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Expression and neural control of myogenic regulatory factor genes during regeneration of mouse soleus
T Launay1, A S Armand, F Charbonnier
1Laboratoire de Biologie du Développement et de la Différenciation Musculaire (EA 2507), Centre Universitaire des Saints-Pères, Université René Descartes, Paris, France.
Abstract:
Given the importance of the myogenic regulatory factors (MRFs) for myoblast differentiation during development, the aims of this work were to clarify the spatial and temporal expression pattern of the four MRF mRNAs during soleus regeneration in mouse after cardiotoxin injury, using in situ hybridization, and to investigate the influence of innervation on the expression of each MRF during a complete degeneration/regeneration process. For this, we performed cardiotoxin injury-induced regeneration experiments on denervated soleus muscle. Myf-5, MyoD, and MRF4 mRNAs were detected in satellite cell-derived myoblasts in the first stages of muscle regeneration analyzed (2--3 days P-I). The Myf-5 transcript level dramatically decreased in young multinucleated myotubes, whereas MyoD and MRF4 transcripts were expressed persistently throughout the regeneration process. Myogenin mRNA was transiently expressed in forming myotubes. These results are discussed with regard to the potential relationships between MyoD and MRF4 in the satellite cell differentiation pathway. Muscle denervation precociously (at 8 days P-I) upregulated both the Myf-5 and the MRF4 mRNA levels, whereas the increase of both MyoD and myogenin mRNA levels was observed later, in the late stages of regeneration (30 days P-I). This significant accumulation of each differentially upregulated MRF during soleus regeneration after denervation suggests that each myogenic factor might have a distinct role in the regulatory control of muscle gene expression. This role is discussed in relation to the expression of the nerve-regulated genes, such as the nAChR subunit gene family. (J Histochem Cytochem 49:887-899, 2001)
Insights
This study reveals how myogenic regulatory factors (MRFs) like MyoD and MRF4 are expressed during mouse soleus muscle regeneration and how denervation affects their patterns, highlighting distinct roles in muscle repair.
Area of Science:
- Muscle regeneration
- Molecular biology
- Developmental biology
Background:
- Myogenic regulatory factors (MRFs) are crucial for myoblast differentiation.
- Understanding MRF expression is key to deciphering muscle development and repair.
- Soleus muscle regeneration provides a model to study these processes.
Purpose of the Study:
- To map the spatial and temporal expression of four MRF mRNAs during mouse soleus muscle regeneration post-cardiotoxin injury.
- To investigate the impact of denervation on MRF expression during muscle degeneration and regeneration.
Main Methods:
- In situ hybridization was used to analyze MRF mRNA expression patterns.
- Cardiotoxin-induced regeneration experiments were performed on both innervated and denervated soleus muscles.
- Analysis spanned early (2-3 days post-injury) to late (30 days post-injury) regeneration stages.
Main Results:
- Myf-5, MyoD, and MRF4 mRNAs were initially found in satellite cell-derived myoblasts.
- MyoD and MRF4 showed persistent expression, while Myf-5 decreased and myogenin was transiently expressed in myotubes.
- Denervation led to early upregulation of Myf-5 and MRF4, and later upregulation of MyoD and myogenin.
Conclusions:
- MyoD and MRF4 may have interconnected roles in the satellite cell differentiation pathway.
- Differential MRF upregulation following denervation suggests distinct roles in regulating muscle gene expression.
- These findings contribute to understanding the interplay between innervation and myogenic factors in muscle repair.