MyoD cannot compensate for the absence of myogenin during skeletal muscle differentiation in murine embryonic stem cells
MyoD cannot compensate for the absence of myogenin during skeletal muscle differentiation in murine embryonic stem cells
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DOI：
10.1006/dbio.2000.9985
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发表时间：
2001-01-15
影响因子：
2.7
通讯作者：
Klein, WH
中科院分区：
文献类型：
--
作者：
Myer, A;Olson, EN;Klein, WH
Myogenin（-/-）小鼠显示严重的骨骼肌缺陷，尽管表达正常水平的MyoD。MyoD补偿肌细胞生成素的失败可以通过蛋白质功能的差异或基因表达模式的差异来解释。为了区分这两种可能性，我们比较了组成型表达的肌细胞生成素和MyoD在由肌细胞生成素（-/-）ES细胞制成的胚状体中支持肌肉分化的能力。从野生型胚胎干细胞分化的胚状体形成广泛的骨骼肌，但从肌细胞生成素（-/-）ES细胞分化的胚状体的肌肉形成能力大大减弱。myogenin（-/-）ES细胞不能产生肌肉是独立于内源性MyoD表达的。通过肌细胞生成素的组成型表达，在肌细胞生成素（-/-）ES细胞中恢复骨骼肌。相比之下，（-/-）MyoD的组成型表达只导致骨骼肌的边缘增强，虽然肌细胞数量大大增加。结果表明，MyoD的组成型表达导致肌细胞生成素（-/-）细胞的成肌定型增强，但也表明定型细胞在没有肌细胞生成素的情况下形成肌片的能力受损。因此，尽管它们有相关性，但肌细胞生成素在肌肉形成中的作用与MyoD不同，并且这种区别不能仅仅通过它们的表达特性的差异来解释。(C)2000学术出版社
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. (C) 2000 Academic Press