Mouse Nkd1, a Wnt antagonist, exhibits oscillatory gene expression in the PSM under the control of Notch signaling
Mouse Nkd1, a Wnt antagonist, exhibits oscillatory gene expression in the PSM under the control of Notch signaling
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DOI：
10.1016/j.mod.2004.08.003
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发表时间：
2004-12-01
影响因子：
2.6
通讯作者：
Saga, Y
中科院分区：
文献类型：
--
作者：
Ishikawa, A;Kitajima, S;Saga, Y
在脊椎动物胚胎发生过程中，沿着体轴的重复结构的形成依赖于体节前中胚层（PSM）的分裂产生体节。Notch信号在PSM细胞形成体节的分子钟的产生和调节中起着至关重要的作用，为PSM细胞形成体节提供空间信息。在筛选参与体节发生的新基因中，我们确定了编码Wnt拮抗剂Nkd 1的基因，该基因以振荡方式转录，并可能代表分子钟成分的新成员。nkd 1的转录在Wnt 3a的亚纯型突变体--残留尾（vt/vt）的PSM中被极度下调，而nkd 1振荡具有与疯缘（L-fng）转录相似的相位，并且它们在Hes 7（Notch信号传导的负调节因子）缺陷的胚胎中被阻止。这些结果表明，nkd 1的转录需要Wnt 3a，其振荡模式取决于Hes 7的功能，Wnt信号被假定为Notch信号的上游，但我们在这项研究中证明，Wnt信号相关的基因也可能受到Notch信号的调控。总的来说，我们的数据表明，Notch和Wnt信号的相互作用，以及它们各自的负反馈回路，功能是组织体节发生所需的分割时钟。(C)2004爱思唯尔爱尔兰有限公司保留所有权利。
During vertebrate embryogenesis, the formation of reiterated structures along the body axis is dependent upon the generation of the somite by segmentation of the presomitic mesoderm (PSM). Notch signaling plays a crucial role in both the generation and regulation of the molecular clock that provides the spatial information for PSM cells to form somites. In a screen for novel genes involved in somitogenesis, we identified a gene encoding a Wnt antagonist, Nkd1, which is transcribed in an oscillatory manner, and may represent a new member of the molecular clock constituents. The transcription of nkd1 is extremely downregulated in the PSM of vestigial tail (vt/vt), a hypomorphic mutant of Wnt3a, whereas nkd1 oscillations have a similar phase to lunatic fringe (L-fng) transcription and they are arrested in Hes7 (a negative regulator of Notch signaling) deficient embryos. These results suggest that the transcription of nkd1 requires Wnt3a, and that its oscillation patterns depend upon the function of Hes7 Wnt signaling has been postulated to be upstream of Notch signaling but we demonstrate in this study that a Wnt-signal-related gene may also be regulated by Notch signaling. Collectively, our data suggest that the reciprocal interaction of Notch and Wnt signals, and of their respective negative feedback loops, function to organize the segmentation clock required for somitogenesis. (C) 2004 Elsevier Ireland Ltd. All rights reserved.