Abstract：
Different signaling mechanisms concur to ensure robust tissue patterning and cell fate instruction during animal development. Most of these mechanisms rely on signaling proteins that are produced, transported, and detected. The spatiotemporal dynamics of signaling molecules are largely unknown, yet they determine signal activity\'s spatial range and time frame. Here, we use the Caenorhabditis elegans embryo to study how Wnt ligands, an evolutionarily conserved family of signaling proteins, dynamically organize to establish cell polarity in a developing tissue. We identify how Wnt ligands, produced in the posterior half of the embryos, spread extracellularly to transmit information to distant target cells in the anterior half. With quantitative live imaging and fluorescence correlation spectroscopy, we show that Wnt ligands diffuse through the embryo over a timescale shorter than the cell cycle, in the intercellular space, and outside the tissue below the eggshell. We extracted diffusion coefficients of Wnt ligands and their receptor Frizzled and characterized their co-localization. Integrating our different measurements and observations in a simple computational framework, we show how fast diffusion in the embryo can polarize individual cells through a time integration of the arrival of the ligands at the target cells. The polarity established at the tissue level by a posterior Wnt source can be transferred to the cellular level. Our results support a diffusion-based long-range Wnt signaling, which is consistent with the dynamics of developing processes.
摘要：
不同的信号传导机制可以确保动物发育过程中强大的组织模式和细胞命运指导。这些机制大多依赖于所产生的信号蛋白，运输,并检测到。信号分子的时空动力学在很大程度上是未知的，然而，他们确定信号活动的空间范围和时间框架。这里,我们使用秀丽隐杆线虫胚胎来研究Wnt配体，一个进化上保守的信号蛋白家族，动态组织以在发育中的组织中建立细胞极性。我们确定了Wnt配体，在胚胎的后半部产生，向细胞外传播以将信息传输到前半部的远处靶细胞。用定量实时成像和荧光相关光谱，我们显示Wnt配体在比细胞周期短的时间尺度上通过胚胎扩散，在细胞间空间，在蛋壳下面的组织外面。我们提取了Wnt配体及其受体Frizzled的扩散系数，并表征了它们的共定位。将我们不同的测量和观察整合在一个简单的计算框架中，通过配体到达靶细胞的时间积分，我们显示了胚胎中的扩散速度如何使单个细胞极化。由后部Wnt源在组织水平建立的极性可以转移到细胞水平。我们的结果支持基于扩散的远程Wnt信号，这与发展过程的动态是一致的。
