β-catenin is essential and sufficient for skeletal Myogenesis in P19 cells
β-catenin is essential and sufficient for skeletal Myogenesis in P19 cells
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DOI：
10.1074/jbc.m112141200
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发表时间：
2002-05-03
影响因子：
4.8
通讯作者：
Skerjanc, IS
中科院分区：
文献类型：
--
作者：
Petropoulos, H;Skerjanc, IS
Wnt 1和Wnt 3a是已知在分化体节的肌节中诱导肌发生中起作用的信号传导因子。这两种因子都可能通过一种保守的途径来调节它们的信号，该途径导致β-连环蛋白/Lef 1的转录调节。β-连环蛋白和Lef 1在MyoD表达之前存在于肌节中。我们已经利用P19细胞系统来研究Wnt 3a可以激活MyoD表达和随后的骨骼肌发育的机制。我们分离出了稳定表达Wnt 3a或活化的β-连环蛋白的P19细胞系，并发现与对照细胞相比，这些细胞的聚集会诱导肌生成。Pax 3、Gli 2、Mox 1和Six 1在MyoD表达之前在Wnt 3a和β-连环蛋白诱导的分化期间表达。此外，我们通过显性负性β-连环蛋白/锯齿状嵌合体的过表达表明，β-连环蛋白的核功能对于P19细胞中的骨骼肌发生至关重要。原条因子存在，但表达的Pax 3，Mox 1，Gli 2，Six 1在这些细胞中丢失，表明核β-连环蛋白是必不可少的规范中胚层前体肌细胞谱系。因此，通过β-连环蛋白起作用的Wnt信号传导对于P19细胞中的骨骼肌发生是必要且充分的。
Wnt1 and Wnt3a are signaling factors known to play a role in the induction of myogenesis in the myotome of the differentiating somite. Both factors may transduce their signal by a conserved pathway that leads to transcriptional regulation by beta-catenin/Lef1. beta-Catenin and Lef1 are found in the myotome prior to MyoD expression. We have utilized the P19 cell system to study the mechanisms by which Wnt3a may activate MyoD expression and subsequent skeletal muscle development. We have isolated P19 cell lines that stably express either Wnt3a or activated beta-catenin and found that aggregation of these cells results in the induction of myogenesis compared with control cells. Pax3, Gli2, Mox1, and Six1 were expressed during Wnt3a and beta-catenin-induced differentiation prior to MyoD expression. Furthermore, we have shown that the nuclear function of beta-catenin was essential for skeletal myogenesis in P19 cells by overexpression of a dominant negative beta-catenin/engrailed chimera. Primitive streak factors were present, but expression of Pax3, Mox1, Gli2, and Six1 was lost in these cells, indicating that nuclear beta-catenin is essential for specification of mesodermal precursors to the myogenic lineage. Therefore, Wnt signaling, acting via beta-catenin, is necessary and sufficient for skeletal myogenesis in P19 cells.