Fiche publication
Date publication
mars 2002
Journal
The International journal of developmental biology
Auteurs
Membres identifiés du Cancéropôle Est :
Pr DEDIEU Stéphane
Tous les auteurs :
Dedieu S, Mazères G, Cottin P, Brustis JJ
Lien Pubmed
Résumé
The myogenic factors, MyoD, myogenin, Myf5 and MRF4, can activate skeletal muscle differentiation when overexpressed in non-muscular cells. Gene targeting experiments have provided much insight into the in vivo functions of MRF and have defined two functional groups of MRFs. MyoD and Myf5 may be necessary for myoblast determination while myogenin and MRF4 may be required later during differentiation. However, the specific role of these myogenic factors has not been clearly defined during one important stage of myogenesis: the fusion of myoblasts. Using cultured C2C12 mouse muscular cells, the time-course of these proteins was analyzed and a distinct expression pattern in fusing cells was revealed. In an attempt to clarify the role of each of these regulators during myoblast fusion, an antisense strategy using oligonucleotides with phosphorothioate backbone modification was adoped. The results showed that the inhibition of myogenin and Myf5 activity is capable of significantly preventing fusion. Furthermore, the inhibition of MyoD can wholly arrest the engaged fusion process in spite of high endogenous expression of both myogenin and Myf5. Consequently, each MRF seems to have, at this defined step of myogenesis, a specific set of functions that can not be substituted for by the others and therefore may regulate a distinct subset of muscle-specific genes at the onset of fusion.
Mots clés
Animals, Blotting, Western, Cell Differentiation, Cell Line, Cells, Cultured, DNA-Binding Proteins, Densitometry, Luciferases, metabolism, Mice, Models, Statistical, Muscle Proteins, metabolism, Muscles, cytology, MyoD Protein, metabolism, Myogenic Regulatory Factor 5, Myogenin, metabolism, Oligonucleotides, Antisense, pharmacology, Plasmids, metabolism, Protein Binding, Time Factors, Trans-Activators, Transfection
Référence
Int. J. Dev. Biol.. 2002 Mar;46(2):235-41
