The involvement of Frodo in TCF-dependent signaling and neural tissue development
The involvement of Frodo in TCF-dependent signaling and neural tissue development
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DOI：
10.1242/dev.01369
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发表时间：
2004-10-01
期刊：
影响因子：
4.6
通讯作者：
Sokol, SY
中科院分区：
文献类型：
--
作者：
Hikasa, H;Sokol, SY
Frodo是Wnt信号转导的一种新的保守调节因子，已通过其与Dishevelled（Wnt信号转导的细胞内组分）的关联来鉴定。为了进一步了解Frodo的功能，我们使用特定的吗啉代反义寡核苷酸分析了它在神经发育中的作用。我们发现，弗罗多和密切相关的Dapper协同调节头部发育和形态发生。这两个基因都是神经组织形成所需的细胞自主性基因，如泛神经标记sox 2和nrp 1所定义的。相比之下，β-连环蛋白不需要泛神经标志物的表达，但参与前后图案的控制。在中胚层中，Frodo和Dapper对于组织者基因chordin、cerberus和Xnr 3的表达是必不可少的，但它们对于siamois和goosecoid的表达是不必要的，而siamois和goosecoid是β-连环蛋白信号传导的既定目标。去除任一基因的胚胎显示对TCF 3-VP 16（一种β-连环蛋白非依赖性转录激活因子）的转录应答降低。而弗罗多的C末端结合Dishevelled，我们证明保守的N-末端结构域与TCF 3。基于这些观察结果，我们提出Frodo和Dapper将Dsh和TCF连接起来，以平行于β-连环蛋白的途径调节Wnt靶基因。
Frodo is a novel conserved regulator of Wnt signaling that has been identified by its association with Dishevelled, an intracellular component of Wnt signal transduction. To understand further how Frodo functions, we have analyzed its role in neural development using specific morpholino antisense oligonucleotides. We show that Frodo and the closely related Dapper synergistically regulate head development and morphogenesis. Both genes were cell-autonomously required for neural tissue formation, as defined by the pan-neural markers sox2 and nrp1. By contrast, beta-catenin was not required for pan-neural marker expression, but was involved in the control of the anteroposterior patterning. In the mesoderm, Frodo and Dapper were essential for the expression of the organizer genes chordin, cerberus and Xnr3, but they were not necessary for the expression of siamois and goosecoid, established targets of beta-catenin signaling. Embryos depleted of either gene showed a decreased transcriptional response to TCF3-VP16, a beta-catenin-independent transcriptional activator. Whereas the C terminus of Frodo binds Dishevelled, we demonstrate that the conserved N-terminal domain associates with TCF3. Based on these observations, we propose that Frodo and Dapper link Dsh and TCF to regulate Wnt target genes in a pathway parallel to that of beta-catenin.