Oscillatory lunatic fringe activity is crucial for segmentation of the anterior but not posterior skeleton
Oscillatory lunatic fringe activity is crucial for segmentation of the anterior but not posterior skeleton
复制标题
DOI：
10.1242/dev.006742
复制
发表时间：
2008-03-01
期刊：
影响因子：
4.6
通讯作者：
Cole, Susan E.
中科院分区：
文献类型：
--
作者：
Shifley, Emily T.;VanHorn, Kellie M.;Cole, Susan E.
Notch通路在脊椎动物的体细胞发育过程中起着多方面的作用，在节钟和头端/尾端(R/C)体节的形成过程中发挥作用。疯狂边缘蛋白(Lfng)编码一种糖基转移酶，调节Notch信号，其表达模式表明在这两个过程中都有作用。为了分析Lfng在体细胞发生中所起的作用，建立了一个新的等位基因，它在分段时钟内缺乏循环Lfng的表达，但在R/C体节模式形成期间保持表达(Lfng(Delta FCE1))。在Lfng(Delta FCE1)胚胎的PSM中，在没有Lfng振荡表达的情况下，Notch的激活是普遍存在的。Lfng(Delta FCE1)小鼠在胸椎和腰椎骨骼中表现出严重的节段性表型。然而，Lfng(Delta FCE1)小鼠的骶椎和尾椎受到的影响很小，这表明Lfng的振荡表达和周期Notch激活在胸腰椎中轴骨骼的分段(初级身体形成)中是重要的，但对于骶椎和尾椎的发育(次级身体形成)是必不可少的。此外，我们发现在这两个发育阶段，周期Lfng的缺失对其他时钟基因的表达有不同的影响。最后，我们发现Lfng(Delta FCE1)胚胎经历了相对正常的R/C体节模式，证实了Lfng在分段时钟中的作用与其在体节模式中的功能不同。这些结果表明，在前轴/后轴发育的不同阶段，分段时钟可能采用不同的调节机制，并揭示了分段时钟与初级和次级身体形成过程之间以前不为人知的联系。
The Notch pathway plays multiple roles during vertebrate somitogenesis, functioning in the segmentation clock and during rostral/caudal (R/C) somite patterning. Lunatic fringe (Lfng) encodes a glycosyltransferase that modulates Notch signaling, and its expression patterns suggest roles in both of these processes. To dissect the roles played by Lfng during somitogenesis, a novel allele was established that lacks cyclic Lfng expression within the segmentation clock, but that maintains expression during R/C somite patterning (Lfng(Delta FCE1)). In the absence of oscillatory Lfng expression, Notch activation is ubiquitous in the PSM of Lfng(Delta FCE1) embryos. Lfng(Delta FCE1) mice exhibit severe segmentation phenotypes in the thoracic and lumbar skeleton. However, the sacral and tail vertebrae are only minimally affected in Lfng(Delta FCE1) mice, suggesting that oscillatory Lfng expression and cyclic Notch activation are important in the segmentation of the thoracic and lumbar axial skeleton (primary body formation), but are largely dispensable for the development of sacral and tail vertebrae (secondary body formation). Furthermore, we find that the loss of cyclic Lfng has distinct effects on the expression of other clock genes during these two stages of development. Finally, we find that Lfng(Delta FCE1) embryos undergo relatively normal R/C somite patterning, confirming that Lfng roles in the segmentation clock are distinct from its functions in somite patterning. These results suggest that the segmentation clock may employ varied regulatory mechanisms during distinct stages of anterior/posterior axis development, and uncover previously unappreciated connections between the segmentation clock, and the processes of primary and secondary body formation.