Roël Giulietta, Hamilton Fiona S, Gent Yoony, Bain Andrew A, Destrée Olivier, Hoppler Stefan
Netherlands Institute for Developmental Biology (NIOB), Hubrecht Laboratorium, Uppsalalaan 8, 3584CT, Utrecht, The Netherlands.
Curr Biol. 2002 Nov 19;12(22):1941-5. doi: 10.1016/s0960-9822(02)01280-0.
Wnt signaling functions repeatedly during embryonic development to induce different but specific responses. What molecular mechanisms ensure that Wnt signaling triggers the correct tissue-specific response in different tissues? Early Xenopus development is an ideal model for addressing this fundamental question, since there is a dramatic change in the response to Wnt signaling at the onset of zygotic gene transcription: Wnt signaling components encoded by maternal mRNA establish the dorsal embryonic axis; zygotically expressed Xwnt-8 causes almost the opposite, by promoting ventral and lateral and restricting dorsal mesodermal development. Although Wnt signaling can function through different signal transduction cascades, the same beta-catenin-dependent, canonical Wnt signal transduction pathway mediates Wnt signaling at both stages of Xenopus development. Here we show that, while the function of the transcription factor XTcf-3 is required for early Wnt signaling to establish the dorsal embryonic axis, closely related XLef-1 is required for Wnt signaling to pattern the mesoderm after the onset of zygotic transcription. Our results show for the first time that different transcription factors of the Lef/Tcf family function in different tissues to bring about tissue-specific responses downstream of canonical Wnt signaling.
Wnt信号在胚胎发育过程中反复发挥作用，以诱导不同但特定的反应。哪些分子机制确保Wnt信号在不同组织中触发正确的组织特异性反应？非洲爪蟾的早期发育是解决这个基本问题的理想模型，因为在合子基因转录开始时，对Wnt信号的反应发生了巨大变化：由母体mRNA编码的Wnt信号成分建立了胚胎的背轴；合子表达的Xwnt-8通过促进腹侧和外侧发育并限制背侧中胚层发育，几乎产生相反的效果。尽管Wnt信号可以通过不同的信号转导级联发挥作用，但相同的β-连环蛋白依赖性经典Wnt信号转导途径在非洲爪蟾发育的两个阶段介导Wnt信号。我们在此表明，虽然转录因子XTcf-3的功能是早期Wnt信号建立胚胎背轴所必需的，但密切相关的XLef-1是合子转录开始后Wnt信号对中胚层进行模式化所必需的。我们的结果首次表明，Lef/Tcf家族的不同转录因子在不同组织中发挥作用，以在经典Wnt信号下游产生组织特异性反应。
