometimes directly causing death. The myogenic process is guided by various environmental cues and regulated by distinct signaling pathways, resulting in the activation of specific transcription factors and subsequent reprogramming of gene expression. The mammalian target of rapamycin (mTOR) is a Ser/Thr kinase that controls a wide spectrum of cellular and developmental processes including regulation of skeletal myogenesis. In my dissertation work, I investigate the mechanisms of myogenic regulation, with a focus on the signaling network assembled by mTOR. Various processes of skeletal muscle differentiation and remodeling were known to be inhibited by the mTOR-specific inhibitor, rapamycin. In cultured myoblasts, the target of rapamycin – mTOR – had been reported to regulate differentiation at different stages through distinct mechanisms, including one that is independent of mTOR kinase activity. However, there had been no in vivo evidence to validate those mTOR myogenic mechanisms in vitro. In Chapter II, I show that rapamycin impairs injury-induced muscle regeneration. To validate the role of mTOR with genetic evidence and to probe the mechanism of mTOR function, I have generated and characterized transgenic mice expressing two mutants of mTOR under the control of human skeletal actin (HSA) promoter – rapamycin-resistant (RR) and RR/kinase-inactive (RR/KI) mTOR. My results show that muscle regeneration in rapam…
abstract: Skeletal muscle is composed of post-mitotic multinucleated myofibers. During embryonic skeletal myogenesis, cells in somites commit to myogenic lineage and differentiate into myoblasts, which then fuse to form multinucleated myofibers. Post-natal growth, repair, and maintenance of skeletal muscle are dependent on muscle satellite cells, which in response to stimuli differentiate and fuse to form new myofibers. Developmental or post-natal failure of skeletal myogenesis results in diverse muscular dystrophies and atrophies, largely impairing life quality and sometimes directly causing death. The myogenic process is guided by various environmental cues and regulated by distinct signaling pathways, resulting in the activation of specific transcription factors and subsequent reprogramming of gene expression. The mammalian target of rapamycin (mTOR) is a Ser/Thr kinase that controls a wide spectrum of cellular and developmental processes including regulation of skeletal myogenesis. In my dissertation work, I investigate the mechanisms of myogenic regulation, with a focus on the signaling network assembled by mTOR. Various processes of skeletal muscle differentiation and remodeling were known to be inhibited by the mTOR-specific inhibitor, rapamycin. In cultured myoblasts, the target of rapamycin – mTOR – had been reported to regulate differentiation at different stages through distinct mechanisms, including one that is independent of mTOR kinase activity. However, there had been no in vivo evidence to validate those mTOR myogenic mechanisms in vitro. In Chapter II, I show that rapamycin impairs injury-induced muscle regeneration. To validate the role of mTOR with genetic evidence and to probe the mechanism of mTOR function, I have generated and characterized transgenic mice expressing two mutants of mTOR under the control of human skeletal actin (HSA) promoter – rapamycin-resistant (RR) and RR/kinase-inactive (RR/KI) mTOR. My results show that muscle regeneration in rapam…
author: Ge, Yejing
language: en
keywords: mTOR, myogenesis, myoblast differentiation, microRNA, miRNA, mammalian target of rapamycin (mTOR), Ribonucleic acid (RNA)
date published: 2012-06-27T21:30:20Z
date modified: 2026-07-22T22:25:30Z
provider: University of Illinois - Urbana-Champaign
publisher: Networked Digital Library of Theses and Dissertations
type: WebPage
source organization: University of Illinois at Urbana-Champaign

PropertyValue
property ID: Handle
value: http://hdl.handle.net/2142/32047