PMID: 11934152Apr 6, 2002Paper

Involvement of myogenic regulator factors during fusion in the cell line C2C12

The International Journal of Developmental Biology
Stéphane DedieuJean-Jacques Brustis

Abstract

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 o...Continue Reading

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