title: Reduced Notch signalling leads to postnatal skeletal muscle hypertrophy in Pofut1cax/cax mice.
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.affiliation: Univ. Limoges, INRA, UMR 1061, UGMA, 87060 Limoges, France.
authors.forename: Bilal
authors.initials: B
authors.lastname: Al Jaam
authors.affiliation: Univ. Limoges, INRA, UMR 1061, UGMA, 87060 Limoges, France.
authors.forename: Katy
authors.initials: K
authors.lastname: Heu
authors.affiliation: Univ. Limoges, INRA, UMR 1061, UGMA, 87060 Limoges, France.
authors.forename: Florian
authors.initials: F
authors.lastname: Pennarubia
authors.affiliation: Univ. Limoges, INRA, UMR 1061, UGMA, 87060 Limoges, France.
authors.forename: Alexandre
authors.initials: A
authors.lastname: Segelle
authors.affiliation: Univ. Limoges, INRA, UMR 1061, UGMA, 87060 Limoges, France.
authors.forename: Laetitia
authors.initials: L
authors.lastname: Magnol
authors.affiliation: Univ. Limoges, INRA, UMR 1061, UGMA, 87060 Limoges, France.
authors.forename: Agnès
authors.initials: A
authors.lastname: Germot
authors.affiliation: Univ. Limoges, INRA, UMR 1061, UGMA, 87060 Limoges, France sebastien.legardinier@unilim.fr.
authors.forename: Sébastien
authors.identifier: 0000-0001-5923-5689
authors.initials: S
authors.lastname: Legardinier
authors.affiliation: Univ. Limoges, INRA, UMR 1061, UGMA, 87060 Limoges, France.
authors.forename: Véronique
authors.initials: V
authors.lastname: Blanquet
authors.affiliation: Univ. Limoges, INRA, UMR 1061, UGMA, 87060 Limoges, France.
authors.forename: Abderrahman
authors.initials: A
authors.lastname: Maftah
mesh_terms: D000818:Animals; D002454:Cell Differentiation; D002462:Cell Membrane / Q000378:metabolism; D002478:Cells, Cultured; D005647:Fucosyltransferases / Q000235:genetics / Q000378:metabolism*; D015870:Gene Expression; D006984:Hypertrophy; D008024:Ligands; D051379:Mice; D008809:Mice, Inbred C3H; D024510:Muscle Development; D018482:Muscle, Skeletal / Q000254:growth & development* / Q000378:metabolism*; D017570:MyoD Protein / Q000235:genetics / Q000378:metabolism; D032446:Myoblasts / Q000166:cytology / Q000502:physiology*; D051763:PAX7 Transcription Factor / Q000235:genetics / Q000378:metabolism; D051880:Receptors, Notch / Q000235:genetics / Q000378:metabolism*; D032496:Satellite Cells, Skeletal Muscle / Q000166:cytology / Q000502:physiology; D015398:Signal Transduction; D013234:Stem Cells
chemical_list: D008024:Ligands; D017570:MyoD Protein; D051763:PAX7 Transcription Factor; D051880:Receptors, Notch; D005647:Fucosyltransferases; C539426:Pofut1 protein, mouse
keywords: Notch; POFUT1; hypertrophy; satellite cells; skeletal muscles