Jul 13, 2016

R-spondin1 regulates muscle progenitor cell fusion through control of antagonist Wnt signaling pathways

BioRxiv : the Preprint Server for Biology
Floriane LacourFabien Le Grand

Abstract

Tissue regeneration requires the selective activation and repression of specific signaling pathways in stem cells. As such, the Wnt signaling pathways have been shown to control stem cell fate. In many cell types, the R-Spondin (Rspo) family of secreted proteins acts as potent activators of the canonical Wnt/β-catenin pathway. Here, we identify Rspo1 as a mediator of skeletal muscle tissue repair. Firstly we show that Rspo1-null muscles do not display any abnormalities at the basal level. However deletion of Rspo1 results in global alteration of muscle regeneration kinetics following acute injury. We found that muscle stem cells lacking Rspo1 show delayed differentiation. Transcriptome analysis further demonstrated that Rspo1 is required for the activation of Wnt/β-catenin target genes in muscle cells. Furthermore, muscle cells lacking Rspo1 fuse with a higher frequency than normal cells, leading to larger myotubes containing more nuclei both in vitro and in vivo. We found the increase in muscle fusion was dependent on up-regulation of non-canonical Wnt7a/Fzd7/Rac1 signaling. We conclude that antagonistic control of canonical and non-canonical Wnt signaling pathways by Rspo1 in muscle stem cell progeny is important for restitut...Continue Reading

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Mentioned in this Paper

In Vivo
Biochemical Pathway
RSPO1 gene
Genes
Muscle Cells
Antagonist Muscle Action
Tissue Regeneration
Gene Deletion Abnormality
Gene Deletion
WNT7A

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