Overexpression of facioscapulohumeral muscular dystrophy region gene 1 causes primary defects in myogenic stem cells

Alexandros Xynos, Maria Victoria Neguembor, Roberta Caccia, Danilo Licastro, Alessandro Nonis, Clelia Di Serio, Elia Stupka, Davide Gabellini

Research output: Contribution to journalArticle

Abstract

Overexpression of facioscapulohumeral muscular dystrophy region gene 1 (FRG1) in mice, frogs and worms leads to muscular and vascular abnormalities. Nevertheless, the mechanism that follows FRG1 overexpression and finally leads to muscular defects is currently unknown. Here, we show that the earliest phenotype displayed by mice overexpressing FRG1 is a postnatal muscle-growth defect. Long before the development of muscular dystrophy, FRG1 mice also exhibit a muscle regeneration impairment. Ex vivo and in vivo experiments revealed that FRG1 overexpression causes myogenic stem cell activation and proliferative, clonogenic and differentiation defects. A comparative gene expression profiling of muscles from young pre-dystrophic wild-type and FRG1 mice identified differentially expressed genes in several gene categories and networks that could explain the emerging tissue and myogenic stem cell defects. Overall, our study provides new insights into the pathways regulated by FRG1 and suggests that muscle stem cell defects could contribute to the pathology of FRG1 mice.

Original languageEnglish
Pages (from-to)2236-2245
Number of pages10
JournalJournal of Cell Science
Volume126
Issue number10
DOIs
Publication statusPublished - May 2013

Keywords

  • Epigenetics
  • Muscle stem cells
  • Muscular dystrophy

ASJC Scopus subject areas

  • Cell Biology

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