Dubrulle Julien, Pourquié Olivier
Stowers Institute for Medical Research, 1000 East 50th Street, 64110 Kansas City, Missouri, USA.
Nature. 2004 Jan 29;427(6973):419-22. doi: 10.1038/nature02216.
Formation and patterning of the vertebrate embryo occur in a head-to-tail sequence. This progressive mode of body formation from the posterior end of the embryo requires a strict temporal coordination of tissue differentiation--a process involving fibroblast growth factor (FGF) signalling. Here we show that transcription of fgf8 messenger RNA is restricted to the growing posterior tip of the embryo. fgf8 mRNA is progressively degraded in the newly formed tissues, resulting in the formation of an mRNA gradient in the posterior part of the embryo. This fgf8 mRNA gradient is translated into a gradient of FGF8 protein, which correlates with graded phosphorylation of the kinase Akt, a downstream effector of FGF signalling. Such a mechanism provides an efficient means to monitor the timing of FGF signalling, coupling the differentiation of embryonic tissues to the posterior elongation of the embryo. In addition, this mechanism provides a novel model for morphogen gradient formation.
脊椎动物胚胎的形成和模式化是按从头到尾的顺序进行的。这种从胚胎后端开始的身体逐步形成模式需要组织分化的严格时间协调——这一过程涉及成纤维细胞生长因子(FGF)信号传导。我们在此表明,fgf8信使核糖核酸的转录局限于胚胎正在生长的后端。fgf8信使核糖核酸在新形成的组织中逐渐降解,导致在胚胎后部形成一个信使核糖核酸梯度。这个fgf8信使核糖核酸梯度被翻译成FGF8蛋白梯度,这与FGF信号传导的下游效应物激酶Akt的分级磷酸化相关。这样一种机制提供了一种监测FGF信号传导时间的有效手段,将胚胎组织的分化与胚胎的后端延伸联系起来。此外,这种机制为形态发生素梯度的形成提供了一个新模型。