Jamb and Jamc Are Essential for Vertebrate Myocyte Fusion
Jamb and Jamc Are Essential for Vertebrate Myocyte Fusion
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DOI：
10.1371/journal.pbio.1001216
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发表时间：
2011-12-01
期刊：
影响因子：
9.8
通讯作者：
Wright, Gavin J.
中科院分区：
文献类型：
--
作者：
Powell, Gareth T.;Wright, Gavin J.
细胞融合是包括骨骼肌在内的多种组织发育所必需的。在脊椎动物中，人们对这一过程知之甚少，并且缺乏融合所需的体内验证的细胞表面嗜异性受体对。鉴定融合细胞之间的基本细胞表面相互作用是阐明细胞融合的分子机制的重要步骤。我们在这里表明，斑马鱼直系同源物的JAM-B和JAM-C受体是必不可少的融合的肌细胞前体形成合胞肌纤维。jamb和jamc在发育中的肌肉中动态共表达，并编码物理相互作用的受体。任何一个基因的遗传性突变都会阻止体内肌细胞融合，导致单核细胞过多，但在其他方面明显正常，功能性快缩肌纤维。移植实验表明，Jamb和Jamc受体必须在相邻细胞（反式）之间相互作用才能发生融合。我们还发现jamc异位表达在prdm 1a突变型慢肌前体中，这些前体与其他肌细胞不适当地融合，这表明通过调节jamc表达来控制肌细胞融合对肌肉的生长和形成有重要意义。我们发现的受体-配体对融合在体内至关重要，了解负责的分子机制，在脊椎动物肌细胞融合和调节有重要意义。
Cellular fusion is required in the development of several tissues, including skeletal muscle. In vertebrates, this process is poorly understood and lacks an in vivo-validated cell surface heterophilic receptor pair that is necessary for fusion. Identification of essential cell surface interactions between fusing cells is an important step in elucidating the molecular mechanism of cellular fusion. We show here that the zebrafish orthologues of JAM-B and JAM-C receptors are essential for fusion of myocyte precursors to form syncytial muscle fibres. Both jamb and jamc are dynamically co-expressed in developing muscles and encode receptors that physically interact. Heritable mutations in either gene prevent myocyte fusion in vivo, resulting in an overabundance of mononuclear, but otherwise overtly normal, functional fast-twitch muscle fibres. Transplantation experiments show that the Jamb and Jamc receptors must interact between neighbouring cells (in trans) for fusion to occur. We also show that jamc is ectopically expressed in prdm1a mutant slow muscle precursors, which inappropriately fuse with other myocytes, suggesting that control of myocyte fusion through regulation of jamc expression has important implications for the growth and patterning of muscles. Our discovery of a receptor-ligand pair critical for fusion in vivo has important implications for understanding the molecular mechanisms responsible for myocyte fusion and its regulation in vertebrate myogenesis.