title: Satellite-like cells contribute to pax7-dependent skeletal muscle repair in adult zebrafish.
abstract: Satellite cells, also known as muscle stem cells, are responsible for skeletal muscle growth and repair in mammals. Pax7 and Pax3 transcription factors are established satellite cell markers required for muscle development and regeneration, and there is great interest in identifying additional factors that regulate satellite cell proliferation, differentiation, and/or skeletal muscle regeneration. Due to the powerful regenerative capacity of many zebrafish tissues, even in adults, we are exploring the regenerative potential of adult zebrafish skeletal muscle. Here, we show that adult zebrafish skeletal muscle contains cells similar to mammalian satellite cells. Adult zebrafish satellite-like cells have dense heterochromatin, express Pax7 and Pax3, proliferate in response to injury, and show peak myogenic responses 4-5 days post-injury (dpi). Furthermore, using a pax7a-driven GFP reporter, we present evidence implicating satellite-like cells as a possible source of new muscle. In lieu of central nucleation, which distinguishes regenerating myofibers in mammals, we describe several characteristics that robustly identify newly-forming myofibers from surrounding fibers in injured adult zebrafish muscle. These characteristics include partially overlapping expression in satellite-like cells and regenerating myofibers of two RNA-binding proteins Rbfox2 and Rbfoxl1, known to regulate embryonic muscle development and function. Finally, by analyzing pax7a; pax7b double mutant zebrafish, we show that Pax7 is required for adult skeletal muscle repair, as it is in the mouse.
authors.affiliation: Departments of Molecular Genetics and Biological Chemistry and Pharmacology, The Ohio State University, Columbus, OH 43210, USA; Center for Muscle Health and Neuromuscular Disorders, The Ohio State University and Nationwide Children's Hospital, Columbus, OH 43210, USA.
authors.forename: Michael A
authors.initials: MA
authors.lastname: Berberoglu
authors.affiliation: Departments of Molecular Genetics and Biological Chemistry and Pharmacology, The Ohio State University, Columbus, OH 43210, USA; Center for Muscle Health and Neuromuscular Disorders, The Ohio State University and Nationwide Children's Hospital, Columbus, OH 43210, USA.
authors.forename: Thomas L
authors.initials: TL
authors.lastname: Gallagher
authors.affiliation: Departments of Molecular Genetics and Biological Chemistry and Pharmacology, The Ohio State University, Columbus, OH 43210, USA; Center for Muscle Health and Neuromuscular Disorders, The Ohio State University and Nationwide Children's Hospital, Columbus, OH 43210, USA.
authors.forename: Zachary T
authors.initials: ZT
authors.lastname: Morrow
authors.affiliation: Departments of Molecular Genetics and Biological Chemistry and Pharmacology, The Ohio State University, Columbus, OH 43210, USA; Center for Muscle Health and Neuromuscular Disorders, The Ohio State University and Nationwide Children's Hospital, Columbus, OH 43210, USA.
authors.forename: Jared C
authors.initials: JC
authors.lastname: Talbot
authors.affiliation: Departments of Molecular Genetics and Biological Chemistry and Pharmacology, The Ohio State University, Columbus, OH 43210, USA; Center for Muscle Health and Neuromuscular Disorders, The Ohio State University and Nationwide Children's Hospital, Columbus, OH 43210, USA.
authors.forename: Kimberly J
authors.initials: KJ
authors.lastname: Hromowyk
authors.affiliation: Massachusetts General Hospital Cancer Center, Harvard Medical School, Charlestown, MA 02129, USA; Department of Molecular Pathology and Regenerative Medicine, Massachusetts General Hospital, Charlestown, MA 02129, USA; Harvard Stem Cell Institute, Cambridge, MA 02138, USA.
authors.forename: Inês M
authors.initials: IM
authors.lastname: Tenente
authors.affiliation: Massachusetts General Hospital Cancer Center, Harvard Medical School, Charlestown, MA 02129, USA; Department of Molecular Pathology and Regenerative Medicine, Massachusetts General Hospital, Charlestown, MA 02129, USA; Harvard Stem Cell Institute, Cambridge, MA 02138, USA.
authors.forename: David M
authors.initials: DM
authors.lastname: Langenau
authors.affiliation: Departments of Molecular Genetics and Biological Chemistry and Pharmacology, The Ohio State University, Columbus, OH 43210, USA; Center for Muscle Health and Neuromuscular Disorders, The Ohio State University and Nationwide Children's Hospital, Columbus, OH 43210, USA. Electronic address: amacher.6@osu.edu.
authors.forename: Sharon L
authors.initials: SL
authors.lastname: Amacher
mesh_terms: D000375:Aging / Q000502:physiology*; D000818:Animals; D030801:Animals, Genetically Modified; D001483:Base Sequence; D002454:Cell Differentiation; D002467:Cell Nucleus / Q000378:metabolism; D049109:Cell Proliferation; D049452:Green Fluorescent Proteins / Q000378:metabolism; D008954:Models, Biological; D024510:Muscle Development; D018485:Muscle Fibers, Skeletal / Q000378:metabolism / Q000473:pathology; D018482:Muscle, Skeletal / Q000473:pathology* / Q000648:ultrastructure; D051762:PAX2 Transcription Factor / Q000378:metabolism*; D032496:Satellite Cells, Skeletal Muscle / Q000378:metabolism* / Q000473:pathology / Q000648:ultrastructure; D019076:Transgenes; D014945:Wound Healing; D015027:Zebrafish / Q000378:metabolism*; D029961:Zebrafish Proteins / Q000378:metabolism*
chemical_list: D051762:PAX2 Transcription Factor; D029961:Zebrafish Proteins; C000619973:pax7a protein, zebrafish; D049452:Green Fluorescent Proteins
keywords: Muscle injury; Muscle stem cells; Myogenesis; Pax transcription factors; Rbfox RNA-binding proteins