Barx2 is expressed in satellite cells and is required for normal muscle growth and regeneration.
Barx2 is expressed in satellite cells and is required for normal muscle growth and regeneration.
复制标题
Barx2在卫星细胞中表达，是正常肌肉生长和再生所必需的。
DOI：
10.1002/stem.777
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发表时间：
2012-02
期刊：
影响因子：
--
通讯作者：
Makarenkova HP
中科院分区：
文献类型：
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作者：
Meech R;Gonzalez KN;Barro M;Gromova A;Zhuang L;Hulin JA;Makarenkova HP
肌肉的生长和再生是通过一系列时空依赖的信号转导和转录级联来调节的。虽然控制肌发生的转录程序已被广泛研究，但参与这一过程的转录调节因子的全部谱远未被定义。各种同源结构域转录因子已被证明在肌肉发育和肌肉卫星细胞依赖性修复中发挥重要作用。在这里，我们表明，同源结构域因子Barx 2是胚胎和成人成肌细胞的一个新的标志物，是正常的出生后肌肉生长和修复所必需的。Barx 2与Pax 7共表达，Pax 7是卫星细胞的典型标志物，并且在肌肉损伤后在卫星细胞中上调。缺乏Barx 2基因的小鼠表现出出生后肌肉生长减少、肌肉萎缩和肌肉修复缺陷。此外，Barx 2的缺失延迟了控制再生肌肉增殖和分化的基因的表达。与体内观察结果一致，从Barx 2 −/−小鼠培养的卫星细胞衍生的成肌细胞显示相对于野生型或Barx 2 +/−小鼠的增殖和分化能力降低。Barx 2 −/−成肌细胞显示分化相关因子肌细胞生成素以及细胞粘附和基质分子的表达减少。最后，我们发现缺乏Barx 2和肌营养不良蛋白基因表达的小鼠具有严重的早发性肌病。总之，这些数据表明，Barx 2是肌肉生长和修复的重要调节因子，通过控制卫星细胞增殖和分化发挥作用。
Muscle growth and regeneration are regulated through a series of spatiotemporally dependent signaling and transcriptional cascades. Although the transcriptional program controlling myogenesis has been extensively investigated, the full repertoire of transcriptional regulators involved in this process is far from defined. Various homeodomain transcription factors have been shown to play important roles in both muscle development and muscle satellite cell-dependent repair. Here, we show that the homeodomain factor Barx2 is a new marker for embryonic and adult myoblasts and is required for normal postnatal muscle growth and repair. Barx2 is coexpressed with Pax7, which is the canonical marker of satellite cells, and is upregulated in satellite cells after muscle injury. Mice lacking the Barx2 gene show reduced postnatal muscle growth, muscle atrophy, and defective muscle repair. Moreover, loss of Barx2 delays the expression of genes that control proliferation and differentiation in regenerating muscle. Consistent with the in vivo observations, satellite cell-derived myoblasts cultured from Barx2−/− mice show decreased proliferation and ability to differentiate relative to those from wild-type or Barx2+/− mice. Barx2−/− myoblasts show reduced expression of the differentiation-associated factor myogenin as well as cell adhesion and matrix molecules. Finally, we find that mice lacking both Barx2 and dystrophin gene expression have severe early onset myopathy. Together, these data indicate that Barx2 is an important regulator of muscle growth and repair that acts via the control of satellite cell proliferation and differentiation.