A significant reduction of the diaphragm in mdx:MyoD-/-(9th) embryos suggests a role for MyoD in the diaphragm development.
To further investigate the role of MyoD during skeletal myogenesis, we backcrossed mdx mutant mice (lacking dystrophin) with MyoD knock-out mice to obtain viable mice with MyoD allele on a pure mdx background. However, after nine generations of backcrossing, it was not possible to obtain a viable mdx:MyoD-/- phenotype (designated as: mdx:MyoD-/-(9th)). The compound-mutant embryos were examined just before birth. Essentially normal Myf5-dependent and most of the MyoD-dependent musculature was observed. By contrast, the skeletal muscle compartment of the diaphragm was significantly reduced. The mesenchymal compartment of the diaphragm was intact and no herniations were observed. Other examined organs (e.g., liver, kidney, brain, etc.) showed no histological abnormalities. Pulmonary hypoplasia was determined as the cause of neonatal death. Therefore, using a different approach, our new data supplement our previous findings and suggest an essential role for MyoD in development of skeletal muscle of the diaphragm. The failure of mdx:MyoD-/-(9th) diaphragm to develop normally is not caused by a reduced number of satellite cells, but from the inability of stem cells to progress through the myogenic program. Our data also suggest that functions of MyoD and Myf5 (and the respective muscle precursor cell sub-populations) are not entirely redundant by term, as previously suggested, since Myf5 is not capable of fully substituting for MyoD in the diaphragm development.
D000818:Animals; D004268:DNA-Binding Proteins; D003964:Diaphragm / Q000196:embryology*; D016189:Dystrophin / Q000235:genetics / Q000378:metabolism; D005121:Extremities / Q000196:embryology; D005804:Genes, Lethal; D051379:Mice; D018101:Mice, Inbred mdx; D024510:Muscle Development / Q000502:physiology; D009124:Muscle Proteins / Q000378:metabolism; D018482:Muscle, Skeletal / Q000196:embryology; D017570:MyoD Protein / Q000235:genetics* / Q000378:metabolism; D051787:Myogenic Regulatory Factor 5; D015534:Trans-Activators
D004268:DNA-Binding Proteins; D016189:Dystrophin; D009124:Muscle Proteins; C497418:Myf5 protein, mouse; D017570:MyoD Protein; D051787:Myogenic Regulatory Factor 5; D015534:Trans-Activators