title: Numb-deficient satellite cells have regeneration and proliferation defects.
abstract: The adaptor protein Numb has been implicated in the switch between cell proliferation and differentiation made by satellite cells during muscle repair. Using two genetic approaches to ablate Numb, we determined that, in its absence, muscle regeneration in response to injury was impaired. Single myofiber cultures demonstrated a lack of satellite cell proliferation in the absence of Numb, and the proliferation defect was confirmed in satellite cell cultures. Quantitative RT-PCR from Numb-deficient satellite cells demonstrated highly up-regulated expression of p21 and Myostatin, both inhibitors of myoblast proliferation. Transfection with Myostatin-specific siRNA rescued the proliferation defect of Numb-deficient satellite cells. Furthermore, overexpression of Numb in satellite cells inhibited Myostatin expression. These data indicate a unique function for Numb during the initial activation and proliferation of satellite cells in response to muscle injury.
authors.affiliation: School of Life Sciences, Arizona State University, Tempe, AZ 85287-4501.
authors.forename: Rajani M
authors.initials: RM
authors.lastname: George
authors.forename: Stefano
authors.initials: S
authors.lastname: Biressi
authors.forename: Brian J
authors.initials: BJ
authors.lastname: Beres
authors.forename: Erik
authors.initials: E
authors.lastname: Rogers
authors.forename: Amanda K
authors.initials: AK
authors.lastname: Mulia
authors.forename: Ronald E
authors.initials: RE
authors.lastname: Allen
authors.forename: Alan
authors.initials: A
authors.lastname: Rawls
authors.forename: Thomas A
authors.initials: TA
authors.lastname: Rando
authors.forename: Jeanne
authors.initials: J
authors.lastname: Wilson-Rawls
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D017609:Barium Compounds; D015153:Blotting, Western; D001837:Body Weights and Measures; D049109:Cell Proliferation; D002712:Chlorides; D005434:Flow Cytometry; D005455:Fluorescent Antibody Technique; D008565:Membrane Proteins / Q000172:deficiency*; D051379:Mice; D018345:Mice, Knockout; D024510:Muscle Development / Q000235:genetics / Q000502:physiology*; D009419:Nerve Tissue Proteins / Q000172:deficiency*; D034622:RNA Interference; D034741:RNA, Small Interfering / Q000235:genetics; D012038:Regeneration / Q000235:genetics / Q000502:physiology*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D032496:Satellite Cells, Skeletal Muscle / Q000378:metabolism / Q000502:physiology*
chemical_list: D017609:Barium Compounds; D002712:Chlorides; D008565:Membrane Proteins; D009419:Nerve Tissue Proteins; C106293:Numb protein, mouse; D034741:RNA, Small Interfering; C024986:barium chloride
keywords: conditional mutation; myogenesis; skeletal muscle; stem cell