title: Nfix Regulates Temporal Progression of Muscle Regeneration through Modulation of Myostatin Expression.
abstract: Nfix belongs to a family of four highly conserved proteins that act as transcriptional activators and/or repressors of cellular and viral genes. We previously showed a pivotal role for Nfix in regulating the transcriptional switch from embryonic to fetal myogenesis. Here, we show that Nfix directly represses the Myostatin promoter, thus controlling the proper timing of satellite cell differentiation and muscle regeneration. Nfix-null mice display delayed regeneration after injury, and this deficit is reversed upon in vivo Myostatin silencing. Conditional deletion of Nfix in satellite cells results in a similar delay in regeneration, confirming the functional requirement for Nfix in satellite cells. Moreover, mice lacking Nfix show reduced myofiber cross sectional area and a predominant slow twitching phenotype. These data define a role for Nfix in postnatal skeletal muscle and unveil a mechanism for Myostatin regulation, thus providing insights into the modulation of its complex signaling pathway.
authors.affiliation: Department of Biosciences, University of Milan, Via Celoria 26, 20133 Milan, Italy.
authors.forename: Giuliana
authors.initials: G
authors.lastname: Rossi
authors.affiliation: Department of Biosciences, University of Milan, Via Celoria 26, 20133 Milan, Italy.
authors.forename: Stefania
authors.initials: S
authors.lastname: Antonini
authors.affiliation: Department of Biosciences, University of Milan, Via Celoria 26, 20133 Milan, Italy.
authors.forename: Chiara
authors.initials: C
authors.lastname: Bonfanti
authors.affiliation: Department of Biosciences, University of Milan, Via Celoria 26, 20133 Milan, Italy.
authors.forename: Stefania
authors.initials: S
authors.lastname: Monteverde
authors.affiliation: Department of Biosciences, University of Milan, Via Celoria 26, 20133 Milan, Italy.
authors.forename: Chiara
authors.initials: C
authors.lastname: Vezzali
authors.affiliation: Stem Cells and Development, Department of Developmental & Stem Cell Biology, CNRS UMR 3738, Institut Pasteur, 25 Rue du Dr. Roux, 75015 Paris, France.
authors.forename: Shahragim
authors.initials: S
authors.lastname: Tajbakhsh
authors.affiliation: Department of Biosciences, University of Milan, Via Celoria 26, 20133 Milan, Italy; Institute of Inflammation and Repair, University of Manchester, Oxford Road, M13 9PL Manchester, UK.
authors.forename: Giulio
authors.initials: G
authors.lastname: Cossu
authors.affiliation: Department of Biosciences, University of Milan, Via Celoria 26, 20133 Milan, Italy. Electronic address: graziella.messina@unimi.it.
authors.forename: Graziella
authors.initials: G
authors.lastname: Messina
mesh_terms: D000818:Animals; D002454:Cell Differentiation; D002460:Cell Line; D002478:Cells, Cultured; D020868:Gene Silencing; D008822:Mice, Transgenic; D018485:Muscle Fibers, Skeletal / Q000502:physiology*; D032446:Myoblasts / Q000502:physiology; D055435:Myostatin / Q000235:genetics* / Q000378:metabolism; D051839:NFI Transcription Factors / Q000502:physiology*; D012038:Regeneration
chemical_list: C525912:Mstn protein, mouse; D055435:Myostatin; D051839:NFI Transcription Factors; C497650:Nfix protein, mouse
keywords: Myostatin; Nfix; regeneration; satellite cells; skeletal muscle