McQueeney Kelly, Soufer Renee, Dealy Caroline N
Department of BioStructure and Function, University of Connecticut Health Center, 263 Farmington Avenue, Farmington, CT 06030, USA.
Dev Growth Differ. 2002 Aug;44(4):315-25. doi: 10.1046/j.1440-169x.2002.00647.x.
The fibroblast growth factor (FGF) and beta-catenin-dependent Wnt signaling pathways are key regulators of vertebrate limb development. FGF10 induces expression of Wnt3a, which regulates the formation and FGF8 expression of the apical ectodermal ridge (AER). In amelic limbless limbs, an AER fails to form and FGF8 is not expressed, despite expression of FGF10. It has been found that Wnt3a is initially expressed in limbless ectoderm, although subsequently is drastically reduced. In addition, changes in the expression pattern or level of several Frizzled receptors, Axin, Lef1/Tcf1 and beta-catenin have been found in limbless limbs. Notably, while normal wing buds respond to LiCl-stimulated activation of beta-catenin-dependent signaling by forming ectopic, FGF8-expressing AER, LiCl was unable to induce an AER in limbless wing buds. The results of this study suggest that the limbless gene is required for beta-catenin-dependent Wnt signaling in limb ectoderm leading to FGF8 expression and AER formation.
成纤维细胞生长因子（FGF）和β-连环蛋白依赖性Wnt信号通路是脊椎动物肢体发育的关键调节因子。FGF10诱导Wnt3a的表达，Wnt3a调节顶端外胚层嵴（AER）的形成和FGF8的表达。在无肢肢体中，尽管有FGF10的表达，但AER未能形成且FGF8未表达。已发现Wnt3a最初在无肢外胚层中表达，尽管随后急剧减少。此外，在无肢肢体中还发现了几种卷曲受体、轴蛋白、Lef1/Tcf1和β-连环蛋白的表达模式或水平的变化。值得注意的是，虽然正常的翅芽通过形成异位的、表达FGF8的AER对LiCl刺激的β-连环蛋白依赖性信号激活作出反应，但LiCl无法在无肢翅芽中诱导AER形成。这项研究的结果表明，无肢基因是肢体外胚层中β-连环蛋白依赖性Wnt信号传导所必需的，该信号传导导致FGF8表达和AER形成。
