An HMGA2-IGF2BP2 Axis Regulates Myoblast Proliferation and Myogenesis
Copyright policy )An HMGA2-IGF2BP2 Axis Regulates Myoblast Proliferation and Myogenesis
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.
- University of Iowa United States
- Harvard University Press United States
- Massachusetts General Hospital United States
- Novartis (Switzerland) Switzerland
- Center for Neuroscience and Regenerative Medicine United States
Mice, Knockout, Satellite Cells, Skeletal Muscle, Sp1 Transcription Factor, HMGA2 Protein, Down-Regulation, RNA-Binding Proteins, Cell Differentiation, Muscle Development, Receptor, IGF Type 1, Mice, Inbred C57BL, Myoblasts, Proto-Oncogene Proteins c-myc, Mice, Protein Biosynthesis, Animals, Female, Muscle, Skeletal, Cells, Cultured, Developmental Biology, Cell Proliferation
Mice, Knockout, Satellite Cells, Skeletal Muscle, Sp1 Transcription Factor, HMGA2 Protein, Down-Regulation, RNA-Binding Proteins, Cell Differentiation, Muscle Development, Receptor, IGF Type 1, Mice, Inbred C57BL, Myoblasts, Proto-Oncogene Proteins c-myc, Mice, Protein Biosynthesis, Animals, Female, Muscle, Skeletal, Cells, Cultured, Developmental Biology, Cell Proliferation
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