mTOR controls embryonic and adult myogenesis via mTORC1

Nathalie Rion1, Perrine Castets1, Shuo Lin1

  • 1Biozentrum, University of Basel, CH-4056 Basel, Switzerland.

Development (Cambridge, England)
|March 16, 2019
PubMed

Insights

The mechanistic target of rapamycin complex 1 (mTORC1) is crucial for muscle stem cell proliferation and fusion during development and regeneration. Its absence leads to perinatal death and impaired muscle repair, highlighting mTORC1

Area of Science:

  • Cell Biology
  • Developmental Biology
  • Muscle Regeneration

Background:

  • Muscle fiber formation requires coordinated regulation of progenitor cell proliferation, differentiation, and fusion.
  • Intracellular signal coordination during myogenesis is not fully understood.

Purpose of the Study:

  • To investigate the role of the cell-growth regulator mTOR, specifically mTOR complex 1 (mTORC1) and mTOR complex 2 (mTORC2), in mouse muscle progenitor cells.
  • To elucidate the function of mTORC1 and mTORC2 in embryonic and adult myogenesis.

Main Methods:

  • Elimination of essential components of mTORC1 and mTORC2 in mouse muscle progenitors.
  • Analysis of developmental and injury-induced muscle regeneration phenotypes.

Main Results:

  • Inactivation of mTORC1, but not mTORC2, in developing muscle leads to perinatal death.
  • mTORC1 deficiency in adult muscle stem cells severely impairs injury-induced muscle regeneration.
  • Defects in proliferation and fusion capacity of muscle progenitors were observed in mTORC1-deficient cells.
  • mTORC1-deficient muscle progenitors retained partial myogenic function.

Conclusions:

  • mTORC1, not mTORC2, is a critical regulator of both embryonic and adult myogenesis.
  • The study identifies mTORC1 as a key factor in muscle development and repair.
  • Alternative pathways may partially compensate for the loss of mTORC1 function.

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