title: An HMGA2-IGF2BP2 axis regulates myoblast proliferation and myogenesis.
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.
authors.affiliation: Novartis Institutes for Biomedical Research, Cambridge, MA 02139, USA.
authors.forename: Zhizhong
authors.initials: Z
authors.lastname: Li
authors.forename: Jason A
authors.initials: JA
authors.lastname: Gilbert
authors.forename: Yunyu
authors.initials: Y
authors.lastname: Zhang
authors.forename: Minsi
authors.initials: M
authors.lastname: Zhang
authors.forename: Qiong
authors.initials: Q
authors.lastname: Qiu
authors.forename: Krishnan
authors.initials: K
authors.lastname: Ramanujan
authors.forename: Tea
authors.initials: T
authors.lastname: Shavlakadze
authors.forename: John K
authors.initials: JK
authors.lastname: Eash
authors.forename: Annarita
authors.initials: A
authors.lastname: Scaramozza
authors.forename: Matthew M
authors.initials: MM
authors.lastname: Goddeeris
authors.forename: David G
authors.initials: DG
authors.lastname: Kirsch
authors.forename: Kevin P
authors.initials: KP
authors.lastname: Campbell
authors.forename: Andrew S
authors.initials: AS
authors.lastname: Brack
authors.forename: David J
authors.initials: DJ
authors.lastname: Glass
mesh_terms: D000818:Animals; D002454:Cell Differentiation; D049109:Cell Proliferation; D002478:Cells, Cultured; D015536:Down-Regulation; D005260:Female; D025743:HMGA2 Protein / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D024510:Muscle Development; D018482:Muscle, Skeletal / Q000166:cytology* / Q000378:metabolism / Q000502:physiology; D032446:Myoblasts / Q000166:cytology* / Q000378:metabolism* / Q000502:physiology; D014176:Protein Biosynthesis; D016271:Proto-Oncogene Proteins c-myc / Q000096:biosynthesis; D016601:RNA-Binding Proteins / Q000378:metabolism*; D017526:Receptor, IGF Type 1 / Q000096:biosynthesis; D032496:Satellite Cells, Skeletal Muscle / Q000378:metabolism; D016329:Sp1 Transcription Factor / Q000096:biosynthesis
chemical_list: D025743:HMGA2 Protein; C559768:IGF2BP2 protein, mouse; C489428:Myc protein, mouse; D016271:Proto-Oncogene Proteins c-myc; D016601:RNA-Binding Proteins; D016329:Sp1 Transcription Factor; D017526:Receptor, IGF Type 1