Tanaka Shingo, Hosokawa Hiroshi, Weinberg Eric S, Maegawa Shingo
Graduate School of Biostudies, Kyoto University, Kyoto 606-8501, Japan.
Department of Intelligence Science and Technology, Graduate School of Informatics, Kyoto University, Kyoto 606-8501, Japan.
Dev Biol. 2017 Apr 15;424(2):189-197. doi: 10.1016/j.ydbio.2017.02.018. Epub 2017 Mar 1.
The ability of the Spemann organizer to induce dorsal axis formation is dependent on downstream factors of the maternal Wnt/β-catenin signaling pathway. The fibroblast growth factor (FGF) signaling pathway has been identified as one of the downstream components of the maternal Wnt/β-catenin signaling pathway. The ability of the FGF signaling pathway to induce the formation of a dorsal axis with a complete head structure requires chordin (chd) expression; however, the molecular mechanisms involved in this developmental process, due to activation of FGF signaling, remain unclear. In this study, we showed that activation of the FGF signaling pathway induced the formation of complete head structures through the expression of chd and dickkopf-1b (dkk1b). Using the organizer-deficient maternal mutant, ichabod, we identified dkk1b as a novel downstream factor in the FGF signaling pathway. We also demonstrate that dkk1b expression is necessary, after activation of the FGF signaling pathway, to induce neuroectoderm patterning along the anteroposterior (AP) axis and for formation of complete head structures. Co-injection of chd and dkk1b mRNA resulted in the formation of a dorsal axis with a complete head structure in ichabod embryos, confirming the role of these factors in this developmental process. Unexpectedly, we found that chd induced dkk1b expression in ichabod embryos at the shield stage. However, chd failed to maintain dkk1b expression levels in cells of the shield and, subsequently, in the cells of the prechordal plate after mid-gastrula stage. In contrast, activation of the FGF signaling pathway maintained the dkk1b expression from the beginning of gastrulation to early somitogenesis. In conclusion, activation of the FGF signaling pathway induces the formation of a dorsal axis with a complete head structure through the expression of chd and subsequent maintenance of dkk1b expression levels.
施佩曼组织者诱导背轴形成的能力取决于母体Wnt/β-连环蛋白信号通路的下游因子。成纤维细胞生长因子（FGF）信号通路已被确定为母体Wnt/β-连环蛋白信号通路的下游成分之一。FGF信号通路诱导具有完整头部结构的背轴形成的能力需要脊索蛋白（chd）的表达；然而，由于FGF信号激活，参与这一发育过程的分子机制仍不清楚。在本研究中，我们表明FGF信号通路的激活通过chd和dickkopf-1b（dkk1b）的表达诱导了完整头部结构的形成。利用缺乏组织者的母体突变体ichabod，我们确定dkk1b是FGF信号通路中的一个新的下游因子。我们还证明，在FGF信号通路激活后，dkk1b的表达对于沿前后（AP）轴诱导神经外胚层模式形成以及形成完整的头部结构是必要的。共注射chd和dkk1b mRNA导致ichabod胚胎中形成具有完整头部结构的背轴，证实了这些因子在这一发育过程中的作用。出乎意料的是，我们发现chd在盾形期的ichabod胚胎中诱导了dkk1b的表达。然而，chd未能维持盾形期细胞中dkk1b的表达水平，随后在原肠胚中期后也未能维持前索板细胞中dkk1b的表达水平。相反，FGF信号通路的激活从原肠胚形成开始到早期体节形成维持了dkk1b的表达。总之，FGF信号通路的激活通过chd的表达以及随后维持dkk1b的表达水平诱导了具有完整头部结构的背轴形成。
