Ras-dva1 small GTPase regulates telencephalon development in Xenopus laevis embryos by controlling Fgf8 and Agr signaling at the anterior border of the neural plate
Ras-dva1 small GTPase regulates telencephalon development in Xenopus laevis embryos by controlling Fgf8 and Agr signaling at the anterior border of the neural plate
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DOI：
10.1242/bio.20147401
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发表时间：
2014-03-15
期刊：
影响因子：
2.4
通讯作者：
Zaraisky, Andrey G.
中科院分区：
文献类型：
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作者：
Tereshina, Maria B.;Ermakova, Galina V.;Zaraisky, Andrey G.
我们之前发现小GTP酶Ras-dva1对于非洲爪蟾的端脑发育至关重要，因为Ras-dva1控制Fgf8介导的FoxG1表达的诱导，FoxG1是关键的端脑调节因子。然而，在本报告中，我们表明 Ras-dva1 和 FoxG1 在不同的细胞组中表达； Ras-dva1 在前神经皱襞的外层表达，而 FoxG1 和 Fgf8 在端脑衍生的内层被激活。我们通过证明 Ras-dva1 参与外层细胞接收到的 Fgf8 信号的转导来解决这个悖论，而 Fgf8 信号反过来又发送刺激内层中 FoxG1 表达的反馈信号。我们发现这种反馈信号是通过分泌的 Agr 蛋白传递的，该蛋白的表达在 Ras-dva1 和同源域转录因子 Otx2 的介导下在外层被激活。反过来，Agrs 对于维持前神经板边缘细胞中 Fgf8 和 FoxG1 的表达至关重要。我们的发现揭示了一种基于神经板前缘神经和非神经区室之间 Fgf8 和 Agr 信号交换的新型反馈环机制，并证明了 Ras-dva1 在该机制中的关键作用。
We previously found that the small GTPase Ras-dva1 is essential for the telencephalic development in Xenopus laevis because Ras-dva1 controls the Fgf8-mediated induction of FoxG1 expression, a key telencephalic regulator. In this report, we show, however, that Ras-dva1 and FoxG1 are expressed in different groups of cells; whereas Ras-dva1 is expressed in the outer layer of the anterior neural fold, FoxG1 and Fgf8 are activated in the inner layer from which the telencephalon is derived. We resolve this paradox by demonstrating that Ras-dva1 is involved in the transduction of Fgf8 signal received by cells in the outer layer, which in turn send a feedback signal that stimulates FoxG1 expression in the inner layer. We show that this feedback signal is transmitted by secreted Agr proteins, the expression of which is activated in the outer layer by mediation of Ras-dva1 and the homeodomain transcription factor Otx2. In turn, Agrs are essential for maintaining Fgf8 and FoxG1 expression in cells at the anterior neural plate border. Our finding reveals a novel feedback loop mechanism based on the exchange of Fgf8 and Agr signaling between neural and non-neural compartments at the anterior margin of the neural plate and demonstrates a key role of Ras-dva1 in this mechanism.