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

Autor: Agnès Germot, Bilal Al Jaam, Katy Heu, Abderrahman Maftah, Laetitia Magnol, Florian Pennarubia, Sébastien Legardinier, Alexandre Segelle, Véronique Blanquet
Přispěvatelé: Unité de Génétique Moléculaire Animale (UMR GMA), Université de Limoges (UNILIM)-Institut National de la Recherche Agronomique (INRA), Lebanese Association for Scientific Research (LASeR), European Union (FEDER), Limousin Regional Council
Rok vydání: 2016
Předmět:
0301 basic medicine
[SDV]Life Sciences [q-bio]
Cellular differentiation
Gene Expression
hypertrophie
Ligands
Muscle Development
Muscle hypertrophy
Myoblasts
Mice
satellite cell
pofut1
Myocyte
lcsh:QH301-705.5
Cells
Cultured
satellite cells
Mice
Inbred C3H
Receptors
Notch
Stem Cells
General Neuroscience
mammifère
PAX7 Transcription Factor
muscle squelettique
Cell Differentiation
Fucosyltransferases
medicine.anatomical_structure
Notch proteins
Stem cell
Signal transduction
hypertrophy
Signal Transduction
Research Article
notch
medicine.medical_specialty
Satellite Cells
Skeletal Muscle
Immunology
Notch signaling pathway
Biology
General Biochemistry
Genetics and Molecular Biology
03 medical and health sciences
cellule satellite
Internal medicine
medicine
POFUT1
skeletal muscle
Animals
Muscle
Skeletal
MyoD Protein
[SDV.GEN]Life Sciences [q-bio]/Genetics
Research
Cell Membrane
Skeletal muscle
[SDV.GEN.GA]Life Sciences [q-bio]/Genetics/Animal genetics
030104 developmental biology
Endocrinology
lcsh:Biology (General)
skeletal muscles
Zdroj: Open Biology, Vol 6, Iss 9 (2016)
Open Biology
Open Biology, Royal Society, 2016, 6 (9), ⟨10.1098/rsob.160211⟩
Open biology 9 (6), . (2016)
ISSN: 2046-2441
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-mediatedO-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 thePofut1gene on postnatal muscle growth in mutant Pofut1cax/cax(cax, compact axial skeleton) mice and differentiation of their satellite cell-derived myoblasts (SCDMs). Pofut1cax/caxmice exhibited muscle hypertrophy, no hyperplasia and a decrease in satellite cell numbers compared with wild-type C3H mice. In agreement with these observations, Pofut1cax/caxSCDMs differentiated earlier concomitant with reducedPax7expression and decrease in PAX7+/MYOD−progenitor cells.In vitrobinding 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-mediatedO-fucosylation of NOTCH receptors regulates myogenic cell differentiation and affects postnatal muscle growth in mice.
Databáze: OpenAIRE
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