myf-5 and myoD genes are activated in distinct mesenchymal stem cells and determine different skeletal muscle cell lineages
myf-5 and myoD genes are activated in distinct mesenchymal stem cells and determine different skeletal muscle cell lineages
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DOI：
10.1002/j.1460-2075.1996.tb00361.x
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发表时间：
1996-01-15
期刊：
影响因子：
11.4
通讯作者：
Arnold, HH
中科院分区：
文献类型：
--
作者：
Braun, T;Arnold, HH
在小鼠中靶向失活肌生成决定基因myf-5和myoD导致中度（Myf-5）或无肌肉表型（MyoD），并且缺乏这两个基因的双敲除突变体不能发育任何骨骼肌。为了确定这种明显的遗传冗余的机制，我们研究了两个基因之间的功能重叠的基础，在这里，我们证明了Myf-5和MyoD不在同一个肌肉前体细胞中表达，而是决定了来自独立定向干细胞群体的不同肌肉细胞谱系，选择性消融表达Myf-5的肌肉前体细胞分化ES细胞不会阻止MyoD依赖性肌肉细胞分化。正常表达Myf-5的早期肌肉祖细胞不发育成后来出现的MyoD细胞，即使当myf-5基因已经失活时。因此，脊椎动物中的骨骼肌系统从两个独立的细胞谱系发育，并且互补mag发生在细胞水平，但不在一个细胞内的不同肌生成因子基因之间。
Targeted inactivation of the myogenic determination genes myf-5 and myoD in mice resulted in moderate (Myf-5) or no muscle phenotypes (MyoD) and double knock-out mutants lacking both genes failed to develop any skeletal muscle, In order to determine the mechanism of this apparent genetic redundancy we investigated the basis of functional overlap between the two genes, Here we demonstrate that Myf-5 and MyoD are not expressed within the same muscle precursor cell, but rather determine different muscle cell lineages arising from independently committed stem cell populations, Selective ablation of Myf-5-expressing muscle precursors from differentiating ES cells does not prevent MyoD-dependent muscle cell differentiation. The early muscle progenitor cells which normally express Myf-5 do not develop into later appearing MyoD cells, even when the myf-5 gene has been inactivated, Thus skeletal musculature in vertebrates develops from two separate cell lineages and complementation mag occur at the cellular level, but not between different myogenic factor genes within one cell.