title: ErbB3 binding protein-1 (Ebp1) controls proliferation and myogenic differentiation of muscle stem cells.
abstract: Satellite cells are resident stem cells of skeletal muscle, supplying myoblasts for post-natal muscle growth, hypertrophy and repair. Many regulatory networks control satellite cell function, which includes EGF signalling via the ErbB family of receptors. Here we investigated the role of ErbB3 binding protein-1 (Ebp1) in regulation of myogenic stem cell proliferation and differentiation. Ebp1 is a well-conserved DNA/RNA binding protein that is implicated in cell growth, apoptosis and differentiation in many cell types. Of the two main Ebp1 isoforms, only p48 was expressed in satellite cells and C2C12 myoblasts. Although not present in quiescent satellite cells, p48 was strongly induced during activation, remaining at high levels during proliferation and differentiation. While retroviral-mediated over-expression of Ebp1 had only minor effects, siRNA-mediated Ebp1 knockdown inhibited both proliferation and differentiation of satellite cells and C2C12 myoblasts, with a clear failure of myotube formation. Ebp1-knockdown significantly reduced ErbB3 receptor levels, yet over-expression of ErbB3 in Ebp1 knockdown cells did not rescue differentiation. Ebp1 was also expressed by muscle cells during developmental myogenesis in mouse. Since Ebp1 is well-conserved between mouse and chick, we switched to chick to examine its role in muscle formation. In chick embryo, Ebp1 was expressed in the dermomyotome, and myogenic differentiation of muscle progenitors was inhibited by specific Ebp1 down-regulation using shRNA electroporation. These observations demonstrate a conserved function of Ebp1 in the regulation of embryonic muscle progenitors and adult muscle stem cells, which likely operates independently of ErbB3 signaling.
authors.affiliation: King's College London, Randall Division of Cell & Molecular Biophysics, New Hunt's House, Guy's Campus, London SE1 1UL, England, UK.
authors.forename: Nicolas
authors.initials: N
authors.lastname: Figeac
authors.affiliation: EMBL Australia, Australian Regenerative Medicine Institute (ARMI), Monash University, Building 75, Clayton, Victoria 3800, Australia.
authors.forename: Olivier
authors.initials: O
authors.lastname: Serralbo
authors.affiliation: EMBL Australia, Australian Regenerative Medicine Institute (ARMI), Monash University, Building 75, Clayton, Victoria 3800, Australia.
authors.forename: Christophe
authors.initials: C
authors.lastname: Marcelle
authors.affiliation: King's College London, Randall Division of Cell & Molecular Biophysics, New Hunt's House, Guy's Campus, London SE1 1UL, England, UK. Electronic address: peter.zammit@kcl.ac.uk.
authors.forename: Peter S
authors.initials: PS
authors.lastname: Zammit
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D002454:Cell Differentiation; D049109:Cell Proliferation; D002478:Cells, Cultured; D002642:Chick Embryo; D004268:DNA-Binding Proteins; D018507:Gene Expression Regulation, Developmental; D051379:Mice; D008810:Mice, Inbred C57BL; D008969:Molecular Sequence Data; D024510:Muscle Development / Q000502:physiology*; D018482:Muscle, Skeletal / Q000378:metabolism; D009132:Muscles / Q000378:metabolism*; D032446:Myoblasts / Q000378:metabolism; D009687:Nuclear Proteins / Q000378:metabolism* / Q000502:physiology; D016601:RNA-Binding Proteins; D020893:Receptor, ErbB-3 / Q000378:metabolism; D017386:Sequence Homology, Amino Acid; D015398:Signal Transduction; D013234:Stem Cells / Q000166:cytology*
chemical_list: D004268:DNA-Binding Proteins; D009687:Nuclear Proteins; C095938:Pa2g4 protein, mouse; D016601:RNA-Binding Proteins; D020893:Receptor, ErbB-3
keywords: Development; Ebp1; ErbB3; Myogenesis; Regeneration; Satellite cell; Skeletal muscle; Stem cell