Merzdorf Christa S, Sive Hazel L
Whitehead Institute for Biomedical Research and Massachusetts Institute of Technology, Cambridge, USA.
Int J Dev Biol. 2006;50(7):611-7. doi: 10.1387/ijdb.052110cm.
The zic1 gene plays an important role in early patterning of the Xenopus neurectoderm. While Zic1 does not act as a neural inducer, it synergizes with the neural inducing factor Noggin to activate expression of posterior neural genes, including the midbrain/hindbrain boundary marker engrailed-2. Since the Drosophila homologue of zic1, odd-paired (opa), regulates expression of the wingless and engrailed genes and since Wnt proteins posteriorize neural tissue in Xenopus, we asked whether Xenopus Zic1 acted through the Wnt pathway. Using Wnt signaling inhibitors, we demonstrate that an active Wnt pathway is required for activation of en-2 expression by zic1. Consistent with this result, Zic1 induces expression of several wnt genes, including wnt1, wnt4 and wnt8b. wnt1 gene expression activates expression of engrailed in various organisms, including Xenopus, as demonstrated here. Together, our data suggest that zic1 is an upstream regulator of several wnt genes and that the regulatory relationships between opa, wingless and engrailed seen in Drosophila are also present in vertebrates.
zic1基因在非洲爪蟾神经外胚层的早期模式形成中发挥重要作用。虽然Zic1并非神经诱导因子，但它能与神经诱导因子Noggin协同作用，激活包括中脑/后脑边界标志物engrailed-2在内的后脑神经基因的表达。由于zic1在果蝇中的同源物odd-paired（opa）可调控无翅基因（wingless）和engrailed基因的表达，且Wnt蛋白能使非洲爪蟾的神经组织向后方分化，因此我们探究了非洲爪蟾Zic1是否通过Wnt信号通路发挥作用。使用Wnt信号抑制剂，我们证明zic1激活en-2表达需要活跃的Wnt信号通路。与此结果一致，Zic1可诱导包括wnt1、wnt4和wnt8b在内的多个wnt基因的表达。本文证明，wnt1基因表达可激活包括非洲爪蟾在内的多种生物中engrailed基因的表达。我们的数据共同表明，zic1是多个wnt基因的上游调节因子，并且在果蝇中观察到的opa、无翅基因和engrailed之间的调控关系在脊椎动物中也存在。
