Institute for Frontier Life and Medical Sciences, Kyoto University, Kyoto, 606-8507, Japan; Kyoto University Graduate School of Medicine, Kyoto, 606-8501, Japan.
Institute for Frontier Life and Medical Sciences, Kyoto University, Kyoto, 606-8507, Japan; Institute for Integrated Cell-Material Sciences, Kyoto University, Kyoto, 606-8501, Japan.
Gene Expr Patterns. 2020 Jan;35:119094. doi: 10.1016/j.gep.2019.119094. Epub 2019 Dec 31.
During somite segmentation, the expression of clock genes such as Hes7 oscillates synchronously in the presomitic mesoderm (PSM). This synchronous oscillation slows down in the anterior PSM, leading to wave-like propagating patterns from the posterior to anterior PSM. Such dynamic expression depends on Notch signaling and is critical for somite formation. However, it remains to be determined how slowing oscillations in the anterior PSM are controlled, and whether the expression of the Notch ligand Delta-like1 (Dll1) oscillates on the surface of individual PSM cells, as postulated to be responsible for synchronous oscillation. Here, by using Dll1 fluorescent reporter mice, we performed live-imaging of Dll1 expression in PSM cells and found the oscillatory expression of Dll1 protein on the cell surface regions. Furthermore, a comparison of live-imaging of Dll1 and Hes7 oscillations revealed that the delay from Dll1 peaks to Hes7 peaks increased in the anterior PSM, suggesting that the Hes7 response to Dll1 becomes slower in the anterior PSM. These results raise the possibility that Dll1 protein oscillations on the cell surface regulate synchronous Hes7 oscillations, and that the slower response of Hes7 to Dll1 leads to slower oscillations in the anterior PSM.
在体节形成过程中，时钟基因（如 Hes7）在体节前中胚层（PSM）中同步表达。这种同步振荡在前 PSM 中减慢，导致从后到前 PSM 的波状传播模式。这种动态表达依赖于 Notch 信号，对体节形成至关重要。然而，目前尚不清楚如何控制前 PSM 中振荡的减缓，以及 Notch 配体 Delta-like1（Dll1）的表达是否在单个 PSM 细胞表面振荡，正如推测的那样，这是同步振荡的原因。在这里，我们使用 Dll1 荧光报告小鼠，对 PSM 细胞中的 Dll1 表达进行了实时成像，发现 Dll1 蛋白在细胞表面区域呈振荡表达。此外，对 Dll1 和 Hes7 振荡的实时成像比较表明，Dll1 峰到 Hes7 峰的延迟在前 PSM 中增加，表明 Hes7 对 Dll1 的反应在前 PSM 中变得更慢。这些结果表明，细胞表面上的 Dll1 蛋白振荡可能调节同步的 Hes7 振荡，而 Hes7 对 Dll1 的反应较慢导致前 PSM 中的振荡减缓。
