TGFβ signalling acts as a molecular brake of myoblast fusion

Nat Commun. 2021 Feb 2;12(1):749. doi: 10.1038/s41467-020-20290-1.

Abstract

Fusion of nascent myoblasts to pre-existing myofibres is critical for skeletal muscle growth and repair. The vast majority of molecules known to regulate myoblast fusion are necessary in this process. Here, we uncover, through high-throughput in vitro assays and in vivo studies in the chicken embryo, that TGFβ (SMAD2/3-dependent) signalling acts specifically and uniquely as a molecular brake on muscle fusion. While constitutive activation of the pathway arrests fusion, its inhibition leads to a striking over-fusion phenotype. This dynamic control of TGFβ signalling in the embryonic muscle relies on a receptor complementation mechanism, prompted by the merging of myoblasts with myofibres, each carrying one component of the heterodimer receptor complex. The competence of myofibres to fuse is likely restored through endocytic degradation of activated receptors. Altogether, this study shows that muscle fusion relies on TGFβ signalling to regulate its pace.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Communication / physiology
  • Cell Differentiation / physiology
  • Cell Fusion
  • Chickens
  • Immunohistochemistry
  • In Situ Hybridization
  • Mice
  • Muscle Fibers, Skeletal / drug effects*
  • Muscle Fibers, Skeletal / metabolism
  • Myoblasts / cytology*
  • Myoblasts / metabolism*
  • Myofibrils / metabolism
  • Signal Transduction / physiology
  • Transforming Growth Factor beta / metabolism*

Substances

  • Transforming Growth Factor beta