Wang S, Krinks M, Lin K, Luyten F P, Moos M
Laboratory of Developmental Biology, Food and Drug Administration, Bethesda, Maryland 20892, USA.
Cell. 1997 Mar 21;88(6):757-66. doi: 10.1016/s0092-8674(00)81922-4.
We isolated a Xenopus homolog of Frzb, a newly described protein containing an amino-terminal Frizzled motif. It dorsalized Xenopus embryos and was expressed in the Spemann organizer during early gastrulation. Unlike Frizzled proteins, endogenous Frzb was soluble. Frzb was secretable and could act across cell boundaries. In several functional assays, Frzb antagonized Xwnt-8, a proposed ventralizing factor with an expression pattern complementary to that of Frzb. Furthermore, Frzb blocked induction of MyoD, an action reported recently for a dominant-negative Xwnt-8. Frzb coimmunoprecipitated with Wnt proteins, providing direct biochemical evidence for Frzb-Wnt interactions. These observations implicate Frzb in axial patterning and support the concept that Frzb binds and inactivates Xwnt-8 during gastrulation, preventing inappropriate ventral signaling in developing dorsal tissues.
我们分离出了一种非洲爪蟾Frzb的同源物，Frzb是一种新发现的蛋白质，其氨基端含有卷曲蛋白（Frizzled）基序。它使非洲爪蟾胚胎背化，并在原肠胚形成早期在施佩曼组织者中表达。与卷曲蛋白不同，内源性Frzb是可溶的。Frzb可分泌，并能跨越细胞边界发挥作用。在几项功能分析中，Frzb拮抗Xwnt - 8，Xwnt - 8是一种推测的腹化因子，其表达模式与Frzb互补。此外，Frzb阻断MyoD的诱导，这一作用最近也在显性负性Xwnt - 8中报道过。Frzb与Wnt蛋白共免疫沉淀，为Frzb与Wnt的相互作用提供了直接的生化证据。这些观察结果表明Frzb参与轴向模式形成，并支持这样的概念，即在原肠胚形成过程中，Frzb结合并使Xwnt - 8失活，从而防止发育中的背侧组织出现不适当的腹侧信号传导。
