Loading…

TGFβ signaling curbs cell fusion and muscle regeneration

Fusion of muscle progenitor cells is necessary for skeletal muscle development and repair. Cell fusion is a multistep process involving cell migration, adhesion, membrane remodeling and actin-nucleation pathways to generate multinucleated myotubes. While the cellular and molecular mechanisms promoti...

Full description

Saved in:
Bibliographic Details
Published in:Nature communications 2021-02, Vol.12 (750)
Main Authors: Girardi, Francesco, Taleb, Anissa, Giordani, Lorenzo, Datye, Asiman, Ebrahimi, Majid, Gamage, Dilani, Millay, Douglas, Gilbert, Penney, Le Grand, Fabien, Bottanelli, Francesca, Cadot, Bruno, Campelo, Felix, Curran, Scott, Davidson, Patricia M, Dey, Gautam, Raote, Ishier, Straube, Anne, Swaffer, Matthew P
Format: Article
Language:English
Subjects:
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary:Fusion of muscle progenitor cells is necessary for skeletal muscle development and repair. Cell fusion is a multistep process involving cell migration, adhesion, membrane remodeling and actin-nucleation pathways to generate multinucleated myotubes. While the cellular and molecular mechanisms promoting muscle cell fusion have been intensely investigated in recent years, molecular brakes restraining cell–cell fusion events to control syncytia formation have remained elusive. Here, we show that transforming growth factor beta (TGFβ) signaling is active in adult muscle cells throughout the fusion process and reduce muscle cell fusion independently of the differentiation step. In contrast, inhibition of TGFβ signaling enhances cell fusion and promotes branching between myotubes. Pharmacological modulation of the pathway in vivo perturbs muscle regeneration after injury. Exogenous addition of TGFβ protein results in a loss of muscle function while inhibition of the TGFβ pathway induces the formation of giant myofibres. Transcriptome analyses and functional assays revealed that TGFβ acts on actin dynamics and reduce cell spreading through modulation of actin-based protrusions. Together our results reveal a signaling pathway that limits mammalian myoblast fusion and add a new level of understanding to the molecular regulation of myogenesis.
ISSN:2041-1723
2041-1723
DOI:10.1242/jcs.249607