Myf-5 and myoD genes are activated in distinct mesenchymal stem cells and determine different skeletal muscle cell lineages
Related Experiment Videos
1Department of CCell and Molecular Biology, University of Braunschweig, Germany.
Abstract:
Targeted inactivation of the myogenic determination genes myf-5 and myoD in mice resulted in moderate (Myf-5) or no muscle phenotypes (MyoD) and double knock-out mutants lacking both genes failed to develop any skeletal muscle. In order to determine the mechanism of this apparent genetic redundancy we investigated the basis of functional overlap between the two genes. Here we demonstrate that Myf-5 and MyoD are not expressed within the same muscle precursor cell, but rather determine different muscle cell lineages arising from independently committed stem cell populations. Selective ablation of Myf-5-expressing muscle precursors from differentiating ES cells does not prevent Myo-D-dependent muscle differentiation. The early muscle progenitor cells which normally express Myf-5 do not develop into later appearing MyoD cells, even when the myf-5 gene has been inactivated. Thus skeletal musculature in vertebrates develops from two separate cell lineages and complementation may occur at the cellular level, but not between different myogenic factor genes within one cell.
Insights
Skeletal muscle development in mice relies on two distinct cell lineages, not overlapping genes. Myf-5 and MyoD myogenic factors determine separate muscle cell populations, revealing a cellular-level complementation mechanism.
Area of Science:
- Developmental Biology
- Genetics
- Muscle Biology
Background:
- Myogenic determination genes Myf-5 and MyoD play crucial roles in skeletal muscle development.
- Inactivation of Myf-5 or MyoD alone results in minimal or no muscle defects, respectively, but double knockouts lack skeletal muscle.
- This suggests potential genetic redundancy and functional overlap between Myf-5 and MyoD.
Purpose of the Study:
- To investigate the mechanism behind the apparent genetic redundancy between Myf-5 and MyoD.
- To determine if Myf-5 and MyoD function within the same muscle precursor cells or in distinct lineages.
- To elucidate the basis of functional overlap between these two key myogenic factors.
Main Methods:
- Targeted gene inactivation in mice to create single and double knockout mutants.
- Investigation of gene expression patterns in muscle precursor cells.
- Selective ablation of Myf-5-expressing muscle precursors from differentiating embryonic stem (ES) cells.
Main Results:
- Myf-5 and MyoD are expressed in distinct muscle precursor cell populations, not within the same cell.
- Muscle precursor cells expressing Myf-5 commit to specific lineages and do not develop into MyoD-expressing cells, even when Myf-5 is inactivated.
- Selective ablation of Myf-5 precursors does not impede MyoD-dependent muscle differentiation, indicating separate lineage determination.
Conclusions:
- Vertebrate skeletal muscle develops from at least two separate, independently committed cell lineages.
- Complementation in muscle development occurs at the cellular level between distinct lineages, not through functional overlap of different myogenic factor genes within a single cell.
- Myf-5 and MyoD act in parallel pathways to specify distinct muscle cell fates.