Journal article
An HMGA2-IGF2BP2 Axis Regulates Myoblast Proliferation and Myogenesis
Developmental cell, Vol.23(6), pp.1176-1188
12/11/2012
DOI: 10.1016/j.devcel.2012.10.019
PMID: 23177649
Abstract
A group of genes that are highly and specifically expressed in proliferating skeletal myoblasts during myogenesis was identified. Expression of one of these genes, Hmga2, increases coincident with satellite cell activation, and later its expression significantly declines correlating with fusion of myoblasts into myotubes. Hmga2 knockout mice exhibit impaired muscle development and reduced myoblast proliferation, while overexpression of HMGA2 promotes myoblast growth. This perturbation in proliferation can be explained by the finding that HMGA2 directly regulates the RNA-binding protein IGF2BP2. Add-back of IGF2BP2 rescues the phenotype. IGF2BP2 in turn binds to and controls the translation of a set of mRNAs, including c-myc, Sp1, and Igf1r. These data demonstrate that the HMGA2-IGF2BP2 axis functions as a key regulator of satellite cell activation and therefore skeletal muscle development.
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► HMGA2 expression is required for normal myoblast proliferation ► Hmga2 knockout mice are deficient in skeletal muscle growth and development ► HMGA2 directly regulates the transcription of Igf2bp2 ► IGF2BP2 promotes myoblast growth, likely via translation of c-Myc, IGF1R, and/or Sp1
Li et al. find that the transcription factor HMGA2 is specifically expressed during muscle satellite stem cell activation and contributes to this process by activating the target gene Igf2bp2. IGF2BP2 (also known as IMP2) in turn promotes the translation of mRNAs important for myoblast growth and proliferation.
Details
- Title: Subtitle
- An HMGA2-IGF2BP2 Axis Regulates Myoblast Proliferation and Myogenesis
- Creators
- Zhizhong Li - Novartis Institutes for Biomedical Research, Cambridge, MA 02139, USAJason A Gilbert - Novartis Institutes for Biomedical Research, Cambridge, MA 02139, USAYunyu Zhang - Novartis Institutes for Biomedical Research, Cambridge, MA 02139, USAMinsi Zhang - Department of Pharmacology and Cancer Biology, Duke University Medical Center, Durham, NC 27710, USAQiong Qiu - Department of Radiation Oncology, Duke University Medical Center, Durham, NC 27710, USAKrishnan Ramanujan - Novartis Institutes for Biomedical Research, Cambridge, MA 02139, USATea Shavlakadze - Novartis Institutes for Biomedical Research, Cambridge, MA 02139, USAJohn K Eash - Novartis Institutes for Biomedical Research, Cambridge, MA 02139, USAAnnarita Scaramozza - Center of Regenerative Medicine, Massachusetts General Hospital and Harvard Stem Cell Institute, Harvard University, Boston, MA 02114, USAMatthew M Goddeeris - Howard Hughes Medical Institute, Senator Paul D. Wellstone Muscular Dystrophy Cooperative Research Center Department of Molecular Physiology and Biophysics, Department of Neurology, and Department of Internal Medicine, Roy J. and Lucille A. Carver College of Medicine, The University of Iowa, Iowa City, IA 52242, USADavid G Kirsch - Department of Pharmacology and Cancer Biology, Duke University Medical Center, Durham, NC 27710, USAKevin P Campbell - Howard Hughes Medical Institute, Senator Paul D. Wellstone Muscular Dystrophy Cooperative Research Center Department of Molecular Physiology and Biophysics, Department of Neurology, and Department of Internal Medicine, Roy J. and Lucille A. Carver College of Medicine, The University of Iowa, Iowa City, IA 52242, USAAndrew S Brack - Center of Regenerative Medicine, Massachusetts General Hospital and Harvard Stem Cell Institute, Harvard University, Boston, MA 02114, USADavid J Glass - Novartis Institutes for Biomedical Research, Cambridge, MA 02139, USA
- Resource Type
- Journal article
- Publication Details
- Developmental cell, Vol.23(6), pp.1176-1188
- Publisher
- Elsevier Inc
- DOI
- 10.1016/j.devcel.2012.10.019
- PMID
- 23177649
- ISSN
- 1534-5807
- eISSN
- 1878-1551
- Language
- English
- Date published
- 12/11/2012
- Academic Unit
- Neurology; Molecular Physiology and Biophysics; Iowa Neuroscience Institute
- Record Identifier
- 9984020890502771
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