Hubrecht Laboratorium, Nederlands Instituut voor Ontwikkelingsbiologie, Utrecht, The Netherlands.
Dev Dyn. 2010 Jan;239(1):126-39. doi: 10.1002/dvdy.22020.
Hox transcription factors play an essential role in patterning the anteroposterior axis during embryogenesis and exhibit a complex array of spatial and temporal patterns of expression. Their earliest onset of expression in vertebrates is during gastrulation in a temporally collinear sequence in the presomitic/ventrolateral mesoderm, and it is not clear which upstream signal transduction events initiate this expression. Using Xenopus, we present evidence that Xwnt8 is necessary for initiation of this collinear sequence by activating Hox-1 expression in three Hox clusters: hoxd, hoxa, and hoxb. All three labial genes appear to be direct targets of canonical Wnt signaling through Tcf/Lef. In addition, Xwnt8 loss- and gain-of-function leads to indirect regulation of other Hox genes: Hoxb4, Hoxd4, Hoxa7, Hoxc6, and Hoxc8. These findings shed new light on the early role of Wnt8 as well as of a proposed WNT gradient in patterning the Xenopus central nervous system (Kiecker and Niehrs [2001] Development 128:4189-4201).
Hox 转录因子在胚胎发生过程中对前后轴的模式形成起着至关重要的作用，并表现出复杂的时空表达模式。它们在脊椎动物中的最早表达是在原肠胚期（gastrulation），在体节/腹外侧中胚层（presomitic/ventrolateral mesoderm）中以时间上的共线性序列表达，目前尚不清楚哪些上游信号转导事件引发了这种表达。我们使用非洲爪蟾（Xenopus）提供了证据，表明 Xwnt8 通过激活三个 Hox 簇（hoxd、hoxa 和 hoxb）中的 Hox-1 表达，对这种共线性序列的启动是必要的。所有三个唇基因似乎都是通过 Tcf/Lef 对经典 Wnt 信号的直接靶标。此外，Xwnt8 的功能丧失和获得性功能导致其他 Hox 基因的间接调节：Hoxb4、Hoxd4、Hoxa7、Hoxc6 和 Hoxc8。这些发现为 Wnt8 以及拟议的 WNT 梯度在模式形成中的早期作用提供了新的线索，该梯度在非洲爪蟾中枢神经系统（Kiecker 和 Niehrs [2001] Development 128:4189-4201）中。
