TGFβ signaling curbs cell fusion and muscle regeneration

Francesco Girardi, Anissa Taleb, Majid Ebrahimi, Asiman Datye, Dilani G. Gamage, Cécile Peccate, Lorenzo Giordani, Douglas P. Millay, Penney M. Gilbert, Bruno Cadot and Fabien Le Grand ()
Additional contact information
Francesco Girardi: Centre de Recherche en Myologie
Anissa Taleb: Centre de Recherche en Myologie
Majid Ebrahimi: University of Toronto
Asiman Datye: University of Toronto
Dilani G. Gamage: Cincinnati Children’s Hospital Medical Center
Cécile Peccate: Centre de Recherche en Myologie
Lorenzo Giordani: Centre de Recherche en Myologie
Douglas P. Millay: Cincinnati Children’s Hospital Medical Center
Penney M. Gilbert: University of Toronto
Bruno Cadot: Centre de Recherche en Myologie
Fabien Le Grand: Centre de Recherche en Myologie

Nature Communications, 2021, vol. 12, issue 1, 1-16

Abstract: Abstract Muscle cell fusion is a multistep process involving cell migration, adhesion, membrane remodeling and actin-nucleation pathways to generate multinucleated myotubes. However, molecular brakes restraining cell–cell fusion events have remained elusive. Here we show that transforming growth factor beta (TGFβ) pathway is active in adult muscle cells throughout fusion. We find TGFβ signaling reduces cell fusion, regardless of the cells’ ability to move and establish cell-cell contacts. In contrast, inhibition of TGFβ signaling enhances cell fusion and promotes branching between myotubes in mouse and human. Exogenous addition of TGFβ protein in vivo during muscle regeneration results in a loss of muscle function while inhibition of TGFβR2 induces the formation of giant myofibers. Transcriptome analyses and functional assays reveal that TGFβ controls the expression of actin-related genes to reduce cell spreading. TGFβ signaling is therefore requisite to limit mammalian myoblast fusion, determining myonuclei numbers and myofiber size.

Date: 2021
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Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:12:y:2021:i:1:d:10.1038_s41467-020-20289-8

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DOI: 10.1038/s41467-020-20289-8

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