Laboratori d'Investigació, Hospital Universitari Arnau de Vilanova, Departament de Ciències Mèdiques Bàsiques, IRBLleida-University of Lleida, Lleida, Spain.
J Neurosci Res. 2010 Nov 1;88(14):3011-23. doi: 10.1002/jnr.22464.
Wnt factors regulate neural stem cell development and neuronal connectivity. Here we investigated whether Wnt-3a and Wnt-3, expressed in the developing spinal cord, regulate proliferation and the neuronal differentiation of spinal cord neural precursors (SCNP). Wnt-3a promoted a sustained increase of SCNP proliferation and decreased the expression of cyclin-dependent kinase inhibitors. In contrast, Wnt-3 transiently enhanced SCNP proliferation and increased neurogenesis through β-catenin signaling. Furthermore, both Wnt-3a and Wnt-3 stimulated neurite outgrowth in SCNP-derived neurons through β-catenin- and TCF4-dependent transcription. Glycogen synthase kinase-3β inhibitors mimicked Wnt signaling and promoted neurite outgrowth in established cultures. We conclude that Wnt-3a and Wnt-3 factors signal through the canonical Wnt/β-catenin pathway to regulate different aspects of SCNP development. These findings may be of therapeutic interest for the treatment of neurodegenerative diseases and nerve injury.
Wnt 因子调节神经干细胞发育和神经元连接。在这里，我们研究了发育中的脊髓中表达的 Wnt-3a 和 Wnt-3 是否调节脊髓神经前体细胞（SCNP）的增殖和神经元分化。Wnt-3a 促进 SCNP 增殖的持续增加，并降低细胞周期蛋白依赖性激酶抑制剂的表达。相比之下，Wnt-3 通过 β-连环蛋白信号短暂增强 SCNP 增殖并增加神经发生。此外，Wnt-3a 和 Wnt-3 均通过 β-连环蛋白和 TCF4 依赖性转录刺激 SCNP 衍生神经元的轴突生长。糖原合酶激酶-3β抑制剂模拟 Wnt 信号并促进已建立培养物中的轴突生长。我们得出结论，Wnt-3a 和 Wnt-3 因子通过经典的 Wnt/β-连环蛋白途径发出信号，以调节 SCNP 发育的不同方面。这些发现可能对治疗神经退行性疾病和神经损伤具有治疗意义。
