Institute for Frontier Life and Medical Sciences, Kyoto University, Kyoto, 606-8507, Japan.
Graduate School of Medicine, Kyoto University, Kyoto, 606-8501, Japan.
Cell Mol Life Sci. 2021 Feb;78(4):1221-1231. doi: 10.1007/s00018-020-03655-z. Epub 2020 Oct 4.
During embryogenesis, the processes that control how cells differentiate and interact to form particular tissues and organs with precise timing and shape are of fundamental importance. One prominent example of such processes is vertebrate somitogenesis, which is governed by a molecular oscillator called the segmentation clock. The segmentation clock system is initiated in the presomitic mesoderm in which a set of genes and signaling pathways exhibit coordinated spatiotemporal dynamics to establish regularly spaced boundaries along the body axis; these boundaries provide a blueprint for the development of segment-like structures such as spines and skeletal muscles. The highly complex and dynamic nature of this in vivo event and the design principles and their regulation in both normal and abnormal embryogenesis are not fully understood. Recently, live-imaging has been used to quantitatively analyze the dynamics of selected components of the circuit, particularly in combination with well-designed experiments to perturb the system. Here, we review recent progress from studies using live imaging and manipulation, including attempts to recapitulate the segmentation clock in vitro. In combination with mathematical modeling, these techniques have become essential for disclosing novel aspects of the clock.
在胚胎发生过程中,控制细胞如何分化并相互作用以形成具有精确时间和形状的特定组织和器官的过程至关重要。这样的过程的一个突出例子是脊椎动物体节发生,它由一个称为节段钟的分子振荡器控制。节段钟系统在体节中胚层中启动,其中一组基因和信号通路表现出协调的时空动力学,沿着身体轴建立规则间隔的边界;这些边界为脊椎和骨骼肌肉等类似节段的结构的发育提供了蓝图。这个体内事件的高度复杂和动态性质以及正常和异常胚胎发生中的设计原则及其调控尚未完全了解。最近,活体成像已被用于定量分析电路的选定组件的动力学,特别是与精心设计的实验相结合以扰乱系统。在这里,我们回顾了使用活体成像和操作的最新进展,包括试图在体外再现节段钟的尝试。与数学建模相结合,这些技术对于揭示时钟的新方面变得至关重要。