TY - JOUR TI - Direct visualization of a native Wnt in vivo reveals that a long-range Wnt gradient forms by extracellular dispersal AU - Pani, Ariel M AU - Goldstein, Bob A2 - Nusse, Roel A2 - Bronner, Marianne E VL - 7 PY - 2018 DA - 2018/08/14 SP - e38325 C1 - eLife 2018;7:e38325 DO - 10.7554/eLife.38325 UR - https://doi.org/10.7554/eLife.38325 AB - Wnts are evolutionarily conserved signaling proteins with essential roles in development and disease that have often been thought to spread between cells and signal at a distance. However, recent studies have challenged this model, and whether long-distance extracellular Wnt dispersal occurs and is biologically relevant is debated. Understanding fundamental aspects of Wnt dispersal has been limited by challenges with observing endogenous ligands in vivo, which has prevented directly testing hypotheses. Here, we have generated functional, fluorescently tagged alleles for a C. elegans Wnt homolog and for the first time visualized a native, long-range Wnt gradient in a living animal. Live imaging of Wnt along with source and responding cell membranes provided support for free, extracellular dispersal. By limiting Wnt transfer between cells, we confirmed that extracellular spreading shapes a long-range gradient and is critical for neuroblast migration. These results provide direct evidence that Wnts spread extracellularly to regulate aspects of long-range signaling. KW - Wnt KW - morphogen KW - diffusion KW - extracellular signaling JF - eLife SN - 2050-084X PB - eLife Sciences Publications, Ltd ER -