Primary cilia in satellite cells are the mechanical sensors for muscle hypertrophy

Weijun Li, Zhenhong Zhu, Kai He, Xiaoyu Ma, Robert J. Pignolo, Gary C. Sieck, Jinghua Hu, Haitao Wang

Research output: Contribution to journalArticlepeer-review


Skeletal muscle atrophy is commonly associated with aging, immobilization, muscle unloading, and congenital myopathies. Generation of mature muscle cells from skeletal muscle satellite cells (SCs) is pivotal in repairing muscle tissue. Exercise therapy promotes muscle hypertrophy and strength. Primary cilium is implicated as the mechanical sensor in some mammalian cells, but its role in skeletal muscle cells remains vague. To determine mechanical sensors for exercise-induced muscle hypertrophy, we established three SC-specific cilium dysfunctional mouse models—Myogenic factor 5 (Myf5)-Arf-like Protein 3 (Arl3)2/2, Paired box protein Pax-7 (Pax7)-Intraflagellar transport protein 88 homolog (Ift88)2/2, and Pax7-Arl32/2—by specifically deleting a ciliary protein ARL3 in MYF5-expressing SCs, or IFT88 in PAX7-expressing SCs, or ARL3 in PAX7-expressing SCs, respectively. We show that the Myf5-Arl32/2 mice develop grossly the same as WT mice. Intriguingly, mechanical stimulation-induced muscle hypertrophy or myoblast differentiation is abrogated in Myf5-Arl32/2 and Pax7-Arl32/2 mice or primary isolated Myf5-Arl32/2 and Pax7-Ift882/2 myoblasts, likely due to defective cilia-mediated Hedgehog (Hh) signaling. Collectively, we demonstrate SC cilia serve as mechanical sensors and promote exercise-induced muscle hypertrophy via Hh signaling pathway.

Original languageEnglish (US)
Article numbere2103615119
JournalProceedings of the National Academy of Sciences of the United States of America
Issue number24
StatePublished - Jun 14 2022


  • exercise
  • mechanical stimulation
  • muscle hypertrophy
  • primary cilia

ASJC Scopus subject areas

  • General


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