脊椎动物的脊柱来源于体节,体节是胚胎发生过程中的过渡性结构。体节的形成过程被称为体节发生（somitogenesis）。胚胎发育过程中正确的分节保证了脊椎动物具有正常的体轴，因此体节发生在时间和空间上受到严格的遗传控制，对体节发生的分子机制的研究是发育生物学中的重要课题。之前的研究证明，Wnt 和FGF信号途径以及转录因子Mespo等参与了体节发生，但具体的分子机制目前尚所知甚少。生化与细胞所丁小燕研究员带领研究人员通过对下游转录因子Mespo的研究，探讨了在体节发生中Wnt和FGF信号途径控制体节发生的可能作用方式，成果发表于2007年3月出版的《Developmental Biology》杂志。
研究者们用Morpholino基团修饰的寡核苷酸（Mo）阻断Mespo在体内的功能，发现爪蟾的体节发生被破坏。同时，对Wnt在爪蟾轴旁中胚层表达区域的确定，以及改变Wnt信号途径的活性检查体节发生，表明Wnt信号途径存在于预决定体节中胚层；而且Mespo的表达受到Wnt信号途径的调节。研究者通过克隆Mespo 5’上游调控序列，用转基因实验证明了该序列包含指导Mespo在预决定体节中胚层表达所需的调控元件。该序列上存在一个LEF/TCF结合位点，此位点是Mespo在预决定体节中胚层表达所必需的，在体内，LEF1蛋白结合在此位点上。进一步的研究发现，FGF信号下游作用因子AKT存在于预决定体节中胚层，在该区域AKT存在活化的磷酸化形式；而且，在预决定体节区域, PI3-K/AKT信号途径通过调节?-catenin的入核，参与了Mespo的表达调控。
本文揭示了转录因子Mespo在爪蟾体节发生中的作用，以及Mespo表达的转录调控机制。Wnt信号途径在爪蟾体节发生中的作用，Wnt信号途径通过调控Mespo这个关键转录调控因子的表达控制了体节发生。PI3-K/AKT信号途径也通过调控Mespo的表达参与体节发生。因此，Wnt和PI3-K/AKT信号途径通过协同调节Mespo的表达，从而使体节发生过程受到严格的时间和空间调控。
部分英文原文：
Developmental Biology
Volume 304, Issue 2 , 15 April 2007, Pages 836-847
Genomes & Developmental Control
Wnt/β-catenin signaling controls Mespo expression to regulate segmentation during Xenopus somitogenesis
Jinhu Wang1, a, b, Shangwei Li1, a, b, Yuelei Chena, b and Xiaoyan Ding, a, b,
aLaboratory of Molecular Cell Biology, Key Laboratory of Stem Cell Biology, Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, 320 Yue Yang Road, Shanghai 200031, China
bGraduate School of Chinese Academy of Sciences, 320 Yue Yang Road, Shanghai 200031, China
Received 12 May 2006; revised 17 November 2006; accepted 14 December 2006. Available online 21 December 2006.
Abstract
The vertebral column is derived from somites, which are transient segments of the paraxial mesoderm that are present in developing vertebrates. The strict spatial and temporal regulation of somitogenesis is of crucial developmental importance. Signals such as Wnt and FGF play roles in somitogenesis, but details regarding how Wnt signaling functions in this process remain unclear. In this study, we report that Wnt/β-catenin signaling regulates the expression of Mespo, a basic–helix–loop–helix (bHLH) gene critical for segmental patterning in Xenopus somitogenesis. Transgenic analysis of the Mespo promoter identifies Mespo as a direct downstream target of Wnt/β-catenin signaling pathway. We also demonstrate that activity of Wnt/β-catenin signaling in somitogenesis can be enhanced by the PI3-K/AKT pathway. Our results illustrate that Wnt/β-catenin signaling in conjunction with PI3-K/AKT pathway plays a key role in controlling development of the paraxial mesoderm.
Keywords: AKT; Paraxial mesoderm; PI3-K; Wnt; Xenopus laevis
Corresponding author. Fax: +86 21 34230165.
1 These authors contributed equally to this work.
