β-Catenin gain of function in muscles impairs neuromuscular junction formation
β-Catenin gain of function in muscles impairs neuromuscular junction formation
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DOI：
10.1242/dev.080705
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发表时间：
2012-06
期刊：
影响因子：
4.6
通讯作者：
Haitao Wu;Yisheng Lu;Arnab Barik;Anish Joseph;M. Taketo;W. Xiong;L. Mei
中科院分区：
文献类型：
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作者：
Haitao Wu;Yisheng Lu;Arnab Barik;Anish Joseph;M. Taketo;W. Xiong;L. Mei
神经肌肉连接（NMJ）的形成需要运动神经元和肌肉细胞之间的适当相互作用。β-连环蛋白是肌细胞形成NMJ所必需的。为了了解潜在的机制，我们研究了β-catenin功能增益（GOF）对NMJ发育的影响。在肌肉中特异性表达稳定β-catenin的HSA-β-catflox(ex3)/+小鼠中，运动神经末梢出现广泛的去血循环和树状化。膈肌内可见异位肌，受膈神经异位支支配。此外，脊髓轴突的广泛生长和分支在GOF小鼠中是明显的。这些结果表明，肌肉中β-连环蛋白的增加改变了突触前分化。突触后，HSA-β-catflox(ex3)/+膈肌的AChR簇分布在更宽的区域，提示肌肉β-catenin GOF干扰了将AChR簇限制在肌纤维中间区域的信号。而稳定的β-catenin在运动神经元中的表达对NMJ的形成没有影响。这些观察结果提供了额外的遗传证据，证明NMJ的突触前和突触后发育需要肌肉中β-连环蛋白活性的复杂平衡。
Neuromuscular junction (NMJ) formation requires proper interaction between motoneurons and muscle cells. β-Catenin is required in muscle cells for NMJ formation. To understand underlying mechanisms, we investigated the effect of β-catenin gain of function (GOF) on NMJ development. In HSA-β-catflox(ex3)/+ mice, which express stable β-catenin specifically in muscles, motor nerve terminals became extensively defasciculated and arborized. Ectopic muscles were observed in the diaphragm and were innervated by ectopic phrenic nerve branches. Moreover, extensive outgrowth and branching of spinal axons were evident in the GOF mice. These results indicate that increased β-catenin in muscles alters presynaptic differentiation. Postsynaptically, AChR clusters in HSA-β-catflox(ex3)/+ diaphragms were distributed in a wider region, suggesting that muscle β-catenin GOF disrupted the signal that restricts AChR clustering to the middle region of muscle fibers. Expression of stable β-catenin in motoneurons, however, had no effect on NMJ formation. These observations provide additional genetic evidence that pre- and postsynaptic development of the NMJ requires an intricate balance of β-catenin activity in muscles.