Transfer of polarity information via diffusion of Wnt ligands in C. elegans embryos

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. •Wnt ligands are detected away from their source cells in C. elegans embryos•Spreading of Wnt is consistent with diffusion in the extracellular space•Ligands can transfer polarity information from the tissue scale to target cells Recouvreux et al. show that Wnt ligands in C. elegans embryos diffuse extracellularly. They measure their diffusion properties with fluorescence correlation spectroscopy. Using numerical simulations, they show that diffusion alone can transfer polarity information at the cell level in a time frame consistent with development.