Kengaku M, Capdevila J, Rodriguez-Esteban C, De La Peña J, Johnson R L, Izpisúa Belmonte J C, Tabin C J
Department of Genetics, Harvard Medical School, 200 Longwood Avenue, Boston, MA 02115, USA.
Science. 1998 May 22;280(5367):1274-7. doi: 10.1126/science.280.5367.1274.
The apical ectodermal ridge (AER) is an essential structure for vertebrate limb development. Wnt3a is expressed during the induction of the chick AER, and misexpression of Wnt3a induces ectopic expression of AER-specific genes in the limb ectoderm. The genes beta-catenin and Lef1 can mimic the effect of Wnt3a, and blocking the intrinsic Lef1 activity disrupts AER formation. Hence, Wnt3a functions in AER formation through the beta-catenin/LEF1 pathway. In contrast, neither beta-catenin nor Lef1 affects the Wnt7a-regulated dorsoventral polarity of the limb. Thus, two related Wnt genes elicit distinct responses in the same tissues by using different intracellular pathways.
顶端外胚层嵴（AER）是脊椎动物肢体发育的关键结构。Wnt3a在鸡AER诱导过程中表达，Wnt3a的错误表达会诱导肢体外胚层中AER特异性基因的异位表达。β-连环蛋白和Lef1基因可模拟Wnt3a的作用，而阻断Lef1的内在活性会破坏AER的形成。因此，Wnt3a通过β-连环蛋白/LEF1途径在AER形成中发挥作用。相比之下，β-连环蛋白和Lef1均不影响Wnt7a调节的肢体背腹极性。因此，两个相关的Wnt基因通过使用不同的细胞内途径在同一组织中引发不同的反应。
