TY - JOUR
T1 - Thoracic skeletal defects in myogenin- and MRF4-deficient mice correlate with early defects in myotome and intercostal musculature
AU - Vivian, Jay L.
AU - Olson, Eric N.
AU - Klein, William H.
N1 - Funding Information:
We thank Renee Valdez for providing probes and assisting in mouse transport and Jennifer Knapp for helpful discussions on in situ hybridization. We acknowledge the Muscular Dystrophy Association and the Welch Foundation for supporting this work.
PY - 2000/8/1
Y1 - 2000/8/1
N2 - Myogenin and MRF4 are skeletal muscle-specific bHLH transcription factors, critical for muscle development. In addition to a variety of skeletal muscle defects, embryos homozygous for mutations in myogenin or MRF4 display phenotypes in the thoracic skeleton, including rib fusions and sternal defects. These skeletal defects are likely to be secondary because myogenin and MRF4 are not expressed in the rib cartilage or sternum. In this study, the requirement for myogenin and MRF4 in thoracic skeletal development was further examined. When a hypomorphic allele of myogenin and an MRF4-null mutation were placed together, the severity of the thoracic skeletal defects was greatly increased and included extensive rib cartilage fusion and fused sternebrae. Additionally, new rib defects were observed in myogenin/MRF4 compound mutants, including a failure of the rib cartilage to contact the sternum. These results suggested that myogenin and MRF4 share overlapping functions in thoracic skeletal formation. Spatial expression patterns of skeletal muscle-specific markers in myogenin, and MRF4-mutant embryos revealed early skeletal muscle defects not previously reported. MRF4-/- mice displayed abnormal intercostal muscle morphology, including bifurcation and fusion of adjacent intercostals, myogenin/ MRF4-mutant combinations displayed ventral myotome defects, including a failure to express normal levels of myf5. The results suggested that the early muscle defects observed in myogenin and MRF4 mutants may cause subsequent thoracic skeletal defects, and that myogenin and MRF4 have overlapping functions in ventral myotome differentiation and intercostal muscle morphogenesis. (C) 2000 Academic Press.
AB - Myogenin and MRF4 are skeletal muscle-specific bHLH transcription factors, critical for muscle development. In addition to a variety of skeletal muscle defects, embryos homozygous for mutations in myogenin or MRF4 display phenotypes in the thoracic skeleton, including rib fusions and sternal defects. These skeletal defects are likely to be secondary because myogenin and MRF4 are not expressed in the rib cartilage or sternum. In this study, the requirement for myogenin and MRF4 in thoracic skeletal development was further examined. When a hypomorphic allele of myogenin and an MRF4-null mutation were placed together, the severity of the thoracic skeletal defects was greatly increased and included extensive rib cartilage fusion and fused sternebrae. Additionally, new rib defects were observed in myogenin/MRF4 compound mutants, including a failure of the rib cartilage to contact the sternum. These results suggested that myogenin and MRF4 share overlapping functions in thoracic skeletal formation. Spatial expression patterns of skeletal muscle-specific markers in myogenin, and MRF4-mutant embryos revealed early skeletal muscle defects not previously reported. MRF4-/- mice displayed abnormal intercostal muscle morphology, including bifurcation and fusion of adjacent intercostals, myogenin/ MRF4-mutant combinations displayed ventral myotome defects, including a failure to express normal levels of myf5. The results suggested that the early muscle defects observed in myogenin and MRF4 mutants may cause subsequent thoracic skeletal defects, and that myogenin and MRF4 have overlapping functions in ventral myotome differentiation and intercostal muscle morphogenesis. (C) 2000 Academic Press.
KW - MRF4
KW - Muscle gene expression
KW - Myogenesis
KW - Myogenin
KW - Thoracic skeletal development
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U2 - 10.1006/dbio.2000.9788
DO - 10.1006/dbio.2000.9788
M3 - Article
C2 - 10898959
AN - SCOPUS:0034254339
SN - 0012-1606
VL - 224
SP - 29
EP - 41
JO - Developmental Biology
JF - Developmental Biology
IS - 1
ER -