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 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.

中文翻译：

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通过线虫胚胎中 Wnt 配体的扩散传递极性信息

不同的信号机制共同确保动物发育过程中稳健的组织模式和细胞命运指令。大多数这些机制依赖于产生、运输和检测的信号蛋白。信号分子的时空动力学在很大程度上是未知的，但它们决定了信号活动的空间范围和时间范围。在这里，我们利用胚胎来研究 Wnt 配体（一种进化上保守的信号蛋白家族）如何动态组织以在发育组织中建立细胞极性。我们确定了胚胎后半部产生的 Wnt 配体如何在细胞外传播，以将信息传递到前半部的远处靶细胞。通过定量实时成像和荧光相关光谱，我们发现 Wnt 配体在比细胞周期更短的时间尺度内扩散到胚胎、细胞间隙和蛋壳下组织外部。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到一个简单的计算框架中，我们展示了胚胎中的扩散如何通过配体到达靶细胞的时间积分来极化单个细胞。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长程 Wnt 信号传导，这与发育过程的动态一致。