Stra13 regulates satellite cell activation by antagonizing Notch signaling

Satellite cells play a critical role in skeletal muscle regeneration in response to injury. Notch signaling is vital for satellite cell activation and myogenic precursor cell expansion but inhibits myogenic differentiation. Thus, precise spatial and temporal regulation of Notch activity is necessary...

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Bibliographic Details
Published in:The Journal of cell biology 2007-05, Vol.177 (4), p.647-657
Main Authors: Sun, Hong, Li, Li, Vercherat, Cécile, Gulbagci, Neriman Tuba, Acharjee, Sujata, Li, Jiali, Chung, Teng-Kai, Thin, Tin Htwe, Taneja, Reshma
Format: Article
Language:English
Subjects:
Animals
Basic Helix-Loop-Helix Transcription Factors - deficiency
Basic Helix-Loop-Helix Transcription Factors - genetics
Basic Helix-Loop-Helix Transcription Factors - physiology
Cell Differentiation - genetics
Cell division
Cell growth
Cell Line
Cell Proliferation
Cells
Cells, Cultured
Homeodomain Proteins - genetics
Homeodomain Proteins - physiology
Humans
Mice
Mice, Inbred C3H
Mice, Knockout
Musculoskeletal diseases
Receptors, Notch - antagonists & inhibitors
Receptors, Notch - physiology
Rodents
Satellite Cells, Skeletal Muscle - cytology
Satellite Cells, Skeletal Muscle - metabolism
Signal Transduction - genetics
Signal Transduction - physiology
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Summary:Satellite cells play a critical role in skeletal muscle regeneration in response to injury. Notch signaling is vital for satellite cell activation and myogenic precursor cell expansion but inhibits myogenic differentiation. Thus, precise spatial and temporal regulation of Notch activity is necessary for efficient muscle regeneration. We report that the basic helix-loop-helix transcription factor Stra13 modulates Notch signaling in regenerating muscle. Upon injury, Stra13⁻/⁻ mice exhibit increased cellular proliferation, elevated Notch signaling, a striking regeneration defect characterized by degenerated myotubes, increased mononuclear cells, and fibrosis. Stra13⁻/⁻ primary myoblasts also exhibit enhanced Notch activity, increased proliferation, and defective differentiation. Inhibition of Notch signaling ex vivo and in vivo ameliorates the phenotype of Stra13⁻/⁻ mutants. We demonstrate in vitro that Stra13 antagonizes Notch activity and reverses the Notch-imposed inhibition of myogenesis. Thus, Stra13 plays an important role in postnatal myogenesis by attenuating Notch signaling to reduce myoblast proliferation and promote myogenic differentiation.
ISSN:0021-9525
1540-8140
DOI:10.1083/jcb.200609007