McKendry R, Hsu S C, Harland R M, Grosschedl R
Department of Molecular and Cell Biology, University of California at Berkeley 94720, USA.
Dev Biol. 1997 Dec 15;192(2):420-31. doi: 10.1006/dbio.1997.8797.
The Xenopus nodal-related 3 gene (Xnr3) is expressed in the Spemann organizer of the embryo and encodes a member of the transforming growth factor beta family that mediates some activities of the organizer. Xnr3 is transcriptionally activated by wnt signaling during gastrulation in the Xenopus embryo. Here we show that a small region of the Xnr3 promoter is sufficient to confer wnt-inducible transcription. By mutational analysis of the promoter, we have identified two distinct sequence elements required for the response to wnt signals. One regulatory sequence interacts with a factor which accumulates in Xenopus gastrulae independent of wnt signaling. The other functionally important site can bind mammalian LEF-1 protein, a member of the LEF-1/TCF family of transcription factors. In addition, misexpression of LEF-1 in embryo explants induces transcription of the endogenous Xnr3 gene. Taken together, these data provide further evidence for a role of LEF-1/TCF proteins in wnt signaling and identify the Spemann organizer-specific gene Xnr3 as a direct target of these transcription factors in vertebrates.
非洲爪蟾结节相关基因3（Xnr3）在胚胎的施佩曼组织者中表达，编码转化生长因子β家族的一个成员，该成员介导组织者的一些活性。在非洲爪蟾胚胎原肠胚形成过程中，Xnr3受Wnt信号转录激活。在此我们表明，Xnr3启动子的一个小区域足以赋予Wnt诱导的转录。通过对启动子的突变分析，我们鉴定出两个对Wnt信号响应所需的不同序列元件。一个调控序列与一种在非洲爪蟾原肠胚中积累且不依赖Wnt信号的因子相互作用。另一个功能重要位点可结合哺乳动物LEF-1蛋白，它是LEF-1/TCF转录因子家族的成员。此外，在胚胎外植体中过表达LEF-1可诱导内源性Xnr3基因的转录。综上所述，这些数据为LEF-1/TCF蛋白在Wnt信号传导中的作用提供了进一步证据，并确定施佩曼组织者特异性基因Xnr3是脊椎动物中这些转录因子的直接靶标。
