Tsukushi controls ectodermal patterning and neural crest specification in Xenopus by direct regulation of BMP4 and X-delta-1 activity
Tsukushi controls ectodermal patterning and neural crest specification in Xenopus by direct regulation of BMP4 and X-delta-1 activity
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DOI：
10.1242/dev.02178
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发表时间：
2006-01-01
期刊：
影响因子：
4.6
通讯作者：
Tanaka, H
中科院分区：
文献类型：
--
作者：
Kuriyama, S;Lupo, G;Tanaka, H
在非洲爪蟾中，外胚层模式依赖于BMP信号的中外侧梯度，在表皮中较高，在神经外胚层中较低。神经嵴细胞在神经板和表皮之间的边界处被指定，处于BMP信号传导的中间水平。我们最近描述了一种新的分泌蛋白，Tsukushi（TSK），它作为一个BMP拮抗剂在鸡原肠胚形成。在这里，我们报告了非洲爪蟾TSK基因（X-TSK），并表明它参与了神经嵴的特化。原肠胚形成后，X-TSK表达在神经板的前外侧边缘（包括假定的神经嵴区域）积累。在功能获得性实验中，X-TSK可以强烈增强背外侧中胚层或外胚层外植体中的X-Wnt 8的神经嵴特化，而在原肠胚形成后的胚胎的外侧外胚层中的X-TSK mRNA的电穿孔可以诱导体内神经嵴标记物的表达。相比之下，外植体或胚胎中X-TSK的耗尽损害神经嵴特化。与其鸡同源物类似，X-TSK通过直接结合BMP 4作为BMP拮抗剂起作用。然而，X-TSK也可以通过调节Delta-Notch信号通路间接调节神经板边缘的BMP 4 mRNA表达。我们表明，X-TSK直接结合到X-delta-1的细胞外区域，并调节Delta依赖的Notch活性。我们认为X-TSK通过直接调节神经外胚层和非神经外胚层之间边界的BMP和Delta活性在神经嵴形成中起关键作用。
In Xenopus, ectodermal patterning depends on a mediolateral gradient of BMP signaling, higher in the epidermis and lower in the neuroectoderm. Neural crest cells are specified at the border between the neural plate and the epidermis, at intermediate levels of BMP signaling. We recently described a novel secreted protein, Tsukushi (TSK), which works as a BMP antagonist during chick gastrulation. Here, we report on the Xenopus TSK gene (X-TSK), and show that it is involved in neural crest specification. X-TSK expression accumulates after gastrulation at the anterior-lateral edges of the neural plate, including the presumptive neural crest region. In gain-of-function experiments, X-TSK can strongly enhance neural crest specification by the dorsolateral mesoderm or X-Wnt8 in ectodermal explants, while the electroporation of X-TSK mRNA in the lateral ectoderm of embryos after gastrulation can induce the expression of neural crest markers in vivo. By contrast, depletion of X-TSK in explants or embryos impairs neural crest specification. Similarly to its chick homolog, X-TSK works as a BMP antagonist by direct binding to BMP4. However, X-TSK can also indirectly regulate BMP4 mRNA expression at the neural plate border via modulation of the Delta-Notch signaling pathway. We show that X-TSK directly binds to the extracellular region of X-delta-1, and modulates Delta-dependent Notch activity. We propose that X-TSK plays a key role in neural crest formation by directly regulating BMP and Delta activities at the boundary between the neural and the non-neural ectoderm.