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Reduced Notch signalling leads to postnatal skeletal muscle hypertrophy in Pofut1cax/cax mice.
Open Biol. 2016 09; 6(9)OB

Abstract

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 Pofut1(cax/cax) (cax, compact axial skeleton) mice and differentiation of their satellite cell-derived myoblasts (SCDMs). Pofut1(cax/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, Pofut1(cax/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.

Authors+Show Affiliations

Univ. Limoges, INRA, UMR 1061, UGMA, 87060 Limoges, France.Univ. Limoges, INRA, UMR 1061, UGMA, 87060 Limoges, France.Univ. Limoges, INRA, UMR 1061, UGMA, 87060 Limoges, France.Univ. Limoges, INRA, UMR 1061, UGMA, 87060 Limoges, France.Univ. Limoges, INRA, UMR 1061, UGMA, 87060 Limoges, France.Univ. Limoges, INRA, UMR 1061, UGMA, 87060 Limoges, France.Univ. Limoges, INRA, UMR 1061, UGMA, 87060 Limoges, France sebastien.legardinier@unilim.fr.Univ. Limoges, INRA, UMR 1061, UGMA, 87060 Limoges, France.Univ. Limoges, INRA, UMR 1061, UGMA, 87060 Limoges, France.

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

27628322

Citation

Al Jaam, Bilal, et al. "Reduced Notch Signalling Leads to Postnatal Skeletal Muscle Hypertrophy in Pofut1cax/cax Mice." Open Biology, vol. 6, no. 9, 2016.
Al Jaam B, Heu K, Pennarubia F, et al. Reduced Notch signalling leads to postnatal skeletal muscle hypertrophy in Pofut1cax/cax mice. Open Biol. 2016;6(9).
Al Jaam, B., Heu, K., Pennarubia, F., Segelle, A., Magnol, L., Germot, A., Legardinier, S., Blanquet, V., & Maftah, A. (2016). Reduced Notch signalling leads to postnatal skeletal muscle hypertrophy in Pofut1cax/cax mice. Open Biology, 6(9). https://doi.org/10.1098/rsob.160211
Al Jaam B, et al. Reduced Notch Signalling Leads to Postnatal Skeletal Muscle Hypertrophy in Pofut1cax/cax Mice. Open Biol. 2016;6(9) PubMed PMID: 27628322.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Reduced Notch signalling leads to postnatal skeletal muscle hypertrophy in Pofut1cax/cax mice. AU - Al Jaam,Bilal, AU - Heu,Katy, AU - Pennarubia,Florian, AU - Segelle,Alexandre, AU - Magnol,Laetitia, AU - Germot,Agnès, AU - Legardinier,Sébastien, AU - Blanquet,Véronique, AU - Maftah,Abderrahman, PY - 2016/07/16/received PY - 2016/08/24/accepted PY - 2016/9/16/entrez PY - 2016/9/16/pubmed PY - 2017/6/8/medline KW - Notch KW - POFUT1 KW - hypertrophy KW - satellite cells KW - skeletal muscles JF - Open biology JO - Open Biol VL - 6 IS - 9 N2 - 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 Pofut1(cax/cax) (cax, compact axial skeleton) mice and differentiation of their satellite cell-derived myoblasts (SCDMs). Pofut1(cax/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, Pofut1(cax/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. SN - 2046-2441 UR - https://www.unboundmedicine.com/medline/citation/27628322/Reduced_Notch_signalling_leads_to_postnatal_skeletal_muscle_hypertrophy_in_Pofut1cax/cax_mice_ L2 - https://royalsocietypublishing.org/doi/10.1098/rsob.160211?url_ver=Z39.88-2003&rfr_id=ori:rid:crossref.org&rfr_dat=cr_pub=pubmed DB - PRIME DP - Unbound Medicine ER -