The brain expressed x-linked gene 1 (Bex1) regulates myoblast fusion.
The brain expressed x-linked gene 1 (Bex1) regulates myoblast fusion.
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DOI：
10.1016/j.ydbio.2015.11.007
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发表时间：
2016-01-01
影响因子：
2.7
通讯作者：
Kuang S
中科院分区：
文献类型：
--
作者：
Jiang C;Wang JH;Yue F;Kuang S
骨骼肌发育（肌发生）是一个复杂但精确协调的过程，涉及肌源性祖细胞（成肌细胞）增殖、分化和融合的时空调节。在这里，我们确定大脑表达的X连锁基因1（Bex1）作为一个短暂的，发育调控基因参与成肌细胞融合。Bex1表达在成体肌肉或静止肌肉干细胞（卫星细胞）中检测不到。然而，在胚胎肌发生过程中，Bex1强烈表达的myogenin+分化成肌细胞，而不是Pax7+增殖成肌细胞。有趣的是，Bex1最初定位在细胞质中，然后易位到细胞核中。在成人肌肉再生过程中，Bex1在新再生的肌纤维中高度表达，并且在成熟过程中表达迅速下调。一致地，在培养的成肌细胞中，Bex1在增殖阶段不表达，但在诱导成肌分化时瞬时表达，遵循与体内所见相似的细胞质至细胞核易位模式。通过功能获得和丧失的研究，我们发现Bex1的过度表达促进了原代成肌细胞的融合，而不影响成肌分化和肌细胞生成素的表达。相反，Bex1基因敲除的成肌细胞表现出明显的融合缺陷，即使它们表达正常水平的肌细胞生成素并正常分化。这些结果阐明了Bex1通过调节成肌细胞融合在肌发生中的新作用。
Skeletal muscle development (myogenesis) is a complex but precisely orchestrated process involving spatiotemporal regulation of the proliferation, differentiation and fusion of myogenic progenitor cells (myoblasts). Here we identify brain expressed x-linked gene 1 (Bex1) as a transient, developmentally regulated gene involved in myoblast fusion. Bex1 expression is undetectable in adult muscles or in quiescent muscle stem cells (satellite cells). During embryonic myogenesis, however, Bex1 is robustly expressed by myogenin+ differentiating myoblasts, but not by Pax7+ proliferating myoblasts. Interestingly, Bex1 is initially localized in the cytoplasm and then translocates into the nucleus. During adult muscle regeneration, Bex1 is highly expressed in newly regenerated myofibers and the expression is rapidly downregulated during maturation. Consistently, in cultured myoblasts, Bex1 is not expressed at the proliferation stage but transiently expressed upon induction of myogenic differentiation, following a similar cytoplasm to nucleus translocation pattern as seen in vivo. Using gain- and loss-of-function studies, we found that overexpression of Bex1 promotes the fusion of primary myoblasts without affecting myogenic differentiation and myogenin expression. Conversely, Bex1 knockout myoblasts exhibit obvious fusion defects, even though they express normal levels of myogenin and differentiate normally. These results elucidate a novel role of Bex1 in myogenesis through regulating myoblast fusion.