MyoD cannot compensate for the absence of myogenin during skeletal muscle differentiation in murine embryonic stem cells.
myogenin (-/-) mice display severe skeletal muscle defects despite expressing normal levels of MyoD.   The failure of MyoD to compensate for myogenin could be explained by distinctions in protein function   or by differences in patterns of gene expression. To distinguish between these two possibilities, we   compared the abilities of constitutively expressed myogenin and MyoD to support muscle   differentiation in embryoid bodies made from myogenin (-/-) ES cells. Differentiated embryoid bodies   from wild-type embryonic stem (ES) cells made extensive skeletal muscle, but embryoid bodies from   myogenin (-/-) ES cells had greatly attenuated muscle-forming capacity. The inability of myogenin (-/-)   ES cells to generate muscle was independent of endogenous MyoD expression. Skeletal muscle was   restored in myogenin (-/-) ES cells by constitutive expression of myogenin. In contrast, constitutive   expression of MyoD resulted in only marginal enhancement of skeletal muscle, although myocyte   numbers greatly increased. The results indicated that constitutive expression of MyoD led to enhanced   myogenic commitment of myogenin (-/-) cells but also indicated that committed cells were impaired in   their ability to form muscle sheets without myogenin. Thus, despite their relatedness, myogenin's role in   muscle formation is distinct from that of MyoD, and the distinction cannot be explained merely by   differences in their expression properties.
Myer
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Department of Biochemistry and Molecular Biology and Graduate Program in Genes and Development, The University of Texas M.D. Anderson Cancer Center, Houston 77030, USA.
Olson
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Klein
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D000818:Animals; D002454:Cell Differentiation; D002455:Cell Division; D018274:Electroporation; D018507:Gene Expression Regulation, Developmental; D018257:Helix-Loop-Helix Motifs; D051379:Mice; D018345:Mice, Knockout; D018482:Muscle, Skeletal / Q000166:cytology / Q000196:embryology*; D017570:MyoD Protein / Q000235:genetics / Q000502:physiology*; D018008:Myogenin / Q000235:genetics / Q000502:physiology*; D018995:Myosin Heavy Chains / Q000032:analysis / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013234:Stem Cells / Q000166:cytology / Q000502:physiology*; D014158:Transcription, Genetic; D014162:Transfection
D017570:MyoD Protein; C503801:Myog protein, mouse; D018008:Myogenin; D018995:Myosin Heavy Chains