Yang Jing, Wu Jinling, Tan Change, Klein Peter S
Department of Medicine (Hematology-Oncology) Institute, University of Pennsylvania School of Medicine, 364 Clinical Research Building, 415 Curie Blvd, Philadelphia, PA 19104, USA.
Development. 2003 Dec;130(23):5569-78. doi: 10.1242/dev.00762. Epub 2003 Oct 1.
The Wnt/beta-catenin pathway plays important roles during embryonic development and growth control. The B56 regulatory subunit of protein phosphatase 2A (PP2A) has been implicated as a regulator of this pathway. However, this has not been investigated by loss-of-function analyses. Here we report loss-of-function analysis of PP2A:B56epsilon during early Xenopus embryogenesis. We provide direct evidence that PP2A:B56epsilon is required for Wnt/beta-catenin signaling upstream of Dishevelled and downstream of the Wnt ligand. We show that maternal PP2A:B56epsilon function is required for dorsal development, and PP2A:B56epsilon function is required later for the expression of the Wnt target gene engrailed, for subsequent midbrain-hindbrain boundary formation, and for closure of the neural tube. These data demonstrate a positive role for PP2A:B56epsilon in the Wnt pathway.
Wnt/β-连环蛋白信号通路在胚胎发育和生长控制过程中发挥着重要作用。蛋白磷酸酶2A（PP2A）的B56调节亚基被认为是该信号通路的一种调节因子。然而，尚未通过功能丧失分析对此进行研究。在此，我们报告了非洲爪蟾胚胎早期发育过程中PP2A:B56ε的功能丧失分析。我们提供了直接证据，表明PP2A:B56ε在Dishevelled上游和Wnt配体下游的Wnt/β-连环蛋白信号传导中是必需的。我们表明，母体PP2A:B56ε功能对于背侧发育是必需的，而PP2A:B56ε功能随后对于Wnt靶基因engrailed的表达、随后的中脑-后脑边界形成以及神经管闭合也是必需的。这些数据证明了PP2A:B56ε在Wnt信号通路中具有正向作用。
