Hedgehog signaling regulates MyoD expression and activity

Anastassia Voronova, Erin Coyne, Ashraf Al Madhoun, Joel V. Fair, Neven Bosiljcic, Catherine St-Louis, Grace Li, Sherry Thurig, Valerie A. Wallace, Nadine Wiper-Bergeron, Ilona S. Skerjanc

Research output: Contribution to journalArticle

24 Citations (Scopus)

Abstract

The inhibition of MyoD expression is important for obtaining muscle progenitors that can replenish the satellite cell niche during muscle repair. Progenitors could be derived from either embryonic stem cells or satellite cells. Hedgehog (Hh) signaling is important for MyoD expression during embryogenesis and adult muscle regeneration. To date, the mechanistic understanding of MyoD regulation by Hh signaling is unclear. Here, we demonstrate that the Hh effector, Gli2, regulates MyoD expression and associates with MyoD gene elements. Gain- and loss-of-function experiments in pluripotent P19 cells show that Gli2 activity is sufficient and required for efficient MyoD expression during skeletal myogenesis. Inhibition of Hh signaling reduces MyoD expression during satellite cell activation in vitro. In addition to regulating MyoD expression, Hh signaling regulates MyoD transcriptional activity, and MyoD activates Hh signaling in myogenic conversion assays. Finally, Gli2, MyoD, and MEF2C form a protein complex, which enhances MyoD activity on skeletal muscle-related promoters. We therefore link Hh signaling to the function and expression of MyoD protein during myogenesis in stem cells.

Original languageEnglish
Pages (from-to)4389-4404
Number of pages16
JournalJournal of Biological Chemistry
Volume288
Issue number6
DOIs
Publication statusPublished - 8 Feb 2013

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    Voronova, A., Coyne, E., Al Madhoun, A., Fair, J. V., Bosiljcic, N., St-Louis, C., Li, G., Thurig, S., Wallace, V. A., Wiper-Bergeron, N., & Skerjanc, I. S. (2013). Hedgehog signaling regulates MyoD expression and activity. Journal of Biological Chemistry, 288(6), 4389-4404. https://doi.org/10.1074/jbc.M112.400184