Alpha sarcoglycan is required for FGF-dependent myogenic progenitor cell proliferation in vitro and in vivo

Marco Cassano, Arianna Dellavalle, Francesco Saverio Tedesco, Mattia Quattrocelli, Stefania Crippa, Flavio Ronzoni, Agnese Salvade, Emanuele Berardi, Yvan Torrente, Giulio Cossu, Maurilio Sampaolesi

Research output: Contribution to journalArticle

Abstract

Mice deficient in α-sarcoglycan (Sgca-null mice) develop progressive muscular dystrophy and serve as a model for human limb girdle muscular dystrophy type 2D. Sgca-null mice suffer a more severe myopathy than that of mdx mice, the model for Duchenne muscular dystrophy. This is the opposite of what is observed in humans and the reason for this is unknown. In an attempt to understand the cellular basis of this severe muscular dystrophy, we isolated clonal populations of myogenic progenitor cells (MPCs), the resident postnatal muscle progenitors of dystrophic and wild-type mice. MPCs from Sgca-null mice generated much smaller clones than MPCs from wild-type or mdx dystrophic mice. Impaired proliferation of Sgca-null myogenic precursors was confirmed by single fiber analysis and this difference correlated with Sgca expression during MPC proliferation. In the absence of dystrophin and associated proteins, which are only expressed after differentiation, SGCA complexes with and stabilizes FGFR1. Deficiency of Sgca leads to an absence of FGFR1 expression at the membrane and impaired MPC proliferation in response to bFGF. The low proliferation rate of Sgca-null MPCs was rescued by transduction with Sgca-expressing lentiviral vectors. When transplanted into dystrophic muscle, Sgca-null MPCs exhibited reduced engraftment. The reduced proliferative ability of Sgca-null MPCs explains, at least in part, the severity of this muscular dystrophy and also why wild-type donor progenitor cells engraft efficiently and consequently ameliorate disease.

Original languageEnglish
Pages (from-to)4523-4533
Number of pages11
JournalDevelopment
Volume138
Issue number20
DOIs
Publication statusPublished - Oct 15 2011

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Sarcoglycans
Stem Cells
Cell Proliferation
Muscular Dystrophies
Inbred mdx Mouse
Sarcoglycanopathies
Dystrophin-Associated Proteins
In Vitro Techniques
Muscles
Duchenne Muscular Dystrophy
Muscular Diseases
Clone Cells

Keywords

  • Cell therapy
  • Limb girdle muscular dystrophy
  • Mouse
  • Myogenic progenitor cells

ASJC Scopus subject areas

  • Developmental Biology
  • Molecular Biology

Cite this

Cassano, M., Dellavalle, A., Tedesco, F. S., Quattrocelli, M., Crippa, S., Ronzoni, F., ... Sampaolesi, M. (2011). Alpha sarcoglycan is required for FGF-dependent myogenic progenitor cell proliferation in vitro and in vivo. Development, 138(20), 4523-4533. https://doi.org/10.1242/dev.070706

Alpha sarcoglycan is required for FGF-dependent myogenic progenitor cell proliferation in vitro and in vivo. / Cassano, Marco; Dellavalle, Arianna; Tedesco, Francesco Saverio; Quattrocelli, Mattia; Crippa, Stefania; Ronzoni, Flavio; Salvade, Agnese; Berardi, Emanuele; Torrente, Yvan; Cossu, Giulio; Sampaolesi, Maurilio.

In: Development, Vol. 138, No. 20, 15.10.2011, p. 4523-4533.

Research output: Contribution to journalArticle

Cassano, M, Dellavalle, A, Tedesco, FS, Quattrocelli, M, Crippa, S, Ronzoni, F, Salvade, A, Berardi, E, Torrente, Y, Cossu, G & Sampaolesi, M 2011, 'Alpha sarcoglycan is required for FGF-dependent myogenic progenitor cell proliferation in vitro and in vivo', Development, vol. 138, no. 20, pp. 4523-4533. https://doi.org/10.1242/dev.070706
Cassano M, Dellavalle A, Tedesco FS, Quattrocelli M, Crippa S, Ronzoni F et al. Alpha sarcoglycan is required for FGF-dependent myogenic progenitor cell proliferation in vitro and in vivo. Development. 2011 Oct 15;138(20):4523-4533. https://doi.org/10.1242/dev.070706
Cassano, Marco ; Dellavalle, Arianna ; Tedesco, Francesco Saverio ; Quattrocelli, Mattia ; Crippa, Stefania ; Ronzoni, Flavio ; Salvade, Agnese ; Berardi, Emanuele ; Torrente, Yvan ; Cossu, Giulio ; Sampaolesi, Maurilio. / Alpha sarcoglycan is required for FGF-dependent myogenic progenitor cell proliferation in vitro and in vivo. In: Development. 2011 ; Vol. 138, No. 20. pp. 4523-4533.
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