McGrew M J, Dale J K, Fraboulet S, Pourquié O
Laboratoire de génétique et de physiologie du développement (LGPD), Developmental Biology Institute of Marseille (IBDM), CNRS-INSERM-Université de la méditerranée-AP de Marseille, France.
Curr Biol. 1998 Aug 27;8(17):979-82. doi: 10.1016/s0960-9822(98)70401-4.
The most obvious segments of the vertebrate embryo are the trunk mesodermal somites which give rise to the segmented vertebral column and the skeletal muscles of the body. Mechanistic insights into vertebrate somitogenesis have recently been gained from observations of rhythmic expression of the avian hairy-related gene (c-hairy1) in chick presomitic mesoderm (PSM), suggesting the existence of a molecular clock linked to somite segmentation ([1]; reviewed in [2]). Here, we show that lunatic Fringe (IFng), a vertebrate homolog of the Drosophila Fringe gene, is also expressed rhythmically in PSM. The PSM expression of IFng was observed as coordinated pulses of mRNA resembling the expression of c-hairy1. We show that c-hairy1 and IFng expression in the PSM are coincident, indicating that both genes are responding to the same segmentation clock. The genes were found to differ in their regulation, however; in contrast to c-hairy1, IFng mRNA oscillations required continued protein synthesis, suggesting that IFng could be acting downstream of c-hairy1 in the clock mechanism. In Drosophila, Fringe has been shown to play a role in modulating Notch-Delta signalling [3,4], a pathway which in vertebrates has been implicated in defining somite boundaries [5-9]. These observations place the segmentation clock upstream of the Notch-Delta pathway during vertebrate somitogenesis.
脊椎动物胚胎中最明显的部分是躯干中胚层体节，它们发育形成分节的脊柱和身体的骨骼肌。最近，通过观察鸡胚前体节中胚层（PSM）中禽源毛相关基因（c-hairy1）的节律性表达，人们对脊椎动物体节发生的机制有了深入了解，这表明存在一个与体节分割相关的分子时钟（[1]；综述见[2]）。在此，我们发现果蝇边缘基因（Fringe）在脊椎动物中的同源物——疯狂边缘（lunatic Fringe，Lfng）在PSM中也有节律性表达。Lfng在PSM中的表达表现为协调的mRNA脉冲，类似于c-hairy1的表达。我们发现c-hairy1和Lfng在PSM中的表达是同步的，这表明这两个基因都对同一个分割时钟做出反应。然而，我们发现这两个基因在调控方面存在差异；与c-hairy1不同，Lfng mRNA的振荡需要持续的蛋白质合成，这表明Lfng可能在时钟机制中作用于c-hairy1的下游。在果蝇中，边缘基因已被证明在调节Notch-Delta信号传导中发挥作用[3,4]，而在脊椎动物中，该信号通路与确定体节边界有关[5-9]。这些观察结果表明，在脊椎动物体节发生过程中，分割时钟位于Notch-Delta信号通路的上游。
