Wild-type myoblasts rescue the ability of myogenin-null myoblasts to fuse in vivo.
Skeletal muscle is formed via a complex series of events during embryogenesis. These events include commitment of mesodermal precursor cells, cell migration, cell-cell recognition, fusion of myoblasts, activation of structural genes, and maturation. In mice lacking the bHLH transcription factor myogenin, myoblasts are specified and positioned correctly, but few fuse to form multinucleated fibers. This indicates that myogenin is critical for the fusion process and subsequent differentiation events of myogenesis. To further define the nature of the myogenic defects in myogenin-null mice, we investigated whether myogenin-null myoblasts are capable of fusing with wild-type myoblasts in vivo using chimeric mice containing mixtures of myogenin-null and wild-type cells. Chimeric embryos demonstrated that myogenin-null myoblasts readily fused in the presence of wild-type myoblasts. However, chimeric myofibers did not express wild-type levels of muscle-specific gene products, and myofibers with a high percentage of mutant nuclei appeared abnormal, suggesting that the wild-type nuclei could not fully rescue mutant nuclei in the myofibers. These data demonstrate that myoblast fusion can be uncoupled from complete myogenic differentiation and that myogenin regulates a specific subset of genes with diverse function. Thus, myogenin appears to control not only transcription of muscle structural genes but also the extracellular environment in which myoblast fusion takes place. We propose that myogenin regulates the expression of one or more extracellular or cell surface proteins required to initiate the muscle differentiation program.
Myer
A
A
Department of Biochemistry and Molecular Biology, The University of Texas M. D. Anderson Cancer Center, Houston 77030, USA.
Wagner
D S
DS
Vivian
J L
JL
Olson
E N
EN
Klein
W H
WH
D000818:Animals; D002459:Cell Fusion / Q000502:physiology*; D002678:Chimera / Q000235:genetics; D005260:Female; D018507:Gene Expression Regulation, Developmental; D006822:Hybrid Cells / Q000201:enzymology; D051379:Mice; D008822:Mice, Transgenic; D009124:Muscle Proteins / Q000235:genetics / Q000502:physiology; D018482:Muscle, Skeletal / Q000166:cytology / Q000196:embryology* / Q000201:enzymology; D018008:Myogenin / Q000235:genetics / Q000502:physiology*; D011247:Pregnancy; D001616:beta-Galactosidase / Q000378:metabolism
D009124:Muscle Proteins; C503801:Myog protein, mouse; D018008:Myogenin; D001616:beta-Galactosidase