Sonic hedgehog promotes proliferation and differentiation of adult muscle cells: Involvement of MAPK/ERK and PI3K/Akt pathways

Dafna Elia, Dorit Madhala, Eti Ardon, Ram Reshef, Orna Halevy

Research output: Contribution to journalArticlepeer-review


Sonic hedgehog (Shh) has been reported to act as a mitogen and survival factor for muscle satellite cells. However, its role in their differentiation remains ambiguous. Here, we provide evidence that Shh promotes the proliferation and differentiation of primary cultures of chicken adult myoblasts (also termed satellite cells) and mouse myogenic C2 cells. These effects are reversed by cyclopamine, a specific chemical inhibitor of the Shh pathway. In addition, we show that Shh and its downstream molecules are expressed in adult myoblast cultures and localize adjacent to Pax7 in muscle sections. These gene expressions are regulated during postnatal muscle growth in chicks. Most importantly, we report that Shh induces MAPK/ERK and phosphoinositide 3-kinase (PI3K)-dependent Akt phosphorylation and that activation of both signaling pathways is essential for Shh's signaling in muscle cells. However, the effect of Shh on Akt phosphorylation is more robust than that on MAPK/ERK, and data suggest that Shh influences these pathways in a manner similar to IGF-I. By exploiting specific chemical inhibitors of the MAPK/ERK and PI3K/Akt signaling pathways, UO126 and Ly294002, respectively, we demonstrate that Shh-induced Akt phosphorylation, but not that of MAPK/ERK, is required for its promotive effects on muscle cell proliferation and differentiation. Taken together, we suggest that Shh acts in an autocrinic manner in adult myoblasts, and provide first evidence of a role for PI3K/Akt in Shh signaling during myoblast differentiation.

Original languageEnglish
Pages (from-to)1438-1446
Number of pages9
JournalBiochimica et Biophysica Acta - Molecular Cell Research
Issue number9
StatePublished - Sep 2007
Externally publishedYes

Bibliographical note

Funding Information:
We thank David Bumcrot and Andrew McMahon for protocols. This study was supported in part by a grant from the EEU 6th Framework Program Network of Excellence MYORES. O. Halevy holds the Charles Charkowsky Chair in Poultry Science and Animal Hygiene.


  • Akt
  • Differentiation
  • MAPK
  • Satellite cells
  • Signal transduction
  • Skeletal muscle
  • Sonic hedgehog

ASJC Scopus subject areas

  • Molecular Biology
  • Cell Biology


Dive into the research topics of 'Sonic hedgehog promotes proliferation and differentiation of adult muscle cells: Involvement of MAPK/ERK and PI3K/Akt pathways'. Together they form a unique fingerprint.

Cite this