title: Hedgehog signaling regulates MyoD expression and activity.
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.
authors.affiliation: Department of Biochemistry, Microbiology, and Immunology, Dasman Diabetes Institute, Dasman 15462, Kuwait.
authors.forename: Anastassia
authors.initials: A
authors.lastname: Voronova
authors.forename: Erin
authors.initials: E
authors.lastname: Coyne
authors.forename: Ashraf
authors.initials: A
authors.lastname: Al Madhoun
authors.forename: Joel V
authors.initials: JV
authors.lastname: Fair
authors.forename: Neven
authors.initials: N
authors.lastname: Bosiljcic
authors.forename: Catherine
authors.initials: C
authors.lastname: St-Louis
authors.forename: Grace
authors.initials: G
authors.lastname: Li
authors.forename: Sherry
authors.initials: S
authors.lastname: Thurig
authors.forename: Valerie A
authors.initials: VA
authors.lastname: Wallace
authors.forename: Nadine
authors.initials: N
authors.lastname: Wiper-Bergeron
authors.forename: Ilona S
authors.initials: IS
authors.lastname: Skerjanc
mesh_terms: D000818:Animals; D002460:Cell Line; D005786:Gene Expression Regulation / Q000502:physiology*; D053823:Hedgehog Proteins / Q000235:genetics / Q000378:metabolism*; D051741:Kruppel-Like Transcription Factors / Q000235:genetics / Q000378:metabolism; D064326:MEF2 Transcription Factors; D051379:Mice; D008822:Mice, Transgenic; D046912:Multiprotein Complexes / Q000235:genetics / Q000378:metabolism; D024510:Muscle Development / Q000502:physiology; D017570:MyoD Protein / Q000096:biosynthesis*; D018006:Myogenic Regulatory Factors / Q000235:genetics / Q000378:metabolism; D039904:Pluripotent Stem Cells / Q000166:cytology / Q000378:metabolism*; D032496:Satellite Cells, Skeletal Muscle / Q000166:cytology / Q000378:metabolism*; D015398:Signal Transduction / Q000502:physiology*; D000075746:Zinc Finger Protein Gli2
chemical_list: C000618551:Gli2 protein, mouse; D053823:Hedgehog Proteins; D051741:Kruppel-Like Transcription Factors; D064326:MEF2 Transcription Factors; C578041:Mef2c protein, mouse; D046912:Multiprotein Complexes; D017570:MyoD Protein; C057363:MyoD1 myogenic differentiation protein; D018006:Myogenic Regulatory Factors; D000075746:Zinc Finger Protein Gli2