Denervation of mouse skeletal muscle differentially affects the expression of the jun and fos proto-oncogenes.
The mRNA levels of the jun and fos proto-oncogenes, whose products are part of the transcription regulatory complex AP1, were investigated after denervation of the lower-leg muscles of adult mice. The levels of the four transcripts studied varied in a non-coordinated manner after muscle denervation. As early as 1.5 h after sciatic nerve section, c-fos mRNA reached a maximum and then returned to basal level at 6 h, while c-jun and jun-B mRNA levels increased after 24 h and remained elevated for at least 8 days. In contrast, jun-D mRNA levels did not change after denervation. In situ hybridization experiments revealed different patterns of spatial localization of the c-jun and jun-D transcripts. Labeling of dividing cells by the thymidine analog bromo-deoxyuridine demonstrated that proliferating cells were at least 40-fold less abundant than those expressing c-jun. Thus, denervation rapidly and differentially modulates the expression of genes coding for the AP1 transcription factor subunits in differentiated muscle cells. The possibility that these proto-oncogenes might be involved in the trans-synaptic regulation of muscle-specific gene expression is discussed.
Bessereau
J L
JL
UA CNRS D1284 Neurobiologie Moléculaire, Département des Biotechnologies, Institut Pasteur, Paris, France.
Fontaine
B
B
Changeux
J P
JP
D000818:Animals; D001973:Bromodeoxyuridine; D002455:Cell Division; D004268:DNA-Binding Proteins / Q000096:biosynthesis / Q000235:genetics*; D005786:Gene Expression Regulation; D051379:Mice; D008815:Mice, Inbred Strains; D009121:Muscle Denervation; D024510:Muscle Development; D009132:Muscles / Q000502:physiology*; D011505:Protein-Tyrosine Kinases / Q000378:metabolism; D011518:Proto-Oncogene Proteins / Q000096:biosynthesis / Q000235:genetics*; D016760:Proto-Oncogene Proteins c-fos; D016755:Proto-Oncogene Proteins c-jun; D011519:Proto-Oncogenes; D012333:RNA, Messenger / Q000378:metabolism*; D014157:Transcription Factors / Q000096:biosynthesis / Q000235:genetics*
D004268:DNA-Binding Proteins; D011518:Proto-Oncogene Proteins; D016760:Proto-Oncogene Proteins c-fos; D016755:Proto-Oncogene Proteins c-jun; D012333:RNA, Messenger; D014157:Transcription Factors; D011505:Protein-Tyrosine Kinases; D001973:Bromodeoxyuridine