Wnt/Lef1 signaling acts via Pitx2 to regulate somite myogenesis
Wnt/Lef1 signaling acts via Pitx2 to regulate somite myogenesis
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DOI：
10.1016/j.ydbio.2009.10.023
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发表时间：
2010-01-15
影响因子：
2.7
通讯作者：
Munsterberg, Andrea
中科院分区：
文献类型：
--
作者：
Abu-Elmagd, Muhammad;Robson, Lesley;Munsterberg, Andrea
Wnt信号通路参与体节、肢和鳃弓肌的发生，但其机制和作用尚不清楚。我们现在表明，Wnt信号通过Lef 1的行为，以调节体节中的前肌细胞的数量，但不调节肌细胞在肢芽或维护在第一或第二鳃弓。我们还分析了一个假定的下游转录靶的典型Wnt信号，Pitx 2的功能和调节。我们发现，Pitx 2的功能丧失减少了体节中肌源性细胞的数量，而过度表达增加了肌细胞的数量，特别是在肌节的轴上区域。有丝分裂细胞的数量增加，观察到过度表达Pitx 2或激活形式的Lef 1，这表明对细胞增殖的影响。此外，我们表明，Pitx 2的表达是由典型的Wnt信号在轴上体节和第二鳃弓，但不是在肢体或第一鳃弓。这些结果表明，Wnt/Lef 1信号调节轴上肌生成通过Pitx 2，但这种联系是解耦的身体的其他区域，强调独特的分子网络，控制各种肌肉的脊椎动物的发展。(C)2009 Elsevier Inc. All rights reserved.
Wnt signaling has been implicated in somite, limb, and branchial arch myogenesis but the mechanisms and roles are not clear. We now show that Wnt signaling via Lef1 acts to regulate the number of premyogenic cells in somites but does not regulate myogenic initiation in the limb bud or maintenance in the first or second branchial arch. We have also analysed the function and regulation of a putative downstream transcriptional target of canonical Wnt signaling, Pitx2. We show that loss-of-function of Pitx2 decreases the number of myogenic cells in the somite, whereas overexpression increases myocyte number particularly in the epaxial region of the myotome. Increased numbers of mitotic cells were observed following overexpression of Pitx2 or an activated form of Lef1, suggesting an effect on cell proliferation. In addition, we show that Pitx2 expression is regulated by canonical Wnt signaling in the epaxial somite and second branchial arch, but not in the limb or the first branchial arch. These results suggest that Wnt/Lef1 signaling regulates epaxial myogenesis via Pitx2 but that this link is uncoupled in other regions of the body, emphasizing the unique molecular networks that control the development of various muscles in vertebrates. (C) 2009 Elsevier Inc. All rights reserved.