Reduced Notch signalling leads to postnatal skeletal muscle hypertrophy in Pofut1cax/cax mice

Autor: Bilal Al Jaam, Katy Heu, Florian Pennarubia, Alexandre Segelle, Laetitia Magnol, Agnès Germot, Sébastien Legardinier, Véronique Blanquet, Abderrahman Maftah
Jazyk: angličtina
Rok vydání: 2016
Předmět:
Zdroj: Open Biology, Vol 6, Iss 9 (2016)
Druh dokumentu: article
ISSN: 2046-2441
DOI: 10.1098/rsob.160211
Popis: Postnatal skeletal muscle growth results from the activation of satellite cells and/or an increase in protein synthesis. The Notch signalling pathway maintains satellite cells in a quiescent state, and once activated, sustains their proliferation and commitment towards differentiation. In mammals, POFUT1-mediated O-fucosylation regulates the interactions between NOTCH receptors and ligands of the DELTA/JAGGED family, thus initiating the activation of canonical Notch signalling. Here, we analysed the consequences of downregulated expression of the Pofut1 gene on postnatal muscle growth in mutant Pofut1cax/cax (cax, compact axial skeleton) mice and differentiation of their satellite cell-derived myoblasts (SCDMs). Pofut1cax/cax mice exhibited muscle hypertrophy, no hyperplasia and a decrease in satellite cell numbers compared with wild-type C3H mice. In agreement with these observations, Pofut1cax/cax SCDMs differentiated earlier concomitant with reduced Pax7 expression and decrease in PAX7+/MYOD− progenitor cells. In vitro binding assays showed a reduced interaction of DELTA-LIKE 1 ligand (DLL1) with NOTCH receptors expressed at the cell surface of SCDMs, leading to a decreased Notch signalling as seen by the quantification of cleaved NICD and Notch target genes. These results demonstrated that POFUT1-mediated O-fucosylation of NOTCH receptors regulates myogenic cell differentiation and affects postnatal muscle growth in mice.
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