The homeodomain factor Xanf represses expression of genes in the presumptive rostral forebrain that specify more caudal brain regions
The homeodomain factor Xanf represses expression of genes in the presumptive rostral forebrain that specify more caudal brain regions
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DOI：
10.1016/j.ydbio.2007.03.524
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发表时间：
2007-07-15
影响因子：
2.7
通讯作者：
Zaraisky, Andrey G.
中科院分区：
文献类型：
--
作者：
Ermakova, Galina V.;Solovieva, Elena A.;Zaraisky, Andrey G.
在脊椎动物吻侧前脑（RF）的早期发育中，前神经板吻侧区的两个同源异型盒调节因子Otx 2和Pax 6受到抑制，从而进一步引起U型前脑的发育。然而，这种抑制的确切分子机制和意义仍然不清楚。我们现在证明，活性的Anf同源结构域蛋白是必要的和足够的前抑制Otx2和Pax6。具体而言，我们表明，敲低非洲爪蟾Anf，Xanf，反义吗啉代寡核苷酸的结果在前扩展的Otx2和Pax6的表达到推定的RF领土。此外，通过在蛋白质合成不存在的情况下过表达Xanf的可诱导的激活子和抑制子融合变体，我们提出证据表明Xanf可以直接下调Otx 2和Pax 6，但不能下调更rostrally表达的Bf 1，Bf 2，Fgf 8和Nkx 2.4。这些结果解释了Xanf的抑制活性如何区分RF调节器，有利于后前脑的。假设Anf类型的同源异型盒是特定的脊椎动物，我们的数据表明，在进化中出现的Anf可能是一个关键的事件，通过消除同源的现代后前脑调节器的前神经板的喙部的脊椎动物RF发展。(c)2007年爱思唯尔公司All rights reserved.
Early development of the rostral forebrain (RF) in vertebrates is accompanied by the inhibition of two homeobox regulators, Otx2 and Pax6 in the rostral sector of the anterior neural plate, further giving rise to the U. However, the precise molecular mechanism and meaning of this inhibition is still obscure. We now demonstrate that the activity of the Anf homeodomain protein is necessary and sufficient for the anterior inhibition of Otx2 and Pax6. Specifically, we show that knockdown of the Xenopus laevis Anf, Xanf, by antisense morpholino oligonucleotides results in the anterior expansion of Otx2 and Pax6 expression into the presumptive RF territory. Furthemore, by overexpressing hormone-inducible activator- and repressor-fused variants of Xanf in the absence of protein synthesis, we present evidence that Xanf can directly downregulate Otx2 and Pax6 but not the more rostrally expressed Bf1, Bf2, Fgf8 and Nkx2.4. These results explain how the inhibitory activity of Xanf can discriminate RF regulators in favor of posterior forebrain ones. Assuming that the Anf type of homeobox is specific for vertebrates, our data suggest that the emergence of Anf in evolution could be a critical event for RF development in vertebrates through the elimination of homologues of modem posterior forebrain regulators from the rostral sector of the anterior neural plate. (c) 2007 Elsevier Inc. All rights reserved.