An HMGA2-IGF2BP2 axis regulates myoblast proliferation and myogenesis

Dev Cell. 2012 Dec 11;23(6):1176-88. doi: 10.1016/j.devcel.2012.10.019. Epub 2012 Nov 21.


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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Differentiation
  • Cell Proliferation
  • Cells, Cultured
  • Down-Regulation
  • Female
  • HMGA2 Protein / metabolism*
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Muscle Development*
  • Muscle, Skeletal / cytology*
  • Muscle, Skeletal / metabolism
  • Muscle, Skeletal / physiology
  • Myoblasts / cytology*
  • Myoblasts / metabolism*
  • Myoblasts / physiology
  • Protein Biosynthesis
  • Proto-Oncogene Proteins c-myc / biosynthesis
  • RNA-Binding Proteins / metabolism*
  • Receptor, IGF Type 1 / biosynthesis
  • Satellite Cells, Skeletal Muscle / metabolism
  • Sp1 Transcription Factor / biosynthesis


  • HMGA2 Protein
  • IGF2BP2 protein, mouse
  • Myc protein, mouse
  • Proto-Oncogene Proteins c-myc
  • RNA-Binding Proteins
  • Sp1 Transcription Factor
  • Receptor, IGF Type 1

Associated data

  • GEO/GSE41907