Functional association of retinoic acid and hedgehog signaling in Xenopus primary neurogenesis.
Functional association of retinoic acid and hedgehog signaling in Xenopus primary neurogenesis.
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发表时间：
1999-10
期刊：
影响因子：
4.6
通讯作者：
P. Franco;A. Paganelli;S. López;A. Carrasco
中科院分区：
文献类型：
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作者：
P. Franco;A. Paganelli;S. López;A. Carrasco
以前的工作已经表明，维甲酸可以促进非洲爪哇胚胎中前神经元的分化(PapalPulu，N.和Kintner，C.(1996)Development 122,3409-3418)。为了阐明维甲酸在初级神经发生级联反应中的作用，我们研究了维甲酸处理整个胚胎是否会改变一组已知参与神经发生的基因的空间表达。我们发现，维甲酸能扩大神经外胚层的N-微管蛋白、X-NGR-1、X-MyT1、X-&DGR；-1和Gli3结构域，并抑制Zic2和Sonic Hedgehog的表达，而维甲酸拮抗剂则产生相反的变化。相反，声波和带状刺猬的过度表达减少了N-微管蛋白的条纹，扩大了神经板，降低了Gli3的表达，上调了Zic2的表达。因此，维甲酸和刺猬信号对前模式基因Gli3和Zic2以及作用于神经发生级联下游的其他基因具有相反的影响。此外，维甲酸不能挽救Notch(ICD)、Zic2或Sonic Hedgehog对原发神经发生的抑制作用。我们的结果表明，维甲酸的作用非常早，位于声波刺激物的上游，我们提出了一个调节神经板分化和增殖的模型，表明维甲酸可能通过抑制声波刺激物的表达来激活初级神经发生。
Previous work has shown that the posteriorising agent retinoic acid can accelerate anterior neuronal differentiation in Xenopus laevis embryos (Papalopulu, N. and Kintner, C. (1996) Development 122, 3409-3418). To elucidate the role of retinoic acid in the primary neurogenesis cascade, we investigated whether retinoic acid treatment of whole embryos could change the spatial expression of a set of genes known to be involved in neurogenesis. We show that retinoic acid expands the N-tubulin, X-ngnr-1, X-MyT1, X-&Dgr;-1 and Gli3 domains and inhibits the expression of Zic2 and sonic hedgehog in the neural ectoderm, whereas a retinoid antagonist produces opposite changes. In contrast, sonic and banded hedgehog overexpression reduced the N-tubulin stripes, enlarged the neural plate at the expense of the neural crest, downregulated Gli3 and upregulated Zic2. Thus, retinoic acid and hedgehog signaling have opposite effects on the prepattern genes Gli3 and Zic2 and on other genes acting downstream in the neurogenesis cascade. In addition, retinoic acid cannot rescue the inhibitory effect of Notch(ICD), Zic2 or sonic hedgehog on primary neurogenesis. Our results suggest that retinoic acid acts very early, upstream of sonic hedgehog, and we propose a model for regulation of differentiation and proliferation in the neural plate, showing that retinoic acid might be activating primary neurogenesis by repressing sonic hedgehog expression.