Myogenin expression, cell cycle withdrawal, and phenotypic differentiation are temporally separable events that precede cell fusion upon myogenesis.
Myogenin expression, cell cycle withdrawal, and phenotypic differentiation are temporally separable events that precede cell fusion upon myogenesis.
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DOI：
10.1083/jcb.132.4.657
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发表时间：
1996-02
期刊：
影响因子：
--
通讯作者：
Walsh K
中科院分区：
文献类型：
--
作者：
Andrés V;Walsh K
在骨骼肌母细胞的终末分化过程中，细胞融合形成有丝分裂后的多核肌管，不能重新启动DNA合成。在这里，我们研究了在C2C12成肌细胞体外分化过程中这些事件之间的时间关系。在成肌细胞进入分化途径的标志--肌肉生成素的表达细胞首先在肌肉发生过程中被检测到，随后出现了同时表达肌肉生成素和细胞周期抑制物p21的单核细胞。尽管这两种蛋白在有丝分裂原重新刺激的心肌细胞中持续表达，但在血清饥饿培养中的5-溴脱氧尿嘧啶核苷掺入实验表明，生肌素阳性的细胞仍然能够复制DNA。相反，在分化的成肌细胞中，随后p21的表达与有丝分裂后状态的建立相关。在后来的肌肉发生过程中，有丝分裂后(p21阳性)的单核成肌细胞激活了肌肉结构蛋白肌球蛋白重链的表达，然后融合形成多核肌管。因此，尽管分化的承诺是不同步的，但骨骼肌发生是一个高度有序的过程，由时间上可分离的事件组成，从肌生成素表达开始，然后是p21诱导和细胞周期停止，然后是表型分化，最后是细胞融合。
During terminal differentiation of skeletal myoblasts, cells fuse to form postmitotic multinucleated myotubes that cannot reinitiate DNA synthesis. Here we investigated the temporal relationships among these events during in vitro differentiation of C2C12 myoblasts. Cells expressing myogenin, a marker for the entry of myoblasts into the differentiation pathway, were detected first during myogenesis, followed by the appearance of mononucleated cells expressing both myogenin and the cell cycle inhibitor p21. Although expression of both proteins was sustained in mitogen-restimulated myocytes, 5- bromodeoxyuridine incorporation experiments in serum-starved cultures revealed that myogenin-positive cells remained capable of replicating DNA. In contrast, subsequent expression of p21 in differentiating myoblasts correlated with the establishment of the postmitotic state. Later during myogenesis, postmitotic (p21-positive) mononucleated myoblasts activated the expression of the muscle structural protein myosin heavy chain, and then fused to form multinucleated myotubes. Thus, despite the asynchrony in the commitment to differentiation, skeletal myogenesis is a highly ordered process of temporally separable events that begins with myogenin expression, followed by p21 induction and cell cycle arrest, then phenotypic differentiation, and finally, cell fusion.