Smith J C, Conlon F L, Saka Y, Tada M
Division of Developmental Biology, National Institute for Medical Research, London, UK.
Philos Trans R Soc Lond B Biol Sci. 2000 Jul 29;355(1399):923-30. doi: 10.1098/rstb.2000.0627.
The molecular basis of gastrulation is poorly understood. In this paper we address this problem by taking advantage of the observation that the transcription activator Brachyury is essential for gastrulation movements in Xenopus and mouse embryos. We infer from this observation that amongst the target genes of Brachyury are some that are involved in the regulation of gastrulation. In the course of a screen for Brachyury targets we identified Xwnt11. Use of a dominant-negative Xwntll construct confirms that signalling by this class of Wnts is essential for normal gastrulation movements, and further investigation suggests that Xwntll signals not through the canonical Wnt signalling pathway involving GSK-3 and beta-catenin but through another route, which may require small GTPases such as Rho and Rac. Future work will concentrate on elucidating the Xwnt11 signal transduction pathway and on investigating its influence on cell shape and polarity during Xenopus gastrulation.
原肠胚形成的分子基础目前了解甚少。在本文中,我们利用转录激活因子短尾相关蛋白(Brachyury)对非洲爪蟾和小鼠胚胎的原肠胚形成运动至关重要这一观察结果来解决这一问题。我们从这一观察结果推断,短尾相关蛋白的靶基因中有些参与了原肠胚形成的调控。在筛选短尾相关蛋白靶标的过程中,我们鉴定出了Xwnt11。使用显性负性Xwntll构建体证实,这类Wnt信号对于正常的原肠胚形成运动至关重要,进一步研究表明,Xwntll并非通过涉及糖原合成酶激酶3(GSK-3)和β-连环蛋白的经典Wnt信号通路进行信号传导,而是通过另一条途径,这可能需要诸如Rho和Rac等小GTP酶。未来的工作将集中于阐明Xwnt11信号转导途径,并研究其在非洲爪蟾原肠胚形成过程中对细胞形状和极性的影响。