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Denervation of mouse skeletal muscle differentially affects the expression of the jun and fos proto-oncogenes
J L Bessereau1, B Fontaine, J P Changeux
1UA CNRS D1284 Neurobiologie Moléculaire, Département des Biotechnologies, Institut Pasteur, Paris, France.
Abstract:
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.
Insights
Muscle denervation rapidly alters mRNA levels of AP1 transcription factor subunits. While c-fos expression peaks early, c-jun and jun-B increase later, with jun-D remaining unchanged, indicating differential gene regulation.
Area of Science:
- Molecular biology
- Neuroscience
- Muscle physiology
Background:
- The AP1 transcription factor complex, composed of Jun and Fos proto-oncogene products, regulates gene expression.
- Muscle denervation triggers significant cellular and molecular changes in skeletal muscle.
Purpose of the Study:
- To investigate the dynamic changes in mRNA levels of c-fos, c-jun, jun-B, and jun-D proto-oncogenes following muscle denervation in adult mice.
- To determine the spatial expression patterns of specific jun transcripts within denervated muscle tissue.
- To explore the potential role of AP1 proto-oncogenes in the trans-synaptic regulation of muscle gene expression.
Main Methods:
- Sciatic nerve section in adult mice to induce lower-leg muscle denervation.
- Quantitative analysis of mRNA levels for c-fos, c-jun, jun-B, and jun-D using techniques likely including Northern blotting or RT-PCR.
- In situ hybridization to determine the spatial localization of c-jun and jun-D transcripts.
- Bromo-deoxyuridine labeling to identify and quantify proliferating cells.
Main Results:
- Muscle denervation induced non-coordinated changes in the mRNA levels of the four studied transcripts.
- c-fos mRNA levels peaked at 1.5 hours post-denervation and returned to basal levels by 6 hours.
- c-jun and jun-B mRNA levels increased significantly after 24 hours and remained elevated for at least 8 days, while jun-D mRNA levels showed no significant change.
- In situ hybridization revealed distinct spatial expression patterns for c-jun and jun-D.
- Proliferating cells were found to be significantly less abundant than cells expressing c-jun.
Conclusions:
- Denervation rapidly and differentially modulates the expression of genes encoding AP1 transcription factor subunits in differentiated muscle cells.
- The distinct temporal and spatial regulation of jun and fos transcripts suggests specific roles in the denervation response.
- Proto-oncogenes like those coding for AP1 subunits may participate in the trans-synaptic regulation of muscle-specific gene expression after nerve injury.